PORTUGAL COHEN MEITAL (IL)
BLINDERMAN ALEXANDRA (IL)
BARAK DAVID (IL)
MA'OR ZE'EVI (IL)
| WO2022013870A1 | 2022-01-20 | |||
| WO2005121329A2 | 2005-12-22 |
| US20140212513A1 | 2014-07-31 | |||
| US6521267B1 | 2003-02-18 | |||
| JP2016003198A | 2016-01-12 |
CLARISSE G MENDOZA ET AL: "A randomized, double-blind, placebo-controlled clinical trial on the efficacy and safety of 3% Rumex occidentalis cream versus 4% hydroquinone cream in the treatment of melasma among Filipinos", INTERNATIONAL JOURNAL OF DERMATOLOGY, WILEY-BLACKWELL PUBLISHING LTD, UK, vol. 53, no. 11, 30 September 2014 (2014-09-30), pages 1412 - 1416, XP071190379, ISSN: 0011-9059, DOI: 10.1111/IJD.12690
FERREIRA MARTA SALVADOR ET AL: "Trending Anti-Aging Peptides", COSMETICS, vol. 7, no. 4, 1 December 2020 (2020-12-01), pages 91, XP055815937, DOI: 10.3390/cosmetics7040091
| CLAIMS: 1. A composition comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide. 2. The composition according to Claim 1, wherein said Dead Sea extract is a mixture of natural materials obtained from the waters of the Dead Sea, and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea. 3. The composition according to Claim 1, wherein said Dead Sea extract is the saline waters obtained from the Dead Sea. 4. The composition according to Claim 1, wherein said Dead Sea extract is an aqueous solution simulating the salts and minerals content of the Dead Sea water. 5. The composition according to any one of Claims 1 to 4, wherein said Dead Sea extract is the commercially available product Maris Sal. 6. The composition according to any one of Claims 1 to 5, wherein said at least one extract of the plant Rumex is a Rumex occidentalis plant extract. 7. The composition according to any one of Claims 1 to 6, wherein said at least one extract of the plant Rumex is the commercially available Tyrostat™ extract (e.g., Tyrostat™ 09 and/or Tyrostat™ 11). 8. The composition according to any one of Claims 1 to 7, wherein said at least one one extract of the plant Rumex is formulated with at least one additive. 9. The composition according to Claim 8, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive. 10. The composition according to Claim 8 or 9, wherein said additive is Glycerin and/or Ascorbic Acid. 11. The composition according to any one of Claims 1 to 10, wherein said at least one Thioredoxin polypeptide is a human Thioredoxin. 12. The composition according to any one of Claims 1 to 10, wherein said at least one Thioredoxin polypeptide is a plan Thioredoxin. 13. The composition according to any one of Claims 1 to 10, wherein said at least one Thioredoxin polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana). 14. The composition according to any one of Claims 1 to 10 or 13, wherein said at least one Thioredoxin polypeptide is the plant-Thioredoxin-1 (plant-TRX-1). 15. The composition according to Claim 14, wherein said plant-Thioredoxin-1 is Oligopeptide-4 (INCI). 16. The composition according to any one of Claims 1 to 15, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1. 17. The composition according to any one of Claims 1 to 15, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2. 18. The composition according to any one of Claims 1 to 17, wherein said at least one Thioredoxin polypeptide comprises one or more conventional tags. 19. The composition according to any one of Claims 1 to 18, wherein said at least one Thioredoxin polypeptide is the commercially available plant-Thioredoxin-1 PUREOXIN™. 20. The composition according to any one of Claims 1 to 19, wherein said at least one Thioredoxin polypeptide is formulated with at least one additive. 21. The composition according to Claim 20, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive. 22. The composition according to any one of Claims 1 to 21, wherein said Dead Sea extract is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 2.5 % (w/w). 23. The composition according to any one of Claims 1 to 22, wherein said at least one extract of the plant Rumex is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 3.0 % (w/w). 24. The composition according to any one of Claims 1 to 23, wherein said at least one Thioredoxin polypeptide is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 4.0 % (w/w). 25. The composition according to any one of Claims 1 to 24, wherein said composition comprises an active combination of said at least one Dead Sea extract, said at least one extract of the plant Rumex, and said at least one Thioredoxin polypeptide. 26. A combination comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide. 27. The combination according to Claim 26, wherein said at least one Dead Sea extract, said at least one extract of the plant Rumex, and said at least one Thioredoxin polypeptide are as detailed herein above. 28. The combination according to Claim 26 or 27, wherein said Dead Sea extract is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 2.5 % (w/w) (out of the total weight of the combination). 29. The combination according to any one of Claims 26 to 28, wherein said at least one extract of the plant Rumex is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 3.0 % (w/w) (out of the total weight of the combination). 30. The combination according to any one of Claims 26 to 29, wherein said at least one Thioredoxin polypeptide is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 4.0 % (w/w) (out of the total weight of the combination). 31. A kit comprising (i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide, wherein each of components (i), (ii) and (iii), independently of the other, is formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier); and wherein each of (i), (ii) and (iii) are provided in a form that is suitable for concomitant administration with the other. 32. The kit according to Claim 31, wherein said at least one Dead Sea extract, said at least one extract of the plant Rumex, and said at least one Thioredoxin polypeptide are as detailed herein above. 33. The kit according to Claim 31 or 32, wherein said Dead Sea extract is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 2.5 % (w/w) [of the total weight of the formulation thereof or out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)]. 34. The kit according to any one of Claims 31 to 33, wherein said at least one extract of the plant Rumex is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 3.0 % (w/w) [of the total weight of the formulation thereof or out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)]. 35. The kit according to any one of Claims 31 to 34, wherein said at least one Thioredoxin polypeptide is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 4.0 % (w/w) [of the total weight of the formulation thereof or out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)]. 36. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, being selected from a skin-care and pharmaceutical composition, combination or kit, respectively. 37. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in topical application. 38. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, being a synergistic composition, combination or a kit, respectively. 39. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, being in the form selected from a lotion, an ointment, a gel, a mask, a toner, an essence, a cream, a water in oil or oil in water emulsion, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semisolid, or a liquid make-up, a foundation, and an eye make-up. 40. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, further comprising at least one additive selected from a diluent, a preservative, an abrasive, an anticaking agent, an antistatic agent, a binder, a buffer, a dispersant, an emollient, an emulsifier, a co-emulsifiers, a fiberous material, a film forming agent, a fixative, a foaming agent, a foam stabilizer, a foam booster, a gellant, a lubricant, a moisture barrier agent, a plasticizer, a preservative, a propellant, a stabilizer a surfactant, a suspending agent, a thickener, a wetting agent, and a liquefier. 41. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, further comprising at least one additive selected from an anti-acne agent, an anti-aging agent, an antibacterial agent, an anti-cellulites agent, an antidandruff agent, an antifungal agent, an anti-inflammatory agent, an anti-irritation agent, an antimicrobial agent, an antioxidant agent, an antiperspirant agent, an antiseptic agent, a cell stimulant, a cleansing agent, a conditioner, a deodorant, a depilatory, a detergent, an enzyme, an essential oil, an exfoliant, a fungicide, a glosser, hair conditioner, hair set resin, hair sheen agent, hair waving agent, a humectants, a moisturizer, an ointment base, a perfume, a protein, a skin calming agent, a skin cleanser, a skin conditioner, a skin healing agent, a skin lightening agent, a skin protectant, a skin smoothing agent, a skin softening agent, a skin soothing agent, a sunscreen agent, a tanning accelerator, vitamins, a colorant, and a flavoring agent. 42. The composition according to any one of Claims 1 to 25 or the combination according to any one of Claims 26 to 30, for use in the preparation of a cosmetic/skin- care or a pharmaceutical formulation. 43. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject. 44. The composition, combination or kit for use according to Claim 43, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by topical application of said composition, combination or the ingredients comprised within said kit onto the skin. 45. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject. 46. The composition, combination or kit for use according to Claim 45, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application. 47. A method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of the composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the ingredients comprised within the kit according to any one of Claims 31 to 35, onto the skin of a subject. 48. The method according to Claim 47, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application. 49. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear. 50. The composition, combination or kit for use according to Claim 49, wherein said improving is associated with inhibition of melanin synthesis induced by topical application of said composition or combination or the ingredients comprised within said kit onto the skin. 51. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in a method of improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear, wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject. 52. The composition, combination or kit for use according to Claim 51, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application. 53. A method of improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear, wherein said method comprises topical application of the composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the ingredients comprised within the kit according to any one of Claims 31 to 35, onto the skin of a subject. 54. The method according to Claim 53, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application. 55. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in treating and/or preventing at least one disease or disorder of the skin. 56. The composition, combination or kit for use according to Claim 55, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by topical application of said composition or combination or the ingredients comprised within said kit onto the skin. 57. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject. 58. The composition, combination or kit for use according to Claim 57, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application. 59. A method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of the composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the ingredients comprised within the kit according to any one of Claims 31 to 35, onto the skin of a subject. 60. The method according to Claim 59, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application. 61. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in treating and/or preventing inflammation of the skin of a subject. 62. The composition, combination or kit for use according to Claim 61, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by topical application of said composition or combination or the ingredients comprised within said kit onto the skin. 63. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in a method of treating and/or preventing inflammation of the skin of a subject wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject. 64. The composition, combination or kit for use according to Claim 63, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application. 65. A method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of the composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the ingredients comprised within the kit according to any one of Claims 31 to 35, onto the skin of a subject. 66. The method according to Claim 65, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application. 67. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in inhibiting and/or reducing skin melanin formation. 68. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the kit according to any one of Claims 31 to 35, for use in a method of inhibiting and/or reducing skin melanin formation wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject. 69. A method of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of the composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30 or the ingredients comprised within the kit according to any one of Claims 31 to 35, onto the skin of a subject. 70. A lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semisolid, or a liquid make-up, a foundation, and an eye make-up, comprising the composition according to any one of Claims 1 to 25 or the combination according to any one of Claims 26 to 30. 71. The kit according to any one of Claims 31 to 35 wherein the components thereof are in the form of a lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up. 72. Use of the composition according to any one of Claims 1 to 25 or the combination according to any one of Claims 26 to 30 in the manufacture of a pharmaceutical formulation or a skin care formulation. 73. Use of the composition according to any one of Claims 1 to 25 or the combination according to any one of Claims 26 to 30 in the manufacture of a pharmaceutical formulation or a skin care formulation for one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation. 74. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30, or the kit according to any one of Claims 31 to 35, for use in one or more of: improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation. 75. The composition according to any one of Claims 1 to 25, the combination according to any one of Claims 26 to 30, or the kit according to any one of Claims 31 to 35, for use in one or more of: improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation. |
FIELD OF THE INVENTION
This invention relates to skin care compositions and utilizing same e.g., as skin lucent and anti-pigmentation.
BACKGROUND OF THE INVENTION
Therapeutic and cosmetic skin formulations are aimed at providing the skin with beneficial health and appearance. Skin glow and luminance are of interest both in terms of beauty and health.
Natural products such as plant extracts are known in their anti-pigmentation effect on the skin, providing it with lighter appearance and even tone.
For example, Kojic acid is a chelation agent produced by several species of fungi, especially Aspergillus oryzae. It is a mild inhibitor of pigment formation in animal tissues and is used in cosmetics to lighten skin color.
Arbutin is a glycosylated hydroquinone extracted from the bearberry plant in the genus Arctostaphylos . Applied topically, it inhibits tyrosinase and thus prevents the formation of melanin, the primary determinant of skin color.
While Kojic Acid and Arbutin serve as the golden standard for skin lightening, utilizing same might be problematic in terms of side effects such as contact dermatitis that can be manifested as redness, irritation, itchiness, rashes, swollen skin, pain and discomfort.
SUMMARY OF THE INVENTION
The inventors of the present invention have developed an active combination of a natural extract originated from the Dead Sea, an extract originated from the Rumex plant, and Thioredoxin polypeptide.
As the present application will further disclose, the combination of the present disclosure has proven to have skin care and therapeutic attributes.
For example, combinations of the present invention have illustrated a potent inhibition of melanin synthesis, hence, possessing anti-pigmentation properties. The combinations of the present invention have also illustrated beneficial redox activity. Further, they illustrated a synergistic antioxidation activity which is beneficial e.g., for the stability of the combination when provided admixed, for its effect on the skin, and the ability to maintain low quantity of each individual component to avoid toxicity, while maintaining at least the same biological effect.
These beneficial features of the combinations of the present disclosure illustrated no accompanying side effects of toxicity and inflammation, whereas such undesired effects were associated with known, e.g., reference, skin lightening natural products.
Furthermore, the combinations of the present disclosure advantageously prevented inflammation. This effect was illustrated in a skin model in which the combination of the invention prevented elevation of the level of the cytokine IL-8 (a pro- inflammatory cytokine). The effect on cytokine IL-8 that was observed with the combination was opposite to the effect observed with each individual component constituting the combination i.e., the individual components illustrated an increase effect on the cytokine IL-8 level.
Non-limiting advantageous attributes of the combinations of the present invention that may be associate with skin melanin function are skin glow, lucent, radiance, antipigmentation, even tone and clear. These attributes are advantageous inter-alia in terms of the ability of the combinations of the invention to inhibit age-related skin damage and/or to treat or prevent skin diseases and/or disorders that are associate with hyper melanin formation.
Thus, the present invention provides in a first one of its aspects a composition comprising (as an active combination) at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
In another one of its aspects the present invention provides a combination comprising, at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
In another one of its aspects the present invention provides a combination comprising (i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide, wherein each of components (i), (ii) and (iii), independently of the other, is formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier). In a further one of its aspects the present invention provides a kit comprising (i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide, wherein each of components (i), (ii) and (iii), independently of the other, is formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier); and wherein each of (i), (ii) and (iii) are provided in a form that is suitable for concomitant administration with the other.
In yet a further one of its aspects the present invention provides skin-care composition and/or formulation and/or combination and/or kit; and/or a pharmaceutical composition and/or formulation and/or combination and/or kit.
Yet, in a further one of its aspects the present invention provides a composition and/or a combination for use in the preparation of a skin-care and/or a pharmaceutical formulation.
In another one of its aspects the present invention provides an anti-pigmentation composition/combination/formulation/kit.
In a further one of its aspects the present invention provides a skin lucent composition/combination/formulation/kit.
In yet a further one of its aspects the present invention provides a skin lucent boosting composition/combination/formulation/kit.
Yet, in a further one of its aspects the present invention provides a skin lightening/whitening/brightening composition/combination/formulation/kit.
In a further one of its aspects the present invention provides a skin lightening and skin tone illumination composition/combination/formulation/kit.
In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin. In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
In another one of its aspects the present invention provides a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In a further one of its aspects the present invention provides a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
In yet a further one of its aspects the present invention provides a composition and/or a combinations and/or a kit for use in improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear.
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said improving is associated with inhibition of melanin synthesis induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin. In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
In yet a further one of its aspects the present invention provides a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing at least one disease or disorder of the skin.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing at least one disease or disorder of the skin, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin.
In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
In another one of its aspects the present invention provides a method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In a further one of its aspects the present invention provides a method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing inflammation of the skin of a subject.
In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing inflammation of the skin of a subject, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject. In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
Yet in a further one of its aspects the present invention provides a method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In another one of its aspects the present invention provides a method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in inhibiting and/or reducing skin melanin formation.
In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use a method of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a method of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In another one of its aspects the present invention provides the use of a composition and/or a combination according to the invention in the manufacture of a pharmaceutical formulation and/or a skin care formulation (e.g., for the intended use/s as indicated herein above and below).
In a further one of its aspects the present invention provides the use of a composition and/or a combination according to the invention in the manufacture of a pharmaceutical formulation and/or a skin care formulation for one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; inhibiting and/or reducing skin melanin formation.
Yet, in a further one of its aspects the present invention provides the composition and/or the combination according to the invention and/or the kit of the invention, for use in one or more of: improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
In a further one of its aspects the present invention provides the composition and/or the combination according to the invention and/or the kit of the invention, for use in one or more of: improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
In yet a further one of its aspects the present invention provides a method for one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation, wherein said method comprises topical administration of the composition and/or combination according to the invention to a subject in need thereof.
In another one of its aspects the present invention provides a method for one or more of: improving (or providing) one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation, wherein said method comprises topical administration of the composition and/or combination according to the invention to a subject in need thereof.
In a further one of its aspects the present invention provides a non-therapeutic method for one or more of: improving (or providing) one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation, wherein said method comprises topical administration of the composition and/or combination according to the invention to a subject in need thereof.
Yet, in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use as disclosed herein and/or exemplified, wherein said composition and/or a combination and/or a kit comprise a synergistic active combination of at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
The various methods and/or uses of the compositions and/or combinations and/or the ingredients comprised within the kit according to the invention, as disclosed herein above and below (e.g., cosmetic and/or therapeutic), may be associate with one or more of inhibition of skin melanin formation and reduction in IL-8 skin levels induced/caused by the compositions/combinations/ingredients of the present invention.
The various methods and/or uses of the compositions and/or combinations and/or the ingredients comprised within the kit according to the invention, as disclosed herein above and below (e.g., cosmetic and/or therapeutic), may be associate with one or more of inhibition of skin melanin formation and reduction in IL-8 skin levels induced/caused by the compositions/combinations/ingredients of the present invention, and with the redox and anti-oxidation activity of the compositions/combinations/ingredients of the present invention.
The methods and/or the uses of the compositions and/or combinations and/or ingredients comprised within the kits of the invention, as disclosed herein above and below, may be associated with and/or mediated by and/or affected by and/or related to the to skin melanin formation (for example, the inhibition thereof e.g., via inhibition of tyrosinase enzymatic activity).
The therapeutic and/or cosmetic effects illustrated by the compositions and/or combinations and/or ingredients comprised within the kits of the present invention may be associated with and/or mediated by and/or affected by and/or related to skin melanin formation (for example, the inhibition thereof e.g., via inhibition of tyrosinase enzymatic activity).
In yet a further one of its aspects the present invention provides one or more of a lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semisolid, or a liquid make-up, a foundation, and an eye make-up comprising the composition and/or the combination according to the invention.
Yet, in a further one of its aspects the present invention provides one or more of a lotion, an ointment, a gel, a mask, a toner, an essence, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up comprising the composition and/or the combination according to the invention.
In another one of its aspect the present invention provides a kit according the invention, wherein the components thereof are in the form of a lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up.
In another one of its aspect the present invention provides a kit according the invention, wherein the components thereof are in the form of a lotion, an ointment, a gel, a mask, a toner, an essence, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up.
The present invention also provides compositions, combinations, kits, uses and methods as herein defined and exemplified.
The methods and/or uses disclosed herein may be cosmetic methods or uses.
The methods and/or uses disclosed herein may be any one of therapeutic or non- therapeutic methods or uses.
BRIEF DESCRIPTION OF THE DRAWINGS
In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:
Figure 1 represents melanin secretion observed with B 16 melanocyte cell culture without (black) and in the presence (grey, white) of the whitening agent Kojic acid at various time points.
Figure 2 represents melanin secretion observed with B 16 melanocyte cell culture without (black) and in the presence (grey, white) of the whitening agent Arbutin at various time points.
Figure 3 represents melanin secretion observed with B 16 melanocyte cell culture without (black) and in the presence (grey, white) of the Dead Sea extract Osmoter™ at various time points.
Figure 4 represents melanin secretion observed with B 16 melanocyte cell culture without (black) and in the presence (grey, white) of the Thioredoxin polypeptide PUREOXIN™ at various time points.
Figure 5 represents melanin secretion observed with B 16 melanocyte cell culture without (black) and in the presence (grey, white) of the Rumex plant extract TYROSTAT™- 11 at various time points.
Figure 6 represents melanin secretion observed with B 16 melanocyte cell culture, untreated and in the presence of Kojic acid, Arbutin, Osmoter™ (OSM), Sea-water (SW), PUREOXIN™ (P), Tyrostat™-l l (T), and various combination of these ingredients, including a complex according to some embodiments of the invention, after 96 hours.
Figure 7 represents melanin secretion observed with B 16 melanocyte cell culture, untreated and in the presence of Kojic acid, Arbutin, Osmoter™ (OSM), Sea-water (SW), PUREOXIN™ (P), Tyrostat™-l l (T), and various combination of these ingredients, including a complex according to some embodiments of the invention, after 144 hours.
Figures 8A-8J represent microscope pictures of B16 skin cells untreated and treated with Kojic acid, Arbutin, Osmoter™ (OSM), Sea-water (SW), PUREOXIN™ (P), Tyrostat™-l l (T), and various combination of these ingredients, including a complex according to some embodiments of the invention, after 144 hours.
Figure 9 represents melanin secretion observed with B 16 melanocyte cell culture, untreated and in the presence of Kojic acid, Arbutin, Osmoter™, PUREOXIN™ (P), Tyrostat™-l l (T), and various combinations of these ingredients, including a complex according to some embodiments of the invention, after 96 hours. Figures 10A-10L represent microscope pictures of B16 skin cells untreated and treated with Kojic acid, Arbutin, Osmoter™, PUREOXIN™ (P), Tyrostat™- 11 (T), and various combinations of these ingredients, including a complex according to some embodiments of the invention, after 96 hours.
Figure 11 represents Tyrosinase activity in B16 melanocyte cell lysate without (untreated) and in the presence of Kojic acid, Arbutin, Osmoter™, PUREOXIN™, Tyrostat ™-l l, and various combinations of these ingredients, according to some embodiments of the invention, after 96 hours of incubation.
Figure 12 represent the IL-8 level in culture media in a skin model after 16 days of incubation and irradiation with UVA 27 mJ/cm2. The skin was untreated and treated with Arbutin, PUREOXIN™, Tyrostat™- 11 , Osmoter™ and a complex of
PUREOXIN™, Tyrostat™- 11 and Osmoter™, according to some embodiments of the invention.
Figure 13 represents Oxygen Radical Absorbance Capacity (ORAC) assay results observed with several samples including individual ingredients and a complex according to some embodiments of the invention.
Figure 14 represents 2,6-Dichlorophenolindophenol (DCPIP) assay results observed with several samples including individual ingredients and a complex according to some embodiments of the invention.
DETAILED DESCRIPTION OF THE INVENTION
Various embodiments will be detailed herein in connection with the disclosed invention. It is noted that one or more of these embodiments may be applicable to one or more aspects of the invention disclosed herein above and below. It is further noted that one or more embodiments which are detailed in connection with the compositions of the invention, may also be applicable to the other aspects of the invention as detailed herein e.g., combinations, formulations, kits, methods, uses and vice-versa.
The wording compositions/combinations/formulations/kits; or the wording composition/combination/formulation/kit; or composition/s and/or formulation/s and/or combination/s and/or kit/s; or any lingual variations thereof; or order of the wording thereof, are envisaged as being relevant to any one of the composition/s, combination/s, formulation/s and kit/s of the present disclosure, or at times, as being relevant to one or more of same, mutatis mutandis.
The wording composition/s and/or formulation/s and/or combination/s and/or the ingredients comprises within the kit/s; or any lingual variations thereof; or order of the wording thereof, are envisaged as being relevant to any one of the composition/s, combination/s, formulation/s and kit/s of the present disclosure, or at times, as being relevant to one or more of same, mutatis mutandis.
The present invention provides in one of its aspects a combination comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
On some embodiments the at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide of the invention constitute an active combination.
As used herein, the expression "active combination" refers to the ability of the combination to exert one or more protective/preventive skin-care/therapeutic effect, as disclosed herein. Neither of the components constituting the combination is regarded as a carrier, diluent or excipient.
In some embodiments the active combination is referred to herein as a complex ', at times as “an active complex , even at times as Osmoter Lucent-boosting complex
In some embodiments the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide may be present in the same composition/formulation.
In some embodiments the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide may be present in different compositions/formulations e.g., in a form that is suitable for administration in conjunction with the other.
In some embodiments the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide may be admixed in a single composition and/or formulation or may present as individual ingredients in individual compositions and/or formulations configured to be administered concomitantly.
In some embodiments the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide may be present in different composition/formulation, wherein each of the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide, independently of the other, may be formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier).
In some embodiments, the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide may be present in different composition/formulation, wherein each of the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide, independently of the other, may be formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier), and wherein the one or more of an adjuvant, an excipient, a diluent or a carrier for each of the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide may be the same or different.
In some embodiments, the one or more of adjuvant, excipient, diluent or carrier of the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide, may be the same for each of the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide.
In some embodiments, the one or more of adjuvant, excipient, diluent or carrier of the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide, may be different and compatible with each other e.g., for topical administration.
Thus, the present invention provides in another one of its aspects a composition comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
In another one of its aspects the present invention provides a composition comprising an active combination of at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
In yet a further one of its aspects the present invention provides a combination comprising (i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide, wherein each of components (i), (ii) and (iii), independently of the other, is formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier).
Yet in a further one of its aspects the present invention provides a kit comprising
(i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide, wherein each of components (i), (ii) and (iii), independently of the other, is formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier); and wherein each of (i),
(ii) and (iii) are provided in a form that is suitable for concomitant administration with the other.
In some embodiments the kit may further comprise instructions for use.
