Compositions and methods for treating and preventing skin damage

Abstract

Provided herein are compositions and methods for the treatment and prevention of skin damage. In particular, provided herein are compositions that reverse, prevent, and / or slow age-related skin damage.

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 by reference in its entirety herein.

[0002] Field of Disclosure Provided herein are compositions and methods for the treatment and prevention of skin damage. In particular, provided herein are compositions that reverse, prevent and / or slow age-related skin damage. [Background technology]

[0003] Background of the disclosure Skin is the outermost organ of the body and has various functions and has a great influence on the appearance and figure. The total weight of the skin is about 3-5 kg ​​of body weight, depending on the body weight of the individual. The skin is composed of various cells and special structures, covers the outer surface of the body, and functions as a primary barrier against the external environment, including moisture conservation, temperature regulation, protection of the body from external stimuli such as UV, and protection from bacterial infection. In addition, the skin protects the body from physical or chemical injuries, infections caused by microorganisms (e.g., bacteria, fungi, and parasites), UV damage, dryness, etc., and also functions as a sensory receptor in response to various external stimuli, and recognizes foreign antigens to generate immune cells.

[0004] Accumulative oxidative damage is believed to play an important role in the pathophysiology of many chronic diseases associated with aging. A prominent feature of aged human skin is its reduced strength and function due to fragmentation and reduced production of type I collagen fibers, which constitute the majority of the dermis. Summary of the Invention [Problem to be solved by the invention]

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

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

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

[0008] For example, in some embodiments, provided herein are compositions comprising, consisting essentially of, or consisting of two or more (e.g., 2, 3, or all) components selected from, e.g., 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 compositions comprising, consisting essentially of, or consisting of two or more (e.g., two 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 Curcurama longa extract, Osmanthus fragrans flower extract, and Spinacia oleracea 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, Rubus fruticosus leaf extract, and Centipeda cuminghamii 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 flower extract, and Spinacia oleracea 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 any particular 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 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 Centipede cunnighamii 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 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).

[0015] Further embodiments provide methods of repairing damaged skin, comprising administering a composition comprising two or more (e.g., two, three, 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 to treat one or more signs or symptoms of skin damage.

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

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

[0018] In some embodiments, the skin damage is age-related skin damage. In some embodiments, the one or more signs or symptoms are selected from, for example, wrinkles, age spots, loss of elasticity, and increased dryness. In some embodiments, the composition inhibits cortisol production in the subject's skin. In some embodiments, the composition prevents or reduces inflammation in the subject's skin. In some embodiments, the composition is applied at least daily (e.g., for one or more days to one or more weeks or one or more years, or indefinitely).

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

[0020] Further provided is one or more of the compositions described herein for use in the treatment and / or prevention of one or more signs or symptoms of skin damage in a subject.

[0021] Further embodiments are described herein. [Brief description of the drawings]

