Naringenin preparations

Abstract

The present invention provides compositions comprising naringenin. The compositions of the present invention can be administered topically to the skin of a subject. The present invention further provides a method of administering a composition comprising naringenin for the improvement or treatment of a skin condition. The compositions of the present invention can also be applied to improve the overall appearance of the skin. The present invention relates to compositions comprising naringenin, and to methods of using compositions for treating, protecting, and / or altering (e.g., improving) skin conditions and / or aesthetic appearance, including, for example, treating, preventing, ameliorating, reducing and / or eliminating fine lines and / or wrinkles of the skin, and / or improving the aesthetic appearance of fine lines and / or wrinkles of the skin.

Description

[Technical Field]

[0001] I. Field of Invention The present invention relates to a naringenin preparation and a method for using the preparation to treat local conditions in a subject. [Background technology]

[0002] II. Background of the Invention The epidermis and its appendages (e.g., hair, nails, sebaceous glands, and sweat glands) of mammals provide a barrier to prevent harmful elements from entering the body and essential bodily fluids. As the first line of defense against various physical traumas from the environment, the epidermis must protect itself and the underlying tissues. The epidermis is also exposed to mutagenic ultraviolet radiation. In hairless or sparsely haired areas, such as most of human skin, the epidermis is thicker than hairy skin, and the skin in these areas plays a primarily protective role. Constant attacks on the epidermis necessitate autoregeneration, making it a prime example of adult tissue undergoing continuous and rapid flux.

[0003] Aged skin differs from youthful skin in both appearance and function. The aged epidermis shows decreased keratinocyte proliferation and becomes physically thinner, primarily due to the decline of interpapillary ridges. In addition to thinning, aging slows wound healing, prolongs epidermal turnover, and impairs barrier formation. The skin appears thin, wrinkled, bruised, and rough. Wrinkles and bruising can also result from aging-related changes in the dermis. The dermis, too, is characteristically thinner in older adults. Aged 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, reconstructive capacity, and basal cell structure. For example, interpapillary ridges may disappear, and basal cells may no longer be able to produce villous projections into the dermis. Epidermal cell turnover decreases by up to 50% in older adults compared to younger adults.

[0004] For example, the number of melanocytes can decrease by 8-20% every decade. In older adults, Langerhans cells are fewer, and those present are often functionally impaired. For instance, in women, collagen synthesis decreases by up to 30% within four years of menopause. The number of collagen and elastic fibers also decreases. The dermis also becomes less echogenic to ultrasound, which coincides with changes in collagen and elastic tissue. [Overview of the project] [Means for solving the problem]

[0005] III. Outline of the Invention The present invention relates to naringenin compositions and methods for using compositions to treat, protect and / or alter (e.g., improve) the condition and / or aesthetic appearance of the skin, including, for example, treating, preventing, ameliorating, reducing and / or eliminating fine lines and / or wrinkles of the skin, and / or improving the aesthetic appearance of fine lines and / or wrinkles of the skin. In certain embodiments, the compositions of the present invention lead to increased resilience of the skin and / or hair. In certain embodiments, the compositions of the present invention lead to increased elasticity of the skin. In certain embodiments, the compositions of the present invention prevent skin damage.

[0006] The use of naringenin-containing compositions for skincare has not been widely practiced in the field of skincare. This invention recognizes that naringenin-containing compositions can be used in the development of compositions that may have beneficial effects on the skin. In particular, topical administration of naringenin to improve skin conditions, including enhancing the appearance of the skin, by topical administration of a composition containing an effective amount of naringenin, was not known in the art. Beneficially, this invention is the first to recognize that topical compositions containing naringenin can be used to improve the condition of a skin subject or to treat any disease related to the skin subject. In one embodiment, this invention includes a composition for topical administration containing an effective amount of naringenin. An effective amount of naringenin in the composition is an amount of naringenin that may be effective in treating, improving, or otherwise affecting the underlying condition of the skin. This invention recognizes that naringenin is poorly soluble or insoluble in water. The present invention also recognizes that naringenin is poorly soluble or insoluble in oils, for example, naringenin is insoluble in Helianthus annuus (sunflower) seed oil. In certain embodiments of the present invention, naringenin is dissolved in a solvent selected from the group consisting of dimethyl isosorbide, ethoxydiglycol, isopropyl lauryl sarcosinate, pentylene glycol, propanediol, 1,2-hexanediol, and / or butylene glycol. In certain preferred embodiments, naringenin is dissolved in dimethyl isosorbide. In certain embodiments, naringenin is dissolved in isopropyl lauryl sarcosinate. In certain embodiments, naringenin is dissolved in ethoxydiglycol. In certain embodiments, the solvent is glycol. In certain embodiments, the glycol is selected from the group consisting of pentylene glycol, butylene glycol, and any combination thereof. In certain embodiments, the solvent is selected from the group consisting of phenylpropanol, 1,2-hexanediol, propanediol, isopentyldiol, 1,2-heptanediol, and any combination thereof.

[0007] In certain embodiments, the solvent is 1,2-heptanediol, 1,2-hexanediol, 1,2-propanediol, butylene glycol, C 15~19 Alkanes, Capric Acid / Caprylic Triglyceride, Dibutyl Adipate, Diisopropyl Adipate, Dimethyl Isosorbide, Dipropylene Glycol, Ethanol, Ethoxydiglycol, Isoamyl Laurate, Isohexadecane, Isopentyl Diol, Isopropyl Myristate, Isopropyl Lauroyl Sarcosinate, Jojoba Oil, Meadowfoam Seed Oil, Mineral Oil, Neopentyl Glycol Diethylhexanoate, Octyldodecanol, Oleyl Alcohol, Pentylene Glycol, Phenylpropanol, Polysorbate 20, Propanediol, Safflower Seed Oil, Squalene, Sunflower Oil, t-Butyl Alcohol, Tributyl Citrate, O-Acetyl Citrate Tributyl Citrate, Tri-C 15~19 Selected from the group consisting of alkyl, triethyl citrate, triethyl O-acetylcitrate, and triisostearin.

[0008] In certain embodiments, the composition containing naringenin is anhydrous. In certain embodiments, the composition contains oil as the sole solvent. In certain embodiments, the composition containing naringenin is an emulsion. In certain embodiments, the composition containing naringenin is a microemulsion. In certain embodiments, the composition of the present invention is encapsulated. In certain embodiments, naringenin may be microencapsulated.

[0009] In another embodiment, the present invention relates to stable compositions of naringenin. In certain embodiments, the compositions of the present invention are stable under storage conditions. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least two years. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least one year. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least six months. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least three months.

[0010] Stability studies conducted using naringenin dissolved in dimethyl isosorbide, isopropyl sarcosinate, and ethoxydiglycol have demonstrated that naringenin undergoes less than 10% degradation when stored for a duration of one month under accelerated stability conditions. These results demonstrate that the compositions of the present invention can be stable for a duration of at least two years under ambient conditions. In certain embodiments, ambient conditions mean that the composition is stable when stored at room temperature (in the range of about 15°C to about 25°C).

[0011] In certain embodiments, the composition contains naringenin at a concentration of about 5 nM to about 2500 nM. In certain embodiments, the composition contains naringenin at a concentration of about 10 nM to about 2000 nM. In certain embodiments, the composition contains naringenin at a concentration of about 20 nM to about 1000 nM. In certain embodiments, the composition contains naringenin at a concentration of about 10 nM to about 20 nM.

[0012] In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.0001 w / w% to about 5.0 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.0001 w / w% to about 1.0 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.001 w / w% to about 0.5 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.01 w / w% to about 0.5 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.1 w / w% to about 0.5 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.45 w / w%.

[0013] In certain embodiments, the compositions of the present invention can be administered to the target skin as topical compositions. The compositions of the present invention may be included in any formulation suitable for topical administration. In certain embodiments, the compositions of the present invention are fluids, emulsions, encapsulations, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, emulsions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, color cosmetics, and / or hair treatments. In certain embodiments, the compositions of the present invention also include additives. These additives 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 certain embodiments, the preservative in the composition is an antimicrobial preservative or a chelating agent. In certain embodiments, the solvent of the present invention is dimethyl isosorbide. In certain embodiments, the solvent of the present invention is lauroyl sarcosinate isopropyl. In certain embodiments, the solvent of the present invention is ethoxydiglycol.

[0014] The compositions of the present invention can be prepared by a variety of methods. For example, the compositions can be prepared by dissolving or dispersing naringenin and optional additives provided herein in a carrier (e.g., water, saline solution, aqueous dextrose, glycerol, glycol, ethanol, or analogues) or solvent to form solutions, colloids, liposomes, emulsions, complexes (including inclusion complexes), coacervates, or suspensions. In certain embodiments, the compositions of the present invention may also contain additional additives such as wetting agents, emulsifiers, cosolvents, solubilizers, pH buffering agents, and analogues (e.g., sodium acetate, sodium citrate, cyclodextrins and derivatives, sorbitan monolaurate, triethanolamine acetate, triethanolamine oleate, hydroxyethylpiperazine, and analogues). In certain embodiments, the compositions of the present invention may further include one or more additional additives selected from the group consisting of carriers, additives, or diluents, including, but not limited to, absorbents, anti-irritants, antibacterial agents, anti-acne agents, antioxidants, colorants / pigments, moisturizers, emulsifiers, film-forming / retaining agents, fragrances, leave-on exfoliants, formula drugs, preservatives, scrub agents, silicones, skin-identical agents / skin-repairing agents, slip agents, sunscreen activators, surfactants / cleansing agents, penetration enhancers, and thickeners.

[0015] In certain embodiments, the composition of the present invention comprises naringenin and a preservative in an oil / water emulsion.

[0016] In certain embodiments, the composition of the present invention comprises naringenin and a preservative dissolved in a solvent.

[0017] In certain embodiments, the composition of the present invention comprises naringenin, a solvent for solubilizing naringenin, and a preservative in an oil / water emulsion.

[0018] In certain embodiments, the composition of the present invention comprises naringenin, a solvent for solubilizing naringenin, a diluent, and a preservative.

[0019] In certain embodiments, the composition of the present invention comprises naringenin, a solvent for solubilizing naringenin, a thickening agent, an optional diluent, and a preservative.

[0020] In certain embodiments, the composition of the present invention comprises naringenin, a solvent for solubilizing naringenin, and one or more additives selected from the group consisting of a diluent, an absorbent, an antioxidant, a skin softening agent, an emulsifier, a thickening agent, a surfactant, and / or a preservative.

[0021] In certain embodiments, the additives included in the composition are water, dimethyl isosorbide, glycerin, caprylic / capric triglyceride, propanediol, sunflower seed oil, ethoxydiglycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerin / sebacic acid copolymer, diheptyl succinate, naringenin, lecithin, decylene glycol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidyl alcohol, behenyl alcohol, arachidyl glucoside, phenethyl alcohol, 1,2 - hexanediol, hydrogenated olive oil, olea europaea (olive) fruit oil, olea europaea (olive) oil unsaponifiables, hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer, citric acid, sodium acetylated hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and / or ethylhexyl glycerin.

[0022] In certain aspects, the present invention provides that the composition of the present invention is synergistic. The composition provided by the present invention is beneficial because of the enhanced stability of the components in the composition due to their synergistic effect, as well as the resulting stability and effectiveness. In certain embodiments, the present invention provides that the composition of the present invention is more effective and stable compared to when administered or stored as individual components. The composition of the present invention may also act synergistically when administered with other treatments for the treatment of the conditions described herein.

[0023] In certain embodiments of the present invention, compositions containing naringenin exhibit antioxidant activity. In certain embodiments, the antioxidant activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.0001 w / w% or higher. In certain embodiments, the antioxidant activity of naringenin in the compositions of the present invention is active at a concentration of about 0.0005 w / w% or higher.

[0024] Advantageously, compositions of the present invention containing naringenin exhibiting antioxidant activity are effective in treating and / or preventing oxidative damage. In certain embodiments, compositions of the present invention containing naringenin exhibiting antioxidant activity are effective in treating skin and / or hair damaged by reactive oxygen species, as well as protecting the skin in question from other environmental aggressors that may cause damage. In certain other embodiments, compositions of the present invention containing naringenin exhibiting antioxidant activity are effective in preventing skin and / or hair damage caused by reactive oxygen species, including damage caused by environmental aggressors.

[0025] In certain embodiments of the present invention, compositions containing naringenin exhibit elastase enzyme inhibition. In certain embodiments, the elastase enzyme inhibitory activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.02 w / w% or higher. In certain embodiments, the elastase enzyme inhibitory activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.1 w / w% or higher. Advantageously, compositions containing naringenin exhibiting elastase enzyme inhibitory activity are effective in promoting skin elasticity. In certain embodiments, compositions of the present invention containing naringenin exhibiting elastase enzyme inhibition are effective in reducing fine lines and / or wrinkles of the skin. In certain embodiments, compositions of the present invention containing naringenin exhibiting elastase enzyme inhibition are effective in preventing the formation of fine lines and / or wrinkles of the skin.

[0026] In certain embodiments of the present invention, compositions containing naringenin exhibit glycation inhibition. In certain embodiments, the glycation inhibition activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.005 w / w% or higher. In certain embodiments, the glycation inhibition activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.008 w / w% or higher. Advantageously, compositions containing naringenin exhibiting glycation inhibition activity are effective in supporting and promoting the resilience of skin and / or hair.

[0027] In certain embodiments of the present invention, compositions containing naringenin exhibit anti-inflammatory activity. In certain embodiments, compositions containing naringenin exhibit anti-inflammatory activity at concentrations of 0.0001 w / w% or higher. In certain embodiments, compositions containing naringenin exhibit anti-inflammatory activity at concentrations of 0.0045 w / w% or higher. In certain embodiments, the anti-inflammatory activity of naringenin in the compositions of the present invention is demonstrated by a decrease in the anti-inflammatory markers IL-6 and / or TNF-α in stressed keratinocytes. In certain embodiments, the anti-inflammatory activity is demonstrated in human epidermal keratinocytes. Chemokines produced by activated keratinocytes and immune cells can damage skin tissue near the targets of the inflammatory response. Modulation of the immune response is crucial for maintaining skin homeostasis. If that modulation is functioning optimally, the cellular inflammatory response should disrupt skin homeostasis. Advantageously, the anti-inflammatory activity of compositions containing naringenin is beneficial in maintaining skin homeostasis and promoting skin health.