In some embodiments the composition and/or combination and/or kit of the invention comprises an active combination of at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
In some embodiments the composition and/or combination and/or kit of the invention comprises an active combination of at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide, wherein the combination is a synergistic combination.
In some embodiments the composition of the invention is a synergistic composition.
In some embodiments the combination of the invention is a synergistic combination.
In some embodiments the ingredients (i), (ii) and (iii) constituting the kit of the invention illustrate at least one synergistic effect when administered concomitantly.
In some embodiments the ingredients (i), (ii) and (iii) constituting the kit of the invention act in a synergistic manner e.g., illustrating at least one synergistic effect when administered concomitantly.
As used herein the term "Dead Sea extract" refers to a mixture of natural materials obtained from the waters of the Dead Sea and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea.
In some embodiments the Dead Sea extract is a mixture of natural materials (e.g., salts, minerals) obtained from the waters of the Dead Sea. In some embodiments the Dead Sea extract is Dead Sea water (herein abbreviated DSW) (or a concentrate thereof) or an aqueous solution having substantially the same salt and mineral content of the Dead Sea water (or a concentrate thereof).
In some embodiments, the Dead Sea extract is the Dead Sea water.
In some embodiments the “Dead Sea water " refers to the saline waters obtained from the Dead Sea (Israel or Jordan) region or an aqueous solution prepared by dissolving Dead Sea minerals and salts in an aqueous medium which simulate such natural solution, namely having substantially identical parameters characteristic of that measured for the natural DSW, said parameters being salts content/concentrations, minerals content/concentrations, cations and anions content/concentrations, ratio of divalent cations to monovalent cations, and optionally also one or more of TDS (Total Dissolved Salt, w/v), soluble natural substances, and other parameters known to define or characterize natural DSW.
In some embodiments, the Dead Sea extract is the Dead Sea water which may be obtained directly from the Dead Sea filtered water substantially having the same salt content (a hypersaline concentration) as that of the unfiltered Dead Sea water, or Dead Sea water treated by any one or more of various other methods employed to e.g., remove organic matter and residual contaminants therefrom.
It is noted that the Dead Sea water is not sea water from a sea different from the Dead Sea but it rather specific to the Dead Sea water that are reach with salts and minerals e.g., as disclosed herein.
In some embodiments, the Dead Sea extract is an artificial aqueous solution simulating the content of DSW i.e., having substantially identical content as that of DSW.
In some embodiments, the Dead Sea extract is an aqueous solution having substantially identical salts content, minerals content, salts concentration and mineral concentrations as that of DSW.
In some embodiments, the Dead Sea extract is an aqueous solution having substantially identical salts content, minerals content, salts concentration, minerals concentrations, concentration of a particular cation or anion, ratio of divalent cations to monovalent cations, TDS, soluble natural substances and other parameters known to define or characterize natural DSW.
In some embodiments, the Dead Sea extract is an aqueous solution simulating the salts and minerals content of Dead Sea water. In some embodiments, the Dead Sea extract is an aqueous solution simulating the salt content (a hypersaline concentration) of DSW i.e., having salt content substantially identical to that of DSW.
In some embodiments, the Dead Sea extract is an aqueous solution simulating the mineral content of DSW i.e., having mineral content substantially identical to that of DSW.
In some embodiments, the Dead Sea extract is an aqueous solution simulating the salt content (a hypersaline concentration) and the mineral content of DSW i.e., having salt content substantially identical to that of DSW, mineral content substantially identical to that of DSW and ratio of divalent cations to monovalent cations substantially identical to that of DSW.
In some embodiments, the Dead Sea water having:
1. a specific density of 1.25-1.35 g/ml,
2. pH = 4.6-5.6 (at 25°C), and/or
3. less than 100 cfu/g of non-pathogenic microbes.
The Dead Sea water having the above physical characteristics is a concentrated extract of Dead Sea water comprising (among other metal salt ions) Ca +2 , Mg +2 , Na + and K + and high concentrations of anions such as CT and Br".
In some embodiments, the DSW is a clear colorless viscous liquid (at 25°C).
In some embodiments, the concentrations of these ions are, as assessed by a water analysis carried out by the Geological Survey of Israel:
Calcium (Ca +2 ): 35,000-40,000 mg/L
Chloride (CT): 320,000-370,000 mg/L
Magnesium (Mg +2 ): 92,000-95,000 mg/L
Sodium (Na + ): 1800-3200 mg/L
Potassium (K + ): 2,500 mg/L, and
Bromide (Bf): 10,000-12,000 mg/L.
Other minerals may also exist in the waters.
In some embodiments, the Dead Sea Water comprises:
Calcium (Ca +2 ): 35,000-40,000 mg/L
Chloride (CT): 320,000-370,000 mg/L
Magnesium (Mg +2 ): 92,000-95,000 mg/L Sodium (Na + ): 2400-3200 mg/L Potassium (K + ): 2,500 mg/L, and Bromide (Bf): 10,000-12,000 mg/L.
Other minerals may also exist in the waters.
In some embodiments, the Dead Sea Water comprises: Calcium (Ca +2 ): 5,000-10,000 mg/L Chloride (Cl’): 315,000-360,000 mg/L Magnesium (Mg +2 ): 100,000-150,000 mg/L Sodium (Na + ): 1800-2200 mg/L Potassium (K + ): 1,000-2,000 mg/L, and Bromide (Bf): 5,000-10,000 mg/L.
Other minerals may also exist in the waters.
In some further embodiments, the Dead Sea Water comprises: Calcium (Ca +2 ) 34,000 - 40,000 mg/L
Chloride (Cl’) 320,000 - 370,000 mg/ L
Magnesium (Mg +2 ) 90,000 - 95,000 mg/L
Potassium (K + ) 1,300 - 2,200 mg/L
Sodium (Na + ) I,500 - 2,800 mg/L
Bromide (Bf) I I,000 - 15,000 mg/L.
Other minerals may also exist in the waters.
In some embodiments, the Dead Sea Water comprises:
Calcium (Ca +2 ): 38,000 mg/L
Chloride (C1‘): 345,000 mg/L
Magnesium (Mg +2 ): 92,500 mg/L
Sodium (Na + ): 2000 mg/L
Strontium (Sr +2 ): 800 mg/L
Potassium (K + ): 1,400 mg/L, and Bromide (Bf): 11,500 mg/L.
Other minerals may also exist in the waters.
In some embodiments, the Dead Sea Water comprises:
Calcium (Ca +2 ): 38,000 mg/L
Chloride (C1‘): 345,000 mg/L
Magnesium (Mg +2 ): 92,500 mg/L Sodium (Na + ): 2000 mg/L
Strontium (Sr +2 ): 800 mg/L
Potassium (K + ): 1,400 mg/L, and Bromide (Bf): 11,500 mg/L.
Other minerals may also exist in the waters.
In some embodiments, the DSW is natural DSW which has undergone protreatment i.e., having been concentrated by allowing water to evaporate, for example through solar evaporation, thereafter reconstituted to afford a solution.
In some embodiments the Dead Sea extract is Dead Sea Water preparation commercially available as "Maris Sal" or “ Maris Aqua or "Aqua, Maris Sal" (AHAVA,
Israel) referred to herein below also as “Osmoter”.
The Osmoter is a concentrated Dead Sea water that has a high concentration of salts e.g., magnesium, calcium, strontium, bromine, boron and lithium which are characteristic Dead Sea minerals. The Osmoter has high ratio of divalent cations, mainly magnesium and calcium vs. monovalent cations, mainly potassium and sodium.
In some embodiments the ratio between the magnesium and calcium divalent cations to the potassium and sodium monovalent cations in the Osmoter is [92, 500mg/l+38,000mg/l]/[1400mg/l+2000mg/l]=130, 500/3400=38.38.
In some embodiments, the Osmoter is the product: Geological Survey - Ministry of National Infrastructures, State of Israel, especially for AHAVA-Dead Sea Laboratories CAS# INCI Monograph ID: 11089), also known as Dead Sea Works LTD.
In some embodiments, the Osmoter comprises the following ions: Mg +2 (92,500 mg/L), Ca +2 (38,000 mg/L), K + (1,400 mg/L), Na + (2,000 mg/L), Sr +2 (800 mg/L), Cl’ (345,000 mg/L) and Br’ (11,500 mg/L). Other minerals may also exist in the Osmoter.
In some embodiments, the Osmoter has the following composition:
Salt normality (N) Salt normality (N)
Na 0.118 (2.720 g/1) Rb 3.5 x 10' 6 (<3 x IO' 4 g/1)
K 0.054 (2.100 g/1) Sb <1.6 x 10' 7 (<2 x 10' 5 g/1)
Ca 0.873 (35.000 g/1) Sr 7.6 x 10' 3 (0.670 g/1)
Mg 3.815 (92.700 g/1) V <7.9 x 10' 5 (<0.004 g/1)
Ba 6.6 x 10' 5 (0.009 g/1) Th <8.6 x 10’ 8 (<2 x 10’ 5 g/1)
Cd <1.8 x 10' 7 (<2 x 10' 5 g/1) U <8.4 x 10’ 8 (<2 x 10’ 5 g/1)
Co <3.4 x 10' 5 (<0.002 g/1) Zn <3.06 x 10' 5 (<0.002 g/1) Cu <3.15 x 10' 5 (<0.004 g/1)
Cr <3.85 x IO' 4 (<0.02 g/1) Cl 9.75 (346 g/1)
Fe <3.58 x IO' 5 (<0.002 g/1) Br 0.175 (14 g/1)
Li 5.76 x IO' 3 (0.040 g/1) B 0.011 (0.120 g/1)
Mn 1.82 x IO' 4 (0.010 g/1) As 2.7 x IO' 5 (0.002 g/1)
Mo <1.04 x 10' 6 (<10‘ 4 g/1) I 6.30 x IO' 7 (8 x IO' 8 g/1)
Ni <3.4 x IO' 5 (<0.002 g/1) SiO2 <3.33 x IO' 4 (<0.02 g/1)
Pb <9.6 x 10' 8 (<2 x IO' 5 ) SiO4 <2.2 x IO' 3 (<0.2 g/1)
In some embodiments the ratio between the magnesium and calcium divalent cations to the potassium and sodium monovalent cations in the Dead Sea extract e.g.,
Dead Sea water, is between about 20 to about 55, inclusive. At time it is about 20.0, 21.0,
22.0, 23.0, 24.0, 25.0, 26.0, 27.0, 28.0, 29.0, 30.0, 31.0, 32.0, 33.0, 34.0, 35.0, 36.0, 37.0, 38.0, 39.0, 40.0, 41.0, 42.0, 43.0, 44.0, 45.0, 46.0, 47.0, 48.0, 49.0, 50.0, 51.0, 52.0, 53.0, 54.0 and about 55.0. In some embodiments said ratio is about 23.7, at times about 25.9, at times about 27.0, at times about 29.5, at times about 38.1, at times about 38.4, at times about 40.0, at time about 44.0, even at times about 53.6. Any value which is between any one of the above values is within the scope of the present disclosure.
In some embodiments the Dead Sea extract is Dead Sea mud.
In some embodiments the Dead Sea extract is typically an active fraction having by itself at least one attribute which may be enhanced in a combination with one or more of the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.01% (w/w). At time is it about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%. 0.08%, 0.09%, 0.10%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%,
0.16%, 0.17%. 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%,
0.27%. 0.28%, 0.29%, 0.30%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%.
0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%. 0.48%,
0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%. 0.58%, 0.59%,
0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%. 0.68%, 0.69%, 0.70%,
0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%. 0.78%, 0.79%, 0.80%, 0.81%
0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%. 0.88%, 0.89%, 0.90%, 0.91%, 0.92%,
0.93%, 0.94%, 0.95%, 0.96%, 0.97%. 0.98%, 0.99%, 1.00%, 1.10%, 1.10%, 1.11% 1.12%, 1.13%, 1.14%, 1.15%, 1.16%, 1.17%. 1.18%, 1.19%, 1.20%, 1.21%, 1.22%, 1.23%, 1.24%, 1.25%, 1.26%, 1.27%. 1.28%, 1.29%, 1.30%, 1.31%, 1.32%, 1.33%, 1.34%, 1.35%, 1.36%, 1.37%. 1.38%, 1.39%, 1.40%, 1.41%, 1.42%, 1.43%, 1.44%, 1.45%, 1.46%, 1.47%. 1.48%, 1.49%, 1.50%, 1.51%, 1.52%, 1.53%, 1.54%, 1.55%, 1.56%, 1.57%. 1.58%, 1.59%, 1.60%, 1.61%, 1.62%, 1.63%, 1.64%, 1.65%, 1.66%, 1.67%. 1.68%, 1.69%, 1.70%, 1.71%, 1.72%, 1.73%, 1.74%, 1.75%, 1.76%, 1.77%. 1.78%, 1.79%, 1.80%, 1.81%, 1.82%, 1.83%, 1.84%, 1.85%, 1.86%, 1.87%. 1.88%, 1.89%, 1.90%, 1.91%, 1.92%, 1.93%, 1.94%, 1.95%, 1.96%, 1.97%. 1.98%, 1.99%, 2.00%, 2.10%, 2.11%, 2.12%, 2.13%, 2.14%, 2.15%, 2.16%, 2.17%. 2.18%, 2.19%, 2.20%, 2.21%, 2.22%, 2.23%, 2.24%, 2.25%, 2.26%, 2.27%. 2.28%, 2.29%, 2.30%, 2.31%, 2.32%, 2.33%, 2.34%, 2.35%, 2.36%, 2.37%. 2.38%, 2.39%, 2.40%, 2.41%, 2.42%, 2.43%, 2.44%, 2.45%, 2.46%, 2.47%. 2.48%, 2.49%, 2.50%, 2.51%, 2.52%, 2.53%, 2.54%, 2.55%, 2.56%, 2.57%. 2.58%, 2.59%, 2.60%, 2.61%, 2.62%, 2.63%, 2.64%, 2.65%, 2.66%, 2.67%. 2.68%, 2.69%, 2.70%, 2.71%, 2.72%, 2.73%, 2.74%, 2.75%, 2.76%, 2.77%. 2.78%, 2.79%, 2.80%, 2.81%, 2.82%, 2.83%, 2.84%, 2.85%, 2.86%, 2.87%. 2.88%, 2.89%, 2.90%, 2.91%, 2.92%, 2.93%, 2.94%, 2.95%, 2.96%, 2.97%. 2.98%, 2.99%, 3.00%, 3.10%, 3.11%, 3.12%, 3.13%, 3.14%, 3.15%, 3.16%, 3.17%. 3.18%, 3.19%, 3.20%, 3.21%, 3.22%, 3.23%, 3.24%, 3.25%, 3.26%, 3.27%. 3.28%, 3.29%, 3.30%, 3.31%, 3.32%, 3.33%, 3.34%, 3.35%, 3.36%, 3.37%. 3.38%, 3.39%, 3.40%, 3.41%, 3.42%, 3.43%, 3.44%, 3.45%, 3.46%, 3.47%. 3.48%, 3.49%, 3.50%, 3.51%, 3.52%, 3.53%, 3.54%, 3.55%, 3.56%, 3.57%. 3.58%, 3.59%, 3.60%, 3.61%, 3.62%, 3.63%, 3.64%, 3.65%, 3.66%, 3.67%. 3.68%, 3.69%, 3.70%, 3.71%, 3.72%, 3.73%, 3.74%, 3.75%, 3.76%, 3.77%. 3.78%, 3.79%, 3.80%, 3.81%, 3.82%, 3.83%, 3.84%, 3.85%, 3.86%, 3.87%. 3.88%, 3.89%, 3.90%, 3.91%, 3.92%, 3.93%, 3.94%, 3.95%, 3.96%, 3.97%. 3.98%, 3.99%, 4.00%, 4.10%, 4.11%, 4.12%, 4.13%, 4.14%, 4.15%, 4.16%, 4.17%. 4.18%, 4.19%, 4.20%, 4.21%, 4.22%, 4.23%, 4.24%, 4.25%, 4.26%, 4.27%. 4.28%, 4.29%, 4.30%, 4.31%, 4.32%, 4.33%, 4.34%, 4.35%, 4.36%, 4.37%. 4.38%, 4.39%, 4.40%, 4.41%, 4.42%, 4.43%, 4.44%, 4.45%, 4.46%, 4.47%. 4.48%, 4.49%, 4.50%, 4.51%, 4.52%, 4.53%, 4.54%, 4.55%, 4.56%, 4.57%.
4.58%, 4.59%, 4.60%, 4.61%, 4.62%, 4.63%, 4.64%, 4.65%, 4.66%, 4.67%. 4.68%,
4.69%, 4.70%, 4.71%, 4.72%, 4.73%, 4.74%, 4.75%, 4.76%, 4.77%. 4.78%, 4.79%,
4.80%, 4.81%, 4.82%, 4.83%, 4.84%, 4.85%, 4.86%, 4.87%. 4.88%, 4.89%, 4.90%,
4.91%, 4.92%, 4.93%, 4.94%, 4.95%, 4.96%, 4.97%. 4.98%, 4.99% and about 5.00% (w/w). Any value which is between any one of the above values and/or any range between one or more of the above values is within the scope of the present disclosure.
It is noted that, in some embodiments, with respect to the concentrations of the various components of the kit of the invention (e.g., at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide), in some embodiments the concentrations are as detailed herein above and below. At times, the concentration of each of the component may be of higher value taking into consideration the mixing of the various components of the kit upon concomitant administration that may result with dilution of the components (e.g., 3 times dilution). Thus, in some embodiments the concentrations provided herein above and below with respect to the components of the kit of the invention are envisaged as the concentrations after the dilution thereof upon mixing via concomitant application. In some other embodiments the concentrations provided herein above and below with respect to the components of the kit of the invention are at least 2 times, at times at least 3 times, event at times at least 5 times higher than the concentrations detailed herein above and below [(e.g., 5.0 % times 2, 3 or 5 i.e., 10 %, 15 % or 25 %, respectively), (e.g., 4.0 % times 2, 3 or 5 i.e., 8.0 %, 12.0 % or 20.0 %, respectively) (e.g., 3.0 % times 2, 3 or 5 i.e., 6.0 %, 9.0 % or 12.0%, respectively) (e.g., 2.5 % times 2, 3 or 5 i.e., 5.0%, 7.5 % or 12.5%, respectively), and upon concomitant topical application the dilution thereof results with a value as detailed herein above and below.
In some embodiments the components of the kit of the invention (e.g., at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide) are present in the kit at a concentration as detailed herein above and below given as w/w % of the total weight of the formulation of each component thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 5.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 4.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 3.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 2.50% (w/w), inclusive the end points values.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 2.40% (w/w), at times between about 0.01% to about 2.00% (w/w), at times between about 0.01% to about 1.50% (w/w), at times between about 0.01% to about 1.00% (w/w), at times between about 0.05% to about 2.40% (w/w), at times between about 0.05% to about 2.00% (w/w), at times between about 0.05% to about 1.50% (w/w), at times between about 0.05% to about 1.00% (w/w), at times between about 0.10% to about 2.40% (w/w), at times between about 0.10% to about 2.00% (w/w), at times between about 0.10% to about 1.50% (w/w), at times between about 0.10% to about 1.00% (w/w), at times between about 0.20% to about 2.40% (w/w), at times between about 0.20% to about 2.00% (w/w), at times between about 0.20% to about 1.50% (w/w), at times between about 0.20% to about 1.00% (w/w), at times between about 0.30% to about 2.40% (w/w), at times between about 0.30% to about 2.00% (w/w), at times between about 0.30% to about 1.50% (w/w), at times between about 0.30% to about 1.00% (w/w), at times between about 0.40% to about 2.40% (w/w), at times between about 0.40% to about 2.00% (w/w), at times between about 0.40% to about 1.50% (w/w), at times between about 0.40% to about 1.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.5% to about 2.40% (w/w), at times between about 0.5% to about 2.00% (w/w), at times between about 0.5% to about 1.50% (w/w), at times between about 0.5% to about 1.00% (w/w), inclusive the end points values. In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.1% (w/w) inclusive.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.2% (w/w) inclusive.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.3% (w/w) inclusive.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.4% (w/w) inclusive.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.5% (w/w) inclusive.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.1 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.2 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.3 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.4 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.5 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.6 % (w/w). In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.7 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.8 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.9 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 1.0 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 1.5 % (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 2.0 % (w/w).
The terms "plan extract", “ extract of the plant or any lingual variations thereof are used herein in their broadest definition. The terms relate to a fraction obtained from one or more parts of the plant [e.g., roots, leaves, stems, seeds, fruits, flowers, shoot and barks (peel)] or from the whole plant. The extract is typically an active fraction having by itself at least one attribute which may be enhanced in the combination according to the invention.
In some embodiments the Rumex plant extract is an extract obtained according to known procedures or is a commercially available extract, e.g., as disclosed. The extract may be a pure (neat) extract, or an extract formulated along with a predetermined amount of one or more additives such as a stabilizer, an adjuvant, an excipient, a diluent, a carrier, a filler, an antioxidant or any other inert additive. In some embodiments the additive may be any one of the above noted additives or any combination thereof.
The origin of the at least one Rumex plant extract employed in the compositions/combinations/formulations/kits of the present invention may vary. In some embodiments the Rumex plant from which the extract is obtained may be one native to the designated origin or otherwise grown outside of this origin region, naturally, e.g., due to natural invasion, or for commercial purposes, horticulture purposes or for any other reason.
In some embodiments the Rumex extract is derived from plants of the Rumex genus which is found in Canadian Prairies.
In some embodiments the Rumex extract is derived from plants of the Rumex genus which is found in Western North America.
In some embodiments the at least one Rumex plant extract is a Rumex occidentalis plant extract.
Rumex occidentalis is a flowering plant species belonging to the family Polygonaceae. It is also known as western dock.
In some embodiments the Rumex occidentalis extract is derived from plants found in Western North America.
In some embodiments the at least one Rumex plant extract is a whole plant Rumex occidentalis extract.
In some embodiments the at least one Rumex plant extract is a whole plant Rumex occidentalis, Polygonaceae, extract.
In some embodiments the Rumex plant extract may be obtained commercially.
In some embodiments the Rumex plant extract is the commercially available Tyrostat™ extract, by Lucas Meyer Cosmetics (IFF), extracted from the northern Canadian Prairies plant Rumex Occidentalis .
Two grades of Tyrostat™ extract are available: Tyrostat™ 09 (regular version) and Tyrostat™ 11 (with ascorbic acid).
In some embodiments the Rumex plant extract is the commercially available Tyrostat™ 09 Rumex occidentalis extract having the following product description: INCI NAME TYROSTATTM-09
Water (1) (and) Glycerin (2) (and) Rumex Occidentalis Extract (3)
CAS TYROSTATTM-09
7732-18-5 (1), 56-81-5 (2), - (3)
EINECS TYROSTATTM-09
231-791-2 (1), 200-289-5 (2), - (3) In some embodiments the Rumex plant extract is the commercially available Tyrostat™ 11 Rumex occidentalis extract, having the following product descreption: INCI name - TYROSTAT™- 11
Water (1) (and) Glycerin (1,2,3-Propanetriol) (2) (and) Rumex Occidentalis Extract (3) (and) Ascorbic Acid (4).
CAS - TYROSTAT™- 11
7732-18-5 (1), 56-81-5 (2), - (3), 50-81-7 (4)
EINECS TYROSTAT™-11
231-791-2 (1) 200-289-5 (2), - (3), 200-066-2 (4).
Appearance: Orange-red, transparent to slightly cloudy solution with a color stable.
In some embodiments the Rumex extract (e.g., Rumex Occidentalis extract) may be formulated with at least one additive. In some embodiments the additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any combination thereof. In some embodiments the additive is an inert additive.
In some embodiments the Rumex extract (e.g., Rumex Occidentalis extract) may be formulated along with a predetermined amount of at least one additive such as a stabilizer, diluent, carrier, filler, antioxidant or any other inert additive.
In some embodiments the additive is Glycerin and/or Ascorbic Acid.
In some embodiments the additive may be any one of the above noted additives or any combination thereof.
In some embodiments the additive may be a non-natural additive.
In some embodiments the additive may be a natural additive.
In some embodiments the Rumex extract (e.g., Rumex Occidentalis extract) may further comprise at least one stabilizer.
In some embodiments the stabilizer may be a non-natural stabilizer.
In some embodiments the stabilizer may be a natural stabilizer.
In some embodiments the Rumex extract is an aqueous extract.
In some embodiments the Rumex extract is a water-soluble extract.
In some embodiments the Rumex extract is an oil extract.
In some embodiments the Rumex extract (e.g., Rumex Occidentalis extract) is as herein described and exemplified.
In some embodiments the Rumex plant extract e.g., Rumex Occidentalis is typically an active fraction having by itself at least one attribute which may be enhanced in a combination with one or more of the at least one Dead Sea extract and the at least one Thioredoxin polypeptide.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.01% (w/w). At time is it about 0.01%, 0.02%,
0.03%, 0.04%, 0.05%, 0.06%, 0.07%. 0.08%, 0.09%, 0.10%, 0.11%, 0.12%, 0.13%,
0.14%, 0.15%, 0.16%, 0.17%. 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%,
0.25%, 0.26%, 0.27%. 0.28%, 0.29%, 0.30%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%,
0.36%, 0.37%. 0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%,
0.47%. 0.48%, 0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%.
