Formulations of calycosin

WO2024233743A3PCT designated stage expired Publication Date: 2025-01-23DEBUT BIOTECHNOLOGY INC
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Patent Information

Application Number
PCT/US2024/028513
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-05-10
Filing Date
2024-05-09
Publication Date
2025-01-23

AI Technical Summary

Technical Problem

Aged skin experiences decreased keratinocyte proliferation, thinning, impaired barrier formation, and slowed wound healing, leading to issues like wrinkles and reduced skin elasticity, for which existing treatments lack effective topical solutions.

Method used

Topical compositions containing calycosin, dissolved in solvents like dimethyl isosorbide, are developed to improve skin resilience, elasticity, and aesthetic appearance by enhancing antioxidant activity, elastase enzyme inhibition, and glycation inhibition, while modulating gene expression to address fine lines, wrinkles, and skin damage.

Benefits of technology

The calycosin compositions demonstrate robust antioxidant activity, elastase inhibition, and glycation inhibition, effectively reducing fine lines and wrinkles, improving skin elasticity, and enhancing skin lightening and brightening, providing a stable and effective topical treatment for aged skin.

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Abstract

The invention provides compositions comprising calycosin. The compositions of the invention may be administered topically, on the skin of the subject. The invention further provides methods of administration of compositions comprising calycosin for amelioration or treatment of a skin condition. The compositions of the invention may also be applied for improving the general appearance of the skin.
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Description

