Compositions and methods for treating and preventing skin damage

Abstract

To provide compositions and methods for treating and preventing skin damage.SOLUTION: As a composition that reverses, prevents and / or slows age-related skin damage, a composition formulated for topical administration is provided, comprising two or more components selected from the group consisting of Curcuma longa root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract.SELECTED DRAWING: Figure 1

Description

Technical Field

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

[0002] Field of Disclosure Compositions and methods for treating and preventing skin damage are provided herein. Specifically, compositions are provided herein that reverse, prevent and / or slow age-related skin damage.

Background Art

[0003] Background of the Disclosure The skin is the outermost organ of the body, has various functions, and has a great impact on appearance and posture. The total weight of the skin is about 3-5 kg of body weight, depending on the individual's body weight. The skin consists of various cells and special structures, covers the outer surface of the body, and functions as a primary barrier against the external environment (including water retention, temperature regulation, protection of the body from external stimuli such as UV, and protection from bacterial infections). Furthermore, the skin protects the body from physical or chemical injuries, infections caused by microorganisms (e.g., bacteria, fungi, and parasites), UV damage, drying, etc., and also functions as a sensory receptor in response to various external stimuli, and recognizes foreign antigens and produces immune cells.

[0004] Accumulating oxidative damage is thought to play an important role in the pathophysiology of many chronic diseases associated with aging. A prominent feature of aged human skin is the reduction in skin strength and function due to fragmentation and reduced production of type I collagen fibers, which make up most of the dermis.

Summary of the Invention

Problems to be Solved by the Invention

[0005] Accordingly, there is a need for improved skin care agents that prevent the effects of aging on the skin.

Means for Solving the Problem

[0006] Summary of the Disclosure In this specification, compositions and methods for the treatment and prevention of skin damage are provided. Specifically, in this specification, compositions are provided that reverse, prevent and / or delay age-related skin damage.

[0007] The compositions and methods described in this specification synergistically function to provide extracts of natural products that prevent and / or treat signs and symptoms of aging in the skin.

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

[0009] Further embodiments provide a composition that comprises, consists essentially of, or consists of two or more (e.g., 2 or all) components selected from, for example, Malpighia emarginata extract, Rubus fruticosus leaf extract or Centipeda cunninghamii extract (e.g., Centipeda cunninghamii leaf / stem extract), wherein the composition is formulated for topical administration.

[0010] Still other embodiments provide a composition comprising, consisting essentially of, or consisting of an extract of Curcurama longa, an extract of Osmanthus fragrans flower, and an extract of Spinacia oleracea leaf, wherein the composition is formulated for topical administration.

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

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

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

[0014] The present disclosure is not limited to specific concentrations of the disclosed extracts. For example, in some embodiments, the Malpighia emarginata extract is present in this composition at a concentration of 0.1 to 1.0 wt% (e.g., 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.9, 0.9, or 1.0 wt%); the Rubus fruticosus leaf extract is present in this composition at a concentration of 0.05 to 0.5 wt% (e.g., 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, or 0.5 wt%); the Centipeda cunninghami extract is present in this composition at a concentration of 0.25 to 1.25 wt% (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 wt%); the Osmanthus fragrans flower extract is present in this composition at a concentration of 0.5 to 1.5 wt% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4, or 1.5 wt%); the Spinacia oleracea leaf extract is present in this composition at a concentration of 0.5 to 1.5 wt% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4, or 1.5 wt%); and the Curcuma longa extract is present in this composition at a concentration of 0.5 to 1.5 wt% (e.g., 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1., 1.4, or 1.5 wt%).

[0015] Further embodiments provide a method of repairing damaged skin, comprising administering a composition comprising two or more (e.g., 2, 3, or all) components selected from, for example, Malpighia emarginata extract, Curcurama longa extract, Osmanthus fragrans flower extract, or Spinacia oleracea leaf extract, wherein the composition is formulated for topical administration to the skin of a subject under conditions such that it treats one or more signs or symptoms of skin damage.

[0016] In some embodiments, for example, there is provided a method of preventing skin damage, which includes administering a composition comprising two or more (e.g., two or all) components selected from Malpighia emarginata extract, Rubus fruticosus leaf extract, or Centipeda cunninghami extract, wherein the composition is formulated for topical administration to the skin of a subject under conditions such that one or more signs or symptoms of the skin are prevented.

[0017] In a further embodiment, there is provided a method of treating and / or preventing skin damage, which includes administering to a subject in need thereof the composition described herein.

[0018] In some embodiments, the skin damage is age-related skin damage. In some embodiments, one or more signs or symptoms are selected from, for example, wrinkles, spots, reduced 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 applied at least daily (e.g., over a period of one or more days to one week or one year or indefinitely).

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

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

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

[0022]

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Mode for Carrying Out the Invention

[0023] Definitions As used herein, the term “in vitro” refers to an artificial environment and processes or reactions occurring within an artificial environment. Examples of 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 within a natural environment.

[0024] As used herein, the term “effective amount” refers to an amount of a composition (e.g., a composition described herein) sufficient to produce a beneficial or desired result. The effective amount may 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.

[0025] As used herein, the term “administer” refers to the act of giving a drug, prodrug, or other agent or therapeutic treatment (e.g., a composition described herein) to a physiological system (e.g., a subject or an in vivo, in vitro, or ex vivo cell, tissue, and organ). Exemplary routes of administration to the human body can be via the eye (ophthalmic), mouth (oral), skin (transdermal), nose (nasal), lung (inhalation), oral mucosa (buccal), ear, injection (e.g., intravenous, subcutaneous, intratumoral, intraperitoneal, etc.), topical administration, and the like.

