Formulations of eriodicytol

Abstract

The present invention provides compositions comprising ruscogenin. The compositions of the present invention can be topically applied to the skin of a subject. The present invention further provides methods of applying compositions comprising ruscogenin to improve or treat a skin condition. The compositions of the present invention can also be applied to improve the overall appearance of the skin.

Description

Technical Field

[0001] This invention relates to formulations of senna and methods of applying the formulations to the local symptoms of a subject. Background Technology

[0002] The mammalian epidermis, along with its appendages (such as hair, nails, sebaceous glands, and sweat glands), provides a barrier that keeps harmful elements out of the body and essential fluids inside. As the first line of defense against various physical environmental damages, the epidermis must protect itself and the underlying tissues. The epidermis is also exposed to mutagenic ultraviolet radiation. In areas without hair or with sparse hair (such as most human skin), the epidermis is thicker than hairy skin, and in these locations, the skin primarily serves a protective function. The continuous attack on the epidermis necessitates self-renewal, making it a typical example of an adult tissue undergoing a continuous and rapid flux of radiation.

[0003] Aging skin differs from youthful skin in both appearance and function. The aging epidermis exhibits reduced keratinocyte proliferation and is physically thinner, primarily due to the degeneration of the epithelial 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 be caused by age-related changes in the dermis. The dermis of older adults is also typically thinner. Aging fibroblasts are less likely to synthesize normal amounts of collagen, elastin, laminin glycosaminoglycans, and fibronectin. In such cases, the dermis may lack elasticity, strength, vascular support, remodeling capacity, and matrix. For example, the epithelial ridges may be erased, and basal cells may no longer show villous projections into the dermis. Epidermal cell turnover is reduced by up to 50% in older adults compared to younger adults.

[0004] For example, the number of melanocytes may decrease by 8-20% every decade. Older adults have fewer Langerhans cells, and these cells are often impaired in function. For instance, within four years of menopause in women, collagen synthesis decreases by up to 30%. The amount of collagen and elastin fibers also decreases. The dermis may also show a decreased echogenicity to ultrasound, consistent with changes in collagen and elastin tissue. Summary of the Invention

[0005] This invention relates to compositions of senna, and methods of using these compositions to treat, protect, and / or alter (e.g., improve) skin conditions and / or aesthetic appearance, including, for example, treating, preventing, improving, reducing, and / or eliminating fine lines and / or wrinkles and / or improving the aesthetic appearance of fine lines and / or wrinkles. In some embodiments, the compositions of the invention improve skin and / or hair resilience. In some embodiments, the compositions of the invention improve skin elasticity. In some embodiments, the compositions of the invention prevent skin damage. In some embodiments, the compositions of the invention prevent scar tissue formation during wound healing.

[0006] The topical application of compositions containing sennaol in the field of human skin is not yet known. Specifically, the topical application of sennaol to improve skin condition (including enhancing skin appearance) by topically applying a composition containing an effective amount of sennaol is not known in the art. Advantageously, the present invention recognizes for the first time that topical compositions containing sennaol can be used to improve skin condition or treat any skin-related disease in a subject.

[0007] On one hand, the present invention provides a composition for topical application comprising an effective amount of sennaol. An effective amount of sennaol is the amount of sennaol that effectively treats, improves, or otherwise affects the underlying condition of the skin. The present invention recognizes that sennaol is poorly soluble or insoluble in water. The present invention also recognizes that sennaol is poorly soluble or insoluble in oils; for example, sennaol is insoluble in sunflower (Helianthus Annuus) seed oil. Additionally, sennaol is only minimally soluble in pentylene glycol and caprylic / capric triglycerides. In some embodiments of the invention, sennaol is dissolved in a solvent selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, isopropyl lauroyl sarcosinate, and any combination thereof. In some preferred embodiments, sennaol is dissolved in dimethyl isosorbide. In some embodiments, the composition containing sennaol is anhydrous. In some embodiments, the composition comprises an oil as the sole solvent.

[0008] In some embodiments, the composition containing senna is an emulsion. In some embodiments, the emulsion is an oil / water emulsion. In some embodiments, the composition further comprises a solvent. In some embodiments, the solvent is selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, lauroyl sarcosine isopropyl ester, and any combination thereof. In some embodiments, the solvent in the composition is dimethyl isosorbide. In some embodiments, the solvent in the composition is ethoxydiethylene glycol. In some embodiments, the solvent in the composition is lauroyl sarcosine isopropyl ester. In some embodiments, the solvent in the composition is a glycol. In some embodiments, the glycol is selected from the group consisting of: pentanediol, butanediol, propylene glycol, and any combination thereof.

[0009] In some embodiments, sennaol is dissolved in a solvent selected from the group consisting of: 1,2-heptanediol, 1,2-hexanediol, 1,2-propanediol, butanediol, C 15-19 Alkanes, decanoic acid / caprylic acid triglycerides, dibutyl adipate, diisopropyl adipate, dimethyl isosorbide, dipropylene glycol, ethanol, ethoxydiethylene glycol, isoamyl laurate, isohexadecane, isopentyl glycol, isopropyl myristate, isopropyl lauroyl sarcosinate, jojoba oil, meadowfoam seed oil, mineral oil, neopentyl glycol diethylhexanoate, octyl dodecyl alcohol, oleyl alcohol, pentylene glycol, phenylpropanol, polysorbate 20, propylene glycol, safflower seed oil, squalane, squalene, sunflower oil, tert-butanol, tributyl limonene, tert-butyl-O-acetyl citrate, triC citrate 15-19 Alkyl esters, triethyl citrate, O-acetylated triethyl citrate, and triisostearin.

[0010] The compositions of the present invention are stable under environmental conditions during storage. This is advantageous because the compositions of the present invention can be stored prior to administration to a subject. No previously known storage-resistant formulations of sennaol exist. Storage-resistant formulations of sennaol would provide a convenient option for compositions intended for use in patients with various skin conditions and / or seeking a choice in skin appearance.

[0011] In some preferred embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least two (2) years of storage. In some embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least one year of storage. In some embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least six (6) months of storage. In some embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least three (3) months of storage.

[0012] In some embodiments, the composition exhibits less than about 5% degradation when stored at 50°C for one (1) month. In some embodiments, the composition exhibits less than about 10% degradation when stored at 50°C for one (1) month. In some embodiments, the composition exhibits less than about 10% degradation when stored at 40°C for one (1) month. In some embodiments, the composition exhibits less than about 1% degradation when stored at 25°C and / or 4°C for one (1) month. In some embodiments, the composition exhibits less than about 10% degradation when stored at 40°C for three (3) months. In some embodiments, the composition exhibits less than about 10% degradation when stored at 25°C for three (3) months. In some embodiments, the composition exhibits less than about 10% degradation when stored at 25°C for six (6) months. In some embodiments, the composition exhibits less than about 5% degradation when stored at 4°C for three (3) months.

[0013] The high stability of the compositions of the present invention under accelerated stabilization conditions indicates that the compositions of the present invention will be stable under environmental conditions for at least 2 years. In some embodiments, the compositions comprise sennaol dissolved in dimethyl isosorbide, lauroyl sarcosinate, and ethoxydiethylene glycol.

[0014] Surprisingly, the stability of sennaol depends on the pH of the composition. The present invention recognizes that sennaol degrades at a higher rate if the pH of the composition is not within the optimal pH range. Therefore, in some embodiments, the compositions of the present invention contain buffers and / or pH adjusters to maintain the pH of the composition within the optimal range, thereby minimizing the degradation of sennaol under environmental conditions. In some embodiments, the pH of the composition is from about 4 to about 8. In some embodiments, the pH of the composition is from about 4 to about 7. In some embodiments, the pH of the composition is from about 4 to about 6. In some embodiments, the pH of the composition is from about 4 to about 5. Figure 1 Data on the stability of the compositions of the present invention relative to the pH of the solution are provided.

[0015] In some embodiments, the composition has a pH of about 4. In some embodiments, the composition containing sennaol and a pH of about 4 has less than about 10% degradation when stored at 50°C for one (1) month.

[0016] In some embodiments, the composition has a pH of about 5. In some embodiments, the composition containing sennaol and a pH of about 5 exhibits less than about 10% degradation when stored at 50°C for one (1) month. In some embodiments, the composition containing sennaol and a pH of about 5 exhibits less than about 20% degradation when stored at 50°C for one (1) month.

[0017] In some embodiments, the composition has a pH of about 6. In some embodiments, the composition containing sennaol and a pH of about 6 exhibits less than about 10% degradation when stored at 50°C for one (1) month. In some embodiments, the composition containing sennaol and a pH of about 6 exhibits less than about 20% degradation when stored at 50°C for one (1) month.

[0018] In some embodiments, the composition has a pH of about 7. In some embodiments, the composition containing sennaol and a pH of about 7 exhibits less than about 20% degradation when stored at 50°C for one (1) month. In some embodiments, the composition containing sennaol and a pH of about 6 exhibits less than about 25% degradation when stored at 50°C for one (1) month.

[0019] In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 5 nM to about 5 mM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 10 nM to about 4 mM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 5 nM to about 2500 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 10 nM to about 2000 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 20 nM to about 1000 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 10 nM to about 20 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 5 μM to about 3750 μM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 50 μM to about 3000 μM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 50 μM to about 3000 μM.

[0020] In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.0001% w / w to about 5.0% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.0001% w / w to about 1.0% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.001% w / w to about 0.5% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.01% w / w to about 0.5% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.1% w / w to about 0.5% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.5% w / w.

[0021] In some aspects, the compositions of the present invention can be applied topically to the skin of a subject. The compositions of the present invention can be included in any formulation suitable for topical application. In some embodiments, the compositions of the present invention are fluids, emulsions, encapsulations, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, cosmetics, and / or hair care products. In some embodiments, the compositions of the present invention further include excipients. These excipients may be selected from the group consisting of solvents, emulsifiers, preservatives, antioxidants, emollients, thickeners, penetration enhancers, surfactants, diluents, fillers, carriers, and / or pH control agents. In some embodiments, the preservatives in the composition are antimicrobial preservatives or chelating agents. In some embodiments, the excipients in the composition are selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, diol, lauroyl sarcosinate isopropyl ester, 1,2-hexanediol, propylene glycol, phenylpropanol, isopentyl glycol, 1,2-heptanediol, water, glycerin, hydrogenated ethylhexyl olive oil, hydrogenated olive oil unsaponifiables, polyglycerol-6-distearate, jojoba ester, polyglycerol-3-beeswax, cetyl alcohol, cetearyl oleate, sorbitan oleate, hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, sunflower seed oil, caprylic / capric triglyceride, phenoxyethanol, decanediol, and 1,2-hexanediol.

[0022] The compositions of the present invention can be prepared by various methods. As an example, the compositions can be prepared by dissolving, dispersing, etc., senna and optional excipients as provided herein in a carrier (e.g., water, saline, dextran aqueous solution, glycerol, glycol, ethanol, etc.) or solvent to form a solution, colloid, liposome, emulsion, complex (including inclusion complexes), coagulated layer, or suspension. In some embodiments, the compositions of the present invention may also contain additional excipients, such as wetting agents, emulsifiers, cosolvents, solubilizers, pH buffers, etc. (e.g., sodium acetate, sodium citrate, cyclodextrin and its derivatives, sorbitol monolaurate, triethanolamine acetate, triethanolamine oleate, hydroxyethylpiperazine, etc.). In some embodiments, the compositions of the present invention may further comprise one or more additional excipients selected from the group consisting of: carriers, excipients, or diluents, including but not limited to absorbents, anti-irritants, antibacterial agents, anti-acne agents, antioxidants, colorants / pigments, emollients (humectants), emulsifiers, film-forming / retaining agents, fragrances, no-rinse exfoliants, prescription drugs, preservatives, scrubs, silicones, skin-skin-soothing / repairing agents, slippers, sunscreen active ingredients, surfactants / detergents, penetration enhancers, and thickeners.

[0023] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion and a preservative.

[0024] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, and a preservative.

[0025] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, a diluent, and a preservative.

[0026] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, a thickener, optionally a diluent, and a preservative.

[0027] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, and one or more excipients selected from the group consisting of: diluents, absorbents, antioxidants, emollients, emulsifiers, thickeners, surfactants, and / or preservatives.

[0028] In some embodiments, the excipients included in the composition are water, dimethyl isosorbide, glycerol, caprylic / capric triglyceride, propylene glycol, sunflower seed oil, ethoxydiethylene glycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerol / sebaceous acid copolymer, diheptyl succinate, naringenin, lecithin, decanediol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidonic acid, behenol, arachidonic acid glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olive (olea europaea) fruit oil, olive (olive) oil unsaponifiables, hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, citric acid, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and / or ethylhexylglycerin.

