JOUY CHANTAL (FR)
| WO1994023717A1 | 1994-10-27 |
| EP2359702A1 | 2011-08-24 | |||
| JP2014114290A | 2014-06-26 |
| CLAIMS 1 . A composition comprising, in a physiologically acceptable aqueous medium: a) hesperetin, and b) at least one compound with solubility parameters in the Hansen solubility space such that 10.5 < δ3 < 20 and 13.5 < δά < 25.5. 2. The composition as claimed in the preceding claim, characterized in that said compound (b) has solubility parameters in the Hansen solubility space such that 10.5 < δ3 < 19.6 and 15.5 < δά < 20, preferably is a solvent for hesperetin. 3. The composition as claimed in either of the preceding claims, characterized in that said compound (b) is chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units), dipropylene glycol and dimethyl isosorbide, and a mixture thereof. 4. The composition as claimed in any one of the preceding claims, characterized in that said compound (b) is present in a content ranging from 0.1 % to 70% by weight, preferably ranging from 2% to 40% by weight and preferentially ranging from 5% to 30% by weight relative to the total weight of the composition. 5. The composition as claimed in any one of the preceding claims, characterized in that hesperetin is present in a content ranging from 0.05% to 10% by weight, preferably ranging from 0.10% to 5% by weight and preferentially ranging from 0.10% to 2.5% by weight relative to the total weight of the composition. 6. The composition as claimed in any one of the preceding claims, characterized in that compound (b) and hesperetin are present in a compound (b)/hesperetin mass ratio at least equal to 2, especially ranging from 2 to 50 and preferably ranging from 5 to 20. 7. The composition as claimed in any one of the preceding claims, in which said solvent is PEG-8 (polyethylene glycol containing 8 ethylene glycol units) and the PEG-8/hesperetin mass ratio is at least equal to 2, for example ranging from 2 to 30 and preferably ranging from 3 to 10. 8. The composition as claimed in any one of the preceding claims, in which said compound (b) is dipropylene glycol, and the dipropylene glycol/hesperetin mass ratio is at least equal to 2, for example ranging from 2 to 50 and preferably ranging from 5 to 20. 9. Composition according to any one of the preceding claims, characterized in that it is in the form of a water-in-oil or oil-in-water emulsion, preferably an oil-in-water emulsion. 10. The composition as claimed in any one of the preceding claims, characterized in that it is a cosmetic composition. 1 1. A cosmetic process for treating keratin materials, comprising the application to the keratin materials, such as the skin, of a composition as claimed in any one of the preceding claims. 12. A cosmetic treatment process for caring for and/or making up and/or cleansing keratin materials, especially the skin, comprising the application to said keratin materials, especially the skin, of a composition as defined in any one of claims 1 to 10. 13. A cosmetic process for preventing and/or treating the signs of aging of the skin, comprising at least one step of topical application to the keratin materials, such as the skin, of a composition as defined in any one of claims 1 to 10. |
The present invention relates to a composition, preferably a cosmetic composition, com- prising hesperetin and at least one compound with particular solubility parameters in the Hansen solubility space.
Hesperetin is an organic compound of the flavanone family, which is a subgroup of the flavonoids. It is found in nature mainly in the form of its heteroside, hesperidin, which is present in fruits of the Citrus genus.
Hesperetin is an advantageous substance as an antioxidant, and for treating the signs of aging of the skin.
However, this compound, which is in solid form at room temperature and has a high melt- ing point (220°C), is difficult to dissolve, and especially is sparingly soluble in water and glycerol.
Now, it is necessary for this compound to be formulated in a solubilized form in order to fully exploit its activity, and it is also preferable for its solubilization to be maintained over time in order to avoid any recrystallization during storage of compositions comprising such a compound.
The object of the present invention is, precisely, to propose a novel galenical formulation of hesperetin that can overcome the abovementioned drawbacks, and thus to incorporate this compound in a form that is solubilized and long-lasting, and this novel galenical formulation of hesperetin makes it possible especially to improve the efficacy of the active agent for treating keratin materials such as the skin.