0.58%, 0.59%, 0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%. 0.68%,
0.69%, 0.70%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%. 0.78%, 0.79%,
0.80%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%. 0.88%, 0.89%, 0.90%,
0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%. 0.98%, 0.99%, 1.00%, 1.10%,
1.10%, 1.11%, 1.12%, 1.13%, 1.14%, 1.15%, 1.16%, 1.17%. 1.18%, 1.19%, 1.20%,
1.21%, 1.22%, 1.23%, 1.24%, 1.25%, 1.26%, 1.27%. 1.28%, 1.29%, 1.30%, 1.31%,
1.32%, 1.33%, 1.34%, 1.35%, 1.36%, 1.37%. 1.38%, 1.39%, 1.40%, 1.41%, 1.42%,
1.43%, 1.44%, 1.45%, 1.46%, 1.47%. 1.48%, 1.49%, 1.50%, 1.51%, 1.52%, 1.53%,
1.54%, 1.55%, 1.56%, 1.57%. 1.58%, 1.59%, 1.60%, 1.61%, 1.62%, 1.63%, 1.64%,
1.65%, 1.66%, 1.67%. 1.68%, 1.69%, 1.70%, 1.71%, 1.72%, 1.73%, 1.74%, 1.75%,
1.76%, 1.77%. 1.78%, 1.79%, 1.80%, 1.81%, 1.82%, 1.83%, 1.84%, 1.85%, 1.86%,
1.87%. 1.88%, 1.89%, 1.90%, 1.91%, 1.92%, 1.93%, 1.94%, 1.95%, 1.96%, 1.97%.
1.98%, 1.99%, 2.00%, 2.10%, 2.11%, 2.12%, 2.13%, 2.14%, 2.15%, 2.16%, 2.17%.
2.18%, 2.19%, 2.20%, 2.21%, 2.22%, 2.23%, 2.24%, 2.25%, 2.26%, 2.27%. 2.28%,
2.29%, 2.30%, 2.31%, 2.32%, 2.33%, 2.34%, 2.35%, 2.36%, 2.37%. 2.38%, 2.39%,
2.40%, 2.41%, 2.42%, 2.43%, 2.44%, 2.45%, 2.46%, 2.47%. 2.48%, 2.49%, 2.50%,
2.51%, 2.52%, 2.53%, 2.54%, 2.55%, 2.56%, 2.57%. 2.58%, 2.59%, 2.60%, 2.61%,
2.62%, 2.63%, 2.64%, 2.65%, 2.66%, 2.67%. 2.68%, 2.69%, 2.70%, 2.71%, 2.72%,
2.73%, 2.74%, 2.75%, 2.76%, 2.77%. 2.78%, 2.79%, 2.80%, 2.81%, 2.82%, 2.83%,
2.84%, 2.85%, 2.86%, 2.87%. 2.88%, 2.89%, 2.90%, 2.91%, 2.92%, 2.93%, 2.94%,
2.95%, 2.96%, 2.97%. 2.98%, 2.99%, 3.00%, 3.10%, 3.11%, 3.12%, 3.13%, 3.14%,
3.15%, 3.16%, 3.17%. 3.18%, 3.19%, 3.20%, 3.21%, 3.22%, 3.23%, 3.24%, 3.25%,
3.26%, 3.27%. 3.28%, 3.29%, 3.30%, 3.31%, 3.32%, 3.33%, 3.34%, 3.35%, 3.36%, 3.37%. 3.38%, 3.39%, 3.40%, 3.41%, 3.42%, 3.43%, 3.44%, 3.45%, 3.46%, 3.47%.
3.48%, 3.49%, 3.50%, 3.51%, 3.52%, 3.53%, 3.54%, 3.55%, 3.56%, 3.57%. 3.58%,
3.59%, 3.60%, 3.61%, 3.62%, 3.63%, 3.64%, 3.65%, 3.66%, 3.67%. 3.68%, 3.69%,
3.70%, 3.71%, 3.72%, 3.73%, 3.74%, 3.75%, 3.76%, 3.77%. 3.78%, 3.79%, 3.80%,
3.81%, 3.82%, 3.83%, 3.84%, 3.85%, 3.86%, 3.87%. 3.88%, 3.89%, 3.90%, 3.91%,
3.92%, 3.93%, 3.94%, 3.95%, 3.96%, 3.97%. 3.98%, 3.99%, 4.00%, 4.10%, 4.11%,
4.12%, 4.13%, 4.14%, 4.15%, 4.16%, 4.17%. 4.18%, 4.19%, 4.20%, 4.21%, 4.22%,
4.23%, 4.24%, 4.25%, 4.26%, 4.27%. 4.28%, 4.29%, 4.30%, 4.31%, 4.32%, 4.33%,
4.34%, 4.35%, 4.36%, 4.37%. 4.38%, 4.39%, 4.40%, 4.41%, 4.42%, 4.43%, 4.44%,
4.45%, 4.46%, 4.47%. 4.48%, 4.49%, 4.50%, 4.51%, 4.52%, 4.53%, 4.54%, 4.55%,
4.56%, 4.57%. 4.58%, 4.59%, 4.60%, 4.61%, 4.62%, 4.63%, 4.64%, 4.65%, 4.66%,
4.67%. 4.68%, 4.69%, 4.70%, 4.71%, 4.72%, 4.73%, 4.74%, 4.75%, 4.76%, 4.77%.
4.78%, 4.79%, 4.80%, 4.81%, 4.82%, 4.83%, 4.84%, 4.85%, 4.86%, 4.87%. 4.88%,
4.89%, 4.90%, 4.91%, 4.92%, 4.93%, 4.94%, 4.95%, 4.96%, 4.97%. 4.98%, 4.99% and and about 5.00% (w/w). Any value which is between any one of the above values and/or any range between one or more of the above values is within the scope of the present disclosure.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 5.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 4.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 3.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 3.00% (w/w), at times about 0.01% to about 2.50% (w/w), at times between about 0.01% to about 2.00% (w/w), at times between about 0.01% to about 1.50% (w/w), at times between about 0.01% to about 1.00% (w/w), at times between about 0.05% to about 3.00% (w/w), at times between about 0.05% to about 2.50% (w/w), at times between about 0.05% to about 2.00% (w/w), at times between about 0.05% to about 1.50% (w/w), at times between about 0.05% to about 1.00% (w/w), at times between about 0.10% to about 3.00% (w/w), at times between about 0.10% to about 2.50% (w/w), at times between about 0.10% to about 2.00% (w/w), at times between about 0.10% to about 1.50% (w/w), at times between about 0.10% to about 1.00% (w/w), at times between about 0.20% to about 3.00% (w/w), at times between about 0.20% to about 2.50% (w/w), at times between about 0.20% to about 2.00% (w/w), at times between about 0.20% to about 1.50% (w/w), at times between about 0.20% to about 1.00% (w/w), at times between about 0.25% to about 3.00% (w/w), at times between about 0.25% to about 2.50% (w/w), at times between about 0.25% to about 2.00% (w/w), at times between about 0.25% to about 1.50% (w/w), at times between about 0.25% to about 1.00% (w/w), at times between about 0.30% to about 3.00% (w/w), at times between about 0.30% to about 2.50% (w/w), at times between about 0.30% to about 2.00% (w/w), at times between about 0.30% to about 1.50% (w/w), at times between about 0.30% to about 1.00% (w/w), at times between about 0.40% to about 3.00% (w/w), at times between about 0.40% to about 2.50% (w/w), at times between about 0.40% to about 2.00% (w/w), at times between about 0.40% to about 1.50% (w/w), at times between about 0.40% to about 1.00% (w/w), at times between about 0.50% to about 3.00% (w/w), at times between about 0.50% to about 2.50% (w/w), at times between about 0.50% to about 2.00% (w/w), at times between about 0.50% to about 1.50% (w/w), at times between about 0.50% to about 1.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.05 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.10 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.15 % (w/w) inclusive. In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.20 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.25 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.50 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 1.00 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 1.50 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 2.00 % (w/w) inclusive.
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.05 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.10 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.15 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.20 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.25 % (w/w). In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.50 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.60 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.70 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.80 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.90 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 1.00 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 1.50 % (w/w).
In some embodiments the concentration of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 2.00 % (w/w).
In some embodiments the at least one Thioredoxin polypeptide is a protein.
In some embodiments the at least one Thioredoxin polypeptide is a protein, in particular, from a class of small redox proteins.
The origin of the at least one Thioredoxin polypeptide (e.g., protein) employed in the compositions/combinations/formulations/kits of the present invention may vary.
In some embodiments the Thioredoxin polypeptide (e.g., protein) is a human Thioredoxin.
In some embodiments the at least one Thioredoxin protein is a human Thioredoxin e.g., encoded by TXN and TXN2 genes. In some embodiments the at least one Thioredoxin protein is a plant Thioredoxin.
In some embodiments the Thioredoxin polypeptide (e.g., protein) is a plant Thioredoxin.
In some embodiments the Thioredoxin polypeptide (e.g., protein) may be obtained commercially.
In some embodiments the plant Thioredoxin is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana).
In some embodiments the Thioredoxin polypeptide (e.g., protein) is the plant- Thioredoxin-1 (referred to herein also as plant-TRX- ).
In some embodiments the plant- Thioredoxin-1 is Oligopeptide-4 (INCI).
In some embodiments the plant-Thioredoxin-1 is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant.
In some embodiments the Thioredoxin protein/polypeptide may be produced utilizing wild plants, whole non-GM plants, as bio-factories: the synthetic gene cloning may comprise plant seeding, plant cultivation and vegetalized plasmid followed by mechanical introduction of synthetic transcript, scale-up of expression system and harvesting, plant (e.g., leave extract or any other part thereof), isolation, purification and analysis.
In some embodiments the plant-Thioredoxin-1 is a synthetic protein obtainable (or obtained) by gene cloning utilizing the plant Nicotiana benthamiana.
In some embodiments the plant-Thioredoxin-1 is the commercially available PUREOXIN™ (by LipoTrue).
In some embodiments the Thioredoxin polypeptide (e.g., protein) is water soluble.
In some embodiments the Thioredoxin polypeptide is of the SEQ ID NO. 1.
In some embodiments the Thioredoxin polypeptide is of the SEQ ID NO. 2.
The term polypeptide " as used herein refers to amino acid residues, connected by peptide bonds. A polypeptide sequence is generally reported from the N-terminal end containing free amino group to the C-terminal end containing free carboxyl group and may include any polymeric chain of amino acids. In some embodiments, a polypeptide has an amino acid sequence that occurs in nature. In some embodiments, a polypeptide has an amino acid sequence that does not occur in nature. In some embodiments, a polypeptide has an amino acid sequence that contains portions that occur in nature separately from one another (i.e., from two or more different organisms, for example, human and non-human portions). In some embodiments, a polypeptide has an amino acid sequence that is engineered in that it is designed and/or produced through action of the hand of man. For example, the amino acid sequence may comprise a conventional tag that is used for purification of proteins from host organisms. In some embodiments the amino acid sequence may comprise one or more conventional tags e.g. His-Tag etc. In some embodiments the conventional tag, e.g. His-Tag, may be located at the N- or C- terminus of the polypeptide.
More specifically, “Amino acid sequence” or “peptide sequence” is the order in which amino acid residues connected by peptide bonds, lie in the chain in peptides and proteins. The sequence is generally reported from the N-terminal end containing free amino group to the C-terminal end containing amide. Amino acid sequence is often called peptide, protein sequence if it represents the primary structure of a protein, however one must discern between the terms “Amino acid sequence” or “peptide sequence” and “protein”, since a protein is generally defined as an amino acid sequence folded into a specific three-dimensional configuration and that had typically undergone post- translational modifications, such as phosphorylation, acetylation, glycosylation, manosylation, amidation, carboxylation, sulfhydryl bond formation, cleavage and the like.
It should be appreciated that the invention encompasses the use of any variant or derivative of the polypeptides of the invention and any polypeptides that are substantially identical or homologue to the polypeptides of the invention. The term "derivative" is used to define amino acid sequences (polypeptide), with any insertions, deletions, substitutions and modifications to the amino acid sequences (polypeptide) that do not alter the activity of the original polypeptides. By the term “derivative” it is also referred to homologues, variants and analogues thereof. Proteins orthologs or homologues having a sequence homology or identity to the protein in accordance with the invention, may share at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher, specifically as compared to the entire sequence of the protein in accordance with the invention, for example, any of the proteins that comprise the amino acid sequence as denoted by SEQ ID NO. 1 and/or SEQ ID NO. 2. Specifically, homologs that comprise or consist of an amino acid sequence that is identical in at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher to SEQ ID NO. 1 and/or SEQ ID NO. 2
In some embodiments, derivatives refer to polypeptides, which differ from the polypeptides specifically defined in the present invention by insertions, deletions or substitutions of amino acid residues. It should be appreciated that by the terms insertion/*" . deletion/* ' or substitution/*" . as used herein it is meant any addition, deletion or replacement, respectively, of amino acid residues to the polypeptides disclosed by the invention, of between 1 to 50 amino acid residues, between 20 to 1 amino acid residues, and specifically, between 1 to 10 amino acid residues. More particularly, insertion/s, deletion/s or substitution/s may be of any one of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. It should be noted that the insertion/s, deletion/s or substitution/s encompassed by the invention may occur in any position of the modified peptide, as well as in any of the N' or C termini thereof.
With respect to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a “conservatively modified variant where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants and interspecies homologues of the invention.
For example, substitutions may be made wherein an aliphatic amino acid (G, A, I, L, or V) is substituted with another member of the group, or substitution such as the substitution of one polar residue for another, such as arginine for lysine, glutamic for aspartic acid, or glutamine for asparagine. Each of the following eight groups contains other exemplary amino acids that are conservative substitutions for one another:
1) Alanine (A), Glycine (G);
2) Aspartic acid (D), Glutamic acid (E);
3) Asparagine (N), Glutamine (Q);
4) Arginine (R), Lysine (K);
5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V);
6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W);
7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M).
Thus, in some embodiments, the invention relates to polypeptides or any derivatives thereof, specifically a derivative that comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more conservative substitutions to the amino acid sequences as denoted by SEQ ID NO. 1 and/or SEQ ID NO. 2 More specifically, amino acid substitutions ' are the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, i.e., conservative amino acid replacements. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. For example, nonpolar hydrophobic amino acids are selected from the group consisting of Valine (V), Isoleucine (I), Leucine (L), Methionine (M), Phenylalanine (F), Tryptophan (W), Cysteine (C), Alanine (A), Tyrosine (Y), Histidine (H), Threonine (T), Serine (S), Proline (P), Glycine (G), Arginine (R) and Lysine (K); “polar” amino acids are selected from the group consisting of Arginine (R), Lysine (K), Aspartic acid (D), Glutamic acid (E), Asparagine (N), Glutamine (Q); “positively charged” amino acids are selected form the group consisting of Arginine (R), Lysine (K) and Histidine (H) and wherein “acidic” amino acids are selected from the group consisting of Aspartic acid (D), Asparagine (N), Glutamic acid (E) and Glutamine (Q).
Variants of the polypeptides of the invention may have at least 80% sequence similarity or identity, often at least 85% sequence similarity or identity, 90% sequence similarity or identity, or at least 95%, 96%, 97%, 98%, or 99% sequence similarity or identity at the amino acid level, with the protein of interest, such as the various polypeptides of the invention.
In some embodiments the at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1.
In some embodiments the at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2.
In some embodiments the at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1, each of which optionally further comprises a conventional tag e.g., His-Tag.
In some embodiments the at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2, each of which optionally further comprises a conventional tag e.g., His-Tag. In some embodiments the Thioredoxin polypeptide (e.g., protein) may be formulated along with a predetermined amount of at least one additive such as a stabilizer, diluent, carrier, filler, antioxidant or any other inert additive.
In some embodiments the Thioredoxin polypeptide (e.g., protein) may be formulated with at least one additive. In some embodiments the additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any combination thereof. In some embodiments the additive is an inert additive.
In some embodiments the additive may be any one of the above noted additives or any combination thereof.
In some embodiments the additive may be a non-natural additive.
In some embodiments the additive may be a natural additive.
In some embodiments Thioredoxin polypeptide (e.g., protein) may further comprises at least one stabilizer.
In some embodiments the stabilizer may be a non-natural stabilizer.
In some embodiments the stabilizer may be a natural stabilizer.
In some embodiments the Thioredoxin polypeptide (e.g., protein) is as herein described and exemplified.
In some embodiments the Thioredoxin polypeptide (e.g., protein) is typically an active fraction having by itself at least one attribute which may be enhanced in a combination with one or more of the at least one Dead Sea extract and the at least one
Rumex plant extract e.g., Rumex Occidentalis.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.01% (w/w). At time is it about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%. 0.08%, 0.09%, 0.10%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%,
0.16%, 0.17%. 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%,
0.27%. 0.28%, 0.29%, 0.30%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%.
0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%. 0.48%,
0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%. 0.58%, 0.59%,
0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%. 0.68%, 0.69%, 0.70%,
0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%. 0.78%, 0.79%, 0.80%, 0.81%
0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%. 0.88%, 0.89%, 0.90%, 0.91%, 0.92%,
0.93%, 0.94%, 0.95%, 0.96%, 0.97%. 0.98%, 0.99%, 1.00%, 1.10%, 1.10%, 1.11% 1.12%, 1.13%, 1.14%, 1.15%, 1.16%, 1.17%. 1.18%, 1.19%, 1.20%, 1.21%, 1.22%, 1.23%, 1.24%, 1.25%, 1.26%, 1.27%. 1.28%, 1.29%, 1.30%, 1.31%, 1.32%, 1.33%, 1.34%, 1.35%, 1.36%, 1.37%. 1.38%, 1.39%, 1.40%, 1.41%, 1.42%, 1.43%, 1.44%, 1.45%, 1.46%, 1.47%. 1.48%, 1.49%, 1.50%, 1.51%, 1.52%, 1.53%, 1.54%, 1.55%, 1.56%, 1.57%. 1.58%, 1.59%, 1.60%, 1.61%, 1.62%, 1.63%, 1.64%, 1.65%, 1.66%, 1.67%. 1.68%, 1.69%, 1.70%, 1.71%, 1.72%, 1.73%, 1.74%, 1.75%, 1.76%, 1.77%. 1.78%, 1.79%, 1.80%, 1.81%, 1.82%, 1.83%, 1.84%, 1.85%, 1.86%, 1.87%. 1.88%, 1.89%, 1.90%, 1.91%, 1.92%, 1.93%, 1.94%, 1.95%, 1.96%, 1.97%. 1.98%, 1.99%, 2.00%, 2.10%, 2.11%, 2.12%, 2.13%, 2.14%, 2.15%, 2.16%, 2.17%. 2.18%, 2.19%, 2.20%, 2.21%, 2.22%, 2.23%, 2.24%, 2.25%, 2.26%, 2.27%. 2.28%, 2.29%, 2.30%, 2.31%, 2.32%, 2.33%, 2.34%, 2.35%, 2.36%, 2.37%. 2.38%, 2.39%, 2.40%, 2.41%, 2.42%, 2.43%, 2.44%, 2.45%, 2.46%, 2.47%. 2.48%, 2.49%, 2.50%, 2.51%, 2.52%, 2.53%, 2.54%, 2.55%, 2.56%, 2.57%. 2.58%, 2.59%, 2.60%, 2.61%, 2.62%, 2.63%, 2.64%, 2.65%, 2.66%, 2.67%. 2.68%, 2.69%, 2.70%, 2.71%, 2.72%, 2.73%, 2.74%, 2.75%, 2.76%, 2.77%. 2.78%, 2.79%, 2.80%, 2.81%, 2.82%, 2.83%, 2.84%, 2.85%, 2.86%, 2.87%. 2.88%, 2.89%, 2.90%, 2.91%, 2.92%, 2.93%, 2.94%, 2.95%, 2.96%, 2.97%. 2.98%, 2.99%, 3.00%, 3.10%, 3.11%, 3.12%, 3.13%, 3.14%, 3.15%, 3.16%, 3.17%. 3.18%, 3.19%, 3.20%, 3.21%, 3.22%, 3.23%, 3.24%, 3.25%, 3.26%, 3.27%. 3.28%, 3.29%, 3.30%, 3.31%, 3.32%, 3.33%, 3.34%, 3.35%, 3.36%, 3.37%. 3.38%, 3.39%, 3.40%, 3.41%, 3.42%, 3.43%, 3.44%, 3.45%, 3.46%, 3.47%. 3.48%, 3.49%, 3.50%, 3.51%, 3.52%, 3.53%, 3.54%, 3.55%, 3.56%, 3.57%. 3.58%, 3.59%, 3.60%, 3.61%, 3.62%, 3.63%, 3.64%, 3.65%, 3.66%, 3.67%. 3.68%, 3.69%, 3.70%, 3.71%, 3.72%, 3.73%, 3.74%, 3.75%, 3.76%, 3.77%. 3.78%, 3.79%, 3.80%, 3.81%, 3.82%, 3.83%, 3.84%, 3.85%, 3.86%, 3.87%. 3.88%, 3.89%, 3.90%, 3.91%, 3.92%, 3.93%, 3.94%, 3.95%, 3.96%, 3.97%. 3.98%, 3.99%, 4.00%, 4.10%, 4.11%, 4.12%, 4.13%, 4.14%, 4.15%, 4.16%, 4.17%. 4.18%, 4.19%, 4.20%, 4.21%, 4.22%, 4.23%, 4.24%, 4.25%, 4.26%, 4.27%. 4.28%, 4.29%, 4.30%, 4.31%, 4.32%, 4.33%, 4.34%, 4.35%, 4.36%, 4.37%. 4.38%, 4.39%, 4.40%, 4.41%, 4.42%, 4.43%, 4.44%, 4.45%, 4.46%, 4.47%. 4.48%, 4.49%, 4.50%, 4.51%, 4.52%, 4.53%, 4.54%, 4.55%, 4.56%, 4.57%.
4.58%, 4.59%, 4.60%, 4.61%, 4.62%, 4.63%, 4.64%, 4.65%, 4.66%, 4.67%. 4.68%,
4.69%, 4.70%, 4.71%, 4.72%, 4.73%, 4.74%, 4.75%, 4.76%, 4.77%. 4.78%, 4.79%,
4.80%, 4.81%, 4.82%, 4.83%, 4.84%, 4.85%, 4.86%, 4.87%. 4.88%, 4.89%, 4.90%,
4.91%, 4.92%, 4.93%, 4.94%, 4.95%, 4.96%, 4.97%. 4.98%, 4.99% and about 5.00% (w/w). Any value which is between any one of the above values and/or any range between one or more of the above values is within the scope of the present disclosure.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 5.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 4.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 3.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.01% to about 4.00% (w/w), at times about 0.01% to about 3.50% (w/w), at times about 0.01% to about 3.00% (w/w), at times about 0.01% to about 2.50% (w/w), at times between about 0.01% to about 2.00% (w/w), at times between about 0.01% to about 1.50% (w/w), at times between about 0.01% to about 1.00% (w/w), at times between about 0.05% to about 4.00% (w/w), at times between about 0.05% to about 3.50% (w/w), at times between about 0.05% to about 3.00% (w/w), at times between about 0.05% to about 2.50% (w/w), at times between about 0.05% to about 2.00% (w/w), at times between about 0.05% to about 1.50% (w/w), at times between about 0.05% to about 1.00% (w/w), at times between about 0.10% to about 4.00% (w/w), at times between about 0.10% to about 3.50% (w/w), at times between about 0.10% to about 3.00% (w/w), at times between about 0.10% to about 2.50% (w/w), at times between about 0.10% to about 2.00% (w/w), at times between about 0.10% to about 1.50% (w/w), at times between about 0.10% to about 1.00% (w/w), at times between about 0.20% to about 4.00% (w/w), at times between about 0.20% to about 3.50% (w/w), at times between about 0.20% to about 3.00% (w/w), at times between about 0.20% to about 2.50% (w/w), at times between about 0.20% to about 2.00% (w/w), at times between about 0.20% to about 1.50% (w/w), at times between about 0.20% to about 1.00% (w/w), at times between about 0.25% to about 4.00% (w/w), at times between about 0.25% to about 3.50% (w/w), at times between about 0.25% to about 3.00% (w/w), at times between about 0.25% to about 2.50% (w/w), at times between about 0.25% to about 2.00% (w/w), at times between about 0.25% to about 1.50% (w/w), at times between about 0.25% to about 1.00% (w/w), at times between about 0.30% to about 4.00% (w/w), at times between about 0.30% to about 3.50% (w/w), at times between about 0.30% to about 3.00% (w/w), at times between about 0.30% to about 2.50% (w/w), at times between about 0.30% to about 2.00% (w/w), at times between about 0.30% to about 1.50% (w/w), at times between about 0.30% to about 1.00% (w/w), at times between about 0.40% to about 4.00% (w/w), at times between about 0.40% to about 3.50% (w/w), at times between about 0.40% to about 3.00% (w/w), at times between about 0.40% to about 2.50% (w/w), at times between about 0.40% to about 2.00% (w/w), at times between about 0.40% to about 1.50% (w/w), at times between about 0.40% to about 1.00% (w/w), at times between about 0.50% to about 4.00% (w/w), at times between about 0.50% to about 3.50% (w/w), at times between about 0.50% to about 3.00% (w/w), at times between about 0.50% to about 2.50% (w/w), at times between about 0.50% to about 2.00% (w/w), at times between about 0.50% to about 1.50% (w/w), at times between about 0.50% to about 1.00% (w/w), at times between about 0.60% to about 4.00% (w/w), at times between about 0.60% to about 3.50% (w/w), at times between about 0.60% to about 3.00% (w/w), at times between about 0.60% to about 2.50% (w/w), at times between about 0.60% to about 2.00% (w/w), at times between about 0.60% to about 1.50% (w/w), at times between about 0.60% to about 1.00% (w/w), at times between about 0.70% to about 4.00% (w/w), at times between about 0.70% to about 3.50% (w/w), at times between about 0.70% to about 3.00% (w/w), at times between about 0.70% to about 2.50% (w/w), at times between about 0.70% to about 2.00% (w/w), at times between about 0.70% to about 1.50% (w/w), at times between about 0.70% to about 1.00% (w/w), at times between about 0.60% to about 4.00% (w/w), at times between about 0.80% to about 3.50% (w/w), at times between about 0.80% to about 3.00% (w/w), at times between about 0.80% to about 2.50% (w/w), at times between about 0.80% to about 2.00% (w/w), at times between about 0.80% to about 1.50% (w/w), at times between about 0.80% to about 1.00% (w/w), at times between about 0.90% to about 4.00% (w/w), at times between about 0.90% to about 3.50% (w/w), at times between about 0.90% to about 3.00% (w/w), at times between about 0.90% to about 2.50% (w/w), at times between about 0.90% to about 2.00% (w/w), at times between about 0.90% to about 1.50% (w/w), at times between about 1.00% to about 4.00% (w/w), at times between about 1.00% to about 3.50% (w/w), at times between about 1.00% to about 3.00% (w/w), at times between about 1.00% to about 2.50% (w/w), at times between about 1.00% to about 2.00% (w/w), at times between about 1.00% to about 1.50% (w/w), at times between about 1.25% to about 4.00% (w/w), at times between about 1.25% to about 3.50% (w/w), at times between about 1.25% to about 3.00% (w/w), at times between about 1.25% to about 2.50% (w/w), at times between about 1.25% to about 2.00% (w/w), at times between about 1.50% to about 4.00% (w/w), at times between about 1.50% to about 3.50% (w/w), at times between about 1.50% to about 3.00% (w/w), at times between about 1.50% to about 2.50% (w/w), at times between about 1.50% to about 2.00% (w/w), inclusive the end points values.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.05 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.10 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.15 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.20 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.25 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.50 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 1.00 % (w/w), inclusive. In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 1.50 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 2.00 % (w/w), inclusive.
