CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and all advantages of U.S. Provisional Application No. 63/419,787, filed October 27, 2022, and U.S. Provisional Application No. 63/448,528, filed February 27, 2023, the contents of which are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

[0002] The present invention relates generally to topical cosmetic compositions and methods for preparing cosmetic compositions and, more specifically, to a composition for promoting moisture absorption, moisture retention, and esthetic feel in skin of a subject.

BACKGROUND OF THE INVENTION

[0003] Conventionally, oils have received limited use in cosmetic formulations, thereby minimizing the attention given to the processing of cosmetic compositions including oils. Recently there has been an increased focus on the use of pure/natural oils as ingredients in cosmetic products. However, despite the increase in the use of these oils in cosmetic products, the efficacy and esthetics of these products remains less than satisfactory.

[0004] In view of the foregoing, there remains an opportunity to provide improved topical compositions for administering to skin of a subject that promote moisturization and esthetics. There also remains an opportunity to provide improved methods of preparing such skin compositions, and improved methods of promoting moisture absorption and retention in skin.

BRIEF SUMMARY OF THE INVENTION

[0005] A topical composition for administration to a subject is provided. The composition comprises: i) fermented squalane oil; ii) fermented caprylic/capric triglyceride (MCT) oil; and iii) fermented oil extract of Salvia hispanica seed. The fermented oils are present in the composition in an amount effective to promote moisture absorption and retention in skin of the subject. The topical composition provides better absorption, increased hydration, better esthetic feel, and is more easily spreadable than prior compositions including oils.

[0006] In various embodiments, a method of promoting moisture absorption and retention in skin of a subject comprises topically administering the composition to the skin of the subject.

[0007] A method of preparing a topical composition is also provided. The method comprises mixing squalane oil, caprylic/capric triglyceride (MCT) oil, and oil extract of Salvia hispanica seed to form a mixture, adding a bacteria strain to the mixture, subjecting the mixture to fermentation for a time period of at least 48 hours, and subjecting the fermented mixture to high pressure homogenization to form a nanoemulsion.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 is a plot showing the moisturizing durability of a fermented oil composition in accordance with embodiments of the disclosure, compared to an unfermented oil composition;

[0009] Figure 2 is a graph of the results of a skin hydration study (mean ± SEM, *p<0.05);

[0010] Figure 3 is an arrangement of images of skin hydration over time, taken during the skin hydration study; and

[0011] Figure 4 is a plot showing the percentage of positive answers to a self-assessment questionnaire regarding efficacy and usability.

DETAILED DESCRIPTION OF THE CURRENT EMBODIMENTS

[0012] A topical composition for administration to a subject is disclosed. The topical composition comprises at least fermented squalane oil, fermented caprylic/capric triglyceride (MCT) oil, and fermented oil extract of Salvia hispanica seed. The composition is described below, followed by description of associated uses and methods. The topical composition has improved characteristics, which, as illustrated by the Examples, can be used to maintain the moisturization of a subject’s skin upon administration of the topical composition thereto.

[0013] As will be understood in view of this disclosure, the composition is not particularly limited aside from the inclusion of the three fermented oils, as well as the method of preparing the composition which includes fermenting the oils followed by microfluidization. As such, the composition may be formulated as a topical composition (e.g., a cosmetic composition), and may be utilized as a unique and stand-alone therapeutic or in combination with other therapeutics compatible therewith.

[0014] The composition is usefiil for treating, preventing, and/or ameliorating various conditions, such as those associated with dry skin. Specifically, as will be appreciated in view of the description and examples below, the composition of the present embodiments is believed to be capable of improving absorption by skin, increasing skin hydration, improving the skin microbiome, and improving skin esthetics including texture and spreadability.

[0015] As introduced above, the topical composition comprises, optionally consists essentially of, or optionally consists of at least fermented caprylic/capric triglyceride (MCT) oil, fermented squalane oil, and fermented oil extract of Salvia hispanica seed.

[0016] Caprylic/capric triglyceride oil is produced by combining fatty acids (medium-chain triglycerides or MCTs) with glycerin. The fatty acids are obtained from oils such as coconut oil, or as in the present case, from palm oil (e.g., RSPO-certified MB (mass balance) grade palm oil, i.e. sustainable palm oil from certified sources mixed with conventional palm oil). Specific examples of caprylic/capric triglyceride oils are known in art. As such, caprylic/capric triglyceride oil may be purchased or otherwise obtained commercially from various sources, prepared (e.g. using any conventional technique(s) known in the art), or combinations thereof. The caprylic/capric triglyceride oil may be present in the topical composition in an amount of at least 49.9% by weight, alternatively greater than 49.9%, alternatively greater than 59.9%, alternatively greater than 69.9%, alternatively greater than 79.9%, or alternatively greater than 89.9%. In some embodiments, the caprylic/capric triglyceride oil may be present in the range of approximately 49.9 to 99% by weight, alternatively in the range of 85 to 98.9% by weight, alternatively in the range of 86 to 98%, alternatively in the range of 87 to 97%, alternatively in the range of 88 to 96%, or alternatively in the range of 89 to 95%.

[0017] Squalane oil is derived from the hydrogenation and complete saturation of squalene. The squalene used to produce squalane was originally obtained from shark livers, but is now also derived from plant sources such as olive oil, rice, and in the present case, sugar cane. Specific examples of squalane oils are known in art. As such, squalane oil may be purchased or otherwise obtained commercially from various sources, prepared (e.g. using any conventional technique(s) known in the art), or combinations thereof. Squalane oil may be present in the topical composition in an amount of at least 1.0% by weight and up to 50.0% by weight, alternatively in the range of approximately 1.0 to 15.0% by weight, alternatively in the range of 1.0 to 12.0% by weight, or alternatively in the range of 1.0 to 10.0% by weight.