[0022] [Figure 1]An exemplary protocol for screening agents for the prevention of oxidatively induced skin damage is presented. [Diagram 2] An exemplary protocol for screening agents for the prevention and repair of oxidatively induced skin damage is presented. [Diagram 3] An exemplary protocol for screening agents for the reversal and prevention of oxidatively induced skin damage is presented. [Figure 4] FIG. 1 shows the prevention of aging-induced skin damage by a combination of botanical extracts. [Diagram 5] FIG. 1 shows the prevention of aging-induced skin damage by a combination of botanical extracts. [Figure 6] FIG. 1 shows the repair of aging-induced skin damage by a combination of botanical extracts. [Figure 7] FIG. 1 shows the repair of aging-induced skin damage by a combination of botanical extracts. [Figure 8] 1 shows protection against premature loss of collagen production by a combination of botanical extracts. [Figure 9] 1 shows protection against premature loss of collagen production by a combination of botanical extracts. [Figure 10] 1 shows the restoration of collagen production by a combination of botanical extracts. [Figure 11] 1 shows protection against premature collagen degradation by a combination of botanical extracts. [Figure 12] 1 shows protection against collagen degradation by a combination of botanical extracts. [Figure 13] 1 shows the reversal of collagen degradation by a combination of botanical extracts. [Figure 14] 1 shows inhibition of inflammatory responses by a combination of botanical extracts. [Figure 15] 1 shows inhibition of inflammatory responses by a combination of botanical extracts. [Figure 16] 1 shows inhibition of cellular stress response by a combination of botanical extracts. [Figure 17] 1 shows inhibition of cellular stress response by a combination of botanical extracts. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] definition As used herein, the term "in vitro" refers to an artificial environment and to processes or reactions that occur within 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 a cell) and to processes or reactions that occur 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 effect a beneficial or desired result. An 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 "administration" refers to the act of providing a drug, prodrug or other agent or therapeutic treatment (e.g., compositions described herein) to a physiological system (e.g., a subject or cells, tissues and organs in vivo, in vitro, or ex vivo). Exemplary routes of administration to the human body can be via the eye (ophthalmic), mouth (oral), skin (transdermal), nose (nasal), lungs (inhalation), oral mucosa (buccal), ear, injection (e.g., intravenous, subcutaneous, intratumoral, intraperitoneal, etc.), topical administration, etc.

[0026] As used herein, the term "co-administration" refers to the administration to a subject of at least two agents (e.g., 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. Those skilled in the art will understand that the formulations and / or routes of administration of the various agents or treatments used may vary. The appropriate dosage for co-administration can be easily determined by those skilled in the art. In some embodiments, when agents or treatments are co-administered, 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 detrimental effect on a subject, cell, or tissue compared to the same cell or tissue prior to administration of the toxic agent.

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

[0029] The terms "pharmacologically acceptable" or "pharmacologically acceptable" as used herein refer to a composition that does not substantially elicit an adverse reaction, e.g., a toxic reaction, an allergic reaction, or an immune reaction, when administered to a subject.

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

[0031] As used herein, the term "pharmaceutical acceptable carrier" refers to any of the standard pharmaceutical carriers, 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 and absorption retarding agents, disintegrants (such as potato starch or sodium starch glycolate), and the like. The composition may also include stabilizers and preservatives. For examples of carriers, stabilizers and adjuvants, 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 (e.g., prokaryotic and eukaryotic cells). Included within the scope of this term are continuous cell lines (e.g., having a significant phenotype), primary cell cultures, transformed cell lines, finite cell lines (e.g., non-transformed cells), bacterial cultures, and any other population of cells maintained in vitro, in or on solid or liquid media.

[0033] As used herein, the term "sample" is used in its broadest sense. In one sense, it is meant to include specimens or cultures obtained from any source, as well as biological and environmental samples. Biological samples may be obtained from animals (including humans) and include liquids, solids, tissues, and gases. Biological samples include blood products such as plasma, serum, etc. However, such examples are not intended to limit the types of samples applicable to the present invention.

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

[0035] Oxidative exposure leads to elevated intracellular levels of reactive oxygen species (ROS) that promote cellular and molecular changes resembling the dermal fibroblast phenotype in aged / photoaged human skin. Characteristics of this phenotype include impaired TGF-beta pathway leading to decreased production of proteins such as type I procollagen that constitute the extracellular matrix of the skin, and upregulation of the AP-1 transcription factor pathway that drives the production of collagen-degrading matrix metalloproteinases and pro-inflammatory cytokines.

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

[0037] In this screening method, compounds were applied after oxidative exposure, and then cells were allowed to age for another 5 days. This work found that some compounds could restore collagen homeostasis by downregulating matrix metalloproteinase 1 (MMP-1) and increasing type I procollagen. Further experiments described herein tested botanical extracts and combinations thereof in cell-based models of skin aging. These combined models revealed a ranking of the potency of extracts for beneficial anti-aging activity. Importantly, this study revealed new combinations of botanicals for both preventing skin aging and repairing aged skin.