[0029] In certain aspects of the invention, compositions containing senna exhibit antioxidant activity. In some embodiments, the antioxidant activity of senna in the compositions of the invention has been demonstrated at concentrations of about 0.00016% w / w or higher. Advantageously, the antioxidant activity of compositions containing senna has been demonstrated in both aqueous and organic solvent systems. Therefore, the present invention provides compositions that maintain antioxidant activity in both aqueous and organic solvents. Advantageously, compositions of the present invention containing senna exhibit antioxidant activity that can effectively treat and / or prevent oxidative damage. In some embodiments, compositions of the present invention containing senna exhibit antioxidant activity that can effectively treat skin and / or hair damaged by reactive oxygen species and protect it from other environmental aggressors that may damage the subject's skin. In some other embodiments, compositions of the present invention containing senna exhibit antioxidant activity that can effectively prevent damage to skin and / or hair by reactive oxygen species, including damage caused by environmental aggressors.

[0030] In certain aspects of the invention, compositions containing senna exhibit elastase inhibition. In some embodiments, the elastase-inhibiting activity of senna in the compositions of the invention has been demonstrated at concentrations of about 0.008% w / w or higher. Advantageously, compositions containing senna exhibit elastase-inhibiting activity, effectively promoting skin elasticity. In some embodiments, compositions of the invention containing senna exhibit elastase inhibition, effectively reducing fine lines and / or wrinkles in the skin. In some embodiments, compositions of the invention containing senna exhibit elastase-inhibiting effects, effectively preventing the formation of fine lines and / or wrinkles in the skin.

[0031] In certain aspects of the invention, compositions containing senna exhibit inhibition of glycation. In some embodiments, the glycation-inhibiting activity of senna in the compositions of the invention has been demonstrated at concentrations of about 0.002% w / w or higher. Advantageously, compositions containing senna exhibit glycation-inhibiting activity, effectively supporting and promoting skin and / or hair elasticity.

[0032] In some embodiments of the invention, the compositions of the invention (containing senna) regulate the gene expression of one or more genes associated with local symptoms. In some embodiments, administration of the composition containing senna alters one or more functions associated with the regulated genes, wherein the one or more functions are selected from the group consisting of: (i) the formation of fine lines or wrinkles on the skin, (ii) inflammation, (iii) skin elasticity, (iv) prevention of scar formation during wound healing, and / or (v) any combination thereof.

[0033] In some aspects, the present invention provides a method for treating localized symptoms by applying a topical composition comprising an effective amount of senna. In some embodiments, the present invention provides a method for preventing fine lines or wrinkles on the skin of a subject by applying the compositions provided herein. In some embodiments, the present invention provides a method for supporting skin firmness and improving / maintaining skin elasticity by applying the compositions provided herein. In some embodiments, the present invention provides a method for preventing skin and hair damage from reactive oxidants by applying the compositions provided herein. In some embodiments, the present invention provides a method for protecting skin from environmental aggressors by applying the compositions provided herein. In some embodiments, the present invention provides a method for improving skin and / or hair resilience by applying the compositions provided herein. In some embodiments, the present invention provides a method for preventing glycation by applying the compositions provided herein. Glycation is known to be associated with wrinkling, loss of elasticity, and aging of the skin. In some embodiments, the present invention provides a method for reducing skin damage by applying the compositions provided herein.

[0034] In some embodiments, application of a composition containing sennaol alters the expression and / or function of one or more genes selected from the group consisting of: MMP10, THBS1, TOP2A, TFPI2, MMP1, FN1, KCTD4, ATP12A, ALDH1A3, MKI67, FST, SLC13A5, IL6, IL23A, TNF, IL24, MMP3, MMP9 and / or PPFIA4.

[0035] In some embodiments, application of a composition containing sennaol results in downregulation of the expression and / or activity of MMP10, THBS1, TOP2A, TFPI2, MMP1, FN1, KCTD4, ATP12A, ALDH1A3, MKI67, FST, SLC13A5, IL6, IL23A, TNF, IL24, MMP3, and / or MMP9.

[0036] In some embodiments, the application of the composition upregulates the expression and / or activity of PPFIA4.

[0037] In some embodiments, the application of the composition enhances its anti-inflammatory activity. In some embodiments, the anti-inflammatory activity of the composition is modulated by downregulating the expression and / or activity of IL6, IL23a, TNF, and / or IL24.

[0038] In some embodiments, the application of the composition produces anti-aging activity. In some embodiments, the anti-aging activity of the composition containing sennaol is modulated by downregulating the expression and / or activity of MMP10, MMP9, MMP3 and MMP1.

[0039] In some embodiments, application of a composition containing senna enhances the maintenance of skin barrier lipids. In some embodiments, the maintenance of skin barrier lipids is modulated by upregulating the expression and / or activity of PPFIA4.

[0040] In some embodiments, application of a composition containing sennaol induces prevention of scar tissue formation after wound healing. In some embodiments, prevention of scar tissue formation after wound healing is modulated by downregulating the expression and / or activity of THBS1.

[0041] In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 10 (MMP10) activity and / or expression by at least about ten (10) times. In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 10 (MMP10) activity and / or expression by about twenty-five (25) times.

[0042] In some embodiments, application of the composition containing sennaol resulted in a downregulation of thrombocytopenic purpura protein 1 (THBS1) activity and / or expression by at least about ten (10) times. In some embodiments, application of the composition containing sennaol resulted in a downregulation of thrombocytopenic purpura protein 1 (THBS1) activity and / or expression by about fifteen (15) times.

[0043] In some embodiments, application of the composition containing senna resulted in a downregulation of DNA topoisomerase II-α (TOP2A) activity and / or expression by at least about ten (10)-fold. In some embodiments, application of the composition containing senna resulted in a downregulation of DNA topoisomerase II-α (TOP2A) activity and / or expression by about fifteen (15)-fold. In some embodiments, application of the composition containing senna resulted in a downregulation of DNA topoisomerase II-α (TOP2A) activity and / or expression by about twenty (20)-fold.

[0044] In some embodiments, administration of the composition comprising senna resulted in a downregulation of the activity and / or expression of tissue factor pathway inhibitor 2 (TFPI2) by at least about ten (10)-fold. In some embodiments, administration of the composition comprising senna resulted in a downregulation of the activity and / or expression of tissue factor pathway inhibitor 2 (TFPI2) by about fifteen (15)-fold. In some embodiments, administration of the composition comprising senna resulted in a downregulation of the activity and / or expression of tissue factor pathway inhibitor 2 (TFPI2) by about twenty (20)-fold.

[0045] In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 1 (MMP1) activity and / or expression by at least about two (2) times. In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 1 (MMP1) activity and / or expression by about ten (10) times.

[0046] In some embodiments, application of the composition results in a downregulation of fibronectin 1 (FN1) activity and / or expression by at least about two (2) times. In some embodiments, application of the composition results in a downregulation of fibronectin 1 (FN1) activity and / or expression by about ten (10) times.

[0047] In some embodiments, application of the composition resulted in a downregulation of the activity and / or expression of the potassium-containing channel tetramerization domain 4 (KCTD4) by at least about five (5) times. In some embodiments, application of the composition resulted in a downregulation of the activity and / or expression of the potassium-containing channel tetramerization domain 4 (KCTD4) by about fifteen (15) times.

[0048] In some embodiments, application of the composition containing senna resulted in a downregulation of the activity and / or expression of the non-gastric α2 subunit of the ATPase H+ / K+ transporter (ATP12A) by at least about two (2) times. In some embodiments, application of the composition containing senna resulted in a downregulation of the activity and / or expression of the non-gastric α2 subunit of the ATPase H+ / K+ transporter (ATP12A) by about ten (10) times.

[0049] In some embodiments, application of a composition containing sennaol resulted in a downregulation of the activity and / or expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3) by at least about two (2) times. In some embodiments, application of a composition containing sennaol resulted in a downregulation of the activity and / or expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3) by about ten (10) times.

[0050] In some embodiments, administration of the composition containing sennaol resulted in a downregulation of the activity and / or expression of the proliferation marker Ki-67 (MKI67) by at least about two (2) times. In some embodiments, administration of the composition containing sennaol resulted in a downregulation of the activity and / or expression of the proliferation marker Ki-67 (MKI67) by about ten (10) times.

[0051] In some embodiments, administration of a composition containing senna resulted in a downregulation of follistatin (FST) activity and / or expression by at least about two (2) times. In some embodiments, administration of a composition containing senna resulted in a downregulation of follistatin (FST) activity and / or expression by about ten (10) times.

[0052] In some embodiments, application of a composition containing senna resulted in a downregulation of the activity and / or expression of solute carrier family 13 member 5 (SLC13A5) by at least about five (5) times. In some embodiments, application of a composition containing senna resulted in a downregulation of the activity and / or expression of solute carrier family 13 member 5 (SLC13A5) by about fifteen (15) times.

[0053] In some embodiments, application of the composition containing senna resulted in a downregulation of interleukin-6 (IL6) activity and / or expression by at least about five (5) times. In some embodiments, application of the composition containing senna resulted in a downregulation of interleukin-6 (IL6) activity and / or expression by about twenty (20) times.

[0054] In some embodiments, application of the composition containing senna resulted in a downregulation of interleukin-23 (IL23) activity and / or expression by at least about two (2) times. In some embodiments, application of the composition containing senna resulted in a downregulation of interleukin-23 (IL23) activity and / or expression by about five (5) times.

[0055] In some embodiments, application of the composition containing senna resulted in a downregulation of tumor necrosis factor (TNF) activity and / or expression by at least about ten (10) times. In some embodiments, application of the composition containing senna resulted in a downregulation of tumor necrosis factor (TNF) activity and / or expression by about two hundred and fifty (250) times.

[0056] In some embodiments, application of the composition containing sennaol resulted in a downregulation of interleukin 24 (IL24) activity and / or expression by at least about ten (10) times. In some embodiments, application of the composition containing sennaol resulted in a downregulation of interleukin 24 (IL24) activity and / or expression by about seventy (70) times.

[0057] In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 3 (MMP3) activity and / or expression by at least about ten (10) times. In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 3 (MMP3) activity and / or expression by about fifty (50) times.

[0058] In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 9 (MMP9) activity and / or expression by at least about two (2) times. In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 9 (MMP9) activity and / or expression by about eight (8) times.

[0059] In some embodiments, application of the composition containing senna resulted in an upregulation of PTPRF interacting protein α4 (PPFIA4) activity and / or expression by at least about five (5) times. In some embodiments, application of the composition containing senna resulted in an upregulation of PTPRF interacting protein α4 (PPFIA4) activity and / or expression by about thirty (30) times. Attached Figure Description

[0060] Figure 1 Stability data for compositions containing senna are provided. Detailed Implementation

[0061] Sacred herbol Epimedium is a naturally occurring polyphenol primarily found in the yerba da Santa Clause plant. (Venditti et al., Deng et al., Pharmacological Activity of Eriodictyol: The Major Natural Polyphenolic Flavanone, *Evidence-Based Complementary and Alternative Medicine*). Evidence-Based Complementary and Alternative Medicine (Article ID 6681352) , 2020. Senna is a well-known natural bitter masking agent used in the food industry (especially in wine), and its toxicity is expected to be very low or zero. To the best of our knowledge, there are no reported toxicity results for senna.

[0062] This invention provides compositions of sennaol. The chemical structure of sennaol is shown below:

[0063] Eriodictyol possesses anti-inflammatory activity, which is evidenced by its ability to reduce inflammatory markers in macrophages. Eriodictyol also exhibits anti-inflammatory activity in mice, alleviating symptoms of atopic dermatitis. (Park et al., Effect of eriodictyol on the development of atopic dermatitis-like lesions in ICR mice, *Bulletin of Biology and Pharmacy*). Biol Pharm Bull )》, 2013;36(8): 1375-9.

[0064] In addition, sennaol reduces neuroinflammation and alleviates hypererythema by acting on the TRPV1 receptor. Deng et al., Pharmacological activity of sennaol: major natural polyphenol flavanones, *Evidence-Based Complementary and Alternative Medicine*, 2020, Article ID 6681352. Neurological research has been further extended to neurodegenerative diseases, where sennaol alleviates cognitive decline in mice by acting on the Nrf2 / HO-1 pathway. Li et al., Eriodictyolameliorates cognitive dysfunction in APP / PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation, *Molecular Medicine*. Molecular Medicine In the context of skin, eriodictyol reduces melanogen production in melanoma cells by inhibiting tyrosinase and protecting the skin from UVA-induced photodamage and apoptosis. (Imen et al., Anti-melanogenesis and anti-genotoxic activities of eriodictyol in murine melanoma (B16-F10) and primary human keratinocyte cells, Life Sciences, 2022, 28, 11.) Life Science. )》 2015, 135-173; Nakashima et al., Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna), Bioorganic & Medicinal Chemistry Letters ( Bioorg Med Chem Lett.)》, 2015, 25(13), 2702-6; Lee et al., The Anti-apoptotic and Anti-oxidant Effect of Eriodictyol on UV-Induced Apoptosis in Keratinocytes, Bulletin of Biology and Pharmacy, January 2007; 30(l):32-7.

[0065] Senna also exhibits antioxidant, cardioprotective, anticancer, antidiabetic, and hepatoprotective activities.

[0066] Composition of sennaol: On one hand, the present invention provides compositions comprising sennaol. In some embodiments, the present invention provides compositions comprising sennaol suitable for application to the skin of a subject.