[0018] The oil extract of Salvia hispanica seed, i.e. hispanica seed oil which is also known as chia seed oil, is obtained from extracting oil from the seeds of the Salvia hispanica plant. Salvia hispanica may be simply referred to as S. hispanica or by its common name chia. S. hispanica is a flowering herb primarily cultivated for its edible seeds (“chia seeds”) that are rich in fatty acids including omega-3 fatty acids such as alpha-linolenic acid, omega-6 fatty acids, and omega-9 fatty acids. Specific examples of S. hispanica seed oils are known in art. As such, S. hispanica seed oil may be purchased or otherwise obtained commercially from various sources, prepared (e.g. using any conventional technique(s) known in the art), or combinations thereof. For example, S. hispanica seed oil may be obtained by mechanical extraction such as by using a screw press, or by solvent extraction using solvents such as pentane, hexane, heptane, or octane in an immersion-type or percolation-type extractor. Solvent remaining in the oil after extraction may be removed in one or more distillation columns. However, it should be understood that S. hispanica seed oil alternatively may be obtained by other extraction methods such as aqueous extraction or CO2 extraction. In various embodiments, S. hispanica seed oil may be present in the topical composition in an amount in the range of approximately 0.05 to 0.15% by weight. In farther embodiments, S. hispanica seed oil may be present in an amount in the range of 0.06 to 0.14% by weight, 0.07 to 0.13% by weight, 0.08 to 0.12% by weight, 0.09 to 0.11% by weight. [0019] To prepare the topical composition, the caprylic/capric triglyceride (MCT) oil, squalane oil, and S. hispanica seed oil are combined together in the range of proportions described above and mixed. The mixture is then subjected to fermentation by inoculation (introduction) of a bacteria strain such as but not limited o a, Lactobacillus reuteri strain. Lactobacillus reuteri may be simply referred to as L. reuteri and is a lactic acid bacterium. In certain embodiments, the Lactobacillus reuteri strain may be specifically Lactobacillus reuteri CH53. The mixture may be cultured for a period of hours or days, for example, at least 12 hours, alternatively at least 24 hours, alternatively at least 36 hours, or alternatively the fermentation is allowed to proceed for at least 48 hours. In various embodiment, the fermentation may be conducted at a temperature in the range of approximately 33 to 41 °C. In farther embodiments, the temperature may be in the range of 34 to 40 °C, 35 to 39 °C, or 36 to 38 °C. In yet farther embodiments, the temperature may be approximately 37 °C.

[0020] After the fermentation of the mixture is complete, the mixture may be filtered by any suitable filtration technique and hence concentrated by removal of any unwanted byproducts of the fermentation process. Next, the fermented oil mixture is subjected to high pressure homogenization (microfluidization) to form a nanoemulsion. The high pressure homogenization may be carried out using a high shear homogenizer (microfluidizer), and may be performed at a pressure in the range of approximately 1,000 to 1,500 psi. The high pressure homogenization may be performed more than once, for example three times. In various embodiments, the high pressure homogenization may result in a particle size reduction to an average particle size of less than approximately 150 nm. In farther embodiments, the average particle size may be less than 140 nm, less than 130 nm, less than 120 nm, less than 110 nm, or less than 100 nm. In some embodiments, the resulting average particle size may be in the range of approximately 90 to 110 nm. In farther embodiments, the resulting average particle size may be in the range of 95 to 105 nm, or may be approximately 100 nm. After high pressure homogenization, the mixture may be subjected to a final filtration. [0021] Without being bound by any particular theory, it is believed that the fermentation and/or microfluidization treatments of the oil mixture are a critical component of the improved performance of the topical composition (as illustrated in the Examples section below).

[0022] In various embodiments, the topical composition may further include one or more supplemental components. More specifically, in addition to the fermented oils of caprylic/capric triglyceride (MCT), squalane, and Salvia hispanica seed, the topical composition may further comprise, optionally further consist essentially of, or optionally fiirther consist of at least one or more of glyceryl caprylate, tocopherol, and/or the oil extract of Helianthus Annuus seed.

[0023] In certain embodiments, only one of the three supplemental components is present in the composition. In other embodiments, only two of the three supplemental components are present in the composition. In yet other embodiments, all three of the supplemental components are present in the composition.

[0024] Glyceryl caprylate is a plant-derived, naturally occurring additive. Specific examples of glyceryl caprylate are known in art. As such, glyceryl caprylate may be purchased or otherwise obtained commercially from various sources, prepared (e.g. using any conventional technique(s) known in the art), or combinations thereof. In various embodiments, glyceryl caprylate may be present in the topical composition in an amount in the range of approximately 0.5 to 1.5% by weight. In fiirther embodiments, glyceryl caprylate may be present in the range of 0.6 to 1.4% by weight, 0.7 to 1.3% by weight, 0.8 to 1.2% by weight, or 0.9 to 1.1% by weight.

[0025] Tocopherols (TCPs) are methylated phenols, some of which have vitamin E activity. Tocopherols include alpha-tocopherol, beta-tocopherol, gamma-tocopherol, and delta- tocopherol. Each tocopherol includes stereoisomers, only one of which is naturally occurring. As such, tocopherol may be purchased or otherwise obtained commercially from various sources, prepared (e.g. using any conventional technique(s) known in the art), or combinations thereof. In various embodiment, tocopherol may be present in the topical composition in an amount in the range of approximately 0.16 to 0.26% by weight. In fiirther embodiments, tocopherol may be present in the range of 0.17 to 0.25% by weight, 0.18 to 0.24% by weight, 0.19 to 0.23% by weight, or 0.20 to 0.22% by weight.