[0038] The combination of botanical extracts described herein has been shown to target multiple pathways and inhibit cortisol activity, affecting skin aging, as shown in the skin oxidative exposure aging model. Exemplary compositions are described herein.

[0039] I. Composition 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 compound reverses visible or other signs of aging in the skin, including, but not limited to, wrinkles, age spots, loss of elasticity, dry skin, loss of firmness, or dryness. In some embodiments, the compound corrects imbalances in collagen homeostasis found in aged skin and / or reduces inflammation in the skin. Exemplary, non-limiting examples of compositions of the present disclosure are described herein. In some embodiments, the composition comprises, consists essentially of, or consists of one or more components in the table below.

[0040] [Table 1] TIFF0007671762000002.tif206166

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

[0042] In some exemplary embodiments, the composition comprises two or more (e.g., 2, 3, or all) components selected from, e.g., Malpighia emarginata fruit extract, Curcuma longa root extract, Osmanthus fragrans flower extract, or Spinacia oleracea leaf extract; e.g., Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, or Centipeda cuminungumi leaf / stem extract; Curcurama longa longa) root extract, Osmanthus fragrans flower extract, and Spinacia oleracea leaf extract; Malpighia emarginata fruit extract, Rubus fruticosus leaf extract, and Centipeda cunnilingus 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 particular concentration of the extracts 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 Centipede cunnilingus 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 1.2% by weight). 5% by weight); 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); 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 Curcuma longa root 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).

[0044] In some embodiments, a 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, liquids, mouthwashes and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.

[0046] Pharmaceutical compositions of the present disclosure include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components, including, but not limited to, preformed liquids, self-emulsifying solids, and self-emulsifying semisolids.

[0047] The composition may further comprise other additional components conventionally found in pharmaceutical compositions. Thus, for example, the composition may comprise additional compatible pharma- ceutically active substances, such as antipruritic agents, astringents, local anesthetics or anti-inflammatory agents, or may comprise additional substances useful in physically compounding various dosage forms of the composition, such as dyes, flavor additives, preservatives, antioxidants, opacifiers, thickeners and stabilizers. However, such substances, when added, should not unduly inhibit the biological activity of the components of the composition. The formulation may be sterilized and, if desired, mixed with auxiliary substances that do not adversely interact with the active agents of the formulation, such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts that affect osmotic pressure, buffers, colorants, flavor additives and / or aromatic substances.

[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 pharma- ceutically acceptable forms. The compositions of the present invention may also contain various known and conventional cosmetic ingredients, so long as they do not adversely affect the desired results.

[0049] A cosmetically acceptable vehicle acts as a diluent, dispersant or carrier for other materials present in the composition, thereby aiding in the distribution of the composition when it 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 as a combination of one or more vehicles:

[0051] Emollients include stearyl alcohol, glyceryl monoricinoleate, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecyl-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, and oleyl alcohol. These include, but are not limited to, stearates, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cottonseed oil, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose 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.

[0052] As used herein, "emollient" refers to a material used to prevent or relieve dryness and to protect the skin. A wide variety of suitable emollients are known and may be used herein. Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), 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 monoglycerides.

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

[0058] 6. Alkyl esters of fatty acids having 10-20 carbon atoms. Methyl, isopropyl, 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, dihexyldecyl 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, ricinol 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 thereto.

[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 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, hydrogenolysis of lanolin, ethoxylated hydrogenated lanolin, ethoxylated sorbitol lanolin, and liquid and semi-solid lanolin absorption bases are examples of emollients 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 glycols and derivatives, hexylene glycol (2-methyl-2,4-pentanediol), 1,3-butylene glycol, 1,2,6-hexanetriol, ethoxyhexadiol USP (2-ethyl-1,3-hexanediol), C 15 -C 18 Vicinal glycols and polyoxypropylene derivatives of trimethylpropane are examples of this class of materials.

[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 sorbitol of various ethylene oxide contents, forming a mixture 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.