[0067] On one hand, the present invention provides a composition for topical application comprising an effective amount of sennaol. An effective amount of sennaol is the amount of sennaol that effectively treats, improves, or otherwise affects underlying conditions of the skin. The present invention recognizes that sennaol is poorly soluble or insoluble in water. The present invention also recognizes that sennaol is poorly soluble or insoluble in oils; for example, sennaol is insoluble in sunflower seed oil. Additionally, sennaol is only minimally soluble in pentylene glycol and caprylic / capric triglycerides. In some embodiments of the invention, sennaol is dissolved in a solvent selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, isopropyl lauroyl sarcosinate, and any combination thereof. In some preferred embodiments, sennaol is dissolved in dimethyl isosorbide. In some embodiments, the composition containing sennaol is anhydrous. In some embodiments, the composition comprises an oil as the sole solvent.

[0068] In some embodiments, sennaol is dissolved in a solvent selected from the group consisting of: 1,2-heptanediol, 1,2-hexanediol, 1,2-propanediol, butanediol, C 15-19 Alkanes, decanoic acid / caprylic acid triglycerides, dibutyl adipate, diisopropyl adipate, dimethyl isosorbide, dipropylene glycol, ethanol, ethoxydiethylene glycol, isoamyl laurate, isohexadecane, isopentyl glycol, isopropyl myristate, isopropyl lauroyl sarcosinate, jojoba oil, meadowfoam seed oil, mineral oil, neopentyl glycol diethylhexanoate, octyl dodecyl alcohol, oleyl alcohol, pentylene glycol, phenylpropanol, polysorbate 20, propylene glycol, safflower seed oil, squalene, sunflower oil, tert-butanol, tributyl limonene, tert-butyl-O-acetyl citrate, triC citrate 15-19Alkyl esters, triethyl citrate, O-acetylated triethyl citrate, and triisostearin.

[0069] Table 1 below contains solubility data for sennaol in various solvents.

[0070] Table 1: Solubility of sennaol

[0071] As can be clearly seen from the data provided above, sennaol is soluble in dimethyl isosorbide, ethoxydiethylene glycol, and isopropyl lauroyl sarcosinate, as well as any combination thereof. However, sennaol has minimal solubility in many other commonly used solvents.

[0072] In some embodiments, the composition containing senna is an emulsion. In some embodiments, the emulsion is an oil / water emulsion. In some embodiments, the composition further comprises a solvent. In some embodiments, the solvent is selected from the group consisting of dimethyl isosorbide, ethoxydiethylene glycol, lauroyl sarcosine isopropyl ester, and any combination thereof. In some embodiments, the solvent in the composition is dimethyl isosorbide. In some embodiments, the solvent in the composition is ethoxydiethylene glycol. In some embodiments, the solvent in the composition is lauroyl sarcosine isopropyl ester.

[0073] In some preferred embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least two (2) years of storage. In some embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least one year of storage. In some embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least six (6) months of storage. In some embodiments, the senna-containing compositions of the present invention are stable under environmental conditions for at least three (3) months of storage.

[0074] In some embodiments, the composition exhibits less than about 5% degradation when stored at 50°C for one (1) month. In some embodiments, the composition exhibits less than about 10% degradation when stored at 50°C for one (1) month. In some embodiments, the composition exhibits less than about 10% degradation when stored at 40°C for one (1) month. In some embodiments, the composition exhibits less than about 1% degradation when stored at 25°C and / or 4°C for one (1) month. In some embodiments, the composition exhibits less than about 10% degradation when stored at 40°C for three (3) months. In some embodiments, the composition exhibits less than about 10% degradation when stored at 25°C for three (3) months. In some embodiments, the composition exhibits less than about 10% degradation when stored at 25°C for six (6) months. In some embodiments, the composition exhibits less than about 5% degradation when stored at 4°C for three (3) months.

[0075] The high stability of the compositions of the present invention under accelerated stabilization conditions indicates that the compositions of the present invention will be stable under environmental conditions for at least 2 years. In some embodiments, the compositions comprise sennaol dissolved in dimethyl isosorbide, lauroyl sarcosinate, and ethoxydiethylene glycol.

[0076] Table 2 below provides stability data for sennaol in dimethyl isosorbide: Table 2: Stability Data

[0077] As can be clearly seen from the data provided in Table 2, the compositions containing sennaol exhibit good stability and minimal degradation. The representative data provided in Table 2 confirm that the compositions of the present invention containing sennaol, dissolved in dimethyl isosorbide, are stable when tested under accelerated conditions. Therefore, the compositions of the present invention are stable even after storage under ambient conditions for at least 2 years.

[0078] Surprisingly, the stability of sennaol depends on the pH of the composition. The present invention recognizes that sennaol degrades at a higher rate if the pH of the composition is not within the optimal pH range. Therefore, in some embodiments, the compositions of the present invention contain buffers and / or pH adjusters to maintain the pH of the composition within the optimal range, thereby minimizing the degradation of sennaol under environmental conditions. In some embodiments, the pH of the composition is from about 4 to about 8. In some embodiments, the pH of the composition is from about 4 to about 7. In some embodiments, the pH of the composition is from about 4 to about 6. In some embodiments, the pH of the composition is from about 4 to about 5. Figure 1 Data on the stability of the compositions of the present invention relative to the pH of the solution are provided.

[0079] In some embodiments, the composition has a pH of about 4. In some embodiments, when stored at 50°C for one (1) month, the composition containing sennaol and a pH of about 4 has less than about 10% degradation. In some embodiments, when stored at 50°C for two (2) months, the composition containing sennaol and a pH of about 4 has less than about 10% degradation.

[0080] In some embodiments, the composition has a pH of about 5. In some embodiments, the composition containing sennaol and a pH of about 5 exhibits less than about 10% degradation when stored at 50°C for one (1) month. In some embodiments, the composition containing sennaol and a pH of about 5 exhibits less than about 20% degradation when stored at 50°C for one (1) month.

[0081] In some embodiments, the composition has a pH of about 6. In some embodiments, the composition containing sennaol and a pH of about 6 exhibits less than about 10% degradation when stored at 50°C for one (1) month. In some embodiments, the composition containing sennaol and a pH of about 6 exhibits less than about 20% degradation when stored at 50°C for one (1) month.

[0082] In some embodiments, the composition has a pH of about 7. In some embodiments, the composition containing sennaol and a pH of about 7 exhibits less than about 20% degradation when stored at 50°C for one (1) month. In some embodiments, the composition containing sennaol and a pH of about 6 exhibits less than about 25% degradation when stored at 50°C for one (1) month.

[0083] In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 5 nM to about 5 mM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 10 nM to about 4 mM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 5 nM to about 2500 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 10 nM to about 2000 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 20 nM to about 1000 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 10 nM to about 20 nM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 5 μM to about 3750 μM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 50 μM to about 3000 μM. In some embodiments, the compositions of the present invention comprise sennaol at a concentration of about 50 μM to about 3000 μM.

[0084] In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.0001% w / w to about 5.0% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.0001% w / w to about 1.0% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.001% w / w to about 0.5% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.01% w / w to about 0.5% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.1% w / w to about 0.5% w / w. In some embodiments, sennaol is present in the compositions of the present invention at a concentration of about 0.5% w / w.

[0085] In some aspects, the compositions of the present invention can be applied topically to the skin of a subject. The compositions of the present invention can be included in any formulation suitable for topical application. In some embodiments, the compositions of the present invention are fluids, emulsions, encapsulations, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, cosmetics, and / or hair care products. In some embodiments, the compositions of the present invention further include excipients. These excipients may be selected from the group consisting of solvents, emulsifiers, preservatives, antioxidants, emollients, thickeners, penetration enhancers, surfactants, diluents, fillers, carriers, and / or pH control agents. In some embodiments, the preservatives in the composition are antimicrobial preservatives or chelating agents.

[0086] The compositions of the present invention can be prepared by various methods. As an example, the compositions can be prepared by dissolving, dispersing, etc., senna and optional excipients as provided herein in a carrier (e.g., water, saline, dextran aqueous solution, glycerol, glycol, ethanol, etc.) or solvent to form a solution, colloid, liposome, emulsion, complex (including inclusion complexes), coagulated layer, or suspension. In some embodiments, the compositions of the present invention may also contain additional excipients, such as wetting agents, emulsifiers, cosolvents, solubilizers, pH buffers, etc. (e.g., sodium acetate, sodium citrate, cyclodextrin and its derivatives, sorbitol monolaurate, triethanolamine acetate, triethanolamine oleate, hydroxyethylpiperazine, etc.). In some embodiments, the compositions of the present invention may further comprise one or more additional excipients selected from the group consisting of: carriers, excipients, or diluents, including but not limited to absorbents, anti-irritants, antibacterial agents, anti-acne agents, antioxidants, colorants / pigments, emollients (humectants), emulsifiers, film-forming / retaining agents, fragrances, no-rinse exfoliants, prescription drugs, preservatives, scrubs, silicones, skin-skin-soothing / repairing agents, slippers, sunscreen active ingredients, surfactants / detergents, penetration enhancers, and thickeners.

[0087] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion and a preservative.

[0088] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, and a preservative.

[0089] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, a diluent, and a preservative.

[0090] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, a thickener, optionally a diluent, and a preservative.

[0091] In some embodiments, the compositions of the present invention comprise: sennaol in an oil / water emulsion, a solvent for dissolving sennaol, and one or more excipients selected from the group consisting of: diluents, absorbents, antioxidants, emollients, emulsifiers, thickeners, surfactants, and / or preservatives.

[0092] In some embodiments, the excipients included in the composition are water, dimethyl isosorbide, glycerol, caprylic / capric triglyceride, propylene glycol, sunflower seed oil, ethoxydiethylene glycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerol / sebaceous acid copolymer, diheptyl succinate, lecithin, decanediol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidonic acid, behenol, arachidonic acid glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olive fruit oil, unsaponifiables of olive oil, hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, citric acid, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and / or ethylhexylglycerin.

[0093] The compositions of the present invention can be prepared by various methods. As an example, the compositions can be prepared by dissolving, dispersing, etc., senna and optional excipients as provided herein in a carrier (e.g., water, saline, dextran aqueous solution, glycerol, glycol, ethanol, etc.) or solvent to form a solution, colloid, liposome, emulsion, complex (including inclusion complexes), coagulated layer, or suspension. In some embodiments, the compositions of the present invention may also contain auxiliary substances such as wetting agents, emulsifiers, cosolvents, solubilizers, pH buffers, etc. (e.g., sodium acetate, sodium citrate, cyclodextrin and its derivatives, sorbitol monolaurate, triethanolamine acetate, triethanolamine oleate, hydroxyethylpiperazine, etc.). In some embodiments, the compositions of the present invention may further comprise one or more additional excipients selected from the group consisting of: carriers, excipients, or diluents, including but not limited to absorbents, anti-irritants, antibacterial agents, anti-acne agents, antioxidants, colorants / pigments, emollients (humectants), emulsifiers, film-forming / retaining agents, fragrances, no-rinse exfoliants, prescription drugs, preservatives, scrubs, silicones, skin-skin-soothing / repairing agents, slippers, sunscreen active ingredients, surfactants / detergents, penetration enhancers, and thickeners.

[0094] Absorbents are substances added to topical products to absorb water- and oil-soluble or finely dispersed substances. Topical absorbents can also be used as thickeners in various formulations, including face creams, lipsticks, shampoos, and calamine lotions. In some embodiments, absorbents may include, but are not limited to, alcohols (ethanol, methanol, isopropanol, SD alcohol [especially denatured alcohol] and benzyl alcohol), bauxite (alumina), aluminum hydroxychloride, aluminum hydroxide, magnesium aluminum silicate, aluminum silicate, aluminum starch octenyl succinate, aluminum sulfate, ammonium chloride, bentonite, bismuth oxychloride, boron nitride, calcium carbonate, carnauba wax, charcoal, kaolin, clay, coopernica cerifera wax, corn starch, fuller's earth, hydrolyzed corn starch, iron powder, kaolin, sodium magnesium lithium silicate, magnesium, magnesium carbonate, magnesium hydroxide, montmorillonite, nylon-12, rice starch, silica, silicates, silk powder, clay powder, sodium carbonate, sodium polyacrylate, and zeolite.

[0095] Anti-irritants are substances added to topical products to reduce inflammation, especially inflammation caused by the application of the product itself. Excipients included as anti-irritants or anti-inflammatory agents 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, and yarrow (…). Achillea millefolium ), adenosine, citric acid, adenosine triphosphate, Aloe barbadensis, Aloe barbadensis leaf juice extract, aloe extract, aloe juice, hydrogenated olive oil, hydrogenated palm glycerol ester, hydrolyzed silk, hydroquinone, aloe and / or α-biazinool.

[0096] In some embodiments, the compositions of the present invention may further include a humectant. Humectants (or moisturizers) are important cosmetic ingredients that prevent moisture loss, thereby maintaining the skin's natural hydration. Some humectants may also actively attract moisture. In some embodiments, the humectant may be selected from the group consisting of: sodium hyaluronate, acetylated sodium hyaluronate, hydrolyzed sodium hyaluronate, propylene glycol, hexanediol, panthenol, pentanediol, and butylene glycol.

