Compositions and Methods for Treating and Preventing Skin Damage

Abstract

The present disclosure provides compositions and methods for treating and preventing skin damage. In particular, the present disclosure provides compositions for reversing, preventing, and / or slowing age-related skin damage.

Description

[0001] This application claims the priority of U.S. Provisional Patent Application Serial No. 62 / 952,931, filed on December 23, 2019, which is incorporated herein by reference in its entirety. TECHNICAL FIELD

[0002] Compositions and methods for treating and preventing skin damage are provided herein. In particular, compositions for reversing, preventing, and / or slowing age-related skin damage are provided. BACKGROUND ART

[0003] The skin is the outermost organ of the body, and it has various functions and significantly affects appearance and image. Depending on a person's weight, the total skin weight is about 3 - 5 kg of body weight. The skin is composed of various cells and specific structures and covers the outer surface of the body to serve as the main barrier against the external environment, including preserving moisture, regulating temperature, protecting the body from external stimuli (such as UV), and protecting the body from bacterial infections. In addition, the skin protects the body from physical or chemical damage, infections caused by microorganisms (such as bacteria, fungi, and parasites), UV damage, dryness, etc., and it also acts as a sensory receptor in response to various external stimuli and recognizes foreign antigens to produce immune cells.

[0004] Cumulative oxidative damage is thought to play a key role in the pathophysiology of many aging-related chronic diseases. A prominent feature of aging human skin is the reduced dermal strength and function due to the breakage and reduced production of type I collagen fibrils, which make up the main part of the dermis.

[0005] Therefore, there is a need for improved skin care agents that prevent the effects of aging on the skin. SUMMARY OF THE INVENTION

[0006] Compositions and methods for treating and preventing skin damage are provided herein. In particular, compositions for reversing, preventing, and / or slowing age-related skin damage are provided.

[0007] The compositions and methods described herein provide a synergistic effect of extracts of natural products for preventing and / or treating the signs and symptoms of skin aging.

[0008] For example, in some embodiments, compositions are provided herein that comprise, consist essentially of, or consist of: two or more (e.g., 2, 3, or all) components selected from the following: Malpighia emarginata Malpighia emarginata extract (e.g., Malpighia emarginata fruit extract), Curcuma longa Curcuma longa extract (e.g., Curcuma longa root extract), Osmanthus fragrans Osmanthus fragrans flower extract, or Spinacia oleracea Spinacia oleracea) leaf extract, wherein the composition is formulated for topical administration.

[0009] Additional embodiments provide a composition comprising, consisting essentially of, or consisting of: two or more (e.g., 2 or all) components selected from the group consisting of: Malpighia emarginata extract, blackberry ( Rubus fruticosus ) leaf extract or Centipeda minima ( Centipeda cunninghamii ) extract (e.g., Centipeda minima leaf / stem extract), wherein the composition is formulated for topical administration.

[0010] Yet other embodiments provide a composition comprising, consisting essentially of, or consisting of: Curcuma longa ( Curcurama longa ) extract, Osmanthus fragrans extract, and spinach leaf extract, wherein the composition is formulated for topical administration.

[0011] Specific embodiments provide a composition comprising, consisting essentially of, or consisting of: Malpighia emarginata extract, blackberry leaf extract, and Centipeda minima extract, wherein the composition is formulated for topical administration.

[0012] Certain embodiments provide a composition comprising, consisting essentially of, or consisting of: Malpighia emarginata extract 、 Curcuma longa extract, Osmanthus fragrans extract, and spinach leaf extract, wherein the composition is formulated for topical administration.

[0013] In some embodiments, the composition is a solution, cream, lotion, gel, ointment, salve, or spray.

[0014] The present disclosure is not limited to a specific concentration of the disclosed extracts. For example, in some embodiments, the Malpighia emarginata extract is present in the composition at a concentration of 0.1-1.0% (e.g., 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.9, 0.9 or 1.0%) by weight; the blackberry leaf extract is present in the composition at a concentration of 0.05-0.5% (e.g., 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45 or 0.5%) by weight; the Centipeda minima extract is present in the composition at a concentration of 0.25-1.25% (e.g., 0.25, 0.35, 0.45, 0.55, 0.65, 0.75, 0.85, 0.95, 1.05, 1.15 or 1.25%) by weight; the Osmanthus fragrans extract is present in the composition at a concentration of 0.5-1.5% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4 or 1.5%) by weight; the spinach leaf extract is present in the composition at a concentration of 0.5-1.5% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4 or 1.5%) by weight; and the turmeric extract is present in the composition at a concentration of 0.5-1.5% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4 or 1.5%) by weight.

[0015] Additional embodiments provide methods of repairing damaged skin, including administering a composition comprising two or more (e.g., 2, 3 or all) of the following components selected from: for example, Malpighia emarginata extract, turmeric extract 、 Osmanthus fragrans extract or spinach leaf extract, wherein the composition is formulated for topical administration to the skin of a subject under conditions such that the composition treats one or more signs or symptoms of skin damage.

[0016] In some embodiments, provided herein are methods of preventing skin damage, including administering a composition comprising two or more (e.g., 2 or all) of the following components selected from: for example, Malpighia emarginata extract, blackberry leaf extract or Centipeda minima extract, wherein the composition is formulated for topical administration to the skin of a subject under conditions such that the composition prevents one or more signs or symptoms of skin damage.

[0017] In further embodiments, provided herein are methods of treating and / or preventing skin damage, including: administering a composition as described herein to a subject in need thereof.

[0018] In some embodiments, the skin injury is an age-related skin injury. In some embodiments, the one or more signs or symptoms are selected, for example, from wrinkles, age spots, decreased elasticity, and increased dryness. In some embodiments, the composition inhibits cortisol production in the skin of the subject. In some embodiments, the composition prevents or reduces inflammation in the skin of the subject. In some embodiments, the composition is administered at least daily (e.g., for one or more days up to one or more weeks or one or more years or an indefinite period).

[0019] Also provided herein is the use of a composition as described herein for treating and / or preventing one or more signs or symptoms of skin injury in a subject.

[0020] Also provided herein are one or more compositions as described herein for treating and / or preventing one or more signs or symptoms of skin injury in a subject.

[0021] Additional embodiments are described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Exemplary protocols for screening agents for preventing oxidant-induced skin injury are shown.

[0023] Figure 2 Exemplary protocols for screening agents for preventing and repairing oxidant-induced skin injury are shown.

[0024] Figure 3 Exemplary protocols for screening agents for reversing and preventing oxidant-induced skin injury are shown.

[0025] Figure 4 Prevention of aging-induced skin injury by combinations of plant extracts is shown.

[0026] Figure 5 Prevention of aging-induced skin injury by combinations of plant extracts is shown.

[0027] Figure 6 Repair of aging-induced skin injury by combinations of plant extracts is shown.

[0028] Figure 7 Repair of aging-induced skin injury by combinations of plant extracts is shown.

[0029] Figure 8 Protection from early loss of collagen production by combinations of plant extracts is shown.

[0030] Figure 9 Protection from early loss of collagen production by combinations of plant extracts is shown.

[0031] Figure 10 Showing restoration of collagen production by a combination of plant extracts.