[0072] 20. Amides, such as fatty acid amides, ethoxylated fatty acid amides, solid fatty acid 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, gum, colloidal silica, sodium polyacrylate, tetraalkyl and / or trialkylaryl ammonium smectites, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, carboxyvinyl polymers, sodium carboxymethylcellulose, and / or ethylene glycol monostearate.

[0074] The compositions may optionally contain sunscreens, such as inorganic and organic sunscreens, to provide protection from the harmful effects of excessive exposure to sunlight during use of the compositions of the present invention.

[0075] The composition may also optionally contain titanium dioxide, zinc oxide having an average particle size of 1-300 nm, iron oxide having an average particle size of 1-300 nm, silica such as fumed silica having an average particle size of 1-100 nm as a sunscreen. When used as an ingredient in the emulsions according to the invention, silica provides protection from infrared radiation.

[0076] In some embodiments, the composition is an emulsion when an oil or oily substance (emollient) is present, usually together with an emulsifier, to provide either a water-in-oil emulsion or an oil-in-water emulsion (depending largely on the average hydrophilic lipophilic balance (HLB) of the emulsifier used). If a water-in-oil emulsion is required, the emulsifier selected should usually have an average HLB value of 1-6. If an oil-in-water emulsion is required, the emulsifier selected should have an average HLB value of 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 (Registered Trademark) , 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 more than one emulsifier may be used if desired. The amount of emulsifier or mixtures thereof that may optionally be incorporated in the composition is from 1 to 50%, from 2 to 20%, or from 2 to 10% by weight of the composition.

[0079] The composition may also contain water, typically up to 95% by weight, for example from 5 to 95% by weight.

[0080] The composition may also optionally include a high molecular weight silicone surfactant, which may also act as an emulsifier, either in place of or in addition to the optional emulsifiers mentioned above.

[0081] If present in the composition, the amount of silicone surfactant will typically be up to 25% by weight of the emulsion, preferably from 0.5 to 15%.

[0082] Examples of conventional additives that may be optionally used include preservatives, such as para-hydroxybenzoate esters; antioxidants, such as butyl hydroxytoluene; moisturizers, such as glycerol, ethoxylated glycerin, such as glycereth-26, sorbitol, 2-pyrrolidone-5-carboxylate, dibutyl phthalate, gelatin, polyethylene glycol, such as PEG 200-600; buffers with bases, such as triethanolamine or sodium hydroxide; waxes, such as beeswax, ozokerite wax, paraffin wax; plant extracts, such as Aloe Vera, cornflower, witch hazel, elderflower, cucumber; and 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 anti-inflammatory and / or anti-inflammatory agents. Natural anti-inflammatory and / or anti-inflammatory agents are preferred. For example, licorice and its extracts, dipotassium glycyrrhizinate, oats and oat extracts, candelilla wax, alpha bisabolol, aloe vera, manjistha (extracted from plants of the Rubia genus, specifically Rubia cordifolial) and guggul (extracted from plants of the Commiphora genus, specifically Commiphora Mukul) may be used.

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

[0085] In some embodiments, the pharmaceutical or cosmetic composition comprises (a) a 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 once, twice, five times, ten times, or more. In some embodiments, the composition is administered for a week, a month, a year, or indefinitely.

[0087] II. Application 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 compositions are 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., 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.

[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 cuminghamii 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, age spots, reduced elasticity, and increased dryness). In some embodiments, the composition inhibits cortisol production in the subject's skin. In some embodiments, the composition prevents or reduces inflammation in the subject's skin.

[0090] In some embodiments, the composition is applied at least daily (eg, for a period of one or more days to one or more weeks or a year or more, or indefinitely). EXAMPLES

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

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

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

[0094] The botanicals were tested in the oxidative exposure aging model described in Figures 1 to 3. The test was carried out in three steps, divided into five routes: 1. Early prevention of aging phenotypes a. Activation of antioxidant pathways was measured by survival and proliferation endpoints. Botanicals were added prior to oxidative exposure and their ability to prevent the formation of the senescent phenotype was measured.