[0097] In some embodiments, the compositions of the present invention may further include a slip agent. The term "slip agent" is used to describe a series of ingredients that can help other ingredients diffuse and penetrate the skin. The slip agent may also have humectant (hygroscopic) properties. In some embodiments, the slip agent may include, but is not limited to, amino-terminated polydimethylsiloxane, bis-PEG-18 methyl ether dimethylsiloxane, diphenylpropyl dimethylsiloxane, butanediol, cetyl dimethylsiloxane, cetyl dimethylsiloxane copolyol, cetyl PEG / PPG-10 / 1-dimethylsiloxane, cyclohexylsiloxane, cyclomethylsiloxane, cyclopentylsiloxane, cyclotetrasiloxane, decanediol, diisostearoyltrimethylolpropane siloxysilicate, dimethylsiloxane, dimethylsiloxane copolyol, dimethylsiloxane crosspolymer, dimethylsiloxane alcohol, dipropylene glycol, hexanediol, hydrolyzed silk, isododecane, methylsiloxane, methyltrimethylsiloxane, methylsiloxane Mannuronic acid ester, methylsiloxane PEG-7 glyceryl cocoate, PEG-10 dimethylsiloxane, PEG-10 dimethylsiloxane / vinyl dimethylsiloxane crosspolymer, PEG-12 dimethylsiloxane, PEG / PPG-18 / 18 dimethylsiloxane, PEG / PPG-20 / 15 dimethylsiloxane, pentane glycol, phenyltrimethylsiloxane, polymethylsilsesquioxane, PPG-3 benzyl ether myristate, dimethylsilane dioxide, silk powder, siloxane, simethicone, sorbitol, stearyl dimethylsiloxane, stearyl methylsiloxane, triethoxyoctylsilane, trimethylsiloxysilicate, xylitol, and zinc stearate.

[0098] In some embodiments, the compositions of the present invention may further include a diluent and / or a carrier. The diluent and / or carrier may include, but is not limited to, polyethylene glycol (such as PEG200, PEG300, PEG400, PEG540, PEG600, PEG1450, or mixtures thereof) and coconut oil (such as propylene glycol dicaprate, coconut oil alcohol-caprylate / caprylate, propylene glycol dicaprate / caprylate, caprylic / capric triglyceride, caprylic / capric / lauric triglyceride, caprylic / capric / linoleic triglyceride, tricaprol, tricaprol, triglyceride trioleate, neopentyl glycol diacrylate / caprylate, caprylic / capric / palmitic acid / stearic acid triglyceride, or mixtures thereof).

[0099] In some embodiments, the compositions of the present invention may further include emollients. Emollients are soft, waxy, lubricating, and thickening substances added to cosmetic / dermatological products to prevent moisture loss and to soften and soothe the skin. In some embodiments, emollients may include, but are not limited to, 10-hydroxydecanoic acid, acetylated glyceryl castor oil, acetylated hydrogenated cottonseed glyceryl ester, acetylated lanolin, acetylated lanolin alcohol, acetylated palm kernel glyceryl ester, agar, algae extracts, alginate, almond oil, squalane, squalene, α-glucan oligosaccharides, amino-terminated polydimethylsiloxane, and *Synostemma pentaphyllum* (…). Anacystis nidulans Extracts, apricot kernel oil, arachidonic acid, arachidonic acid, arachidonic acid, arachidonic acid, arachidonic acid propionate, C 10-30 Cholesterol / lanosterol esters, benzoic acid C 12-15 Alkyl esters, C 12-18 acid triglycerides, C 18-36 Triglycerides, candelilla wax, cannabis ( Cannabis sativa L.) oil, caprylic / capric triglycerides, capryloyl methylsiloxane, carrot oil, safflower (Carthamus tinctorius) oil, American pecan ( Carya illinoensis oil, castor oil isostearate succinate, castor oil, fir fern ( Caulerpa taxifolia Extracts and / or phospholipids.

[0100] In some embodiments, the compositions of the present invention may further comprise film-forming / retaining agents. Film-forming / retaining agents are substances added to cosmetic / dermatological products that help leave a soft, tacky, and continuous coating on the skin. This film has water-binding properties and leaves a smooth feel on the skin. In some embodiments, film-forming / retaining agents may include, but are not limited to, acrylates, acrylate copolymers, acrylate / acrylate C... 10-30Alkyl ester crosspolymers, acrylate / dimethylsiloxane copolymers, adipic acid / neopentyl glycol / trimethicone copolymers, allyl methacrylate crosspolymers, carnauba wax, cellulose gum, carnauba wax, dextrin, diisopropyl adipate, glyceryl polymethacrylate, hydrolyzed wheat protein, hydroxyethyl cellulose, locust bean, neopentyl glycol diheptate, PEG-40 hydrogenated castor oil, polyacrylamide, polyacrylate-17, polyglucuronic acid, polyglycerol methacrylate, polyisobutylene, polymethyl methacrylate, polyquaternium-10, polyquaternium, polyvinyl alcohol, polyvinylpyrrolidone, propylene carbonate, PVM / MA (polyvinyl methyl ether / maleic acid) dodecene crosspolymers, PVP [poly(vinylpyrrolidone)] copolymers, PVP / dimethylaminoethyl-methacrylate, sodium carbomer. Carbomer, sodium polyacrylate, styrene / acrylate copolymer, triethoxyoctylsilane crosslinker, VA (vinyl acetate) / crotonate, VA / crotonate copolymer, VP (vinylpyrrolidone) / eicosene copolymer and VP / hexadecene copolymer.

[0101] In some embodiments, the compositions of the present invention may further comprise excipients associated with the fragrance of the formulation. The fragrance component is a single volatile and / or aromatic plant oil (or synthetic derivative oil) or a mixture thereof, which imparts aroma and odor to cosmetic / dermatological products. The level of fragrance used varies depending on the product type. In some embodiments, the composition of the formulation may contain up to about 0.01% by weight of fragrance. In some embodiments, fragrances (e.g., synthetic and aromatic plant extracts) may include, but are not limited to, acacia (…). Acacia farnesiana Extracts of Ariocarpus santalinus and Pterocarpus santalinus ( Aerocarpus santalinus, ), amyl cinnamate, amyl salicylate, sage oil, wild fennel ( Anethum graveolens Angelica dahurica ( ) Angelica archangelica Root oil, anisaldehyde, fennel, lemon balm extract, Peru balm, bay leaf oil, bergamot oil, bitter orange blossom, rosewood oil, costus oil, frankincense (Boswellia carterii), butylated phenyl methyl propionaldehyde, ylang-ylang ( cananga ) extract, ylang-ylang ( Cananga odorata Cardamom, cedarwood, cherry extract, limon ( Citrus aurantifolia ),lime( Citrus aurantium ), lime extract, citron ( Citrus medica limonium ), Perilla oil, Myrrh ( CommiphoraMyrrha extract, coriander, zucchini, cyclamen aldehyde, dill extract, ethyl vanillin, eugenol, farnesol, farnesyl acetate, Ferula galbaniflua, pine needle oil, sea hygroscopic aldehyde, fennel ( Foeniculum vulgare Extracts of frankincense, frankincense, and styrax ( galbanum Florida Gardenia ( Gardenia Florida extract, grapefruit oil, guaiac wood, guaiac wood ( Guaiacum officinale ), methyl dihydrojasmonate, hexylcinnamaldehyde, hyssop, star anise ( Illicium vernum ), Iris florentina extract, jasmine oil, jasmine flower ( Jasminium grandiflorum ), daffodil extract, laurel ( Laurus nobilis Lauryl lactate, Lavender oil, and Lavender angustifolia (Lavender stenoptera) Lavandula angustifolia ), real lavender ( Lavandula officinalis ), lavender extract and oil, lemon, lemon balm, lemongrass oil, angelica ( Levisticum officinale Root extract, lime oil and extract, limonene, linalool, Litsea cubeba ( Litsea cubeba ), mandarin orange oil or extract, marjoram, lemon balm ( Melissa officinalis Peppermint Mentha piperita ), fragrant cauliflower ( Mentha spicata Spearmint () Mentha viridis ), menthol, menthone, menthoxypropanediol and menthyl lactate.

[0102] In some embodiments, the compositions of the present invention may further include preservatives. Preservatives are substances that prevent bacterial, microbial, or fungal contamination of cosmetic / dermatological products, thereby increasing the shelf life of the product and improving consumer safety. Some of these agents also have a stabilizing effect, enabling them to maintain the function of various active ingredients, including antioxidants (vitamins), emulsifiers, and surfactants. In some embodiments, preservatives may include, but are not limited to, 1,2-hexanediol, benzoic acid, benzyl chloride, borax, bromonitol, butylparaben, caprylyl glycol, chlorophenol, xylene, chlorophenoxyacetic acid, decanediol, dehydroacetic acid, diazoalkylurea, DMDM ​​hydantoin, ethylhexylglycerin, ethylparaben, formaldehyde-releasing preservatives, and germabens. II. Poria cocos (hoelen), hydroxyacetophenone, imidazolidinyl urea, iodopropyl butyl carbamate, isobutylparaben, methylchloroisothiazolinone, methyldibromoglutaronitrile, methylisothiazolinone, methylparaben, o-cymene-5-ol, phenoxyethanol, phenoxyisopropanol, phytosphingosine, polyaminopropyl biguanide, potassium sorbate, propylparaben, quaternary ammonium salt-15, sodium benzoate, sodium citrate, sodium dehydroacetate, sodium hexametaphosphate, sodium hydroxymethylglycine, phenylethanol, sodium lactobionate, sodium metabisulfite, sodium sulfite, sorbic acid and benzoin ( styrax benzoin ).

[0103] In some aspects of this invention, the pharmaceutical composition is an emulsion. The emulsion composition of this invention may further include an emulsifier. An emulsifier is a substance added to cosmetic / dermatological products to help prevent the separation of different components (such as oil and water) in the emulsion. There are two types of emulsifiers. Oil-in-water (O / W) emulsifiers encapsulate oil droplets in water, while water-in-oil (W / O) emulsifiers encapsulate water droplets in oil. W / O emulsifiers are used to increase the oiliness (e.g., night creams and sunscreens). O / W emulsifiers are more commonly used in moisturizing products (e.g., body washes, day creams).

[0104] In some embodiments, the compositions of the present invention may further include surfactants. Surfactants are compounds that reduce surface tension or interfacial tension. Reducing surface tension makes liquids more easily diffuse, while reducing the interfacial tension between water and oil / lipids (the interface between two surfaces) allows them to mix. Surfactants can be anionic, amphoteric, nonionic, and / or quaternary ammonium agents. Surfactants are the basis of all personal care products and can also have wetting, conditioning, degreasing, emulsifying, and thickening effects. In some embodiments, the emulsifier, surfactant, and detergent may include, but are not limited to, ammonium lauryl ether sulfate, ammonium lauroyl sulfate, arachidonic acid glucoside, behenic acid, bis-PEG-18 methyl ether dimethylsilane, C20-40 alkanol polyether-40, cocamidopropyl betaine, cocamidopropyl dimethylamine, cocamidopropyl hydroxysulfonate betaine, cocoyl glucoside, coconut oil, decyl glucoside, diceryl phosphate, dihydrocholesterol polyether-30, disodium cocoamphodiacetate, disodium cocoyl glutamate, lauryl amino acid, etc. Sodium propionate, glyceryl behenate, hydrogenated vegetable oil glycerides citrate, isohexadecane, isostearamide DEA, lauroamphocarboxyglycine, lauryl ether-23, lauryl ether-4, lauryl ether-7, lauroyl PEG-9 polydimethylsiloxane, lauroyl alcohol, lauroyl glucoside, magnesium lauryl ether sulfate, magnesium oleyl ether sulfate, myristic acid, nonyl alcohol ether, oleic acid, oleyl ether 10, palmitic acid, palmitic acid, PEG-60 almond glyceride, PEG-75 shea butter glyceride, PEG 90M, PEG-10 dimethylsiloxane, PEG-10 dimethylsiloxane / vinyl dimethylsiloxane crosspolymer, PEG-10 rapeseed sterol, PEG-100 stearate, PEG-12 dimethylsiloxane, 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 sorbitol laurate, PEG / PPG-17 / 6 copolymer (polyethylene glycol) / polypropylene glycol-17 / 6 copolymer), PEG / PPG-18 / 18 dimethylsiloxane, PEG / PPG-20 / 15 dimethylsiloxane, poloxamer 184, poloxamer 407, poloxamer, polyglycerol-3-beeswax, polyglycerol-4 isostearate, polyglycerol-6 isostearate, polysorbate 20, polysorbate 60, polysorbate 80, potassium cetyl phosphate, potassium hydroxide, potassium myristate, PPG-12-butanol polyether-16, PPG-26-butanol polyether-26, sage ( Salvia officinalis soapwort () Saponaria officinalisExtracts, soapwort, sodium C14-16 olefin sulfonate, sodium cetearyl sulfate, sodium cocoamphoacetate, sodium cocoate, sodium cocoyl glutamate, sodium cocoyl hydroxyethyl sulfonate, sodium dilauramide glutamine lysine, sodium hexametaphosphate, sodium hydroxide, sodium lauryl ether sulfate, sodium lauryl ether-13 formate, sodium lauroyl amphotericate, sodium lauroyl lactylate, sodium lauroyl sarcosinate, sodium lauroyl gluconate, sodium lauroyl sulfate, sodium cocoyl methyl taurate, sodium methyl taurate, sodium myristyl ether sulfate, sodium palm kernel oleate, sodium palm oleate, PEG-7 olive oil formate, sodium tridecane ether sulfate, stearyl ether-20, TEA-lauroyl sulfate (triethanolamine lauroyl sulfate) and PEG-20 ester of sanjimoyl ether.