[0032] Figure 11 Showing protection from early collagen degradation by a combination of plant extracts.

[0033] Figure 12 Showing protection from collagen degradation by a combination of plant extracts.

[0034] Figure 13 Showing reversal of collagen degradation by a combination of plant extracts.

[0035] Figure 14 Showing inhibition of inflammatory response by a combination of plant extracts.

[0036] Figure 15 Showing inhibition of inflammatory response by a combination of plant extracts.

[0037] Figure 16 Showing inhibition of cellular stress response by a combination of plant extracts.

[0038] Figure 17 Showing inhibition of cellular stress response by a combination of plant extracts.

[0039] Definition

[0040] As used herein, the term "in vitro" refers to an artificial environment and processes or reactions occurring in an artificial environment. In vitro environments include, but are not limited to, test tubes and cell cultures. The term "in vivo" refers to a natural environment (e.g., an animal or cell) and processes or reactions occurring in a natural environment.

[0041] As used herein, the term "effective amount" refers to the amount of a composition (e.g., the compositions described herein) sufficient to achieve a beneficial or desired result. The effective amount can be administered in one or more administrations, applications, or dosages and is not intended to be limited to a particular formulation or route of administration.

[0042] As used herein, the term "administer" refers to the act of giving a drug, prodrug, or other agent or therapeutic treatment (e.g., the compositions described herein) to a physiological system (e.g., a subject or in vivo, in vitro, or ex vivo cells, tissues, and organs). Exemplary routes of administration to a human can be by the eye (ophthalmic), mouth (oral), skin (transdermal), nose (nasal), lung (inhalant), oral mucosa (buccal), ear, by injection (e.g., intravenous, subcutaneous, intratumoral, intraperitoneal, etc.), topical administration, etc.

[0043] As used herein, the term "co-administering" refers to administering to a subject at least two agents (e.g., a combination of a composition as described herein and an agent known to prevent or reverse skin aging) or therapies. In some embodiments, the co-administration of two or more agents or therapies is concurrent. In other embodiments, the first agent / therapy is administered before the second agent / therapy. Those skilled in the art will understand that the formulations and / or routes of administration of the various agents or therapies used may vary. Those skilled in the art can readily determine the appropriate dosages for co-administration. In some embodiments, when agents or therapies are co-administered, the corresponding agents or therapies are administered at lower dosages than are suitable for administration alone. Thus, co-administration is particularly desirable in embodiments in which the co-administration of agents or therapies reduces the required dosages of one or more potentially harmful (e.g., toxic) agents.

[0044] As used herein, the term "toxicity" refers to any adverse or harmful effect on a subject, cell, or tissue as compared to the same cell or tissue prior to administration of a poison.

[0045] As used herein, the term "pharmaceutical composition" refers to a combination of an active agent (such as those described herein) and an inert or active carrier such that the composition is particularly suitable for in vitro, in vivo, or ex vivo diagnostic or therapeutic use.

[0046] As used herein, the term "pharmaceutically acceptable" or "pharmacologically acceptable" refers to a composition that, when administered to a subject, produces substantially no adverse reactions such as toxicity, allergic, or immunological responses.

[0047] As used herein, the term "topical" refers to applying the compositions of the present invention to the surfaces of skin and mucosal cells and tissues (e.g., alveolar, buccal, lingual, masticatory, or nasal mucosa, and other tissues and cells lining hollow organs or body cavities).

[0048] As used herein, the term "pharmaceutically acceptable carrier" refers to any standard pharmaceutical carrier, including but not limited to phosphate buffered saline solution, water, emulsions (such as oil / water or water / oil emulsions), and various types of wetting agents, any and all solvents, dispersion media, coatings, sodium lauryl sulfate, isotonic agents, and absorption delaying agents, disintegrating agents (such as potato starch or sodium starch glycolate), etc. The composition may also contain stabilizers and preservatives. For example, carriers, stabilizers, and adjuvants. (See, e.g., Martin, Remington's Pharmaceutical Sciences, 15th ed., Mack Publ. Co., Easton, Pa. (1975), which is incorporated herein by reference).

[0049] As used herein, the term "cell culture" refers to any in vitro culture of cells, including, for example, prokaryotic and eukaryotic cells. The term includes continuous cell lines (e.g., having an infinite proliferation phenotype), primary cell cultures, transformed cell lines, finite cell lines (e.g., non-transformed cells), bacterial cultures in or on solid or liquid media, and any other cell population maintained in vitro.

[0050] As used herein, the term "sample" is used in its broadest sense. In one sense, it means to include specimens or cultures obtained from any source, as well as biological and environmental samples. Biological samples can be obtained from animals (including humans) and include fluids, solids, tissues, and gases. Biological samples include blood products, such as plasma, serum, etc. However, such examples should not be construed as limiting the types of samples applicable to the present invention. Detailed Description

[0051] Compositions and methods for treating and preventing skin damage are provided herein. In particular, compositions for reversing, preventing, and / or slowing age-related skin damage are provided herein.

[0052] Oxidative exposure leads to an increase in intracellular reactive oxygen species (ROS) levels, which promotes cellular and molecular alterations similar to the phenotype of dermal fibroblasts in aged / photoaged human skin. Characteristic features of this phenotype include impairment of the TGF-β pathway, which causes a decrease in the production of proteins (such as procollagen type I) that constitute the dermal extracellular matrix, and upregulation of the AP-1 transcription factor pathway, which drives the production of collagen-degrading matrix metalloproteinases and pro-inflammatory cytokines.

[0053] An improvement of the method for inducing fibroblast senescence by exposing primary human adult somatic cells, fibroblasts, to H2O2 in a defined protocol (He et al., AGE (2014) 36:1079-1094) is used to assay plant extracts and their combinations. For example, as described in the following experimental section, extracts with preventive activity can be screened by adding the extract prior to the peroxide. In addition, compounds can be added after peroxide treatment (e.g., after the aging period) to identify extracts with activity for repairing aged skin.

[0054] In the screening method, a compound is administered after oxidative exposure, and then the cells are aged for an additional 5 days. This work led to the discovery that several compounds are able to restore collagen homeostasis by downregulating matrix metalloproteinase 1 (MMP-1) and increasing procollagen type I. Additional experiments described herein test plant extracts and their combinations in a cell-based skin aging model. These complex models reveal the ranking of the efficacy of extracts for beneficial anti-aging activity. Importantly, the tests reveal new combinations of botanicals for preventing skin aging as well as repairing aged skin.

[0055] As shown in the skin oxidative exposure aging model, the combination of plant extracts described herein targets multiple pathways and is capable of inhibiting cortisol activity shown to affect skin aging. Exemplary compositions are described herein.

[0056] I. Compositions

[0057] As described herein, in some embodiments, the present disclosure provides a composition comprising one or more plant extracts for treating, preventing, alleviating, and / or reversing the signs or symptoms of skin aging. In some embodiments, the compounds reverse visible or other signs of aging of the skin, such as including but not limited to wrinkles, age spots, reduced elasticity, dry skin, loss of firmness, or dryness. In some embodiments, the compounds restore the imbalance of collagen homeostasis found in aging skin and / or reduce inflammation in the skin. Exemplary, non-limiting examples of the compositions of the present disclosure are described herein. In some embodiments, the composition comprises one or more components of the following table, consists essentially of one or more components of the following table, or consists of one or more components of the following table.