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.05 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.10 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.15 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.20 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.25 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.30 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.40 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.50 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.60 % (w/w). In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.70 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.80 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.90 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 1.00 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 1.50 % (w/w).
In some embodiments the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 2.00 % (w/w).
In some embodiments the ratio between the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide in the composition and/or formulation and/or combination and/or kit of the invention is about 0.05:0.1 :2, at times about 2:1 :40. In some embodiments the ratio is based on volume. In some embodiments the ratio is based on weight.
In some embodiments the ratio between the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide in the composition and/or formulation and/or combination and/or kit of the invention is between about 0.05:0.1 :2 to about 2: 1 :40. Any value which is between these ratios is within the scope of the present disclosure.
In some embodiments the ratio between the ingredients in the kit of the invention is a ratio between the weight percentages of each individual ingredient in its own formulation e.g., in its own compartment. In some embodiments the ratio between the ingredients in the kit of the invention is a ratio between the volume percentages of each individual ingredient in its own formulation e.g., in its own compartment.
In some embodiments the composition and/or combination and/or kit of the invention comprises at least one Dead Sea extract, at least one extract of the plant Rumex being the Rumex Occidentalis plant, and at least one Thioredoxin polypeptide being a plant-Thioredoxin- 1.
In some embodiments the composition and/or combination and/or kit of the invention comprises at least one Dead Sea extract, at least one extract of the plant Rumex being the Rumex Occidentalis plant, and at least one Thioredoxin polypeptide being a plant-Thioredoxin- 1, wherein the plant-Thioredoxin- 1 polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing the plant Nicotiana benthamiana.
In some embodiments the composition and/or combination and/or kit of the invention comprises at least one Dead Sea extract, at least one extract of the plant Rumex being the Rumex Occidentalis plant, and at least one plant-Thioredoxin- 1 being Oligopeptide-4.
In some embodiments the composition and/or combination and/or kit of the invention comprises at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide (e.g., protein), wherein the at least one Dead Sea extract is Dead Sea water (or a concentrate thereof), or an artificial aqueous solution having substantially the same salt and mineral content of the Dead Sea water (or a concentrate thereof), wherein the at least one extract of the plant Rumex is an extract of the Rumex Occidentalis plant, and wherein the at least one Thioredoxin polypeptide (e.g., protein) is a plant-Thioredoxin- 1.
In some embodiments the composition and/or combination and/or kit of the invention comprises at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin protein, wherein the at least one Dead Sea extract is Dead Sea water (or a concentrate thereof), or an artificial aqueous solution having substantially the same salt and mineral content of the Dead Sea water (or a concentrate thereof), wherein the at least one extract of the plant Rumex is an extract of the Rumex Occidentalis plant, and wherein the at least one Thioredoxin protein is a plant-Thioredoxin- 1 obtainable (or obtained) by gene cloning utilizing the plant Nicotiana benthamiana. In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.1 % to about 5.00% (w/w), at times at between about 0.1 % to about 2.40% (w/w), at times between about 0.1% to about 2.00% (w/w), at times between about 0.1% to about 1.50% (w/w), at times between about 0.1% to about 1.00% (w/w), inclusive the end points values, the concentration of the at least one extract of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.05% to about 5.00% (w/w), at times at between about 0.05% to about 3.00% (w/w), at times at between about 0.05% to about 2.00% (w/w) inclusive the end points values, and the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.05% to about 5.00% (w/w), at times at between about 0.05% to about 4.00% (w/w), at times at between about 0.05% to about 2.00% (w/w) inclusive the end points values.
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.1 % to about 0.50% (w/w), inclusive the end points values, the concentration of the at least one extract of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 0.05% to about 0.50% (w/w) inclusive the end points values, and the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at between about 1.00% to about 2.00% (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.1 % (w/w), the concentration of the at least one extract of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is about 0.05% (w/w), and the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is about 2.00% (w/w).
In some embodiments the concentration of the Dead Sea extract (e.g., Dead Sea water) in the composition and/or formulation and/or combination and/or kit of the invention is at least about about 0.1 % (w/w) (inclusive), the concentration of the at least one extract of the Rumex extract (e.g., Rumex Occidentalis extract) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 0.05% (w/w) (inclusive), and the concentration of the Thioredoxin polypeptide (e.g., protein) in the composition and/or formulation and/or combination and/or kit of the invention is at least about 2.00% (w/w) (inclusive).
Without wishing to be bound by theory, in the composition and/or formulation and/or combination and/or kit of the invention, apart from being by itself an active ingredient that beneficially affects the skin (cosmetically and/or pharmaceutically), the at least one Dead Sea extract may serve as an adjuvant and/or a booster of one or more of the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide e.g., to improve/enhance the activity (cosmetically and/or pharmaceutically) illustrated by the one or more of the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide.
In some embodiments the at least one Dead Sea extract may boost the activity of the at least one Thioredoxin polypeptide.
Non limiting examples of attributes that are related to the commercially available Thioredoxin polypeptide PUREOXIN™ (by LipoTrue), which may be boosted by the compositions/combinations/formulations/kits of the present invention e.g., by the at least one Dead Sea extract, are one or more of: protect the skin against inflammaging; protect the skin from photoaging; decrease the content of superficial melanin helping to lighten and illuminate skin tone.
In some embodiments, one or more of the above noted attributes may be improved and/or enhanced by utilizing the composition and/or combination and/or formulations and/or kit of the invention. The one or more of the above noted attributes are within the scope of the present disclosure.
In some embodiments the at least one Dead Sea extract may boost the activity of the at least one extract of the plant Rumex.
Non limiting examples of attributes that are related to the commercially available Tyrostat™ extract of the plant Rumex, which may be boosted by the compositions/combinations/formulations/kits of the present invention e.g., by the at least one Dead Sea extract, are one or more of: skin whitening/lightening/brightening; reduction of skin pigmentation; reduction of skin erythema and redness; reduction of melanin production; reduction of the appearance of age spots. In some embodiments, one or more of the above noted attributes may be improved and/or enhanced by utilizing the composition and/or combination and/or formulations and/or kit of the invention. The one or more of the above noted attributes are within the scope of the present disclosure.
In some embodiments the at least one Dead Sea extract may boost the activity of the at least one Thioredoxin polypeptide and the activity of the at least one extract of the plant Rumex.
Non limiting examples of attributes that may be boosted by the compositions/combinations/formulations/kits of the present invention by the at least one Dead Sea extract are one or more of: protect the skin against inflammaging; protect the skin from photoaging; decrease the content of superficial melanin helping to lighten and illuminate skin tone; skin whitening/lightening/brightening; reduction of skin pigmentation; reduction of skin erythema and redness; reduction of melanin production; reduction of the appearance of age spots. The one or more of the above noted attributes are within the scope of the present disclosure.
Without wishing to be bound by theory, in the composition and/or formulation and/or combination and/or kit of the invention, apart from being by itself an active ingredient, any one of the ingredients of the present invention i.e., the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide, may serve as an adjuvant and/or a booster of one or more of the other e.g., to improve/ enhance the activity (cosmetically and/or pharmaceutically) illustrated by one or more of the other ingredients.
Thus, without wishing to be bound by theory, in the composition and/or formulation and/or combination and/or kit of the invention, apart from being by itself an active ingredient that beneficially affects the skin (cosmetically and/or pharmaceutically), the at least one extract of the plant Rumex may serve as an adjuvant and/or a booster of one or more of the at least one Dead Sea extract, and the at least one Thioredoxin polypeptide e.g., to improve/enhance the activity (cosmetically and/or pharmaceutically) illustrated by the one or more of the at least one Dead Sea extract, and the at least one Thioredoxin polypeptide.
Also, without wishing to be bound by theory, in the composition and/or formulation and/or combination and/or kit of the invention, apart from being by itself an active ingredient that beneficially affects the skin (cosmetically and/or pharmaceutically), the at least one Thioredoxin polypeptide may serve as an adjuvant and/or a booster of one or more of the at least one extract of the plant Rumex, and the at least one Dead Sea extract e.g., to improve/enhance the activity (cosmetically and/or pharmaceutically) illustrated by the one or more of the at least one extract of the plant Rumex, and the at least one Dead Sea extract.
In some embodiments attributes of the compositions and/or combinations and/or formulations and/or kits of the present invention may be associate with skin melanin function. Non-limiting advantageous attributes are skin glow, lucent, radiance, antipigmentation, even and clear tone. In some embodiments these attributes may be advantageous inter-alia in terms of the ability of the combinations of the invention to inhibit age-related skin damage and/or to treat or prevent skin diseases and/or disorders that are associate with hyper melanin formation.
In some embodiments one or more of the aforementioned attributes and/or uses are within the scope of the present disclosure.
In some embodiments the compositions and/or combinations and/or formulations and/or kits of the invention are synergistic compositions and/or combinations and/or formulations and/or kits (the latter comprise synergistic combination of the ingredients of the invention i.e., the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide that once concomitantly applied onto the skin they provide at least one synergistic effect).
It is noted that the amount of any one the at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide necessary to bring about the aforementioned attributes and/or utilities of the compositions/formulations/combinations/kits of the present invention is not fixed perse and might be dependent upon the user's skin type and, where present, the severity and extent of the patient's skin condition. Generally, the ingredients contained in the composition/formulation/formulation/kit of the invention are topically applied in effective amounts to skin areas such as hyper pigmentation and/or aged skin areas etc. in need thereof.
Without wishing to be bound by theory, by combining the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide of the present invention, there might be a decrease in their toxicity profiles or the potential of a skin irritation in sensitive individuals. An enhanced efficacy may also occur e.g., of one or more of the attributes detailed herein above and below.
Further without wishing to be bound by theory, the composition/formulation/combination/kit comprising the at least one Dead Sea extract, the at least one extract of the plant Rumex, and the at least one Thioredoxin polypeptide of the present invention, may be advantageous compared to a composition/formulation/combination/kit having only one or two of the above ingredients, for example, since each ingredient may act on the skin in different way/mechanism (e.g., by affecting melanin synthesis via tyrosinase inhibition and/or other mechanisms). Hence, there might be an enhanced effect when the aforementioned ingredients are combined compared to the use of a single ingredient or two ingredients out of the above noted three ingredients. Therefore, the combinations of the present invention are beneficial for use on the skin. They are also beneficial due to their illustrated redox effect and antioxidation effect.
In some embodiments the composition/formulation/combination/kit of the invention may inhibit the formation of melanin. In some embodiments melanin formation may be reduced by at least 10%, at times by at least 20%, at times by at least 30%, at times by at least 40%, at times by at least 50%, at times by at least 60% or even at times by at least 70% compared to golden standard ingredients (e.g., Kojic Acid), and/or compared to an untreated skin, and/or compared to composition/formulation/combination/kit comprising one or two of the active ingredients e.g., not containing the triple complex of the present invention, the latter comprises the three ingredients as follows: (i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide.
The concentration of melanin in the skin may be measured by means known in the art. The measurement may be performed in one measurement regimen e.g., after one week of treatment, e.g., topical application of at least once daily. Further measurements may follow e.g., after two, at times three, at times four or more weeks of treatment.
In some embodiments the composition/formulation/combination/kit of the invention may inhibit the formation of melanin to an extent that is greater than 10%, at times 20%, at times 30%, at times 40%, at times 50%, at times 60% or even at times at least 70% compared to golden standard ingredients (e.g., Kojic Acid), and/or compared to an untreated skin and/or compared to composition/formulation/combination/kit comprising one or two of the active ingredients e.g., not containing the triple complex of the present invention.
In some embodiments the composition/formulation/combination/kit of the invention may inhibit the formation of melanin to an extent of about 1.5 times, even 2.0 times, even 3.0 times more compared to golden standard ingredients (e.g., Kojic Acid), and/or compared to an untreated skin, and/or compared to composition/formulation/combination/kit comprising one or two of the active ingredients e.g., not containing the triple complex of the present invention.
The compositions/combinations of the present invention may be made into a wide variety of product forms suitable for, e.g., topical administration onto the skin of a subject.
Thus, in another one of its aspects, the present invention provides one or more of a lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semisolid, or a liquid make-up, a foundation, and an eye make-up comprising the composition and/or the combination according to the invention.
In a further one of its aspects the present invention provides one or more of a lotion, an ointment, a gel, a mask, a toner, an essence, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid makeup, a foundation, and an eye make-up comprising the composition and/or the combination according to the invention.
In some embodiments the aforementioned forms may form part of the kit of the invention e.g., each of the ingredients of the kit may be formulated in the aforementioned forms.
In another one of its aspect the present invention provides a kit according the invention, wherein the components thereof are in the form of a lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up.
In another one of its aspect the present invention provides a kit according the invention, wherein the components thereof are in the form of a lotion, an ointment, a gel, a mask, a toner, an essence, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up. In some embodiments, the composition/combination of the invention is formulated as a lotion.
In some embodiments, the composition/combination of the invention is formulated as an emulsion.
In some embodiments, the composition/combination of the invention is formulated as a facial formulation.
In some embodiments, the composition/combination of the invention is formulated as a body formulation.
In some embodiments, the composition/combination of the invention is formulated as a leave on formulation.
In some embodiments, the composition/combination of the invention is formulated as rinse off formulation.
As used herein, a “leave on” (in contrary to “rinse off") composition/formulation/combination refers to a composition/formulation/combination that may be in prolonged contact with the skin and can be applied to a skin region without the need to remove it from the skin (e.g., by wiping or rinsing it off) in any way.
In some embodiments, the leave-on composition/formulation/combination may be adapted to be applied to a skin region and to be left on the skin for a time sufficient to achieve end result.
The viscosity of the compositions/combinations according to the invention may vary depending on the form (i.e., lotion, cream, etc.), concentration of the active combination, the carrier, the purpose (i.e., cosmetic or therapeutic), end user and other parameters.
The compositions/combinations/formulations/kits according to the invention (cosmetic or therapeutic) may comprise at least one dermatological, cosmetically or pharmaceutically acceptable additive selected amongst inert and effect-inducing additives. Such additives are necessary for example for storage purposes, stability of the formulation, texture of the formulation for topical application and the like.
In some embodiments, the inert additive is selected from a diluent, a preservative, an abrasive, an anti-caking agent, an antistatic agent, a binder, a buffer, a dispersant, an emollient, an emulsifier, a co-emulsifiers, a fibrous material, a film forming agent, a fixative, a foaming agent, a foam stabilizer, a foam booster, a gallant, a lubricant, a moisture barrier agent, an opacifier (e.g., styrene/acrylamide copolymer), a plasticizer, a preservative, a propellant, a stabilizer, a surfactant, a suspending agent, a thickener, a wetting agent, and a liquefier.
In some embodiments the additive may be any one of the above noted additives or any combination thereof.
In some embodiments the additive may be any one of a stabilizer, an adjuvant, an excipient, a diluent, a carrier, a filler, an antioxidant or any combination thereof.
In some embodiments, the at least one inert additive is a smoothness enhancer ingredient, such as silica.
In some embodiments, the at least one inert additive is a skin delivery agent.
In some embodiments, the at least one inert additive is of an encapsulated form e.g., protected from oxidation.
In some embodiments, the at least one inert additive is an antioxidant (e.g., Vitamin C) in an encapsulated form.
In some embodiments, the at least one inert additive is a chelator (e.g., synthetic EDTA) that stabilizes the composition/formulation (e.g., the presence thereof avoid redox/oxidation of one or more ingredients of the composition/formulation/combination).
In some embodiments, in the compositions/combinations/formulations of the present invention the one or more additives (e.g., dermatological, cosmetically or pharmaceutically acceptable additive) complete the content of the compositions/combinations/formulations to 100% (w/w). In some embodiments the total cumulative content of such additives, at times including water, may be at least about 85% (w/w), at times at least about 90.0% (w/w), at times at least about 95.0% (w/w), event at times at least about 95.6% (w/w). In some embodiments the same applies mutatis- mutandis to the individual formulations that constitute the kit of the invention.
In some embodiments the additive may be a non-natural additive.
In some embodiments the additive may be a natural additive.
Further non limiting additives that may form part of the compositions/combinations/formulations/kits of the present invention are one or more of: a solvent, an emulsion stabilizer, an emulsifier, a skin/hair conditioning agent, an emollient, a humectant, a surfactant, a preservative, a film forming agent, anti-static agent, viscosity controlling agent, chelator, suspending agent and an antioxidant.
In some embodiments one or more of the additives of the invention may be synthetic or natural (e.g., from a plant/vegetable). In some embodiments the compositions/combinations/formulations/kits of the present invention may comprise at least one additive, preferably being a non-natural additive.
In some embodiments the compositions/combinations/formulations/kits of the present invention may comprise at least one additive, preferably being a synthetic additive.
In some embodiments, each of the at least one dermatological, cosmetically or pharmaceutically acceptable additives may constitute between about 0.05 to 15% of the total weight of the compositions/combinations/formulations (and at times same constituting the kit of the invention). In some embodiments, the at least one additive constitutes between 0.05% and 10% or between 0.05% and 8%, or between 0.05% and 7%, or between 0.05% and 6%, or between 0.05% and 5% of the total weight of the compositions/combinations/formulations (and at times same constituting the kit of the invention).
In some embodiments, the at least one inert additive is a diluent being selected from water, Bisabolol, propane diol, propylene glycol, butylene glycol, glycerin, safflower oil or any mixtures thereof.
In some embodiments, the at least one inert additive is a preservative being selected from one or more of methylparaben, methyldibromo glutaronitrile, phenethyl alcohol, glyceryl caprilate, propylparaben, methylisothiazolinone, decylene glycol, dehydroacetic acid, phenoxyethanol, benzoic acid, 2-methyl-2H-isothiazoline-3-one, polyethylene glycol monococoate, polyethylene glycol dicocoate, polyethylene Glycol, iodopropynyl butylcarbamate, 1 ,2-hexanediol, caprylyl glycol, imidazolidinyl urea, DMDM Hydantoin, Ipbc, MIT, and 2,3-bronopol.
In some embodiments, the at least one inert additive is a synthetic preservative necessary for preserving the formulations of the invention for long storage and/or use purposes.
In further embodiments, the inert additive is an emulsifier being selected from one or more of cetyl hydroxyethylcellulose, cetyl alcohol, ceteth-20 (a polyethylene glycol derivative of cetyl alcohol), cetearyl olivate, cetyl palmitate, sorbitan olivate, sorbitan palmitate, stearates, steareth-20 (polyethylene glycol ethers of stearic acid- octadecyl polyoxyethylene ether), and steareth-25. In some embodiments, the stearate is selected from PEG-40 stearate, glyceryl steatrate, sorbitan tri stearate, stearyl alcohol or any mixtures thereof.
In some embodiments, the stearate is glyceryl stearate.
In still other embodiments, the inert additive is an emollient, being selected from vegetable and animal fats and oils such as castor oil, hydrogenated castor oil, cocoa butter, safflower oil, cottonseed oil, corn oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil, sesame oil, squalene, phytosqalene, kikui oil, chamomilla recutita (matricaria) flower oil, hypericum perforatum oil, soybean oil and vitis vinifera (grape) seed oil; acetoglyceride esters, such as acetylated monoglycerides; alkyl esters of fatty acids having 10 to 24 carbon atoms which include, but are not limited to, methyl, isopropyl, and butyl esters of fatty acids such as hexyl laurate, isohexyl laurate, ethylhexyl palmitate, isohexyl palmitate, isopropyl palmitate, octyl palmitate, decyloleate, isodecyl oleate, hexadecyl stearate decyl stearate, isopropyl isostearate, diisopropyl adipate, diisohexyl adipate, dihexyldecyl adipate, diisopropyl sebacate, lauryl lactate, myristyl lactate, and cetyl lactate; alkenyl esters of fatty acids having 10 to 20 carbon atoms such as oleyl myristate, oleyl stearate, and oleyl oleate; fatty acids having 10 to 20 carbon atoms such as pelargonic, lauric, myristic, palmitic, stearic, isostearic, hydroxystearic, oleic, linoleic, ricinoleic, arachidic, behenic, and erucic acids; fatty alcohols having 10 to 20 carbon atoms such as lauryl, myristyl, cetyl, hexadecyl, stearyl, isostearyl, hydroxystearyl, oleyl, ricinoleyl, behenyl, erucyl, and 2-octyl dodecanyl alcohols; fatty alcohol ethers such as propoxylated fatty alcohols of 10 to 20 carbon atoms which include, but are not limited to, lauryl, cetyl, stearyl, isostearyl, oleyl, and cholesterol alcohols, having attached thereto from 1 to 50 propylene oxide groups; lanolin and lanolin derivatives such as lanolin, lanolin oil, lanolin wax, lanolin alcohols, lanolin fatty acids, isopropyl lanolate, ethoxylated lanolin, ethoxylated lanolin alcohols, ethoxylated cholesterol, propoxylated lanolin alcohols, acetylated lanolin alcohols, lanolin alcohols linoleate, lanolin alcohols ricinoleate, acetate of lanolin alcohols ricinoleate, acetate of ethoxylated alcohols-esters, hydrogenolysis of lanolin, ethoxylated sorbitol lanolin, and liquid and semisolid lanolin absorption bases; polyhydric alcohol esters such as ethylene glycol mono and di-fatty acid esters, diethylene glycol mono-and di-fatty acid esters, polyethylene glycol (200-6000) mono-and di-fatty acid esters, propylene glycol mono-and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, glyceryl mono-and di-fatty acid esters, polyglycerol polyfatty esters, ethoxylated glyceryl monostearate, 1,2-butylene glycol monostearate, 1,2-butylene glycol distearate, polyoxyethylene polyol fatty acid ester, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters; Wax esters such as beeswax, spermaceti, myristyl myristate, stearyl stearate; forming a mixture of ether esters; vegetable waxes including, but not limited to, carnauba and candelilla waxes; surface active silicone derivatives such as cyclopentasiloxane PEG/PPG-18/18 dimethicone, dimethicone, dimethicone crosspolymer, cyclomethicone, cyclomethicone&dimethiconol; caprylic/capric triglyceride; and cholesterol fatty acid esters and any mixtures thereof.
In some embodiments, each of the at least one inert additive may constitute between about 0.05 to 15% of the total weight of the composition/combination/formulation (and at times same constituting the kit of the invention). In some embodiments, the at least one inert additive constitutes between 0.05% and 10% or between 0.05% and 8%, or between 0.05% and 7%, or between 0.05% and 6%, or between 0.05% and 5% of the total weight of the composition/combination/formulation (and at times same constituting the kit of the invention).