The inventors have discovered, unexpectedly, that the combination of hesperetin with at least one compound having particular solubility parameters in the Hansen solubility space enables hesperetin to be solubilized while avoiding its recrystallization, especially after storage for two months at room temperature (25°C).
More precisely, a subject of the invention is a composition, especially a cosmetic composi- tion, comprising, in a physiologically acceptable aqueous medium:
a) hesperetin, and
b) at least one compound with solubility parameters in the Hansen solubility space such that 10.5 < δ 3 < 20 and 13.5 < δ ά < 25.5 as defined below.
Hesperetin is a compound of chemical structure:
Hesperetin is also known as 3',5,7-trihydroxy-4'-methoxyflavanone, or (S)-2,3-dihydro- 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1 -benzopyran-4-one (CAS No.: 520-33- 2).
Hesperetin is especially available under the trade name Hesperetin Purified® from the company Ferrer Grupo-Exquim (Ferrer), or under the name FMLT HespeSphere 1 .0® from the company Biospectrum, Inc., or under the name GFX® from the company Industrial Research Limited, or under the name Jeju Citrus Aglyconoid Liposome® from the company.
Hesperetin may be present in the composition according to the invention in a content ranging from 0.001 % to 10% by weight, particularly ranging from 0.05% to 10% by weight, preferably ranging from 0.1 % to 5% by weight, preferentially ranging from 0.1 % to 2.5% by weight and better still ranging from 0.1 % to 1 % by weight relative to the total weight of the composition.
The composition according to the invention comprises at least one compound (b) with solubility parameters in the Hansen solubility space such that:
10.5 < δ 3 < 20 and 13.5 < δ ά < 25.5.
Said compound (b) is present in the composition according to the invention in an effective amount, i.e. in an amount that is sufficient to dissolve the hesperetin. Preferably, said compound (b) is a solvent for hesperetin. More particularly, the composition according to the invention comprises at least one compound (b) which is a solvent, preferably an organic solvent, with solubility parameters in the Hansen solubility space such that:
10.5 < δ 3 < 20 and 13.5 < δ ά < 25.5.
A solvent is a substance, which is liquid at its working temperature, which has the property of dissolving, or of chemically diluting, without itself being modified.
The term "organic solvent" refers to solvents that are organic compounds which contain carbon atoms.
The composition according to the invention particularly comprises an effective amount of at least one compound (b) with solubility parameters in the Hansen solubility space such that:
10.5 < δ 3 < 20 and 13.5 < δο < 25.5.
The global solubility parameter δ according to the Hansen solubility space is defined in the article "Solubility parameter values" by Eric A. Grulke in the book "Polymer Handbook", 3rd Edition, Chapter VI I , pages 519-559, by the relationship: δ = (δ 2 = δ + δ ρ 2 + h 2 ) m in which
- δ ά characterizes the London dispersion forces derived from the formation of dipoles in- duced during molecular impacts,
- δ ρ characterizes the Debye interaction forces between permanent dipoles,
- 6 h characterizes the specific interaction forces (such as hydrogen bonding, acid/base, donor/acceptor, etc.). The definition of solvents in the Hansen three-dimensional solubility space is described in the article by CM. Hansen: "The three-dimensional solubility pa- rameters", J. Paint Technol. 39, 105 (1967).
The parameter 8 a is defined by the following relationship: δ 3 2 = δ ρ 2 + 8 h 2 = δ 2 - δ The parameters δ ά , δ ρ , 8 h s and 8 a are expressed in (J/cm 3 ) 1 ' 2 .