[0058]

[0059] Extracts are obtained, for example, from commercial sources or by extraction. Commercial sources include but are not limited to Malpighia emarginata fruit extract (Access Business Group, LLC, Ada, MI); blackberry leaf extract (SymMatrix, obtained from Symrise, Holzminden, Germany); Centipeda minima leaf / stem extract (Plantolin BG, obtained from Bio Actives Export, Melbourne, Australia); spinach leaf extract (Access Business Group, LLC); turmeric extract (HerbEx turmeric root extract, obtained from Biospectrum, through Clariant, Muttenz, Switzerland); and osmanthus flower extract (DermalRx Lushield, obtained from Biocogent, Stony Brook, NY).

[0060] In some exemplary embodiments, the composition comprises, consists essentially of, or consists of: two or more (e.g., 2, 3, or all) components selected from, for example, Malpighia emarginata fruit extract, Curcuma longa root extract, Osmanthus fragrans flower extract, or Spinacia oleracea leaf extract; two or more (e.g., 2 or all) components selected from, for example, Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, or Centipeda minima leaf / stem extract; Curcuma longa root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract; Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, and Centipeda minima leaf / stem extract; or Malpighia emarginata fruit extract, Curcuma longa root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract.

[0061] The present disclosure is not limited to the specific concentrations of the disclosed extracts. For example, in some embodiments, the Malpighia emarginata fruit extract is present in the composition at a concentration of 0.1 - 1.0% (e.g., 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.9, 0.9, or 1.0%) by weight; the Rubus fruticosus leaf extract is present in the composition at a concentration of 0.05 - 0.5% (e.g., 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, or 0.5%) by weight; the Centipeda minima leaf / stem extract is present in the composition at a concentration of 0.25 - 1.25% (e.g., 0.25, 0.35, 0.45, 0.55, 0.65, 0.75, 0.85, 0.95, 1.05, 1.15, or 1.25%) by weight; the Osmanthus fragrans flower extract is present in the composition at a concentration of 0.5 - 1.5% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4, or 1.5%) by weight; the Spinacia oleracea leaf extract is present in the composition at a concentration of 0.5 - 1.5% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4, or 1.5%) by weight; and the Curcuma longa root extract is present in the composition at a concentration of 0.5 - 1.5% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4, or 1.5%) by weight.

[0062] In some embodiments, the compounds (e.g., those described herein) are formulated for administration to the skin in a composition (e.g., a pharmaceutical composition, a nutritional composition, or a cosmetic).

[0063] Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids, mouthwashes, and powders. Conventional pharmaceutical carriers, aqueous, powder, or oily bases, thickening agents, etc. may be necessary or desirable.

[0064] The pharmaceutical compositions of the present disclosure include, but are not limited to, solutions, emulsions, and lipid-containing formulations. These compositions can be produced from a variety of components, including but not limited to preformed liquids, self-emulsifying solids, and self-emulsifying semi-solids.

[0065] The compositions can additionally contain other auxiliary components conventionally found in pharmaceutical compositions. Thus, for example, the compositions can contain additional compatible pharmaceutically active materials, such as antipruritics, astringents, local anesthetics, or anti-inflammatory agents, or can contain additional materials useful for physically formulating the various dosage forms of the composition, such as dyes, flavoring agents, preservatives, antioxidants, opacifying agents, thickening agents, and stabilizers. However, when such materials are added, they should not unduly interfere with the biological activity of the components of the composition. The formulations can be sterilized and, if desired, mixed with adjuvants that do not interact harmfully with the active agent of the formulation, such as lubricants, preservatives, stabilizers, wetting agents, emulsifying agents, salts affecting osmotic pressure, buffers, colorants, flavoring agents, and / or aromatic substances, etc.

[0066] The compositions of the present disclosure can be formulated as solutions, gels, lotions, creams, ointments, oil-in-water emulsions, water-in-oil emulsions, or other pharmaceutically acceptable forms. The compositions of the present invention can also contain various known and conventional cosmetic ingredients, provided they do not adversely affect the desired results.

[0067] Cosmetically acceptable vehicles act as diluents, dispersants, or carriers for the other materials present in the composition to facilitate their distribution when the composition is applied to the skin.

[0068] Vehicles other than water can include liquid or solid emollients, solvents, humectants, thickening agents, and powders. For example, the following vehicles can be used alone or in combination as one or more vehicles.

[0069] Emollients include but are not limited to stearyl alcohol, glyceryl monocastor oil, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecane-2-ol, isocetyl alcohol, eicosanol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, dibutyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cottonseed oil, olive oil, palm kernel oil, rapeseed oil, safflower oil, evening primrose oil, soybean oil, sunflower oil, avocado oil, sesame seed oil, coconut oil, peanut oil, castor oil, acetylated lanolin alcohol, petrolatum, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, and / or myristyl myristate.

[0070] As used herein, "emollient" refers to a material for preventing or alleviating dryness and for protecting the skin. A variety of suitable emollients are known and can be used herein. Sagarin, Cosmetics, Science and Technology, 2nd Edition, Volume 1, pages 32 - 43 (1972), which is incorporated herein by reference, contains many examples of suitable materials. Examples of useful classes of emollients include the following:

[0071] 1. Hydrocarbon oils and waxes. Examples include mineral oil, petrolatum, paraffin wax, purified ozokerite, native ozokerite, microcrystalline wax, polyethylene, and perhydrosqualene.

[0072] 2. Silicone oils, such as dimethylpolysiloxane, methylphenylpolysiloxane, water - soluble and alcohol - soluble siloxane diol copolymers.

[0073] 3. Triglycerides, such as vegetable and animal fats and oils. Examples include castor oil, safflower oil, cottonseed oil, corn oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil, sesame oil, and soybean oil.

[0074] 4. Acetylated glycerides, such as acetylated monoglycerides.

[0075] 5. Ethoxylated glycerides, such as ethoxylated monostearin.

[0076] 6. Alkyl esters of fatty acids having 10 - 20 carbon atoms. Methyl, isopropyl, and butyl esters of fatty acids are particularly useful in the present invention. Examples of other useful alkyl esters include hexyl laurate, isohexyl laurate, isohexyl palmitate, isopropyl palmitate, decyl oleate, isodecyl oleate, cetyl stearate, decyl oleate, isodecyl oleate, cetyl stearate, decyl stearate, isopropyl isostearate, diisopropyl adipate, diisohexyl adipate, dihexyl decyl adipate, diisopropyl sebacate, lauryl lactate, myristyl lactate, and cetyl lactate.

[0077] 7. Alkenyl esters of fatty acids having 10 - 20 carbon atoms. Examples include oleyl myristate, oleyl stearate, and oleyl oleate.

[0078] 8. Fatty acids having 10 - 20 carbon atoms. Suitable examples include pelargonic acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, hydroxystearic acid, oleic acid, linoleic acid, ricinoleic acid, arachidic acid, behenic acid, and erucic acid.