[0028] In certain embodiments of the present invention, the composition is a composition comprising naringenin that can be applied to the skin as a mask. In certain embodiments, the mask may be for overnight application. Thus, in certain embodiments, the application of the mask results in a refreshed appearance of the skin.

[0029] In certain embodiments, the present invention provides a sunscreen containing naringenin. In certain embodiments, a sunscreen containing naringenin provides all-broad spectrum photoprotection, repairs damage caused by inflammatory aging, and maintains firmness.

[0030] In certain embodiments, the present invention provides an enhanced eye cream containing naringenin. In certain embodiments, the eye cream provides firmness and moisture to the skin and reduces visible signs of inflammatory aging.

[0031] In certain embodiments of the present invention, a composition comprising naringenin modulates the expression of one or more genes related to a local condition. In certain embodiments, administration of a composition comprising naringenin alters one or more functions related to the modulated gene, where one or more functions are selected from the group consisting of (i) altering the appearance of the skin or improving a condition that leads to an undesirable appearance of the skin, (ii) forming fine lines or wrinkles of the skin, (iii) inflammation, (iv) maintaining barrier support, and (v) altering the appearance of the skin by altering cell turnover or cell recycling. In certain embodiments, administration of a composition containing naringenin alters the expression and / or function of one or more genes selected from the group consisting of LCE5A, KRT77, ALOXE3, KRT1, HPGD, MUCL1, CASP14, WFDC12, KRT10, DNASE1L2, IL37, SERPINB12, HAL, UPK1A, CALML5, LCE2B, MIR205, CCL11, CSF2, IL23A, IL11, BMP6, IL13RA2, C2CD4A, NR4A2, C2CD4B, FGF2, FABP4, GDF15, THBS1, HSPA1A, PTGS2, and / or DKK1.

[0032] In certain embodiments, administration of a composition containing naringenin leads to the upregulation of LCE5A, KRT77, ALOXE3, KRT1, HPGD, MUCL1, CASP14, WFDC12, KRT10, DNASE1L2, IL37, SERPINB12, HAL, UPK1A, CALML5, LCE2B, and / or MIR205. In certain embodiments, administration of a composition containing naringenin leads to the downregulation of CCL11, CSF2, IL23A, IL11, BMP6, IL13RA2, C2CD4A, NR4A2, C2CD4B, FGF2, FABP4, GDF15, THBS1, HSPA1A, PTGS2, and / or DKK1.

[0033] In certain embodiments of the present invention, administration of a composition containing naringenin enhances anti-inflammatory activity. In certain embodiments, administration of a composition containing naringenin enhances anti-inflammatory activity because it leads to downregulation of CSF2, IL23A, IL11, IL13RA2, C2CD4A, NR4A2, FABP4, GDF15, and / or PTGS2. In certain embodiments, administration of a composition containing naringenin enhances anti-inflammatory activity because it leads to upregulation of HPGD. In certain embodiments, administration of a composition containing naringenin results in downregulation of CSF2 expression and / or activity to at most about 1 / 15. In certain embodiments, administration of a composition containing naringenin results in downregulation of IL23A expression and / or activity to at most about 1 / 15. In certain embodiments, administration of a composition containing naringenin results in downregulation of IL11 expression and / or activity to at most about 1 / 10. In certain embodiments, administration of a composition containing naringenin results in a downregulation of IL13RA2 expression and / or activity to at most about one-tenth. In certain embodiments, administration of a composition containing naringenin results in a downregulation of C2CD4A expression and / or activity to at most about one-tenth. In certain embodiments, administration of a composition containing naringenin results in a downregulation of NR4A2 expression and / or activity to at most about one-tenth. In certain embodiments, administration of a composition containing naringenin results in a downregulation of FABP4 expression and / or activity to at most about one-fifth. In certain embodiments, administration of a composition containing naringenin results in a downregulation of GDF15 expression and / or activity to at most about one-fifth. In certain embodiments, administration of a composition containing naringenin results in a downregulation of PTGS2 expression and / or activity to at most about one-fifth. In certain embodiments, administration of a composition containing naringenin results in at least about a 10-fold upregulation of HPGD expression and / or activity.

[0034] In certain embodiments of the present invention, administration of a composition containing naringenin enhances skin barrier strength and / or maintenance of skin barrier lipids. In certain embodiments, administration of a composition containing naringenin enhances skin barrier strength and / or maintenance of skin barrier lipids because it leads to the upregulation of LCE5A, KRT77, ALOXE3, KRT1, CASP14, KRT10, and / or LCE2B. In certain embodiments, administration of a composition containing naringenin results in at least about 30-fold upregulation of LCE5A expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about 10-fold upregulation of KRT77 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about 10-fold upregulation of ALOXE3 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about 5-fold upregulation of KRT1 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about a 10-fold upregulation of CASP14 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about a 5-fold upregulation of KRT10 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about a 5-fold upregulation of LCE2B expression and / or activity.

[0035] In certain embodiments of the present invention, administration of a composition containing naringenin leads to enhanced cell turnover and / or cell recycling. Beneficially, this enhancement of cell turnover and / or cell recycling leads to an anti-aging effect. In certain embodiments, the anti-aging effect may be demonstrated by a reduction and / or prevention of the formation of fine lines and / or wrinkles in the skin. In certain embodiments, administration of a composition containing naringenin enhances cell turnover and / or cell recycling in the skin because the administration of the composition leads to the upregulation of DNASE1L2, SERPINB12, UPK1A, CALML5 and / or MIR205. In certain embodiments, administration of a composition containing naringenin enhances cell turnover and / or cell recycling in the skin because the administration of the composition leads to the downregulation of BMP6 and / or HSPA1A. In certain embodiments, administration of a composition containing naringenin results in at least a five-fold upregulation of DNASE1L2 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about a 10-fold upregulation of SERPINB12 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about a 10-fold upregulation of UPK1A expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about a 5-fold upregulation of CALML5 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about a 5-fold upregulation of MIR205 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in downregulation of BMP6 expression and / or activity to as little as one-tenth. In certain embodiments, administration of a composition containing naringenin results in downregulation of HSPA1A expression and / or activity to as little as one-fifth.

[0036] In certain embodiments, administration of a composition containing naringenin to a subject leads to the treatment or prevention of a local condition in the subject by modulating the level of expression or activity of one or more genes that may be involved in the local condition. In certain embodiments, administration of a composition containing naringenin alters one or more functions associated with the modulated gene, where one or more functions are selected from the group consisting of (i) cell turnover, (ii) inflammation, (iii) barrier support, and (iv) any combination thereof. [Brief explanation of the drawing]

[0037] [Figure 1] Figure 1 provides data on the application of compositions containing naringenin to the skin. [Modes for carrying out the invention]

[0038] V. Detailed explanation Naringenin Naringenin is a flavonoid commonly found in various citrus fruits. Naringenin is also known as (2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one, (2S)-4',5,7-trihydroxyflavan-4-one, naringetol, saliprol, or saliprol. The chemical structure of naringenin is shown below. [ka]

[0039] Naringenin has been demonstrated to possess numerous biological activities, including anti-inflammatory properties, antioxidant activity, pain management, wound healing, and attenuation of fatty liver disease. Rebello Cj et al. Safety and pharmacokinetics of naringenin: A randomized, controlled, single-ascending-dose clinical trial. Diabetes Obes Metab. 2020 (1):91-98, Martinez RM et al. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice. J Nat Prod. 2015 Jul 24;78(7):1647-55, Pinho-Ribeiro FA, et al. Naringenin reduces inflammatory pain in mice. Neuropharmacology. 2016,105:508-519, Wang Q, et al. Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3 / NF-κB pathway in mice. Br J Pharmacol. 2020 Apr;177(8):1806-1821.

[0040] Naringenin is generally considered safe for oral administration and has been shown to increase the antioxidant markers superoxide dismutase and glutathione when consumed orally. (Al-Roujayee AS. Naringenin improves the healing process of thermally-induced skin damage in rats. J Int Med Res. 2017 Apr;45(2):570-582.) In a mouse model, intraperitoneal naringenin treatment effectively inhibited edema, reduced cytokine production, inhibited UVB-induced skin damage, and reduced symptoms associated with atopic dermatitis.Karuppagounder V et al. Naringenin ameliorates skin inflammation and accelerates phenotypic reprogramming from M1 to M2 macrophage polarization in atopic dermatitis NC / Nga mouse model. Exp Dermatol. 2016 May;25(5):404-7、Kim TH et al. The inhibitory effect of naringenin on atopic dermatitis induced by DNFB in NC / Nga mice. Life Sci. 2013 Oct 10;93(15):516-24、Martinez RM, et al. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice. PLoS One. 2016, 11(1): e0146296、Pinho-Ribeiro Faet al. The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-κB activation. J Nutr Biochem. 2016 Jul 33:8-14。

[0041] Furthermore, topical application of naringenin and alginate hydrogel to wounded mice resulted in more rapid wound closure. In in vitro models, a similar mechanism of action has been suggested in human skin cells, with a 10 μM dose protecting HaCaT immortalized keratinocytes from UVB-induced apoptosis, and separate studies have shown skin barrier repair in a psoriasis model. (El-Mahdy MA et al. Naringenin protects HaCaT human keratinocytes against UVB-induced apoptosis and enhances the removal of cyclobutane pyrimidine dimers from the genome. Photochem Photobiol. 2008 Mar-Apr;84(2):307-16; Alalaiwe A, et al. Development of flavanone and its derivatives as topical agents against psoriasis: The prediction of therapeutic efficiency through skin permeation evaluation and cell-based assay. Int J Pharm. 2020 May 15;581:119256.)

[0042] However, the use of compositions containing an effective amount of naringenin for topical application to improve local conditions has not been demonstrated to date. The present invention provides compositions containing naringenin for administration to human skin. In one embodiment, the present invention provides the use of compositions containing naringenin in topical cosmetic formulations as an anti-inflammatory agent having barrier-repairing and antioxidant properties.

[0043] Naringenin composition In one embodiment, the present invention provides a composition comprising naringenin. In a particular embodiment, the present invention provides a composition comprising naringenin suitable for administration to the skin of a target.

[0044] The present invention recognizes that naringenin is poorly soluble or insoluble in water. The present invention also recognizes that naringenin is poorly soluble or insoluble in oils; for example, naringenin is insoluble in Helianthus annuus (sunflower) seed oil. The present invention recognizes that the solvent used to prepare the naringenin composition should be one of the solvents permitted for use in cosmetic formulations. In certain embodiments of the present invention, naringenin is dissolved in a solvent selected from the group consisting of dimethyl isosorbide, ethoxydiglycol, lauroyl sarcosinate isopropyl, pentylene glycol, propanediol, 1,2-hexanediol, and / or butylene glycol. In certain preferred embodiments, naringenin is dissolved in dimethyl isosorbide. In certain embodiments, naringenin is dissolved in lauroyl sarcosinate isopropyl. In certain embodiments, naringenin is dissolved in ethoxydiglycol. In certain embodiments, the solvent is glycol. In certain embodiments, the glycol is selected from the group consisting of pentylene glycol, butylene glycol, and any combination thereof. In certain embodiments, the solvent is selected from the group consisting of phenylpropanol, 1,2-hexanediol, propanediol, isopentyldiol, 1,2-heptanediol, and any combination thereof.

[0045] In certain embodiments, the solvent is 1,2-heptanediol, 1,2-hexanediol, 1,2-propanediol, butylene glycol, C 15~19Alkanes, Capric Acid / Caprylic Triglyceride, Dibutyl Adipate, Diisopropyl Adipate, Dimethyl Isosorbide, Dipropylene Glycol, Ethanol, Ethoxydiglycol, Isoamyl Laurate, Isohexadecane, Isopentyl Diol, Isopropyl Myristate, Isopropyl Lauroyl Sarcosinate, Jojoba Oil, Meadowfoam Seed Oil, Mineral Oil, Neopentyl Glycol Diethylhexanoate, Octyldodecanol, Oleyl Alcohol, Pentylene Glycol, Phenylpropanol, Polysorbate 20, Propanediol, Safflower Seed Oil, Squalene, Sunflower Oil, t-Butyl Alcohol, Tributyl Citrate, O-Acetyl Citrate Tributyl Citrate, Tri-C 15~19 Selected from the group consisting of alkyl, triethyl citrate, triethyl O-acetylcitrate, and triisostearin.

[0046] Table 1 provides solubility data for naringenin in several solvents. [Table 1-1] [Table 1-2]

[0047] In certain embodiments, the composition containing naringenin is anhydrous. In certain embodiments, the composition contains oil as the sole solvent. In certain embodiments, the composition containing naringenin is an emulsion. In certain embodiments, the composition containing naringenin is a microemulsion. In certain embodiments, the composition of the present invention is encapsulated. In certain embodiments, the naringenin may be microencapsulated.

[0048] In another embodiment, the present invention relates to stable compositions of naringenin. In certain embodiments, the compositions of the present invention are stable under storage conditions. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least two years. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least one year. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least six months. In certain embodiments, a composition containing naringenin is stable under ambient conditions for a period of at least three months. The present invention usefully provides that naringenin solutions dissolved in dimethyl isosorbide, lauroyl sarcosinate isopropyl, and ethoxydiglycol have increased solubility and storage stability. Since naringenin is insoluble in sunflower oil and other commonly used solvents, the increased solubility in dimethyl isosorbide, lauroyl sarcosinate isopropyl, and ethoxydiglycol is surprising and unexpected.