[0001]Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application FORMULATIONS OF CALYCOSIN I. FIELD OF THE INVENTION ^ The invention is related to formulations of calycosin and methods of using the formulations for topical conditions in a subject. II. BACKGROUND OF THE INVENTION Mammalian epidermis and its appendages (e.g., hair, nail, sebaceous and sweat glands)^ provide a barrier to keep harmful elements out of the body and essential body fluids in. As the first line of defense against the various physical traumas of the environment, the epidermis must protect itself as well as the underlying tissues. The epidermis is also exposed to mutagenic ultraviolet radiation. In nonhaired or sparsely haired regions such as most human skin, the epidermis is thicker than that of furred skin, and in these locations the skin functions primarily^ in a protective role. The constant assaults on the epidermis necessitate self-renewal, making the epidermis a prime example of an adult tissue that undergoes continual and rapid flux. Aged skin differs from youthful skin both in appearance and in function. The aged epidermis demonstrates decreased keratinocyte proliferation and is physically thinner, but mostly from decline of the rete ridges. In addition to thinning, aging slows wound healing,^ prolongs epidermal turnover, and impairs barrier formation. The skin appears thin, wrinkled, bruised, and rough. Wrinkling and bruising can also result from aging-related changes in the dermis. The dermis, too, is characteristically thinner in aged persons. Aged fibroblasts are less likely to synthesize normal amounts of collagen, elastin, laminin glycosaminoglycans, and fibronectin. The dermis can, in such cases, lack elasticity, strength, vessel support, remodeling^ abilities, and ground substances. For example, rete ridges can be effaced, and basal cells can no longer display villous projections into the dermis. Epidermal cell turnover is reduced up to 50% in the aged as compared to youth. For example, melanocyte numbers can decrease 8-20% per decade. There are fewer Langerhans cells in the aged, and those present are often functionally impaired. Collagen^ synthesis decreases, for example, up to 30% within 4 years of menopause in women. The 1 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application numbers of collagen and elastic fibers are also decreased. The dermis can also become less echogenic to ultrasounds, consistent with changes in collagen and elastic tissues. III. SUMMARY OF THE INVENTION ^ The invention relates to compositions of calycosin, and methods of using the compositions for treating, protecting, and / or altering (e.g., improving) the condition and / or aesthetic appearance of skin, including, for example, treating, preventing, ameliorating, reducing and / or eliminating fine lines and / or wrinkles of skin and / or improving the aesthetic appearance of fine lines and / or wrinkles of skin. In certain embodiments, the compositions of the invention lead to increase in^ skin and / or hair resiliency. In certain embodiments, the compositions of the invention lead to increase in elasticity of the skin. In certain embodiments, the compositions of the invention prevent skin damage. Topical administration of calycosin was not known in the field. In particular, the topical administration of calycosin for improving the condition of skin, including enhancing the^ appearance of the skin, by topical administration of a composition comprising an effective amount of calycosin was not known in the field. Beneficially, the invention recognizes, for the first time, that topical compositions comprising calycosin may be used for improving the condition of the skin or for treatment of any ailment related to the skin of a subject. In one aspect, the invention includes a composition for topical administration comprising an effective amount of calycosin.^ The effective amount of calycosin is an amount of calycosin that would be effective in treating, ameliorating, or otherwise impacting the underlying condition of the skin. The invention recognizes that calycosin is poorly soluble or insoluble in water. The invention also recognizes that calycosin is also poorly soluble or insoluble in oil, for example, calycosin is insoluble in Helianthus Annuus (Sunflower) Seed Oil. In certain embodiments of the invention, calycosin is^ dissolved in a solvent selected from a group consisting of: dimethyl isosorbide, ethoxydiglycol, isopropyl lauryl sarcosinate, pentylene glycol, propanediol, 1,2-hexanediol, and / or butylene glycol. In certain preferred embodiments, calycosin is dissolved in dimethyl isosorbide. In certain embodiments, the composition comprising calycosin is anhydrous. In certain embodiments, the composition comprises oil as the only solvent. 2 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain embodiments, calycosin is dissolved in a solvent selected from a group consisting of: 1,2 heptanediol, 1,2 hexanediol, 1,2 propanediol, butylene glycol, C15-19 alkane, capric / caprylic triglyceride, dibutyl adipate, diisopropyl adipate, dimethyl isosorbide, dipropylene glycol, ethanol, ethoxydiglycol, isoamyl laurate, isohexadecane, isopentyldiol, isopropyl myristate, isoproyl lauryl^ sarcosinate, jojoba oil, meadowfoam seed oil, mineral oil, neopentyl glycol diethylhexanoate, octyldodecanol, oleyl alcohol, pentylene glycol, phenylpropanol, polysorbate 20, propanediol, safflower seed oil, squalene, sunflower oil, t-butyl alcohol, tributyl citrate, tributyl-O-acetylcitrate, tri-C15-19alkyl citrate, triethyl citrate, triethyl O-acetylcitrate, and triisostearin. Thus, in certain embodiments, the composition comprises an emulsion. Preferably, the^ emulsion is oil / water emulsion. In certain embodiments, the composition further comprises dimethyl isosorbide. In certain embodiments, calycosin is dissolved in dimethyl isosorbide. The compositions of the invention are wherein the composition are stable under storage for at least 3 months. This is beneficial because the compositions of the invention may be stored prior to administration to the subjects. In certain embodiments, wherein the compositions of the invention^ have less than about 10% degradation when stored at 4 ^ or 25 ^ for one (1) month. In certain embodiments, the compositions of the invention have less than about 15% degradation when stored at 40 ^ for one (1) month. In certain embodiments, the composition comprises calycosin in a concentration of about 5 nM to about 2500 nM. In certain embodiments, the composition comprises calycosin in a^ concentration of about 10 nM to about 2000 nM. In certain embodiments, the composition comprises calycosin in a concentration of about 20nM nM to about 1000 nM. In certain embodiments, the composition comprises calycosin in a concentration of about 10 nM to about 20 nM. In certain embodiments, in the compositions of the invention, calycosin is present in a concentration of about 0.0001% to about 5.0% w / w. In certain other embodiments, calycosin is^ present in a concentration of 0.0005% to about 2.0% w / w. In certain other embodiments, calycosin is present in a concentration of 0.0007% to about 1.0% w / w. In certain other embodiments, calycosin is present in a concentration of 0.001% to about 0.75% w / w. In certain other embodiments, calycosin is present in a concentration of 0.001% to about 0.75% w / w. In certain other embodiments, calycosin is present in a concentration of about 0.5% w / w. 3 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain aspects, the compositions of the invention may be administered as a topical composition on the skin of the subject. The compositions of the invention may be included in any formulation suitable for topical administration. In certain embodiments, the composition of the invention is a fluid, emulsion, encapsulation, suspension, solid, semi-solid, jelly, paste, gel,^ hydrogel, ointment, lotion, emulsion, cream, foam, mousse, liquid, spray, suspension, dispersion, powder, aerosol, color cosmetic, and / or hair treatment. In certain embodiments, the compositions of the invention also include excipients. These excipients may be selected from a group consisting of: solvent, emulsifier, preservative, antioxidant, emollient, thickening agent, penetration enhancer, surfactant, diluent, filler, carrier, and / or pH control agent. In certain embodiments, the^ preservative in the composition is an antimicrobial preservative or chelating agent. In certain embodiments, the solvent of the invention is dimethyl isosorbide. The compositions of the invention may be prepared by various methods. As an example, the compositions may be prepared by dissolving, dispersing, etc. calycosin as provided herein and optional excipients in a carrier (e.g., water, saline, aqueous dextrose, glycerol, glycols, ethanol or^ the like) or a solvent to form a solution, colloid, liposome, emulsion, complexes (including inclusion complexes), coacervate, or suspension. In certain embodiments, the compositions of the current invention can also contain additional excipients such as wetting agents, emulsifying agents, co-solvents, solubilizing agents, pH buffering agents, and the like (e.g., sodium acetate, sodium citrate, cyclodextrins and derivatives, sorbitan monolaurate, triethanolamine acetate,^ triethanolamine oleate, hydroxyethylpiperazine and the like). In certain embodiments, the compositions of the invention may further include one or more additional excipients selected from a group consisting of: carriers, excipients, or diluents including, but not limited to, absorbents, anti-irritants, antibacterials, anti-acne agents, antioxidants, coloring agents / pigments, emollients (moisturizers), emulsifiers, film-forming / holding agents, fragrances, leave-on exfoliants,^ prescription drugs, preservatives, scrub agents, silicones, skin-identical / repairing agents, slip agents, sunscreen actives, surfactants / detergent cleansing agents, penetration enhancers, and thickeners. In certain embodiments, the compositions of the invention comprise: calycosin, in an oil / water emulsion, and a preservative. 4 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain embodiments, the compositions of the invention comprise: calycosin, in an oil / water emulsion, a solvent for solubilizing calycosin, and a preservative. In certain embodiments, the compositions of the invention comprise calycosin, in an oil / water emulsion, a solvent for solubilizing calycosin, a diluent, and a preservative. ^ In certain embodiments, the compositions of the invention comprise: calycosin, in an oil / water emulsion, a solvent for solubilizing calycosin, a thickener, optionally a diluent, and a preservative. In certain embodiments, the compositions of the invention comprise: calycosin, in an oil / water emulsion, a solvent for solubilizing calycosin, and one or more excipients selected from^ the group consisting of: diluents, absorbents, antioxidants, emollients, emulsifiers, thickeners, surfactants, and / or preservatives. In certain embodiments, the excipients included in the composition are water, dimethyl isosorbide, glycerin, caprylic / capric triglyceride, propanediol, sunflower seed oil, ethoxydiglycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate,^ capryloyl glycerin / sebacic acid copolymer, diheptyl succinate, naringenin, lecithin, decylene glycol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidyl alcohol, behenyl alcohol, arachidyl glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olea europaea (olive) fruit oil, olea europaea (olive) oil unsponifiables, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, citric acid, sodium acetylated hyaluronate, sodium^ hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and / or ethylhexylglycerin. In certain aspects, the invention provides that the compositions of the inventions are synergistic. The compositions provided in the invention are beneficial because of their enhanced stability due to the synergistic effects of the ingredients in the composition and the resulting^ stability and efficacy. In certain embodiments, the invention provides that the compositions of the invention are more efficacious and stable as compared to when they are administered or stored as individual ingredients. The compositions of the invention may also act synergistically when administered along with other therapies for treatment of the conditions described herein. 