[0079] 9. Fatty alcohols having 10 - 20 carbon atoms. Lauryl alcohol, myristyl alcohol, cetyl alcohol, hexadecyl alcohol, stearyl alcohol, isostearyl alcohol, hydroxystearyl alcohol, oleyl alcohol, ricinoleyl alcohol, behenyl alcohol, and brassidyl alcohol, as well as 2 - octyldodecanol are examples of satisfactory fatty alcohols.

[0080] 10. Fatty alcohol ethers. Ethoxylated fatty alcohols having 10 - 20 carbon atoms include lauryl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, and cholesterol to which are attached 1 - 50 ethylene oxide groups or 1 - 50 propylene oxide groups.

[0081] 11. Ether - esters, such as fatty acid esters of ethoxylated fatty alcohols.

[0082] 12. Lanolin and derivatives. Lanolin, lanolin oil, lanolin wax, lanolin alcohol, lanolin fatty acids, isopropyl lanolate, ethoxylated lanolin, ethoxylated lanolin alcohol, ethoxylated cholesterol, propoxylated lanolin alcohol, acetylated lanolin, acetylated lanolin alcohol, lanolin alcohol linoleate, lanolin alcohol ricinoleate, acetate of lanolin alcohol ricinoleate, acetate of ethoxylated alcohol - esters, hydrogenated lanolin, ethoxylated hydrogenated lanolin, ethoxylated sorbitol lanolin, and liquid and semi - solid lanolin absorption matrices are illustrative of emollients derived from lanolin.

[0083] 13. Polyols and polyether derivatives. Propylene glycol, dipropylene glycol, polypropylene glycol 2000 and 4000, polyoxyethylene polyoxyethylene glycol, polyoxypropylene polyoxyethylene glycol, glycerol, sorbitol, ethoxylated sorbitol, hydroxypropyl sorbitol, polyethylene glycol 200 - 6000, methoxypolyethylene glycol 350, 550, 750, 2000 and 5000, poly[ethylene oxide] - homopolymer (100,000 - 5,000,000), polyalkylene glycols and derivatives, hexylene glycol (2 - methyl - 2,4 - pentanediol), 1,3 - butanediol, 1,2,6 - hexanetriol, ethylhexyl glycol USP (2 - ethyl - 1,3 - hexanediol), C 15 -C 18 Polyoxypropylene derivatives of vicinal glycols and trimethylolpropane are examples of such materials.

[0084] 14. Polyol esters. Ethylene glycol mono-fatty acid esters and di-fatty acid esters, diethylene glycol mono-fatty acid esters and di-fatty acid esters, dipropylene glycol mono-fatty acid esters and di-fatty acid esters, polyethylene glycol (200 - 6000) mono-fatty acid esters and di-fatty acid esters, propylene glycol mono-fatty acid esters and di-fatty acid esters, polypropylene glycol 2000 mono-oleate, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glyceryl mono-fatty acid esters and di-fatty acid esters, polyglycerol poly-fatty acid esters, ethoxylated glyceryl monostearate, 1,3-butanediol monostearate, 1,3-butanediol distearate, polyoxyethylene polyol fatty acid esters, sorbitan fatty acid esters and polyoxyethylene sorbitan fatty acid esters are satisfactory polyol esters used herein.

[0085] 15. Wax esters, such as beeswax, spermaceti, myristyl myristate, stearyl stearate.

[0086] 16. Beeswax derivatives, such as polyoxyethylene sorbitol beeswax. These are reaction products of beeswax with ethoxylated sorbitol of different ethylene oxide contents, forming ether-ester mixtures.

[0087] 17. Vegetable waxes, including carnauba wax and candelilla wax.

[0088] 18. Phospholipids, such as lecithin and its derivatives.

[0089] 19. Sterols. Examples thereof are cholesterol and cholesterol fatty acid esters.

[0090] 20. Amides, such as fatty acid amides, ethoxylated fatty acid amides, solid fatty acid alkanolamides.

[0091] The vehicle may also include propellants, such as propane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide; and solvents, such as ethanol, isopropanol, acetone, ethylene glycol monomethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether; or powders, such as chalk, talc, bleaching earth, kaolin, starch, gum, colloidal silica, sodium polyacrylate, tetraalkyl and / or trialkyl aryl ammonium hectorite, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, pyrogenic silica, carboxyvinyl polymer, sodium carboxymethyl cellulose and / or ethylene glycol monostearate.

[0092] The composition may optionally contain sunscreens, such as inorganic and organic sunscreens, to provide protection from the harmful effects of overexposure to sunlight during use of the composition of the present invention.

[0093] The composition may also optionally contain titanium dioxide with an average particle size of 1-300 nm, zinc oxide, iron oxide with an average particle size of 1-300 nm, and silica with an average particle size of 1-100 nm (such as pyrogenic silica) as a sunscreen. It should be noted that when silica is used as a component in the emulsion according to the present invention, it can provide protection from infrared radiation.

[0094] In some embodiments, the composition is an emulsion, in which case an oil or oily material (emollient) is usually present together with an emulsifier to provide a water-in-oil emulsion or an oil-in-water emulsion, which mainly depends on the average hydrophilic-lipophilic balance (HLB) of the emulsifier used. When a water-in-oil emulsion is required, one or more selected emulsifiers should generally have an average HLB value of 1-6. When an oil-in-water emulsion is required, the average HLB value of one or more selected emulsifiers should be >6.

[0095] Examples of suitable emulsifiers include but are not limited to sorbitan trioleate, sorbitan trioleate, glyceryl monooleate, glyceryl monostearate, glyceryl monolaurate, sorbitan sesquioleate, sorbitan monooleate, sorbitan monostearate, polyoxyethylene, stearyl ether, polyoxyethylene sorbitol, beeswax derivatives, PEG 200 dilaurate, sorbitan monopalmitate, polyoxyethylene (3.5), nonylphenol, PEG 200 monostearate, sorbitan monolaurate, PEG 400 dioleate, polyoxyethylene (5) monostearate, polyoxyethylene (4) sorbitan monostearate, polyoxyethylene (4) lauryl ether, polyoxyethylene (5) sorbitan monooleate, PEG 300 monooleate, polyoxyethylene (20) sorbitan tristearate, polyoxyethylene (20) sorbitan trioleate, polyoxyethylene (8) monostearate, PEG 400 monooleate, PEG 400 monostearate, polyoxyethylene 10 monooleate, polyoxyethylene (10) stearyl ether, polyoxyethylene (10) cetyl ether, polyoxyethylene (9.3) octylphenol, polyoxyethylene (4) sorbitan monolaurate, PEG 600 monooleate, PEG 1000 dilaurate, polyoxyethylene sorbitol, lanolin derivatives, polyoxyethylene (12) lauryl ether, PEG 1500 dioleate, polyoxyethylene (14) laurate, polyoxyethylene (20) Tween, sorbitan monostearate, polyoxyethylene 20 sorbitan monooleate, polyoxyethylene (20) stearyl ether, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) cetyl ether, polyoxyethylene (25) oxypropylene monostearate, polyoxyethylene (20) sorbitol monolaurate, polyoxyethylene (23) lauryl ether, polyoxyethylene (50) monostearate, and / or PEG 4000 monostearate.