[0095] 2. A midlife aging phenotype prior to the acquisition of a permanent aging phenotype Early protection / recovery: inhibition of the AP-1 / MMP1 collagen damage pathway. Botanicals were added after oxidative exposure and before fibroblasts acquire a permanent senescent phenotype.

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

[0097] 3. Fully Acquired Senescence Phenotype a. Recovery: Inhibition of the AP-1 / MMP1 collagen damage pathway. Botanicals were added after fibroblasts had stabilized to a senescent phenotype.

[0098] b. Recovery: Protection of the TGF-beta / collagen production pathway. The botanicals were added after fibroblasts had stabilized into a senescent phenotype.

[0099] This study revealed a unique hierarchy of potency of botanicals for inhibition of different aging pathways at different stages of aging (early, intermediate and fully acquired) (Tables 1-5). The findings indicated that the unique combination of active botanicals provided more comprehensive anti-aging benefits than the single agents.

[0100] Antioxidant response element assay Antioxidant response element (6X: GTGACxxxGCA (SEQ ID NO: 1) HepG2 cells stably transfected with a luciferase receptor construct (pGL4.27) under the control of , were plated in white-walled collagen-coated plates at a density of 30,000 cells per well in minimal tissue culture medium containing 10% serum. After 24 hours, the individual components (acerola cherry (AC), blackberry powder (BB) and Centipeda cumininha extract (CC)) were diluted in tissue culture medium and added to the wells at the specified concentrations. The three components were also combined in a ratio of AC:BB:CC of 0.5:0.1:0.75, respectively. The combinations were diluted to various concentrations and added to the test wells. After 48 hours, cells were lysed and luciferase was quantified using a luciferase assay (Biotium, Inc., Hayward, CA) according to the manufacturer's instructions. Data are presented as % response of untreated wells. The individual component responses at a particular dose are shown as stacked bars labeled "Predicted" in Figure 4. These are the predicted ARE responses when combined plus sample effects. Combination treatments using the same individual doses are shown in Figure 4 and are shown as bars labeled "Actual" in Figure 4. This represents the response of the combination, indicating synergistic activity.

[0101] Heme oxygenase (HOX) AG01518 fibroblasts were maintained in MEM + 2% charcoal stripped 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 stripped FBS. They were treated with individual components of the preventive and repair complexes as well as various dilutions of specific preventive and repair complexes for 18 hours. The preventive complexes included acerola cherry (AC), blackberry powder (BB) and Centipede cuminhinumii extract (CC), while the repair complexes included various concentrations of spinach leaf (SL; NF7321A), Osmantheis (OF; RN2407) and turmeric (T; (RN2404)). 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 treated expression value was divided by the average expression value of the untreated control to calculate the HOX fold expression level relative to the untreated control. Data are shown as % response of untreated wells. The effect of individual components at a particular dose on HOX gene response is shown as stacked bar graphs labeled "Predicted" in Figures 5 and 6. These are the predicted values ​​of the ARE response when the samples act individually. The combination agent treatment using the same individual doses together "in combination" is shown in Figures 5 and 6 and is shown as a bar graph labeled "Actual" in Figures 5 and 6. The Actual bar graph represents the response when the components act synergistically.

[0102] Human dermal fibroblast repair assay Human dermal fibroblast (HDF) cells were grown in DMEM medium (growth medium) in 6-well plates. At 70% confluency, the cells were first washed with phosphate-buffered saline (PBS) and then treated with 150 μM H2O2 for 1 hour in 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. Following two consecutive days of H2O2 treatment, the human dermal fibroblast cells were treated with the components in the "repair complex" individually or in combination (day 1). The cells were grown for another 4 days. Then, on day 5, the cells were lysed and RNA was isolated using the RNAeasy mini kit from Qiagen (Germantown, MD). The different sets of RNA were then quantified via absorbance at 260 nm. Total RNA was then converted to cDNA using the iscript cDNA synthesis kit from Bio-RAD (Hercules, CA). The cDNA was then diluted 5-fold and 5 μl was used per qPCR reaction. qPCR was performed using Sso advances Universal SYBR green supermix from Bio-RAD (Hercules, CA). Primers were purchased from Qiagen (Germantown, MD).