[0026] As used herein, the term "co - administration" refers to the administration to a subject of at least two agents (e.g., the compositions described herein) in combination with an agent or treatment known to prevent or reverse skin aging. In some embodiments, the co - administration of two or more agents or treatments is simultaneous. In other embodiments, the first agent / treatment is administered before the second agent / treatment. One of ordinary skill in the art understands that the formulation and / or route of administration of the various agents or treatments used may vary. Appropriate dosages for co - administration can be readily determined by one of ordinary skill in the art. In some embodiments, when agents or treatments are co - administered simultaneously, each agent or treatment is administered at a lower dosage than the dosage appropriate for its administration alone. Thus, co - administration is particularly desirable in embodiments where the co - administration of agents or treatments reduces the required dosage of a potentially harmful (e.g., toxic) agent.

[0027] 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 the administration of a toxicant.

[0028] As used herein, the term "pharmaceutical composition" refers to a combination of an active agent (e.g., those described herein) and an inert or active carrier that makes a composition particularly suitable for in vitro, in vivo, or ex vivo diagnostic or therapeutic use.

[0029] The terms "pharmaceutically acceptable" or "pharmacologically acceptable", as used herein, refer to compositions that do not substantially cause adverse reactions, such as toxic, allergic, or immunological reactions, when administered to a control.

[0030] As used herein, the term "topically" refers to the application of the compositions of the present invention to the surface of cells and tissues of the skin and mucosa (e.g., alveolar, buccal, tongue, gingival, or nasal mucosa, as well as other tissues and cells along the luminal organs or body cavities).

[0031] As used herein, the term "pharmaceutically acceptable carrier" refers to any of the standard pharmaceutical carriers, including, but not limited to, phosphate buffered saline aqueous solutions, water, emulsions (such as oil / water or water / oil emulsions), and various kinds of wetting agents, any and all solvents, dispersion media, coatings, sodium lauryl sulfate, isotonic agents and absorption delaying agents, disintegrants (such as potato starch or sodium starch glycolate), etc. The composition may also include stabilizers and preservatives. See, for example, Martin, Remington’s Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, Pa. (1975), which is incorporated herein by reference.

[0032] As used herein, the term "cell culture" refers to the in vitro culture of any cells (such as prokaryotic and eukaryotic cells). Within the scope of this term are subcultured cell lines (such as those having important phenotypes), primary cell cultures, transformed cell lines, finite cell lines (such as non-transformed cells), bacterial cultures, and any other cell populations maintained in vitro, in solid or liquid media or on media.

[0033] As used herein, the term "sample" is used in its broadest sense. In one meaning, it means a specimen or culture obtained from any source, as well as biological samples and environmental samples. Biological samples may be obtained from animals (including humans) and include liquids, solids, tissues and gases. Biological samples include blood preparations such as plasma, serum. However, such examples are not to be construed as limiting the types of samples applicable to the present invention.

[0034] Detailed Description of the Disclosure Compositions and methods for the treatment and prevention of skin damage are provided herein. Specifically, compositions are provided herein that reverse, prevent and / or slow age-related skin damage.

[0035] Oxidative exposure results in an increase in the intracellular levels of reactive oxygen species (ROS), which promote cell and molecular changes similar to the phenotype of skin fibroblasts in aged / photoaged human skin. The characteristics of this phenotype include impairment of the TGF-beta pathway, which leads to a decrease in the production of proteins such as type I procollagen that make up the extracellular matrix of the skin, and upregulation of the AP-1 transcription factor pathway, which drives the production of collagen-degrading matrix metalloproteinases and pro-inflammatory cytokines.

[0036] A modification of the described method for a defined regimen (He et al., AGE (2014) 36:1079-1094) involving fibroblast senescence by exposing primary human adult fibroblasts to H2O2 was used to assay botanical extracts and their combinations. For example, as described in the experimental section below, extracts with preventive activity can be screened by adding the extract prior to hydrogen peroxide. Further, compounds may be added after hydrogen peroxide treatment (e.g., after the aging period) to identify extracts with restored aged skin activity.

[0037] In this screening method, compounds were applied after oxidative exposure and the cells were then aged for an additional 5 days. This work found that several compounds were able to restore collagen homeostasis by downregulating matrix metalloproteinase 1 (MMP-1) and increasing type I procollagen. Further experiments described herein tested botanical extracts and their combinations in a cell-based model of skin aging. These complex models revealed the ranking of the efficacy of extracts for beneficial anti-aging activity. Importantly, this study revealed new combinations of botanicals for both the prevention of skin aging and the repair of aged skin.

[0038] The combinations of botanical extracts described herein target multiple pathways and can inhibit cortisol activity, as shown in a cutaneous oxidative exposure aging model, and have been shown to affect skin aging. Exemplary compositions are described herein.

[0039] I. Compositions As described herein, in some embodiments, the present disclosure provides a composition comprising one or more botanical extracts for use in treating, preventing, delaying, and / or reversing signs or symptoms of aging in the skin. In some embodiments, the compounds reverse visible or other signs of skin aging (such as, but not limited to, wrinkles, spots, loss of elasticity, dry skin, loss of firmness, or dryness). In some embodiments, the compounds correct imbalances in collagen homeostasis found in aged skin and / or reduce inflammation in the skin. Non-limiting examples of exemplary compositions of the present disclosure are described herein. In some embodiments, the composition comprises, consists essentially of, or consists of one or more of the components in the table below.