[0026] The oil extract of Helianthus Annuus seed, which is also known as sunflower seed oil, is obtained from extracting oil from the seeds of the Helianthus Annuus plant. Helianthus Annuus may be simply referred to as H. Annuus or by its common name sunflower. H. Annuus is an annual forb primarily cultivated for its ornamental flower head and edible seeds (“sunflower seeds”) which may be eaten whole or from which sunflower oil is extracted. Specific examples of H. Annuus seed oils are known in art. As such, H. Annuus seed oil may be purchased or otherwise obtained commercially from various sources, prepared (e.g. using any conventional technique(s) known in the art), or combinations thereof. For example, H. Annuus seed oil may be obtained by mechanical extraction such as by using a screw press, or by solvent extraction using solvents such as pentane, hexane, heptane, or octane in an immersion-type or percolationtype extractor. Solvent remaining in the oil after extraction may be removed in one or more distillation columns. However, it should be understood that H. Annuus seed oil alternatively may be obtained by other extraction methods such as aqueous extraction or CO2 extraction. In various embodiments, H. Annuus seed oil may be present in the topical composition in an amount in the range of approximately 0.04 to 0.14% by weight. In further embodiments, H. Annuus seed oil may be present in the range of 0.05 to 0.13% by weight, 0.06 to 0.12% by weight, 0.07 to 0.11 % by weight, or 0.08 to 0.10% by weight.

Definitions

[0027] In order to provide a clear and consistent understanding of the specification and claims, the following definitions are provided.

[0028] “Improving the appearance of skin” and “improving the aesthetic appearance of skin” are used interchangeably herein to designate an aesthetic improvement in the appearance of skin. Representative improvements may include, but are not limited to, favorable characteristics and/or properties related skin thickness, elasticity, resiliency, moisturization, smoothness, tone, texture, radiance, luster, brightness, clarity, contour, firmness, tautness, suppleness, softness, sensitivity, pore size, or combinations thereof. These terms may also be used to designate an improvement in an adverse skin condition. Representative adverse conditions affecting by, resulting in or resulting from such an adverse skin condition include, but are not limited to, psoriasis, eczema, seborrhea, dermatitis, sunburn, estrogen imbalance, hyperpigmentation, hypopigmentation, discoloration, yellowing, freckles, skin atrophy, skin breakout, skin fragility, dryness, tactile roughness, chapping, sagginess, thinning, hyperplasia, fibrosis, enlarged pores, cellulite formation, bruising, acne formation, apoptosis, cellular differentiation, cellular dedifferentiation, prevention of tumor induction or tumor progression, viral infections, fungal infections, bacterial infections, spider veins (telangectasia), hirsutism, rosacea, pruritis, calluses, warts, coms, or combinations thereof.

[0029] The terms “composition” or “formulation” refer to a product that treats, improves, promotes, increases, manages, controls, maintains, optimizes, modifies, reduces, inhibits, or prevents a particular condition associated with a natural state, biological process or disease or disorder. For example, a composition or a formulation improves the hydration, feel, and/or appearance of skin. The terms composition and formulation include, but are not limited to, pharmaceutical (i.e., drug), over-the counter (OTC), cosmetic, that include an effective amount of the fermented oils. Exemplary compositions and/or formulations include cream, cosmetic lotion, pack or powder, or as an emulsion, lotion, liniment foam, or ointment. Preferred compositions are formulated for topical application/administration.

[0030] As used herein, the term “effective amount” or “therapeutically effective amount” of a pure compound, composition, and/or active agent or ingredient, or a combination thereof refers to an amount effective at dosages and for periods of time sufficient to achieve a desired result. For example, the “effective amount” or “therapeutically effective amount” refers to that amount of a pure compound, composition, active agent or ingredient, or a combination thereof of this invention which, when administered to a subject (e.g., mammal, such as a human), is sufficient to effect treatment, such as improving the hydration, feel, and/or appearance of skin. The amount of a composition, active agent or ingredient of this disclosure that constitutes an “effective amount” or “therapeutically effective treatment” will vary depending on the active agent, compound, or composition, the condition being treated and its severity, the manner of administration, the duration of treatment, or the age of the subject to be treated, but can be determined routinely by one of ordinary skill in the art having regard to his own knowledge and to this disclosure.

[0031] The term “pharmaceutically acceptable” means those drugs, medicaments, extracts or inert ingredients, which are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, incompatibility, instability, irritation, and the like, commensurate with a reasonable benefit/risk ratio.

[0032] The terms “applying” and “administering” are defined as providing a composition to a subject via a route known in the art, including but not limited to topical, parenteral, buccal, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In preferred embodiments, topical routes of administering the described composition are suitable.

[0033] As used herein, the term “subject” or “individual” includes mammals to which a composition may be administered. Non-limiting examples of mammals include humans, nonhuman primates, rodents (including transgenic and non-transgenic mice) or the like. In some embodiments, the subject is a mammal, and in some embodiments, the subject is human. Compositions (or Formulations')

[0034] The composition may include any amount of the fermented oils, which will be selected based on the number and types of components being utilized in the composition as a whole. In general, the fermented oils are present in the composition in an amount effective to promote hydration in skin of the subject.

[0035] In certain embodiments, composition comprises the fermented oils in an amount of from 1 to 5000, optionally of from 2 to 2000 mg, optionally of from 5 to 1750, optionally of from 10 to 1500, optionally of from 15 to 1250, optionally of from 20 to 1000, optionally of from 25 to 750, optionally of from 30 to 500, optionally of from 35 to 500, optionally of from 40 to 500, optionally of from 45 to 450, optionally of from 50 to 450, or optionally of from 50 to 400, mg. However, amounts outside and/or overlapping with these ranges may also be utilized. For example, it is to be appreciated that the ranges described above with respect to the amount of each fermented oil in the fermented oil mixture may equally apply to the amount of each fermented oil in the composition as a whole.