In other embodiments, the effect-inducing additive is selected from an anti-acne agent, an anti-aging agent, an antibacterial agent, an anti-cellulites agent, an antidandruff agent, an antifungal agent, an anti-inflammatory agent, an anti-irritation agent (e.g., allantoin, Aloe Barbadensis leaf juice), an antimicrobial agent, an antioxidant (e.g., butylated hydroxyanisole, propyl gallate, an antiperspirant agent, an antiseptic agent, a cell stimulant, a cleansing agent, a conditioner, a deodorant, a fragrance ingredient (e.g., perfume, limonene), a depilatory, a detergent, an enzyme, an essential oil, an exfoliant, a fungicide, a glosser, hair conditioner (hair conditioner agent), hair set resin, hair sheen agent, hair waving agent, a humectants (e.g., Erythritol, Homarine HC1, Ceratonia Siliqua (carob bean) gum), a moisturizer (e.g., sodium hyaluronate), an ointment base, a perfume, a protein, a skin calming agent, a skin cleanser, a skin conditioner (skin conditioning agent) , a skin healing agent, a skin lightening agent, a skin protectant, a skin smoothing agent, a skin softening agent, a skin soothing agent, a sunscreen agent, a tanning accelerator, vitamins, a colorant, and a flavoring agent.
In some embodiments, the at least one additive is a sunscreen, such as Ethyl hexyl methoxy cinnamate or titanium dioxide. In some embodiments, each of the at least one effect-inducing additive may constitute between about 0.05 to 15% of the total weight of the compositions/combinations/formulations (and at times same constituting the kit of the invention). In some embodiments, the at least one inert additive constitutes between 0.05% and 10% or between 0.05% and 8%, or between 0.05% and 7%, or between 0.05% and 6%, or between 0.05% and 5% of the total weight of the compositions/combinations/formulations (and at times same constituting the kit of the invention).
The cosmetic or pharmaceutical compositions/combinations/formulations/kits of the invention may also comprise pharmaceutical actives useful in the form of a chemical substance, material or compound, e.g., suitable for topical administration, to induce a desired local or systemic effect. Non-limiting examples of such actives are an antibiotic, an antiviral agent, an analgesic (e.g. ibuprofen, acetyl salicylic acid, naproxen, and the like), an antihistamine, an anti-inflammatory agent, an antipruritic, an antipyretic, an anesthetic agent, a diagnostic agent, a hormone, an antifungal agent, an antimicrobial agent, a cutaneous growth enhancer, a pigment modulator, an antiproliferative, an antipsoriatic, a retinoid, an anti-acne medicament (e.g. benzoyl peroxide, sulfur, and the like), an antineoplastic agent, a phototherapeutic agent, a keratolys (e.g. resorcinol, salicylic acid, and the like) and mixtures thereof.
In some embodiments or one or more of the ingredients (i), (ii) and (iii) of the kit my comprise one or more additives as herein described.
Application of a composition/combination/formulation of the invention (and at times same constituting the kit of the invention), and/or the constituents of the kit of the invention, onto the skin of a subject, for cosmetic/skin-care or therapeutic purposes may be in a single dose, in multiple doses, in a continuous or intermittent manner, depending, for example, upon the subject's physiological condition, whether the purpose of the administration is cosmetic or therapeutic/prophylactic and other factors known to the medical practitioner. At times, the application of a composition/combination/formulation of the invention (and at times same constituting the kit of the invention), and/or the constituents of the kit of the invention, may be essentially continuous over a pre-selected period of time or may be in a series of spaced doses.
The composition/combination/formulation of the invention (and at times same constituting the kit of the invention) are typically prepared by combining the ingredients of the active combination in appropriate concentrations. Other active or inert additives selected by one of skill in the art may optionally be added. The absolute weight of a given active agent included in a unit dose can vary widely. For example, about 0.1 microgram to about 5 g, or about 1 microgram to about 1 g, or about 10 microgram to about 500 mg, of at least one of the components can be administered by topical administration.
In another one of its aspects the present invention provides skin-care composition and/or formulation and/or combination and/or kit; and/or a pharmaceutical composition and/or formulation and/or combination and/or kit.
In a further one of its aspects the present invention provides a composition and/or a combination for use in the preparation of a skin-care and/or a pharmaceutical formulation.
The compositions/combination/formulation/kits of the invention, being substantially for topical use, may be (or comprise, with respect to the kit) a skin-care formulation or a therapeutic formulation.
In some embodiments, the compositions/combination/formulation/kits of the invention are skin-care or dermo-pharmaceutical compositions (including, e.g., toiletries, health and beauty aids and cosmeceuticals) used for cosmetic and personal skin-care applications.
The terms "cosmetic" or "skin care" in connection with the compositions/combinations/formulation/kits of the invention relate to compositions/combinations/formulations/kits of the invention that can be used for cosmetic purposes, purposes of hygiene or skin-care or as a basis for delivery of one or more pharmaceutical ingredients. It is also possible that these compositions/combinations/formulations/kits are used for two or more of these same purposes at one time. For example, a medicated dandruff shampoo may be used as a personal care product, i.e., to provide clean hair, and at the same time have pharmacological properties.
In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin.
In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
In another one of its aspects the present invention provides a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In a further one of its aspects the present invention provides a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
In yet a further one of its aspects the present invention provides a composition and/or a combinations and/or a kit for use in improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear (or providing the skin with same).
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear (or providing the skin with same), wherein said improving (or providing) is associated with inhibition of melanin synthesis induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin.
In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear (or providing the skin with same), wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear (or providing the skin with same), wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
In yet a further one of its aspects the present invention provides a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear (or providing the skin with same), wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear (or providing the skin with same), wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said improving (or providing) is associated with inhibition of melanin synthesis induced by said topical application.
In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing at least one disease or disorder of the skin.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing at least one disease or disorder of the skin, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin.
In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
In another one of its aspects the present invention provides a method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In a further one of its aspects the present invention provides a method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
Yet in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing inflammation of the skin of a subject.
In another one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in treating and/or preventing inflammation of the skin of a subject, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in a method of treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject, and wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
Yet in a further one of its aspects the present invention provides a method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In another one of its aspects the present invention provides a method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject, and wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
In a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use in inhibiting and/or reducing skin melanin formation.
In yet a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use a method of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of said composition and/or combination and/or the ingredients comprised within said kit onto the skin of a subject.
Yet in a further one of its aspects the present invention provides a method of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of a composition and/or a combination and/or the ingredients comprised within a kit according to the invention onto the skin of a subject.
In another one of its aspects the present invention provides the use of a composition and/or a combination according to the invention in the manufacture of a pharmaceutical formulation and/or a skin care formulation (e.g., for the intended use/s as indicated herein above and below).
In a further one of its aspects the present invention provides the use of a composition and/or a combination according to the invention in the manufacture of a pharmaceutical formulation and/or a skin care formulation for one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
Yet, in a further one of its aspects the present invention provides the composition and/or the combination according to the invention and/or the kit of the invention, for use in one or more of: improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
In a further one of its aspects the present invention provides the composition and/or the combination according to the invention and/or the kit of the invention, for use in one or more of: improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
In yet a further one of its aspects the present invention provides a method for one or more of: improving (or providing) one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation, wherein said method comprises topical administration of the composition and/or combination according to the invention to a subject in need thereof.
In another one of its aspects the present invention provides a method for one or more of: improving (or providing) one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation, wherein said method comprises topical administration of the composition and/or combination according to the invention to a subject in need thereof.
In a further one of its aspects the present invention provides a non-therapeutic method for one or more of: improving (or providing) one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation, wherein said method comprises topical administration of the composition and/or combination according to the invention to a subject in need thereof.
Yet, in a further one of its aspects the present invention provides a composition and/or a combination and/or a kit for use as disclosed herein and/or exemplified, wherein said composition and/or a combination and/or a kit comprise a synergistic active combination of at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
The various methods and/or uses of the compositions and/or combinations and/or the ingredients comprised within the kit according to the invention, as disclosed herein above and below (e.g., cosmetic and/or therapeutic), may be associate with one or more of inhibition of skin melanin formation and reduction in IL-8 skin levels induced/caused by the compositions/combinations/ingredients of the present invention.
The various methods and/or uses of the compositions and/or combinations and/or the ingredients comprised within the kit according to the invention, as disclosed herein above and below (e.g., cosmetic and/or therapeutic), may be associate with one or more of inhibition of skin melanin formation and reduction in IL-8 skin levels induced/caused by the compositions/combinations/ingredients of the present invention, and with the redox and anti-oxidation activity of the compositions/combinations/ingredients of the present invention. The methods and/or the uses of the compositions and/or combinations and/or ingredients comprised within the kits of the invention, as disclosed herein above and below, may be associated with and/or mediated by and/or affected by and/or related to the to skin melanin formation (for example, the inhibition thereof e.g., via inhibition of tyrosinase enzymatic activity).
The therapeutic and/or cosmetic effects illustrated by the compositions and/or combinations and/or ingredients comprised within the kits of the present invention may be associated with and/or mediated by and/or affected by and/or related to skin melanin formation (for example, the inhibition thereof e.g., via inhibition of tyrosinase enzymatic activity).
In some embodiments, the cosmetic compositions/combinations/formulations/kits are for (or for use in, or for use in a method for) promoting bodily attractiveness, cover or mask the physical manifestations of a disorder or disease, modulate or alleviate wrinkling, unevenness and dryness in the skin of a mammal. The compositions additionally regulate skin condition and signs of skin aging (all perceptible manifestations as well as any other macro or micro effects) by regulating visible and/or tactile discontinuities in skin texture, including fine lines, wrinkles, enlarged pores, roughness and other skin texture discontinuities associated with aged skin with reduced irritation and dryness.
In some embodiments, the cosmetic compositions/combinations/formulations/kits are anti-pigmentation compositions/combinations/formulations/kits.
In some embodiments, anti-pigmentation is envisaged as preventing and/or reducing pigmentation.
In another one of its aspects the present invention provides an anti-pigmentation composition/combination/formulation/kit.
In a further one of its aspects the present invention provides a skin lucent composition/combination/formulation/kit.
In yet a further one of its aspects the present invention provides a skin lucent boosting composition/combination/formulation/kit.
Yet, in a further one of its aspects the present invention provides a skin lightening/whitening/brightening composition/combination/formulation/kit.
In a further one of its aspects the present invention provides a skin lightening and skin tone illumination composition/combination/formulation/kit. In some embodiments the compositions/combinations/formulations/kits of the invention are anti-pigmentation compositions/combinations/formulations/kits.
In some embodiments the compositions/combinations/formulations/kits of the invention are skin lucent compositions/combinations/formulations/kits.
In some embodiments the compositions/combinations/formulations/kits of the invention are skin lucent boosting compositions/combinations/formulations/kits.
In some embodiments the compositions and/or combinations and/or formulations and/or kits of the invention are skin lightening/whitening/brightening compositions/combinations/formulations/kits.
In some embodiments the compositions/combinations/formulations/kits of the invention are skin lightening and skin tone illumination compositions/combinations/formulations/kits.
In some embodiments the compositions/combinations/formulations/kits of the invention are one or more of: an anti-pigmentation, a skin lucent (at times a skin lucent boosting), a skin lightening/whitening/brightening, and skin lightening and skin tone illumination compositions/combinations/formulations/kits. The term “aging” may be envisaged as one or more of changes experienced by the skin with age (chrono-aging), through exposure to the sun (photo-aging) and to environmental agents (such as tobacco smoke, extreme climatic conditions of cold, heat, or wind, chemical contaminants or pollutants). The term may also encompass one or more of external visible and/or perceptible changes through touch, such as and not restricted to, the development of discontinuities on the skin such as wrinkles, fine lines, furrows, irregularities or roughness, increase in the size of pores, loss of elasticity, loss of firmness, loss of smoothness, loss of the capacity to recover from deformation, sagging of the skin such as sagging cheeks, the appearance of bags under the eyes or the appearance of a double chin, among others, changes to the color of the skin such as marks, reddening, bags under the eyes or the appearance of hyperpigmented areas such as age spots or freckles among others, anomalous differentiation, uneven skin tone, sagging orange-peel skin, loss of collagen structure and other histological changes of the stratum corneum, of the dermis, epidermis, vascular system (for example the appearance of spider veins or telangiectasias) or of those tissues close to the skin, among others.
The term “photoaging” may refer to a set of processes due to the prolonged exposure of the skin to ultraviolet radiation which result in the premature aging of the skin, and present the same physical characteristics as aging, such as and not restricted to, flaccidity, sagging, and changes to the color or irregularities in the pigmentation.
The changes of the skin due to aging (e.g. chrono-aging, photoaging and/or environmental aging) may also be referred to as the symptoms or signs of skin aging.
In some embodiments the symptoms or signs of skin aging are resulted from skin hyper pigmentation.
In some embodiments the symptoms or signs of skin aging are changes to the color of the skin such as marks, reddening, bags under the eyes or the appearance of hyperpigmented areas such as age spots or freckles among others, anomalous differentiation, uneven skin tone, sagging and orange-peel skin.
In some embodiments the symptoms or signs of skin aging are changes to the color or irregularities in the pigmentation.
In some embodiments treatment and/or preventing and/or inhibiting one or more of the above undesired skin changes is within the scope of the present invention.
In some embodiments aging refers to changes experienced by the skin with age (chrono-aging).
In some embodiments aging refers to changes experienced by the skin through exposure to the sun (photo-aging).
In some embodiments aging refers to changes experienced by the skin through exposure to environmental agents.
In some embodiments the compositions/formulations/combinations/kits of the present invention may be used to prevent or combat symptoms or signs of skin aging e.g., such as those detailed herein. For example, prevent and/or combat one ore more of from changes to the color of the skin such as marks, reddening, bags under the eyes or the appearance of hyperpigmented areas such as age spots or freckles among others, anomalous differentiation, uneven skin tone, sagging and orange-peel skin.
In some embodiments the compositions/formulations/combinations/kits of the present invention may be used to prevent or combat symptoms or signs of skin hyperpigmentation.
In some embodiments the compositions/formulations/combinations/kits of the present invention may be used to prevent or combat symptoms or signs of skin associated with skin hyper melanin formation. In some embodiments the compositions/formulations/combinations/kits of the present invention may be used to attenuate the degree of pigmentation of the skin (at times of the hair).
Non-limiting examples of skin disorders/conditions/diseases that may be prevented and/or treated and/or improved e.g., by topical application of the compositions/formulations/combinations/kits of the invention that are related to hyperpigmentation and/or being induced by melanin are one or more of: hormonal related pigmentation alterations; melasma; lentigo; piebaldism; Addison's disease; hypersensitivity to ultraviolet radiation due to agents favoring the action of radiation (phototoxins); or hyperpigmentation resulting from an inflammatory lesion (e.g., spots associated to acne, eczemas, scars or depilation).
In some embodiments the skin disorder/condition/disease may be associate with hyper melanin formation.
In some embodiments the compositions/formulations/combinations/kits of the invention may be used in cases wherein areas of an individual's skin have lower melanin densities than in the surrounding areas. Said type of hypopigmented spots are known as vitiligo. Though it would be desirable to be able to restore pigmentation in the areas affected by vitiligo with topical application, a reduction of the degree of pigmentation of the non-affected surrounding skin to reduce the contrast between both areas may be achieved by topical application of the compositions/formulations/combinations/kits of the invention.
In some embodiments the skin condition is a non-medical condition e.g., associated with normal skin conditions.
In some embodiments the skin condition is a medical condition e.g., associate with pathological skin conditions.
In some embodiments the disease and/or disorder disclosed herein is a nonmedical condition e.g., associated with normal skin conditions.
In some embodiments the disease and/or disorder disclosed herein is a medical condition e.g., associate with pathological skin conditions.
In some embodiments the methods/uses disclosed herein are non-therapeutic methods/uses e.g., associated with normal skin conditions.
In some embodiments the methods/uses disclosed herein are therapeutic methods/uses e.g., associate with pathological skin conditions. In some embodiments the methods disclosed herein are non-therapeutic methods e.g., associated with normal skin conditions.
In some embodiments the methods disclosed herein are therapeutic methods e.g., associate with pathological skin conditions.
In some embodiments the compositions/formulations/combinations/kits of the invention are cosmetic compositions/formulations/combinations/kits.
In some embodiments the compositions/formulations/combinations/kits of the invention are therapeutic compositions/formulations/combinations/kits e.g., pharmaceutical.
In some embodiments, the compositions/formulations/combinations/kits are topical compositions/formulations/combinations/kits e.g., cosmetic or pharmaceutical.
In another one of its aspects the present invention provides compositions for use as herein described and exemplified.
In another one of its aspects the present invention provides a compositions/formulations/combinations/kits for use as disclosed herein and exemplified, wherein the compositions/formulations/combinations/kits comprise a synergistic active combination of at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
In some embodiments the compositions/formulations/combinations/kits of the invention are cosmetic compositions/formulations/combinations/kits.
In some embodiments the compositions/formulations/combinations/kits are pharmaceutical compositions/formulations/combinations/kits.
In some embodiments the compositions/formulations/combinations/kits are for topical application.
In some embodiments the compositions/formulations/combinations/kits are synergistic compositions/formulations/combinations/kits.
In some embodiments the compositions/formulations/combinations/kits of the invention are pharmaceutical compositions/formulations/combinations/kits used in the treatment and/or prevention of at least one disease or disorder (e.g., of the skin).
The composition/combinations of the invention, in some embodiments, are formulated for use in the treatment of a disease or disorder.
Thus, the present invention also provides a method of therapeutic treatment or prophylaxis of such disease or disorder. In some embodiments the disease or disorder is skin related.
In some embodiments the administration disclosed herein is topical administration.
In some embodiments, the disease or disorder of the skin is a secondary condition, e.g., inflammation, being related to an existing condition.
In further embodiments, the disease or disorder of the skin are age-related.
In some embodiments, the disease or disorder of the skin may be associated with hyper melanin formation.
In some embodiments, the methods/uses disclosed herein may be associate with non-medical condition/s of the skin.
In some embodiments, the methods/uses disclosed herein may be associate with medical condition/s of the skin.
In some embodiments, the methods disclosed herein may be associate with nonmedical condition/s of the skin.
In some embodiments, the methods disclosed herein may be associate with medical condition/s of the skin.
The term "topical" as used herein above and below refers to the application of a composition/combination/formulation according to the invention (or same constituting the kit of the invention) and/or the ingredients that constitute the kit of the invention directly onto at least a portion of a subject's skin (human's or non-human's skin) so as to achieve a desired effect, e.g., cosmetic or therapeutic effect, at the site of application. In some embodiments, the desired effect is achieved at the site of application without inducing one or more systemic effects. In other embodiments, at least a partial systemic effect may be induced which contributes to the induction of at least one desired effect.
The term "skin" as used herein above and below may to any part of the human or animal skin, including the whole surface thereof, hair and nails. At times, the term may refer to any part of the human or animal skin, including the whole surface thereof excluding hair and nails.
In some embodiments, topical application onto the skin of a subject is envisaged as topical application onto at least a region of the skin of the subject e.g., a region in need of the topical application. In some embodiments the attributes of the compositions/combinations/formulations/kits of the invention detailed herein above and below may be applicable for lightening the color of facial (e.g., hirsutism) and body hair.
The term “treatment” as used herein above and below refers to administration (e.g., topical) of an effective amount of a composition/combination/formulation of the present invention (and at times same, constituting the kit of the invention) effective to ameliorate undesired symptoms associated with a disease/disorder (e.g., skin disease), to prevent the manifestation of such symptoms before they occur, to slow down the progression of the disease, slow down the deterioration of symptoms, to enhance the onset of remission period, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, or to prevent the disease form occurring or a combination of one or more of the above.
In some embodiments the disease and/or disorder is a non-medical condition e.g., associated with normal skin conditions.
In some embodiments the disease and/or disorder is a medical condition e.g., associate with pathological skin conditions.
The present invention also provides compositions, combinations, formulations, kits, uses and methods as herein defined and exemplified.
The methods and/or uses disclosed herein may be cosmetic methods and/or uses.
The methods and/or uses disclosed herein may be any one of therapeutic or non- therapeutic methods and/or uses.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of an extract of the Apple of Sodom (AoS) (Calotropis Procera).
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of an extract of the Dunaliella alga.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of Myrrh tree extract.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of Silybum extract.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of Jujube extract. In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of Myrrh tree extract and Silybum extract.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of one or more of Myrrh tree extract, Silybum extract and Jujube extract.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of an extract of Haloarchaea.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of one or more of: an extract of the Apple of Sodom (AoS) (Calotropis Procera ,' an extract of the Dunaliella alga; Myrrh tree extract; Silybum extract; Jujube extract; and an extract of Haloarchaea.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of an extract selected from the group consisting of: an extract of the Apple of Sodom (AoS) (Calotropis Procera): an extract of the Dunaliella alga; Myrrh tree extract; Silybum extract; Jujube extract; an extract of Haloarchaea; and any combination thereof.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of one or more of: an extract of the Apple of Sodom (AoS) Calotropis Procera),' Myrrh tree extract; Silybum extract; Jujube extract; and an extract of Haloarchaea.
In some embodiments the compositions/combinations/formulations/kits of the invention are devoid of an extract selected from the group consisting of: an extract of the Apple of Sodom (AoS) (Calotropis Procera ,' Myrrh tree extract; Silybum extract; Jujube extract; an extract of Haloarchaea; and any combination thereof.
In some embodiments of the invention, the composition/combination/formulation/kit illustrate upon topical application on or more of: inhibition of melanin synthesis; synergistic antioxidant activity; prevention of elevation of the level of cytokine IL-8 upon exposure to UVA light.
The "effective amount", whether a therapeutically or cosmetically effective amount for purposes herein, is determined by such considerations as may be known in the art. The amount must be effective to achieve one or more of the above desired therapeutic or cosmetic effects, depending, inter alia, on the type and severity of the disease/disorder to be treated and the treatment regime. The effective amount is typically determined in appropriately designed clinical trials (dose range studies) and the person versed in the art will know how to properly conduct such trials in order to determine the effective amount. As generally known, an effective amount depends on a variety of factors including the affinity of the ligand to the receptor, its distribution profile, a variety of pharmacological parameters such as half-life on the skin, on undesired side effects, if any, on factors such as age and gender, etc.
It is noted that the embodiments provided herein above and below in connection with a specific aspect of the invention may be applicable mutatis-mutandis to the other disclosed aspects of the invention. For example, embodiments disclosed herein in connection with the compositions of the invention and/or the constitutes thereof are applicable mutatis-mutandis to formulations of the invention, to combinations of the invention, to kits of the invention, to uses of same, to methods utilizing same etc.
As used herein above and below the term "about" refers to ± 10% of the indicated value.
Unless otherwise noted, the percentages of the various ingredients of the compositions of the present disclosure are provided herein in weight per weight ratio (w/w).
It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.
As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "an extract" or "at least one extract" may independently include a plurality of extracts, including a variety thereof.
It is noted that various embodiments detailed herein above in connection with a specific aspect may be applicable to one or more other aspects of the invention mutatis mutandis. Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.
DETAILED DESCRIPTION OF EMBODIMENTS
The following examples are not in any way intended to limit the scope of the invention as claimed.
Example 1: Dead Sea Extract
A commercial preparation of a Dead Sea extract referred to herein as “Osmoter” or " Osmoter™" or “Mineral Skin Osmoter” was used. The preparation is also known as “Maris Sal” or “Maris Aqua (Dead Sea Water, DSW). The preparation is referred to herein below in the Examples and Figures also as “OSM”
Product name: Dead Sea Works LTD. The product comprises the following ions: Mg +2 (92,500 mg/L), Ca +2 (38,000 mg/L), K + (1,400 mg/L), Na + (2,000 mg/L), Sr +2 (800 mg/L), Cl" (345,000 mg/L) and Br" (11,500 mg/L).
Solutions comprising Dead Sea Water were prepared by dilutions of the “Osmoter” preparation in DDW (double distilled water). Various concentrations of the “Osmoter” preparation were used e.g., 0.1%, 0.25% and 0.5% (v/v). It is noted that the density of the studied solutions was very close to 1, thus, the v/v % presented herein is comparable to a w/w %.
Example 2: Regular Sea Water (SW)
Regula sea water (different from Dead Sea water) was used for comparison purposes (See below). To this end, sea water (SW) from the Mediterranean Sea was used. The regular sea water was sent to analysis. Table 1 below details the Sea water analysis. Table 1: Sea water analysis
Example 3: Rumex Extract
The following plant extract was used:
Product name: TYROSTAT™ (Lucas Meyer Cosmetics). Extracted from the northern Canadian Prairies plant Rumex Occidentalis.
In particular, the Tyrostat™-11 version was used:
INCI name - TYROSTAT™- 11
Water (1) (and) Glycerin (1,2,3-Propanetriol) (2) (and) Rumex Occidentalis Extract (3) (and) Ascorbic Acid (4).
CAS - TYROSTAT™- 11
7732-18-5 (1), 56-81-5 (2), - (3), 50-81-7 (4)
EINECS TYROSTAT™-11
231-791-2 (1) 200-289-5 (2), - (3), 200-066-2 (4)
Appearance: Orange-red, transparent to slightly cloudy solution with a color stable.