Preferably, the compound (b) has solubility parameters such that
10.5 < δ 3 < 19.6 and 15.5 < δο < 20 Compound (b) used according to the invention may be chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units) (δ 3 = 14.80; δ ά = 17.90); dipropylene glycol (δ 3 = 19.48; δο = 16.20), dimethyl isosorbide (δ β = 10.76; δ ά = 17.42), or a mixture thereof. Preferably, compound (b) is chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units); dipropylene glycol and dimethyl isosorbide.
Particularly preferably, compound (b) is chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units) and dipropylene glycol.
The compound(s) (b) may be present in the composition according to the invention in a content ranging from 0.1 % to 70% by weight, preferably ranging from 2% to 40% by weight and preferentially ranging from 5% to 30% by weight relative to the total weight of the composition.
According to one embodiment, compound (b) in accordance with the invention and hes- peretin described previously may be present in the composition according to the invention in a compound (b)/hesperetin mass ratio at least equal to 2, especially ranging from 2 to 50 and preferably ranging from 5 to 20.
According to a preferred embodiment, compound (b) in accordance with the invention is PEG-8 (polyethylene glycol containing 8 ethylene glycol units), and this said compound (b) and hesperetin are present in the composition according to the invention in a PEG- 8/hesperetin mass ratio which is at least equal to 2, for example ranging from 2 to 30 and preferably ranging from 3 to 10.
According to a preferred embodiment, compound (b) in accordance with the invention is dipropylene glycol, and this said compound (b) and hesperetin are present in the composition according to the invention in a dipropylene glycol/hesperetin mass ratio which is at least equal to 2, for example ranging from 2 to 50 and preferably ranging from 5 to 20.
A subject of the present invention is also the use in a composition, preferably a cosmetic composition, of at least one compound (b) with solubility parameters in the Hansen solubility space such that: 10.5 < δ 3 < 20 and 13.5 < δ ά < 25.5 as defined above, as solvent for hesperetin.
More particularly, a subject of the invention is the use in a composition, preferably a cosmetic composition, of at least one compound (b) chosen from PEG-8 (polyethylene glycol containing 8 ethylene glycol units); dipropylene glycol and dimethyl isosorbide and/or a mixture thereof, as solvent for hesperetin.
The compositions used according to the invention contain a physiologically acceptable medium, i.e. a medium that is suitable for the topical administration of a composition, i.e. that is compatible with human keratin materials such as the skin, the scalp, the hair and the nails. According to the invention, a physiologically acceptable medium is preferentially a cosmetically acceptable medium, that is to say a medium which is free of any unpleasant odor or appearance and which is entirely compatible with the topical administration route.
According to the invention, the term "keratin materials" means the skin, of the body, face and/or area around the eyes, the lips, the nails, mucous membranes, the eyelashes, the eyebrows, bodily hair, the scalp and/or head hair, or any other area of bodily skin. More particularly, the keratin materials according to the invention are the scalp, the hair and/or the skin.
Preferably, the keratin materials according to the invention are the scalp and/or the hair. Preferably, the keratin materials according to the invention are the skin.
The term "skin" means all of the skin of the body, and preferably the skin of the face, neckline, neck, arms and forearms, or even more preferably still the skin of the face, in particular of the forehead, nose, cheeks, chin and area around the eyes.
As specified hereinbelow, hesperetin is advantageously present in the compositions in accordance with the invention in a dissolved form.
By way of example, the composition according to the invention may be intended to be administered topically, i.e. by application at the surface of the keratin material under consideration, such as the skin under consideration.
The composition of the invention may be a cosmetic composition (i.e. intended for cosmetic purposes) or a dermatological composition. Preferentially, according to the invention, the composition is a cosmetic composition and even more preferentially a cosmetic composition for topical application.
The term "cosmetic composition" especially means a substance or a preparation intended to be brought into contact with the various superficial parts of the human body, in particular the epidermis, the bodily-hair and head-hair systems, the nails, the lips and the oral mucous membranes, with a view, exclusively or mainly, to cleansing them, making them more attractive, fragrancing them, modifying their appearance, protecting them, keeping them in good condition, or correcting body odors.