[0105] In some embodiments, the compositions of the present invention may further comprise one or more thickeners. Thickeners are substances added to cosmetic / dermatological products to enhance the consistency, volume, and viscosity of the cosmetic product, thereby providing greater stability and better performance. While some thickeners also have emulsifying or gelling properties, most thickeners have the ability to retain water on the skin and therefore can act as moisturizers. Thickeners can be entirely natural, such as waxes, but can also be synthetic or semi-synthetic. In some embodiments, thickeners may include, but are not limited to, gum arabic, acetylated glycerin castor oil, acetylated hydrogenated cottonseed glyceryl ester, acetylated palm kernel glyceryl ester, acrylate / stearyl alcohol polyether-20 methacrylate copolymer, agar, and *Ipomoea quamoclit* (…). Ahnfeltia concinna Extracts of ) , extracts of ahnfeltia , and winged seaweed ( Alaria esculenta ), algae, algae extracts, alginate, alkylamides, marshmallow ( Althaea rosea ), medicinal marshmallow ( Althea officinalis ), bauxite, aluminum hydroxide, aluminum stearate, ammonium acryloyldimethyl taurate / VP copolymer, and *Synthia spp.* Anacystis nidulans Extracts of arachidic acid, arachidonic acid, arachidonic acid, arachidonic acid, arachidonic acid propionate, arrowroot, Artemia extract, and bladderwort ( Ascophyllum nodosum Ascorbic acid methyl silanol pectinate, Asparagopsis armata extract, beeswax, behenic acid, behenyltrimethylammonium chloride, behenol, bis-diglyceryl polyacryladiate, bismuth oxychloride, benzoic acid C 12-15 Alkyl esters, C 12-18 acid triglycerides, C 13-14 Isoalkanes, C 18-36Triglycerides, Candelilla wax, Caprylic / Capric triglycerides, Carbomer, Carbopol, Carnauba wax, Carrageenan, Pteris vittata extract, Cellulose, Cellulose gum, Cephalosporin, White beeswax, Cephalosporin, Cetearyl alcohol polyether-20, Cetearyl alcohol, Cetearyl ethylhexanoate, Cetearyl glucoside, Caprylic cetearyl ester, Cetyl alcohol, Cetyl dimethylsiloxane copolyol, Cetyl hydroxyethyl cellulose, Cetyl palmitate, Cetyl PEG / PPG-10 / 1-dimethylsiloxane, Chlorella ( chlorella Irish moss ( Chondrus crispus ), cocamide DEA and MEA, cocoyl glycerol, soft-haired pine algae ( Codium tomentosum Extracts, carnauba wax, coral algae ( Corallina officinalis Extracts, Coral Algae ( Corallina DEA oleyl alcohol polyether 10 phosphate, diethanolamine (DEA), di-PPG-3 myristyl ether adipate, dimethylsiloxane crosspolymer, dimethylsiloxane / vinyldimethylsiloxane crosspolymer, polyacrylate crosspolymer, 2-acrylamido-2-methylpropanesulfonate ammonium crosspolymer, sodium polyacryloyl dimethyl taurate, tara gum and / or dioleyl alcohol dioleyl ester.

[0106] In some embodiments, the compositions of the present invention may further comprise one or more chelating agents. A chelating agent is any of a variety of components that bind to metal ions or metal compounds to prevent these metal ions or metal compounds from adhering to surfaces (such as skin, hair, or clothing) or causing contamination (such as in the case of trace iron). In some embodiments, the chelating agent may include, but is not limited to, tetrasodium EDTA, sodium phytate, and / or tetrahydroxypropylethylenediamine.

[0107] In some embodiments, the compositions of the present invention comprise one or more buffers and / or pH adjusters. The buffers and / or pH adjusters (also known as pH controllers) are present in the compositions of the present invention to maintain the pH of the solution within an optimal range. In some embodiments, the one or more buffers and / or pH adjusters are selected from the group consisting of: phosphates / phosphates, citric acid / citrates, tromethamine, histidine, lactic acid, gluconic acid, aspartic acid, glutamic acid, tartaric acid, glutamic acid, succinic acid, malic acid, fumaric acid, and / or α-ketoglutarate.

[0108] In some embodiments, the excipients included in the composition are water, dimethyl isosorbide, glycerol, caprylic / capric triglyceride, propylene glycol, sunflower seed oil, ethoxydiethylene glycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerol / sebaceous acid copolymer, diheptyl succinate, naringenin, lecithin, decanediol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidonic acid, behenol, arachidonic acid glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olive fruit oil, unsaponifiables of olive oil, hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, citric acid, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and / or ethylhexylglycerin.

[0109] Table 3 provides a list of excipients that can be used in exemplary compositions of the present invention and their approximate concentrations.

[0110] Table 3: Exemplary excipients and their concentration ranges:

[0111] succinol, used to treat local symptoms : Advantageously, it has been found that sennaol affects genes and signaling pathways involved in several localized symptoms. In one aspect, the present invention provides methods for treating, protecting, and / or altering (e.g., improving) skin conditions and / or aesthetic appearance using these compositions, including, for example, treating, preventing, improving, reducing, and / or eliminating fine lines and / or wrinkles and / or improving the aesthetic appearance of fine lines and / or wrinkles. In some embodiments, the compositions of the present invention improve skin and / or hair resilience. In some embodiments, the compositions of the present invention improve skin elasticity. In some embodiments, the compositions of the present invention prevent skin damage.

[0112] In one aspect, the present invention includes a composition for topical application comprising an effective amount of sennaol. An effective amount of sennaol is an amount of sennaol that is effective in treating, improving, or otherwise affecting underlying conditions of the skin.

[0113] In certain aspects of the invention, compositions containing senna exhibit antioxidant activity. In some embodiments, the antioxidant activity of senna in the compositions of the invention has been demonstrated at concentrations of about 0.00016% w / w or higher. Advantageously, the antioxidant activity of compositions containing senna has been demonstrated in both aqueous and organic solvent systems. Therefore, the present invention provides compositions that maintain antioxidant activity in both aqueous and organic solvents. Advantageously, compositions of the present invention containing senna exhibit antioxidant activity that can effectively treat and / or prevent oxidative damage. In some embodiments, compositions of the present invention containing senna exhibit antioxidant activity that can effectively treat skin and / or hair damaged by reactive oxygen species and protect it from other environmental aggressors that may damage the subject's skin. In some other embodiments, compositions of the present invention containing senna exhibit antioxidant activity that can effectively prevent damage to skin and / or hair by reactive oxygen species, including damage caused by environmental aggressors.

[0114] As shown in Examples 2 and 3, the compositions containing sennaol effectively exhibit robust antioxidant activity in both aqueous and organic solvent systems. The IC50 of the antioxidant activity calculated in the aqueous solvent system... 50 The value is 0.00062% w / w. The IC50 value for the antioxidant activity calculated in the organic solvent system is... 50 The value was 0.0002% w / w. These results indicate that the compositions containing sennaol have robust antioxidant activity. In some embodiments, the compositions containing sennaol can be used to treat symptoms of the skin caused by oxidation or excessive oxidation in a subject. In some embodiments, the compositions containing sennaol are applied to treat and / or prevent damage to the skin or hair caused by reactive oxygen species and to protect it from environmental aggressors.

[0115] In certain aspects of the invention, compositions containing senna exhibit elastase inhibition. In some embodiments, the elastase-inhibiting activity of the compositions of the invention, senna, has been demonstrated at concentrations of about 0.008% w / w or higher. Data on elastase inhibition for therapeutic purposes of enzyme inhibition are provided in Example 4. IC50 of elastase inhibition of compositions containing senna 50 The value is 0.107% w / w. Advantageously, compositions containing senna exhibit elastase inhibitory activity, effectively promoting skin elasticity. In some embodiments, compositions of the present invention containing senna exhibit elastase inhibition, effectively reducing fine lines and / or wrinkles in the skin. In some embodiments, compositions of the present invention containing senna exhibit elastase inhibitory activity, effectively preventing the formation of fine lines and / or wrinkles in the skin.

[0116] In certain aspects of the invention, compositions containing senna exhibit inhibition of glycation. In some embodiments, the glycation-inhibiting activity of the compositions of the invention, senna, has been demonstrated at concentrations of about 0.002% w / w or higher. Data on elastase inhibition for the treatment of glycation inhibition are provided in Example 5. IC50 of glycation inhibition of compositions containing senna 50 The value is 0.0088% w / w. Advantageously, compositions containing sennaol exhibit glycation-inhibiting activity, effectively supporting and promoting skin and / or hair elasticity.

[0117] Regulation of gene expression and / or activity In some embodiments of the invention, the compositions of the invention (containing senna) regulate the gene expression of one or more genes associated with local symptoms. In some embodiments, application of the composition containing senna alters one or more functions associated with the regulated genes, wherein the one or more functions are selected from the group consisting of: (i) the formation of fine lines or wrinkles on the skin, (ii) inflammation, (iii) skin elasticity, (iv) prevention of scar formation during wound healing, and / or (v) any combination thereof.

[0118] In some embodiments, application of a composition containing senna alters the expression and / or function of one or more genes selected from the group consisting of: MMP10, THBS1, TOP2A, TFPI2, MMP1, FN1, KCTD4, ATP12A, ALDH1A3, MKI67, FST, SLC13A5, IL6, IL23A, TNF, IL24, MMP3, MMP9, and / or PPFIA4. Example 6 (Table 9) provides an overview of gene regulation performed by a composition containing senna.

[0119] In some embodiments, application of a composition containing sennaol results in downregulation of the expression and / or activity of MMP10, THBS1, TOP2A, TFPI2, MMP1, FN1, KCTD4, ATP12A, ALDH1A3, MKI67, FST, SLC13A5, IL6, IL23A, TNF, IL24, MMP3, and / or MMP9.

[0120] In some embodiments, the application of the composition upregulates the expression and / or activity of PPFIA4.

[0121] In some embodiments, the application of the composition enhances its anti-inflammatory activity. In some embodiments, the anti-inflammatory activity of the composition is modulated by downregulating the expression and / or activity of IL6, IL23a, TNF, and / or IL24.

[0122] In some embodiments, the application of the composition produces anti-aging activity. In some embodiments, the anti-aging activity of the composition containing sennaol is modulated by downregulating the expression and / or activity of MMP10, MMP9, MMP3 and MMP1.

[0123] In some embodiments, application of a composition containing senna enhances the maintenance of skin barrier lipids. In some embodiments, the maintenance of skin barrier lipids is modulated by upregulating the expression and / or activity of PPFIA4.

[0124] In some embodiments, application of a composition containing sennaol induces prevention of scar tissue formation after wound healing. In some embodiments, prevention of scar tissue formation after wound healing is modulated by downregulating the expression and / or activity of THBS1.

[0125] In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 10 (MMP10) activity and / or expression by at least about ten (10) times. In some embodiments, application of the composition containing sennaol resulted in a downregulation of matrix metallopeptidase 10 (MMP10) activity and / or expression by about twenty-five (25) times.

[0126] Platelet-reactive protein 1 (THBS1) plays a role in the proliferation of overgrown scar cells. In some embodiments, overgrown scar cells play a role in scar formation during wound healing. Therefore, downregulation of THBS1 prevents scar formation during wound healing. In some embodiments, administration of a composition containing sennaol results in a downregulation of THBS1 activity and / or expression by at least about ten (10)-fold. In some embodiments, administration of a composition containing sennaol results in a downregulation of THBS1 activity and / or expression by about fifteen (15)-fold.

[0127] DNA topoisomerase II-α (TOP2A) is an enzyme whose expression is elevated in tumors. It is an enzyme that controls and alters the topological state of DNA during transcription. In some embodiments, application of a composition containing sennaol results in a downregulation of DNA topoisomerase II-α (TOP2A) activity and / or expression by at least about ten (10)-fold. In some embodiments, application of a composition containing sennaol results in a downregulation of DNA topoisomerase II-α (TOP2A) activity and / or expression by about fifteen (15)-fold. In some embodiments, application of a composition containing sennaol results in a downregulation of DNA topoisomerase II-α (TOP2A) activity and / or expression by about twenty (20)-fold.