[0096] It should be understood that if desired, two or more emulsifiers can be employed. The amount of emulsifier or mixture thereof that can optionally be incorporated into the composition is 1 - 50%, 2 - 20%, or 2 - 10% by weight of the composition.

[0097] The composition can also contain water, typically up to 95% by weight, such as 5 - 95% by weight.

[0098] The composition can also optionally contain a high molecular weight silicone surfactant, which can also act as an emulsifier, in place of or in addition to the optional one or more emulsifiers already mentioned.

[0099] When present in the composition, the amount of silicone surfactant is typically up to 25% by weight of the emulsion, preferably 0.5 - 15% by weight.

[0100] Examples of conventional auxiliaries that can be optionally employed include preservatives such as parabens; antioxidants such as butylated hydroxytoluene; humectants such as glycerol, ethoxylated glycerol such as glycerol polyether - 26, sorbitol, 2 - pyrrolidone - 5 - carboxylate, dibutyl phthalate, gelatin, polyethylene glycol such as PEG 200 - 600; buffers and bases such as triethanolamine or sodium hydroxide; waxes such as beeswax, ozokerite, paraffin wax; plant extracts such as aloe, cornflower, witch hazel, elder flower, cucumber; and acerola ferment, thickeners; activity enhancers; colorants; and fragrances. The cosmetic auxiliaries can make up the balance of the composition.

[0101] It may also be desirable to incorporate anti - inflammatory and / or anti - irritant agents. Preferably natural anti - inflammatory and / or anti - irritant agents. For example, licorice and its extracts, dipotassium glycyrrhizate, oats and oat extracts, candelilla wax, α - bisabolol, aloe, Manjistha (extracted from plants of the Rubia genus, especially Rubia cordifolia) and Guggal (extracted from plants of the Commiphora genus, especially Commiphora Mukul) can be used.

[0102] Additional skin-beneficial agents can also be incorporated alone or in admixture, such as ceramides, glycosphingolipids, pseudoceramides, sphingolipids (such as sphingomyelin), cerebrosides, sulfatides, and gangliosides, sphingosine, dihydrosphingosine, phytosphingosine, phospholipids. Fatty acids can also be combined with these skin-beneficial agents. For example, ceramides and glycosphingolipids include those described in U.S. Patent Nos. 5,589,178, 5,661,118, and 5,688,752, the relevant portions of which are incorporated herein by reference. For example, pseudoceramides include those described in U.S. Patent Nos. 5,198,210, 5,206,020, and 5,415,855, the relevant disclosures of which are incorporated herein by reference.

[0103] In some embodiments, the pharmaceutical or cosmetic composition contains a) the composition described herein; and b) one or more other agents useful for treating, preventing, or reversing skin aging.

[0104] In some embodiments, the composition is administered in a maintenance or continuous manner (e.g., once or more times a day, twice or more times a day, once or more times a week, etc.). In some embodiments, the composition is administered continuously (e.g., via a skin patch, bandage, or timed-release formulation). In some embodiments, the composition is administered one, two, five, ten, or more times. In some embodiments, the composition is administered over a period of weeks, months, years, or indefinitely.

[0105] II. Uses

[0106] As described herein, it has been found that the compositions of the present disclosure are useful for treating, preventing, or slowing skin damage (e.g., age-related skin damage). In some embodiments, the composition is optimized for reversing or preventing skin damage. For example, in some embodiments, a composition for repairing damaged skin (e.g., reversing skin damage) comprises, consists essentially of, or consists of two or more (e.g., 2, 3, or all) components selected from, for example, Malpighia emarginata fruit extract, Curcuma longa root extract, Osmanthus fragrans flower extract, or Spinacia oleracea leaf extract.

[0107] In some embodiments, a composition for preventing skin damage comprises, consists essentially of, or consists of two or more (e.g., 2 or all) components selected from, for example, Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, or Centipeda minima stem / leaf extract.

[0108] In some embodiments, the compositions described herein are administered to prevent or alleviate one or more symptoms of skin damage (e.g., wrinkles, age spots, reduced elasticity, and increased dryness). In some embodiments, the compositions inhibit cortisol production in the skin of a subject. In some embodiments, the compositions prevent or alleviate inflammation in the skin of a subject.

[0109] In some embodiments, the compositions are administered at least daily (e.g., for one or more days to one or more weeks or one or more years or an indefinite period).

[0110] Experiment

[0111] The following examples are provided to demonstrate and further illustrate certain embodiments of the disclosure and should not be construed as limiting its scope.

[0112] Example 1

[0113] This example describes the screening of plant extracts for the prevention and repair of aging-related skin damage.

[0114] The following compositions were used in this example: Prevention: 0.5% Acerola cherry, 0.1% Blackberry, 0.75% Centipeda minima; Repair: 1% Osmanthus fragrans, 1% Spinach, 1% Turmeric.

[0115] In Figures 1 - 3 the oxidative exposure aging model described above, the botanicals were tested. The testing was carried out in 3 steps divided into 5 pathways:

[0116] 1. Early prevention of aging phenotypes

[0117] a. Activation of the antioxidant pathway measured by survival and proliferation endpoints. The botanicals were added prior to oxidative exposure and their ability to prevent the formation of aging phenotypes was measured.

[0118] 2. Middle-aged aging phenotypes before the acquisition of a permanent aging phenotype

[0119] a. Early protection / restoration: Inhibition of the AP-1 / MMP1 collagen damage pathway. The botanicals were added after oxidative exposure and before the fibroblasts acquired a permanent aging phenotype.

[0120] b. Early protection / restoration: Protection of the TGF-β / collagen production pathway. The botanicals were added after oxidative exposure but before the fibroblasts acquired a permanent aging phenotype.

[0121] 3. Fully acquired aging phenotype

[0122] a. Restoration: Inhibition of the AP-1 / MMP1 collagen damage pathway. The botanicals were added after the fibroblasts had stabilized into an aging phenotype.

[0123] b. Restoration: Protection of the TGF-β / collagen production pathway. Phytomedicine is added after fibroblasts are stabilized into the senescent phenotype.

[0124] Testing reveals a unique ranking order (Tables 1 - 5) of the effectiveness of phytomedicine in inhibiting different aging pathways at different aging stages (early, mid, and fully acquired). This finding indicates that a unique combination of active phytomedicines provides more comprehensive anti-aging benefits than single agents.

[0125] Antioxidant Response Element Assay

[0126] HepG2 cells stably transfected with a luciferase reporter gene construct (pGL4.27) under the control of the antioxidant response element (6X: GTGACxxxGCA (SEQ ID NO:1) were plated at a density of 30,000 cells / well in white-wall collagen-coated plates of minimum essential tissue culture medium containing 10% serum. After 24 hours, each component (acerola cherry (AC), blackberry powder (BB), and centipeda minima extract (CC)) was diluted in tissue culture medium and added to the wells at specific concentrations. Additionally, the three components were combined at a ratio of AC:BB:CC of 0.5:0.1:0.75. The combination was diluted to various concentrations and added to the test wells. After 48 hours, the cells were lysed, and luciferase was quantified using a luciferase assay according to the manufacturer's instructions (Biotium, Inc., Hayward, CA). The data were expressed as the percentage of the response of the untreated wells. In Figure 4 the response of individual components at specific doses is represented by stacked bars labeled "expected". These are the expected values of the ARE response if the sample effects were added together. In Figure 4 the treatment with the combination using the same individual doses is shown, and the bars labeled "actual" in Figure 4 represent the response of the combination, and they show synergistic activity.