5 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain aspects of the invention, the compositions comprising calycosin demonstrate antioxidant activity. In certain embodiments, the compositions of the invention, the antioxidant activity of calycosin is demonstrated at concentrations of about 0.00005% w / w or higher. Advantageously, the compositions of the invention comprising calycosin, demonstrating^ antioxidant activity, are effective for treating and / or preventing oxidation damage. In certain embodiments, the compositions of the invention comprising calycosin, demonstrating antioxidant activity, are effective for treatment of skin and / or hair damaged by reactive oxygen species and protection from other environmental aggressors that may damage the skin of the subject. In certain other embodiments, the compositions of the invention comprising calycosin, demonstrating^ antioxidant activity, are effective for prevention of skin and / or hair damage by reactive oxygen species, including the damage caused by environmental aggressors. In certain aspects of the invention, the compositions comprising calycosin demonstrate elastase enzyme inhibition. In certain embodiments, the compositions of the invention, the elastase enzyme inhibition activity of calycosin is demonstrated at concentrations of about 0.05% w / w or^ higher. Advantageously, the compositions comprising calycosin, demonstrating elastase enzyme inhibition activity, are effective for promoting the elasticity of the skin. In certain embodiments, the compositions of the invention comprising calycosin, demonstrating elastase enzyme inhibition, are effective in reduction of fine lines and / or wrinkles in the skin. In certain embodiments, the compositions of the invention comprising calycosin, demonstrating elastase enzyme inhibition, are^ effective in prevention of formation of fine lines and / or wrinkles in the skin. In certain aspects of the invention, the compositions comprising calycosin demonstrate inhibition of glycation. In certain embodiments, the compositions of the invention, the glycation inhibition activity of calycosin is demonstrated at concentrations of about 0.25% w / w or higher. Advantageously, the compositions comprising calycosin, demonstrating glycation inhibition^ activity, are effective for supporting and promoting skin and / or hair resiliency. In certain aspects of the invention, the compositions comprising calycosin promote skin lightening and / or brightening. In certain embodiments, the compositions comprising calycosin at least a concentration of 0.01% w / w, have about 1% higher L value (reflecting the lightening of the skin), as compared to skin treated with a corresponding composition lacking calycosin. 6 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain aspects of the invention, a composition comprising calycosin modulates expression of one more genes that is related to a topical condition. In certain embodiments, administration of composition comprising calycosin alters one or more of a function related with the modulated genes, wherein the one or more function is selected from the group consisting of:^ (i) lightening / brightening of the skin, (ii) formation of fines lines or wrinkles on the skin, (iii) inflammation, (iv) melanin synthesis, and (v) collagen degradation. In certain embodiments, the one or more genes are selected from a group consisting of: (i) MUCL1, (ii) KLK6, (iii) PSAPL1, (iv) S100A7, (v) IL37, and (vi) MMP1. In certain embodiments, administration of a composition comprising calycosin leads to down-regulation of MUCL1, KLK6, PSAPL1, S100A7, IL37,^ and / or MMP1. In certain embodiments, the administration of the compositions of the invention comprising calycosin enhances anti-inflammatory activity. In certain embodiments, the administration of the compositions of the invention comprising calycosin enhances maintenance of skin barrier lipids. In certain embodiments, the administration of the compositions of the invention comprising^ calycosin enhances the maintenance of collagen network to prevent formation of fine lines and / or wrinkles in the skin. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes involved in promoting melanogenesis. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes^ involved promoting inflammation. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes involved in degradation of skin barrier lipids. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes involved in degradation of molecules involved in barrier function restoration. In certain embodiments, the administration of the composition comprising calycosin^ results in downregulation of genes involved in degradation of molecules involved in degradation of collagen. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of expression and / or activity of mucin like 1 (MUCL1) gene. MUCL1 gene is involved in melanogenesis. In certain embodiments, the decreased expression and / or activity of^ MUCL1 indicates inhibition of melanogenesis. In certain embodiments, the administration of the 7 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application composition comprising calycosin results in about ten (10) fold expression of MUCL1. Since the administration of the composition comprising calycosin results in downregulation of MUCL1, it also results in the decrease in melanogenesis. In certain embodiments, administration of a composition comprising calycosin leads to^ downregulation of kallikrein related peptidase 6 (KLK6) and / or interleukin (IL37). KLK6 is a protease that promotes inflammation. IL37 is also involved in the inflammatory pathway. Thus, downregulation of KLK6 and / or IL37 leads to an anti-inflammatory response. In certain embodiments, administration of a composition comprising calycosin leads to at least about twenty- five (25) fold downregulation of KLK6. In certain embodiments, administration of a composition^ comprising calycosin leads to about fifteen (15) fold downregulation of IL37. In certain embodiments, administration of a composition comprising calycosin leads to downregulation of prosaposin like 1 (PSAPL1) gene. PSAPL1 is involved in lysosomal degradation of sphingolipids. Thus, downregulation of PSAPL1 supports lipid barrier maintenance. The support of barrier lipid maintenance plays a role in the appearance and / or^ elasticity of the skin. In certain embodiments, administration of a composition comprising calycosin leads to about twenty-five (25) fold downregulation of PSAPL1. In certain embodiments, administration of a composition comprising calycosin leads to downregulation of S100 calcium binding protein A7 (S100A7) gene. S100A7 is a signaling molecule, which is highly expressed in dermatitis and psoriasis. Downregulation of S100A7^ supports the lipid barrier maintenance. The support of barrier lipid maintenance plays a role in the appearance and / or elasticity of the skin. In certain embodiments, administration of a composition comprising calycosin leads to at least about fifteen (15) fold downregulation of S100A7. In certain embodiments, administration of a composition comprising calycosin leads to prevention of fine lines and / or wrinkles on the skin. The formation of fine lines and / or wrinkles^ on the skin, in part, is due increased collagen degradation. In certain embodiments, administration of a composition comprising calycosin leads to downregulation of matrix metalloproteinase 1 (MMP1). The downregulation of expression and / or activity of MMP1 results in decrease in breakdown of collagen. In certain embodiments of the invention, the administration of the composition comprising calycosin leads to at least about five (5) fold downregulation of MMP1. 8 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain embodiments, administration of a composition comprising calycosin to a subject leads to the treatment of prevention of a topical condition of the subject through the modulation of levels of expression or activity of one or genes that may be involved in the topical condition. In certain embodiments, administration of a composition comprising calycosin alters one or more of^ a function related with the modulated genes, wherein the one or more function is selected from the group consisting of: (i) maintenance of skin barrier, (ii) collagen expression, (iii) collagen degradation, (iv) inflammation, (v) tissue atrophy, (vi) muscle loss, and (vii) melanin production. IV. BRIEF DESCRIPTION OF DRAWINGS FIG. 1A is a picture of the solution with 0.5% w / w calycosin in oil / water emulsion. ^ FIG. 1B is a picture of 0.72% w / w calycosin solubilized in dimethyl isosorbide. FIG. 2 is a chart of stability of calycosin in dimethyl isosorbide. FIG. 3 provides the data pertaining to gene modulation expression. V. DETAILED DESCRIPTION Calycosin ^ Calycosin is a naturally occurring compound found in astragalus membranaceus. Calycosin is commonly used in traditional Chinese Medicine for its known anti-inflammatory and anti-cancer properties Deng M, et al. Calycosin: a Review of its Pharmacological Effects and Application Prospects. Expert Rev Anti Infect Ther. 2021 Jul;19(7):911-925. The chemical structure of calycosin is provided below: ^ Calycosin may also to as: or 3',7-dihydroxy-4'- methoxyisoflavone. 9 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Calcycosin has been shown to effectively reduce inflammation resulting from exposure to pollution particles and to suppress hydrogen peroxide induced damage in nerve cells and tissue. Lu CY, et al. Calycosin alleviates H2O2-induced astrocyte injury by restricting oxidative stress through the Akt / Nrf2 / HO-1 signaling pathway. Environ Toxicol., 2022 Apr;37(4):858-867; Wang^ C, et al. Calycosin Alleviates Injury in Airway Epithelial Cells Caused by PM 2.5 Exposure via Activation of AMPK Signalling. Evid Based Complement Alternat Med. 2021 May 4; 2021:8885716. Calycosin also upregulates Nrf2 in nerve cells and thus may have neuroprotective effects. Calcysoin also suppress melanin synthesis and tyrosinase activity in B1F10 mouse^ melanoma cells via dose-dependent inhibition of CREB and p38 phosphorylation and MIF downregulation indicating a potential mechanistic role for melanogenesis inhibition in human cells Wu KC, et al. Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA / CREB and p38 MAPK Signaling Pathways. Int J Mol Sci. 2022 Jan 25;23(3):1358. Calcyosin also inhibits NF-kB and PI3K / AKT signaling in chondrocytes,^ preventing inflammatory pathway induction and inflammatory apoptosis. Shi X, et al. Calycosin mitigates chondrocyte inflammation and apoptosis by inhibiting the PI3K / AKT and NF-^B pathways. J Ethnopharmacol.2022 Oct 28;297:115536. Because PI3K / AKT and NF-^B pathways contribute to aging appearance of the skin, the inhibition of these pathways by calycosin, may result in antiaging effects of compositions comprising calycosin. Calycosin increases viability of^ cells stressed by formation of advanced glycation end products in diabetic rat models. An F, et al. Calycosin ameliorates advanced glycation end product-induced neurodegenerative changes in cellular and rat models of diabetes-related Alzheimer's disease. Chem Biol Interact. 2022 Dec 1;368:110206. Calycosin demonstrates anti-cancer, anti-inflammatory, neuroprotective, and^ hepatoprotective activity. Nonetheless, topical applications of calycosin for amelioration of skin conditions or increasing the appearance of the skin was not known. Topical administration of calycosin was not known in the field. In particular, the topical administration of calycosin for improving the condition of skin, including enhancing the appearance of the skin, by topical administration of a composition comprising an effective amount of calycosin was not known in^ the field. Beneficially, the invention recognizes, for the first time, that topical compositions 10 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application comprising calycosin may be used for improving the condition of the skin or for treatment of any ailment related to the skin of a subject. Compositions of calycosin In one aspect, the invention provides compositions comprising calcycosin. In certain^ embodiments, the invention provides compositions comprising calycosin that are suitable for administration on the skin of the subject. The invention recognizes that calycosin is poorly soluble or insoluble in water. The invention also recognizes that calycosin is also poorly soluble or insoluble in oil, for example, calycosin is insoluble in Helianthus Annuus (Sunflower) Seed Oil. The invention recognizes that^ the solvent used for preparing calycosin compositions should be any solvent acceptable to be used in cosmetic formulations. In certain embodiments, calycosin is dissolved in a solvent selected from a group consisting of: 1,2 heptanediol, 1,2 hexanediol, 1,2 propanediol, butylene glycol, C15-19 alkane, capric / caprylic triglyceride, dibutyl adipate, diisopropyl adipate, dimethyl isosorbide, dipropylene glycol, ethanol,^ ethoxydiglycol, isoamyl laurate, isohexadecane, isopentyldiol, isopropyl myristate, isoproyl lauryl sarcosinate, jojoba oil, meadowfoam seed oil, mineral oil, neopentyl glycol diethylhexanoate, octyldodecanol, oleyl alcohol, pentylene glycol, phenylpropanol, polysorbate 20, propanediol, safflower seed oil, squalene, sunflower oil, t-butyl alcohol, tributyl citrate, tributyl-O-acetylcitrate, tri-C15-19 alkyl citrate, triethyl citrate, triethyl O-acetylcitrate, and