[0103] Data are expressed as percentage inhibition of MMP1 response. Individual component responses at a particular dose are shown as stacked bars labeled "Predicted" in Figure 7. These are predicted values ​​from this assay when combined with sample effects. Combination treatments using the same individual doses are shown as bars labeled "Actual" and represent the response of the combination. This combination shows synergistic activity since the response is much higher than the sum of the individual responses at the same concentration.

[0104] [Table 2]

[0105] [Table 3]

[0106] [Table 4]

[0107] [Table 5]

[0108] [Table 6]

[0109] Example 2 Components of a preventive complex protect against 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. Fibroblasts were treated with the indicated preventive complex components derived from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cuminghamii (Centipeda) either alone or in combination for 2 days. Fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour on 2 consecutive days (oxidative exposure). After each oxidative exposure, the medium was replaced with fresh medium containing FBS and 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, conditioned medium was collected for measurement of type I procollagen protein by ELISA. Type I procollagen protein levels were normalized to fibroblast cell number. The relative concentrations of the preventive complex components were 0.5:0.1:0.75 cherry:blackberry:centipeda. The results are shown in Figure 8. Data are representative of three independent experiments.

[0110] A preventive complex component improves type I procollagen production in adult human dermal fibroblasts: A model for early treatment of skin aging Primary adult human dermal fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 24 hours. Fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour on 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, cells were cultured in medium containing the indicated preventive complex components from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cuminhinum (Centipeda), either alone or in combination. Six days after the second oxidative exposure, the medium was replaced with 2% FBS-containing medium (without preventive complex components), and 12 hours later, conditioned medium was collected for measurement of type I procollagen protein by ELISA. Levels of type I procollagen protein were normalized to fibroblast cell number. The relative concentrations of the preventive complex components were 0.5:0.1:0.75 cherry:blackberry:centipeda. The results are shown in Figure 9. Data are representative of two independent experiments.

[0111] Components of a repair complex restore type I procollagen production in adult human dermal fibroblasts: A rejuvenating model of skin aging Human dermal fibroblasts were cultured to confluence in DMEM medium containing 10% fetal bovine serum (FBS). Fibroblasts were then placed in serum-free DMEM and exposed to 200 μM H2O2 for 1 h on two consecutive days (oxidative exposure). After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS. Five days after oxidative exposure, fibroblasts were harvested by trypsinization, counted, and equal numbers of fibroblasts were cultured in 24-well plates in medium containing 10% FBS. Two days later, fibroblasts were treated with the indicated repair complex components derived from spinach extract (Spinach), Osmanthus fragrans flower extract (Osmanthus), or Curcuma longa extract (Curcumin), either alone or in combination, for six days. The medium was then replaced with 2% FBS-containing medium (without repair complex components) and after 12 hours, 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 1:1:1 spinach:osmanthus:curcumin. The results are shown in Figure 10. Data are representative of two independent experiments.

[0112] Components of a preventive complex protect against collagen-degrading matrix metalloproteinase I in adult human dermal fibroblasts: A preventive model for skin aging Primary adult human dermal fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 24 hours. Fibroblasts were treated with the indicated preventive complex components derived from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cumininha (Centipeda) either alone or in combination for 2 days. Fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour on 2 consecutive days (oxidative exposure). After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS and 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, conditioned medium was collected for measurement of matrix metalloproteinase I protein by ELISA. Matrix metalloproteinase I protein levels were normalized to fibroblast cell count. The relative concentrations of the preventive complex components were 0.5:0.1:0.75 cherry:blackberry:centipeda. The results are shown in Figure 11. Data are representative of three independent experiments.