[0040] [Table 1] TIFF2025108640000003.tif206166

[0041] The extract can be obtained, for example, from commercial sources or by extraction. Examples of commercial sources include Malpighia emarginata fruit extract (Access Business Group, LLC, Ada, MI); Rubus fruticosus leaf extract (from SymMatrix, Symrise, Holzminden, Germany); Centipeda cunninghamiifolia leaf / stem extract (from Plantolin BG, Bio Actives Export, Melbourne, Australia); Spinacia oleracea leaf extract (Access Business Group, LLC); Curcuma longa root extract (from HerbEx Curcuma Extract, Biospectrum through Clariant, Muttenz, Switzerland); and Osmanthus fragrans flower extract (DermalRx Lushield, Biocogent, Stony Brook, NY), but are not limited thereto.

[0042] In some exemplary embodiments, the composition comprises, consists essentially of, or consists of two or more (e.g., two, three, or all) components selected from, for example, Malpighia emarginata fruit extract, Curcuma longa root extract, Osmanthus fragrans flower extract, or Spinacia oleracea leaf extract; for example, Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, or Centipeda cunninghamiifolia 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 cunninghamiifolia leaf / stem extract or Malpighia emarginata fruit extract, Curcuma longa root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract.

[0043] The present disclosure is not limited to a specific concentration of the extract of the present disclosure. For example, in some embodiments, the Malpighia emarginata fruit extract is present in the composition at a concentration of 0.1 to 1.0% by weight (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 to 0.5% by weight (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 cunninghamiifolia leaf / stem extract is present in the composition at a concentration of 0.25 to 1.25% by weight (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 to 1.5% by weight (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 to 1.5% by weight (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 extract root is present in the composition at a concentration of 0.5 to 1.5% by weight (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).

[0044] In some embodiments, the compound (e.g., those described herein) is formulated in a composition (e.g., a pharmaceutical composition, a functional food composition, or a cosmetic) for administration to the skin.

[0045] Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, solutions, mouthwashes, and powders. Conventional pharmaceutical carriers, aqueous, powder or oil-based, thickeners, etc. may be required or desirable.

[0046] Examples of the pharmaceutical compositions of the present disclosure include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions can be produced from various components (including, but not limited to, pre-formed liquids, self-emulsifying solids, and self-emulsifying semi-solids).

[0047] This composition may further contain other additional components conventionally found in pharmaceutical compositions. Thus, for example, the composition may contain additional pharmaceutically active substances of suitability, such as antipruritics, astringents, local anesthetics, or anti-inflammatory agents, etc., or additional substances useful in physically formulating various dosage forms of the composition, such as dyes, flavor additives, preservatives, antioxidants, opacifiers, thickeners, and stabilizers, etc. However, when such substances are added, they should not unduly inhibit the biological activity of the components of this composition. This formulation may be sterilized, and if desired, may be mixed with auxiliaries that do not have a harmful interaction with the active agent of this formulation, such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts affecting osmotic pressure, buffers, colorants, flavor additives, and / or aromatic substances, etc.

[0048] The compositions of the present disclosure may 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 may also contain various known and conventional cosmetic ingredients, provided that they do not adversely affect the desired results.

[0049] A cosmetically acceptable vehicle acts as a diluent, dispersant, or carrier for other substances present in the composition, facilitating its dispersion when the composition is applied to the skin.

[0050] Vehicles other than water may include liquid or solid emollients, solvents, humectants, thickeners, and powders. For example, the following vehicles may be used alone or in combination of one or more vehicles.

[0051] Examples of emollients include stearyl alcohol, glyceryl monolinoleate, 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, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, di-n-butyl 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 seed oil, perilla oil, soybean oil, sunflower seed oil, avocado oil, sesame 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, but are not limited thereto.

[0052] As used herein, "emollient" refers to a substance used for the prevention or reduction of dryness and for the protection of the skin. A wide variety of suitable emollients are known and can be used herein. Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), which is incorporated herein by reference, contains numerous examples of suitable materials. Examples of useful classes of emollients include the following:

[0053] 1. Hydrocarbon oils and waxes. Examples include mineral oil, petrolatum, paraffin, ceresin, ozokerite, microcrystalline wax, polyethylene, and perhydrosqualene.

[0054] 2. Silicone oils, such as dimethylpolysiloxane, methylphenylpolysiloxane, water-soluble and alcohol-soluble silicone glycol copolymers.

[0055] 3. Triglyceride esters, 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.

[0056] 4. Acetoglyceride esters, such as acetylated monoglyceride.

[0057] 5. Ethoxylated glycerides, such as ethoxylated glyceryl monostearate.

[0058] 6. Alkyl esters of fatty acids having 10 to 20 carbon atoms. Methyl esters, isopropyl esters, and butyl esters of fatty acids are particularly useful herein. Examples of other useful alkyl esters include hexyl laurate, isohexyl laurate, isohexyl palmitate, isopropyl palmitate, decyl oleate, isodecyl oleate, hexadecyl stearate, decyl oleate, isodecyl oleate, hexadecyl stearate, decyl stearate, isopropyl isostearate, diisopropyl adipate, diisohexyl adipate, dihexyl decyl adipate, diisopropyl sebacate, lauryl lactate, myristyl lactate, and cetyl lactate.

[0059] 7. Alkenyl esters of fatty acids having 10 to 20 carbon atoms. Examples include oleyl myristate, oleyl stearate, and oleyl oleate.

[0060] 8. Fatty acids having 10 to 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.