The compositions according to the invention may be in the form of aqueous solutions, aqueous-alcoholic solutions, oil-in-water (O/W) emulsions, water-in-oil (W/O) emulsions or multiple emulsions (triple: W/O/W or 0/W/O), or aqueous gels. These compositions are prepared according to the usual methods.
The composition may comprise at least one oil. As oils that may be used, examples that may be mentioned include:
- hydrocarbon-based oils of plant origin, such as liquid triglycerides of fatty acids containing from 4 to 10 carbon atoms, for instance heptanoic or octanoic acid triglycerides, or alternatively, for example, sunflower oil, corn oil, soybean oil, marrow oil, grapeseed oil, sesame seed oil, hazelnut oil, apricot oil, macadamia oil, arara oil, castor oil, avocado oil, caprylic/capric acid triglycerides, for instance those sold by the company Stearineries Dubois or those sold under the names Miglyol 810, 812 and 818 by the company Dynamit Nobel, jojoba oil and shea butter oil;
- synthetic esters and ethers, especially of fatty acids, for instance the oils of formulae R1 COOR2 and R10R2 in which R1 represents a fatty acid residue containing from 8 to 29 carbon atoms and R2 represents a branched or unbranched hydrocarbon-based chain containing from 3 to 30 carbon atoms, for instance Purcellin oil, isononyl isononanoate, isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl stearate, 2-octyldodecyl eru- cate or isostearyl isostearate; hydroxylated esters, for instance isostearyl lactate, octyl hydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate or triisocetyl citrate; fatty alcohol heptanoates, octanoates or decanoates; polyol esters, for instance propylene glycol dioctanoate, neopentyl glycol diheptanoate and diethylene glycol diisononanoate; and pentaerythritol esters, for instance pentaerythrityl tetraisostearate;
- linear or branched hydrocarbons of mineral or synthetic origin, such as volatile or nonvolatile liquid paraffins, and derivatives thereof, petroleum jelly, polydecenes, and hydro- genated polyisobutene such as Parleam oil;
- fatty alcohols containing from 8 to 26 carbon atoms, for instance cetyl alcohol, stearyl alcohol and a mixture thereof (cetylstearyl alcohol), octyldodecanol, 2-butyloctanol, 2- hexyldecanol, 2-undecylpentadecanol, oleyl alcohol or linoleyl alcohol;
- silicone oils, for instance volatile or non-volatile polymethylsiloxanes (PDMS) with a line- ar or cyclic silicone chain, which are liquid or pasty at room temperature, especially cy- clopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; polydime- thylsiloxanes comprising alkyl, alkoxy or phenyl groups, which are pendent or at the end of a silicone chain, these groups containing from 2 to 24 carbon atoms; phenylsilicones, for instance phenyl trimethicones, phenyl dimethicones, phenyltrimethylsiloxydiphen- ylsiloxanes, diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes or 2-phenylethyl trimethylsiloxy silicates, and polymethylphenylsiloxanes;
- mixtures thereof.
In the list of oils mentioned above, the term "hydrocarbon-based oil" means any oil mainly comprising carbon and hydrogen atoms, and possibly ester, ether, fluoro, carboxylic acid and/or alcohol groups. The composition according to the invention may comprise substances that are solid at room temperature (25°C), for instance fatty acids comprising from 8 to
30 carbon atoms, such as stearic acid, lauric acid, palmitic acid and oleic acid; waxes such as lanolin, beeswax, carnauba wax or candelilla wax, paraffin waxes, microcrystal- line waxes, ceresin or ozokerite, and synthetic waxes such as polyethylene waxes and Fischer-Tropsch waxes.