triisostearin. ^ In certain preferred embodiments of the invention, calycosin is dissolved in a solvent selected from a group consisting of: dimethyl isosorbide, ethoxydiglycol, isopropyl lauryl sarcosinate, pentylene glycol, propanediol, 1,2-hexanediol, and / or butylene glycol. In certain preferred embodiments, calycosin is dissolved in dimethyl isosorbide. Table 1 provides the solubility data for calycosin in several solvents. ^ Table 1: Solubility of calycosin Solvent Solubility (%w / w) 11 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Dimethyl Isosorbide 0.72 As evident from the data provided above, calycosin is soluble in dimethyl isosorbide. FIG. 1B provides a picture of a solution of calycosin dissolved in dimethyl isosorbide. Thus, in certain embodiments, the composition comprises an emulsion. Preferably, the^ emulsion is oil / water emulsion. FIG. 1A provides a picture of calycosin formulated in oil / water emulsion. In certain embodiments, the composition further comprises dimethyl isosorbide. In certain embodiments, the calycosin is dissolved in dimethyl isosorbide. The compositions of the invention are wherein the composition is stable under storage for at least two (2) months. This is beneficial^ because the compositions of the invention may be stored prior to administration to the subjects. In certain embodiments, wherein the compositions of the invention have less than about 10% degradation when stored at 4 ^ or 25 ^ for 1 month. In certain embodiments, the compositions of the invention have less than about 15% degradation when stored at 40 ^ for 1 months. FIG.2 provides the data for stability calycosin dissolved in dimethyl isosorbide. The invention^ beneficially provides that solutions of calycosin dissolved in dimethyl isosorbide have increased solubility and are shelf stable. Since calycosin is not soluble in sunflower oil and other commonly used solvents, the increased solubility in dimethyl isosorbide is surprising and unexpected. In certain embodiments, the composition comprises calycosin in a concentration of about 5 nM to about 2500 nM. In certain embodiments, the composition comprises calycosin in a^ concentration of about 10 nM to about 2000 nM. In certain embodiments, the composition comprises calycosin in a concentration of about 20nM nM to about 1000 nM. In certain embodiments, the composition comprises calycosin in a concentration of about 10 nM to about 20 nM. In certain embodiments, in the compositions of the invention, calycosin is present in a concentration of about 0.0001% to about 5.0% w / w. In certain other embodiments, calycosin is^ present in a concentration of 0.0005% to about 2.0% w / w. In certain other embodiments, calycosin 12 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application is present in a concentration of 0.0007% to about 1.0% w / w. In certain other embodiments, calycosin is present in a concentration of 0.001% to about 0.75% w / w. In certain other embodiments, calycosin is present in a concentration of 0.001% to about 0.75% w / w. In certain other embodiments, calycosin is present in a concentration of about 0.5% w / w. ^ In certain aspects, the compositions of the invention may be administered as a topical composition on the skin of the subject. The compositions of the invention may be included in any formulation suitable for topical administration. In certain embodiments, the composition of the invention is a fluid, emulsion, encapsulation, suspension, solid, semi-solid, jelly, paste, gel, hydrogel, ointment, lotion, emulsion, cream, foam, mousse, liquid, spray, suspension, dispersion,^ powder, aerosol, color cosmetic, and / or hair treatment. In certain embodiments, the compositions of the invention also include excipients. These excipients may be selected from a group consisting of: solvent, emulsifier, preservative, antioxidant, emollient, thickening agent, penetration enhancer, surfactant, diluent, filler, carrier, and / or pH control agent. In certain embodiments, the preservative in the composition is an antimicrobial preservative or chelating agent. In certain^ embodiments, the solvent of the invention is dimethyl isosorbide. The compositions of the invention may be prepared by various methods. As an example, the compositions may be prepared by dissolving, dispersing, etc. calycosin as provided herein and optional excipients in a carrier (e.g., water, saline, aqueous dextrose, glycerol, glycols, ethanol or the like) or a solvent to form a solution, colloid, liposome, emulsion, complexes (including^ inclusion complexes), coacervate, or suspension. In certain embodiments, the compositions of the current invention can also contain auxiliary substances such as wetting agents, emulsifying agents, co-solvents, solubilizing agents, pH buffering agents, and the like (e.g., sodium acetate, sodium citrate, cyclodextrins and derivatives, sorbitan monolaurate, triethanolamine acetate, triethanolamine oleate, hydroxyethylpiperazine and the like). In certain embodiments, the^ compositions of the invention may further include one or more additional excipients selected from a group consisting of: carriers, excipients, or diluents including, but not limited to, absorbents, anti-irritants, antibacterials, anti-acne agents, antioxidants, coloring agents / pigments, emollients (moisturizers), emulsifiers, film-forming / holding agents, fragrances, leave-on exfoliants, prescription drugs, preservatives, scrub agents, silicones, skin-identical / repairing agents, slip 13 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application agents, sunscreen actives, surfactants / detergent cleansing agents, penetration enhancers, and thickeners. Absorbents are substances which are added to topical products to take up water and oil- soluble dissolved or finely dispersed substances. Topical absorbents can also be used as thickeners^ in a wide variety of formulations including facial creams, lipsticks, shampoos and calamine lotions. In some embodiments, absorbents may include, but are not limited to, alcohol (ethyl alcohol, methanol, isopropyl alcohol, SD alcohol [especially denatured alcohol] and benzyl alcohol), alumina (aluminum oxide), aluminum chlorohydrate, aluminum hydroxide, aluminum magnesium silicate, aluminum silicate, aluminum starch octenylsuccinate, aluminum sulfate,^ ammonium chloride, bentonite, bismuth oxychloride, boron nitride, calcium carbonate, carnauba wax, charcoal, China clay, clay, Copernicia cerifera wax, cornstarch, fuller's earth, hydrolyzed corn starch, iron powder, kaolin, lithium magnesium sodium silicate, magnesium, magnesium carbonate, magnesium hydroxide, montmorillonite, nylon-12, rice starch, silica, silicate, silk powder, silt, sodium carbonate, sodium polyacrylates, and zeolite. ^ Anti-Irritants are substances which are added to topical products to reduce inflammation, especially, the inflammation resulting from the application of the product itself. The excipients included as anti-irritants that perform the function of anti-irritants or anti-inflammatories may have more than one function. For example, many antioxidants also function as anti-irritants. In some embodiments, anti-irritants and / or antioxidants may include, but are not limited to, Acacia senegal,^ acetylsalicylic acid, Achillea millefolium, adenosine, citric acid, adenosine triphosphateAloe barbadensis, aloe barbadensis leaf juice extract, aloe extract, aloe juice, hydrogenated olive oil, hydrogenated palm glycerides, hydrolyzed silk, hydroquinone, aloe vera, and / or alpha bisabolol. In certain embodiments, the compositions of the invention may further include humectants. Humectants (or moisturizers) are important cosmetic ingredients that prevent loss of moisture^ thereby retaining the skin’s natural moisture. Some humectants also can actively attract moisture. In certain embodiments, the humectants may be selected from a group consisting of sodium hyaluronate, sodium acetylated hyaluronate, hydrolyzed sodium hyaluronate, propylene glycol, hexylene glycol, and butylene glycol. 14 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain embodiments, the compositions of the invention may further include slip agents. The term “slip agent” is used to describe a range of ingredients which can help other ingredients spread over the skin and penetrate into the skin. Slip agents can also have humectant (hygroscopic) properties. In some embodiments, slip agents may include, but are not limited to, amodimethicone,^ bis-PEG-18 methyl ether dimethyl silane, bis-phenylpropyl dimethicone, butylene glycol, cetyl dimethicone, cetyl dimethicone copolyol, cetyl PEG / PPG-10 / 1-dimethicone, cyclohexasiloxane, cyclomethicone, cyclopentasiloxane, cyclotetrasiloxane, decylene glycol, diisostearoyl trimethylolpropane siloxy silicate, dimethicone, dimethicone copolyol, dimethicone crosspolymer, dimethiconol, dipropylene glycol, hexylene glycol, hydrolyzed silk, isododecane, methicone,^ methyl trimethicone, methylsilanol mannuronate, methylsilanol PEG-7 glyceryl cocoate, Good, PEG-10 dimethicone, PEG-10 dimethicone / vinyl dimethicone crosspolymer, PEG-12 dimethicone, PEG / PPG-18 / 18 dimethicone, PEG / PPG-20 / 15 dimethicone, pentylene glycol, phenyl trimethicone, polymethylsilsesquioxane, PPG-3 benzyl ether myristate, silica dimethyl silylate, silk powder, siloxane, simethicone, sorbitol, stearyl dimethicone, stearyl methicone,^ triethoxycaprylylsilane, trimethylsiloxysilicate, xylitol, and zinc stearate. In certain embodiments, the compositions of the invention may further include diluents, and / or carriers. Diluents and / or carriers may include, but are not limited to, polyethylene glycols (such as PEG200, PEG300, PEG400, PEG540, PEG600, PEG1450 or mixtures thereof) and coconut oils (such as propylene glycol dicaprate, coco-caprylate / caprate, propylene glycol^ dicaprylate / dicaprate, caprylic / capric triglyceride, caprylic / capric / lauric triglyceride, caprylic / capric / linoleic triglyceride, tricaprin, tricaprylin, glyceryl trioleate, neopentyl glycol dicaprylate / dicaprate, caprylic / capric / palmitic / stearic triglceride, or mixtures thereof). In certain embodiments, the compositions of the invention may further include emollients. Emollients are supple, waxlike, lubricating, thickening substances which are added to^ cosmetic / dermatological products to prevent water loss and have a softening and soothing effect on the skin.^ In some embodiments, emollients may include, but are not limited to, 10- hydroxydecanoic acid, acetyl glyceryl ricinoleate, acetylated castor oil, acetylated hydrogenated cottonseed glyceride, acetylated lanolin,^ acetylated lanolin alcohol, acetylated palm kernel glycerides, agar, algae extract, algin, almond oil, squalane, squalene, Į-glucan oligosaccharide,^ amodimethicone, Anacystis nidulans extract, apricot kernel oil, arachidic acid, arachidonic acid, 15 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application arachidyl alcohol, arachidyl propionate, C10-30 cholesterol / lanosterol esters, C12-15 alkyl benzoate, C12-18 acid triglyceride, C18-36 acid triglyceride, candelilla wax, Cannabis sativa L. oil, caprylic / capric triglyceride, caprylyl methicone, carrot oil, Carthamus tinctorius oil, Carya illinoensis oil, castor isostearate succinate, castor oil, Caulerpa taxifolia extract, and / or^ cephalin. In certain embodiments, the compositions of the invention may further include film- forming / holding agents. Film-Forming / Holding agents are substances which are added to cosmetic / dermatological products to help leave a pliable, cohesive, and continuous covering over the skin. This film has water-binding properties and leaves a smooth feel on skin. In some^ embodiments, film-forming / holding agents may include, but are not limited to, acrylate, acrylates copolymer, acrylates / C10-30 alkyl acrylate crosspolymer, acrylates / dimethicone copolymer, adipic acid / neopentyl glycol / trimellitic anhydride copolymer, allyl methacrylates crosspolymer, carnauba wax, cellulose gum, Copernicia cerifera wax, dextrin, diisopropyl adipate, glyceryl polymethacrylate, hydrolyzed wheat protein, hydroxyethylcellulose, locust bean, neopentyl glycol^ diheptanoate, PEG-40 hydrogenated castor oil, polyacrylamide, polyacrylate-17, polyglucuronic acid, polyglyceryl methacrylate, polyisobutene, polymethyl methacrylate, polyquaternium-10, polyquaterniums, polyvinyl alcohol, polyvinylpyrrolidone, propylene carbonate, PVM / MA (polyvinyl methyl ether / maleic acid) decadiene crosspolymer, PVP [poly(vinylpyrrolidone)] copolymer, PVP / dimethylaminoethyl-methacrylate, sodium carbomer, sodium polyacrylate,^ styrene / acrylates copolymer, triethoxycaprylylsilane crosspolymer, VA (vinyl acetate) / crotonates, VA / crotonates copolymer, VP (vinylpyrrolidone) / eicosene copolymer, and VP / hexadecene copolymer. In certain embodiments, the compositions of the invention may further include excipients related to the fragrance