[0061] 9. Fatty alcohols having 10 to 20 carbon atoms. Lauryl alcohol, myristyl alcohol, cetyl alcohol, hexadecyl alcohol, stearyl alcohol, isostearyl alcohol, hydroxystearyl alcohol, oleyl alcohol, ricinoleyl alcohol, behenyl alcohol, and erucyl alcohol, as well as 2-octyldodecanol, are examples of saturated fatty alcohols.

[0062] 10. Fatty alcohol ethers. Examples of ethoxylated fatty alcohols having 10 to 20 carbon atoms include lauryl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oelyl alcohol, and cholesterol alcohol having 1 to 50 ethylene oxide groups or 1 to 50 propylene oxide groups attached.

[0063] 11. Ether-esters, such as fatty acid esters of ethoxylated fatty alcohols.

[0064] 12. Lanolin and derivatives. Lanolin, lanolin oil, lanolin wax, lanolin alcohol, lanolin fatty acid, 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-ester, hydrocracking of lanolin, ethoxylated hydrogenated lanolin, ethoxylated sorbitol lanolin, and liquid and semi-solid lanolin absorption bases are examples of softening agents derived from lanolin.

[0065] 13. Polyhydric alcohols 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 glycol and derivatives, hexylene glycol (2-methyl-2,4-pentanediol), 1,3-butylene glycol, 1,2,6-hexanetriol, ethexadiol USP (2-ethyl-1,3-hexanediol), C 15 -C 18 Vicinal glycols, and polyoxypropylene derivatives of trimethylolpropane are examples of substances of this class.

[0066] 14. Polyhydric alcohol esters. Ethylene glycol mono- and di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, polyethylene glycol (200 - 6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol poly-fatty acid esters, ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene polyol fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters are saturated polyhydric alcohol esters for use herein.

[0067] 15. Wax esters, such as beeswax, spermaceti, myristyl myristate, stearyl stearate.

[0068] 16. Beeswax derivatives, such as polyoxyethylene sorbitol beeswax. These are reaction products of beeswax with ethoxylated sorbitols of various ethylene oxide contents, forming mixtures of ether-esters.

[0069] 17. Vegetable waxes, including carnauba wax and candelilla wax.

[0070] 18. Phospholipids, such as lecithin and derivatives.

[0071] 19. Sterols. Cholesterol and cholesterol fatty acid esters are examples thereof.

[0072] 20. Amides, such as fatty acid amides, ethoxylated fatty acid amides, solid fatty alcohol alkanolamides.

[0073] The vehicle may also include propellants, such as propane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide; and solvents, such as ethyl alcohol, isopropanol, acetone, ethylene glycol monomethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, or powders, such as chalk, talc, fuller's earth, kaolin, starch, rubber, colloidal silica, sodium polyacrylate, tetraalkyl and / or trialkylaryl ammonium smectite, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, and / or ethylene glycol monostearate.

[0074] This composition may optionally include sunscreens, such as inorganic and organic sunscreens, and provides protection from the harmful effects of excessive exposure to sunlight during use of the composition of the present invention.

[0075] This composition may also optionally contain, as a sunscreen, silica such as titanium dioxide, zinc oxide having an average particle size of 1 to 300 nm, iron oxide having an average particle size of 1 to 300 nm, and fumed silica having an average particle size of 1 to 100 nm. When used as a component in an emulsion according to the present invention, the silica provides protection from infrared irradiation.

[0076] In some embodiments, when an oil or oily substance (plasticizer) is present, usually together with an emulsifier, to provide either an oil-in-water emulsion or a water-in-oil emulsion (largely depending on the average hydrophilic-lipophilic balance (HLB) of the emulsifier used), the composition is an emulsion. If an oil-in-water emulsion is required, the emulsifier selected must usually have an average HLB value of 1 to 6. If a water-in-oil emulsion is required, the emulsifier selected must have an average HLB value greater than 6.

[0077] Examples of suitable emulsifiers include, but are not limited to: sorbitan trioleate, sorbitan trioleate, glycerol monooleate, glycerol monostearate, glycerol 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.

[0078] It is understood that, if desired, more than one emulsifier may be used. The amount of the emulsifier or mixture thereof that may optionally be incorporated into the composition is 1 to 50 wt%, 2 to 20 wt%, or 2 to 10 wt% of the composition.

[0079] This composition may also contain water, usually up to 95 wt%, for example 5 to 95 wt%.

[0080] This composition may also optionally contain a high molecular weight silicone surfactant that can also act as an emulsifier, instead of or in addition to the above-mentioned optional emulsifiers.

[0081] When present in this composition, the amount of the silicone surfactant will usually be up to 25 wt% of the emulsion, preferably 0.5 to 15 wt%.

[0082] Examples of conventional additives that may optionally be used include preservatives such as para-hydroxybenzoate esters; antioxidants such as butylhydroxytoluene; humectants such as glycerol, ethoxylated glycerol such as glycereth-26, sorbitol, 2-pyrrolidone-5-carboxylate, dibutyl phthalate, gelatin, polyethylene glycol such as PEG 200 - 600; buffer solutions combined with bases such as triethanolamine or sodium hydroxide; waxes such as beeswax, ozokerite wax, paraffin wax; plant extracts such as Aloe Vera, cornflower, American mandrake, elderflower, cucumber; as well as acerola cherry ferment, thickeners; activity enhancers; colorants; and fragrances. Cosmetic additives can form the balance of the composition.

[0083] It may also be desirable to incorporate an anti-inflammatory agent and / or an inflammation inhibitor. Natural anti-inflammatory agents and / or inflammation inhibitors are preferred. For example, licorice and its extracts, dipotassium glycyrrhizinate, aloe vera and aloe vera extracts, candelilla wax, alpha bisabolol, aloe vera, manjistha (a plant of the genus Rubia, specifically extracted from Rubia cordifolial), and guggul (a plant of the genus Commiphora, specifically extracted from Commiphora Mukul) may be used.