[0049] Table 2 provides data on accelerated stability studies of compositions containing naringenin dissolved in several solvents. [Table 2]

[0050] In certain embodiments, the composition contains naringenin at a concentration of about 5 nM to about 2500 nM. In certain embodiments, the composition contains naringenin at a concentration of about 10 nM to about 2000 nM. In certain embodiments, the composition contains naringenin at a concentration of about 20 nM to about 1000 nM. In certain embodiments, the composition contains naringenin at a concentration of about 10 nM to about 20 nM.

[0051] In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.0001 w / w% to about 5.0 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.0001 w / w% to about 1.0 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.001 w / w% to about 0.5 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.01 w / w% to about 0.5 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.1 w / w% to about 0.5 w / w%. In certain embodiments, naringenin is present in the composition of the present invention at a concentration of about 0.45 w / w%.

[0052] In certain embodiments, the compositions of the present invention can be administered to the target skin as topical compositions. The compositions of the present invention may be included in any formulation suitable for topical administration. In certain embodiments, the compositions of the present invention are fluids, emulsions, capsules, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, emulsions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, colored cosmetics, and / or hair treatments. In certain embodiments, the compositions of the present invention also include additives. These additives 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 certain embodiments, the preservatives in the composition are antimicrobial preservatives or chelating agents.

[0053] The compositions of the present invention can be prepared by a variety of methods. For example, the compositions can be prepared by dissolving or dispersing naringenin and optional additives provided herein in a carrier (e.g., water, saline solution, aqueous dextrose, glycerol, glycol, ethanol, or analogues) or solvent to form solutions, colloids, liposomes, emulsions, complexes (including inclusion complexes), coacervates, or suspensions. In certain embodiments, the compositions of the present invention may also contain auxiliary substances such as wetting agents, emulsifiers, cosolvents, solubilizers, pH buffering agents, and analogues (e.g., sodium acetate, sodium citrate, cyclodextrins and derivatives, sorbitan monolaurate, triethanolamine acetate, triethanolamine oleate, hydroxyethylpiperazine, and analogues). In certain embodiments, the compositions of the present invention may further include one or more additional additives selected from the group consisting of carriers, additives, or diluents, which include, but are not limited to, absorbents, anti-irritants, antibacterial agents, anti-acne agents, antioxidants, colorants / pigments, emollients (moisturizers), emulsifiers, film-forming / retaining agents, fragrances, leave-in exfoliants, formula drugs, preservatives, scrubs, silicones, skin homogenizers / skin repair agents, slippers, sunscreen activators, surfactants / cleansing agents, penetration enhancers, and thickeners.

[0054] Absorbents are substances added to topical products to absorb water-soluble and oil-soluble dissolved or finely dispersed substances. Topical absorbents can also be used as thickeners in a wide variety of formulations, including facial creams, lipsticks, shampoos, and calamine lotions. In some embodiments, the absorbent may include, but is not limited to, alcohols (ethyl alcohol, methanol, isopropyl alcohol, SD alcohol [especially denatured alcohol] and benzyl alcohol), alumina (aluminum oxide), aluminum chlorohydrate, 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, china clay, clay, Copernicia cerifera wax, corn starch, fuller's earth, hydrolyzed corn starch, iron powder, kaolin, sodium lithium magnesium silicate, magnesium, magnesium carbonate, magnesium hydroxide, montmorillonite, nylon-12, rice starch, silica, silicate, silk powder, silt, sodium carbonate, sodium polyacrylate, and zeolite.

[0055] Anti-irritants are substances added to topical products to reduce inflammation, particularly inflammation resulting from the application of the product itself. Additives included as anti-irritants that perform the function of an anti-irritant or anti-inflammatory agent may have two or more functions. 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 gum, acetylsalicylic acid, Achillea millefolium, adenosine, citric acid, adenosine triphosphate, Aloe barbadensis, Aloe barbadensis leaf juice extract, aloe extract, aloe juice, hydrogenated olive oil, hydrogenated palm oil glyceride, hydrolyzed silk, hydroquinone, aloe vera, and / or alpha-bisabolol.

[0056] In certain embodiments, the composition of the present invention may further include a humectant. Humidifiers (or moisturizers) are important cosmetic ingredients that prevent moisture loss and thereby retain the skin's natural moisture. Some humectants can also actively attract moisture. In certain embodiments, the humectant may be selected from the group consisting of sodium hyaluronate, acetylated sodium hyaluronate, hydrolyzed sodium hyaluronate, propylene glycol, hexylene glycol, and butylene glycol.

[0057] In certain embodiments, the composition of the present invention may further include a slip agent. The term “slip agent” is used to describe a variety of ingredients that can help other ingredients spread on the skin and penetrate the skin. Slip agents may also have moisturizing (hygroscopic) properties. In some embodiments, the slip agent may include amodimethicone, bis-PEG-18 methyl ether dimethylsilane, bis-phenylpropyl dimethicone, butylene glycol, cetyl dimethicone, cetyl dimethicone copolyol, cetyl PEG / PPG-10 / 1-dimethicone, cyclohexasiloxane, cyclomethicone, cyclopentasiloxane, cyclotetrasiloxane, decylene glycol, diisostearoyl trimethylolpropanesiloxysilicate, dimethicone, dimethicone copolyol, dimethicone crosspolymer, dimethiconol, dipropylene glycol, hexylene glycol, hydrolyzed silk, isododecane, methicone, methyl trimethicone, methylsilanol Nuronate, methylsilanol PEG-7 glyceryl cocoate, Good, PEG-10 dimethicone, PEG-10 dimethicone / vinyl dimethicone crosspolymer, PEG-12 dimethicone, PEG / PPG-18 / 18 dimethicone, PEG / PPG-20 / 15 dimethicone, pentylene glycol, phenyl trimethicone, polymethylsilsesquioxane, PPG-3 benzyl ether myristate, dimethylsilylated silica, silk powder, siloxane, simethicone, sorbitol, stearyl dimethicone, stearyl methicone, triethoxycaprylylsilane, trimethylsiloxysilicate, xylitol, and zinc stearate may be, but are not limited to, these.

[0058] In certain embodiments, the compositions of the present invention may further include diluents and / or carriers. Diluents and / or carriers may include, but are not limited to, polyethylene glycol (such as PEG200, PEG300, PEG400, PEG540, PEG600, PEG1450, or mixtures thereof) and coconut oil (such as propylene glycol dicaprate, coco-caprylate / caprate, propylene glycol dicaprylate / dicate, caprylic / capric acid triglyceride, caprylic / capric acid / laurate triglyceride, caprylic / capric acid / linoleic acid triglyceride, tricaprin, tricaprylin, glyceryl trioleate, neopentyl glycol dicaprylate / dicate, caprylic / capric acid / palmitic acid / stearic acid triglyceride (triglceride), or mixtures thereof).

[0059] In certain embodiments, the composition of the present invention may further include an emollient. An emollient is a flexible, waxy, lubricating, and thickening substance added to cosmetic / dermatological products that prevents moisture loss and has a softening and soothing effect on the skin. In some embodiments, the emollient may include 10-hydroxydecanoic acid, glyceryl acetylricinoleate, acetylated castor oil, acetylated hydrogenated cottonseed glyceride, acetylated lanolin, acetylated lanolin alcohol, acetylated palm kernel glyceride, agar, algal extract, algin, almond oil, squalane, squalene, α-glucan oligosaccharide, amodimethicone, Anacystis nidulans extract, apricot kernel oil, arachidic acid, arachidonic acid, arachidyl alcohol, arachidyl propionate, C 10~30 Cholesterol / lanosterol ester, C 12~15 Alkylbenzoate, C 12~18 Acid triglycerides, C 18~36Triglyceride, candelilla wax, Cannabis sativa L. oil, caprylic / capric triglyceride, caprylyl methicone, carrot oil, Carthamus tinctorius oil, Carya illinoensis oil, castor oil succinate isostearate, castor oil, Caulerpa taxifolia extract, and / or cephalin may be included, but are not limited thereto.

[0060] In certain embodiments, the composition of the present invention can further include a film-forming / holding agent. A film-forming / holding agent is a substance added to beauty / dermatological products to help leave a flexible, adhesive, continuous film on the skin. This film has the property of binding to water and leaves a smooth feel on the skin. In some embodiments, the film-forming / holding agent includes acrylates, acrylate copolymers, acrylate / C 10~30Alkyl acrylate crosspolymer, acrylate / dimethicone copolymer, adipic acid / neopentyl glycol / trimellitic anhydride copolymer, allyl methacrylate crosspolymer, carnauba wax, cellulose gum, Copernicia cerifera wax, dextrin, diisopropyl adipate, glyceryl polymethacrylate, hydrolyzed wheat protein, hydroxyethylcellulose, locust bean, neopentyl glycol diheptanoate, PEG-40 hydrogenated castor oil, polyacrylamide, polyacrylate-17, polyglucuronic acid, polyglyceryl methacrylate, polyisobutene, polymethyl methacrylate, polyquaternium-10, polyquaternium compounds, polyvinyl alcohol, polyvinylpyrrolidone, propylene carbonate, P This may include, but is not limited to, VM / MA (polyvinyl methyl ether / maleic acid) decadien crosspolymer, PVP [poly(vinylpyrrolidone)] copolymer, PVP / dimethylaminoethyl methacrylate, sodium carbomer, sodium polyacrylate, styrene / acrylate copolymer, triethoxycaprylylsilane crosspolymer, VA (vinyl acetate) / crotonate, VA / crotonate copolymer, VP (vinylpyrrolidone) / eicosene copolymer, and VP / hexadecene copolymer.

[0061] In certain embodiments, the composition of the present invention may further include additives related to the fragrance of the formulation. The fragrance component is a single or blended volatile and / or fragrant vegetable oil (or synthetically derived oil) that imparts aroma and scent to the cosmetic / dermatological product. The level of fragrance used varies depending on the type of product. In some embodiments, the composition of the formulation may contain up to about 0.01% by weight of fragrance. In some embodiments, the fragrance (e.g., synthetic and fragrant plant extracts) may include: Acacia farnesiana extract, Aerocarpus santalinus, amyl cinnamate, amyl salicylate, amyris oil, Anethum graveolens, Angelica archangelica root oil, anisaldehyde, anise, balm mint extract, Peruvian balsam, bay leaf oil, bergamot oil, bitter orange blossom, bois de rose oil, bois oil, Boswellia carterii, butylphenyl methylpropional, cananga extract, Cananga odorata, cardamom, cedarwood, cherry extract, Citrus aurantifolia, Citrus aurantium, Citrus aurantium extract, Citrus medica limonium, clary oil, Commiphora myrrha extract, coriander, Cucurbitea Peponis, cyclamenaldehyde, dill extract, ethyl vanillin, eugenol, farnesol, farnesyl acetate, Ferula galbaniflua, fir needle oil, floral ozone, Foeniculum vulgare extract, frankincense extract, galbanum, Gardenia florida extract, grapefruit oil, guaiac wood, Guaiacum officinale, hedione, hexyl cinnamal, hyssop, Illicium vernum, Iris florentina extract, jasmine oil, Jasminium grandiflorum, jonquil extract, Laurus nobilis, lauryl lactate, lavandin oil, LavandulaThis may include, but is not limited to, angustifolia, Lavandula officinalis, lavender extract and oil, lemon, lemon balm, lemongrass oil, Levisticum officinale root extract, lime oil and extract, limonene, linalool, Litsea cubeba, mandarin orange oil or extract, marjoram, Melissa officinalis, Mentha piperita, Mentha spicata, Mentha viridis, menthol, menthone, menthoxypropanediol, and menthyl lactate.

[0062] In certain embodiments, the composition of the present invention may further contain preservatives. Preservatives are substances that prevent bacterial, microbial, or fungal contamination of cosmetic / dermatological products, thereby increasing the shelf life and consumer safety of the product. Some of these agents also have stabilizing effects that can preserve the function of various active ingredients, including antioxidants (vitamins), emulsifiers, and surfactants. In some embodiments, preservatives include 1,2-hexanediol, benzoic acid, benzothonium chloride, borax, bronopol, butylparaben, caprylyl glycol, chlorophene, chloroxylenol, chlorphenesin, decylene glycol, dehydroacetic acid, diazolidinyl urea, DMDM ​​hydantoin, ethylhexylglycerin, ethylparaben, formaldehyde-releasing preservatives, and Germaben. II may include, but is not limited to, thalene, hydroxyacetophenone, imidazolidinyl urea, iodopropynyl butylcarbamate, isobutylparaben, methylchloroisothiazolinone, methyldibromoglutaronitrile, methylisothiazolinone, methylparaben, o-cymen-5-ol, phenoxyethanol, phenoxyisopropanol, phytosphingosine, polyaminopropyl biguanide, potassium sorbate, propylparaben, quaternium-15, sodium benzoate, sodium citrate, sodium dehydroacetate, sodium hexametaphosphate, sodium hydroxymethylglycine, phenethyl alcohol, sodium lactobionate, sodium metabisulfite, sodium sulfite, sorbic acid, and styrax benzoin.

[0063] In certain embodiments of the present invention, the pharmaceutical composition is an emulsion. The emulsion composition of the present invention may further contain an emulsifier. An emulsifier is a substance added to cosmetic / dermatological products to help prevent dissimilar components (such as oil and water) from separating in the emulsion. There are two types of emulsifiers. Oil-in-water (o / w) emulsifiers trap oil droplets in water, while water-in-oil (w / o) emulsifiers trap water droplets in oil. W / O emulsifiers are used to create a fatty feel (e.g., night creams and sunscreens). O / W emulsifiers are often used in moisturizing products (e.g., body lotions and day creams).