Various concentrations of the Rumex Extract were used e.g., 0.05%, 0.25% and 0.5% (v/v). It is noted that the density of the studied solutions was very close to 1, thus, the v/v % presented herein is comparable to a w/w %. Example 4: Polypeptide
The polypeptide used in the present study was a plant- Thioredoxin-1 (plant- TRX- 1). The polypeptide is contained within the product PUREOXIN™ (LipoTrue).
The INCI name of the polypeptide (that constitutes the active ingredient of the aforementioned product) is Oligopeptide-4.
Oligopeptide-4 is a synthetic polypeptide.
The plant Nicotiana benthamiana (Origin, Australia) is used as a plant model system for transient expression of the protein which is a non-GMO. That is, the protein is a plant-based biotechnological ingredient.
The PUREOXIN™ product is water soluble.
Appearance: solution.
Preservatives: none.
Various concentrations of the PUREOXIN™ were used e.g., 1.0% and 2.0% (v/v). It is noted that the density of the studied solutions was very close to 1, thus, the v/v % presented herein is comparable to a w/w %.
Example 5: Anti-pigmentation activity test - Melanin secretion study utilizing B16 melanocyte cells model
B16 melanocyte is a murine tumor cell line used for research as a model for human skin cancers. B16 cells are used as models for studying the biosynthesis of melanin.
Kojic acid is a chelation agent produced by several species of fungi, especially Aspergillus oryzae. It is a mild inhibitor of pigment formation in animal tissues and is used in cosmetics to lighten skin color.
Arbutin is a glycoside, glycosylated hydroquinone extracted from the bearberry plant in the genus Arctostaphylos . Applied topically, it inhibits tyrosinase and thus prevents the formation of melanin.
Melanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino acid tyrosine is followed by polymerization. The melanin pigments are produced in a specialized group of cells known as melanocytes. Functionally, melanin serves as protection against UV radiation. In the present study the anti pigmentation activity of several samples was tested utilizing the Melanocyte (Bl 6) cell line Model.
Protocol:
B16 melanocyte cell culture was induced by adding Alpha-melanocyte stimulating hormone (a-MSH) treatment. The B 16 cell lines were cultured in Dulbecco’s Modified Eagle Media (DMEM) supplemented with 10% fetal bovine serum, lOOU/mL penicillin, and lOOpg/mL streptomycin and 50mM a-MSH. DMEM without phenol red was used for melanin measurements because phenol red, a pH indicator added to the culture medium, can interfere with absorbance measurements. Cells were cultured at 37°C in a humidified incubator with 5% CO2. Melanocytes were incubated till they reached an initial confluence of 70%. After 24, 48, and 72 hours, the medium was replaced with a fresh medium containing the same treatment as the initial. After 24, 48, 72, and 96 hours, the medium was read at 490nm O.D, and a blank (only medium and treatment without B16 cells) of each well were deducted from the measured O.D. The results are presented on O.D of the melanin at 490mm.
Table 2 below details a list of the samples tested in the assay.
Table 2: Tested samples list - B16 melanocyte cells assay
Results: Figure 1 illustrates the melanin secretion to the medium observed with B16 melanocyte cell culture in the presence of the whitening agent Kojic acid after 24, 48, 72, and 96 hours of incubation. All cells were treated with 50nM of a-MSH. Samples were: Untreated (black), Kojic acid ImM (grey), and Kojic acid 0.5mM (white). * P-value < 0.05, n=4). Figure 1 illustrates that Kojic acid significantly reduced melanin secretion to the medium in B16 melanocytes after 96 hours of incubation.
Figure 2 illustrates the melanin secretion to the medium observed with B16 melanocyte cell culture in the presence of the whitening agent Arbutin after 24, 48, 72, and 96 hours of incubation. All cells were treated with 50nM of a-MSH. Samples were: Untreated (black), Arburin 0.5mM (grey), and Arbutin 0.25mM (white). * P-value < 0.05, n=4). Figure 2 illustrates that Arbutin significantly reduced melanin secretion to the medium in B16 melanocytes after 96 hours of incubation.
Figure 3 illustrates the melanin secretion to the medium observed with B16 melanocyte cell culture in the presence of Osmoter after 24, 48, 72, and 96 hours of incubation. All cells were treated with 50nM of a-MSH. Samples were: Untreated (black), Osmoter 0.5% (v/v) (grey), and Osmoter 0.25% (v/v) (white). * P-value < 0.05, n=4). Figure 3 illustrates that the Osmoter did not affect melanin accumulation on B16 melanocytes.
Figure 4 illustrates the melanin secretion to the medium observed with B16 melanocyte cell culture in the presence of PUREOXIN after 24, 48, 72, and 96 hours of incubation. All cells were treated with 50nM of a-MSH. Samples were: Untreated (black), PUREOXIN 2.0% (v/v) (grey), and PUREOXIN 1.0% (v/v) (white). * P-value < 0.05, n=4). Figure 4 illustrates that PUREOXIN significantly reduced melanin secretion to the medium in B16 melanocytes after 48, 72, and 96 hours.
Figure 5 illustrates the melanin secretion to the medium observed with B16 melanocyte cell culture in the presence of Tyrostat- 11 after 24, 48, 72, and 96 hours of incubation. All cells were treated with 50nM of a-MSH. Samples were: Untreated (black), Tyrostat-11 0.5% (v/v) (grey), and Tyrostat-11 0.25% (v/v) (white). * P-value < 0.05, n=4). Figure 5 illustrates that Tyrostat 11 significantly increased melanin secretion into the medium in B16 melanocytes after 24, 48, 72, and 96 hours.
Similar experiment was performed utilizing the various ingredients alone and in combinations.
Table 3 below details a list of the samples tested in the assay. Table 3: Tested samples list - B16 melanocyte cells assay
Protocol:
B16 melanocyte cell culture was induced by adding Alpha-melanocyte stimulating hormone (a-MSH) treatment. The B 16 cell lines were cultured in Dulbecco’s Modified Eagle Media (DMEM) supplemented with 10% fetal bovine serum, lOOU/mL penicillin, and lOOpg/mL streptomycin and 50mM a-MSH. DMEM without phenol red was used for melanin measurements because phenol red, a pH indicator added to the culture medium, can interfere with absorbance measurements. Cells were cultured at 37°C in a humidified incubator with 5% CO2. Melanocytes were incubated till they reached an initial confluence of 70%. After 24, 48, 72, and 96 hours, the medium was replaced with a fresh medium containing the same treatment as the initial. After 96 and 144 hours, the medium was read at 490nm O.D, and a blank (only medium and treatment without B16 cells) of each well were deducted from the measured O.D. the results are presented on O.D of the melanin at 490mm.
Figure 6 illustrates the melanin secretion to the medium observed with B16 melanocyte cell culture untreated and in the presence of Kojic acid, Arbutin, Osmoter, Sea-water (SW), PUREOXIN (P), Tyrostat (T), and several combinations as detailed in the figure, after 96 hours of incubation. All cells were treated with 50nM of a-MSH. P- value: *<0.01; **<0.001; ***<0.0001, n=21. Figure 6 illustrates that all the samples that contained PUROXINE illustrated a significant reduction in melanin secretion to the medium. The complex i.e., Sample # 9 in Table 3 [PUREOXIN (2%, v/v) + Tyrostat (0.05%, v/v) + Osmoter (0.1%, v/v)] illustrated a significant reduction in melanin secretion compared to the sample with the regular Sea Water (SW) i.e., Sample # 10 in Table 3 [PUREOXIN (2%, v/v) + Tyrostat (0.05%, v/v) + Sea Water (SW) (0.1%, v/v)] indicating that the Osmoter assisted in maintaining the related activity of the PUREOXIN which was decreased in the present of SW. From Figure 6 it seems that Arbutin complied as a negative control, however Kojic acid did not.
Figure 7 illustrates the melanin secretion to the medium observed with B16 melanocyte cell culture untreated and in the presence of Kojic acid, Arbutin, Osmoter, Sea-water (SW), PUREOXIN (P), Tyrostat (T), and several combinations as detailed in the figure, after 144 hours of incubation. All cells were treated with 50nM of a-MSH. P- value: *<0.01; **<0.001; ***<0.0001, n=21. The error bares in Figure 7 are STD deviation. It is noted that in this figure the O.D scale is 5 times larger.
Figure 7 illustrates that all the samples that contained PUROXINE illustrated a significant reduction in melanin secretion to the medium. The complex i.e., Sample # 9 in Table 3 [PUREOXIN (2%, v/v) + Tyrostat (0.05%, v/v) + Osmoter (0.1%, v/v)] illustrated a significant reduction in melanin secretion compared to the sample with the regular Sea Water (SW) i.e., Sample # 10 in Table 3 [PUREOXIN (2%, v/v) + Tyrostat (0.05%, v/v) + Sea Water (SW) (0.1%, v/v)] indicating that the Osmoter assisted in maintaining the related activity of the PUREOXIN which was decreased in the present of SW. From Figure 7 it seems that Kojic acid complied as a negative control, however Arbutin did not.
Figures 8A-8J are microscope pictures (xlOO) of B16 skin cells after 144h incubation with the studied samples as detailed (all samples had 50nM aMSH). The figures are consistent with the above results illustrating melanin accumulation as darker areas in the skin. It is noted that the black areas at the right top and bottom edges in Figure 8G and Figure 8H, and at the right bottom edge in Figure 81 are not related to the skin cells image.
Conclusion:
The complex [PUREOXIN (2%, v/v) + Tyrostat (0.05%, v/v) + Osmoter (0.1%, v/v)] showed potent inhibition of melanin synthesis and PUROXIN as a standalone. Tyrostat alone illustrated a negative effect i.e., it increased melanin secretion which is unexpected in view of its known inhibition effect on Tyrosinase enzymatic activity (without wishing to be bound by theory, the effect of Tyrostat on melanin synthesis might be in a mechanism different form Tyrosinase inhibition). This negative effect was not illustrated in the complex of the present invention i.e., a complex comprising a combination of PUREOXIN, Tyrostat and Osmoter.
Example 6: Anti-pigmentation activity test - Tyrosinase activity study and Melanin secretion study utilizing B16 melanocyte cells model
Tyrosinase is a rate-limiting enzyme found in melanocyte cells that catalyzes the biosynthesis of melanin from tyrosine by oxidation. The enzyme is mainly involved in two distinct reactions of melanin synthesis. Firstly, the hydroxylation of a monophenol, and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin.
In the present study the anti pigmentation activity of several samples was tested utilizing the Melanocyte (Bl 6) cell line Model as detailed above for studying melanin biosynthesis and in addition the activity of the enzyme Tyrosinase was tested.
Protocol:
B16 melanocyte cell culture was induced by adding Alpha-melanocyte stimulating hormone (a-MSH) treatment. The B 16 cell lines were cultured in Dulbecco’s Modified Eagle Media (DMEM) supplemented with 10% fetal bovine serum, lOOU/mL penicillin, and lOOpg/mL streptomycin and 50mM a-MSH. DMEM without phenol red was used for melanin measurements because phenol red, a pH indicator added to the culture medium, can interfere with absorbance measurements. Cells were cultured at 37°C in a humidified incubator with 5% CO2. Melanocytes were incubated till they reached an initial confluence of 70%. After 24 and 48 hours, the medium was replaced with a fresh medium containing the same treatment as the initial. After 96 hours, the medium was read at 490nm O.D, and a blank (only medium and treatment without B16 cells) of each well were deducted from the measured O.D. The results are presented on the O.D of the melanin at 490mm.
The lysate of the cells was prepared by using the kit “Tyrosinase activity assay” utilizing a Colorimetric method (ab252899). The activity was performed with a colorimetric substrate that has an absorption at 510nm. The test was performed for 90 min (total time), and each well was calculated for the protein amount (in pg). The Tyrosinase activity was calculated by the value of (total pmol substrate/[min (90 min) x pg (Protein/well)]).
Table 4 below details a list of the samples tested in the assay.
Table 4: Tested samples list - B16 melanocyte cells assay and Tyrosinase activity
Results:
Figure 9 illustrates melanin secretion to the medium observed with B16 melanocyte cell culture untreated (white, with no aMSH; and dashed white +aMSH) and in the presence of Kojic acid (grey), Arbutin (grey), Osmoter (black), PUREOXIN (black), Tyrostat (black), and several combinations (black) (as detailed in Table 4 and in the figure) after 96 hours of incubation. All cells were treated with 50nM of a-MSH. P- value: *<0.005; n=8. Figure 9 illustrates that both negative and positive controls (no aMSH and Kojic acid/ Arbutin) showed similar results as the previous experiment See Example 5) and as accepted from the literature.
Figures 10A-10L are microscope pictures (xlOO) of B16 skin cells after 96h incubation with the studied samples as detailed in the figures. The figures are consistent with the above results illustrating melanin accumulation as darker areas in the skin. Figure 11 illustrates Tyrosinase activity in B16 melanocyte cell lysate untreated (dashed white +aMSH) and in the presence of Kojic acid (grey), Arbutin (grey), Osmoter (black), PUREOXIN (black), Tyrostat (black), and several combinations (black) (as detailed in Table 4 and in the figure) after 96 hours of incubation. All cells were treated 5 with 50nM of a-MSH. P-value: *<0.005; n=7. All samples were compared to Untreated +aMSH. Figure 11 illustrates that Kojic acid and Arbutin significantly reduced Tyrosinase activity after both 72 and 96 hours. The same applies to the Osmoter. While PUROXIN significantly reduced the melanin accumulation in the medium See above), Figure 11 illustrates that it had dramatically increased the Tyrosinase activity. The 10 complex demonstrated a similar effect as was demonstrated by PUROXIN.
Table 5 below summarizes the above results of the Melanin secretion to the culture medium vs Tyrosinase activity.
Table 5: Melanin secretion to the culture medium results vs Tyrosinase activity
15
Conclusion:
The above results illustrate that PUROXIN caused a significant reduction in melanin synthesis. Adding PUROXIN to Tyrostat or Osmoter or its presence in the Complex had also significantly reduced the biosynthesis of melanin.
20 Surprisingly, PUROXINE illustrated a significant elevation in Tyrosinase activity. This effect was illustrated with all other samples containing PUROXIN as one of the components (as well as the Complex). Without wishing to be bound by theory, this implies that the inhibition effect on melanin synthesis that was observed with PUROXIN is related to a mechanism different from that is known for known Tyrosinase inhibitors such as for example Kojic acid and Arburin.
Without wishing to be bound by theory, the complex might act in a different mechanism compared to the gold standard inhibitors. This might be one of the reasons that the complex of the invention performed better in terms of efficacy, as well as safety as determined in cell viability tests (data not shown).
Example 7: Cytokine IL-8 secretion study utilizing an ex-vivo human skin organ culture (HSOC) model
Interleukin 8 (IL-8) is an interleukin that acts as a pro-inflammatory cytokine. IL-8 is a chemoattractant cytokine produced by a variety of skin cells. Unlike many other cytokines, it has a distinct target specificity for the neutrophil. Interleukin-8 attracts and activates neutrophils in inflammatory regions.
Protocol:
Human skin organ culture: skin tissue was obtained from an abdomen reduction of a healthy woman. It contained the epidermis and dermis layer. The skin organ culture can be maintained for up to 3 weeks, with a daily replacement of the culture medium. Specifically, a human skin organ culture model for biological tests was obtained with informed consent from a 41 years-old healthy woman who underwent abdomen reduction. Samples were cut into approximately 0.8 x 0.8 cm pieces and placed dermal side down and epidermal side up, in 35 mm diameter Petri dishes containing Dulbecco’s Modified Eagle Media (DMEM) with no phenol supplemented with lOOU/mL penicillin, and lOOpg/mL streptomycin and 250mM a-MSH. The culture was incubated at 37°C, under 5% CO2. The HSOC was exposed to 90 min of UVA light at room temperature at a 27 J/cm2 for the first, third and fifth day. The topical sample was placed topically on the HSOC on the second day and was applied topically every 72 hours until the 16 days (5 application intervals). After 16 days, the medium was collected, and the cytokine IL-8 was measured in the culture medium as an indicator of inflammation.
Table 6 below details a list of the samples tested in the assay. Table 6: Tested samples list - HSOC model
* It is noted that the samples were not further diluted due to experimental assay requirements. But the ratio between the ingredients in the complex was maintained i.e., 1:2:40 (Tyrostat: Osmoter: PUREOXIN).
Results:
Figure 12 illustrates the IL-8 level in culture media of HOSC model after 16 days of incubation and irradiation with UVA 27 mJ7cm2. The HSOC was topically applied with Arbutin, Complex (with no dilution), PUREOXIN, Tyrostat and Osmoter. The medium was collected after 16 days after the last medium replacement. All HSOC explants were treated with 250nM of a-MSH. P-value: *<0.05; n=6.
Figure 12 illustrates that there is no significant difference in the IL-8 level of skin that was exposed to UVA (dashed white) and untreated skin.
Figure 12 further illustrates that Arburin, as whitening agent, and served as a control herein, significantly increased the level of IL-8 in the culture medium. This observation is new and surprising, illustrating a disadvantage of the golden standard whitening agent Arburin. Figure 12 further illustrates that while each of the individual components of the Complex i.e., PUREOXIN, Tyeostat and Osmoter, increased the level of IL-8 in the culture medium, the Complex itself beneficially did not illustrate elevation of the level of the IL-8 in the culture media.
Conclusion:
The Complex [PUREOXIN 97% (v/v), Tyeostat 2.3% (v/v), Osmoter 4.7% (v/v)] did not cause elevation of the level of IL-8 in the culture medium, while each individual component thereof illustrated an increase effect on the IL-8 level. The elevation of the IL-8 levels indicates elevation in inflammation. Surprisingly, the complex prevented the formation of inflammation. This effect is a beneficial effect which is unique to the combination of the three ingredients constituting the active Complex.
Example 8: Oxygen Radical Absorbance Capacity (ORAC) study
ORAC. The Oxygen Radical Absorbance Capacity (ORAC) assay is a method that measures the antioxidant capacity of a substance. The ORAC assay measures a fluorescent signal from a probe quenched in the presence of Reactive Oxygen Species (ROS).
Protocol
To a 96 wells plate the following was added: 108 nM fluorescein diluted in PBS, 40 pl of sample / Trolox as standard, and lOOmM of 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH). The plate was read with a fluorescent plate reader at 37°C with the wavelengths of 485/520 for 90 min. The calibration was calculated by a concentration of 500, 250, 125, 62.5, 31.3, 15.6, 7.8, and 0 pM Trolox.
Table 7 below details a list of the samples tested in the study.
Table 7: Tested samples list - ORAC
Results
Figure 13 illustrates the Oxygen Radical Absorbance Capacity (ORAC) assay results of the above tested samples. P-value: *<0.005; n=4. Figure 13 illustrates that the complex had a significant higher ORAC value compared to the other individual components or the sample in which SW was present instead of the Osmoter (Sample 8) (P -value *<0.005).
Table 8 below details the ORAC values of the individual ingredients and the complex that comprises same.
Table 8: ORAC values
Table 8 demonstrates that the Osmoter is inert to ORAC. Table 8 also demonstrates that PUREOXIN and Tyrostat which are known in their skin lightening effect, provide less effective anti-oxidation effect compared to the complex. Furthermore, a synergistic significant effect (of about x 1.6) of the complex over the individual ingredients constituting same was illustrated.
Conclusion:
The complex showed the highest antioxidant activity (oxidants scavenging). A synergic effect in ORAC assay was demonstrated when comparing the complex to the sum of its components.
Example 9: 2,6-Dichlorophenolindophenol (DCPIP) study
DCPIP is used as an indicator for vitamin C and for reducing agents. This reaction is a redox reaction: vitamin C (ascorbic acid) is oxidized to dehydroascorbic acid, and DCPIP is reduced from blue color to the colorless compound DCPIPH2.
Procedure
To a 96 wells plate, a final concentration of 0.5mM DCPIP and sample / Ascorbic acid as standard diluted in DDW were added. The samples were allowed to stand for 60 min, and the plate was read with a plate reader at 600 nm O.D. The samples were calculated according to standards at 0.5, 0.4, 0.3, 0.2, 0.1, and 0.05mM of Ascorbic acid.
Table 9 below details a list of the samples tested in the study. Table 9: Tested samples list - DCPIP
* It is noted that the samples were not further diluted due to experimental assay requirements. But the ratio between the ingredients in the complex was maintained i.e., 1:2:40 (Tyrostat: Osmoter: PUREOXIN).
Results
Figure 14 illustrates the results of the DCPIP assay for reduction potential of the above tested samples. P-value: *<0.0001; n=4. Figure 14 illustrates that the complex (Sample 7) had a significantly higher DCPIP value than the sample in which SW was present instead of the Osmoter (Sample 8), or than the mixture of Puroxine +Tyrostate (Sample 6) (P-value <0.0001). However, the complex had a considerably lower DCPIP value than Tyrostate alone.
Conclusion:
The complex showed efficient reduction properties.
Summary
Melanin synthesis and oxidation are both key factors for hyperpigmentation and skin discoloration.
Oxidation of tyrosine is a key process for melanin biosynthesis (melanogenesis); hence oxidants scavenging by antioxidants can attenuate this process.
Moreover, melanogenesis leads to oxidants overproduction that can cause secondary skin damage, which can decrease antioxidant activity.
The above Examples 5 to 9 indicate that:
The complex illustrated a potent inhibition of melanin synthesis. The complex also illustrated the highest antioxidant activity (oxidants scavenging). A synergic effect in ORAC assay was demonstrated when comparing the complex to the sum of the individual components constituting thereof.
The complex showed the best performing activity in terms of melanogenesis inhibition and antioxidant activity.
Furthermore, the complex prevented inflammation as indicated in its ability to prevent elevation of the level of cytokine IL-8, an effect that was opposite to each individual component thereof, as the latter illustrated an increase effect on the cytokine IL-8 level. The above properties of the complex of the present invention are uniquely beneficial for the skin.
ILLUSTRATIVE EMBODIMENTS
The following embodiments are illustrative and not intended to limit the claimed subject matter.
EMBODIMENT 1 A composition comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
EMBODIMENT 2 The composition according to EMBODIMENT 1, wherein said Dead Sea extract is a mixture of natural materials obtained from the waters of the Dead Sea, and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea.
EMBODIMENT 3 The composition according to EMBODIMENT 1, wherein said Dead Sea extract is the saline waters obtained from the Dead Sea.
EMBODIMENT 4 The composition according to EMBODIMENT 3, wherein the Dead Sea water has a specific density of 1.25-1.35 g/ml, pH of 4.6-5.6 (at 25°C), and less than 100 cfu/g of non-pathogenic microbes.
EMBODIMENT 5 The composition according to any one of EMBODIMENTS 2 to 4, wherein the Dead Sea water comprises Ca +2 , CT, Mg +2 , Na + , K + and Br".
EMBODIMENT 6 The composition according to EMBODIMENT 1, wherein said Dead Sea extract is an aqueous solution simulating the salts and minerals content of the Dead Sea water.
EMBODIMENT 7 The composition according to any one of EMBODIMENTS 1 to 6, wherein said Dead Sea extract is the commercially available product Maris Sal.
EMBODIMENT 8 The composition according to any one of EMBODIMENTS 1 to 7, wherein said at least one extract of the plant Rumex is a Rumex occidentalis plant extract. EMBODIMENT 9 The composition according to any one of EMBODIMENTS 1 to 8, wherein said at least one extract of the plant Rumex is the commercially available Tyrostat™ extract (e.g., Tyrostat™ 09 and/or Tyrostat™ 11).
EMBODIMENT 10 The composition according to any one of EMBODIMENTS 1 to 9, wherein said at least one one extract of the plant Rumex is formulated with at least one additive.
EMBODIMENT 11 The composition according to EMBODIMENT 10, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 12 The composition according to EMBODIMENT 10 or 11, wherein said additive is Glycerin and/or Ascorbic Acid. EMBODIMENT 13 The composition according to any one of EMBODIMENTS 1 to 12, wherein said at least one Thioredoxin polypeptide is a human Thioredoxin.
EMBODIMENT 14 The composition according to any one of EMBODIMENTS 1 to 12, wherein said at least one Thioredoxin polypeptide is a plan Thioredoxin.
EMBODIMENT 15 The composition according to any one of EMBODIMENTS 1 to
14, wherein said at least one Thioredoxin polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana).
EMBODIMENT 16 The composition according to any one of EMBODIMENTS 1 to
15, wherein said at least one Thioredoxin polypeptide is the plant- Thioredoxin-1 (plant- TRX-1).
EMBODIMENT 17 The composition according to EMBODIMENT 16, wherein said plant-Thioredoxin-1 is Oligopeptide-4 (INCI).
EMBODIMENT 18 The composition according to any one of EMBODIMENTS 1 to 17, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1.
EMBODIMENT 19 The composition according to any one of EMBODIMENTS 1 to 17, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2.
EMBODIMENT 20 The composition according to any one of EMBODIMENTS 1 to
19, wherein said at least one Thioredoxin polypeptide is a homologue polypeptide having a sequence homology of at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% to the polypeptide of the SEQ ID NO. 1 or the SEQ ID NO. 2
EMBODIMENT 21 The composition according to any one of EMBODIMENTS 1 to
20, wherein said at least one Thioredoxin polypeptide comprises one or more conventional tags.