[0127] HemOxigenase (HOX)

[0128] Maintain AG01518 fibroblasts in MEM + 2% charcoal-stripped FBS + 1% penicillin / streptomycin / amphotericin B. After plating 20,000 cells / well in a 96-well plate, maintain the cells in MEM + 2% charcoal-stripped FBS. Treat them with individual components of the prevention and repair complex as well as various dilutions of a specific prevention and repair complex for 18 hours. The prevention complex contains Acerola cherry (AC), blackberry powder (BB), and Centipeda minima extract (CC)), while the repair complex contains different concentrations of spinach leaf (SL; NF7321A), osmanthus fragrans (OF; RN2407), and turmeric (T; (RN2404)). After component treatment, lyse the cells and isolate RNA. Use RT-qPCR to quantify HOX expression. Normalize the cycle threshold of each gene to its endogenous housekeeping gene HPRT1. Divide the treated expression value by the average expression value of the untreated control to calculate the HOX fold-expression level above the untreated control. Data are represented as the percentage of response of untreated wells. In Figure 5 and 6 , the effect of individual components at specific doses on HOX gene response is represented by stacked bars labeled "expected". These are the expected values of the ARE response if the samples acted alone. In Figure 5 and 6 , combined treatments using the same individual doses "put together" are shown, and in Figure 5 and 6 , bars labeled "actual" are shown. The actual bars represent the response if the components acted synergistically.

[0129] Human Dermal Fibroblast Repair Assay

[0130] Human dermal fibroblasts (HDF) were grown in DMEM medium (growth medium) in 6-well plates. At 70% confluence, the cells were first washed with phosphate-buffered saline (PBS) and then treated with 150 μM of H2O2 in treatment medium (serum-free growth medium) for 1 hour. After treatment, the cells were washed twice with phosphate-buffered serum (PBS), then growth medium was added to the cells, and the plates were kept in the incubator. The next day, the same treatment (treatment with H2O2) was repeated. On the day after two consecutive days of H2O2 treatment, human dermal fibroblasts were treated (Day 1) with the components in the "repair complex" either individually or in combination. The cells were allowed to grow for four more days. Then the cells were lysed on Day 5, and RNA was isolated using the RNAeasy Mini Kit from Qiagen (Germantown, MD). Then the RNA in each group was quantified via absorption at 260 nm. Then the total RNA was converted to cDNA using the iScript cDNA Synthesis Kit from Bio-RAD (Hercules, CA). Then the cDNA was diluted 5-fold, and 5 μl was used for each qPCR reaction. qPCR was performed using the Sso Advanced Universal SYBR Green Supermix from Bio-RAD (Hercules, CA). Primers were purchased from Qiagen (Germantown, MD).

[0131] Data are represented as the percentage of inhibition of the MMP1 response. In Figure 7 , the responses of individual components at specific doses are represented by stacked bars labeled "expected". These are the expected values of the assay if the sample effects were added together. The combined treatments using the same individual doses are represented by bars labeled "actual" and represent the response of the combination. Since the response at this same concentration is much greater than the sum of the individual responses, the combination exhibits synergy.

[0132]

[0133] Prevention of the aging phenotype: Activation of antioxidant pathways measured by survival and proliferation endpoints.

[0134] Extract / Carrier Company Percentage of the highest non - toxic dose tested Relative effectiveness Turmeric rhizome extract, water Barnet Products 8 1 Propylene glycol, glycerin, water, asparagus stem extract DSM 2 0.61 Water, watercress extract Silab 1.5 0.44 Glycerin, water, alcohol, Persian buckthorn bark extract Bio - Biotanica 6 0.4 Water, glycerin, broad bean seed extract Vincience Biofunctionals 8 0.33 Glycerin, water, holly leaf barberry extract Botanica 5 0.29 Glycerin, tea tree leaf extract Lipotec 2 0.24 Glycerin, blackberry (blackberry) leaf extract Naolys 4 0.24 Glycerin, tea tree leaf extract Lipotec 4 0.23 Water, propylene glycol, tea tree leaf extract Active Concepts 0.5 0.16

[0135]

[0136] Early protection against the middle-aged aging phenotype before the acquisition of the permanent aging phenotype: Inhibition of the AP-1 / MMP1 collagen damage pathway.

[0137] Extract / Carrier Company Percentage of the highest non - toxic dose tested Relative effectiveness Water (and) osmanthus flower extract (and) propylene glycol (and) glycerin Biocogent 3 1 Butylene glycol, water, alcohol, Persian buckthorn bark extract Bio - Biotanica 1 0.68 Water, propylene glycol, Japanese coptis rhizome extract Draco 0.5 0.67 Propylene glycol, water, Persian buckthorn bark extract Bio - Biotanica 2 0.47 Propylene glycol, water, cocoa (cocoa) extract Solabia 2 0.37 Butylene glycol, water, raspberry (blackberry) leaf extract Lipotec 0.5 0.33 Water, acai berry fruit extract Active Concepts 1 0.29 Glycerin, turmeric cell extract Naolys 2 0.28 Water, butylene glycol, polygonum cuspidatum extract Active Concepts 1.5 0.23 Water, butylene glycol, Japanese coptis rhizome extract Draco 1 0.20

[0138]

[0139] Early recovery of the middle-aged aging phenotype before the acquisition of the permanent aging phenotype: Protection of the TGF-β / collagen production pathway.

[0140] Extract / Carrier Company Percentage of the highest non - toxic dose tested Relative effectiveness Water, butylene glycol, alcohol, turmeric (turmeric) root extract Biospectrum 1 1 Glycerin, turmeric cell extract Naolys 2 0.97 Butylene glycol, water, Persian buckthorn bark extract Bio - Biotanica 1 0.91 Butylene glycol, water, Persian buckthorn bark extract Bio - Biotanica 1 0.85 Butylene glycol, water, turmeric (turmeric) root extract Solabia 0.5 0.78 Glycerin, blackberry (blackberry) leaf cell extract Naolys 2 0.74 Glycerin, water, cocoa (cocoa) extract Lipotec 2 0.65 Butylene glycol, water, watercress leaf / stem extract IPC Japan 3 0.64 Glycerin, turmeric extract, pentylene glycol, phytic acid, water Barnet Products 4 0.63 Butylene glycol, water, cocoa (cocoa) extract Oryza Oil & Fat Chemical CO., LTD 1 0.62

[0141]

[0142] Complete recovery of the acquired aging phenotype: Inhibition of the AP-1 / MMP1 collagen damage pathway.