[0064] In certain embodiments, the compositions of the present invention may further include surfactants. Surfactants are compounds that reduce surface tension or interfacial tension. By reducing surface tension, liquids spread more easily, while by reducing interfacial tension (interfacial tension meaning the space between two surfaces) between water and oil / lipids, they mix. Surfactants may be anionic, amphoteric, nonionic, and / or quaternary active substances. Surfactants may form the base of any personal cleansing product and may also have wetting, conditioning, degreasing, emulsifying, and thickening effects. In some embodiments, emulsifiers, surfactants, and detergents include ammonium laureth sulfate, ammonium lauryl sulfate, arachidyl glucoside, behenic acid, bis-PEG-18 methyl ether dimethylsilane, C 20~40Pareth-40, Cocamidopropyl Betaine, Cocamidopropyl Dimethylamine, Cocamidopropyl Hydroxysultaine, Coco-Glucoside, Coconut Oil, Decyl Glucoside, Dicetyl Phosphate, Dihydrocholeth-30, Disodium Cocoamphodiacetate, Disodium Cocoyl Glutamate, Disodium Lauraminopropionate, Glyceryl Behenate, Hydrogenated Vegetable Glycerides Citrate, Isohexadecane, Isostearamide DEA, Lauranhocarboxyglycinate, Laureth-23, Laureth-4, Laureth-7, Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone, Lauryl Alcohol, Lauryl Glucoside, Magnesium Laureth Sulfate, Magnesium Oleth Sulfate, Myristic Acid, Nonoxynol, Oleic Acid, Oleth-10, Palm Nucleic Acid, Palmitic Acid, PEG-60 Almond Glycerides, PEG-75 Shea Butter Glycerides, PEG 90M, PEG-10 Dimethicone, PEG-10 Dimethicone / Vinyl Dimethicone Crosspolymer, PEG-10 Rapeseed Sterol, PEG-100 Stearate, PEG-12 Dimethicone, PEG-120 Methyl Glucose Dioleate, PEG-20 Methyl Glucose Sesquistearate, PEG-40 Stearate, PEG-60 Hydrogenated Castor Oil, PEG-7 Glyceryl Cocoate, PEG-8, PEG-80 Sorbitan Laurate, PEG / PPG-17 / 6 Copolymer (Polyethylene Glycol / Polypropylene glycol-17 / 6 copolymer), PEG / PPG-18 / 18 dimethicone, PEG / PPG-20 / 15 dimethicone, poloxamer 184, poloxamer 407, poloxamer, polyglyceryl-3 beeswax, polyglyceryl-4 isostearate, polyglyceryl-6 isostearate, polysorbate 20, polysorbate 60, polysorbate 80, potassium cetyl phosphate, potassium hydroxide, potassium myristate, PPG-12 buteth-16, PPG-26 buteth-26, Salvia officinalis, Saponaria officinalis extract, soapwort, C 14~16This may include, but is not limited to, sodium olefin sulfonate, sodium cetearyl sulfate, sodium cocoamphoacetate, sodium cocoate, sodium cocoyl glutamate, sodium cocoyl isethionate, sodium dilauramidoglutamidolyninate, sodium hexametaphosphate, sodium hydroxide, sodium laureth sulfate, sodium laureth-13 carboxylate, sodium lauroamphoacetate, sodium lauroyl lactylate, sodium lauroyl sarcosinate, sodium lauryl glucose carboxylate, sodium lauryl sulfate, sodium cocoyl methyl taurate, sodium methyl taurate, sodium mireth sulfate, sodium palm nucleotide, sodium palmitate, sodium PEG-7 olive oil carboxylate, sodium trideceth sulfate, steareth-20, TEA lauryl sulfate (triethanolamine-lauryl sulfate), and tribehenin PEG-20 ester.

[0065] In certain embodiments, the composition 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 cosmetic products, thereby resulting in greater stability and better performance. While some thickeners also possess emulsifying or gelling properties, the majority of thickeners have the ability to retain moisture in the skin and therefore act as moisturizers. Thickeners may be entirely natural, such as waxes, but may also be synthetic or semi-synthetic. In some embodiments, the thickeners include acacia senegal gum, glyceryl acetylricinoleate, acetylated castor oil, hydrogenated acetylated cottonseed glyceride, acetylated palm kernel glyceride, acrylate / steareth-20 methacrylate copolymer, agar, Ahnfeltia concinna extract, Ahnfeltia extract, Alaria esculenta, algae, algal extract, algin, alkylamides, Althaea rosea, Althea officinalis, alumina, aluminum hydroxide, aluminum stearate, ammonium acryloyldimethyltaurate / VP copolymer, Anacystis nidulans extract, arachidic acid, arachidonic acid, arachidyl alcohol, arachidyl propionate, arrowroot, Artemia extract, Ascophyllum nodosum, ascorbyl methylsilanol pectinate, Asparagopsis Armata extract, beeswax, behenic acid, behentrimonium chloride, behenyl alcohol, bis-diglyceryl polyacyladipate, bismuth oxychloride, C 12~15 Alkylbenzoate, C 12~18 Acid triglycerides, C 13~14 Isoparaffin, C 18~36Triglycerides, Candelilla wax, Caprylic / Capric triglycerides, Carbomer, Carbopol, Carnauba wax, Carrageenan, Caulerpa taxifolia extract, Cellulose, Cellulose gum, Cephalin, Cera Alba, Ceresin, Ceteareth-20, Cetearyl alcohol, Cetearyl ethylhexanoate, Cetearyl glucoside, Cetearyl octanoate, Cetyl alcohol, Cetyl dimethicone copolyol, Cetyl hydroxyethylcellulose, Cetyl palmitate, Cetyl PEG / PPG-10 / 1-dimethicone, Chlorella, Chondrus crispus, Cocamide DEA and MEA, Cocoglycerides, Codium tomentosum extract, Copernicia cerifera wax, Corallina This may include, but is not limited to, officinalis extract, Corallina, oleth-10 phosphate DEA, diethanolamine (DEA), di-PPG-3 myristyl ether adipate, dimethicone crosspolymer, dimethicone / vinyl dimethicone crosspolymer, polyacrylate crosspolymer, and / or dimer dilinoleyl dimer dilinoleate.

[0066] In certain embodiments, the composition of the present invention may further comprise one or more chelators. The chelating agent is one of a number of components that bind to metal ions or metal compounds, preventing them from adhering to surfaces (such as skin, hair, or clothing) or causing contamination, as in the case of trace amounts of iron. In some embodiments, the chelators may include, but are not limited to, tetrasodium EDTA, sodium phytate, and / or tetrahydroxypropylethylenediamine.

[0067] In certain embodiments, the additives included in the composition are: water, dimethyl isosorbide, glycerin, caprylic / capric triglyceride, propanediol, sunflower seed oil, ethoxydiglycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerin / sebacate copolymer, diheptyl succinate, naringenin, lecithin, decylene glycol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidyl alcohol, behenyl alcohol, arachidyl glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olive (Olea europaea) fruit oil, olea The ingredients are europaea (olive) oil unsaponifiables, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, citric acid, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and / or ethylhexylglycerin.

[0068] Tables 3-9 list additives that may be used in exemplary compositions of the present invention, along with their approximate concentrations. [Table 3-1] [Table 3-2] [Table 3-3]

[0069] [Table 4]

[0070] [Table 5-1] [Table 5-2] [Table 5-3]

[0071] [Table 6-1] [Table 6-2]

[0072] [Table 7-1] [Table 7-2]

[0073] [Table 8-1] [Table 8-2]

[0074] [Table 9-1] [Table 9-2]

[0075] Treatment of local conditions

[0076] Advantageously, naringenin has been found to affect genes and signaling pathways involved in several local conditions. In one embodiment, the present invention provides a method of using 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 of the skin, and / or improving the aesthetic appearance of fine lines and / or wrinkles of the skin. In certain embodiments, the compositions of the present invention lead to increased resilience of skin and / or hair. In certain embodiments, the compositions of the present invention lead to increased elasticity of the skin. In certain embodiments, the compositions of the present invention prevent skin damage.

[0077] In one embodiment, the present invention comprises a composition for topical administration comprising an effective amount of naringenin. An effective amount of naringenin is an amount of naringenin that is effective in treating, improving or otherwise affecting the underlying condition of the skin.

[0078] In certain embodiments of the present invention, compositions comprising naringenin exhibit antioxidant activity. In certain embodiments, the antioxidant activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.001 w / w% or higher. In certain embodiments, the antioxidant activity of naringenin in an aqueous medium in the compositions of the present invention is demonstrated at a concentration of about 0.005 w / w% or higher. In certain embodiments, the antioxidant activity of naringenin in an organic solvent in the compositions of the present invention is demonstrated at a concentration of about 0.5 w / w% or higher. Advantageously, compositions of the present invention comprising naringenin exhibiting antioxidant activity are effective in treating and / or preventing oxidative damage. In certain embodiments, compositions of the present invention comprising naringenin exhibiting antioxidant activity are effective in treating skin and / or hair damaged by reactive oxygen species, as well as in protecting the target skin from other environmentally aggressive factors that may cause damage. In certain other embodiments, compositions of the present invention comprising naringenin exhibiting antioxidant activity are effective in preventing skin and / or hair damage caused by reactive oxygen species, including damage caused by environmental aggressive factors.

[0079] As demonstrated by the data provided in Examples 4 and 5, compositions containing naringenin are effective in exhibiting strong antioxidant activity in both aqueous and organic solvent systems. The IC of the antioxidant activity calculated in the aqueous solvent system... 50 The value was 0.0058 w / w%. These results demonstrate that compositions containing naringenin have strong antioxidant activity. In certain embodiments, compositions containing naringenin are useful for treating conditions caused by oxidation or excessive oxidation in the target skin. In certain embodiments, compositions containing naringenin are administered for the treatment and / or prevention of skin or hair damage caused by reactive oxygen species, as well as for protection from environmental aggressive factors.

[0080] In certain embodiments of the present invention, compositions containing naringenin exhibit elastase enzyme inhibition. In certain embodiments, the elastase enzyme inhibitory activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.01 w / w% or higher. In certain embodiments, the elastase enzyme inhibitory activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.02 w / w% or higher. In certain embodiments, the elastase enzyme inhibitory activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.1 w / w% or higher. As is evident from the data provided in Example 6, compositions containing naringenin have strong elastase enzyme inhibitory activity. In fact, the calculated IC for elastase inhibition by compositions containing naringenin 50 The value is 0.159 w / w%.

[0081] Advantageously, compositions containing naringenin exhibiting elastase enzyme inhibitory activity are effective in promoting skin elasticity. In certain embodiments, compositions of the present invention containing naringenin exhibiting elastase enzyme inhibitory activity are effective in reducing fine lines and / or wrinkles of the skin. In certain embodiments, compositions of the present invention containing naringenin exhibiting elastase enzyme inhibitory activity are effective in preventing the formation of fine lines and / or wrinkles of the skin.

[0082] In certain embodiments of the present invention, compositions containing naringenin exhibit glycation inhibition. In certain embodiments, the glycation inhibition activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.001 w / w% or higher. In certain embodiments, the glycation inhibition activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.005 w / w% or higher. In certain embodiments, the glycation inhibition activity of naringenin in the compositions of the present invention is demonstrated at a concentration of about 0.008 w / w% or higher. As is evident from the data provided in Example 7, compositions containing naringenin have strong glycation inhibition. In fact, the IC calculated for glycation inhibition by compositions containing naringenin 50The value is 0.019 w / w%. Advantageously, compositions containing naringenin, which exhibits glycation inhibitory activity, are effective in supporting and promoting the resilience of skin and / or hair.

[0083] In certain embodiments of the present invention, compositions containing naringenin exhibit anti-inflammatory activity. In certain embodiments, compositions containing naringenin exhibit anti-inflammatory activity at concentrations of 0.0001 w / w% or higher. In certain embodiments, compositions containing naringenin exhibit anti-inflammatory activity at concentrations of 0.0045 w / w% or higher. In certain embodiments, the anti-inflammatory activity of naringenin in the compositions of the present invention is demonstrated by a decrease in the anti-inflammatory markers IL-6 and / or TNF-α in stressed keratinocytes. In certain embodiments, the anti-inflammatory activity is demonstrated in human epidermal keratinocytes. Chemokines produced by activated keratinocytes and immune cells can damage skin tissue near the targets of the inflammatory response. Modulation of the immune response is crucial for maintaining skin homeostasis. If that modulation is functioning optimally, the cellular inflammatory response should disrupt skin homeostasis. Advantageously, the anti-inflammatory activity of compositions containing naringenin is beneficial in maintaining skin homeostasis and promoting skin health.

[0084] The data provided in Example 8 demonstrate that compositions containing naringenin have strong anti-inflammatory activity. This data demonstrates that naringenin exhibits anti-inflammatory properties by reducing the inflammatory markers IL-6 and TNFα to non-stress levels in stressed keratinocytes.

[0085] In certain embodiments of the present invention, the composition is a composition comprising naringenin that can be applied to the skin as a mask. Thus, in certain embodiments, the application of the mask results in a refreshed appearance of the skin.

[0086] In certain embodiments, the present invention provides a sunscreen containing naringenin. In certain embodiments, the sunscreen containing naringenin provides all-broad spectrum photoprotection, repairs inflammatory damage, and maintains firmness.

[0087] In certain embodiments, the present invention provides an enhanced eye cream containing naringenin. In certain embodiments, the eye cream provides firmness and moisture to the skin and reduces visible signs of inflammation.

[0088] Modulation of gene expression and / or activity In certain embodiments of the present invention, a composition comprising naringenin modulates the expression of one or more genes related to a local condition. In certain embodiments, administration of a composition comprising naringenin alters one or more functions related to the modulated gene, where one or more functions are selected from the group consisting of (i) altering the appearance of the skin or improving a condition that leads to an undesirable appearance of the skin, (ii) forming fine lines or wrinkles of the skin, (iii) inflammation, (iv) maintaining barrier support, and (v) altering the appearance of the skin by altering cell turnover or cell recycling. In certain embodiments, administration of a composition containing naringenin alters the expression and / or function of one or more genes selected from the group consisting of LCE5A, KRT77, ALOXE3, KRT1, HPGD, MUCL1, CASP14, WFDC12, KRT10, DNASE1L2, IL37, SERPINB12, HAL, UPK1A, CALML5, LCE2B, MIR205, CCL11, CSF2, IL23A, IL11, BMP6, IL13RA2, C2CD4A, NR4A2, C2CD4B, FGF2, FABP4, GDF15, THBS1, HSPA1A, PTGS2, and / or DKK1.