of the formulation. Fragrance ingredients are a single or a blend of volatile^ and / or fragrant plant oils (or synthetically derived oils) that impart aroma and odor to cosmetic / dermatological products. The level of fragrance to use varies according to the product type. In some embodiments, the composition of the formulation may contain up to about 0.01% fragrance by weight. In some embodiments, fragrances (e.g., synthetic and fragrant plant extracts) may include, but are not limited to, Acacia farnesiana extract, Aerocarpus santalinus, amyl^ cinnamate, amyl salicylate, amyris oil, Anethum graveolens, Angelica archangelica root oil, 16 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application anisaldehyde, anise, balm mint extract, balsam peru, bay leaf oil, bergamot oil, bitter orange flower, bois de rose oil, bois oil, Boswellia carterii, butylphenyl methylpropional, cananga extract, Cananga odorata, cardamom, cedarwood, cherry extract, Citrus aurantifolia, Citrus aurantium, Citrus aurantium extract, Citrus medica limonium,^ clary oil, Commiphora myrrha extract, coriander, Cucurbitea peponis, cyclamen aldehyde, dill extract, ethyl vanillin, eugenol, farnesol, farnesyl acetate, Ferula galbaniflua, fir needle oil, floralozone, Foeniculum vulgare extract, frankencense extract, galbanum, Gardenia florida extract, grapefruit oil, guaiac wood, Guaiacum officinale, hedione, hexyl cinnamal, hyssop, Illicium vernum, Iris florentina extract, jasmine oil, Jasminium grandiflorum, jonquil^ extract, Laurus nobilis, lauryl lactate, lavandin oil, Lavandula angustifolia, Lavandula officinalis, lavender extract and oil, lemon, lemon balm, lemongrass oil, Levisticum officinale root extract, lime oil and extract, limonene, linalool, Litsea cubeba, mandarin orange oil or extract, marjoram, Melissa officinalis, Mentha piperita, Mentha spicata, Mentha viridis, menthol, menthone, menthoxypropanediol, and menthyl lactate. ^ In certain embodiments, the composition of the invention may further include preservatives. Preservatives are substances which prevent bacterial, microbial or fungal contamination of cosmetic / dermatological products thereby increasing the product's shelf life and consumer safety. Some of these agents also have stabilizing effects able to preserve the function of various active ingredients including anti-oxidants (vitamins), emulsifiers and surfactants. In^ some embodiments, preservatives may include, but are not limited to, 1,2-hexanediol, benzoic acid, benzothonium chloride, borax, bronopol, butylparaben, caprylyl glycol, chlorophene, chloroxylenol, chlorphenesin, decylene glycol, dehydroacetic acid, diazolidinyl urea, DMDM hydantoin, hydroxyacetophenone, ethylhexylglycerin, ethylparaben, formaldehyde-releasing preservative, Germaben II, hoelen, imidazolidinyl urea, iodopropynyl butylcarbamate,^ isobutylparaben, methylchloroisothiazolinone, methyldibromo glutaronitrile, Methylisothiazolinone, methylparaben, o-cymen-5-ol, phenoxyethanol, phenoxyisopropanol, phytosphingosine, polyaminopropyl biguanide, potassium sorbate, propylparaben, quaternium-15, sodium benzoate, sodium citrate, sodium dehydroacetate, sodium hexametaphosphate, sodium hydroxymethylglycinate, phenethyl alcohol, sodium lactobionate, sodium metabisulfite, sodium^ sulfite, sorbic acid, and styrax benzoin. 17 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain aspects of the invention, the pharmaceutical composition is an emulsion. The emulsion compositions of the invention may further include emulsifiers. Emulsifiers are substances which are added to cosmetic / dermatological products to help keep unlike ingredients (such as oil and water) from separating in an emulsion. There are 2 types of emulsifiers. Oil-in-^ water (o / w) emulsifiers keep oil drops packed in water, while water-in-oil (w / o) emulsifiers keep water drops packed in oil. W / O emulsifiers are used for a fatty feel (e.g. night & sun protection creams). O / W emulsifiers are used more in moisturizing products (e.g. body lotions, day creams). In certain embodiments, the compositions of the invention may further include surfactants. Surfactants are compounds that lower surface tension or interfacial tension. Reducing the surface^ tension allows a liquid to spread easier while reducing the interfacial tension (interfacial meaning between two faces) between water and an oil / lipid allows them to mix. Surfactants may have a be anionic, amphoteric, non-ionic, and / or quaternary agents. Surfactants form the base of all personal cleansing products and can also have wetting, conditioning, defatting, emulsifying, & thickening effects. In some embodiments, emulsifiers, surfactants, and detergents may include, but are not^ limited to, ammonium laureth sulfate, ammonium lauryl sulfate, arachidyl glucoside, behenic acid, bis-PEG-18 methyl ether dimethyl silane, C20-40 pareth-40, cocamidopropyl betaine, cocamidopropyl dimethylamine, cocamidopropyl hydroxysultaine, coco-glucoside, coconut oil, decyl glucoside, dicetyl phosphate, dihydrocholeth-30, disodium cocoamphodiacetate, disodium cocoyl glutamate, disodium lauraminopropionate, glyceryl behanate, hydrogenated vegetable^ glycerides citrate, isohexadecane, isostearamide DEA, lauramphocarboxyglycinate, laureth-23, laureth-4, laureth-7, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, lauryl alcohol, lauryl glucoside, magnesium laureth sulfate, magnesium oleth sulfate, myristic acid, nonoxynols, oleic acid, oleth 10, palm kernel acid, palmitic acid, PEG-60 almond glycerides, PEG-75 shea butter glycerides, PEG 90M, PEG-10 dimethicone, PEG-10 dimethicone / vinyl dimethicone^ crosspolymer, PEG-10 rapeseed sterol, PEG-100 stearate, PEG-12 dimethicone, PEG-120 methyl glucose dioleate, PEG-20 methyl glucose sesquistearate, PEG-40 stearate, PEG-60 hydrogenated castor oil, PEG-7 glyceryl cocoate, PEG-8, PEG-80 sorbitan laurate, PEG / PPG-17 / 6 copolymer (polyethylene glycol / polypropylene glycol-17 / 6 copolymer), PEG / PPG-18 / 18 dimethicone, PEG / PPG-20 / 15 dimethicone, poloxamer 184, Poloxamer 407, poloxamers, polyglyceryl-3^ beeswax, polyglyceryl-4 isostearate, polyglyceryl-6 isostearate, polysorbate 20, polysorbate 60, 18 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application polysorbate 80, potassium cetyl phosphate, potassium hydroxide, potassium myristate, PPG-12 buteth-16, PPG-26-Buteth-26, Salvia officinalis, Saponaria officinalis extract, soapwort, sodium C14-16 olefin sulfonate, sodium cetearyl sulfate, sodium cocoamphoacetate, sodium cocoate, sodium cocoyl glutamate, sodium cocoyl isethionate, sodium dilauramidoglutamide lysine,^ sodium hexametaphosphate, sodium hydroxide, sodium laureth sulfate, sodium laureth-13 carboxylate, sodium lauroamphoacetate, sodium lauroyl lactylate, sodium lauroyl sarcosinate, sodium lauryl glucose carboxylate, sodium lauryl sulfate, sodium methyl cocoyl taurate, sodium methyl taurate, sodium myreth sulfate, sodium palm kernelate, sodium palmate, sodium PEG-7 olive oil carboxylate, sodium trideceth sulfate, steareth-20, TEA-lauryl sulfate (triethanolamine-^ lauryl sulfate), and tribehenin PEG-20 esters. In certain embodiments, the compositions of the invention may further include one or more thickeners. Thickeners are substances which are added to cosmetic / dermatological products to enhance the consistency, volume and viscosity of cosmetic products, thereby providing more stability and better performance. While some thickeners have also emulsifying or gelling^ properties, the majority of thickeners have the ability to retain water on the skin and act therefore as moisturizers. Thickeners can be completely natural like waxes but also synthetic or semi- synthetic. In some embodiments, thickeners may include, but are not limited to, Acacia senegal, acetyl glyceryl ricinoleate, acetylated castor oil, acetylated hydrogenated cottonseed glyceride, acetylated palm kernel glycerides, acrylates / steareth-20 methacrylate copolymer, agar, Ahnfeltia^ concinna extract, ahnfeltia extract, Alaria esculenta, algae, algae extract, algin, alkyloamides, Althaea rosea, Althea officinalis, alumina, aluminum hydroxide, aluminum stearate, ammonium acryloyldimethyltaurate / VP copolymer, Anacystis nidulans extract, arachidic acid, arachidonic acid, arachidyl alcohol, arachidyl propionate, arrowroot, artemia extract, Ascophyllum nodosum, ascorbyl methylsilanol pectinate, Asparagopsis armata extract, beeswax, behenic acid,^ behentrimonium chloride, behenyl alcohol, bis-diglyceryl polyacyladipate, bismuth oxychloride, C12-15 alkyl benzoate, C12-18 acid triglyceride, C13-14 isoparaffin, C18-36 acid triglyceride, candelilla wax, caprylic / capric triglyceride, carbomer, carbopol, carnauba wax, carrageenan, Caulerpa taxifolia extract, cellulose, Cellulose gum, cephalin, Cera alba, ceresin, ceteareth-20, cetearyl alcohol, cetearyl ethylhexanoate, cetearyl glucoside, cetearyl octanoate, cetyl alcohol, cetyl^ dimethicone copolyol, cetyl hydroxyethylcellulose, cetyl palmitate, cetyl PEG / PPG-10 / 1- 19 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application dimethicone, chlorella, Chondrus crispus, cocamide DEA and MEA, cocoglycerides, Codium tomentosum extract, Copernicia cerifera wax, Corallina officinalis extract, Corallina , DEA oleth- 10 phosphate, diethanolamine (DEA), di-PPG-3 myristyl ether adipate, dimethicone crosspolymer, dimethicone / vinyl dimethicone crosspolymer, polyacrylate crosspolymer, and / or dimer dilinoleyl^ dimer dilinoleate. In certain embodiments, the compositions of the invention may further include one or more chelators. Chelating agents are any of numerous ingredients that bind with metal ions or metallic compounds, preventing them from adhering to a surface (such as skin, hair, or clothing) or causing contamination, such as in the case of trace amounts of iron. In some embodiments, chelators may^ include, but are not limited to tetrasodium EDTA, sodium phytate, and / or teathydroxypropyl ethylenediamine. In certain embodiments, the excipients included in the composition are water, dimethyl isosorbide, glycerin, caprylic / capric triglyceride, propanediol, sunflower seed oil, ethoxydiglycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate,^ capryloyl glycerin / sebacic acid copolymer, diheptyl succinate, naringenin, lecithin, decylene glycol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidyl alcohol, behenyl alcohol, arachidyl glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olea europaea (olive) fruit oil, olea europaea (olive) oil unsponifiables, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, citric acid, sodium acetylated hyaluronate, sodium^ hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and / or ethylhexylglycerin. Table 2 provides a list of excipients, along with their approximate concentrations, that may be used in the exemplary compositions of the invention. is provided below: Table 2: Excipients in an exemplary composition: Ingredient %w / w 20 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Ethoxydiglycol 0 - 5 Squalane 0 - 2 Calycosin for treatment of topical conditions: Advantageously, it was discovered that calycosin impacts the genes and signaling pathways involved in several topical conditions. In one aspect, the invention provides methods of^ using the compositions for treating, protecting, and / or altering (e.g., improving) the condition and / or aesthetic appearance of skin, including, for example, treating, preventing, ameliorating, reducing and / or eliminating fine lines and / or wrinkles of skin and / or improving the aesthetic 21 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application appearance of fine lines and / or wrinkles of skin. In certain embodiments, the compositions of the invention lead to increase in skin and / or hair resiliency. In certain embodiments, the compositions of the invention lead to increase in elasticity of the skin. In certain embodiments, the compositions of the invention prevent skin damage. ^ In one aspect, the invention includes a composition for topical administration comprising an effective amount of calycosin. The effective amount of calycosin is an amount of calycosin that would be effective in treating, ameliorating, or otherwise impacting the underlying condition of the skin. In certain aspects of the invention, the compositions comprising calycosin promote skin^ lightening and / or brightening. In certain embodiments, the compositions comprising calycosin at least a concentration of 0.01% w / w, have about 1% higher L value (reflecting the lightening of the skin), as compared to skin treated with a corresponding composition lacking calycosin. In certain aspects of the invention, the compositions comprising calycosin demonstrate antioxidant activity. In certain embodiments, the compositions of the invention, the antioxidant^ activity of calycosin is demonstrated at concentrations of about 0.00005% w / w or higher. Advantageously, the