EMBODIMENT 22 The composition according to any one of EMBODIMENTS 1 to
21, wherein said at least one Thioredoxin polypeptide is the commercially available plant- Thioredoxin-1 PUREOXIN™.
EMBODIMENT 23 The composition according to any one of EMBODIMENTS 1 to
22, wherein said at least one Thioredoxin polypeptide is formulated with at least one additive. EMBODIMENT 24 The composition according to EMBODIMENT 23, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 25 The composition according to any one of EMBODIMENTS 1 to
24, wherein said Dead Sea extract is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 2.5 % (w/w).
EMBODIMENT 26 The composition according to any one of EMBODIMENTS 1 to
25, wherein said at least one extract of the plant Rumex is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 3.0 % (w/w).
EMBODIMENT 27 The composition according to any one of EMBODIMENTS 1 to
26, wherein said at least one Thioredoxin polypeptide is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 4.0 % (w/w).
EMBODIMENT 28 A combination comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
EMBODIMENT 29 The combination according to EMBODIMENT 28, wherein said Dead Sea extract is a mixture of natural materials obtained from the waters of the Dead Sea, and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea.
EMBODIMENT 30 The combination according to EMBODIMENT 28, wherein said Dead Sea extract is the saline waters obtained from the Dead Sea.
EMBODIMENT 31 The combination according to EMBODIMENT 30, wherein the Dead Sea water has a specific density of 1.25-1.35 g/ml, pH of 4.6-5.6 (at 25°C), and less than 100 cfu/g of non-pathogenic microbes.
EMBODIMENT 32 The combination according to any one of EMBODIMENTS 29 to 31, wherein the Dead Sea water comprises Ca +2 , CT, Mg +2 , Na + , K + and Br".
EMBODIMENT 33 The combination according to EMBODIMENT 28, wherein said Dead Sea extract is an aqueous solution simulating the salts and minerals content of the Dead Sea water.
EMBODIMENT 34 The combination according to any one of EMBODIMENTS 28 to 33, wherein said Dead Sea extract is the commercially available product Maris Sal. EMBODIMENT 35 The combination according to any one of EMBODIMENTS 28 to 34, wherein said at least one extract of the plant Rumex is a Rumex occidentalis plant extract.
EMBODIMENT 36 The combination according to any one of EMBODIMENTS 28 to
35, wherein said at least one extract of the plant Rumex is the commercially available Tyrostat™ extract (e.g., Tyrostat™ 09 and/or Tyrostat™ 11).
EMBODIMENT 37 The combination according to any one of EMBODIMENTS 28 to
36, wherein said at least one extract of the plant Rumex is formulated with at least one additive.
EMBODIMENT 38 The combination according to EMBODIMENT 37, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 39 The combination according to EMBODIMENT 37 or 38, wherein said additive is Glycerin and/or Ascorbic Acid.
EMBODIMENT 40 The combination according to any one of EMBODIMENTS 28 to 39, wherein said at least one Thioredoxin polypeptide is a human Thioredoxin.
EMBODIMENT 41 The combination according to any one of EMBODIMENTS 28 to 39, wherein said at least one Thioredoxin polypeptide is a plan Thioredoxin.
EMBODIMENT 42 The combination according to any one of EMBODIMENTS 28 to
41, wherein said at least one Thioredoxin polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana).
EMBODIMENT 43 The combination according to any one of EMBODIMENTS 28 to
42, wherein said at least one Thioredoxin polypeptide is the plant- Thioredoxin-1 (plant- TRX-1).
EMBODIMENT 44 The combination according to EMBODIMENT 43, wherein said plant-Thioredoxin-1 is Oligopeptide-4 (INCI).
EMBODIMENT 45 The combination according to any one of EMBODIMENTS 28 to 44, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1.
EMBODIMENT 46 The combination according to any one of EMBODIMENTS 28 to 44, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2. EMBODIMENT 47 The combination according to any one of EMBODIMENTS 28 to
46, wherein said at least one Thioredoxin polypeptide is a homologue polypeptide having a sequence homology of at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% to the polypeptide of the SEQ ID NO. 1 or the SEQ ID NO. 2
EMBODIMENT 48 The combination according to any one of EMBODIMENTS 28 to
47, wherein said at least one Thioredoxin polypeptide comprises one or more conventional tags.
EMBODIMENT 49 The combination according to any one of EMBODIMENTS 28 to
48, wherein said at least one Thioredoxin polypeptide is the commercially available plant- Thioredoxin-1 PUREOXIN™
EMBODIMENT 50 The combination according to any one of EMBODIMENTS 28 to
49, wherein said at least one Thioredoxin polypeptide is formulated with at least one additive.
EMBODIMENT 51 The combination according to EMBODIMENT 50, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 52 The combination according to any one of EMBODIMENTS 28 to
51, wherein said Dead Sea extract is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 2.5 % (w/w) (out of the total weight of the combination).
EMBODIMENT 53 The combination according to any one of EMBODIMENTS 28 to
52, wherein said at least one extract of the plant Rumex is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 3.0 % (w/w) (out of the total weight of the combination).
EMBODIMENT 54 The combination according to any one of EMBODIMENTS 28 to
53, wherein said at least one Thioredoxin polypeptide is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 4.0 % (w/w) (out of the total weight of the combination). EMBODIMENT 55 A kit comprising (i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide, wherein each of components (i), (ii) and (iii), independently of the other, is formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier); and wherein each of (i), (ii) and (iii) are provided in a form that is suitable for concomitant administration with the other.
EMBODIMENT 56 The kit according to EMBODIMENT 55, wherein said Dead Sea extract is a mixture of natural materials obtained from the waters of the Dead Sea, and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea.
EMBODIMENT 57 The kit according to EMBODIMENT 55, wherein said Dead Sea extract is the saline waters obtained from the Dead Sea.
EMBODIMENT 58 The kit according to EMBODIMENT 57, wherein the Dead Sea water has a specific density of 1.25-1.35 g/ml, pH of 4.6-5.6 (at 25°C), and less than 100 cfu/g of non-pathogenic microbes.
EMBODIMENT 59 The kit according to any one of EMBODIMENTS 56 to 58, wherein the Dead Sea water comprises Ca +2 , Cl", Mg +2 , Na + , K + and Br".
EMBODIMENT 60 The kit according to EMBODIMENT 55, wherein said Dead Sea extract is an aqueous solution simulating the salts and minerals content of the Dead Sea water.
EMBODIMENT 61 The kit according to any one of EMBODIMENTS 55 to 60, wherein said Dead Sea extract is the commercially available product Maris Sal.
EMBODIMENT 62 The kit according to any one of EMBODIMENTS 55 to 61, wherein said at least one extract of the plant Rumex is a Rumex occidentalis plant extract.
EMBODIMENT 63 The kit according to any one of EMBODIMENTS 55 to 62, wherein said at least one extract of the plant Rumex is the commercially available Tyrostat™ extract (e.g., Tyrostat™ 09 and/or Tyrostat™ 11).
EMBODIMENT 64 The kit according to any one of EMBODIMENTS 55 to 63, wherein said at least one one extract of the plant Rumex is formulated with at least one additive.
EMBODIMENT 65 The kit according to EMBODIMENT 64, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 66 The kit according to EMBODIMENT 64 or 65, wherein said additive is Glycerin and/or Ascorbic Acid. EMBODIMENT 67 The kit according to any one of EMBODIMENTS 55 to 66, wherein said at least one Thioredoxin polypeptide is a human Thioredoxin.
EMBODIMENT 68 The kit according to any one of EMBODIMENTS 55 to 66, wherein said at least one Thioredoxin polypeptide is a plan Thioredoxin.
EMBODIMENT 69 The kit according to any one of EMBODIMENTS 55 to 68, wherein said at least one Thioredoxin polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana).
EMBODIMENT 70 The kit according to any one of EMBODIMENTS 55 to 69, wherein said at least one Thioredoxin polypeptide is the plant- Thioredoxin-1 (plant-TRX-1).
EMBODIMENT 71 The kit according to EMBODIMENT 70, wherein said plant- Thioredoxin-1 is Oligopeptide-4 (INCI).
EMBODIMENT 72 The kit according to any one of EMBODIMENTS 55 to 70, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1.
EMBODIMENT 73 The kit according to any one of EMBODIMENTS 55 to 70, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2.
EMBODIMENT 74 The kit according to any one of EMBODIMENTS 55 to 73, wherein said at least one Thioredoxin polypeptide is a homologue polypeptide having a sequence homology of at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% to the polypeptide of the SEQ ID NO. 1 or the SEQ ID NO. 2
EMBODIMENT 75 The kit according to any one of EMBODIMENTS 55 to 74, wherein said at least one Thioredoxin polypeptide comprises one or more conventional tags.
EMBODIMENT 76 The kit according to any one of EMBODIMENTS 55 to 75, wherein said at least one Thioredoxin polypeptide is the commercially available plant- Thioredoxin-1 PUREOXIN™.
EMBODIMENT 77 The kit according to any one of EMBODIMENTS 55 to 76, wherein said at least one Thioredoxin polypeptide is formulated with at least one additive.
EMBODIMENT 78 The kit according to EMBODIMENT 77, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 79 The kit according to any one of EMBODIMENTS 55 to 78, wherein said Dead Sea extract is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 2.5 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)].
EMBODIMENT 80 The kit according to any one of EMBODIMENTS 55 to 79, wherein said at least one extract of the plant Rumex is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 3.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)] •
EMBODIMENT 81 The kit according to any one of EMBODIMENT 55 to 80, wherein said at least one Thioredoxin polypeptide is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 4.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)].
EMBODIMENT 82 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, being selected from a skin-care and pharmaceutical composition, combination or kit, respectively.
EMBODIMENT 83 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in topical application.
EMBODIMENT 84 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, being a synergistic composition, combination or a kit respectively (i.e., regarding the kit, the ingredients (i), (ii) and (iii) thereof act in a synergistic manner). EMBODIMENT 85 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, being (i.e., the composition, combination or the ingredients (i), (ii) and (iii) of the kit) in the form selected from a lotion, an ointment, a gel, a mask, a toner, an essence, a cream, a water in oil or oil in water emulsion, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up.
EMBODIMENT 86 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, (i.e., the composition, combination or one or more of the ingredients (i), (ii) and (iii) of the kit), further comprising at least one additive selected from a diluent, a preservative, an abrasive, an anticaking agent, an antistatic agent, a binder, a buffer, a dispersant, an emollient, an emulsifier, a co- emulsifiers, a fiberous material, a film forming agent, a fixative, a foaming agent, a foam stabilizer, a foam booster, a gellant, a lubricant, a moisture barrier agent, a plasticizer, a preservative, a propellant, a stabilizer a surfactant, a suspending agent, a thickener, a wetting agent, and a liquefier.
EMBODIMENT 87 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81 (i.e., the composition, combination or one or more of the ingredients (i), (ii) and (iii) of the kit), further comprising at least one additive selected from an anti-acne agent, an anti-aging agent, an antibacterial agent, an anti-cellulites agent, an antidandruff agent, an antifungal agent, an anti-inflammatory agent, an anti-irritation agent, an antimicrobial agent, an antioxidant agent, an antiperspirant agent, an antiseptic agent, a cell stimulant, a cleansing agent, a conditioner, a deodorant, a depilatory, a detergent, an enzyme, an essential oil, an exfoliant, a fungicide, a glosser, hair conditioner, hair set resin, hair sheen agent, hair waving agent, a humectants, a moisturizer, an ointment base, a perfume, a protein, a skin calming agent, a skin cleanser, a skin conditioner, a skin healing agent, a skin lightening agent, a skin protectant, a skin smoothing agent, a skin softening agent, a skin soothing agent, a sunscreen agent, a tanning accelerator, vitamins, a colorant, and a flavoring agent. EMBODIMENT 88 The composition according to any one of EMBODIMENTS 1 to 27 or the combination according to any one of EMBODIMENTS 28 to 54, for use in the preparation of a cosmetic/skin-care or a pharmaceutical formulation.
EMBODIMENT 89 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject.
EMBODIMENT 90 The composition, combination or kit for use according to EMBODIMENT 89, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by topical application of said composition, combination or the ingredients comprised within said kit onto the skin.
EMBODIMENT 91 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 92 The composition, combination or kit for use according to EMBODIMENT 91, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 93 A method (therapeutic or non-therapeutic) for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the ingredients comprised within the kit according to any one of EMBODIMENTS 55 to 81, onto the skin of a subject.
EMBODIMENT 94 The method according to EMBODIMENT 93, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application. EMBODIMENT 95 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear.
EMBODIMENT 96 The composition, combination or kit for use according to EMBODIMENT 95, wherein said improving is associated with inhibition of melanin synthesis induced by topical application of said composition or combination or the ingredients comprised within said kit onto the skin.
EMBODIMENT 97 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in a method of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 98 The composition, combination or kit for use according to EMBODIMENT 97, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 99 A method (therapeutic or non-therapeutic) of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the ingredients comprised within the kit according to any one of EMBODIMENTS 55 to 81, onto the skin of a subject.
EMBODIMENT 100 The method according to EMBODIMENT 99, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 101 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in treating and/or preventing at least one disease or disorder of the skin.
EMBODIMENT 102 The composition, combination or kit for use according to EMBODIMENT 101, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by topical application of said composition or combination or the ingredients comprised within said kit onto the skin.
EMBODIMENT 103 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 104 The composition, combination or kit for use according to EMBODIMENT 103, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
EMBODIMENT 105 A method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the ingredients comprised within the kit according to any one of EMBODIMENTS 55 to 81, onto the skin of a subject.
EMBODIMENT 106 The method according to EMBODIMENT 105, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
EMBODIMENT 107 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in treating and/or preventing inflammation of the skin of a subject.
EMBODIMENT 108 The composition, combination or kit for use according to EMBODIMENT 107, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by topical application of said composition or combination or the ingredients comprised within said kit onto the skin.
EMBODIMENT 109 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in a method of treating and/or preventing inflammation of the skin of a subject wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 110 The composition, combination or kit for use according to EMBODIMENT 109, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 111 A method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the ingredients comprised within the kit according to any one of EMBODIMENTS 55 to 81, onto the skin of a subject.
EMBODIMENT 112 The method according to EMBODIMENT 111, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 113 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in inhibiting and/or reducing skin melanin formation.
EMBODIMENT 114 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the kit according to any one of EMBODIMENTS 55 to 81, for use in a method of inhibiting and/or reducing skin melanin formation wherein said method comprises topical application of said composition or combination or the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 115 A method (therapeutic or non-therapeutic) of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54 or the ingredients comprised within the kit according to any one of EMBODIMENTS 55 to 81, onto the skin of a subject.
EMBODIMENT 116 A lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up, comprising the composition according to any one of EMBODIMENTS 1 to 27 or the combination according to any one of EMBODIMENTS 28 to 54. EMBODIMENT 117 The kit according to any one of EMBODIMENTS 55 to 81, wherein the components thereof are in the form of a lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up.
EMBODIMENT 118 Use of the composition according to any one of EMBODIMENTS 1 to 27 or the combination according to any one of EMBODIMENTS 28 to 54 in the manufacture of a pharmaceutical formulation or a skin care formulation.
EMBODIMENT 119 Use of the composition according to any one of EMBODIMENTS 1 to 27 or the combination according to any one of EMBODIMENTS 28 to 54 in the manufacture of a pharmaceutical formulation or a skin care formulation for one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
EMBODIMENT 120 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54, or the kit according to any one of EMBODIMENTS 55 to 81, for use in one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
EMBODIMENT 121 The composition according to any one of EMBODIMENTS 1 to 27, the combination according to any one of EMBODIMENTS 28 to 54, or the kit according to any one of EMBODIMENTS 55 to 81, for use in one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation. EMBODIMENT 1A A composition comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
EMBODIMENT 2 A The composition according to EMBODIMENT 1A, wherein said Dead Sea extract is a mixture of natural materials obtained from the waters of the Dead Sea, and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea.
EMBODIMENT 3 A The composition according to EMBODIMENT 1A, wherein said Dead Sea extract is the saline waters obtained from the Dead Sea.
EMBODIMENT 4A The composition according to EMBODIMENT 3A, wherein the Dead Sea water has a specific density of 1.25-1.35 g/ml, pH of 4.6-5.6 (at 25°C), and less than 100 cfu/g of non-pathogenic microbes.
EMBODIMENT 5A The composition according to any one of EMBODIMENTS 2A to 4A, wherein the Dead Sea water comprises Ca +2 , CT, Mg +2 , Na + , K + and Br".
EMBODIMENT 6AThe composition according to EMBODIMENT 1A, wherein said Dead Sea extract is an aqueous solution simulating the salts and minerals content of the Dead Sea water.
EMBODIMENT 7A The composition according to any one of EMBODIMENTS 1 A to 6A, wherein said Dead Sea extract is the commercially available product Maris Sal.
EMBODIMENT 8A The composition according to any one of EMBODIMENTS 1 A to 7 A, wherein said at least one extract of the plant Rumex is a Rumex occidentalis plant extract.
EMBODIMENT 9A The composition according to any one of EMBODIMENTS 1 A to 8A, wherein said at least one extract of the plant Rumex is the commercially available Tyrostat™ extract (e.g., Tyrostat™ 09 and/or Tyrostat™ 11).
EMBODIMENT 10A The composition according to any one of EMBODIMENTS 1A to 9A, wherein said at least one one extract of the plant Rumex is formulated with at least one additive.
EMBODIMENT HA The composition according to EMBODIMENT 10 A, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 12A The composition according to EMBODIMENT 10A or 11 A, wherein said additive is Glycerin and/or Ascorbic Acid.
EMBODIMENT 13A The composition according to any one of EMBODIMENTS 1A to 12A, wherein said at least one Thioredoxin polypeptide is a human Thioredoxin. EMBODIMENT 14A The composition according to any one of EMBODIMENTS 1A to 12A, wherein said at least one Thioredoxin polypeptide is a plan Thioredoxin.
EMBODIMENT 15A The composition according to any one of EMBODIMENTS 1A to 14A, wherein said at least one Thioredoxin polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana).
EMBODIMENT 16A The composition according to any one of EMBODIMENTS 1A to 15 A, wherein said at least one Thioredoxin polypeptide is the plant- Thioredoxin-1 (plant- TRX-1).
EMBODIMENT 17A The composition according to EMBODIMENT 16A, wherein said plant-Thioredoxin-1 is Oligopeptide-4 (INCI).
EMBODIMENT 18A The composition according to any one of EMBODIMENTS 1A to 17A, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1.
EMBODIMENT 19A The composition according to any one of EMBODIMENTS 1A to 17A, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2.
EMBODIMENT 20A The composition according to any one of EMBODIMENTS 1A to 19A, wherein said at least one Thioredoxin polypeptide is a homologue polypeptide having a sequence homology of at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% to the polypeptide of the SEQ ID NO. 1 or the SEQ ID NO. 2.
EMBODIMENT 21A The composition according to any one of EMBODIMENTS 1A to 20A, wherein said at least one Thioredoxin polypeptide comprises one or more conventional tags.
EMBODIMENT 22A The composition according to any one of EMBODIMENTS 1A to 21A, wherein said at least one Thioredoxin polypeptide is the commercially available plant-Thioredoxin-1 PUREOXIN™.
EMBODIMENT 23A The composition according to any one of EMBODIMENTS 1A to 22A, wherein said at least one Thioredoxin polypeptide is formulated with at least one additive.
EMBODIMENT 24A The composition according to EMBODIMENT 23A, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive. EMBODIMENT 25A The composition according to any one of EMBODIMENTS 1A to 24A, wherein said Dead Sea extract is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 2.5 % (w/w).
EMBODIMENT 26A The composition according to any one of EMBODIMENTS 1A to 25 A, wherein said at least one extract of the plant Rumex is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 3.0 % (w/w).
EMBODIMENT 27A The composition according to any one of EMBODIMENTS 1A to 26A, wherein said at least one Thioredoxin polypeptide is present in said composition at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w), e.g., between about 0.01% (w/w) to about 4.0 % (w/w).
EMBODIMENT 28A The composition according to any one of EMBODIMENTS 1A to 27A, being selected from a skin-care and pharmaceutical composition.
EMBODIMENT 29A The composition according to any one of EMBODIMENTS 1A to 27A, for use in topical application.
EMBODIMENT 30A The composition according to any one of EMBODIMENTS 1A to 27A, being a synergistic composition.
EMBODIMENT 31A The composition according to any one of EMBODIMENTS 1A to 27A, being in the form selected from a lotion, an ointment, a gel, a mask, a toner, an essence, a cream, a water in oil or oil in water emulsion, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semisolid, or a liquid make-up, a foundation, and an eye make-up.
EMBODIMENT 32A The composition according to any one of EMBODIMENTS 1A to 27A, further comprising at least one additive selected from a diluent, a preservative, an abrasive, an anticaking agent, an antistatic agent, a binder, a buffer, a dispersant, an emollient, an emulsifier, a co-emulsifiers, a fiberous material, a film forming agent, a fixative, a foaming agent, a foam stabilizer, a foam booster, a gellant, a lubricant, a moisture barrier agent, a plasticizer, a preservative, a propellant, a stabilizer a surfactant, a suspending agent, a thickener, a wetting agent, and a liquefier.
EMBODIMENT 33A The composition according to any one of EMBODIMENTS 1A to 27A, further comprising at least one additive selected from an anti-acne agent, an antiaging agent, an antibacterial agent, an anti-cellulites agent, an antidandruff agent, an antifungal agent, an anti-inflammatory agent, an anti-irritation agent, an antimicrobial agent, an antioxidant agent, an antiperspirant agent, an antiseptic agent, a cell stimulant, a cleansing agent, a conditioner, a deodorant, a depilatory, a detergent, an enzyme, an essential oil, an exfoliant, a fungicide, a glosser, hair conditioner, hair set resin, hair sheen agent, hair waving agent, a humectants, a moisturizer, an ointment base, a perfume, a protein, a skin calming agent, a skin cleanser, a skin conditioner, a skin healing agent, a skin lightening agent, a skin protectant, a skin smoothing agent, a skin softening agent, a skin soothing agent, a sunscreen agent, a tanning accelerator, vitamins, a colorant, and a flavoring agent.
EMBODIMENT 34A The composition according to any one of EMBODIMENTS 1A to 27 A for use in the preparation of a cosmetic/ skin-care or a pharmaceutical formulation. EMBODIMENT 35A The composition according to any one of EMBODIMENTS 1A to 27A, for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject.
EMBODIMENT 36A The composition for use according to EMBODIMENT 35 A, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by topical application of said composition onto the skin.
EMBODIMENT 37A The composition according to any one of EMBODIMENTS 1A to 27A, for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said composition onto the skin of a subject. EMBODIMENT 38A The composition for use according to EMBODIMENT 37 A, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 39A A method (therapeutic or non-therapeutic) for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1A to 27A, onto the skin of a subject.
EMBODIMENT 40A The method according to EMBODIMENT 39 A, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application. EMBODIMENT 41A The composition according to any one of EMBODIMENTS 1A to 27A, for use in improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear.
EMBODIMENT 42A The composition, for use according to EMBODIMENT 41A, wherein said improving is associated with inhibition of melanin synthesis induced by topical application of said composition onto the skin.
EMBODIMENT 43A The composition according to any one of EMBODIMENTS 1A to 27A, for use in a method of improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear, wherein said method comprises topical application of said composition onto the skin of a subject.
EMBODIMENT 44A The composition, for use according to EMBODIMENT 43A, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 45A A method (therapeutic or non-therapeutic) of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 A to 27A onto the skin of a subject.
EMBODIMENT 46A The method according to EMBODIMENT 45A, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 47A The composition according to any one of EMBODIMENTS 1A to 27A, for use in treating and/or preventing at least one disease or disorder of the skin. EMBODIMENT 48A The composition for use according to EMBODIMENT 47A, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by topical application of said composition onto the skin.
EMBODIMENT 49A The composition according to any one of EMBODIMENTS 1A to 27A, for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said composition onto the skin of a subject.
EMBODIMENT 50A The composition, for use according to EMBODIMENT 49A, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application. EMBODIMENT 51 A A method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1A to 27A, onto the skin of a subject.
EMBODIMENT 52A The method according to EMBODIMENT 51 A, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
EMBODIMENT 53A The composition according to any one of EMBODIMENTS 1A to 27A, for use in treating and/or preventing inflammation of the skin of a subject.
EMBODIMENT 54A The composition for use according to EMBODIMENT 53A, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by topical application of said composition onto the skin.
EMBODIMENT 55A The composition according to any one of EMBODIMENTS 1A to 27A, for use in a method of treating and/or preventing inflammation of the skin of a subject wherein said method comprises topical application of said composition onto the skin of a subject.
EMBODIMENT 56A The composition for use according to EMBODIMENT 55 A, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 57A A method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 A to 27A, onto the skin of a subject.
EMBODIMENT 58A The method according to EMBODIMENT 57A, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 59A The composition according to any one of EMBODIMENTS 1 A to 27A, for use in inhibiting and/or reducing skin melanin formation.