[0113] Components of a preventive complex reduce collagen-degrading matrix metalloproteinase I in adult human dermal fibroblasts: A model for early treatment of skin aging Primary adult human dermal fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 24 hours. Fibroblasts were then placed in serum-free DMEM and exposed to 100 μM H2O2 for 1 hour on 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, cells were cultured in medium containing the indicated preventive complex components from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cuminhinum (Centipeda), either alone or in combination. Six days after the second oxidative exposure, the medium was replaced with 2% FBS-containing medium (without repair complex components), and 12 hours later, conditioned medium was collected for measurement of matrix metalloproteinase I protein by ELISA. Matrix metalloproteinase I protein levels were normalized to fibroblast cell count. The relative concentrations of the preventive complex components were 0.5:0.1:0.75 Cherry:Blackberry:Centipede. The results are shown in Figure 12. Data are representative of two independent experiments.

[0114] Components of a repair complex reverse the levels of collagen-degrading matrix metalloproteinase I production in adult human dermal fibroblasts: A rejuvenating model of skin aging Human dermal fibroblasts were cultured to confluence in DMEM medium containing 10% fetal bovine serum (FBS). Fibroblasts were then placed in serum-free DMEM and exposed to 200 μM H2O2 for 1 h on two consecutive days (oxidative exposure). After each oxidative exposure, the medium was replaced with fresh medium containing 10% FBS. Five days after oxidative exposure, fibroblasts were harvested by trypsinization, counted, and equal numbers of fibroblasts were placed into 24-well plates. Two days later, fibroblasts were treated with the indicated repair complex components derived from spinach extract (Spinach), Osmanthus fragrans flower extract (Osmanthus), or Curcuma longa extract (Curcumin), either alone or in combination, for 6 days in medium containing 10% FBS. The medium was then replaced with 2% FBS-containing medium (without repair complex components) and 12 hours later, conditioned medium was collected for measurement of matrix metalloproteinase I protein by ELISA. Matrix metalloproteinase I levels were normalized to fibroblast cell number. The relative concentrations of repair complex components were 1:1:1 spinach:osmanthus:curcumin. The results are shown in Figure 13. Data are representative of two independent experiments.

[0115] The preventive complex components inhibit the production of the inflammatory mediator prostaglandin E2 in human epidermal cells.

[0116] Human skin cells (keratinocytes) were cultured in keratinocyte serum-free growth medium (SGM) to 60-70% confluence. Keratinocytes were then cultured in fresh SGM containing 1% fetal bovine serum (FBS) for 24 hours. The medium was replaced with fresh SGM containing 1% FBS and the indicated preventive complex components from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cuminhinum (centipeda) either alone or in combination. After 6 hours, conditioned medium was collected for measurement of prostaglandin E2 (PGE2) by ELISA. PGE2 levels were normalized to keratinocyte counts. The relative concentrations of preventive complex components were 0.5:0.1:0.75 for cherry:blackberry:centipeda. Results are shown in Figure 14. Data are representative of two independent experiments.

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

[0118] Human skin cells (keratinocytes) were cultured in keratinocyte serum-free growth medium (SGM) to 60-70% confluence. Keratinocytes were then cultured in fresh SGM containing 1% fetal bovine serum (FBS) for 24 hours. The medium was replaced with fresh SGM containing 1% FBS and the indicated repair complex components from spinach extract (Spinach), Osmanthus fragrans flower extract (Osmanthus), or Curcuma longa extract (Curcumin), either alone or in combination. After 6 hours, conditioned medium was collected for measurement of prostaglandin E2 (PGE2) by ELISA. PGE2 levels were normalized to keratinocyte number. The relative concentrations of repair complex components were 1:1:1, spinach:osmanthus:curcumin. Results are shown in Figure 15. Data are representative of two independent experiments.