[0089] In certain embodiments, administration of a composition containing naringenin leads to upregulation of LCE5A, KRT77, ALOXE3, KRT1, HPGD, MUCL1, CASP14, WFDC12, KRT10, DNASE1L2, IL37, SERPINB12, HAL, UPK1A, CALML5, LCE2B, and / or MIR205. In certain embodiments, administration of a composition containing naringenin leads to downregulation of CCL11, CSF2, IL23A, IL11, BMP6, IL13RA2, C2CD4A, NR4A2, C2CD4B, FGF2, FABP4, GDF15, THBS1, HSPA1A, PTGS2, and / or DKK1. Tables 10 and 11 provide data on the upregulation and downregulation of certain genes after administration of a composition containing 1% naringenin, respectively. [Table 10-1] [Table 10-2]

[0090] [Table 11-1] [Table 11-2]

[0091] In certain embodiments of the present invention, administration of a composition containing naringenin enhances anti-inflammatory activity. In certain embodiments, administration of a composition containing naringenin enhances anti-inflammatory activity because it leads to the downregulation of CSF2, IL23A, IL11, IL13RA2, C2CD4A, NR4A2, FABP4, GDF15, and / or PTGS2. In certain embodiments, administration of a composition containing naringenin enhances anti-inflammatory activity because it leads to the upregulation of HPGD.

[0092] Granulocyte-macrophage colony-stimulating factor (CSF2) plays a role in inflammation and arthritis. In certain embodiments of the present invention, downmodulation of CSF2 leads to anti-inflammatory and / or anti-arthritis activity. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of CSF2 expression and / or activity to at most about 1 / 10 to about 1 / 20. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of CSF2 expression and / or activity to at most about 1 / 15. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downmodulation of CSF2 expression and / or activity to about 1 / 18.

[0093] Interleukin 23A (IL23A) plays a role in inflammatory pathways. In certain embodiments of the present invention, downmodulation of IL23A leads to anti-inflammatory activity. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of IL23A expression and / or activity to at most about 1 / 10 to about 1 / 20. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of IL23A expression and / or activity to at most about 1 / 15. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downmodulation of IL23A expression and / or activity to about 1 / 18.

[0094] Interleukin-11 (IL-11) plays a role in certain inflammatory pathways and pathways that may be involved in cancer. In certain embodiments of the present invention, downmodulation of IL-11 leads to anti-inflammatory and / or anticancer activity. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of IL-11 expression and / or activity to at most about 1 / 10 to about 1 / 20. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of IL-11 expression and / or activity to at most about 1 / 10. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downmodulation of IL-11 expression and / or activity to about 1 / 14.

[0095] Interleukin-13 receptor subunit alpha-2 (IL13RA2) plays a role in recovery after inflammatory responses induced by stressors. In certain embodiments, downmodulation of IL13RA2 leads to improved recovery after stressor-induced inflammation. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of IL13RA2 expression and / or activity to at most about 1 / 5 to about 1 / 15. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of IL13RA2 expression and / or activity to at most about 1 / 10. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downmodulation of IL13RA2 expression and / or activity to about 1 / 10.

[0096] C2 calcium-dependent domain-containing 4B (C2CD4B) plays a role in the inflammatory response. In certain embodiments, downmodulation of C2CD4B results in a reduction of inflammation. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of C2CD4B expression and / or activity to at most about 1 / 5 to about 1 / 15. In certain embodiments, administration of a composition containing naringenin results in a downmodulation of C2CD4B expression and / or activity to at most about 1 / 10. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downmodulation of C2CD4B expression and / or activity to about 1 / 8.

[0097] Nuclear receptor subfamily 4 group A member 2 (NR4A2) plays a role in inflammatory responses. In certain embodiments, downmodulation of NR4A2 results in reduced inflammation. In certain embodiments, administration of a composition containing naringenin results in downmodulation of NR4A2 expression and / or activity to as much as about 1 / 5 to about 1 / 15. In certain embodiments, administration of a composition containing naringenin results in downmodulation of NR4A2 expression and / or activity to as much as about 1 / 10. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in downmodulation of NR4A2 expression and / or activity to as much as about 1 / 9.

[0098] Fatty acid-binding protein 4 (FABP4) plays a role in metabolic inflammation from adipose tissue. FABP4 acts at the interface of metabolic and inflammatory pathways in adipocytes and macrophages, playing a crucial role in the development of insulin resistance, diabetes mellitus, and atherosclerosis. In certain embodiments, downregulation of FABP4 leads to a reduction in metabolic inflammation from adipose tissue signaling. In certain embodiments, administration of a composition containing naringenin results in a downregulation of FABP4 expression and / or activity to at most about 2 to about 1 / 10. In certain embodiments, administration of a composition containing naringenin results in a downregulation of FABP4 expression and / or activity to at most about 1 / 5. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downregulation of FABP4 expression and / or activity to about 1 / 7.

[0099] Growth and differentiation factor 15 (GDF15) plays a role in the inflammatory response. In certain embodiments, downregulation of GDF15 results in a reduction of inflammation. In certain embodiments, administration of a composition containing naringenin results in a downregulation of GDF15 expression and / or activity to at most about 2 to about 1 / 10. In certain embodiments, administration of a composition containing naringenin results in a downregulation of GDF15 expression and / or activity to at most about 1 / 5. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downregulation of GDF15 expression and / or activity to about 1 / 6.

[0100] Prostaglandin-endoperoxide synthase 2 (PTGS2) plays a role in the production of signaling molecules involved in inflammatory responses. For example, PTGS2 is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of prostacyclins expressed in inflammation. In certain embodiments, downregulation of PTGS2 leads to a decrease in the production of signaling molecules that lead to inflammation. Therefore, downregulation of PTGS2 leads to a reduction in inflammation. In certain embodiments, administration of a composition containing naringenin results in a downregulation of PTGS2 expression and / or activity to at most about 2 to about 1 / 10. In certain embodiments, administration of a composition containing naringenin results in a downregulation of PTGS2 expression and / or activity to at most about 1 / 5. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in a downregulation of PTGS2 expression and / or activity to about 1 / 6.

[0101] Hydroxyprostaglandin dehydrogenase (HPGD) has anti-inflammatory properties. In particular, it is involved in the degradation of molecules that lead to inflammatory signaling. For example, HPGD is involved in the degradation of prostaglandins involved in inflammatory signaling pathways. In certain embodiments, upmodulation of HPGD expression and / or activity leads to an anti-inflammatory effect. In certain embodiments, upmodulation of HPGD leads to increased degradation of signaling molecules involved in inflammation. Therefore, upmodulation of HPGD leads to a reduction in inflammation. In certain embodiments, administration of a composition containing naringenin results in an upmodulation of HPGD expression and / or activity by at least about 5 to about 20 times. In certain embodiments, administration of a composition containing naringenin results in an upmodulation of HPGD expression and / or activity by at least about 10 times. The data provided in Table 6 demonstrate that administration of a composition containing 1% naringenin results in an upmodulation of HPGD expression and / or activity by about 10 times.

[0102] In certain embodiments of the present invention, administration of a composition containing naringenin enhances the maintenance of skin barrier strength and / or skin barrier lipids. In certain embodiments, administration of a composition containing naringenin enhances the maintenance of skin barrier strength and / or skin barrier lipids because it leads to the upregulation of LCE5A, KRT77, ALOXE3, KRT1, CASP14, KRT10, and / or LCE2B.

[0103] Late cornified envelope protein 5A (LCE5A) is involved in the formation of the protective barrier of the outer skin. LCE5A may also be involved in keratinization. In certain embodiments, upregulation of LCE5A expression and / or activity results in improved formation of the protective barrier of the outer skin. Therefore, administration of a composition containing naringenin that leads to upregulation of LCE5A results in increased skin barrier strength. In certain embodiments, administration of a composition containing naringenin results in at least about 20 to about 50-fold upregulation of LCE5A expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about 25-fold upregulation of LCE5A expression and / or activity. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in about 33-fold upregulation of LCE5A expression and / or activity.

[0104] Keratin 77 (KRT77) is involved in keratin production. In particular, KRT77 encodes epithelial keratin expressed in the skin and eccrine sweat glands. KRT77 encodes keratin 77, a member of the type II keratin family of intermediate filament proteins. Keratin 77 is also known as KRT1B, type II cytoskeleton 1b, type II keratin Kb39, and cytokeratin 1B. In certain embodiments, upregulation of KRT77 expression and / or activity results in enhanced keratin production. Increased keratin production contributes to increased skin barrier strength. In certain embodiments, administration of a composition containing naringenin results in at least about 5 to about 20-fold upregulation of KRT77 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about 10-fold upregulation of KRT77 expression and / or activity. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in approximately 12-fold upregulation of KRT77 expression and / or activity.

[0105] Arachidonic acid lipoxygenase 3 (ALOXE3) is involved in the formation of epidermal lipids. Specifically, ALOXE3 helps produce substances called fatty acid hydroperoxides by adding oxygen molecules to certain fatty acids. The enzyme encoded by ALOXE3 is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR alpha), which is involved in epidermal differentiation. Loss of function of the enzyme encoded by this gene leads to ichthyosis, which implies that this gene plays a role in human skin differentiation. ALOXE3 also helps prevent water loss from the skin. In certain embodiments, administration of a composition containing naringenin results in an upmodulation of ALOXE3, which plays a role in enhancing skin barrier support. In certain embodiments, administration of a composition containing naringenin results in an upmodulation of at least about 5 to about 20 times the expression and / or activity of ALOXE3. In certain embodiments, administration of a composition containing naringenin results in an upmodulation of at least about 10 times the expression and / or activity of ALOXE3. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in an upmodulation of about 12 times the expression and / or activity of ALOXE3.

[0106] Keratin 1 (KRT1) plays a role in maintaining skin strength and resilience. Keratin 1 is produced in keratinocytes in the outer layer of skin (epidermis), including the skin of the palms of the hands and soles of the feet. The keratin 1 protein works in cooperation with either another keratin protein, either keratin 9 or keratin 10, to form molecules called keratin intermediate filaments. These filaments provide strength and resilience to the skin, building a strong network that protects the skin from damage caused by friction and other everyday physical stresses. In certain embodiments, administration of a composition containing naringenin results in an upregulation of KRT1, which plays a role in enhancing skin strength and resilience. In certain embodiments, administration of a composition containing naringenin results in an upregulation of KRT1 expression and / or activity by at least about 2 to about 15 times. In certain embodiments, administration of a composition containing naringenin results in an upregulation of KRT1 expression and / or activity by at least about 5 times. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in approximately seven-fold upregulation of KRT1 expression and / or activity.

[0107] Cysteine-aspartate protease 14 (CASP14) plays a crucial role in the terminal differentiation of keratinocytes, which are essential for skin barrier formation. In certain embodiments, administration of a composition containing naringenin leads to upmodulation of CASP14. In certain embodiments, this upmodulation of CASP14 leads to improved skin barrier formation. In certain embodiments, administration of a composition containing naringenin results in at least about 5 to about 20-fold upmodulation of CASP14 expression and / or activity. In certain embodiments, administration of a composition containing naringenin results in at least about 10-fold upmodulation of CASP14 expression and / or activity. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in about 11-fold upmodulation of CASP14 expression and / or activity.

[0108] Keratin 10 (KRT10) is also involved in keratin production. Keratin is involved in increasing the barrier strength and resilience of the skin. Keratin 10 is produced in keratinocytes in the outer layer of the skin (epidermis). In the fluid-filled space (cytoplasm) within these cells, the keratin 10 protein works in cooperation with a similar protein, keratin 1 (produced from the KRT1 gene), to form molecules called keratin intermediate filaments. These filaments provide strength and resilience to the skin, building a robust network that protects the skin from damage caused by friction and other everyday physical stresses. In certain embodiments, administration of a composition containing naringenin results in an upregulation of KRT10, which plays a role in enhancing skin strength and resilience. In certain embodiments, administration of a composition containing naringenin results in an upregulation of KRT10 expression and / or activity by at least about 2 to about 15 times. In certain embodiments, administration of a composition containing naringenin results in at least approximately 5-fold upregulation of KRT10 expression and / or activity. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in approximately 6-fold upregulation of KRT10 expression and / or activity.

[0109] Late keratinization envelope 2B (LCE2B) plays a role in the formation of precursors of the keratinization envelope of the stratum corneum. It also leads to improved formation of the protective barrier of the outer skin. In certain embodiments, administration of a composition containing naringenin results in upregulation of LCE2B, which plays a role in enhancing the protective barrier of the outer skin. In certain embodiments, administration of a composition containing naringenin results in upregulation of LCE2B expression and / or activity by at least about 5 to about 20 times. In certain embodiments, administration of a composition containing naringenin results in upregulation of LCE2B expression and / or activity by at least about 5 times. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in upregulation of LCE2B expression and / or activity by about 9 times.

[0110] In certain embodiments of the present invention, administration of a composition containing naringenin leads to enhanced cell turnover and / or cell recycling. Beneficially, this enhanced cell turnover and / or cell recycling leads to an anti-aging effect. In certain embodiments, the anti-aging effect may be demonstrated by a reduction and / or prevention of the formation of fine lines and / or wrinkles in the skin. In certain embodiments, administration of a composition containing naringenin enhances cell turnover and / or cell recycling in the skin because the administration of the composition leads to the upregulation of DNASE1L2, SERPINB12, UPK1A, CALML5 and / or MIR205. In certain embodiments, administration of a composition containing naringenin enhances cell turnover and / or cell recycling in the skin because the administration of the composition leads to the downregulation of BMP6 and / or HSPA1A.