[0084] Additional agents beneficial to the skin, such as ceramides, glycoceramides, pseudoceramides, sphingolipids such as sphingomyelin, cerebrosides, sulfatides, and gangliosides, sphingosine, dihydrosphingosine, phytosphingosine, phospholipids may also be incorporated, either separately or in a mixture. Fatty acids may also be combined with these agents beneficial to the skin. For example, ceramides and glycoceramides include those described in U.S. Pat. Nos. 5,589,178, 5,661,118, and 5,688,752, and the relevant portions of these documents are incorporated herein by reference. For example, pseudoceramides include those described in U.S. Pat. Nos. 5,198,210; 5,206,020; and 5,415,855, and the relevant portions of these documents are incorporated herein by reference.

[0085] In some embodiments, the pharmaceutical composition or cosmetic composition comprises (a) the composition described herein; and (b) one or more other agents useful in treating, preventing, or reversing skin aging.

[0086] In some embodiments, the composition is administered in a maintenance or progressive manner (e.g., once or more per day, twice or more per day, once or more per week, etc.). In some embodiments, the composition is administered continuously (e.g., via a skin patch, bandage, or sustained-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 one week, one month, one year, or indefinitely.

[0087] II. Uses As described herein, the compositions of the present disclosure find use in treating, preventing, or delaying skin damage (e.g., aging-related skin damage). In some embodiments, the composition is optimized for either 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., two, three, or all) components selected from, for example, Malpighia emarginata fruit extract, Curcuma longa root extract, Osmanthus fragrans flower extract, or Spinacia oleracea leaf extract.

[0088] In some embodiments, a composition for preventing skin damage comprises, consists essentially of, or consists of two or more (e.g., two or all) components selected from, for example, Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, or Centipeda cunninghami stem / leaf extract.

[0089] In some embodiments, administration of the compositions described herein prevents or reduces one or more symptoms of skin damage (e.g., wrinkles, spots, loss of 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.

[0090] In some embodiments, this composition is applied at least daily (e.g., over a period of 1 day or more to 1 week or 1 year or more or indefinitely).

Examples

[0091] Experiment The following examples are provided to demonstrate and further explain certain embodiments of the present disclosure and are not to be construed as limiting the scope of the present disclosure.

[0092] Example 1 This example describes the screening of botanical extracts for the prevention and repair of aging-related skin damage.

[0093] The following compositions were used in this example: Prevention: 0.5% Acerola cherry, 0.1% Blackberry, 0.75% Centipeda; Repair: 1% Osmanthus, 1% Spinach, 1% Turmeric.

[0094] The botanicals were tested in the oxidative exposure aging model described in FIGS. 1 - 3. The test was carried out in 3 steps and divided into 5 pathways: 1. Early prevention of aging phenotypes a. Activation of the antioxidant pathway was 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.

[0095] 2. Middle-aged aging phenotypes before acquiring permanent aging phenotypes a. Early protection / repair: Inhibition of the AP-1 / MMP1 collagen damage pathway. The botanicals were added after oxidative exposure at a time point before the fibroblasts acquired a permanent aging phenotype.

[0096] b. Early protection / repair: Protection of the TGF-beta / collagen production pathway. The botanicals were added after oxidative exposure but before the fibroblasts acquired a permanent aging phenotype.

[0097] 3. Fully acquired senescence phenotype a. Recovery: inhibition of the AP-1 / MMP1 collagen damage pathway. Botanicals were added after the fibroblasts had stabilized to the senescence phenotype.

[0098] b. Recovery: protection of the TGF-beta / collagen production pathway. Botanicals were added after the fibroblasts had stabilized to the senescence phenotype.

[0099] This study revealed a unique sequence of the efficacy of botanicals for the inhibition of different senescence pathways at different stages of senescence (early, mid, and fully acquired) (Tables 1 - 5). This finding indicated that a unique combination of active botanicals provided a more comprehensive anti-aging benefit than single agents.

[0100] Antioxidant response element assay HepG2 cells stably transfected with a luciferase reporter construct (pGL4.27) under the control of the antioxidant response element (ARE: GTGACxxxGCA (SEQ ID NO: 1) ) were seeded into white-wall collagen-coated plates at a density of 30,000 cells per well in the minimum essential tissue culture medium containing 10% serum. After 24 hours, the individual components (acerola cherry (AC), blackberry powder (BB), and centipeda cunninghami extract (CC)) were diluted in the tissue culture medium and added to the wells at specific concentrations. Also, these three components were combined at a ratio of AC:BB:CC being 0.5:0.1:0.75 respectively. This 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 (Biotium, Inc., Hayward, CA) according to the manufacturer's instructions. The data were presented as the % response of the untreated wells. The individual components that responded at a specific dose were represented as a stacked bar graph labeled "predicted values" in Figure 4. These are the predicted values of the ARE response when the sample effects are added together. The combination treatment using the same individual doses was shown in Figure 4 and represented as a bar graph labeled "measured values" in Figure 4. This represents the response of the combination and indicates synergistic activity.