compositions of the invention comprising calycosin, demonstrating antioxidant activity, are effective for treating and / or preventing oxidation damage. In certain embodiments, the compositions of the invention comprising calycosin, demonstrating antioxidant activity, are effective for treatment of skin and / or hair damaged by reactive oxygen species and^ protection from other environmental aggressors that may damage the skin of the subject. In certain other embodiments, the compositions of the invention comprising calycosin, demonstrating antioxidant activity, are effective for prevention of skin and / or hair damage by reactive oxygen species, including the damage caused by environmental aggressors. As demonstrated from the data provided in Examples 2 and 3, compositions comprising^ calycosin are effective in demonstrating robust antioxidant activity in both aqueous and organic solvent systems. The IC50 values for antioxidant activity calculated in aqueous and organic solvent systems was 0.0004% w / w and 0.027% system respectively. These results demonstrate that compositions comprising calycosin have robust antioxidant activity. In certain embodiments, the compositions comprising calycosin are useful in treatment of conditions caused by oxidation or 22 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application excessive oxidation in the skin of the subject. In certain embodiments, the compositions comprising calycosin are administered for treatment and / or prevention of skin or hair damage by reaction oxygen species and protection from environmental aggressors. In certain aspects of the invention, the compositions comprising calycosin demonstrate^ elastase enzyme inhibition. In certain embodiments, the compositions of the invention, the elastase enzyme inhibition activity of calycosin is demonstrated at concentrations of about 0.05% w / w or higher. As evident from the data provided in Example 4, compositions comprising calycosin have robust elastase enzyme inhibition activity. Advantageously, the compositions comprising calycosin, demonstrating elastase enzyme^ inhibition activity, are effective for promoting the elasticity of the skin. In certain embodiments, the compositions of the invention comprising calycosin, demonstrating elastase enzyme inhibition, are effective in reduction of fine lines and / or wrinkles in the skin. In certain embodiments, the compositions of the invention comprising calycosin, demonstrating elastase enzyme inhibition, are effective in prevention of formation of fine lines and / or wrinkles in the skin. ^ In certain aspects of the invention, the compositions comprising calycosin demonstrate inhibition of glycation. In certain embodiments, the compositions of the invention, the glycation inhibition activity of calycosin is demonstrated at concentrations of about 0.001 w / w or higher. As evident from the data provided in Example 5, compositions comprising calycosin have robust glycation inhibition. Indeed, the calculated IC50 value for glycation inhibition by compositions^ comprising calycosin is 0.004%. Advantageously, the compositions comprising calycosin, demonstrating glycation inhibition activity, are effective for supporting and promoting skin and / or hair resiliency. Genetic expression and / or activity modulation In certain aspects of the invention, a composition comprising calycosin modulates^ expression of one more genes that is related to a topical condition. In certain embodiments, administration of composition comprising calycosin alters one or more of a function related with the modulated genes, wherein the one or more function is selected from the group consisting of: (i) lightening / brightening of the skin, (ii) formation of fines lines or wrinkles on the skin, (iii) inflammation, (iv) melanin synthesis, and (v) collagen degradation. In certain embodiments, the 23 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application one or more genes are selected from a group consisting of: (i) MUCL1, (ii) KLK6, (iii) PSAPL1, (iv) S100A7, (v) IL37, and (vi) MMP1. In certain embodiments, administration of a composition comprising calycosin leads to down-regulation of MUCL1, KLK6, PSAPL1, S100A7, IL37, and / or MMP1. ^ In certain embodiments, the administration of the compositions of the invention comprising calycosin enhances anti-inflammatory activity. This enhancement of anti-inflammatory activity of compositions comprising calycosin may have beneficial effects on the condition and / or appearance of the skin. In certain embodiments, the administration of the compositions of the invention comprising calycosin enhances maintenance of skin barrier lipids. In certain embodiments, the^ administration of the compositions of the invention comprising calycosin enhances the maintenance of collagen network to prevent formation of fine lines and / or wrinkles in the skin. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes involved in promoting melanogenesis. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes^ involved promoting anti-inflammatory responses. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes involved in degradation of skin barrier lipids. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of genes involved in degradation of molecules involved in barrier function restoration. In certain embodiments, the administration of the composition^ comprising calycosin results in downregulation of genes involved in degradation of molecules involved in degradation of collagen. In certain embodiments, the administration of the composition comprising calycosin results in downregulation of expression and / or activity of mucin like 1 (MUCL1) gene. Mucins have pivotal roles in the immune response and can regulate the functions of innate and acquired immune^ responses.^Human melanocytes interact with the endocrine, immune and inflammatory systems, and we hypothesized that the expression of any mucin proteins may be correlated with melanogenesis in skin cells. MUCL1 is involved in melanogenesis. In certain embodiments, the decreased expression and / or activity of MUCL1 indicates inhibition of melanogenesis. In certain embodiments, the administration of the composition comprising calycosin results in about ten (10) 24 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application fold expression of MUCL1. Since the administration of the composition comprising calycosin results in downregulation of MUCL1, it also results in the decrease in melanogenesis. In certain embodiments, administration of a composition comprising calycosin leads to downregulation of kallikrein related peptidase 6 (KLK6) and / or interleukin (IL37). KLK6 is a^ protease that promotes inflammation. KLK6 is a member of the kallikrein subfamily of the peptidase S1 family of serine proteases. Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptor 1 (PAR1) and PAR2. KLK6 levels are elevated in multiple inflammatory and autoimmune conditions, but no definitive role in pathogenesis has been established. Here, we show that skin-^ targeted overexpression of KLK6 causes generalized, severe psoriasiform dermatitis with spontaneous development of debilitating psoriatic arthritis-like joint disease. Billi et al., KLK6 expression in skin induces PAR1-mediated psoriasiform dermatitis and inflammatory joint disease, J. Clin. Invest., 2020, 130(6): 3151-3157. KLK6 levels are increased in multiple skin diseases including psoriasis and atopic dermatitis but normalize rapidly with efficacious therapy.^ IL37 is also involved in the inflammatory pathway. Thus, downregulation of KLK6 and / or IL37 leads to an anti-inflammatory response. In certain embodiments, administration of a composition comprising calycosin leads to at least about twenty-five (25) fold downregulation of KLK6. In certain embodiments, administration of a composition comprising calycosin leads to about fifteen (15) fold downregulation of IL37. ^ In certain embodiments, administration of a composition comprising calycosin leads to downregulation of prosaposin like 1 (PSAPL1) gene. Proactivator polypeptide-like 1 is a protein in humans that is encoded by the PSAPL1 gene. It is a member of the saposin family of proteins. PSAPL1 is involved in lysosomal degradation of sphingolipids. Thus, downregulation of PSAPL1 supports lipid barrier maintenance. The support of barrier lipid maintenance plays a role in the^ appearance and / or elasticity of the skin. In certain embodiments, administration of a composition comprising calycosin leads to about twenty-five (25) fold downregulation of PSAPL1. In certain embodiments, administration of a composition comprising calycosin leads to downregulation of S100 calcium binding protein A7 (S100A7) gene. The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs.^ S100 proteins are localized in the cytoplasm and / or nucleus of a wide range of cells, and involved 25 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100A7 is a signaling molecule, which is highly expressed in dermatitis and psoriasis. S100A7 is overexpressed in hyperproliferative skin diseases, exhibits antimicrobial activities against bacteria and induces immunomodulatory activities. Downregulation of S100A7^ supports the lipid barrier maintenance. The support of barrier lipid maintenance plays a role in the appearance and / or elasticity of the skin. In certain embodiments, administration of a composition comprising calycosin leads to at least about fifteen (15) fold downregulation of S100A7. In certain embodiments, administration of a composition comprising calycosin leads to formation of fine lines and / or wrinkles on the skin. The prevention of formation of fine lines and / or^ wrinkles on the skin, in part, is due increased collagen degradation. In certain embodiments, administration of a composition comprising calycosin leads to downregulation of matrix metalloproteinase 1 (MMP1). The downregulation of expression and / or activity of MMP1 results in decrease in breakdown of collagen. In certain embodiments of the invention, the administration of the composition comprising calycosin leads to at least about five (5) fold downregulation of^ MMP1. In certain embodiments, administration of a composition comprising calycosin to a subject leads to the treatment of prevention of a topical condition of the subject through the modulation of levels of expression or activity of one or genes that may be involved in the topical condition. In certain embodiments, administration of a composition comprising calycosin alters one or more of^ a function related with the modulated genes, wherein the one or more function is selected from the group consisting of: (i) maintenance of skin barrier, (ii) collagen expression, (iii) collagen degradation, (iv) inflammation, (v) tissue atrophy, (vi) muscle loss, and (vii) melanin production. Treatment of topical conditions The current invention recognizes that the compositions comprising calycosin is beneficial^ for treating, protecting and / or improving the condition and / or aesthetic appearance of skin. For example, the compositions of the invention may be effective for altering the aesthetic appearance of skin associated with or affected by, or for treating or preventing, fine lines and / or wrinkles of skin caused by, for example, cellular senescence, environmental damage or dermatoheliosis. The invention also provides methods for stimulating skin cell renewal, increasing cell or tissue 26 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application regeneration, promoting fibroblast proliferation and synthesizing elastin, collagen, proteoglycans, and / or new connective tissue, thereby reducing or improving the appearance of wrinkles, restoring elasticity, resiliency, and / or suppleness to the skin. The compositions of the invention provided herein can be useful for improving the^ aesthetic appearance of skin. Such improvements can include, but are not limited to, all outward visibly and tactilely perceptible manifestations as well as any other macro or micro effects due to skin aging and damage. Such manifestations and effects can be induced or caused by intrinsic factors and / or extrinsic factors, e.g., chronological aging, environmental damage, climate, sun (UV) exposure, smoking, drugs, alcohol consumption, jetlag, night work, changes in circadian^ rhythm, pregnancy, menopause, genetic factors, nutritional factors and / or deficiencies, dehydration, stress, allergies (e.g., to plants, animals, medications, and other substances), exposure to industrial and / or household chemicals, indoor heating and cooling, various disorders and diseases such as arteriosclerosis, diabetes, heart disease, liver disease, and obesity, thinning of the outer layer of skin, decreases in the number of pigment-containing cells, increases in the size of^ pigment-containing cells, changes in the connective tissue, and reduction in the strength and elasticity of the skin. The aesthetic appearance