[0111] Deoxyribonuclease-1-like 2 (DNASE1L2) plays a role in recycling dying cells. Hair, nails, and the keratinized layer of the epidermis, i.e., the stratum corneum, consist of keratinocytes, also known as corneocytes. The process of keratinization involves cross-linking of structural proteins, leading to high mechanical stability of corneocytes, which, along with the formation of stable desmosome links between cells, is essential for the epidermal structure to resist environmental stress. DNASE1L2 is a keratinocyte-specific DNase. DNASE1L2 leads to keratinization of the interfollicular epidermis, while simultaneously causing nuclear degradation in skin appendages and individual epithelium. Therefore, DNASE1L2 plays a crucial role in cell recycling and turnover in the skin. In certain embodiments, administration of a composition containing naringenin leads to upregulation of DNASE1L2, which plays a role in improving the recycling of dying cells and increasing cell turnover / recycling. In certain embodiments, administration of a composition containing naringenin results in an upregulation of DNASE1L2 expression and / or activity by at least about 5 to about 20 times. In certain embodiments, administration of a composition containing naringenin results in an upregulation of DNASE1L2 expression and / or activity by at least about 5 times. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in an upregulation of DNASE1L2 expression and / or activity by about 9 times.

[0112] Serine protease inhibitors (SERPINB12) play a role in the protection of epithelial cells. Intracellular serine protease inhibitors (serpines) are an important family of proteins that protect cells from protease-mediated damage. SERPINB12 is widely expressed and is likely to protect cells, including epithelial cells, from both endogenous and exogenous peptidases. In certain embodiments, compositions containing naringenin lead to upregulation of SERPINB12, which leads to increased protection of epithelial cells. In certain embodiments, administration of a naringenin-containing composition results in an upregulation of SERPINB12 expression and / or activity by at least about 5 to about 20 times. In certain embodiments, administration of a naringenin-containing composition results in an upregulation of SERPINB12 expression and / or activity by at least about 10 times. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in an upregulation of SERPINB12 expression and / or activity by about 13 times.

[0113] Uroplakin 1A (UPK1A) is involved in cell proliferation. Proteins of this family mediate signaling events that play a role in regulating cell development, activation, proliferation, and motility. This encoded protein is found in the asymmetrical unit membrane (AUM), where it can form complexes with other transmembrane 4 superfamily proteins. UP1A may play a role in normal bladder epithelial physiology, possibly in regulating the membrane permeability of superficial umbrella cells, or in stabilizing the apical membrane via AUM / cytoskeleton interactions. In certain embodiments, compositions containing naringenin lead to upregulation of UPK1A, which leads to increased cell proliferation, including cells in the skin and its underlying tissues. In certain embodiments, this exhibits an anti-aging effect. In certain embodiments, administration of compositions containing naringenin results in at least about 5 to about 20-fold upregulation of UPK1A expression and / or activity. In certain embodiments, administration of compositions containing naringenin results in at least about 10-fold upregulation of UPK1A expression and / or activity. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in approximately a 10-fold upregulation of UPK1A expression and / or activity.

[0114] Calmodulin-like 5 (CALML5) plays a role in cell growth. The enzyme encoded by CALML5 is a novel calcium-binding protein expressed in the epidermis and is related to the calmodulin family of calcium-binding proteins. CALML5 plays a crucial role in cell growth and proliferation, including a critical role in the terminal differentiation of keratinocytes. In certain embodiments, administration of a composition containing naringenin leads to an upregulation of CALML5, which leads to increased cell proliferation, including cells in the skin and its underlying tissues. In certain embodiments, this exhibits an anti-aging effect. In certain embodiments, administration of a composition containing naringenin results in an upregulation of CALML5 expression and / or activity by at least about 2 to about 10 times. In certain embodiments, administration of a composition containing naringenin results in an upregulation of CALML5 expression and / or activity by at least about 5 times. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in an upregulation of CALML5 expression and / or activity by about 7 times.

[0115] MicroRNA205 (MIR205) plays a role in the clearance of damaged cells. In certain embodiments, administration of a composition containing naringenin leads to an upregulation of MIR205, which in turn leads to an increase in the clearance of damaged cells. This increase in the clearance of damaged cells leads to enhanced cell turnover and / or recycling, which results in an improved anti-aging effect. Therefore, in certain embodiments, this exhibits an anti-aging effect. In certain embodiments, administration of a composition containing naringenin results in an upregulation of MIR205 expression and / or activity by at least about 2 to about 10 times. In certain embodiments, administration of a composition containing naringenin results in an upregulation of MIR205 expression and / or activity by at least about 5 times. The data provided in Table 10 demonstrate that administration of a composition containing 1% naringenin results in an upregulation of MIR205 expression and / or activity by about 6 times.

[0116] Osteogenic protein 6 (BMP6) plays a role in wound healing. The protein encoded by this gene is a member of the TGFβ superfamily. Osteogenic proteins are known to have the ability to induce bone and cartilage growth. BMP6 can induce all osteogenic markers in mesenchymal stem cells. In certain embodiments, administration of a composition containing naringenin leads to a downregulation of BMP6 expression and / or activity. This results in a reduction of scarring in wound healing. In certain embodiments, this may also lead to an anti-aging effect on the skin. In certain embodiments, administration of a composition containing naringenin results in a downregulation of BMP6 expression and / or activity to as much as about 2 to as much as 1 / 20. In certain embodiments, administration of a composition containing naringenin results in a downregulation of BMP6 expression and / or activity to as much as about 1 / 10. The data provided in Table 11 demonstrate that administration of a composition containing 1% naringenin results in a downregulation of BMP6 expression and / or activity to as much as 1 / 11.

[0117] The heat shock protein family A (Hsp70) member 1A (HSPA1A) plays a role in the removal of senescent cells and / or senescent cell decongestant effects. In certain embodiments, administration of a composition containing naringenin leads to a downregulation of HSPA1A expression and / or activity. This results in increased clearance of senescent cells. In certain embodiments, this may also lead to an anti-aging effect on the skin. In certain embodiments, administration of a composition containing naringenin results in a downregulation of HSPA1A expression and / or activity to as much as about 2 to as much as 1 / 10. In certain embodiments, administration of a composition containing naringenin results in a downregulation of HSPA1A expression and / or activity to as much as about 1 / 5. The data provided in Table 11 demonstrate that administration of a composition containing 1% naringenin results in a downregulation of HSPA1A expression and / or activity to as much as 1 / 6.

[0118] In certain embodiments, administration of a composition containing naringenin to a subject leads to the treatment or prevention of a local condition in the subject by modulating the level of expression or activity of one or more genes that may be involved in the local condition. In certain embodiments, administration of a composition containing naringenin alters one or more functions associated with the modulated gene, where one or more functions are selected from the group consisting of (i) cell turnover, (ii) inflammation, (iii) barrier support, and (iv) any combination thereof.

[0119] Treatment of local conditions The present invention recognizes that compositions containing naringenin are beneficial for treating, protecting, and / or improving the condition and / or aesthetic appearance of the skin. For example, compositions of the present invention may be effective in altering the aesthetic appearance of skin associated with or affected by fine lines and / or wrinkles caused, for example, cellular aging, environmental damage, or skin sunstroke, or in treating or preventing such fine lines and / or wrinkles on such skin. The present invention also provides methods for stimulating skin cell regeneration, increasing cell or tissue regeneration, promoting fibroblast proliferation, synthesizing elastin, collagen, proteoglycans, and / or new connective tissue, thereby reducing or improving the appearance of wrinkles and restoring skin elasticity, resilience, and / or suppleness.

[0120] The compositions of the present invention provided herein may be useful in improving the aesthetic appearance of the skin. Such improvements may include, but are not limited to, any externally visual and tactilely perceptible signs of skin aging and damage, as well as all other macro or micro effects. Such signs and effects may be induced or caused by internal and / or external factors, such as natural aging, environmental damage, climate, sun (UV) exposure, smoking, drugs, alcohol consumption, jet lag, night shifts, changes in circadian rhythms, pregnancy, menopause, genetic factors, nutritional factors and / or malnutrition, dehydration, stress, allergies (e.g., to plants, animals, drug therapy, and other substances), exposure to industrial and / or household chemicals, indoor heating and cooling, various disorders and diseases such as arteriosclerosis, diabetes, heart disease, liver disease, and obesity, thinning of the outer layer of skin, decrease in the number of pigment-containing cells, increase in the size of pigment-containing cells, changes in connective tissue, and decreased strength and elasticity of the skin.

[0121] The aesthetic appearance of the skin can be improved by improving the appearance of skin associated with or affected by one or more of the following: wrinkles, dry skin, sensitive skin, sagging, acne, vitiligo (a skin condition in which brown (pigmentation) is lost from certain areas of the skin), fine lines, sagging skin, dermal thinning, collagen fiber breakdown, loose skin, thinned skin, and skin exposed to ultraviolet radiation. In some embodiments, compositions of the present invention can improve the aesthetic appearance of the skin by reducing the appearance of fine lines on the skin, creating a more youthful skin appearance, reducing bag and / or ring around the eyes, increasing or repairing skin elasticity, resilience and / or suppleness, increasing the apparent thickness, elasticity, flexibility, radiance, glow and plumpness of the skin, improving skin texture, improving the appearance of wrinkled, linear, dry, scaly, aged 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 skin pigmentation (e.g., caused by UV exposure), reducing the appearance of skin discoloration, and lightening and / or decolorizing the skin.

[0122] In certain embodiments, the composition can be used in facial or body skin care, treatment, cleansing, and / or protective products, anti-wrinkle or anti-aging compositions, skin-tightening compositions, skin-whitening compositions, compositions for rough skin, sunscreen compositions, self-tanning compositions or after-sun care compositions, scalp care compositions, shaving preparation compositions, hair removal compositions, or makeup products for facial or body skin.

[0123] In certain embodiments, compositions comprising naringenin are administered to alter the aesthetic appearance of skin associated with or affected by skin conditions / disorders (e.g., skin conditions / disorders involving loss of skin elasticity), or to treat or prevent such skin conditions / disorders.

[0124] In certain embodiments, compositions containing naringenin are administered to improve the skin's barrier function and viability.

[0125] In certain embodiments, a composition comprising naringenin is administered to alter the aesthetic appearance of skin associated with or affected by wrinkles, sagging, and / or loss of skin elasticity.

[0126] In certain embodiments, compositions containing naringenin are administered to alter the aesthetic appearance of skin related to or affected by the deterioration of skin viscoelasticity.

[0127] In certain embodiments, compositions comprising naringenin are administered to alter the aesthetic appearance of skin associated with or affected by one or more of the following: wrinkles and / or fine lines, sagging skin, loss of skin elasticity and / or tension, thinning of the dermis, breakdown of collagen fibers, sagging skin, thinned skin, and internal deterioration of the skin after exposure to ultraviolet radiation.

[0128] In certain embodiments, a composition containing naringenin is administered to reduce the appearance of fine lines and / or wrinkles on the skin.

[0129] In certain embodiments, a composition containing naringenin is administered to reduce the appearance of sagging and / or dark circles around the eyes.

[0130] In certain embodiments, a composition containing naringenin is administered to reduce the appearance of hyperpigmentation.

[0131] In certain embodiments, a composition containing naringenin is administered to improve or increase one or more of the thickness, elasticity, flexibility, radiance, luster, and fullness of the skin.

[0132] In certain embodiments, a composition containing naringenin is administered to improve the texture of the skin.

[0133] In certain embodiments, compositions comprising naringenin are administered to improve the appearance of wrinkled, fringed, dry, scaly, aged, or photodamaged skin.

[0134] In certain embodiments, a composition containing naringenin is administered to alter the aesthetic appearance of skin that is related to or affected by skin discoloration.

[0135] Method of administration In one embodiment, the present invention provides a method for administering a composition containing naringenin. In a particular embodiment, the composition of the present invention is designed for topical administration.

[0136] In certain embodiments, the compositions of the present invention can be administered to the target skin as topical compositions. The compositions of the present invention may be included in any formulation suitable for topical administration. In certain embodiments, the compositions of the present invention may be fluids, emulsions, capsules, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, emulsions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, colored cosmetics, and / or hair treatments.

[0137] In certain other embodiments, compositions comprising naringenin may be prepared and used in the form of aerosol sprays, creams, emulsions, solids, liquids, dispersions, foams, oils, gels, lotions, mousses, ointments, powders, patches, pomades, solutions, pump sprays, sticks, wet wipes (towelettes), soaps, or other forms commonly used in the field of topical administration and / or cosmetic and skincare formulations. The compositions may also be in emulsion form. In addition, the compounds provided herein for use in the compositions provided herein may be used in colored cosmetic compositions such as foundation makeup, blush, eyeshadow, mascara, concealer, eyeliner, lip color, and nail color. Other cosmetic compositions may include perfumes, lipsticks, manicures and pedicures, eye makeup and face makeup, wet wipes, deodorants, hand sanitizers, baby products, bath oils, bubble baths, and butters.

[0138] In a particular embodiment, the composition containing naringenin is approximately 1.0 μg / cm³ 2 ~Approx. 100μg / cm 2 It is administered to the area.