[0036] In specific embodiments of the composition, the formulation comprises: fermented squalane oil; fermented caprylic/capric triglyceride (MCT) oil; fermented oil extract of Salvia hispanica seed; glyceryl caprylate; tocopherol; and the oil extract of Helianthus Annuus seed. Further specific embodiments are illustrated in the table below.

Table 1 : Example Formulation A Table 2: Example Formulation B

Table 3: Example Formulation C

[0037] In general, the composition is not limited in terms of formulation, peripheral ingredients, form, number of functions, etc., aside from comprising the fermented oils. Rather, the composition may be varied, and may be formulated in any fashion consistent with this disclosure.

[0038] Typically, the composition is formulated or otherwise adapted for administration to a mammalian subject (e.g. a human). For example, in various embodiments, the composition is adapted to be topically administrated to a human subject.

[0039] In certain embodiments, the composition is further defined as a topical composition that is formulated for topical administration to the subject. In such embodiments, the composition may also be referred to as a cosmetic composition. In various embodiments, the composition is administered topically by application to the subject’s skin. The subject is typically a human, and can include men and women of various ages. The method/composition of this disclosure is not limited to a particular subject. [0040] The composition can be in various forms. Examples of suitable forms include solids, gels and liquids. For example, the composition can be formulated for application as a gel, cream, lotion, pomade, mousse, powder, or foam for application to the subject’s skin. In another example, the composition can be formulated for spraying onto a subject’s skin. The composition can be formulated to be sprayed as either an aerosol spray or pump spray. In still another example, the composition can be formulated for application using a pre-moistened towelette. In another example, the composition can be formulated as a solid that is rubbed onto the subject’s skin. In another example, the composition is formulated for delivery through a patch that is adhered to the subject’s skin.

[0041] Other than the fermented oils and supplemental components (i.e., the “actives” or “active ingredients”), the composition can include pharmaceutically acceptable additives that are inactives (or “inactive ingredients”) including, but not limited to, excipients, such as diluents and binders; granulating agents; glidants (or flow aids); fillers; lubricants; preservatives; stabilizers; coatings; disintegrants; fragrances; and pigments. The active ingredients and the pharmaceutically acceptable additives can be combined or compounded as desired to form an individual dose that provides the desired amount of active ingredient to the human subject when topically applied.

[0042] Optionally, the composition may include one or more additional components such as additives. Suitable additives include those understood in the art, including but not limited to, moisturizers, emollients, emulsifiers, surfactants, oils, extracts, skin protectants, disinfectants, antiseptics, drugs and drug substances, analgesic compounds, anti-neuralgic compound, antioxidants, blood circulation promoters, antidepressant compounds, anti-anxiety compounds, antistress compounds, sunscreens, insect repellants, preservatives, exfoliants, fragrances, colors, fillers, solvents, vehicles, carriers, other types of additives known to those of skill in the art, and combinations thereof. Such additives may be utilized alone or in combination. In general, the optional additives may be of any type used in personal care products and cosmetic products.

[0043] In various embodiments, the composition comprises at least one component selected from the group consisting of binders, lubricants, glidants, and combinations thereof. In certain embodiments, the composition includes one or more compounds including, but not limited to, methylcellulose, hydroxypropyl methylcellulose, ethyl cellulose, cellulose acetate phthalate, acacia, gums, wax, glycerol monostearate, acrylic acid polymers and copolymers, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, lactose, calcium sulfate, calcium phosphate dibasic, sugar, microcrystalline cellulose (MCC), starch, sodium starch glycolate, polyvinylpyrrolidone, polyethylene glycol, and magnesium stearate. Combinations of such components can be utilized, and such components and other components used in conventional tablets are understood in the art.

Method of Administration

[0044] The composition may be administered or applied as needed, daily, several times per day or in any suitable regimen such that the desired outcome is achieved. In the method of this disclosure, the frequency of administration (e.g. topical application) can depend on several factors, including the desired level of skin hydration. Generally, a regimen includes application of the composition once or twice daily to include an administration in the morning and/or an administration in the evening. The amount and/or frequency of application of the composition may depend on several factors, including the level of desired results and the specific composition.

[0045] Improved skin hydration and feel can be achieved by externally administering the formulations of the present invention. Preferably, the formulations of the present invention are administered with an acceptable carrier. For example, the formulations of the present invention are topically administered in the form of a: solution, gel, lotion, cream, ointment, oil-in-water emulsion, water-in-oil emulsion, stick, spray, paste, mousse, tonic, foundation, or other cosmetically and topically suitable form. Preferably, the products are useful for providing mammalian skin with improved hydration and feel.

[0046] The formulations of the present invention may also contain various known and conventional cosmetic adjuvants so long as they do not detrimentally affect the desired skin improvement and moisturizing effects provided by the formulation. For example, a formulation of the present invention can further include one or more additives or other optional ingredients well known in the art, which can include but are not limited to fillers (e.g., solid, semi-solid, liquid, etc.); carriers; diluents; thickening agents; gelling agents; vitamins, retinoids, and retinols (e.g., vitamin B3, vitamin A, etc.); pigments; fragrances; sunscreens and sunblocks; anti-oxidants and radical scavengers; organic hydroxy acids; exfoliants; skin conditioners; moisturizers; ceramides, pseudoceramides, phospholipids, sphingolipids, cholesterol, glucosamine, pharmaceutically acceptable penetrating agents (e.g., n-decylmethyl sulfoxide, lecithin organogels, tyrosine, lysine, etc.); preservatives; antimicrobial agents; amino acids such as proline, pyrrolidone carboxylic acid, its derivatives and salts, saccharide isomerate, panthenol, buffers together with a base such as triethanolamine or sodium hydroxide; waxes, such as beeswax, ozokerite wax, paraffin wax; plant extracts, such as Aloe Vera, cornflower, witch hazel, elderflower, or cucumber and combinations thereof. Other suitable additives and/or adjuncts are described in U.S. Pat. No. 6,184,247, the entire contents of which are incorporated herein by reference.