These fatty substances may be chosen in a varied manner by a person skilled in the art so as to prepare a composition having the desired properties, for example in terms of consistency or texture. According to one particular embodiment of the invention, the composition according to the invention is a water-in-oil (W/O) or oil-in-water (O/W) emulsion. The proportion of the oily phase of the emulsion may range from 5% to 80% by weight and preferably from 5% to 50% by weight relative to the total weight of the composition. The emulsions generally contain at least one emulsifier chosen especially from amphoteric, anionic, cationic and nonionic emulsifiers, used alone or as a mixture, and optionally a co-emulsifier. The emulsifiers are chosen in an appropriate manner according to the emulsion to be obtained (W/O or O/W emulsion). The emulsifier and the co-emulsifier are generally present in the composition in a proportion ranging from 0.3% to 30% by weight and preferably from 0.5% to 20% by weight relative to the total weight of the composition.
For W/O emulsions, examples of emulsifiers that may be mentioned include dimethicone copolyols, such as the mixture of cyclomethicone and dimethicone copolyol sold under the trade name DC 5225 C by the company Dow Corning, and alkyl dimethicone copolyols such as the lauryl methicone copolyol sold under the name Dow Corning 5200 Formulation Aid by the company Dow Corning, and the cetyl dimethicone copolyol sold under the name Abil EM 90® by the company Goldschmidt. A crosslinked elastomeric solid orga- nopolysiloxane comprising at least one oxyalkylene group, such as those obtained ac- cording to the procedure of Examples 3, 4 and 8 of patent US-A-5 412 004 and of the examples of patent US-A-5 81 1 487, especially the product of Example 3 (synthesis example) of patent US-A-5 412 004, such as the product sold under the reference KSG 21 by the company Shin-Etsu, may also be used as surfactants for W/O emulsions.
For the O/W emulsions, examples of emulsifiers that may be mentioned include nonionic emulsifiers such as oxyalkylenated (more particularly polyoxyethylenated) fatty acid esters of glycerol; oxyalkylenated fatty acid esters of sorbitan; oxyalkylenated (oxyethylenated and/or oxypropylenated) fatty acid esters; oxyalkylenated (oxyethylenated and/or oxypro- pylenated) fatty alcohol ethers; sugar esters such as sucrose stearate; and mixtures thereof, such as the mixture of glyceryl stearate and PEG-40 stearate.
The composition may be an aqueous gel, and may especially comprise common aqueous gelling agents.
In a known manner, the composition according to the invention may also contain adjuvants that are common in cosmetics or dermatology, such as gelling agents, film-forming polymers, preserving agents, fragrances, fillers, UV-screening agents, bactericides, odor absorbers, dyestuffs, plant extracts, cosmetic and dermatological active agents, and salts. The amounts of these various adjuvants are those conventionally used in the field under consideration, for example from 0.01 to 20% of the total weight of the composition.
A further subject of the invention is a cosmetic process for treating keratin materials, com- prising the application to the keratin materials, especially the skin, or the oral administration to an individual, of a composition as described previously.
Said cosmetic treatment process is non-therapeutic.
More particularly, a subject of the invention is also a cosmetic treatment process for caring for, making up and/or cleansing keratin materials, especially the skin, comprising the application to said keratin materials, especially the skin, of a composition according to the invention as described previously.
Said cosmetic treatment process for caring for, making up and/or cleansing the skin is non-therapeutic.
More particularly, a subject of the invention is also a cosmetic process for preventing and/or treating the signs of aging of the skin, comprising at least one step of topical appli- cation to the keratin materials, such as the skin, of a composition according to the invention as described previously.
The signs of aging of the skin to be prevented and/or treated in the cosmetic process according to the invention may be chosen from wrinkles and fine lines, and/or for combating wizened, flaccid and/or thinned skin.
A subject of the present invention is also the cosmetic use of a composition according to the invention as defined previously, for caring for, making up and/or cleansing keratin materials.
More particularly, a subject of the invention is the cosmetic use of a composition as defined previously for caring for the skin, preferably for preventing and/or treating the signs of aging of the skin.