of skin can be improved, for example, by improving the appearance of skin associated with or affected by one or more of wrinkles, dry skin, sensitive skin; wrinkling and sagging; acne; vitiligo (skin condition in which there is a loss of brown color^ (pigment) from areas of skin); fine lines, wizened skin, thinning of the dermis, the degradation of collagen fibers, flaccid skin, thinned skin, and skin exposed to ultraviolet radiation. In some embodiments, the compositions of the invention can improve the aesthetic appearance of skin by decreasing the appearance of fine lines in the skin; creating a more youthful appearance of the skin; decreasing bags and / or rings around the eyes; increasing or restoring the elasticity, resiliency,^ and / or suppleness of the skin; increasing the apparent thickness, elasticity, flexibility, radiance, glow, and plumpness of the skin; improving the fineness of the skin texture; improving the appearance of wrinkles, lined, dry, flaky, aged, and / or photodamaged skin; treating or preventing photodamaged skin; reducing the signs of skin aging; reducing the appearance of hyperpigmentation; treating or preventing hyperpigmentation; treating or preventing pigment 27 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application deposition in the skin (e.g., that caused by UV exposure); reducing the appearance of skin discolorations; and whitening, lightening, and / or bleaching the skin. In certain embodiments, the compositions may be used for care, treatment, cleansing, and / or protective products for facial or body skin; anti-wrinkle or anti-aging^ compositions; skin firming compositions; skin lightening compositions; compositions for irritated skin; sunscreen compositions, artificial tanning (self-tanning) compositions or after-sun care compositions; scalp care compositions; shaving preparation compositions; depilatory compositions; or make-up products for the skin of the face or body. In certain embodiments, the compositions comprising calycosin are administered for^ altering the aesthetic appearance of skin associated with or affected by, or treating or preventing, a skin condition / disorder (e.g., a skin condition / disorder accompanied with a loss of skin elasticity). In certain embodiments, the compositions comprising calycosin are administered for improving the barrier function and viability of the skin. ^ In certain embodiments, the compositions comprising calycosin are administered for altering the aesthetic appearance of skin associated with or affected by wrinkling, sagging, and / or a loss of skin elasticity. In certain embodiments, the compositions comprising calycosin are administered for altering the aesthetic appearance of skin associated with or affected by deteriorations^ in skin viscoelasticity. In certain embodiments, the compositions comprising calycosin are administered for altering the aesthetic appearance of skin associated with or affected by one or more of wrinkles and / or fine lines, wizened skin, a lack of elasticity and / or of tonus of the skin, thinning of the dermis, degradation of collagen fibers, flaccid skin, thinned skin, and the internal degradation of^ the skin following exposure to ultraviolet radiation. In certain embodiments, the compositions comprising calycosin are administered for decreasing the appearance of fine lines and / or wrinkles in the skin. 28 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application In certain embodiments, the compositions comprising calycosin are administered for decreasing the appearance of bags and / or rings around the eyes. In certain embodiments, the compositions comprising calycosin are administered for reducing the appearance of hyperpigmentation. ^ In certain embodiments, the compositions comprising calycosin are administered for improving or increasing one or more of the thickness, elasticity, flexibility, radiance, glow, and plumpness of the skin. In certain embodiments, the compositions comprising calycosin are administered for improving the fineness of skin texture. ^ In certain embodiments, the compositions comprising calycosin are administered for improving the appearance of wrinkled, lined, dry, flaky, aged or photodamaged skin. In certain embodiments, the compositions comprising calycosin are administered for altering the aesthetic appearance of skin associated with or affected by skin discolorations. Methods of Administration: ^ In one aspect, the invention provides methods of administration of the compositions comprising calycosin. In certain embodiments, the invention the compositions of the invention are designed for topical administration. In certain embodiments, the compositions of the invention may be administered as a topical composition on the skin of the subject. The compositions of the invention may be included in any^ formulation suitable for topical administration. In certain embodiments, the composition of the invention is a fluid, emulsion, encapsulation, suspension, solid, semi-solid, jelly, paste, gel, hydrogel, ointment, lotion, emulsion, cream, foam, mousse, liquid, spray, suspension, dispersion, powder, aerosol, color cosmetic, and / or hair treatment. In certain other embodiments, the compositions comprising calycosin may be prepared and^ used in the form of an aerosol spray, cream, emulsion, solid, liquid, dispersion, foam, oil, gel, lotion, mousse, ointment, powder, patch, pomade, solution, pump spray, stick, towelette, soap, or other forms commonly employed in the art of topical administration and / or cosmetic and skin care 29 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application formulation. The compositions can be in an emulsion form. In addition, compounds provided herein used in the compositions provided herein can be used in color cosmetic compositions such as foundation makeups, blushes, eyeshadows, mascaras, concealers, eyeliners, lip colors, nail colors, and so on. Other cosmetic compositions can include perfumes, lipsticks, fingernail and^ toenail polish, eye and facial makeup, towelettes, deodorants, hand sanitizer, baby products, bath oils, bubble baths, and butters. In certain embodiments, the compositions comprising calycosin are administered over an area of about 1.0 ^g / cm2to about 100 ^g / cm2. In certain embodiments, the compositions comprising calycosin are administered for a^ duration till the desired impact in amelioration or prevention of a topical condition is realized. In certain embodiments, the composition comprising calycosin comprises an effective amount of calycosin. The effective amount of calycosin is an amount of calycosin that results in the desired result in the condition of the skin. In certain embodiments, the composition comprising calycosin is administered once a day. In certain embodiments, the composition comprising calycosin is^ administered twice a day. In certain embodiments, the composition comprising calycosin is administered thrice a day. In certain embodiments, the composition comprising calycosin is administered once every two days. In certain embodiments, the composition comprising calycosin is administered once every three days. Examples: ^ Example 1: Exemplary composition comprising calycosin: Table 3 provides an exemplary formulation of calycosin: Table 3: Exemplary composition comprising calycosin: Ingredient %w / w 30 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Sodium Arcylates Copolymer 0.7500 Cetearyl Alcohol 0.6214 Example 2: ABTS antioxidant assay: The 2,2'-Azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) antioxidant assay is designed to evaluate the antioxidant activity of compositions comprising^ calycosin in an aqueous medium. ABTS+ solution is generated as a free radical and used to measure relative ability of a compound to scavenge free radicals. Reduction of the absorbance at 734 nm was standardized to solvent control as an indication of ABTS+ scavenging. 31 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Table 4, provided below, demonstrates the results from these experiments: Table 4: ABTS (aqueous antioxidant assay) radical inhibition Calycosin concentration % Radical (%w / w) Inhibition As evident from the results provided in Table 4 above, compositions comprising calycosin^ demonstrate antioxidant activity at concentrations at low as 0.00008% w / w in aqueous systems. The calculated IC50 value is: 0.0004% w / w. Example 3: DPPH Antioxidant Activity assay The 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant assay is designed to evaluate the antioxidant activity of compositions comprising calycosin in an organic medium. ^ 2,2-diphenyl-1-picrylhydrazyl (DPPH) is a stable free radical used to evaluate free radical scavenging capacity of a material. In the presence of an antioxidant DPPH is reduced, resulting in the formation of a colorless solution. Reduction of absorbance at 517 nm is standardized to solvent control as an indication of DPPH scavenging. Table 5, provided below, provides the antioxidant activity data. ^ Table 5: DPPH Radical Inhibition Calycosin concentration % R di l I hibiti 32 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application As evident from the results provided in Table 6 above, compositions comprising calycosin demonstrate antioxidant activity at concentrations at low as 0.007% w / w in organic solvent systems. The calculated IC50 value is: 0.027% w / w. Example 4: Elastase enzyme inhibition: ^ The assay was conducted to evaluate the elastase enzyme inhibition activity of compositions comprising calycosin. Neutrophil infiltration and neutrophil elastase are both increased in the skin in response to UV stress. Neutrophil elastase has been shown to activate MMP-1 and MMP-2 collagenase in response to low dose UV exposure, harming the extracellular matrix and contributing to^ photoaging and wrinkle formation. The activity of elastase can be further upregulated in the presence of reactive oxygen species. Therefore, inhibition of this enzyme, particularly in combination with antioxidant activity, is effective in delaying wrinkle development and aiding in maintaining skin integrity. This assay is measures release of 4-nitroaniline from an Me-Suc-Ala- Ala-Pro-Val-pNA by human neutrophil elastase and can be quantified at 405 nm by comparing to^ solvent control. Table 6 provides the elastase inhibition activity of compositions comprising calycosin: Table 6: Elastase enzyme inhibition Calycosin concentration % Enzyme Inhibition As evident from the data provide in Table 6, compositions comprising calycosin inhibits^ elastase enzyme activity as low at 0.25% w / w. 33 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Example 5: Glycation inhibition assay: The assay was conducted to evaluate the glycation inhibition activity of compositions comprising calycosin. Nonenzymatic glycation can occur when glucose reacts with proteins, forming a Schiff^ base intermediate that subsequently undergoes Amadori rearrangement to form glycosylated proteins, when they react with skin proteins to form Advanced Glycation End products (AGE). AGE formation can result in loss of skin elasticity and impaired cellular function. The glycation inhibition ability of a compound is measured by change in fluorescence at excitation / emission of 360 nm / 420 nm relative to solvent control: ^ Table 7 provides the data for glycation inhibition. Table 7: Glycation Inhibition Calycosin concentration (%w / w) % Enzyme Inhibition As evident from the data provided in Table 7, compositions comprising calycosin inhibits glycation as low as 0.002% w / w. The IC50 value calculated for glycation inhibition is 0.004%.^ Example 6: Preclinical analysis of lightening and / or brightening effects of compositions comprising calycosin: The experiment was designed to evaluate the impact of compositions comprising calycosin on skin lightening and / or brightening. In preclinical analysis, conducted on in vitro skin tissues, the compositions comprising calycosin resulted in lightening and / or brightening of^ the skin. 34 ^ Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Table 8: Lightening and / or Brightening of skin tissues Calycosin Concentration (%w / w) L value Incorporation by Reference References and citations to other documents, such as patents, patent applications, patent^ publications, journals, books, papers, web contents, publicly accessible databases, have been made throughout this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes. Equivalents Various modifications of the invention and many further embodiments thereof, in addition^ to those shown and described herein, will become apparent to those skilled in the art from the full contents of this document, including references to the scientific and patent literature cited herein. The subject matter herein contains important information, exemplification and guidance that can be adapted to the practice of this invention in its various embodiments and equivalents thereof. 35 ^