[0128] Tissue factor pathway inhibitor 2 (TFPI2) expresses an antimicrobial protein during wound healing. In some embodiments, downregulation of TFPI2 activity and / or expression may contribute to wound healing and / or prevent scar formation during wound healing. In some embodiments, administration of a composition comprising sennaol results in a downregulation of TFPI2 activity and / or expression by at least about ten (10)-fold. In some embodiments, administration of a composition comprising sennaol results in a downregulation of TFPI2 activity and / or expression by about fifteen (15)-fold. In some embodiments, administration of a composition comprising sennaol results in a downregulation of TFPI2 activity and / or expression by about twenty (20)-fold.

[0129] Matrix metallopeptidase 1 (MMP1) expression is an enzyme that may contribute to the aged appearance of the skin. UV irradiation induces increased synthesis and expression of MMP-1 in skin fibroblasts, stimulated by the production of excess reactive oxygen species (ROS), which play a key role in photoaging. Therefore, downregulation of MMP-1 expression and / or activity may result in anti-aging effects on the skin. In some embodiments, application of a composition containing sennaol resulted in a downregulation of MMP1 activity and / or expression by at least about two (2)-fold. In some embodiments, application of a composition containing sennaol resulted in a downregulation of MMP1 activity and / or expression by about ten (10)-fold.

[0130] Fibronectin 1 (FN1) is a protein associated with wound healing. Increased FN1 expression is associated with wound healing. In some embodiments, downregulation of FN1 expression and / or activity may be associated with reduced scar formation during the wound healing process. In some embodiments, application of the composition results in a downregulation of fibronectin 1 (FN1) activity and / or expression by at least about two (2)-fold. In some embodiments, application of the composition results in a downregulation of fibronectin 1 (FN1) activity and / or expression by about ten (10)-fold.

[0131] Potassium-containing channel tetramerizing domain 4 (KCTD4) expression may be involved in protein homologous oligomerization. In some embodiments, application of the composition resulted in a downregulation of the activity and / or expression of potassium-containing channel tetramerizing domain 4 (KCTD4) by at least about five (5) times. In some embodiments, application of the composition resulted in a downregulation of the activity and / or expression of potassium-containing channel tetramerizing domain 4 (KCTD4) by about fifteen (15) times.

[0132] The non-gastric α2 subunit of the ATPase H+ / K+ transporter (ATP12A) encodes the catalytic subunit of an ouabain-sensitive H+ / K+-ATPase that catalyzes the hydrolysis of ATP and the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for potassium uptake in various tissues. In some embodiments, administration of a composition containing sennaol results in a downregulation of the activity and / or expression of the non-gastric α2 subunit of the ATPase H+ / K+ transporter (ATP12A) by at least about two (2)-fold. In some embodiments, administration of a composition containing sennaol results in a downregulation of the activity and / or expression of the non-gastric α2 subunit of the ATPase H+ / K+ transporter (ATP12A) by about ten (10)-fold.

[0133] Aldehyde dehydrogenase 1 family member A3 (ALDH1A3) expresses an enzyme that converts retinaldehyde to retinoic acid. Upregulation of ALDH1A3 is associated with tumorigenesis, and downregulation indicates reduced cell proliferation. In some embodiments, administration of a composition containing sennaol resulted in at least about two (2)-fold downregulation of the activity and / or expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3). In some embodiments, administration of a composition containing sennaol resulted in about ten (10)-fold downregulation of the activity and / or expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3).

[0134] The proliferation marker Ki-67 (MKI67) expresses proteins involved in cell proliferation. Downregulation of MKI67 expression and / or activity is associated with reduced cell proliferation. In some embodiments, administration of a composition containing sennaol resulted in a downregulation of the activity and / or expression of the proliferation marker Ki-67 (MKI67) by at least about two (2)-fold. In some embodiments, administration of a composition containing sennaol resulted in a downregulation of the activity and / or expression of the proliferation marker Ki-67 (MKI67) by about ten (10)-fold.

[0135] Follicle-stabilizing hormone (FST) is a structurally independent single-chain glycoprotein unrelated to inhibin and activin. FST binds to activin with high affinity and antagonizes activin's effects by blocking the binding of activin to its receptor. Downregulation of FST activity and / or expression leads to enhanced keratinocyte proliferation. In some embodiments, administration of a composition containing sennaol results in a downregulation of FST activity and / or expression by at least about two (2)-fold. In some embodiments, administration of a composition containing sennaol results in a downregulation of FST activity and / or expression by about ten (10)-fold.

[0136] Solute carrier family 13 member 5 (SLC13A5) expresses a sodium-dependent citrate cotransporter that can regulate metabolic processes. Downregulation of SLC13A5 activity and / or expression is associated with reduced risk of diabetes and increased lifespan. In some embodiments, the activity of proteins expressed by SLC13A5 may be affected by the activity of interleukin-6. In some embodiments, administration of a composition containing sennaol results in a downregulation of the activity and / or expression of solute carrier family 13 member 5 (SLC13A5) by at least about five (5) times. In some embodiments, administration of a composition containing sennaol results in a downregulation of the activity and / or expression of solute carrier family 13 member 5 (SLC13A5) by about fifteen (15) times.

[0137] Interleukin-6 (IL6) expression is a protein involved in the inflammatory response in vivo. Therefore, downregulation of IL6 activity and / or expression leads to a reduction in the inflammatory response in the skin. In some embodiments, application of a composition containing sennaol results in a downregulation of interleukin-6 (IL6) activity and / or expression by at least about five (5)-fold. In some embodiments, application of a composition containing sennaol results in a downregulation of interleukin-6 (IL6) activity and / or expression by about twenty (20)-fold.

[0138] Interleukin-23 (IL23) expression is a protein involved in the inflammatory response in vivo. Therefore, downregulation of IL23 activity and / or expression leads to a reduction in the inflammatory response in the skin. In some embodiments, application of a composition containing sennaol results in a downregulation of interleukin-23 (IL23) activity and / or expression by at least about two (2) times. In some embodiments, application of a composition containing sennaol results in a downregulation of interleukin-23 (IL23) activity and / or expression by about five (5) times.

[0139] Tumor necrosis factor (TNF) expression is a protein involved in the inflammatory response in vivo. Therefore, downregulation of TNF activity and / or expression leads to a reduction in the inflammatory response in the skin. In some embodiments, application of a composition containing sennaol results in a downregulation of tumor necrosis factor (TNF) activity and / or expression by at least about ten (10)-fold. In some embodiments, application of a composition containing sennaol results in a downregulation of tumor necrosis factor (TNF) activity and / or expression by about two hundred and fifty (250)-fold.

[0140] Interleukin-24 (IL24) expression is a protein involved in the inflammatory response in vivo. Therefore, downregulation of IL24 activity and / or expression leads to a reduction in the inflammatory response of the skin. In some embodiments, application of a composition containing sennaol results in a downregulation of interleukin-24 (IL24) activity and / or expression by at least about ten (10) times. In some embodiments, application of a composition containing sennaol results in a downregulation of interleukin-24 (IL24) activity and / or expression by about seventy (70) times.

[0141] Matrix metallopeptidase 3 (MMP3) expression is involved in several signaling pathways, including collagen degradation and inflammation. Therefore, downregulation of MMP3 activity and / or expression induces anti-aging effects and / or anti-inflammatory responses in the skin. In some embodiments, application of a composition containing sennaol results in a downregulation of MMP3 activity and / or expression by at least about ten (10)-fold. In some embodiments, application of a composition containing sennaol results in a downregulation of MMP3 activity and / or expression by about fifty (50)-fold.

[0142] Matrix metallopeptidase 9 (MMP9) expression is a protein involved in several signaling pathways, including collagen degradation and inflammation. Therefore, downregulation of MMP9 activity and / or expression induces anti-aging effects and / or anti-inflammatory responses in the skin. In some embodiments, application of a composition containing sennaol results in a downregulation of MMP9 activity and / or expression by at least about two (2)-fold. In some embodiments, application of a composition containing sennaol results in a downregulation of MMP9 activity and / or expression by about eight (8)-fold.

[0143] PTPRF interacting protein α4 (PPFIA4) expression is a protein that plays a role in cell adhesion. Therefore, increased PPFIA4 expression leads to enhanced barrier function. In some embodiments, administration of a composition containing sennaol upregulated the activity and / or expression of PTPRF interacting protein α4 (PPFIA4) by at least about five (5)-fold. In some embodiments, administration of a composition containing sennaol upregulated the activity and / or expression of PTPRF interacting protein α4 (PPFIA4) by about thirty (30)-fold.

[0144] Treatment of local symptoms In some aspects, the present invention provides a method for treating localized symptoms by applying a topical composition comprising an effective amount of senna. In some embodiments, the present invention provides a method for preventing fine lines or wrinkles on the skin of a subject by applying the compositions provided herein. In some embodiments, the present invention provides a method for supporting skin firmness and improving / maintaining skin elasticity by applying the compositions provided herein. In some embodiments, the present invention provides a method for preventing skin and hair damage from reactive oxidants by applying the compositions provided herein. In some embodiments, the present invention provides a method for protecting skin from environmental aggressors by applying the compositions provided herein. In some embodiments, the present invention provides a method for improving skin and / or hair resilience by applying the compositions provided herein. In some embodiments, the present invention provides a method for preventing glycation by applying the compositions provided herein. Glycation is known to be associated with wrinkling, loss of elasticity, and aging of the skin. In some embodiments, the present invention provides a method for reducing skin damage by applying the compositions provided herein. In some embodiments, the compositions of the present invention provide a method for preventing scar formation during the wound healing process by applying the compositions provided herein.

[0145] The present invention recognizes that compositions containing senna are beneficial for treating, protecting, and / or improving the condition and / or aesthetic appearance of the skin. For example, the compositions of the present invention can effectively alter the aesthetic appearance of skin associated with or affected by, for example, cellular aging, environmental damage, or photoaging, or treat or prevent fine lines and / or wrinkles caused by, for example, cellular aging, environmental damage, or photoaging. The present invention also provides methods for stimulating skin cell renewal, increasing cell or tissue regeneration, promoting fibroblast proliferation and synthesis of elastin, collagen, proteoglycans, and / or new connective tissue, thereby reducing or improving the appearance of wrinkles and restoring the skin's elasticity, resilience, and / or softness.

[0146] The compositions of the present invention provided herein can be used to improve the aesthetic appearance of the skin. Such improvements may include, but are not limited to, all externally visible and tactilely perceptible manifestations, as well as any other macroscopic or microscopic effects due to skin aging and damage. Such manifestations and effects may be caused by intrinsic and / or extrinsic factors such as: aging, environmental damage, climate, sun (UV) exposure, smoking, drugs, alcohol consumption, jet lag, night work, changes in circadian rhythms, pregnancy, menopause, genetic factors, nutritional factors and / or deficiencies, dehydration, stress, allergies (e.g., allergies to plants, animals, drugs, and other substances), exposure to industrial and / or household chemicals, indoor heating and cooling, various conditions and diseases (such as arteriosclerosis, diabetes, heart disease, liver disease, and obesity), thinning of the outer layer of skin, reduction in the number of pigmented cells, increase in the size of pigmented cells, changes in connective tissue, and decreased skin strength and elasticity.

[0147] For example, the aesthetic appearance of skin can be improved by improving the appearance of skin that is associated with or affected by one or more of the following: wrinkles, dry skin, sensitive skin; wrinkles and sagging; acne; vitiligo (a skin condition in which areas of the skin lose brown (pigment)); fine lines, dry skin, thinning of the dermis, degradation of collagen fibers, loose skin, thinning of the skin, and skin exposed to ultraviolet radiation. In some embodiments, the compositions of the present invention can improve the aesthetic appearance of skin by: reducing the appearance of fine lines in the skin; producing a more youthful appearance; reducing eye bags and / or dark circles around the eyes; improving or restoring the elasticity, resilience, and / or softness of the skin; increasing the apparent thickness, elasticity, suppleness, radiance, luster, and plumpness of the skin; improving the fineness of skin texture; improving the appearance of wrinkled, folded, dry, flaky, aging, and / or photodamaged skin; treating or preventing photodamaged skin; reducing signs of skin aging; reducing the appearance of hyperpigmentation; treating or preventing hyperpigmentation; treating or preventing pigmentation deposits in the skin (e.g., caused by UV exposure); reducing the appearance of skin discoloration; and whitening, brightening, and / or bleaching the skin.

[0148] In some embodiments, these compositions may be used as care, treatment, cleansing and / or protective products for facial or body skin; anti-wrinkle or anti-aging compositions; skin firming compositions; skin brightening compositions; compositions for irritated skin; sun protection compositions, tanning (self-tanning) compositions or after-sun care compositions; scalp care compositions; shaving formulation compositions; hair removal compositions; or cosmetic products for facial or body skin.

[0149] In some embodiments, a composition containing sennaol is applied to alter the aesthetic appearance of skin associated with or affected by a skin condition (e.g., a skin condition / disease with loss of skin elasticity), or to treat or prevent such skin condition / disease.

[0150] In some embodiments, a composition containing senna is applied to improve the skin's barrier function and vitality.