[0047] The formulation can include additional inactive ingredients, including, but not limited to surfactants, co-solvents, and excipients. Surfactants, such as hydrophilic and hydrophobic surfactants, can be included in the formulations. Particular surfactants can be used based on the on the overall composition of the formulation and the intended delivery of the formulation. Useful surfactants include polyethoxylated (PEG) fatty acids, PEG-fatty acid diesters, PEG-fatty acid mono- and di-ester mixtures, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, propylene glycol fatty acid esters, mixtures of propylene glycol esters-glycerol esters, mono- and diglycerides, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, polysaccharide esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, lower alcohol fatty acid esters, ionic surfactants, and mixtures thereof.

[0048] Generally, the formulations of the present invention are topically administered at least on a daily basis for a period of time sufficient to bring about the desired level of improvement in skin hydration and feel. Topical application administration of the formulations of the invention may continue for any suitable period of time. More specifically, within a few hours to within a few days of the initial application, a user may notice the skin has an improved hydration and feel. It should be appreciated that the frequency with which the formulations of the present invention should be applied will vary depending on the desired level of improved hydration and feel. In particular, the degree of cosmetic enhancement will vary directly with the total amount of composition used.

[0049] Useful dosage forms can be prepared by methods and techniques that will be well understood by those of skill in the art.

INDUSTRIAL APPLICABILITY

[0050] This disclosure provides new and usefill topical compositions, including the fermented oils described herein. Such topical compositions can offer potential therapeutic approaches for alleviating dry skin. As such, the compositions and methods described herein are usefiil for skin moisturization. Further, the compositions and methods of this disclosure also improve the skin microbiome balance. [0051] General compositions and product lines provided by this disclosure relate to skin care and cosmetic beauty products utilizing such fermented oils, and specific examples include skin moisturizers utilizing such fermented oils.

[0052] The following examples, illustrating the compositions and methods of this disclosure, are intended to illustrate and not to limit the disclosure.

EXAMPLES

[0053] The moisturizing efficacy of one embodiment of the topical composition was evaluated. The topical composition showed improved absorption and retention of moisture as illustrated in the following Tables and Figures.

Immediate Dermal Moisturizing Effect and Dermal Moisturizing Durability

[0054] The composition was assessed for 12 adults in the age range of 30 to 60. The average age of the subjects was 44.58 years old, with 2 people in their 30’s, 7 people in their 40’s, and 3 people in their ‘50’s. None of the subjects had any specific skin symptoms or any history of disease or pharmaceutical treatment that could affect the test. Each subject waited for 30 minutes in a room under constant temperature and humidity conditions of 22 ± 2 °C and 50 ± 10% humidity prior to the test, and water intake was restricted during the test. The forearm of each subject was used as the test area, and the sample were applied using a 4.5 cm by 3.5 cm long “square” frame at a distance of 5 cm away from the subject’s wrist. The frame was divided into 3 test areas with 1 cm intervals. One of the test areas was used as a non-treated area, another test area was used for a first test sample (composition without fermentation), and the last test area was used for a second test sample (composition according to embodiments of the disclosure, i.e. with fermentation). Approximately 500 pL to 1 mL of sample were applied one time in the respective test areas. Dermal moisture content and moisturizing durability were measured before test sample application, 1 hour after application, 3 hours after application, and 6 hours after application. A Comeometer (CM825) was used to measure dermal moisture and to obtain a hydration index (A.U.), and MoistureMap (MM200) was used to obtain a water density/distribution image.

Evaluation of Skin Moisture Content

[0055] Dermal moisture content was measured using the Comeometer CM825 probe. Dermal moisture content change rate was calculated by the following equation:

(Be fore) -(After)

Dermal moisture content change rate (%) = - - — - - - - X IUU70

(Before) where “Before” was the moisture content measured before the application of test samples, and “After” was the moisture content measured after each prescribed time period (1 hour, 3 hours, 6 hours).

[0056] SPSS Statistics 27 Standard was used to determine the statistical significance of changes in skin measurements before and after administration of the test samples (as well as in the non-treated area), confirming a 95% confidence interval.

[0057] The results are illustrated in the Tables below. The average rates of inhibition can also be appreciated with reference to the Figures.

Table 4: Test Samples

Table 5: Six-Hour Moisturizing Durability

* “Before Use” given a baseline value of zero;

Note: see also Fig. 1 (in which the data is represented graphically)

Table 6: Results of Six-Hour Moisturizing Durability (Comeometer A.U.)

* p<0.05 by repeated measures ANOVA, post hoc Bonferroni correction

** <0.05 by Friedman test, post hoc Wilcoxon signed rank test with Bonferroni correction

*** <0.05 by Independent t-test

Table 7: Results of Six-Hour Moisturizing Durability (MoistureMap: Gray Index A.U.)

[0058] As shown in Table 5 above, Carrier Oil 2 (after fermentation) showed a significant difference between groups with a change of 40.86% 1 hour after application, 40.17% 3 hours after application, and 41.0% 6 hours after application. As shown in Tables 6 and 7 above, Carrier Oil 2 exhibited superb hydration and durability over Carrier Oil 1 (no/before fermentation).

[0059] As shown in Table 7 above, Carrier Oil 2 displayed superb hydration/moisture content and durability over Carrier Oil 1.

Evaluation of Absorption/Esthetic Feel

[0060] Sensitization testing was used to measure dermal absorption and esthetic feeling. Three example compositions including the fermented oils of caprylic/capric triglyceride, squalane, and Salvia hispanica were tested, as well as two comparative example compositions of nonfermented oils of caprylic/capric triglyceride, squalane, and Salvia hispanica. Table 8: Samples

Table 9: Results of Sensitization Testing

[0061] As shown in Tables 8 and 9 above, the efficacy of the fermented oil composition for dermal absorption and esthetic feeling was shown to be better than that of the unfermented oil composition. The composition of Example 2 was found to have the best results.