[0143] Extract / Carrier Company Percentage of the highest non - toxic dose tested Relative effectiveness Propylene glycol, water, Nasturtium officinale leaf extract GreenTech 5 1 Butylene glycol, water, Rubus idaeus leaf extract Lipotec 0.5 0.97 Propylene glycol, water, Arctostaphylos uva - ursi leaf extract Lipotec 1.5 0.64 Propylene glycol, water, Theobroma cacao extract Solabia 2 0.59 Curcuma longa rhizome extract, water Barnet Products 8 0.55 Glycerin, water, Uncaria tomentosa extract Lipotec 2 0.54 Butylene glycol and water and Salvia miltiorrhiza root extract SiLab 1.5 0.38 Water, butylene glycol, alcohol, Curcuma longa root extract Biospectrum 1 0.35 Butylene glycol, water, Theobroma cacao extract Solabia 1 0.29 Butylene glycol, water, Phellodendron amurense bark extract Lipotec 1 0.28

[0144]

[0145] Complete recovery of the acquired aging phenotype: Protection of the TGF-β / collagen production pathway

[0146] Extract / Carrier Company Percentage of the highest non - toxic dose tested Relative effectiveness Butylene glycol, water, Hydrastis canadensis extract Bio - Biotanica 1.5 1 Water, butylene glycol, Coptis japonica rhizome extract Draco 0.5 0.81 Water, propylene glycol, Coptis japonica rhizome extract Draco 1 0.77 Propylene glycol, water, Nasturtium officinale leaf extract GreenTech 4 0.71 Water, propylene glycol, Coptis japonica rhizome extract Draco 0.5 0.60 Water, glycerin, Camellia sinensis leaf extract Active Concepts 0.4 0.59 Water (and) Osmanthus fragrans flower extract (and) propylene glycol (and) glycerin Biocogent 3 0.57 Glycerin, water, Berberis ilicifolia leaf extract Botanica 5 0.56 Butylene glycol, water, Nasturtium officinale extract Lipotec 2 0.55 Butylene glycol, water, Phellodendron amurense bark extract IPC Japan 0.5 0.51

[0147] Example 2

[0148] The preventive complex components prevent the loss of type I procollagen production in adult skin fibroblasts: A preventive model of skin aging

[0149] Primary adult skin fibroblasts were cultured in DMEM medium with 10% fetal bovine serum (FBS) for 24 hours. The fibroblasts were treated with the indicated preventive complex components from acerola cherry (cherry), blackberry leaf (blackberry), or centipeda minima (centipeda) alone or in combination for two days. The fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 (oxidative exposure) for one hour, for two consecutive days. After each oxidative exposure, the medium was replaced with fresh medium containing FBS and one or more preventive complex components. Six days after the second oxidative exposure, the medium was replaced with medium containing 2% FBS (without preventive complex components), and the conditioned medium was collected 12 hours later for measurement of type I procollagen by ELISA. The level of type I procollagen was normalized to the number of fibroblasts. The relative concentrations of the preventive complex components cherry:blackberry:centipeda were 0.5:0.1:0.75. The results are shown in Figure 8 and. The data represent three independent experiments.

[0150] The preventive complex components improve type I procollagen production in adult skin fibroblasts: An early treatment model of skin aging

[0151] Primary adult skin fibroblasts were cultured in DMEM medium with 10% fetal bovine serum (FBS) for 24 hours. The fibroblasts were then placed in serum-free DMEM and exposed to 100 µM H2O2 (oxidative exposure) for one hour for two consecutive days. After each oxidative exposure, the medium was replaced with fresh medium containing FBS. One day after the second oxidative exposure, the cells were cultured in medium containing the indicated preventive complex components from acerola cherry (cherry), blackberry leaf (blackberry), or centipeda minima (centipeda) alone or in combination. Six days after the second oxidative exposure, the medium was replaced with medium containing 2% FBS (without preventive complex components), and the conditioned medium was collected 12 hours later for measuring procollagen type I by ELISA. The level of procollagen type I was normalized to the number of fibroblasts. The relative concentrations of the preventive complex components cherry:blackberry:centipeda were 0.5:0.1:0.75. The results are shown in Figure 9 and. Data represent two independent experiments.

[0152] Restorative complex components restore procollagen type I production in adult skin fibroblasts: A regenerative model of skin aging

[0153] Human skin fibroblasts were cultured in DMEM medium with 10% fetal bovine serum (FBS) until confluent. The fibroblasts were then placed in serum-free DMEM and exposed to 200 µM H2O2 (oxidative exposure) for one hour for two consecutive days. After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS. Five days after the oxidative exposure, the fibroblasts were collected by trypsinization, counted, and equal numbers of fibroblasts were cultured in 24-well plates in medium containing 10% FBS. Two days later, the fibroblasts were treated with the indicated restorative complex components from spinach extract (spinach), flower extract of osmanthus (osmanthus), or turmeric extract (curcumin) alone or in combination for six days. Then the medium was replaced with medium containing 2% FBS (without preventive complex components), and the conditioned medium was collected 12 hours later for measuring procollagen type I by ELISA. The level of procollagen type I was normalized to the number of fibroblasts. The relative concentrations of the restorative complex components spinach:osmanthus:curcumin were 1:1:1. The results are shown in Figure 10 and. Data represent two independent experiments.

[0154] Preventive complex components protect against matrix metalloproteinase I that degrades collagen in adult skin fibroblasts: A preventive model of skin aging

[0155] Primary adult skin fibroblasts were cultured for 24 hours in DMEM medium with 10% fetal bovine serum (FBS). The fibroblasts were treated for two days with the indicated preventive complex components from acerola cherry (cherry), blackberry leaf (blackberry), or centipeda herb (centipeda) alone or in combination. The fibroblasts were then placed in serum-free DMEM and exposed to 100 µM H2O2 (oxidative exposure) for one hour for two consecutive days. After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS and one or more preventive complex components. Six days after the second oxidative exposure, the medium was replaced with medium containing 2% FBS (without preventive complex components), and conditioned medium was collected 12 hours later for measurement of matrix metalloproteinase I protein by ELISA. The level of matrix metalloproteinase I protein was normalized to the number of fibroblasts. The relative concentrations of the preventive complex components cherry:blackberry:centipeda were 0.5:0.1:0.75. The results are shown in Figure 11 and. Data represent three independent experiments.

[0156] Preventive complex components mitigate matrix metalloproteinase I that degrades collagen in adult skin fibroblasts: An early treatment model for skin aging

[0157] Primary adult skin fibroblasts were cultured for 24 hours in DMEM medium with 10% fetal bovine serum (FBS). The fibroblasts were then placed in serum-free DMEM and exposed to 100 µM H2O2 (oxidative exposure) for one hour for two consecutive days. After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS. One day after the second oxidative exposure, the cells were cultured in medium containing the indicated preventive complex components from acerola cherry (cherry), blackberry leaf (blackberry), or centipeda herb (centipeda) alone or in combination. Six days after the second oxidative exposure, the medium was replaced with medium containing 2% FBS (without repair complex components), and conditioned medium was collected 12 hours later for measurement of matrix metalloproteinase I protein by ELISA. The level of matrix metalloproteinase I protein was normalized to the number of fibroblasts. The relative concentrations of the preventive complex components cherry:blackberry:centipeda were 0.5:0.1:0.75. The results are shown in Figure 12 and. Data represent two independent experiments.