Claims

Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application CLAIMS:

1. A composition for topical administration comprising an effective amount of calycosin.

2. The composition of claim 1, wherein the composition comprises an emulsion.

3. The composition of claim 2, wherein the emulsion is an oil / water emulsion.

4. The composition of claim 1, wherein the composition further comprises dimethyl isosorbide.

5. The composition of claim 1, wherein the calycosin is dissolved in dimethyl isosorbide.

6. The composition of claim 5, wherein the composition is stable under storage for at least three (3) months.

7. The composition of claim 5, wherein the composition has less than about 5% degradation when stored at 4 ^ or 25 ^ for one (1) month.

8. The composition of claim 5, wherein the composition has less than about 25% degradation when stored at 40 ^ for one (1) month.

9. The composition of claim 1, wherein calycosin is present in a concentration of about 0.0001% to about 5.0% w / w.

10. The composition of claim 1, wherein calycosin is present in a concentration of about 0.0005% to about 2.0% w / w.

11. The composition of claim 1, wherein calycosin is present in a concentration of 0.0007% to about 1.0% w / w.

12. The composition of claim 1, wherein calycosin is present in a concentration of about 0.001% to about 0.75% w / w. 36 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 13. The composition of claim 1, wherein calycosin is present in a concentration of about 0.5% w / w.

14. The composition of claim 1, wherein the composition is selected from a group consisting of: fluid, emulsion, encapsulation, suspension, solid, semi-solid, jelly, paste, gel, hydrogel, ointment, lotion, emulsion, cream, foam, mousse, liquid, spray, suspension, dispersion, powder, aerosol, color cosmetic, hair treatment, and any combination thereof.

15. The composition of claim 1, wherein the composition further comprises one or more excipients selected from a group consisting of: solvent, emulsifier, preservative, antioxidant, emollient, thickening agent, penetration enhancer, surfactant, diluent, filler, carrier, and / or pH control agent.

16. The composition of claim 15, wherein the preservative is an antimicrobial preservative or chelating agent.

17. The composition of claim 15, wherein the solvent is dimethyl isosorbide.

18. The composition of claim 1, wherein the composition further comprises one or more excipients selected from a group consisting of: water, dimethyl isosorbide, glycerin, caprylic / capric triglyceride, propanediol, sunflower seed oil, ethoxydiglycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerin / sebacic acid copolymer, diheptyl succinate, naringenin, lecithin, decylene glycol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidyl alcohol, behenyl alcohol, arachidyl glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olea europaea (olive) fruit oil, olea europaea (olive) oil unsponifiables, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, citric acid, sodium acetylated hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and ethylhexylglycerin.

19. The composition of claim 1, wherein the composition comprises about 50% to about 70% water (w / w) and about 10% to about 30% (w / w) dimethyl isosorbide. 37 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 20. The composition of claim 1, wherein the composition is: Ingredient %w / w Water 40 - 8038 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 21. A method of treating or preventing a topical condition in a subject by administration of a composition comprising an effective amount of calycosin.

22. The method of claim 21, wherein the administration of the composition prevents fine lines or wrinkles on skin of the subject.

23. The method of claim 21, wherein the administration of the composition leads to supporting firmness and elasticity of skin of the subject.

24. The method of claim 21, wherein the administration of the composition leads to the prevention of skin and hair damaged by reactive oxygen species.

25. The method of claim 21, wherein the administration of the composition leads to protection from environment aggressors on skin.

26. The method of claim 21, wherein the administration of the composition leads to supporting skin elasticity.

27. The method of claim 21, wherein the topical condition is glycation.

28. The method of claim 21, wherein the administration of the composition leads increase in skin and / or hair resiliency.

29. The method of claim 21, wherein the administration of the composition leads to increase in elasticity of skin.

30. The method of claim 21, wherein the administration of the composition leads to prevention of skin damage.

31. The method of claim 21, wherein the composition is administered topically.

32. The method of claim 21, wherein the composition comprises an emulsion.

33. The method of claim 32, wherein the emulsion is an oil / water emulsion. 39 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 34. The method of claim 21, wherein the composition further comprises dimethyl isosorbide.

35. The method of claim 21, wherein the calycosin is dissolved in dimethyl isosorbide.

36. The method of claim 35, wherein the composition is stable under storage for at least three (3) months.

37. The method of claim 35, wherein the composition has less than about 5% degradation when stored at 4 ^ or 25 ^ for one (1) month.

38. The method of claim 35, wherein the composition has less than about 25% degradation when stored at 40 ^ for one (1) month.

39. The method of claim 21, wherein calycosin is present in a concentration of about 0.0001% to about 5.0% w / w.

40. The method of claim 21, wherein calycosin is present in a concentration of about 0.0005% to about 2.0% w / w.

41. The method of claim 21, wherein the calycosin is present in a concentration of 0.0007% to about 1.0% w / w.

42. The method of claim 21, wherein calycosin is present in a concentration of about 0.001% to about 0.75% w / w.

43. The method of claim 21, wherein calycosin is present in a concentration of about 0.5% w / w.

44. The method of claim 21, wherein the composition is selected from a group consisting of: fluid, emulsion, encapsulation, suspension, solid, semi-solid, jelly, paste, gel, hydrogel, ointment, lotion, emulsion, cream, foam, mousse, liquid, spray, suspension, dispersion, powder, aerosol, color cosmetic, and any combination thereof. 40 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 45. The method of claim 21, wherein the composition further comprises one or more excipients selected from a group consisting of: solvent, emulsifier, preservative, antioxidant, emollient, thickening agent, penetration enhancer, surfactant, diluent, filler, carrier and / or pH control agent.

46. The method of claim 45, wherein the preservative is an antimicrobial preservative or a chelating agent.

47. The method of claim 45, wherein the solvent is dimethyl isosorbide.

48. The method of claim 21, wherein the composition further comprises one or more excipients selected from a group consisting of: water, dimethyl isosorbide, glycerin, caprylic / capric triglyceride, propanediol, sunflower seed oil, ethoxydiglycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerin / sebacic acid copolymer, diheptyl succinate, naringenin, lecithin, decylene glycol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidyl alcohol, behenyl alcohol, arachidyl glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olea europaea (olive) fruit oil, olea europaea (olive) oil unsponifiables, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, citric acid, sodium acetylated hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and ethylhexylglycerin.

49. The method of claim 21, wherein the composition comprises about 50% to about 70% water (w / w) and about 10% to about 30% (w / w) dimethyl isosorbide.

50. The method of claim 21, wherein the composition is: Ingredient %w / w41 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application Sodium Arcylates Copolymer 0 - 2 Cetearyl Alcohol 0 - 251. The composition of claim 1, wherein the composition is anhydrous.

52. The composition of claim 1, wherein the composition comprises oil as the only solvent.

53. The method of claim 21, wherein the composition is anhydrous.

54. The method of claim 21, wherein the composition comprises oil as the only solvent. 42 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 55. A method of modulating expression of one or more genes by administration of a composition comprising calycosin, wherein at least one of the genes is related to a topical condition.

56. The method of claim 55, wherein the one or more genes are selected from a group consisting of: (i) MUCL1, (ii) KLK6, (iii) PSAPL1, (iv) S100A7, (v) IL37, and (vi) MMP1.

57. The method of claim 55, wherein the administration of the composition leads to down- regulation of MUCL1, KLK6, PSAPL1, S100A7, IL37, and / or MMP1.

58. The method of claim 55, wherein the administration of the composition enhances anti- inflammatory activity.

59. The method of claim 55, wherein the administration of the composition enhances maintenance of skin barrier lipids.

60. The method of claim 55, wherein the administration of the composition enhances the maintenance of collagen network to prevent formation of fine lines and / or wrinkles in the skin.

61. The method of claim 55, wherein the administration of the composition results in downregulation of genes involved in promoting melanogenesis.

62. The method of claim 55, wherein the administration of the composition results in downregulation of genes involved in promoting anti-inflammatory responses.

63. The method of claim 55, wherein the administration of the composition results in downregulation of genes involved in degradation of skin barrier lipids.

64. The method of claim 55, wherein the administration of the composition results in downregulation of genes involved in degradation of molecules involved in barrier function restoration. 43 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 65. The method of claim 55, wherein the administration of the composition results in downregulation of genes involved in degradation of collagen.

66. The method of claim 61, wherein the administration of the composition results in downregulation of expression and / or activity of MUCL1.

67. The method of claim 62, wherein the administration of the composition results in downregulation of expression and / or activity of KLK6 and / or IL37.

68. The method of claim 63, wherein the administration of the composition results in downregulation of expression and / or activity of PSAPL1.

69. The method of claim 64, wherein the administration of the composition results in downregulation of expression and / or activity of S100A7.

70. The method of claim 65, wherein the administration of the composition results in downregulation of expression and / or activity of MMP1.

71. The method of claim 55, wherein the administration of the composition to a subject leads to the treatment of prevention of a topical condition of the subject.

72. The method of claim 66, wherein the administration of the composition leads to at least about ten (10) fold downregulation of MUCL1.

73. The method of claim 67, wherein the administration of the composition leads to at least about thirty (30) fold downregulation of KLK6.

74. The method of claim 67, wherein the administration of the composition leads to at least about ten (10) fold downregulation of IL37.

75. The method of claim 68, wherein the administration of the composition leads to at least about twenty (20) fold downregulation of PSALP1. 44 ^Attorney Docket No.: DEBU-017 / 01WO 37396 / 141 Patent Application 76. The method of claim 69, wherein the administration of the composition leads to at least about fifteen (15) fold downregulation of S100A7.

77. The method of claim 70, wherein the administration of the composition leads to at least about five (5) fold downregulation of MMP1.

78. The method of claim 55, wherein the administration of composition alters one or more of a function related with the modulated genes, wherein the one or more function is selected from the group consisting of: (i) maintenance of skin barrier, (ii) collagen expression, (iii) collagen degradation, (iv) inflammation, (v) melanin degradation, (vi) maintenance of skin barrier lipids, and (vii) melanin production.

79. The method of claim 55, wherein the composition further comprises a solvent.

80. The method of claim 55, wherein the solvent is selected from a group consisting of: dimethyl isosorbide, ethoxydiglycol, isopropyl lauryl sarcosinate, pentylene glycol, propanediol, 1,2-hexanediol, and / or butylene glycol. 45 ^

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