[0139] In certain embodiments, the composition containing naringenin is administered over a period of time until the desired effect in improving or preventing a local condition is achieved. In certain embodiments, the composition containing naringenin contains an effective amount of naringenin. An effective amount of naringenin is the amount of naringenin that produces the desired result in the condition of the skin. In certain embodiments, the composition containing naringenin is administered once daily. In certain embodiments, the composition containing naringenin is administered twice daily. In certain embodiments, the composition containing naringenin is administered three times daily. In certain embodiments, the composition containing naringenin is administered once every two days. In certain embodiments, the composition containing naringenin is administered once every three days. [Examples]

[0140] (Example 1) Exemplary composition containing naringenin Table 12 provides exemplary formulations of naringenin. [Table 12-1] [Table 12-2]

[0141] (Example 2) Exemplary composition containing naringenin Table 13 provides another exemplary formulation of naringenin. [Table 13-1] [Table 13-2]

[0142] (Example 3) Exemplary composition containing naringenin Table 14 provides another exemplary formulation of naringenin. [Table 14-1] [Table 14-2]

[0143] (Example 4) ABTS Antioxidant Assay The 2,2'-azinobis[3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) antioxidant assay is designed to evaluate the antioxidant activity of naringenin-containing compositions in an aqueous medium. An ABTS+ solution is prepared as a free radical and used to measure the relative ability of the compound to capture free radicals. The decrease in absorbance at 734 nm was standardized against a solvent control as an indicator of ABTS+ capture. Table 15, provided below, shows the results from these experiments. [Table 15]

[0144] As is evident from the results provided in Table 15 above, compositions containing naringenin exhibit antioxidant activity at a low concentration of 0.001 w / w% in aqueous systems. Calculated IC 50 The value is 0.0058 w / w%.

[0145] (Example 5) DPPH Antioxidant Activity Assay The 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant assay is designed to evaluate the antioxidant activity of naringenin-containing compositions in organic media.

[0146] 2,2-diphenyl-1-picrylhydrazyl (DPPH) is a stable free radical used to evaluate the free radical scavenging ability of materials. DPPH is reduced in the presence of an antioxidant, thereby forming a colorless solution. The decrease in absorbance at 517 nm is standardized against a solvent control as an indicator of DPPH scavenging.

[0147] Table 16, provided below, provides antioxidant activity data. [Table 16]

[0148] As is evident from the results provided in Table 16 above, compositions containing naringenin exhibit antioxidant activity at a low concentration of 0.2 w / w% in organic solvent systems.

[0149] (Example 6) Elastase enzyme inhibition This assay was performed to evaluate the elastase enzyme inhibitory activity of compositions containing naringenin.

[0150] Neutrophil infiltration and neutrophil elastase both increase in the skin in response to UV stress. Neutrophil elastase has been shown to activate MMP-1 and MMP-2 collagenases in response to low-dose UV exposure, damaging the extracellular matrix and contributing to photoaging and wrinkle formation. Elastase activity may be further upregulated in the presence of reactive oxygen species. Therefore, inhibition of this enzyme, especially in combination with antioxidant activity, is effective in delaying wrinkle formation and helping to maintain skin integrity. This assay can quantify 4-nitroaniline release from Me-Suc-Ala-Ala-Pro-Val-pNA by human neutrophil elastase at 405 nm by comparing it with a solvent control. Table 17 shows the elastase inhibitory activity of compositions containing naringenin. [Table 17]

[0151] As is evident from the data provided in Table 17, compositions containing naringenin inhibit elastase enzyme activity at a low concentration of 0.02 w / w%. Calculated IC 50 The value is 0.159 w / w%.

[0152] (Example 7) Glycation inhibition assay This assay was performed to evaluate the glycation inhibitory activity of compositions containing naringenin.

[0153] Non-enzymatic glycation can occur when glucose reacts with proteins to form Schiff base intermediates, which then undergo Amadori rearrangement to form glycated proteins, which react with skin proteins to form advanced glycation end products (AGEs). AGE formation can lead to loss of skin elasticity and damage to cellular function. The glycation inhibitory activity of a compound is measured by the change in fluorescence m relative to a solvent control.

[0154] Table 18 provides data on glycation inhibition. [Table 18]

[0155] As is evident from the data provided in Table 18, compositions containing naringenin inhibit glycation at a low concentration of 0.002 w / w%. The calculated IC for glycation inhibition 50 The value is 0.019%.

[0156] (Example 8) Preclinical assay for measuring anti-inflammatory activity This example provides data on anti-inflammatory properties by demonstrating that the inflammatory markers IL-6 and TNFα in stressed keratinocytes are reduced to non-stress levels. Normal human epidermal keratinocytes (NHEKs) were stressed with a cocktail of lipopolysaccharide (LPS) and polyinosinate-polycytidylate sodium salt (Poly:IC), which are external attack factors that can induce an inflammatory response. Subsequently, the stressed cells were treated with the test substance, and the reduction in inflammatory markers was measured by ELISA. Tables 19 and 20, provided below, disclose data on TNFα and IL-6 concentrations in stressed normal human epidermal keratinocytes, respectively. [Table 19]

[0157] [Table 20]

[0158] As is evident from the data provided in Tables 19 and 20, compositions containing naringenin exhibit robust anti-inflammatory activity.

[0159] (Example 9) Sun protection This assay was performed to evaluate the sun protection index (SPF) activity of compositions containing naringenin. The table below provides a comparison of in vitro SPF values ​​between sunscreen formulations and formulations containing naringenin. [Table 21]

[0160] (Example 11) Clinical trials

[0161] This example provides a placebo-controlled, double-blind study with 30 participants per group. Participants use the product twice daily, and skin characteristics are measured at T0, 4 weeks, and 8 weeks. The data from the test is provided in Figure 1 and summarized below. The data provided is as follows: • 97% of the panelists showed improvement in fine lines / wrinkles, compared to only 52% of the panelists who received a placebo. • 97% of the panelists showed improvement in deep wrinkles, compared to only 70% of the panelists who received a placebo. • 88% of the panelists showed improvement in skin redness, compared to 70% of the panelists who received a placebo. • 100% of the panelists showed improvement in skin hydration, compared to only 70% of the panelists who received a placebo. • 100% of the panelists showed improvement in skin elasticity, compared to 48% of the panelists who received a placebo.

[0162] These results demonstrate that formulations containing naringenin clinically prove to help moisturize and improve skin elasticity in 8 weeks, while also reducing the appearance of fine wrinkles in just 4 weeks. (Example 12) Exemplary composition containing naringenin Table 22 provides exemplary formulations of naringenin. [Table 22-1] [Table 22-2]

[0163] (Example 13) Exemplary sunscreen formulations Table 23 provides exemplary formulations of naringenin. [Table 23-1] [Table 23-2]

[0164] (Example 14) Exemplary cream formulation Table 24 provides exemplary formulations of naringenin. [Table 24-1] [Table 24-2]

[0165] (Example 14) Example night mask formulation Table 25 provides exemplary formulations of naringenin. [Table 25]

[0166] Embedding by reference Throughout this disclosure, references and citations are made to other documents, including patents, patent applications, patent publications, articles, books, papers, web content, and publicly available databases. All such documents are incorporated herein by reference in their entirety for any purpose.

[0167] Equal parts In addition to those shown and described herein, various modifications of the invention and many further embodiments will be apparent to those skilled in the art from the entirety of this document, including references to the scientific and patent documents cited herein. The subject matter of this specification includes important information, examples, and guidance that can be adapted to the practice of the invention in various embodiments and equivalents of the invention.

Claims

1. A composition for topical administration containing an effective amount of naringenin.

2. The composition according to claim 1, comprising an emulsion.

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

4. The composition according to claim 1, further comprising a solvent.

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

6. The composition according to claim 4, wherein the solvent is selected from the group consisting of dimethyl isosorbide, ethoxydiglycol, lauroyl sarcosinate isopropyl, glycol, and any combination thereof.

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

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

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

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

11. The composition according to claim 10, wherein the glycol is selected from the group consisting of pentylene glycol, butylene glycol, and any combination thereof.

12. The composition according to claim 4, wherein the solvent is selected from the group consisting of phenylpropanol, 1,2-hexanediol, propanediol, isopentyldiol, 1,2-heptanediol, and any combination thereof.

13. The composition according to claim 1, which is stable under ambient conditions for at least two years of storage.

14. The composition according to claim 1, which is stable under ambient conditions for at least one year of storage.

15. The composition according to claim 1, which is stable under ambient conditions for at least six months of storage.

16. The composition according to claim 1, which is stable under ambient conditions for at least three months of storage.

17. The composition according to claim 1, which exhibits less than 10% decomposition when stored at 70°C for one month.

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

19. The composition according to claim 1, wherein naringenin is present in a concentration of about 0.0001 w / w% to about 1.0 w / w%.

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

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

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

23. The composition according to claim 1, wherein naringenin is present at a concentration of about 0.45 w / w%.

24. The composition according to claim 1, selected from the group consisting of fluids, emulsions, capsules, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, emulsions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, colored cosmetics, hair treatments, and any combination thereof.

25. The composition according to claim 1, further comprising one or more additives selected from the group consisting of solvents, emulsifiers, preservatives, antioxidants, emollients, thickeners, penetration enhancers, surfactants, diluents, fillers, carriers, and / or pH control agents.

26. The composition according to claim 25, wherein the preservative is an antimicrobial preservative or a chelating agent.

27. Water, Dimethyl Isosorbide, Glycerin, Caprylic / Capric Triglyceride, Propanediol, Sunflower Seed Oil, Ethoxydiglycol, Squalane, Sodium Acrylate Copolymer, Cetearyl Alcohol, Phenoxyethanol, Glyceryl Stearate, Capryloyl Glycerin / Sebacate Copolymer, Diheptyl Succinate, Naringenin, Lecithin, Decylene Glycol, Pentylene Glycol, Cetearyl Glucoside, Shea Butter, Palmitic Acid, Arachidyl Alcohol, Behenyl Alcohol, Arachidyl Glucoside, Phenethyl Alcohol, 1,2-Hexanediol, Hydrogenated Olive Oil, Olea Europaea (Olive) Fruit Oil, Olea The composition according to claim 1, further comprising one or more additives selected from the group consisting of europaea (olive) oil unsaponifiables, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, citric acid, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and ethylhexylglycerin.

28. Water, Glycerin, Niacinamide, Squalane, C １４～２２ Alcohol, oil, ethoxydiglycol, propanediol, caprylyl glyceryl ether, lauroyl lysine, panthenol, butylene glycol, C １２～２０ Alkyl glucoside, polyacrylate crosspolymer-6, caprylic / capric triglyceride, caprylhydroxamic acid, shea butter, cetearyl alcohol, palmitic acid, sodium phytate, pentylene glycol, allantoin, hedychium The composition according to claim 1, further comprising one or more additives selected from the group consisting of coronarium root extract, acacia senegal gum, xanthan gum, citric acid, arachidyl alcohol, arachidyl glucoside, behenyl alcohol, hydrogenated olive oil, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, date seed, acetylated sodium hyaluronate, cetearyl glucoside, olive oil, phenethyl alcohol, sodium hyaluronate, ascorbic acid, aloe leaf juice, t-butyl alcohol, sodium hyaluronate crosspolymer, glucose, sorbitan isostearate, hydrolyzed sodium hyaluronate, myristic acid, stearic acid, ethylhexylglycerin, lauric acid, dextran, and tripeptide-1.

29. Squalane, Cetearyl Alcohol, Caprylic / Capric Triglyceride, C １３～１５ Alkane, seed oil, seed wax, stearyl behenate, C １０～１８ The composition according to claim 1, further comprising one or more additives selected from the group consisting of triglycerides, dimethyl isosorbide, polyhydroxystearic acid, silica, glyceryl caprylate, ceramide, glyceryl behenate, and sodium hyaluronate.

30. Water, Ethoxydiglycol, Caprylic / Capric Triglyceride, Shea Butter, Cetearyl Alcohol, Palmitic Acid, Pentylene Glycol, Propanediol, Hydroxyethyl Acrylate / Sodium Acryloyldimethyl Taurate Copolymer, Hydrogenated Olive Oil, Behenyl Alcohol, Arachidyl Alcohol, Arachidyl Glucoside, Olive Oil, Sodium Phytate, Cetearyl Glucoside, Phenethyl Alcohol, Sorbitan Isostearate, Stearic Acid, Glucose, Myristic Acid, Lauric Acid, Citric Acid, Linoleic Acid, Lecithin, Phytosteryl Canola Glyceride, Oleic Acid, Tocopherol, Triolein, Phospholipids, Sphingolipids, Sodium Citrate, p-Anisic Acid, Plant Sterols, C １３～１５ The composition according to claim 1, further comprising one or more additives selected from the group consisting of alkanes, butylene glycol, glycerin, glyceryl stearate, Alteromanus ferment extract, acetylated sodium hyaluronate, sodium hyaluronate, sodium hyaluronate crosspolymer, hydrolyzed sodium hyaluronate, ethylhexylglycerin, sodium acrylate copolymer, Centella asiatica extract, cetyl alcohol, hydroxyacetophenone, 1,2,hexanediol, caprylyl glycol, and sodium hydroxide.

31. below: Table 26-1 Table 26-2 Table 26-3 The composition according to claim 1.

32. below: Table 27 The composition according to claim 1.

33. below: Table 28-1 Table 28-2 Table 28-3 The composition according to claim 1.

34. below: Table 29-1 Table 29-2 The composition according to claim 1.

35. below: Table 30-1 Table 30-2 The composition according to claim 1.

36. below: Table 31-1 Table 31-2 The composition according to claim 1.

37. below: Table 32-1 Table 32-2 The composition according to claim 1.

38. The composition according to claim 1, wherein naringenin is encapsulated.

39. A method for treating or preventing a local condition in a subject by administering a composition containing an effective amount of naringenin.

40. The method according to claim 39, wherein administration of the composition prevents fine wrinkles or wrinkles in the skin of the subject.

41. The method according to claim 39, wherein administration of the composition leads to supporting the firmness and elasticity of the skin of the subject.

42. The method according to claim 39, wherein administration of the composition leads to the prevention of skin and hair damage caused by reactive oxygen species.

43. The method according to claim 39, wherein administration of the composition leads to protection of the skin from environmentally aggressive factors.

44. The method according to claim 39, wherein the administration of the composition leads to supporting skin elasticity.

45. The method according to claim 39, wherein the local state is glycation.

46. The method according to claim 39, wherein administration of the composition leads to an increase in the resilience of the skin and / or hair.

47. The method according to claim 39, wherein administration of the composition leads to an increase in skin elasticity.

48. The method according to claim 39, wherein the administration of the composition leads to the prevention of skin damage.