[0101] Heme oxygenase (HOX) AG01518 fibroblasts were maintained in MEM + 2% charcoal-treated FBS + 1% penicillin / streptomycin / amphotericin B. After seeding 20,000 cells per well in a 96-well plate, the cells were maintained in MEM + 2% charcoal-treated FBS. This was treated with the individual components of the preventive complex and the repair complex as well as various dilutions of specific preventive complexes and repair complexes for 18 hours. The preventive complex contains Acerola cherry (AC), blackberry powder (BB) and Centipeda cuninghamii extract (CC), while the repair complex contains spinach leaves (SL; NF7321A), Osmantheis (OF; RN2407) and turmeric (T; (RN2404)) at various concentrations. After component treatment, the cells were lysed and RNA was isolated. HOX expression was quantified using RT-qPCR. The cycle threshold of each gene was normalized to its internal housekeeping gene, HPRT1. The treatment expression values were divided by the average expression value of the untreated control to calculate the HOX fold-expression level relative to the untreated control. The data are shown as the % response of the untreated wells. The effects of the individual components at specific doses on the HOX gene response are represented as stacked bar graphs labeled "predicted values" in FIGS. 5 and 6. These are the predicted values of the ARE response when the samples act individually. The treatment with the complex substances using the same individual doses "combined" together is shown in FIGS. 5 and 6 and represented as bar graphs labeled "measured values" in FIGS. 5 and 6. This measured value bar graph represents the response when the components act synergistically.

[0102] Human skin fibroblast repair assay Human dermal fibroblasts (HDF) cells were grown in DMEM medium (growth medium) in a 6-well plate. At 70% confluence, the cells were first washed with phosphate-buffered saline (PBS), and then treated with 150 μM H2O2 for 1 hour in a treatment medium (serum-free growth medium). After treatment, the cells were washed twice with phosphate-buffered serum (PBS), then growth medium was added to the cells and the plate was placed in an incubator. The next day, the same treatment (treatment with H2O2) was repeated. On the day following two consecutive days of H2O2 treatment, human dermal fibroblasts were treated individually or in combination with the components in the "repair complex substance" (day 1). The cells were further grown for 4 days. Then, on day 5, the cells were lysed and RNA was isolated using an RNeasy mini kit from Qiagen (Germantown, MD). Next, various sets of RNA were quantified via absorbance at 260 nm. Then, total RNA was converted to cDNA using an iScript cDNA synthesis kit from Bio-RAD (Hercules, CA). Then, the cDNA was diluted 5-fold and 5 μl was used per one qPCR reaction. qPCR was performed using SsoAdvanced Universal SYBR green supermix from Bio-RAD (Hercules, CA). Primers were purchased from Qiagen (Germantown, MD).

[0103] The data are presented as the percentage inhibition of the MMP1 response. The individual components that respond at a specific dose are presented as a stacked bar graph labeled "predicted values" in Figure 7. These are the predicted values from this assay when combined with the sample effect. The combination treatment using the same individual doses is presented as a bar graph labeled "measured values" and represents the response of the combination. Since this response is much higher than the sum of the individual responses at the same concentration, this combination exhibits synergistic activity.

[0104] [Table 2]

[0105]

Table 3

[0106]

Table 4

[0107]

Table 5

[0108]

Table 6

[0109] Example 2 The preventive complex substance component defends against the loss of type I procollagen production in adult human dermal fibroblasts: a preventive model of skin aging Primary adult human dermal fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 24 hours. The fibroblasts were treated with the indicated preventive complex substance components from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cunninghami (centipeda), either alone or in combination, for 2 days. The fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour for 2 consecutive days (oxidative exposure). After each oxidative exposure, the medium was replaced with fresh medium containing FBS and the preventive complex substance component. Six days after the second oxidative exposure, the medium was replaced with 2% FBS-containing medium (without the preventive complex substance component), and 12 hours later, the conditioned medium was collected for measurement of type I procollagen protein by ELISA. The level of type I procollagen protein was normalized to the number of fibroblasts. The relative concentrations of the preventive complex substance components were cherry:blackberry:centipeda at 0.5:0.1:0.75. The results are shown in Figure 8. The data represent 3 independent experiments.

[0110] The preventive complex substance component improves type I procollagen production in adult human dermal fibroblasts: An early treatment model for skin aging Primary adult human dermal fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 24 hours. Subsequently, the fibroblasts were placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour for two consecutive days (oxidative exposure). 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 preventive complex substance components derived from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cunninghami (centipeda), either as a single agent or in combination. Six days after the second oxidative exposure, the medium was replaced with 2% FBS-containing medium (without preventive complex substance components), and 12 hours later, the conditioned medium was collected for measurement of type I procollagen protein by ELISA. The level of type I procollagen protein was normalized to the number of fibroblasts. The relative concentration of the preventive complex substance components was cherry:blackberry:centipeda = 0.5:0.1:0.75. The results are shown in Figure 9. The data represent two independent experiments.

[0111] The repair complex substance component restores type I procollagen production in adult human dermal fibroblasts: A rejuvenation model for skin aging Human dermal fibroblasts were cultured to confluence in DMEM medium containing 10% fetal bovine serum (FBS). The fibroblasts were then placed in serum-free DMEM and exposed to 200 μM H2O2 for 1 hour for 2 consecutive days (oxidative exposure). 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 the same number of fibroblasts were cultured in a 24-well plate in medium containing 10% FBS. Two days later, the fibroblasts were treated for 6 days with the indicated repair complex components derived from spinach extract (spinach), Osmanthus fragrans (Asian sweet olive) flower extract (osmanthus), or Curcuma longa extract (curcumin), either alone or in combination. The medium was then replaced with medium containing 2% FBS (without the repair complex components), and 12 hours later, the conditioned medium was collected for measurement of type I procollagen protein by ELISA. The level of type I procollagen protein was normalized to the number of fibroblasts. The relative concentrations of the repair complex components were spinach:osmanthus:curcumin at 1:1:1. The results are shown in FIG. 10. The data represent two independent experiments.