[0151] In some embodiments, compositions comprising senna are applied to alter the aesthetic appearance of skin associated with or affected by wrinkles, sagging, and / or loss of skin elasticity.

[0152] In some embodiments, a composition containing senna is applied to alter the aesthetic appearance of skin that is associated with or affected by deterioration of skin viscoelasticity.

[0153] In some embodiments, a composition comprising senna is applied to alter the aesthetic appearance of skin associated with or affected by one or more of the following: wrinkles and / or fine lines, dry skin, lack of skin elasticity and / or tension, thinning of the dermis, degradation of collagen fibers, skin laxity, thinning of the skin, and internal degradation of the skin after exposure to ultraviolet radiation.

[0154] In some embodiments, a composition containing senna is applied to reduce the appearance of fine lines and / or wrinkles in the skin.

[0155] In some embodiments, a composition containing senna is applied to reduce the appearance of eye bags and / or dark circles around the eyes.

[0156] In some embodiments, a composition containing senna is applied to reduce the occurrence of hyperpigmentation.

[0157] In some embodiments, a composition containing senna is applied to improve or increase one or more of the following: skin thickness, elasticity, suppleness, radiance, shine, and plumpness.

[0158] In some embodiments, a composition containing senna is applied to improve the smoothness of skin texture.

[0159] In some embodiments, a composition containing senna is applied to improve the appearance of wrinkled, creased, dry, flaky, aged, and / or photodamaged skin.

[0160] In some embodiments, a composition containing sennaol is applied to alter the aesthetic appearance of skin that is associated with or affected by skin discoloration.

[0161] Application method: On one hand, the present invention provides a method for applying a composition comprising senna. In some embodiments, the compositions of the present invention are designed for topical application.

[0162] In some embodiments, the compositions of the present invention may be applied as a topical composition to the skin of a subject. The compositions of the present invention may be included in any formulation suitable for topical application. In some embodiments, the compositions of the present invention are fluids, emulsions, encapsulations, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, cosmetics, and / or hair care products.

[0163] In some other embodiments, compositions containing sennaol can be prepared and used in the following forms: aerosol spray, cream, emulsion, solid, liquid, dispersant, foam, oil, gel, lotion, mousse, ointment, powder, patch, conditioner, solution, pump spray, stick, towel, soap, or other forms commonly used in the fields of cosmetics and skin care formulations. The composition may be in emulsion form. Additionally, the compounds provided herein for use in the compositions provided herein can be used in color cosmetic compositions such as foundation, blush, eyeshadow, mascara, concealer, eyeliner, lip color, nail polish, etc. Other cosmetic compositions may include perfumes, lipsticks, nail polish and toenail polish, eye and face cosmetics, towels, deodorants, hand sanitizers, baby products, bath oils, bubble baths, and butters.

[0164] In some embodiments, at approximately 100 μg / cm 2 Approximately 5 mg / cm 2 The composition containing senna is applied to the skin at a concentration of approximately 200 μg / cm³. In some embodiments, the concentration is approximately 200 μg / cm³. 2 Approximately 4 mg / cm 2 The composition containing senna is applied to the skin at a concentration of approximately 400 μg / cm³. In some embodiments, this is done at a concentration of approximately 400 μg / cm³. 2 Approximately 3 mg / cm 2 The composition containing senna is applied to the skin at a concentration of approximately 1 mg / μg. In some embodiments, the concentration is approximately 1 mg / μg. 2 Approximately 2 mg / cm 2 The composition containing senna is applied to the skin at a concentration of approximately 2 mg / μg. In some embodiments, the concentration is approximately 2 mg / μg. 2 The concentration of the composition containing senna is applied to the skin.

[0165] In some embodiments, the composition comprising senna is applied to the affected area of ​​the skin. The affected area of ​​the skin is an area of ​​skin that needs improvement or suffers from localized symptoms. In some embodiments, at a depth of about 0.5 cm... 2 Approximately 100cm 2 The composition containing sennaol is applied over an area of ​​approximately 1 cm. In some embodiments, it is applied over an area of ​​approximately 1 cm. 2 Approximately 75 cm 2 The composition containing sennaol is applied over an area of ​​approximately 10 cm. In some embodiments, it is applied over an area of ​​approximately 10 cm. 2 Approximately 75 cm 2 The composition containing sennaol is applied over an area of ​​approximately 50 cm². In some embodiments, the composition is applied over an area of ​​approximately 50 cm². 2 The composition containing sennaol is applied to the area.

[0166] In some embodiments, the composition containing senna is applied for a certain duration until the desired effect of improving or preventing local symptoms is achieved. In some embodiments, the composition containing senna contains an effective amount of senna. An effective amount of senna is the amount of senna that produces the desired result in the condition of the skin lesion. In some embodiments, the composition containing senna is applied once daily. In some embodiments, the composition containing senna is applied twice daily. In some embodiments, the composition containing senna is applied three times daily. In some embodiments, the composition containing senna is applied every two days. In some embodiments, the composition containing senna is applied every three days.

[0167] Example Example 1: An exemplary composition containing sennaol: Table 4 provides exemplary compositions containing sennaol.

[0168] Table 4: Exemplary compositions containing sennaol

[0169] Example 2: ABTS Antioxidant Determination: The 2,2'-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) antioxidant assay was designed to evaluate the antioxidant activity of compositions containing sennaol in aqueous media.

[0170] ABTS+ solutions are generated as free radicals and used to measure the relative ability of compounds to scavenge free radicals. The decrease in absorbance at 734 nm was normalized relative to a solvent control as an indicator of ABTS+ scavenging.

[0171] Table 5 below presents the results from these experiments: Table 5: Free radical inhibition by ABTS (aqueous antioxidant assay)

[0172] The results presented in Table 5 above clearly show that, in aqueous systems, compositions containing senna exhibit antioxidant activity at concentrations as low as 0.00016% w / w. The calculated IC50 values... 50 The value is 0.00062% w / w.

[0173] Example 3: Determination of DPPH antioxidant activity The 2,2-diphenyl-1-picrylhydrazine (DPPH) antioxidant assay was designed to evaluate the antioxidant activity of compositions containing sennaol in organic media.

[0174] 2,2-Diphenyl-1-picrylhydrazyl (DPPH) is a stable free radical used to evaluate the free radical scavenging ability of materials. In the presence of an antioxidant, DPPH is reduced, resulting in the formation of a colorless solution. The decrease in absorbance at 517 nm relative to a solvent control is normalized as an indicator of DPPH scavenging.

[0175] Table 6 below provides data on antioxidant activity.

[0176] Table 6: DPPH free radical inhibition

[0177] The results presented in Table 6 above clearly show that, in organic solvent systems, compositions containing senna exhibit antioxidant activity at concentrations as low as 0.00007% w / w. The calculated IC50 values... 50 The value is 0.0002% w / w.

[0178] Example 4: Elastase inhibition: This assay was performed to evaluate the elastase inhibitory activity of the composition containing sennaol.

[0179] In response to UV stress, both neutrophil infiltration and neutrophil elastase in the skin increase. Neutrophil elastase has been shown to activate MMP-1 and MMP-2 collagenases in response to low-dose UV exposure, thereby damaging the extracellular matrix and leading to photoaging and wrinkle formation. Elastase activity can be further upregulated in the presence of reactive oxygen species. Therefore, inhibiting this enzyme, particularly in combination with antioxidant activity, can effectively delay wrinkle development and help maintain skin integrity. This assay measures the release of 4-nitroaniline from human neutrophil elastase in Me-Suc-Ala-Ala-Pro-Val-pNA and can be quantified at 405 nm by comparison with a solvent control.

[0180] Table 7 provides the elastase inhibitory activity of compositions containing senna: Table 7: Elastase Inhibition

[0181] The data provided in Table 7 clearly show that the composition containing sennaol inhibits elastase activity at levels as low as 0.008% w / w. The calculated IC50 values... 50 The value is 0.107% w / w.

[0182] Example 5: Glycation Inhibition Assay: This assay was performed to evaluate the glycation inhibition activity of the composition containing sennaol.

[0183] When glucose reacts with proteins, non-enzymatic glycation may occur, forming Schiff base intermediates. These Schiff base intermediates then react with skin proteins to form advanced glycation end products (AGEs), undergoing Amadori rearrangement to form glycosylated proteins. AGE formation can lead to loss of skin elasticity and impaired cellular function. The glycation inhibitory capacity of the compounds was measured by changes in fluorescence relative to a solvent control at excitation / emission at 360 nm / 420 nm.

[0184] Table 8 provides data on glycation inhibition.

[0185] Table 8: Glycation Inhibition

[0186] The data provided in Table 7 clearly show that the composition containing sennaol inhibits glycation at levels as low as 0.002% w / w. The calculated IC50 values ​​for glycation inhibition are... 50 The value is 0.0088% w / w.

[0187] Example 6: Gene Regulation Table 9 below includes gene regulation data for formulations containing sennaol.

[0188]

[0189] By incorporating references Throughout this disclosure, references and citations have been made to other documents, such as patents, patent applications, patent publications, magazines, books, papers, web content, and publicly available databases. All such documents are hereby incorporated herein by reference in their entirety for all purposes.

[0190] equivalent Based on the entire contents of this document, including references to scientific and patent literature cited herein, various modifications to the invention and many other embodiments thereof will become apparent to those skilled in the art, in addition to those shown and described herein. The subject matter of this document contains important information, illustrations, and guidance that can be adapted to practice the invention in its various embodiments and equivalents.

Claims

1. A composition for topical application comprising an effective amount of sennaol.

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

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

4. The composition according to claim 1, wherein the composition further comprises a solvent.

5. The composition according to claim 4, wherein the solvent is a cosmetic solvent.

6. The composition according to claim 5, wherein the solvent is selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, lauroyl sarcosine isopropyl ester, and any combination thereof.

7. The composition according to claim 6, wherein the solvent is dimethylisosorbitol.

8. The composition according to claim 6, wherein the solvent is ethoxydiethylene glycol.

9. The composition according to claim 6, wherein the solvent is lauroyl sarcosine isopropyl ester.

10. The composition according to claim 1, wherein the composition is stable under ambient conditions and stored for at least two (2) years.

11. The composition according to claim 1, wherein the composition is stable under environmental conditions and under storage for at least one (1) year.

12. The composition according to claim 1, wherein the composition is stable under ambient conditions and stored for at least six (6) months.

13. The composition according to claim 1, wherein the composition is stable under ambient conditions and stored for at least three (3) months.

14. The composition according to claim 1, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 5% degradation.

15. The composition according to claim 1, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

16. The composition according to claim 1, wherein when stored at 40°C for one (1) month, the composition exhibits less than about 10% degradation.

17. The composition according to claim 1, wherein when stored at 25°C and / or 4°C for one (1) month, the composition exhibits less than about 1% degradation.

18. The composition according to claim 1, wherein when stored at 40°C for three (3) months, the composition exhibits less than about 10% degradation.

19. The composition according to claim 1, wherein when stored at 25°C for three (3) months, the composition exhibits less than about 10% degradation.

20. The composition according to claim 1, wherein when stored at 25°C for six (6) months, the composition exhibits less than about 10% degradation.

21. The composition according to claim 1, wherein when stored at 4°C for three (3) months, the composition exhibits less than about 5% degradation.

22. The composition of claim 1, wherein the pH of the composition is from about 4 to about 8.

23. The composition according to claim 1, wherein the pH of the composition is from about 4 to about 7.

24. The composition according to claim 1, wherein the pH of the composition is from about 4 to about 6.

25. The composition according to claim 1, wherein the pH of the composition is about 4 to about 5.

26. The composition according to claim 1, wherein the pH of the composition is about 4.

27. The composition of claim 26, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

28. The composition according to claim 1, wherein the pH of the composition is about 5.

29. The composition according to claim 28, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

30. The composition according to claim 1, wherein the pH of the composition is about 6.

31. The composition of claim 30, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

32. The composition according to claim 1, wherein the pH of the composition is about 7.

33. The composition according to claim 32, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

34. The composition according to claim 1, wherein sennaol is present at a concentration of about 0.0001% w / w to about 5.0% w / w.

35. The composition according to claim 1, wherein sennaol is present at a concentration of about 0.0001% w / w to about 1.0% w / w.

36. The composition according to claim 1, wherein sennaol is present at a concentration of about 0.001% w / w to about 0.5% w / w.

37. The composition according to claim 1, wherein sennaol is present at a concentration of about 0.01% w / w to about 0.5% w / w.

38. The composition according to claim 1, wherein sennaol is present at a concentration of about 0.1% w / w to about 0.5% w / w.

39. The composition according to claim 1, wherein sennaol is present at a concentration of about 0.5% w / w.

40. The composition of claim 1, wherein the composition is selected from the group consisting of: fluids, emulsions, encapsulations, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, cosmetics, hair care products, and any combination thereof.

41. The composition of claim 1, wherein the composition further comprises one or more excipients selected from the group consisting of: solvents, emulsifiers, preservatives, antioxidants, emollients, thickeners, penetration enhancers, surfactants, diluents, fillers, carriers and / or pH control agents.