[0062] Subsequently, the composition of Example 2 was tested for its efficacy on skin microbiome, in comparison to its unfermented counterpart (Comparative Example 2). Two biomarkers were analyzed: i) staphylococcus aureus ATCC 6538 (harmfiil bacteria); and ii) staphylococcus epidermidis ATCC 12228 (beneficial bacteria). The results of the testing showed that the unfermented oil composition (Comparative Example 2) promotes beneficial bacteria but does not inhibit harmful bacteria. On the other hand, the fermented oil composition (Example 2) not only promoted beneficial bacteria but also simultaneously inhibited harmful bacteria. Compared to a control group, the fermented oil composition promoted beneficial bacteria by about 130-160% and inhibited harmful bacteria by about 90%. Hence, applying the fermented oil composition efficiently improves the skin microbiome balance.

Clinical Study to Evaluate the 24-hour Moisture Persistence Effect

[0063] A further clinical study was conducted to evaluate the skin hydration and skin safety of the present topical composition (fermented oil composition) and a non-fermented composition (i.e., the topical composition before fermentation) on human skin. In this study, twenty subjects meeting inclusion and exclusion criteria participated and had either the present topical composition (fermented oil composition) or the non-fermented oil composition applied once on a randomized test site and compared with a control (non-treatment) group. Skin hydration was evaluated and photographed for each subject at designated intervals during the study, including before treatment, 1 hour after treatment, 6 hours after treatment, 12 hours after treatment, and 24 hours after treatment. A safety evaluation was also performed for each subject 1 hour after treatment, 6 hours after treatment, 12 hours after treatment, and 24 hours after treatment. At the end of the study (24 hours after treatment), each subject also completed a self-assessment questionnaire.

[0064] More particularly, twenty subjects ranging in age from 23 to 55 (average age 39.60±12.79 years) who met the inclusion and exclusion criteria completed the clinical evaluation study. More than 20 subjects were initially recruited for the study. The inclusion criteria were as follows: (1) female subjects aged 20 to 55 with no skin abnormality in the forearm area; (2) healthy subjects free from acute and chronic diseases including skin conditions; and (3) subjects who had voluntarily signed the informed consent form after understanding the complete explanation of the purpose and protocol of the study. The exclusion criteria were as follows: (1) women who are pregnant, lactating, or planning to become pregnant within 6 months; (2) subjects who have skin diseases, including active atopic dermatitis, psoriasis, eczema, or active seasonal allergies on the forearm test region; (3) subjects who have used antibacterial agents, immunosuppressants, external skin preparations containing steroids and treatments for chronic skin conditions for more than one month to treat skin conditions on the test region; (4) subjects who have not passed one month since participating in the same study; (5) subjects who used the same or similar efficacy cosmetics and medicines on the test site within one month prior to the start of the study; (6) subjects with chronic diseases (asthma, diabetes, hypertension, etc.); (7) subjects who are continuously on contraceptives, antihistamines, or antiinflammatory drugs; (8) subjects who are employees of the clinical research instituted that conducted the study; and (9) subjects who were considered as inappropriate according to the judgment of the investigator. Subject withdrawal criteria included the following: (1) subjects who have difficulty participating in the research due to obvious adverse reactions; (2) subjects who requested to stop participating; (3) subjects who were inadequate to continuously participate in clinical research, as determined by the researcher (illegal behavior including criminal acts, etc.); (4) subjects who have any skin treatments or medical treatment (cosmetic surgery); (5) subjects who participated in any other research at the same time; (6) subjects who could not follow-up; and (7) any other case in which the subject data could not be included in the research results, such as an omission of major inspection items, data errors, or damage at the end of the study).

[0065] For the study, the test site of each subject was washed and stabilized for 20 minutes in a constant temperature and humidity room, the temperature being 22±2°C and the humidity being 50±5%. Before treatment, the skin hydration of the selected forearm area was measured three times and the average value was obtained using a Comeometer® CM 825 (from C+K, Germany). Subsequently, 50 pL of the test product (fermented topical oil composition or nonfermented topical oil composition) was applied on the specified forearm area (3 x 3 cm) and tapped for absorption. The skin hydration was again measured (3 times each) using the Comeometer® CM 825 at 1 hour after treatment, 6 hours after treatment, 12 hours after treatment, and 24 hours after treatment. Regarding the skin hydration measurements, the epidermis has a characteristic of having a high resistance to electricity. All electrical phenomena are caused by the movement of charges, and capacitance refers to the ability to store these moving charges. In the Comeometer, an electric field is formed between the electrode plates of the probe, and the moisture content in the stratum comeum layer of the epidermis can be measured based on the capacitance generated during measurement. Since the measured capacitance is proportional to the moisture content in the stratum comeum, the higher the measured value the higher the moisture content.

[0066] Photographs of the selected forearm area of each subject were also taken during the study. Specifically, the selected forearm area was photographed using an Epsilon™ El 00 (from Biox, England) before treatment, 1 hour after treatment, 6 hours after treatment, 12 hours after treatment, and 24 hours after treatment. The Epsilon device is capable of taking skin hydration images using a capacitance measurement method that is most widely used for skin hydration measurements, in which the brighter the blue in the image, the higher the amount of skin moisture. [0067] The self-assessment questionnaire included questions related to the efficacy and usability of the products as rated by the subjects on a 6-point scale, with 1 corresponding to “strongly disagree” and 6 corresponding to “strongly agree.” Each subject completed the selfassessment questionnaire 24 hours after treatment. Answers in the range of 4 to 6 points were scored as a positive response. The self-assessment questionnaire included the following ten inquiries: (1) after using the product, it was effective in moisturizing the skin; (2) after using the product, the moisture lasted for a long time; (3) after using the product, skin has softened; (4) after using the product, skin became glossy: (5) after using the product, skin became firm; (6) after using the product, skin became moist; (7) after using the product, skin was improved overall; (8) the product’s spreadability was satisfying; (9) the product’s absorbability was satisfying; and (10) the product was satisfying.