[0112] The preventive complex components protect against collagen-degrading matrix metalloproteinase I in adult human dermal fibroblasts: a preventive model of skin aging Primary adult human dermal fibroblasts were cultured for 24 hours in DMEM medium containing 10% fetal bovine serum (FBS). The fibroblasts were treated for 2 days, either singly or in combination, with the indicated preventive complex components derived from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cunninghami (centipeda). The fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour for 2 consecutive days (oxidative exposure). After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS and the preventive complex components. Six days after the second oxidative exposure, the medium was replaced with 2% FBS-containing medium (without preventive complex components), and 12 hours later, the conditioned medium was collected for measurement of matrix metalloproteinase I protein by ELISA. The levels of matrix metalloproteinase I protein were normalized to the number of fibroblasts. The relative concentrations of the preventive complex components were cherry:blackberry:centipeda at 0.5:0.1:0.75. The results are shown in FIG. 11. The data represent 3 independent experiments.

[0113] Preventive complex components reduce collagen-degrading matrix metalloproteinase I in adult human dermal fibroblasts: An early treatment model for skin aging Primary adult human dermal fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 24 hours. The fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour for two consecutive days (oxidative exposure). 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 preventive complex components from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cunninghami (centipeda), either as a single agent or in combination. Six days after the second oxidative exposure, the medium was replaced with 2% FBS-containing medium (without the repair complex components), and 12 hours later, the conditioned medium was collected for measurement of matrix metalloproteinase I protein by ELISA. The levels of matrix metalloproteinase I protein were normalized to the number of fibroblasts. The relative concentrations of the preventive complex components were cherry:blackberry:centipeda at 0.5:0.1:0.75. The results are shown in Figure 12. The data represent two independent experiments.

[0114] The repair complex components reverse the level of collagen-degrading matrix metalloproteinase I production in adult human dermal fibroblasts: A model for skin aging reversal Human dermal fibroblasts were cultured to confluence in DMEM medium containing 10% fetal bovine serum (FBS). The fibroblasts were then placed in serum-free DMEM and exposed to 200 μM H2O2 for 1 hour for 2 consecutive days (oxidative exposure). 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 the same number of fibroblasts were placed in 24-well plates. Two days later, the fibroblasts were treated with the indicated repair complex components derived from spinach extract (spinach), Osmanthus fragrans (Asian sweet olive) flower extract (Osmanthus), or Curcuma longa extract (curcumin), either alone or in combination, in medium containing 10% FBS for 6 days. The medium was then replaced with medium containing 2% FBS (without repair complex components), and 12 hours later, the conditioned medium was collected for measurement of matrix metalloproteinase I protein by ELISA. The level of matrix metalloproteinase I was normalized to the number of fibroblasts. The relative concentrations of the repair complex components were spinach:Osmanthus:curcumin at 1:1:1. The results are shown in Fig. 13. The data represent two independent experiments.

[0115] The preventive complex component inhibits the production of prostaglandin E2, an inflammatory mediator in human epidermal cells.

[0116] Human skin cells (keratinocytes) were cultured in keratinocyte serum-free growth medium (SGM) until 60 - 70% confluence. Subsequently, the keratinocytes were cultured for 24 hours in fresh SGM containing 1% fetal bovine serum (FBS). The medium was replaced with fresh SGM containing the preventive complex substance components derived from 1% FBS and Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cunninghami (centipeda), either singly or in combination. After 6 hours, the conditioned medium was collected for measurement of prostaglandin E2 (PGE2) by ELISA. The level of PGE2 was normalized to the number of keratinocytes. The relative concentration of the preventive complex substance components was cherry:blackberry:centipeda at 0.5:0.1:0.75. The results are shown in Figure 14. The data represent two independent experiments.

[0117] The repair complex substance components inhibit the production of prostaglandin E2, an inflammatory mediator in human epidermal cells.

[0118] Human skin cells (keratinocytes) were cultured in keratinocyte serum-free growth medium (SGM) until 60 - 70% confluence. Subsequently, the keratinocytes were cultured for 24 hours in fresh SGM containing 1% fetal bovine serum (FBS). The medium was replaced with fresh SGM containing the repair complex substance components derived from 1% FBS and Spinacia oleracea extract (spinach), Osmanthus fragrans (Asian sweet olive) flower extract (osmanthus), or Curcuma longa extract (curcumin), either singly or in combination. After 6 hours, the conditioned medium was collected for measurement of prostaglandin E2 (PGE2) by ELISA. The level of PGE2 was normalized to the number of keratinocytes. The relative concentration of the repair complex substance components was spinach:osmanthus:curcumin at 1:1:1. The results are shown in Figure 15. The data represent two independent experiments.

[0119] The repair complex substance components inhibit the production of cortisol, a stress hormone.

[0120] Human adrenal cells (H295 cells) were cultured in DMEM / F12 (1:1) medium containing 10% Cosmic calf serum (CCS) until 60 - 70% confluence. Then, the cells were cultured in DMEM / F12 (1:1) medium containing 0.1% CSS for 24 hours. Next, the medium was replaced with fresh DMEM / F12 (1:1) medium containing the repair complex substance components from spinach extract (spinach), Osmanthus fragrans (sweet olive) flower extract (Osmanthus), or Curcuma longa extract (curcumin) either singly or in combination. After 22 hours, the conditioned medium was collected for measurement of cortisol by ELISA. The cortisol level was normalized to the cell number. The relative concentration of the repair complex substance components was spinach:Osmanthus:curcumin = 1:1:1. The results are shown in Figure 16. The data represent three independent experiments.