42. The composition according to claim 41, wherein the preservative is an antimicrobial preservative or a chelating agent.

43. The composition according to claim 1, wherein sennaol is encapsulated.

44. The composition of claim 1, wherein the composition further comprises one or more excipients selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, water, glycerol, propylene glycol, ethylhexyl hydrogenated olive oil, hydrogenated olive oil unsaponifiables, polyglycerol-6-distearate, jojoba ester, polyglycerol-3-beeswax, cetyl alcohol, cetearyl oleate, sorbitan oleate, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, sunflower seed oil, caprylic / capric triglyceride, phenoxyethanol, decanediol, and 1,2-hexanediol.

45. The composition according to claim 1, wherein the composition is: 。 46. ​​The composition according to claim 1, wherein the composition is: 。 47. A method for treating or preventing local symptoms in a subject by applying a composition comprising an effective amount of sennaol.

48. The method of claim 47, wherein the application of the composition prevents fine lines or wrinkles on the skin of the subject.

49. The method of claim 47, wherein the application of the composition results in support of the firmness and elasticity of the subject's skin.

50. The method of claim 47, wherein the application of the composition prevents reactive oxygen species from damaging the skin and hair.

51. The method of claim 47, wherein the application of the composition protects the skin from environmental aggressors.

52. The method of claim 47, wherein the application of the composition enables support of skin elasticity.

53. The method of claim 47, wherein the local symptom is glycation.

54. The method of claim 47, wherein the application of the composition results in improved skin and / or hair elasticity.

55. The method of claim 47, wherein the application of the composition results in increased skin elasticity.

56. The method of claim 47, wherein the application of the composition prevents skin damage.

57. The method of claim 47, wherein the composition is applied topically.

58. The method of claim 47, wherein the composition comprises an emulsion.

59. The method of claim 58, wherein the emulsion is an oil / water emulsion.

60. The method of claim 47, wherein the composition further comprises a solvent.

61. The method of claim 60, wherein the solvent is selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, lauroyl sarcosine isopropyl ester, and any combination thereof.

62. The method of claim 58, wherein the solvent is dimethyl isosorbide.

63. The method of claim 58, wherein the solvent is ethoxydiethylene glycol.

64. The method of claim 58, wherein the solvent is lauroyl sarcosine isopropyl ester.

65. The method of claim 47, wherein the composition is stable under ambient conditions and stored for at least two (2) years.

66. The method of claim 47, wherein the composition is stable under ambient conditions and stored for at least one (1) year.

67. The method of claim 47, wherein the composition is stable under ambient conditions for at least six (6) months under storage.

68. The method of claim 47, wherein the composition is stable under ambient conditions for at least three (3) months under storage.

69. The method of claim 47, wherein the composition exhibits less than about 5% degradation when stored at 50°C for one (1) month.

70. The method of claim 47, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

71. The method of claim 47, wherein when stored at 40°C for one (1) month, the composition exhibits less than about 10% degradation.

72. The method of claim 47, wherein the composition exhibits less than about 1% degradation when stored at 25°C and / or 4°C for one (1) month.

73. The method of claim 47, wherein the composition exhibits less than about 10% degradation when stored at 40°C for three (3) months.

74. The method of claim 47, wherein the composition exhibits less than about 10% degradation when stored at 25°C for three (3) months.

75. The method of claim 47, wherein the composition exhibits less than about 10% degradation when stored at 25°C for six (6) months.

76. The method of claim 47, wherein the composition exhibits less than about 5% degradation when stored at 4°C for three (3) months.

77. The method of claim 47, wherein the pH of the composition is from about 4 to about 8.

78. The method of claim 47, wherein the pH of the composition is from about 4 to about 7.

79. The method of claim 47, wherein the pH of the composition is from about 4 to about 6.

80. The method of claim 47, wherein the pH of the composition is about 4 to about 5.

81. The method of claim 47, wherein the pH of the composition is about 4.

82. The method of claim 81, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

83. The method of claim 47, wherein the pH of the composition is about 5.

84. The method of claim 83, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

85. The method of claim 47, wherein the pH of the composition is about 6.

86. The method of claim 85, wherein the composition exhibits less than about 10% degradation when stored at 50°C for one (1) month.

87. The method of claim 47, wherein the pH of the composition is about 7.

88. The method of claim 87, wherein when stored at 50°C for one (1) month, the composition exhibits less than about 10% degradation.

89. The method of claim 47, wherein senna is present at a concentration of about 0.0001% w / w to about 5.0% w / w.

90. The method of claim 47, wherein senna is present at a concentration of about 0.0001% w / w to about 1.0% w / w.

91. The method of claim 47, wherein senna is present at a concentration of about 0.001% w / w to about 0.5% w / w.

92. The method of claim 47, wherein senna is present at a concentration of about 0.01% w / w to about 0.5% w / w.

93. The method of claim 47, wherein senna is present at a concentration of about 0.1% w / w to about 0.5% w / w.

94. The method of claim 47, wherein senna is present at a concentration of about 0.5% w / w.

95. The method of claim 47, wherein the composition is selected from the group consisting of: fluids, emulsions, encapsulations, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, cosmetics, hair care products, and any combination thereof.

96. The method of claim 47, wherein the composition further comprises one or more excipients selected from the group consisting of solvents, emulsifiers, preservatives, antioxidants, emollients, thickeners, penetration enhancers, surfactants, diluents, fillers, carriers and / or pH control agents.

97. The method of claim 96, wherein the preservative is an antimicrobial preservative or a chelating agent.

98. The method of claim 47, wherein the sageol is encapsulated in the composition.

99. The method of claim 47, wherein the composition further comprises one or more excipients selected from the group consisting of: dimethyl isosorbide, ethoxydiethylene glycol, water, glycerin, propylene glycol, ethylhexyl hydrogenated olive oil, hydrogenated olive oil unsaponifiables, polyglycerol-6-distearate, jojoba ester, polyglycerol-3-beeswax, cetyl alcohol, cetearyl oleate, sorbitan oleate, hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, sunflower seed oil, caprylic / capric triglyceride, phenoxyethanol, decanediol, and 1,2-hexanediol.

100. The method of claim 47, wherein the composition is: 。 101. The method of claim 47, wherein the composition is: 。 102. A method for regulating the expression of one or more genes by applying a composition comprising sennaol, wherein at least one of the genes is associated with a local symptom.

103. The method of claim 102, wherein the one or more genes are selected from the group consisting of: MMP10, THBS1, TOP2A, TFPI2, MMP1, FN1, KCTD4, ATP12A, ALDH1A3, MKI67, FST, SLC13A5, IL6, IL23A, TNF, IL24, MMP3, MMP9 and / or PPFIA4.

104. The method of claim 102, wherein the administration of the composition results in downregulation of the expression and / or activity of MMP10, THBS1, TOP2A, TFPI2, MMP1, FN1, KCTD4, ATP12A, ALDH1A3, MKI67, FST, SLC13A5, IL6, IL23A, TNF, IL24, MMP3 and / or MMP9.

105. The method of claim 102, wherein the application of the composition upregulates the expression and / or activity of PPFIA4.

106. The method of claim 102, wherein the application of the composition enhances the anti-inflammatory activity.

107. The method of claim 106, wherein the administration of the composition causes downregulation of the expression and / or activity of IL6, IL23a, TNF and / or IL24.

108. The method of claim 102, wherein the application of the composition produces anti-aging activity.

109. The method of claim 108, wherein the administration of the composition causes downregulation of the expression and / or activity of MMP10, MMP9, MMP3 and MMP1.

110. The method of claim 102, wherein the application of the composition enhances the maintenance of skin barrier lipids.

111. The method of claim 110, wherein the administration of the composition causes an upregulation of PPFIA4 expression and / or activity.

112. The method of claim 102, wherein the application of the composition causes prevention of scar tissue formation after wound healing.

113. The method of claim 112, wherein the application of the composition results in a downregulation of THBS1 expression and / or activity.

114. The method of claim 102, wherein the composition is applied topically.

115. The method of claim 114, wherein the local application is performed on the skin of the patient.

116. The method of claim 102, wherein the administration of the composition results in a downregulation of matrix metallopeptidase 10 (MMP10) activity and / or expression by at least about ten (10) times.

117. The method of claim 102, wherein the administration of the composition results in a downregulation of matrix metallopeptidase 10 (MMP10) activity and / or expression by about twenty-five (25) times.

118. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of platelet-reactive protein 1 (THBS1) by at least about ten (10) times.

119. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of platelet-reactive protein 1 (THBS1) by about fifteen (15) times.

120. The method of claim 102, wherein the application of the composition results in a downregulation of the activity and / or expression of DNA topoisomerase II-α (TOP2A) by at least about ten (10) times.

121. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of DNA topoisomerase II-α (TOP2A) by about fifteen (15) times.

122. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of tissue factor pathway inhibitor 2 (TFPI2) by at least about ten (10) times.

123. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of tissue factor pathway inhibitor 2 (TFPI2) by about fifteen (15) times.

124. The method of claim 102, wherein the administration of the composition causes a downregulation of matrix metallopeptidase 1 (MMP1) activity and / or expression by at least two (2) times.

125. The method of claim 102, wherein the administration of the composition causes a downregulation of matrix metallopeptidase 1 (MMP1) activity and / or expression by about ten (10) times.

126. The method of claim 102, wherein the administration of the composition causes the activity and / or expression of fibronectin 1 (FN1) to be downregulated by at least about two (2) times.

127. The method of claim 102, wherein the application of the composition causes the activity and / or expression of fibronectin 1 (FN1) to be downregulated by about ten (10) times.

128. The method of claim 102, wherein the application of the composition results in a downregulation of the activity and / or expression of the potassium-containing channel tetramerization domain 4 (KCTD4) by at least about five (5) times.

129. The method of claim 102, wherein the application of the composition results in a downregulation of the activity and / or expression of the potassium-containing channel tetramerization domain 4 (KCTD4) by about fifteen (15) times.

130. The method of claim 102, wherein the administration of the composition causes the activity and / or expression of the non-gastric α2 subunit (ATP12A) of the ATPase H+ / K+ transporter to be downregulated by at least about two (2) times.

131. The method of claim 102, wherein the administration of the composition causes the activity and / or expression of the non-gastric α2 subunit (ATP12A) of the ATPase H+ / K+ transporter to be downregulated by about ten (10) times.

132. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3) by at least two (2) times.

133. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3) by about ten (10) times.

134. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of the proliferation marker Ki-67 (MKI67) by at least two (2) times.

135. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of the proliferation marker Ki-67 (MKT67) by about ten (10) times.

136. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of follicle-staphylin (FST) by at least two (2) times.

137. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of follicle-staphylin (FST) by about ten (10) times.

138. The method of claim 102, wherein the application of the composition results in a downregulation of the activity and / or expression of solute carrier family 13 member 5 (SLC13A5) by at least about five (5) times.

139. The method of claim 102, wherein the application of the composition results in a downregulation of the activity and / or expression of solute carrier family 13 member 5 (SLC13A5) by about fifteen (15) times.

140. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of interleukin-6 (IL6) by at least about five (5) times.

141. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of interleukin-6 (IL6) by about twenty (20) times.

142. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of interleukin-23 (IL23) by at least about two (2) times.

143. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of interleukin-23 (IL23) by about five (5) times.

144. The method of claim 102, wherein the administration of the composition causes the activity and / or expression of tumor necrosis factor (TNF) to be downregulated by at least about ten (10) times.

145. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of tumor necrosis factor (TNF) by about 250 (250) times.

146. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of interleukin 24 (IL24) by at least about ten (10) times.

147. The method of claim 102, wherein the administration of the composition results in a downregulation of the activity and / or expression of interleukin 24 (IL24) by about seventy (70) times.

148. The method of claim 102, wherein the application of the composition results in a downregulation of matrix metallopeptidase 3 (MMP3) activity and / or expression by at least about ten (10) times.

149. The method of claim 102, wherein the application of the composition results in a downregulation of matrix metallopeptidase 3 (MMP3) activity and / or expression by about fifty (50) times.

150. The method of claim 102, wherein the administration of the composition results in a downregulation of matrix metallopeptidase 9 (MMP9) activity and / or expression by at least two (2) times.

151. The method of claim 102, wherein the administration of the composition results in a downregulation of matrix metallopeptidase 9 (MMP9) activity and / or expression by about eight (8) times.

152. The method of claim 102, wherein the administration of the composition results in an upregulation of the activity and / or expression of PTPRF interacting protein α4 (PPFIA4) stimulated by about five (5) times.

153. The method of claim 102, wherein the application of the composition upregulates the activity and / or expression of PTPRF interacting protein α4 (PPFIA4) by about thirty (30) times.

154. The method of claim 102, wherein administering the composition to the subject results in the prevention and treatment of local symptoms in the subject.

155. The method of claim 102, wherein the applied composition alters one or more functions associated with the regulated gene, wherein the one or more functions are selected from the group consisting of: (i) maintaining the skin barrier, (ii) anti-aging, (iii) inflammation, (iv) preventing scar formation during wound healing, and (v) maintaining skin barrier lipids.

Images