49. The method according to claim 39, wherein the composition is administered topically.

50. The method according to claim 39, wherein the composition comprises an emulsion.

51. The method according to claim 39, wherein the emulsion is an oil / water emulsion.

52. The method according to claim 39, wherein the composition further comprises a solvent.

53. The method according to claim 39, wherein the solvent is a solvent for cosmetics.

54. The method according to claim 39, wherein the solvent is selected from the group consisting of dimethyl isosorbide, ethoxydiglycol, lauroyl sarcosinate isopropyl, glycol, and any combination thereof.

55. The method according to claim 52, wherein the solvent is dimethyl isosorbide.

56. The method according to claim 52, wherein the solvent is ethoxydiglycol.

57. The method according to claim 52, wherein the solvent is isopropyl lauroyl sarcosinate.

58. The method according to claim 52, wherein the solvent is glycol.

59. The method according to claim 58, wherein the glycol is selected from the group consisting of pentylene glycol, butylene glycol, and any combination thereof.

60. The method according to claim 52, wherein the solvent is selected from the group consisting of phenylpropanol, 1,2-hexanediol, propanediol, isopentyldiol, 1,2-heptanediol, and any combination thereof.

61. The method according to claim 39, wherein the method is stable under ambient conditions for at least two years of storage.

62. The method according to claim 39, wherein the method is stable under ambient conditions for at least one year of storage.

63. The method according to claim 39, wherein the method is stable under ambient conditions for at least six months of storage.

64. The method according to claim 39, wherein the method is stable under ambient conditions for at least three months of storage.

65. The method according to claim 39, wherein the composition exhibits less than 10% decomposition when stored at 70°C for one month.

66. The method according to claim 39, wherein naringenin is present at a concentration of approximately 0.0001 w / w% to approximately 5.0 w / w%.

67. The method according to claim 39, wherein naringenin is present at a concentration of about 0.0001 w / w% to about 1.0 w / w%.

68. The method according to claim 39, wherein naringenin is present at a concentration of approximately 0.001 w / w% to approximately 0.5 w / w%.

69. The method according to claim 39, wherein naringenin is present at a concentration of approximately 0.01 w / w% to approximately 0.5 w / w%.

70. The method according to claim 39, wherein naringenin is present at a concentration of approximately 0.1 w / w% to approximately 0.5 w / w%.

71. The method according to claim 39, wherein naringenin is present at a concentration of approximately 0.45 w / w%.

72. The method according to claim 39, wherein the composition is selected from the group consisting of fluids, emulsions, capsules, suspensions, solids, semi-solids, jellies, pastes, gels, hydrogels, ointments, lotions, emulsions, creams, foams, mousses, liquids, sprays, suspensions, dispersions, powders, aerosols, colored cosmetics, hair treatments, and any combination thereof.

73. The method according to claim 39, wherein the composition further comprises one or more additives selected from the group consisting of solvents, emulsifiers, preservatives, antioxidants, emollients, thickeners, penetration enhancers, surfactants, diluents, fillers, carriers, and / or pH control agents.

74. The method according to claim 73, wherein the preservative is an antimicrobial preservative or a chelating agent.

75. The composition contains water, dimethyl isosorbide, glycerin, caprylic / capric triglyceride, propanediol, sunflower seed oil, ethoxydiglycol, squalane, sodium acrylate copolymer, cetearyl alcohol, phenoxyethanol, glyceryl stearate, capryloyl glycerin / sebacate copolymer, diheptyl succinate, naringenin, lecithin, decylene glycol, pentylene glycol, cetearyl glucoside, shea butter, palmitic acid, arachidyl alcohol, behenyl alcohol, arachidyl glucoside, phenethyl alcohol, 1,2-hexanediol, hydrogenated olive oil, olive (Olea europaea) fruit oil, olive The method according to claim 39, further comprising one or more additives selected from the group consisting of europaea (olive) oil unsaponifiables, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, citric acid, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, sodium phytate, hydrolyzed sodium hyaluronate, and ethylhexylglycerin.

76. The composition comprises water, glycerin, niacinamide, squalane, and C. １４～２２ Alcohol, oil, ethoxydiglycol, propanediol, caprylyl glyceryl ether, lauroyl lysine, panthenol, butylene glycol, C １２～２０ Alkyl glucoside, polyacrylate crosspolymer-6, caprylic / capric triglyceride, caprylhydroxamic acid, shea butter, cetearyl alcohol, palmitic acid, sodium phytate, pentylene glycol, allantoin, hedychium The method according to claim 39, further comprising one or more additives selected from the group consisting of coronarium root extract, acacia senegal gum, xanthan gum, citric acid, arachidyl alcohol, arachidyl glucoside, behenyl alcohol, hydrogenated olive oil, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, date seed, acetylated sodium hyaluronate, cetearyl glucoside, olive oil, phenethyl alcohol, sodium hyaluronate, ascorbic acid, aloe leaf juice, t-butyl alcohol, sodium hyaluronate crosspolymer, glucose, sorbitan isostearate, hydrolyzed sodium hyaluronate, myristic acid, stearic acid, ethylhexylglycerin, lauric acid, dextran, and tripeptide-1.

77. The composition further comprises one or more additives selected from the group consisting of squalane, cetearyl alcohol, caprylic / capric triglyceride, C １３～１５ alkane, seed oil, seed wax, stearyl behenate, C １０～１８ triglyceride, dimethyl isosorbide, polyhydroxystearic acid, silica, glyceryl caprylate, ceramide, glyceryl behenate, and sodium hyaluronate, according to the method of claim 39.

78. The composition includes water, ethoxydiglycol, caprylic / capric triglyceride, shea butter, cetearyl alcohol, palmitic acid, pentylene glycol, propanediol, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, hydrogenated olive oil, behenyl alcohol, arachidyl alcohol, arachidyl glucoside, olive oil, sodium phytate, cetearyl glucoside, phenethyl alcohol, sorbitan isostearate, stearic acid, glucose, myristic acid, lauric acid, citric acid, linoleic acid, lecithin, phytosteryl canola glyceride, oleic acid, tocopherol, triolein, phospholipids, sphingolipids, sodium citrate, p-anisic acid, plant sterols, and C. １３～１５ The method according to claim 39, further comprising one or more additives selected from the group consisting of alkanes, butylene glycol, glycerin, glyceryl stearate, Alteromanus ferment extract, acetylated sodium hyaluronate, sodium hyaluronate, sodium hyaluronate crosspolymer, hydrolyzed sodium hyaluronate, ethylhexylglycerin, sodium acrylate copolymer, Centella asiatica extract, cetyl alcohol, hydroxyacetophenone, 1,2,hexanediol, caprylyl glycol, and sodium hydroxide.

79. The composition is as follows: Table 33-1 Table 33-2 The method according to claim 39.

80. The composition is as follows: Table 34-1 Table 34-2 The method according to claim 39.

81. The composition is as follows: Table 35-1 Table 35-2 The method according to claim 39.

82. The composition is as follows: Table 36-1 Table 36-2 The method according to claim 39.

83. The composition is as follows: Table 37-1 Table 37-2 The method according to claim 39.

84. The composition is as follows: Table 38-1 Table 38-2 The method according to claim 39.

85. The composition is as follows: Table 39 The method according to claim 39.

86. A method for modulating the expression of one or more genes by administering a composition containing naringenin, wherein at least one of the genes is related to a local condition.

87. The method according to claim 86, wherein the one or more genes are selected from the group consisting of LCE5A, KRT77, ALOXE3, KRT1, HPGD, MUCL1, CASP14, WFDC12, KRT10, DNASE1L2, IL37, SERPINB12, HAL, UPK1A, CALML5, LCE2B, MIR205, CCL11, CSF2, IL23A, IL11, BMP6, IL13RA2, C2CD4A, NR4A2, C2CD4B, FGF2, FABP4, GDF15, THBS1, HSPA1A, PTGS2, DKK1, and any combination thereof.

88. The method according to claim 86, wherein administration of the composition leads to the upregulation of LCE5A, KRT77, ALOXE3, KRT1, HPGD, MUCL1, CASP14, WFDC12, KRT10, DNASE1L2, IL37, SERPINB12, HAL, UPK1A, CALML5, LCE2B, and / or MIR205.

89. The method according to claim 86, wherein administration of the composition leads to the downregulation of CCL11, CSF2, IL23A, IL11, BMP6, IL13RA2, C2CD4A, NR4A2, C2CD4B, FGF2, FABP4, GDF15, THBS1, HSPA1A, PTGS2, and / or DKK1.

90. The method according to claim 86, wherein administration of the composition enhances anti-inflammatory activity.

91. The method according to claim 86, wherein administration of the composition enhances the maintenance of skin barrier strength and / or skin barrier lipids.

92. The method according to claim 86, wherein administration of the composition enhances cell turnover and cell recycling.

93. The method according to claim 92, wherein the enhancement of cell turnover and cell recycling has an anti-aging effect.

94. The method according to claim 93, wherein the anti-aging effect leads to the prevention of the formation of fine wrinkles and / or wrinkles of the skin.

95. The method according to claim 90, wherein administration of the composition leads to the downregulation of CSF2, IL23A, IL11, IL13RA2, C2CD4A, NR4A2, FABP4, GDF15, and / or PTGS2.

96. The method according to claim 90, wherein administration of the composition leads to the upregulation of HPGD.

97. The method according to claim 91, wherein administration of the composition leads to the upregulation of LCE5A, KRT77, ALOXE3, KRT1, CASP14, KRT10, and / or LCE2B.

98. The method according to claim 92 or 93, wherein administration of the composition leads to the upregulation of DNASE1L2, SERPINB12, UPK1A, CALML5 and / or MIR205.

99. The method according to claim 92 or 93, wherein administration of the composition leads to downregulation of BMP6 and / or HSPA1A.

100. The method according to claim 86, wherein administration of the composition results in at least about 30-fold upregulation of LCE5A expression and / or activity.

101. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of the expression and / or activity of KRT77.

102. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of ALOXE3 expression and / or activity.

103. The method according to claim 86, wherein administration of the composition results in at least about five-fold upregulation of KRT1 expression and / or activity.

104. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of HPGD expression and / or activity.

105. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of MUCL1 expression and / or activity.

106. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of the expression and / or activity of CASP14.

107. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of the expression and / or activity of WFDC12.

108. The method according to claim 86, wherein administration of the composition results in at least about five-fold upregulation of the expression and / or activity of KRT10.

109. The method according to claim 86, wherein administration of the composition results in at least about five-fold upregulation of DNASE1L2 expression and / or activity.

110. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of IL37 expression and / or activity.

111. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of the expression and / or activity of SERPINB12.

112. The method according to claim 86, wherein administration of the composition results in at least about five-fold upregulation of HAL expression and / or activity.

113. The method according to claim 86, wherein administration of the composition results in at least about a tenfold upregulation of UPK1A expression and / or activity.

114. The method according to claim 86, wherein administration of the composition results in at least about five-fold upregulation of the expression and / or activity of CALML5.

115. The method according to claim 86, wherein administration of the composition results in at least about five-fold upregulation of LCE2B expression and / or activity.

116. The method according to claim 86, wherein administration of the composition results in at least about five-fold upregulation of the expression and / or activity of MIR205.

117. The method according to claim 86, wherein administration of the composition results in a downward regulation of CCL11 expression and / or activity to at most about one-twentieth.

118. The method according to claim 86, wherein administration of the composition results in a downward regulation of CSF2 expression and / or activity to at most about one-fifteenth.

119. The method according to claim 86, wherein administration of the composition results in a downward regulation of IL23A expression and / or activity to at most about one-fifteenth.

120. The method according to claim 86, wherein administration of the composition results in a downward regulation of IL-11 expression and / or activity to at most about one-tenth.

121. The method according to claim 86, wherein administration of the composition results in a downward regulation of BMP6 expression and / or activity to at most about one-tenth.

122. The method according to claim 86, wherein administration of the composition results in a downward regulation of IL13RA2 expression and / or activity to at most about one-tenth.

123. The method according to claim 86, wherein administration of the composition results in a downward regulation of C2CD4A expression and / or activity to at most about one-tenth.

124. The method according to claim 86, wherein administration of the composition results in a downward regulation of NR4A2 expression and / or activity to at most about one-tenth.

125. The method according to claim 86, wherein administration of the composition results in a downward regulation of C2CD4B expression and / or activity to at most about one-fifth.

126. The method according to claim 86, wherein administration of the composition results in a downward regulation of FGF2 expression and / or activity to at most about one-fifth.

127. The method according to claim 86, wherein administration of the composition results in a downward regulation of FABP4 expression and / or activity to at most about one-fifth.

128. The method according to claim 86, wherein administration of the composition results in a downward regulation of GDF15 expression and / or activity to at most about one-fifth.

129. The method according to claim 86, wherein administration of the composition results in a downward regulation of THBS1 expression and / or activity to at most about one-fifth.

130. The method according to claim 86, wherein administration of the composition results in a downward regulation of HSPA1A expression and / or activity to at most about one-fifth.

131. The method according to claim 86, wherein administration of the composition results in a downward regulation of PTGS2 expression and / or activity to at most about one-fifth.

132. The method according to claim 86, wherein administration of the composition results in a downward regulation of DKK1 expression and / or activity to at most about one-fifth.

133. The method according to claim 86, wherein administration of the composition to a subject leads to the treatment or prevention of a local condition of the subject.

134. The method according to claim 86, wherein administration of the composition alters one or more functions associated with the modulated gene, wherein one or more of the functions are selected from the group consisting of (i) cell turnover, (ii) inflammation, (iii) barrier support, and (iv) any combination thereof.

135. The method according to claim 86, wherein the composition further comprises a solvent.

136. The method according to claim 135, wherein the solvent is selected from the group consisting of dimethyl isosorbide, ethoxydiglycol, lauroyl sarcosinate isopropyl, pentylene glycol, propanediol, 1,2-hexanediol, and / or butylene glycol.

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