[0121] The preventive complex substance components inhibit the production of the stress hormone cortisol.

[0122] Human adrenal cells (H295 cells) were cultured in DMEM / F12 (1:1) medium containing 10% Cosmic calf serum (CCS) until 60 - 70% confluence. Then, the cells were cultured in DMEM / F12 (1:1) medium containing 0.1% CSS for 24 hours. Next, the medium was replaced with fresh DMEM / F12 (1:1) containing the preventive complex substance components from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cunninghami (Centipeda) either singly or in combination. After 22 hours, the conditioned medium was collected for measurement of cortisol by ELISA. The cortisol level was normalized to the cell number. The relative concentration of the preventive complex substance components was cherry:blackberry:Centipeda = 0.5:0.1:0.75. The results are shown in Figure 17. The results represent three independent experiments.

[0123] All publications, patents, patent applications, and registration numbers mentioned in the above specification are hereby incorporated by reference in their entirety herein. Although the invention has been described in connection with specific embodiments, the claimed invention should not be unduly limited to such specific embodiments. Indeed, various modifications and variations of the described compositions and methods of the invention will be apparent to those skilled in the art and are intended to be within the scope of the following claims.

Claims

1. A composition formulated for topical administration, comprising two or more constituents selected from the group consisting of Curcuma longa root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract.

2. The composition according to claim 1, comprising three or more of said constituents.

3. The composition according to claim 1, comprising all of said constituents.

4. A composition formulated for topical administration, comprising two or more constituents selected from the group consisting of Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, and Centipeda cunninghamiifolia / stem extract.

5. The composition according to claim 4, comprising all of said constituents.

6. A composition formulated for topical administration, comprising Curcuma longa root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract.

7. A composition formulated for topical administration, comprising Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, and Centipeda cunninghamiifolia / stem extract.

8. A composition formulated for topical administration, comprising Curcuma longa root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract.

9. The composition according to any one of claims 1 to 8, selected from the group consisting of solution, cream, lotion, gel, ointment, plaster, and spray.

10. The composition according to any one of claims 1 to 9, wherein the Malpighia emarginata fruit extract is present in the composition at a concentration of 0.1 to 1.0% by weight.

11. The composition according to claim 10, wherein the Malpighia emarginata fruit extract is present in the composition at a concentration of 0.5% by weight.

12. The composition according to any one of claims 1 to 11, wherein the Rubus fruticosus leaf extract is present in the composition at a concentration of 0.05 to 0.5% by weight.

13. The composition according to claim 12, wherein the Rubus fruticosus leaf extract is present in the composition at a concentration of 0.1% by weight.

14. The composition according to any one of claims 1 to 13, wherein the Centipeda cunninghamiifolia / stem extract is present in the composition at a concentration of 0.25 to 1.25% by weight.

15. The composition according to claim 14, wherein the Centipeda cunninghamiifolia leaf / stem extract is present in the composition at a concentration of 0.75% by weight.

16. The composition according to any one of claims 1 to 15, wherein the Osmanthus fragrans flower extract is present in the composition at a concentration of 0.5 to 1.5% by weight.

17. The composition according to claim 16, wherein the Osmanthus fragrans flower extract is present in the composition at a concentration of 1.0% by weight.

18. The composition according to any one of claims 1 to 17, wherein the Spinacia oleracea leaf extract is present in the composition at a concentration of 0.5 to 1.5% by weight.

19. The composition according to claim 18, wherein the Spinacia oleracea leaf extract is present in the composition at a concentration of 1.0% by weight.

20. The composition according to any one of claims 1 to 19, wherein the Curcuma longa root extract is present in the composition at a concentration of 0.5 to 1.5% by weight.

21. The composition according to claim 20, wherein the Curcuma longa root extract is present in the composition at a concentration of 1.0% by weight.

22. A method for repairing damaged skin, comprising administering the composition to the skin of a subject under conditions such that the composition according to any one of claims 1 to 3 treats one or more signs or symptoms of the skin damage.

23. A method for preventing skin damage, comprising administering the composition to the skin of a subject under conditions such that the composition according to any one of claims 4 to 5 prevents one or more signs or symptoms of the skin damage.

24. A method for treating and / or preventing skin damage, comprising administering the composition according to any one of claims 1 to 21 to a subject in need of treatment and / or prevention of skin damage.

25. The method according to claims 22 to 24, wherein the damage is age-related skin damage.

26. The method according to claims 22 to 25, wherein the one or more signs or symptoms are selected from the group consisting of wrinkles, spots, loss of elasticity and increased dryness.

27. The method according to claims 22 to 26, wherein the composition inhibits cortisol production in the skin of the subject.

28. The method according to claims 22 to 27, wherein the composition prevents or reduces inflammation in the skin of the subject.

29. The method according to claims 22 to 28, wherein the composition is applied at least daily.

30. Use of the composition according to claims 1 to 3 for treating one or more signs or symptoms of skin damage in a subject.

31. Composition according to claims 1 to 3 for use in the treatment of one or more signs or symptoms of skin damage in a subject.

32. Use of the composition according to claims 4 to 5 for preventing one or more signs or symptoms of skin damage in a subject.

33. Composition according to claims 4 to 5 for use in the prevention of one or more signs or symptoms of skin damage in a subject.

34. Use of the composition according to claims 1 to 21 for treating and / or preventing one or more signs or symptoms of skin damage in a subject.

35. Composition according to claims 1 to 21 for use in the treatment and / or prevention of one or more signs or symptoms of skin damage in a subject.

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