[0068] Regarding the safety evaluation, the researchers evaluated subjective and objective signs by clinical observation of the subjects. In the event of an adverse reaction, an adverse reaction report was to be prepared and the principal investigator would determine the relationship of the reaction with the test product. No adverse skin reactions were observed or reported during the study.

[0069] Statistical analysis of the data was accomplished using SPSS® software (from IBM, USA). The normality test was verified through the Shapiro-Wilk test and kurtosis and skewness. The homogeneity between groups was analyzed by the paired Z-test method, and when the p value was greater than 0.1, it was determined that the prior values between groups are homogeneous. Comparison between groups was analyzed by RM- ANOVA (Repeated Measured Analysis of Variance) (p<0.05). Statistical analysis of variables was also performed using RM- ANOVA at <0.05. The rate of change was calculated using the following equation:

\Before treatment — After treatment

Change from before treatment (%) = - — - - x 100

Before treatment

[0070] The results of the study were as follows. When compared with before treatment, both the skin hydration of the fermented topical oil composition (“carrier oil after fermentation”) and the non-fermented topical oil composition (“carrier oil before fermentation”) application groups increased (improved) significantly at all-time points (p<0.05). The change rate for the carrier oil before fermentation group was 81.98%, 58.35%, 39.57%, and 26.30% (p<0.05), and the change rate for the carrier oil after fermentation group was 84.89%, 65.96%, 50.98%, and 39.64% (p<0.05), respectively at each time interval. Comparing these two groups to the control (nontreatment) group, the skin hydration of both carrier oil groups (before and after fermentation) increased (improved) significantly more than the control group at all-time points relative to before treatment (p<0.05). Further, the skin hydration of the carrier oil after fermentation group increased (improved) significantly more than the carrier oil before fermentation group at the time intervals of 6 hours after treatment, 12 hours after treatment, and 24 hours after treatment relative to before treatment (p<0.05). Results of the self-assessment questionnaire revealed that 95% of the subjects answered positively to all the statements regarding the efficacy and usability of the carrier oil. These results are summarized in Tables 10-12 below, as well as Figs. 2-4.

Table 10: Skin hydration statistical analysis between time points (N=20)

¹ Increment of the mean value represents improvement in skin hydration

² If *p<0.05, there is a significant difference in comparison with before treatment Note: see also Fig. 2 (in which the data is represented graphically) Table 11 : Skin hydration statistical analysis between groups (N=20)

¹ If *p<0.05, there is a significant difference in comparison with control

Table 12: Results of positive answers in self-assessment questionnaire (N=20)

Efficacy and usability scale of 1-6 (1: strongly disagree or very bad; 6: strongly agree or very good)

’n: number of positive answers (rated scale 4 to 6)

² %: number of positive answers / total number of subjects (N) x 100

ADDITIONAL EMBODIMENTS

[0071] The following additional embodiments are provided, the numbering of which is not to be construed as designating levels of importance.

[0072] Embodiment 1 relates to a topical composition for administration to skin of a subject, the composition comprising: i) fermented squalane oil; ii) fermented caprylic/capric triglyceride (MCT) oil; and iii) fermented oil extract of Salvia hispanica seed; wherein the fermented oils are present in the composition in an amount effective to promote moisture absorption and retention in skin of the subject.

[0073] Embodiment 2 relates to the composition according to Embodiment 1, wherein the fermented squalane oil is present in an amount of from approximately 1 to 50 wt. % based on the total weight of the topical composition.

[0074] Embodiment 3 relates to the composition according to Embodiment 1 or 2, wherein the fermented caprylic/capric triglyceride (MCT) oil is present in an amount of from approximately 49 to 99 wt. % based on the total weight of the topical composition. [0075] Embodiment 4 relates to the composition according to any one of Embodiments 1 to 3, wherein the fermented oil extract of Salvia hispanica seed is present in an amount of from approximately 0.05 to 0.15 wt. % based on the total weight of the topical composition.

[0076] Embodiment 5 relates to the composition according to any one of Embodiments 1 to 4, wherein the composition farther comprises an oil extract of Helianthus Annuus seed.

[0077] Embodiment 6 relates to the composition according to Embodiment 5, wherein the oil extract of Helianthus Annuus seed is present in an amount of from approximately 0.04 to 0.14 wt. % based on the total weight of the composition.

[0078] Embodiment 7 relates to the composition according to any one of Embodiments 1 to 6, wherein the composition farther comprises glyceryl caprylate.

[0079] Embodiment 8 relates to the composition according to Embodiment 7, wherein the glyceryl caprylate is present in an amount of from approximately 0.5 to 1.5 wt. % based on the total weight of the composition.

[0080] Embodiment 9 relates to the composition according to any one of Embodiments 1 to 8, wherein the composition farther comprises a tocopherol.

[0081] Embodiment 10 relates to the composition according to Embodiment 9, wherein the tocopherol is present in an amount of from approximately 0.16 to 0.26 wt. % based on the total weight of the composition.

[0082] Embodiment 11 relates to a method of promoting moisture absorption and retention in skin of a subject, the method comprising: topically administering an effective amount of a composition to the skin of the subject, wherein the composition is the topical composition according to any one of Embodiments 1 to 10.