EMBODIMENT 60A The composition according to any one of EMBODIMENTS 1A to 27A, for use in a method of inhibiting and/or reducing skin melanin formation wherein said method comprises topical application of said composition onto the skin of a subject. EMBODIMENT 61A A method (therapeutic or non-therapeutic) of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of the composition according to any one of EMBODIMENTS 1 A to 27 A, onto the skin of a subject.
EMBODIMENT 62A A lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up, comprising the composition according to any one of EMBODIMENTS 1 A to 27A.
EMBODIMENT 63A Use of the composition according to any one of EMBODIMENTS 1A to 27A in the manufacture of a pharmaceutical formulation or a skin care formulation.
EMBODIMENT 64A Use of the composition according to any one of EMBODIMENTS 1A to 27A in the manufacture of a pharmaceutical formulation or a skin care formulation for one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
EMBODIMENT 65A The composition according to any one of EMBODIMENTS 1A to 27 A, for use in one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
EMBODIMENT 64A The composition according to any one of EMBODIMENTS 1A to 27 A, for use in one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
Embodiment 65A The composition according to any one of EMBODIMENTS 1A to 27A, wherein said composition comprises an active combination of said at least one Dead Sea extract, said at least one extract of the plant Rumex, and said at least one Thioredoxin polypeptide e.g., as herein disclosed and/or exemplified. EMBODIMENT IB A combination comprising at least one Dead Sea extract, at least one extract of the plant Rumex, and at least one Thioredoxin polypeptide.
EMBODIMENT 2B The combination according to EMBODIMENT IB, wherein said Dead Sea extract is a mixture of natural materials obtained from the waters of the Dead Sea, and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea.
EMBODIMENT 3B The combination according to EMBODIMENT IB, wherein said Dead Sea extract is the saline waters obtained from the Dead Sea.
EMBODIMENT 4B The combination according to EMBODIMENT 3B, wherein the Dead Sea water has a specific density of 1.25-1.35 g/ml, pH of 4.6-5.6 (at 25°C), and less than 100 cfu/g of non-pathogenic microbes.
EMBODIMENT 5B The combination according to any one of EMBODIMENTS 2B to 4B, wherein the Dead Sea water comprises Ca +2 , CT, Mg +2 , Na + , K + and Br".
EMBODIMENT 6B The combination according to EMBODIMENT IB, wherein said Dead Sea extract is an aqueous solution simulating the salts and minerals content of the Dead Sea water.
EMBODIMENT 7B The combination according to any one of EMBODIMENTS IB to 6B, wherein said Dead Sea extract is the commercially available product Maris Sal.
EMBODIMENT 8B The combination according to any one of EMBODIMENTS IB to 7B, wherein said at least one extract of the plant Rumex is a Rumex occidentalis plant extract.
EMBODIMENT 9B The combination according to any one of EMBODIMENTS IB to 8B, wherein said at least one extract of the plant Rumex is the commercially available Tyrostat™ extract (e.g., Tyrostat™ 09 and/or Tyrostat™ 11).
EMBODIMENT 10B The combination according to any one of EMBODIMENTS IB to 9B6, wherein said at least one extract of the plant Rumex is formulated with at least one additive.
EMBODIMENT 11B The combination according to EMBODIMENT 10B, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 12B The combination according to EMBODIMENT 10B or 11B, wherein said additive is Glycerin and/or Ascorbic Acid.
EMBODIMENT 13B The combination according to any one of EMBODIMENTS IB to 12B, wherein said at least one Thioredoxin polypeptide is a human Thioredoxin. - I l l -
EMBODIMENT 14B The combination according to any one of EMBODIMENTS IB to 12B, wherein said at least one Thioredoxin polypeptide is a plan Thioredoxin.
EMBODIMENT 15B The combination according to any one of EMBODIMENTS IB to 14B, wherein said at least one Thioredoxin polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana).
EMBODIMENT 16B The combination according to any one of EMBODIMENTS IB to 15B, wherein said at least one Thioredoxin polypeptide is the plant- Thioredoxin-1 (plant- TRX-1).
EMBODIMENT 17B The combination according to EMBODIMENT 16B, wherein said plant- Thioredoxin-1 is Oligopeptide-4 (INCI).
EMBODIMENT 18B The combination according to any one of EMBODIMENTS IB to 17B, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1.
EMBODIMENT 19B The combination according to any one of EMBODIMENTS IB to 17B, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2.
EMBODIMENT 20B The combination according to any one of EMBODIMENTS IB to 19B, wherein said at least one Thioredoxin polypeptide is a homologue polypeptide having a sequence homology of at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% to the polypeptide of the SEQ ID NO. 1 or the SEQ ID NO. 2.
EMBODIMENT 21B The combination according to any one of EMBODIMENTS IB to 20B, wherein said at least one Thioredoxin polypeptide comprises one or more conventional tags.
EMBODIMENT 22B The combination according to any one of EMBODIMENTS IB to 2 IB, wherein said at least one Thioredoxin polypeptide is the commercially available plant- Thioredoxin-1 PUREOXIN™.
EMBODIMENT 23B The combination according to any one of EMBODIMENTS IB to 22B, wherein said at least one Thioredoxin polypeptide is formulated with at least one additive.
EMBODIMENT 24B The combination according to EMBODIMENT 23B, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive. EMBODIMENT 25B The combination according to any one of EMBODIMENTS IB to 24B, wherein said Dead Sea extract is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 2.5 % (w/w) (out of the total weight of the combination).
EMBODIMENT 26B The combination according to any one of EMBODIMENTS IB to 25B, wherein said at least one extract of the plant Rumex is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 3.0 % (w/w) (out of the total weight of the combination).
EMBODIMENT 27B The combination according to any one of EMBODIMENTS IB to 26B, wherein said at least one Thioredoxin polypeptide is present in said combination at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) (out of the total weight of the combination), e.g., between about 0.01% (w/w) to about 4.0 % (w/w) (out of the total weight of the combination).
EMBODIMENT 28B The combination according to any one of EMBODIMENTS IB to 27B, being selected from a skin-care and pharmaceutical combination.
EMBODIMENT 29B The combination according to any one of EMBODIMENTS IB to 27B, for use in topical application.
EMBODIMENT 30B The combination according to any one of EMBODIMENTS IB to 27B, being a synergistic combination.
EMBODIMENT 31B The combination according to any one of EMBODIMENTS IB to 27B being in the form selected from a lotion, an ointment, a gel, a mask, a toner, an essence, a cream, a water in oil or oil in water emulsion, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semisolid, or a liquid make-up, a foundation, and an eye make-up.
EMBODIMENT 32B The combination according to any one of EMBODIMENTS IB to 27B, further comprising at least one additive selected from a diluent, a preservative, an abrasive, an anticaking agent, an antistatic agent, a binder, a buffer, a dispersant, an emollient, an emulsifier, a co-emulsifiers, a fiberous material, a film forming agent, a fixative, a foaming agent, a foam stabilizer, a foam booster, a gellant, a lubricant, a moisture barrier agent, a plasticizer, a preservative, a propellant, a stabilizer a surfactant, a suspending agent, a thickener, a wetting agent, and a liquefier. EMBODIMENT 33B The composition combination according to any one of EMBODIMENTS IB to 27B, further comprising at least one additive selected from an anti-acne agent, an anti-aging agent, an antibacterial agent, an anti-cellulites agent, an antidandruff agent, an antifungal agent, an anti-inflammatory agent, an anti-irritation agent, an antimicrobial agent, an antioxidant agent, an antiperspirant agent, an antiseptic agent, a cell stimulant, a cleansing agent, a conditioner, a deodorant, a depilatory, a detergent, an enzyme, an essential oil, an exfoliant, a fungicide, a glosser, hair conditioner, hair set resin, hair sheen agent, hair waving agent, a humectants, a moisturizer, an ointment base, a perfume, a protein, a skin calming agent, a skin cleanser, a skin conditioner, a skin healing agent, a skin lightening agent, a skin protectant, a skin smoothing agent, a skin softening agent, a skin soothing agent, a sunscreen agent, a tanning accelerator, vitamins, a colorant, and a flavoring agent.
EMBODIMENT 34B The combination according to any one of EMBODIMENTS IB to 27B, for use in the preparation of a cosmetic/ skin-care or a pharmaceutical formulation. EMBODIMENT 35B The combination according to any one of EMBODIMENTS IB to 27B, for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject.
EMBODIMENT 36B The combination for use according to EMBODIMENT 35B, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by topical application of said combination onto the skin.
EMBODIMENT 37B The combination according to any one of EMBODIMENTS IB to 27B, for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of said combination onto the skin of a subject. EMBODIMENT 38B The combination for use according to EMBODIMENT 37B, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 39B A method (therapeutic or non-therapeutic) for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of the combination according to any one of EMBODIMENTS IB to 27B onto the skin of a subject. EMBODIMENT 40B The method according to EMBODIMENT 39B, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 41B The combination according to any one of EMBODIMENTS IB to 27B, for use in improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear.
EMBODIMENT 42B The combination for use according to EMBODIMENT 4 IB, wherein said improving is associated with inhibition of melanin synthesis induced by topical application of said combination onto the skin.
EMBODIMENT 43B The combination according to any one of EMBODIMENTS IB to 27B, for use in a method of improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear, wherein said method comprises topical application of combination onto the skin of a subject.
EMBODIMENT 44B The combination for use according to EMBODIMENT 43B, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 45B A method (therapeutic or non-therapeutic) of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of the combination according to any one of EMBODIMENTS IB to 27B onto the skin of a subject.
EMBODIMENT 46B The method according to EMBODIMENT 45B, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 47B The combination according to any one of EMBODIMENTS IB to 27B, for use in treating and/or preventing at least one disease or disorder of the skin. EMBODIMENT 48B The combination for use according to EMBODIMENT 47B, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by topical application of said combination onto the skin.
EMBODIMENT 49B The combination according to any one of EMBODIMENTS IB to 27B, for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of said combination onto the skin of a subject. EMBODIMENT 50B The combination for use according to EMBODIMENT 49B, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
EMBODIMENT 51B A method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of the combination according to any one of EMBODIMENTS IB to 27B onto the skin of a subject.
EMBODIMENT 52B The method according to EMBODIMENT 50B, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
EMBODIMENT 53B The combination according to any one of EMBODIMENTS IB to 27B, for use in treating and/or preventing inflammation of the skin of a subject.
EMBODIMENT 54B The combination for use according to EMBODIMENT 53B, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by topical application of said combination onto the skin.
EMBODIMENT 55B The combination according to any one of EMBODIMENTS IB to 27B, for use in a method of treating and/or preventing inflammation of the skin of a subject wherein said method comprises topical application of said combination onto the skin of a subject.
EMBODIMENT 56B The combination for use according to EMBODIMENT 55B, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 57B A method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of the combination according to any one of EMBODIMENTS IB to 27B onto the skin of a subject.
EMBODIMENT 58B The method according to EMBODIMENT 57B, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 59B The combination according to any one of EMBODIMENTS B to 27B, for use in inhibiting and/or reducing skin melanin formation.
EMBODIMENT 60B The combination according to any one of EMBODIMENTS IB to 27B, for use in a method of inhibiting and/or reducing skin melanin formation wherein said method comprises topical application of said combination onto the skin of a subject. EMBODIMENT 61B A method (therapeutic or non-therapeutic) of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of the combination according to any one of EMBODIMENTS IB to 27B onto the skin of a subject.
EMBODIMENT 62B A lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up, comprising the combination according to any one of EMBODIMENTS IB to 27B.
EMBODIMENT 63B Use of the combination according to any one of EMBODIMENTS IB to 27B in the manufacture of a pharmaceutical formulation or a skin care formulation.
EMBODIMENT 64B Use of the combination according to any one of EMBODIMENTS IB to 27B in the manufacture of a pharmaceutical formulation or a skin care formulation for one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
EMBODIMENT 65B The combination according to any one of EMBODIMENTS IB to 27B, for use in one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
EMBODIMENT 66B The combination according to any one of EMBODIMENTS IB to 27B, for use in one or more of: improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation. EMBODIMENT 1C A kit comprising (i) at least one Dead Sea extract, (ii) at least one extract of the plant Rumex, and (iii) at least one Thioredoxin polypeptide, wherein each of components (i), (ii) and (iii), independently of the other, is formulated in admixture with one or more of an adjuvant, an excipient, a diluent or a carrier (being a pharmaceutically acceptable and/or a cosmetically acceptable adjuvant, excipient, diluent or carrier); and wherein each of (i), (ii) and (iii) are provided in a form that is suitable for concomitant administration with the other.
EMBODIMENT 2C The kit according to EMBODIMENT 1C, wherein said Dead Sea extract is a mixture of natural materials obtained from the waters of the Dead Sea, and/or the mud surrounding the Dead Sea and/or the soil bed of the Dead Sea.
EMBODIMENT 3C The kit according to EMBODIMENT 1C, wherein said Dead Sea extract is the saline waters obtained from the Dead Sea.
EMBODIMENT 4C The kit according to EMBODIMENT 3C, wherein the Dead Sea water has a specific density of 1.25-1.35 g/ml, pH of 4.6-5.6 (at 25°C), and less than 100 cfu/g of non-pathogenic microbes.
EMBODIMENT 5C The kit according to any one of EMBODIMENTS 2C to 4C, wherein the Dead Sea water comprises Ca +2 , Cl", Mg +2 , Na + , K + and Br".
EMBODIMENT 6C The kit according to EMBODIMENT 1C, wherein said Dead Sea extract is an aqueous solution simulating the salts and minerals content of the Dead Sea water.
EMBODIMENT 7C The kit according to any one of EMBODIMENTS 1C to 6C, wherein said Dead Sea extract is the commercially available product Maris Sal.
EMBODIMENT 8C The kit according to any one of EMBODIMENTS 1C to 7C, wherein said at least one extract of the plant Rumex is a Rumex occidentalis plant extract. EMBODIMENT 9C The kit according to any one of EMBODIMENTS 1C to 8C, wherein said at least one extract of the plant Rumex is the commercially available Tyrostat™ extract (e.g., Tyrostat™ 09 and/or Tyrostat™ 11).
EMBODIMENT 10C The kit according to any one of EMBODIMENTS 1C to 9C, wherein said at least one one extract of the plant Rumex is formulated with at least one additive.
EMBODIMENT 11C The kit according to EMBODIMENT 10C, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive. EMBODIMENT 12C The kit according to EMBODIMENT 10C or 11C, wherein said additive is Glycerin and/or Ascorbic Acid.
EMBODIMENT 13C The kit according to any one of EMBODIMENTS 1C to 12C, wherein said at least one Thioredoxin polypeptide is a human Thioredoxin.
EMBODIMENT 14C The kit according to any one of EMBODIMENTS 1C to 12C, wherein said at least one Thioredoxin polypeptide is a plan Thioredoxin.
EMBODIMENT 15C The kit according to any one of EMBODIMENTS 1C to 14C, wherein said at least one Thioredoxin polypeptide is a synthetic protein obtainable (or obtained) by gene cloning utilizing a plant (e.g., the plant Nicotiana benthamiana).
EMBODIMENT 16C The kit according to any one of EMBODIMENTS 1C to 15C, wherein said at least one Thioredoxin polypeptide is the plant-Thioredoxin-1 (plant- TRX- 1).
EMBODIMENT 17C The kit according to EMBODIMENT 16C, wherein said plant- Thioredoxin-1 is Oligopeptide-4 (INCI).
EMBODIMENT 18C The kit according to any one of EMBODIMENTS 1C to 16C, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 1, is of the SEQ ID NO. 1 or is a derivative of the SEQ ID NO. 1.
EMBODIMENT 19C The kit according to any one of EMBODIMENTS 1C to 16C, wherein said at least one Thioredoxin polypeptide comprises the SEQ ID NO. 2, is of the SEQ ID NO. 2 or is a derivative of the SEQ ID NO. 2.
EMBODIMENT 20C The kit according to any one of EMBODIMENTS 1C to 19C, wherein said at least one Thioredoxin polypeptide is a homologue polypeptide having a sequence homology of at least 50%, at least 60% and specifically 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% to the polypeptide of the SEQ ID NO. 1 or the SEQ ID NO. 2
EMBODIMENT 21C The kit according to any one of EMBODIMENTS 1C to 20C, wherein said at least one Thioredoxin polypeptide comprises one or more conventional tags.
EMBODIMENT 22C The kit according to any one of EMBODIMENTS 1C to 21C, wherein said at least one Thioredoxin polypeptide is the commercially available plant- Thioredoxin-1 PUREOXIN™.
EMBODIMENT 23C The kit according to any one of EMBODIMENTS 1C to 22C, wherein said at least one Thioredoxin polypeptide is formulated with at least one additive. EMBODIMENT 24C The kit according to EMBODIMENT 23 C, wherein said additive is a stabilizer, a diluent, a carrier, a filler, an antioxidant or any other inert additive.
EMBODIMENT 25C The kit according to any one of EMBODIMENTS 1C to 24C, wherein said Dead Sea extract is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 2.5 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)].
EMBODIMENT 26C The kit according to any one of EMBODIMENTS 1C to 25C, wherein said at least one extract of the plant Rumex is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 3.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)].
EMBODIMENT 27C The kit according to any one of EMBODIMENT 1C to 26C, wherein said at least one Thioredoxin polypeptide is present in said kit at a concentration of between about 0.01% (w/w) to about 5.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)], e.g., between about 0.01% (w/w) to about 4.0 % (w/w) [of the total weight of the formulation thereof or at times out of the total weight of the formulations constituting the kit e.g., the formations of components (i), (ii) and (iii)].
EMBODIMENT 28C The kit according to any one of EMBODIMENTS 1C to 27C, being selected from a skin-care and pharmaceutical kit.
EMBODIMENT 29C The kit according to any one of EMBODIMENTS 1C to 27C, for use in topical application.
EMBODIMENT 30C The kit according to any one of EMBODIMENTS 1C to 27C, being a synergistic kit respectively i.e., the ingredients (i), (ii) and (iii) thereof act in a synergistic manner. EMBODIMENT 31C The kit according to any one of EMBODIMENTS 1C to 27C, wherein the ingredients (i), (ii) and (iii) thereof being in the form selected from a lotion, an ointment, a gel, a mask, a toner, an essence, a cream, a water in oil or oil in water emulsion, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up.
EMBODIMENT 32C The kit according to any one of EMBODIMENTS 1C to 27C, wherein one or more of the ingredients (i), (ii) and (iii) thereof further comprises at least one additive selected from a diluent, a preservative, an abrasive, an anticaking agent, an antistatic agent, a binder, a buffer, a dispersant, an emollient, an emulsifier, a co- emulsifiers, a fiberous material, a film forming agent, a fixative, a foaming agent, a foam stabilizer, a foam booster, a gellant, a lubricant, a moisture barrier agent, a plasticizer, a preservative, a propellant, a stabilizer a surfactant, a suspending agent, a thickener, a wetting agent, and a liquefier.
EMBODIMENT 33C The kit according to any one of EMBODIMENTS 1C to 27C wherein one or more of the ingredients (i), (ii) and (iii) thereof further comprises at least one additive selected from an anti-acne agent, an anti-aging agent, an antibacterial agent, an anti-cellulites agent, an antidandruff agent, an antifungal agent, an anti-inflammatory agent, an anti-irritation agent, an antimicrobial agent, an antioxidant agent, an antiperspirant agent, an antiseptic agent, a cell stimulant, a cleansing agent, a conditioner, a deodorant, a depilatory, a detergent, an enzyme, an essential oil, an exfoliant, a fungicide, a glosser, hair conditioner, hair set resin, hair sheen agent, hair waving agent, a humectants, a moisturizer, an ointment base, a perfume, a protein, a skin calming agent, a skin cleanser, a skin conditioner, a skin healing agent, a skin lightening agent, a skin protectant, a skin smoothing agent, a skin softening agent, a skin soothing agent, a sunscreen agent, a tanning accelerator, vitamins, a colorant, and a flavoring agent.
EMBODIMENT 34C The kit according to any one of EMBODIMENTS 1C to 27C, for use in one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject.
EMBODIMENT 35C The kit for use according to EMBODIMENT 34C, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by topical application of the ingredients comprised within said kit onto the skin. EMBODIMENT 36C The kit according to any one of EMBODIMENTS 1C to 27C, for use in a method for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 37C The kit for use according to EMBODIMENT 36C, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 38C A method (therapeutic or non-therapeutic) for one or more of protecting and/or improving the state of the skin, and preventing and/or treating imperfections of the skin of a subject, wherein said method comprises topical application of the ingredients comprised within the kit according to any one of EMBODIMENTS 1C to 27C onto the skin of a subject.
EMBODIMENT 39C The method according to EMBODIMENT 38C, wherein said protecting and/or improving and/or preventing and/or treating are associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 40C The kit according to any one of EMBODIMENTS 1C to 27C, for use in improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear.
EMBODIMENT 41C The kit for use according to EMBODIMENT 40C, wherein said improving is associated with inhibition of melanin synthesis induced by topical application of the ingredients comprised within said kit onto the skin.
EMBODIMENT 42C The kit according to any one of EMBODIMENTS 1C to 27C, for use in a method of improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear, wherein said method comprises topical application of the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 43C The kit for use according to EMBODIMENT 42C, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 44C A method (therapeutic or non-therapeutic) of improving one or more of skin glow, lucent, radiance, anti-pigmentation, even tone and clear, wherein said method comprises topical application of the ingredients comprised within the kit according to any one of EMBODIMENTS 1C to 27C onto the skin of a subject. EMBODIMENT 45C The method according to EMBODIMENT 44C, wherein said improving is associated with inhibition of melanin synthesis induced by said topical application.
EMBODIMENT 46C The kit according to any one of EMBODIMENTS 1C to 27C, for use in treating and/or preventing at least one disease or disorder of the skin.
EMBODIMENT 47C The kit for use according to EMBODIMENT 46C, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by topical application of the ingredients comprised within said kit onto the skin.
EMBODIMENT 48C The kit according to any one of EMBODIMENTS 1C to 27C, for use in a method of treating and/or preventing at least one disease or disorder of the skin, wherein said method comprises topical application of the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 49C The kit for use according to EMBODIMENT 48C, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
EMBODIMENT 50C A method for treating and/or preventing a disease or disorder of the skin of a subject, wherein said method comprises topical application of the ingredients comprised within the kit according to any one of EMBODIMENTS 1C to 27C onto the skin of a subject.
EMBODIMENT 51C The method according to EMBODIMENT 50C, wherein said treating and/or preventing is associated with one or more of inhibition of melanin synthesis and inflammation inhibition induced by said topical application.
EMBODIMENT 52C The kit according to any one of EMBODIMENTS 1C to 27C, for use in treating and/or preventing inflammation of the skin of a subject.
EMBODIMENT 53C The kit for use according to EMBODIMENT 52C, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by topical application of the ingredients comprised within said kit onto the skin.
EMBODIMENT 54C The kit according to any one of EMBODIMENTS 1C to 27C, for use in a method of treating and/or preventing inflammation of the skin of a subject wherein said method comprises topical application of the ingredients comprised within said kit onto the skin of a subject. EMBODIMENT 55C The kit for use according to EMBODIMENT 54C, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 56C A method for treating and/or preventing inflammation of the skin of a subject, wherein said method comprises topical application of the ingredients comprised within the kit according to any one of EMBODIMENTS 1C to 27C onto the skin of a subject.
EMBODIMENT 57C The method according to EMBODIMENT 56C, wherein said treating and/or preventing is associated with reduction in IL-8 skin levels induced by said topical application.
EMBODIMENT 58C The kit according to any one of EMBODIMENTS 1C to 27C, for use in inhibiting and/or reducing skin melanin formation.
EMBODIMENT 59C The kit according to any one of EMBODIMENTS 1C to 27C, for use in a method of inhibiting and/or reducing skin melanin formation wherein said method comprises topical application of the ingredients comprised within said kit onto the skin of a subject.
EMBODIMENT 60C A method (therapeutic or non-therapeutic) of inhibiting and/or reducing skin melanin formation, wherein said method comprises topical application of the ingredients comprised within the kit according to any one of EMBODIMENTS 1C to 27C onto the skin of a subject.
EMBODIMENT 61C The kit according to any one of EMBODIMENTS 1C to 27C, wherein the components thereof are in the form of a lotion, an ointment, a gel, a mask, a toner, an essence, a shampoo, a moisturizer, a sunscreen, a cream, a stick, a spray, an aerosol, foam, a paste, a mousse, a solid, semi-solid, or a liquid make-up, a foundation, and an eye make-up.
EMBODIMENT 62C The kit according to any one of EMBODIMENTS 1C to 27C, for use in one or more of: improving one or more of skin glow, lucent, radiance, antipigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; treating and/or preventing a disease or disorder of the skin; treating and/or preventing inflammation of the skin of a subject; and inhibiting and/or reducing skin melanin formation.
EMBODIMENT 65C The kit according to any one of EMBODIMENTS 1C to 27C, for use in one or more of: improving one or more of skin glow, lucent, radiance, anti- pigmentation, even tone and clear; protecting and/or improving the state of the skin; preventing and/or treating imperfections of the skin of a subject; and inhibiting and/or reducing skin melanin formation.