[0158] Repair complex components reverse elevated levels of matrix metalloproteinase I production that degrades collagen in adult skin fibroblasts: A regeneration model for skin aging

[0159] Human skin fibroblasts were cultured in DMEM medium with 10% fetal bovine serum (FBS) until confluence. The fibroblasts were then placed in serum-free DMEM and exposed to 200 µM H2O2 (oxidative exposure) for one hour for two consecutive days. After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS. Five days after oxidative exposure, the fibroblasts were collected by trypsinization, counted, and an equal number of cells were placed in 24-well plates. Two days later, the fibroblasts were treated for six days with the indicated repair complex components from spinach extract (spinach), flower extract of Osmanthus fragrans (osmanthus), or turmeric extract (curcumin) alone or in combination in fresh medium containing 10% FBS. The medium was then replaced with medium containing 2% FBS (without repair complex components), and the conditioned medium was collected 12 hours later for measurement of matrix metalloproteinase I protein by ELISA. The levels of matrix metalloproteinase I were normalized to the number of fibroblasts. The relative concentrations of the repair complex components spinach:osmanthus:curcumin were 1:1:1. The results are shown in Figure 13 in. The data represent two independent experiments.

[0160] The preventive complex components inhibit the production of the inflammatory mediator prostaglandin E2 in human epidermal skin cells.

[0161] Human skin cells (keratinocytes) were cultured in keratinocyte serum-free growth medium (SGM) to 60 - 70% confluence. The keratinocytes were then cultured for 24 hours in fresh SGM containing 1% fetal bovine serum (FBS). The medium was replaced with fresh SGM containing 1% FBS and the indicated preventive complex components from acerola cherry (cherry), blackberry leaf (blackberry), or Centipeda minima (centipeda) alone or in combination. The conditioned medium was collected six hours later for measurement of prostaglandin E2 (PGE2) by ELISA. The levels of PGE2 were normalized to the number of keratinocytes. The relative concentrations of the preventive complex components cherry:blackberry:centipeda were 0.5:0.1:0.75. The results are shown in Figure 14 in. The data represent two independent experiments.

[0162] The repair complex components inhibit the production of the inflammatory mediator prostaglandin E2 in human epidermal skin cells.

[0163] Human skin cells (keratinocytes) were cultured in serum-free growth medium (SGM) for keratinocytes to 60 - 70% confluence. Then the keratinocytes were cultured in fresh SGM containing 1% fetal bovine serum (FBS) for 24 hours. Then the medium was replaced with fresh SGM containing 1% FBS and the indicated repair complex components from spinach extract (spinach), flower extract of Osmanthus fragrans (osmanthus), or turmeric extract (curcumin) alone or in combination. The conditioned medium was collected after six hours for measuring prostaglandin E2 (PGE2) by ELISA. The levels of PGE2 were normalized to the number of keratinocytes. The relative concentrations of the repair complex components spinach:osmanthus:curcumin were 1:1:1. The results are shown in Figure 15 in. The data represent two independent experiments.

[0164] The repair complex components inhibit the production of the stress hormone cortisol.

[0165] Human adrenal cells (H295 cells) were cultured in DMEM / F12 (1:1) medium containing 10% enhanced calf serum (CCS) to 60 - 70% confluence. Then the cells were cultured in DMEM / F12 (1:1) medium containing 0.1% CSS for 24 hours. Then the medium was replaced with fresh DMEM / F12 (1:1) medium containing 0.1% CSS and the indicated repair complex components from spinach extract (spinach), flower extract of Osmanthus fragrans (osmanthus), or turmeric extract (curcumin) alone or in combination. The conditioned medium was collected after 22 hours for measuring cortisol by ELISA. The levels of cortisol were normalized to the number of cells. The relative concentrations of the repair complex components spinach:osmanthus:curcumin were 1:1:1. The results are shown in Figure 16 in. The data represent three independent experiments.

[0166] The prevention complex components inhibit the production of the stress hormone cortisol.

[0167] Human adrenal cells (H295 cells) were cultured in DMEM / F12 (1:1) medium containing 10% enhanced calf serum (CCS) to 60 - 70% confluence. Then the cells were cultured in DMEM / F12 (1:1) medium containing 0.1% CSS for 24 hours. Then the medium was replaced with fresh DMEM / F12 (1:1) medium containing 0.1% CSS and the indicated prevention complex components from acerola cherry (cherry), blackberry leaf (blackberry), or Centipeda minima (centipeda) alone or in combination. The conditioned medium was collected after 22 hours for measuring cortisol by ELISA. The levels of cortisol were normalized to the number of cells. The relative concentrations of the prevention complex components cherry:blackberry:centipeda were 0.5:0.1:0.75. The results are shown inFigure 17 The data represent three independent experiments.

[0168] All publications, patents, patent applications, and accession numbers mentioned in the above specification are hereby incorporated by reference in their entirety. Although the invention has been described in connection with specific embodiments, it should be understood that the claimed invention should not be unduly limited to such specific embodiments. Indeed, various modifications and variations of the compositions and methods described herein will be apparent to those of ordinary skill in the art and are intended to fall within the scope of the appended claims. Sequence Listing <110> The Regents of the University of Michigan Jietong International Co., Ltd. <120> Compositions and Methods for Treating and Preventing Skin Injury <130> UM-37824-601 <150> US 62 / 952,931 <151> 2019-12-23 <160> 1 <170> PatentIn version 3.5 <210> 1 <211> 11 <212> DNA <213> Artificial <220> <223> Synthetic <220> <221> misc_feature <222> (6)..(8) <223> n is a, c, g or t <400> 1 gtgacnnngc a 11

Claims

1. A composition for treating and / or preventing skin damage, comprising turmeric root extract, osmanthus flower extract and spinach leaf extract, wherein the composition is formulated for topical administration, and the relative concentrations of the turmeric root extract, osmanthus flower extract and spinach leaf extract are 1:1:

1.

2. The composition according to claim 1, wherein the composition is selected from solutions, creams, lotions, gels, ointments, pastes and sprays.

3. The composition according to claim 1 or 2, wherein the osmanthus flower extract is present in the composition at a concentration of 0.5 - 1.5% by weight, the spinach leaf extract is present in the composition at a concentration of 0.5 - 1.5% by weight, and the turmeric root extract is present in the composition at a concentration of 0.5 - 1.5% by weight.

4. The composition according to claim 3, wherein the osmanthus flower extract is present in the composition at a concentration of 1.0% by weight, the spinach leaf extract is present in the composition at a concentration of 1.0% by weight, and the turmeric root extract is present in the composition at a concentration of 1.0% by weight.

5. Use of the composition according to any one of claims 1 - 4 in the preparation of a medicament for repairing skin damage, comprising: administering the composition according to any one of claims 1 - 4 to the skin of a subject.

6. Use of the composition according to any one of claims 1 - 4 in the preparation of a medicament for treating and / or preventing skin damage, comprising: administering the composition according to any one of claims 1 - 4 to a subject in need thereof.

7. The use according to claim 5 or 6, wherein the damage is age-related skin damage.

8. The use according to claim 5 or 6, wherein the composition inhibits cortisol production in the skin of the subject.

9. The use according to claim 5 or 6, wherein the composition prevents or reduces inflammation in the skin of the subject.

10. The use according to claim 5 or 6, wherein the composition is administered at least daily.

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