In another embodiment, the invention relates to a cosmetic treatment process for caring for, making up and/or cleansing keratin materials, especially the skin, comprising the oral administration, to an individual, of a composition as defined previously.
In another embodiment, the invention also relates to the cosmetic use as defined previously, in which the combination of hesperetin and of at least one organic solvent as defined previously, or the composition comprising it, is used in a food supplement.
The expressions "between... and..." and "ranging from... to..." or "at least..." or "at the least..." should be understood as being limits included, unless otherwise specified.
The examples below of compositions according to the invention are given as illustrations with no limiting nature. The compounds are indicated as their chemical name or their INCI name.
The amounts of the ingredients are expressed as weight percentages.
Example 1 : solubility test
The test compound (solvent) was poured into a beaker and an amount of hesperetin was added with magnetic stirring over 10 minutes. The mixture was then heated at 60°C for 10 minutes with magnetic stirring, and was then left to stand for between 1 hour and 24 hours at room temperature. The mixture was then heated to 60°C and left to cool to room temperature (25°C) over 24 hours. The system was then observed to see if the amount of hesperetin introduced recrystallized or remained dissolved.
The amount of hesperetin that can be dissolved in the test compound was determined in this manner. The maximum value corresponds to the amount at and above which hesperetin stops dissolving in the evaluated solvent.
The following results were obtained in several evaluated compounds (solvents):
Test compound Degree of
solubilization
(weight%)
Ethanol 1 %
Water <1 %
PEG-8 (polyethylene glycol 400 DUB PEG 8® from 20%
Stearinerie Dubois)
Glycerol <1 %
1 ,3-Propanediol (Zemea Propanediol® from DuPont Tate 1 %
and Lyle Bioproducts)
Propylene glycol (1 ,2-Propylene Glycol Care® from BASF) 1 %
Dipropylene glycol (Dipropylene Glycol LO+® from Dow 10%
Chemical)
Butylene glycol (1 ,3 Butylene Glycol® from Alzo) 1 %
Isododecane (Isododecane® from Ineos) <1 %
Isopropyl myristate ester or isopropyl myristate (Palmester <1 %
1510® from KLK Oleo)
Isopropyl N-lauroyl sarcosinate (Eldew SL-205® from 1 %
Ajinomoto) Isononyl isononanoate (isononyl isononanoate (DUB ININ) <1 % © from Stearinerie Dubois)
Dimethyl isosorbide (Arlasolve DMI-LQ-(AP) ® from 20%
Croda )
Hydrogenated polyisobutene (Parleam® from NOF Corpora<1 %
tion)
Phenethyl benzoate (and) benzoic acid (2-phenethyl benzo- <1 %
ate X-Tend 226® from ISP)
2-Octyldodecanol (Isofol 20 N/F® from Sasol) <1 %
Caprylic/capric acid triglycerides (70/30 C8-C10 triglycer<1 %
ides (DUB MCT 7030) © from Stearinerie Dubois)
C12-15 Alkyl benzoate (Finsolv TN® from Innospec Active <1 %
Chemicals)
It was thus found that hesperetin is dissolved very well with PEG-8, dipropylene glycol and dimethyl isosorbide and is very sparingly dissolved with ethanol, 1 ,3-propanediol, propylene glycol, butylene glycol and isopropyl N-lauroyl sarcosinate.
Example 2: Composition according to the invention
A facial care cream (oil-in-water emulsion) according to the formula made having the following composition was prepared:
Procedure:
Phase A was heated at between 80°C and 85°C until all the fatty substances had fully melted (about 85°C). Phase B was heated to 85°C. Phase A was rapidly added to phase
B with very vigorous stirring for 10 minutes. Add A to B. The emulsion was cooled with slow stirring. Phases C to D were added after cooling to room temperature.
Phase E1 was prepared with stirring using a magnetic bar and added at the end of the preparation. The composition is stable and homogeneous after storage for 2 months at 45°C, and may be applied regularly so as to attenuate the signs of aging of the skin.