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

[0120] Human adrenal cells (H295 cells) were cultured in DMEM / F12 (1:1) medium containing 10% Cosmic Calf Serum (CCS) to 60-70% confluence. The cells were then cultured in DMEM / F12 (1:1) medium containing 0.1% CSS for 24 hours. The medium was then replaced with fresh DMEM / F12 (1:1) medium containing 0.1% CSS and the indicated repair complex components from spinach extract (Spinach), Osmanthus fragrans flower extract (Osmanthus), or Curcuma longa extract (Curcumin), either alone or in combination. After 22 hours, conditioned medium was collected for measurement of cortisol by ELISA. Cortisol levels were normalized to cell number. The relative concentrations of the repair complex components were 1:1:1 spinach:osmanthus:curcumin. The results are shown in Figure 16. Data are representative of three independent experiments.

[0121] The preventative complex 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) to 60-70% confluence. The cells were then cultured in DMEM / F12 (1:1) medium containing 0.1% CSS for 24 h. The medium was then replaced with fresh DMEM / F12 (1:1) containing 0.1% CSS and the indicated preventive complex components from Acerola cherry (cherry), Rubus fruticosus blackberry leaf (blackberry), or Centipeda cuminhinum (centipeda) either alone or in combination. After 22 h, conditioned medium was collected for measurement of cortisol by ELISA. Cortisol levels were normalized to cell number. The relative concentrations of preventive complex components were 0.5:0.1:0.75 for cherry:blackberry:centipeda. The results are shown in Figure 17. Results are representative of three independent experiments.

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

Claims

1. 1. A composition formulated for topical administration to the skin of a subject, comprising a Curcuma longa root extract, an Osmanthus fragrans flower extract, and a Spinacia oleracea leaf extract.

2. 10. The composition of claim 1, which is selected from the group consisting of a solution, a cream, a lotion, a gel, an ointment, a salve, and a spray.

3. The composition according to any one of claims 1 to 2, wherein the Osmanthus fragrans flower extract is present in the composition at a concentration of 0.5 to 1.5% by weight.

4. 4. The composition of claim 3, wherein the Osmanthus fragrans flower extract is present in the composition at a concentration of 1.0% by weight.

5. The composition according to any one of claims 1 to 4, wherein the Spinacia oleracea leaf extract is present in the composition at a concentration of 0.5 to 1.5% by weight.

6. 6. The composition of claim 5, wherein the Spinacia oleracea leaf extract is present in the composition at a concentration of 1.0% by weight.

7. The composition according to any one of claims 1 to 6, wherein the Curcuma longa root extract is present in the composition at a concentration of 0.5 to 1.5% by weight.

8. 8. The composition of claim 7, wherein the Curcuma longa root extract is present in the composition at a concentration of 1.0% by weight.

9. 9. The composition of any one of claims 1 to 8 for use in a method of repairing damaged skin, the method comprising administering the composition of any one of claims 1 to 8 to the skin of a subject under conditions such that the composition treats one or more signs or symptoms of damage to the skin.

10. 9. The composition of any one of claims 1 to 8 for use in a method for treating and / or preventing skin damage, said method comprising administering a composition of any one of claims 1 to 8 to a subject in need of treatment and / or prevention of skin damage.

11. The composition according to claim 9 or 10, wherein the damage is age-related skin damage.

12. 10. The composition of claim 9, wherein the one or more signs or symptoms are selected from the group consisting of wrinkles, age spots, loss of elasticity and increased dryness.

13. The composition of any one of claims 9 to 12, wherein the composition inhibits cortisol production in the skin of the subject.

14. The composition of any one of claims 9 to 13, wherein the composition prevents or reduces inflammation in the skin of the subject.

15. The composition according to any one of claims 9 to 14, wherein the composition is applied at least daily.

16. The composition according to any one of claims 1 to 8 for treating one or more signs or symptoms of skin damage in a subject.

17. 9. A composition according to any one of claims 1 to 8 for use in treating one or more signs or symptoms of skin damage in a subject.

18. The composition according to any one of claims 1 to 8 for treating and / or preventing one or more signs or symptoms of skin damage in a subject.

19. A composition according to any one of claims 1 to 8 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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