[0083] Embodiment 12 relates a method of preparing the topical composition according to any one of Embodiments 1 to 10, the method comprising: mixing squalane oil, caprylic/capric triglyceride (MCT) oil, and oil extract of Salvia hispanica seed to form a mixture; adding a bacteria strain to the mixture; subjecting the mixture to fermentation for a time period of at least 48 hours; and subjecting the fermented mixture to high pressure homogenization to form a nanoemulsion.

[0084] Embodiment 13 relates to the method according to Embodiment 12, wherein the bacteria strain is Lactobacillus reuteri CH53.

[0085] Embodiment 14 relates to the method according to Embodiment 12 or 13, wherein the fermentation is conducted at a temperature in the range of approximately 33 to 41 °C. [0086] Embodiment 15 relates to the method according to any one of Embodiments 12 to 14, wherein the high pressure homogenization is performed with a high shear homogenizer.

[0087] Embodiment 16 relates to the method according to Embodiment 15, wherein the high pressure homogenization is performed at a pressure in the range of approximately 1 ,000 to 1 ,500 psi.

[0088] Embodiment 17 relates to the method according to Embodiments 15 or 16, wherein the high pressure homogenization is performed more than once.

[0089] Embodiment 18 relates to the method according to any one of Embodiments 15 to 17, wherein the high pressure homogenization results in an average particle size in the range of approximately 90 to 110 nm.

[0090] Embodiment 19 relates to the method according to any one of Embodiments 12 to 18, the method farther comprising filtering the mixture: (i) after subjecting the mixture to fermentation; (ii) after high pressure homogenization; or (iii) both (i) and (ii).

[0091] Embodiment 20 relates to a topical composition prepared according to the method according to any of one Embodiments 12 to 19.

[0092] Embodiment 21 relates to use of the topical composition according to any one of Embodiments 1 to 10, for moisturizing skin of a subject. Embodiment 21a relates to use of the topical composition according to any one of Embodiments 1 to 10 for the manufacture of a medicament for the treatment of skin, optionally for the moisturization of skin of a subject. Embodiment 21b relates to a medicament for treating skin, optionally for moisturization of skin of a subject, the medicament comprising the topical composition according to any one of Embodiments 1 to 10.

[0093] The terms “comprising” or “comprise” are used herein in their broadest sense to mean and encompass the notions of “including,” “include,” “consist(ing) essentially of,” and “consist(ing) of.” The use of “for example,” “e.g.,” “such as,” and “including” to list illustrative examples does not limit to only the listed examples. Thus, “for example” or “such as” means “for example, but not limited to” or “such as, but not limited to” and encompasses other similar or equivalent examples. The term “about” as used herein serves to reasonably encompass or describe minor variations in numerical values measured by instrumental analysis or as a result of sample handling. Such minor variations may be in the order of ±0-10, ±0-5, or ±0-2.5, % of the numerical values. Further, the term “about” applies to both numerical values when associated with a range of values. Moreover, the term “about” may apply to numerical values even when not explicitly stated.

[0094] Generally, as used herein a hyphen or dash in a range of values is “to” or “through”; a “>” is “above” or “greater-than”; a “>” is “at least” or “greater-than or equal to”; a “<” is “below” or “less-than”; and a “<” is “at most” or “less-than or equal to.” On an individual basis, each of the aforementioned applications for patent, patents, and/or patent application publications, is expressly incorporated herein by reference in its entirety in one or more nonlimiting embodiments.

[0095] It is to be understood that the appended claims are not limited to express and particular compounds, compositions, or methods described in the detailed description, which may vary between particular embodiments which fall within the scope of the appended claims. With respect to any Markush groups relied upon herein for describing particular features or aspects of various embodiments, it is to be appreciated that different, special, and/or unexpected results may be obtained from each member of the respective Markush group independent from all other Markush members. Each member of a Markush group may be relied upon individually and or in combination and provides adequate support for specific embodiments within the scope of the appended claims.

[0096] It is also to be understood that any ranges and subranges relied upon in describing various embodiments of the present invention independently and collectively fall within the scope of the appended claims, and are understood to describe and contemplate all ranges including whole and/or fractional values therein, even if such values are not expressly written herein. One of skill in the art readily recognizes that the enumerated ranges and subranges sufficiently describe and enable various embodiments of the present invention, and such ranges and subranges may be further delineated into relevant halves, thirds, quarters, fifths, and so on. As just one example, a range “of from 0.1 to 0.9” may be farther delineated into a lower third, i.e., from 0.1 to 0.3, a middle third, i.e., from 0.4 to 0.6, and an upper third, i.e., from 0.7 to 0.9, which individually and collectively are within the scope of the appended claims, and may be relied upon individually and/or collectively and provide adequate support for specific embodiments within the scope of the appended claims. In addition, with respect to the language which defines or modifies a range, such as “at least,” “greater than,” “less than,” “no more than,” and the like, it is to be understood that such language includes subranges and/or an upper or lower limit. As another example, a range of “at least 10” inherently includes a subrange of from at least 10 to 35, a subrange of from at least 10 to 25, a subrange of from 25 to 35, and so on, and each subrange may be relied upon individually and/or collectively and provides adequate support for specific embodiments within the scope of the appended claims. Finally, an individual number within a disclosed range may be relied upon and provides adequate support for specific embodiments within the scope of the appended claims. For example, a range “of from 1 to 9” includes various individual integers, such as 3, as well as individual numbers including a decimal point (or fraction), such as 4.1, which may be relied upon and provide adequate support for specific embodiments within the scope of the appended claims.

[0097] The present invention has been described herein in an illustrative manner, and it is to be understood that the terminology which has been used is intended to be in the nature of words of description rather than of limitation. Many modifications and variations of the present invention are possible in light of the above teachings. The present invention may be practiced otherwise than as specifically described within the scope of the appended claims. The subject matter of all combinations of independent and dependent claims, both single and multiple dependent, is herein expressly contemplated.