Topical skin compositions that improve or maintain collagen, elastin, hyaluronic acid, and other extracellular matrix components

Abstract

Disclosed herein are methods and compositions that allow for increased absorption and retention of cosmetically active compounds and pharmaceutical ingredients in the skin. The methods and compositions also affect enzymes that are associated with degradation of the extracellular matrix and production and maintenance of extracellular matrix components. The methods and compositions can be used to improve or maintain the skin matrix production and concurrently inhibit skin matrix degradation enzymes. The methods and compositions can be used for personal care applications, including cosmetic and sunscreen applications. The methods and compositions can also be used for cancer treatment and prevention.

Description

TOPICAL SKIN COMPOSITIONS THAT IMPROVE OR MAINTAIN COLLAGEN, ELASTIN, HYALURONIC ACID, AND OTHER EXTRACELLULAR MATRIX COMPONENTS CROSS-REFERENCE WITH RELATED APPLICATIONS

[0001] This application claims the benefit of U. S. Provisional Application No.63 / 759,973, filed on February 18, 2025, which is hereby incorporated by reference in its entirety and for all purposes as if fully set forth herein.FIELD OF THE INVENTION

[0002] The invention relates to the fields of personal care, cosmetics, and cancer prevention and treatment.BACKGROUND

[0003] The skm is the largest organ of the body with a surface area of approximately 1.7 m², making this tissue one of the most readily accessible tissues for drug delivery. The skin includes 3 main layers, the outer epidermis layer, the central dermis layer, and the lowermost hypodermis layer. The epidermis is also divided into layers, and the outermost layer that is exposed to the environment is the stratum corneum.

[0004] The stratum comeum acts as a barrier, and this barrier is the reason why many compounds and other types of external agents (e.g., UV radiation, allergens, microorganisms, xenobiotics) are hindered from entering the skin. The stratum comeum is composed of dead and compact keratinocytes (comeocytes) embedded in a multilamellar lipid matrix composed mainly of ceramides, fatty' acids, cholesterol, and cholesterol sulfate. The lipids and proteins that compose the stratum comeum. make it a very' compact, dense, and impermeable layer that makes it difficult for compounds to be absorbed.

[0005] Topical drug and cosmetic products are systems that are designed to deliver active ingredients to local skin tissue. These products should act in such a way' as to delivery' active ingredients to the skin while minimizing systemic absorption. Such a delivery' system is difficult to develop m view of the multiple factors that affect skm permeability of drugs.

[0006] Locally -acting drugs can produce unwanted and off-target effects if they become absorbed and reach sites beyond their intended site of action. Absorption-affecting agents have been developed to enhance local absorption and minimize unwanted systemic targeting. Chemical permeation enhancers have been commonly used to enhance the301685781.1. 1.permeation of drugs through the stratum comeum by either fluidizing the stratum comeum lipid bilayer or disrupting keratinocytes. Permeation retarders have been developed to retard the permeation of compounds across the skin in order to reduce systemic and potentially toxic effects of some active ingredients.

[0007] Although interest m the targeting and retention of skin-active products to the skin has grown over the past few years, the majority of research either lacks procedural standardization or leads to product absorption m the skin and unwanted delivery across and through the skin. Therefore, there is a need in the topical product industry for improved products that focus on skin targeting and skin retention.SUMMARY

[0008] The present inventors have developed methods and compositions that allow for increased absorption and retention of cosmetically active compounds and pharmaceuticals in the skin. The methods and compositions also affect enzymes that are associated with degradation of the extracellular matrix and production and maintenance of extracellular matrix components. The methods and compositions can be used to improve or maintain the skin matrix production and concurrently inhibit the skin matrix degradation enzymes. The methods and compositions can be used for personal care applications, including cosmetic and sunscreen applications. The methods and compositions can be used for topical drug applications, including for the treatmen t and prevention of photocarcinogenesis and associated skin cancers.

[0009] In some embodiments, a method for treating skin of a subject in order to improve a condition of the subjects skin comprises topically applying a composition comprising an effective amount of at least one of tannic acid, gallic acid, ellagic acid, niacinamide, resveratrol, doxycycline, curcumin, and zoledronic acid to the subject’s skin. In some embodiments, improving a condition of the skin is selected from the group consisting of reducing collagen degradation, reducing elastin degradation, reducing hyaluronic acid degradation, maintaining or increasing collagen expression, increasing elastin expression, increasing hyaluronic acid production, increasing skin matrix production, inhibiting at least one enzyme responsible for degradation of extracellular matrix, reducing skin wrinkles, and reducing premature ageing. In some embodiments, the at least one enzyme responsible for degradation of extracellular matrix is selected from the group consisting of elastase, collagenase, hyaluronidase, and a matrix metalloproteinase. In some embodiments, the matrix metalloproteinase is matrix metalloproteinase-1.301685781.1 - 2 -

[0010] Some embodiments of the present disclosure are directed to a method for increasing epidermal permeability of at least one topically-applied compound having at least one cosmetic effect, retaining at least one topically-applied compound having at least one cosmetic effect in the dermis while avoiding systemic absorption of the topically-applied compound, and / or increasing an effect of at least one topically-applied compound having at least one cosmetic effect. In some embodiments, the method comprises topically applying a composition comprising the at least one compound having at least one cosmetic effect and an effective amount of at least one surfactant and / or at least one polymer. In some embodiments, the at least one surfactant and / or at least one polymer is selected from the group consisting of Tween 20, Tween 40, Tween 60, Tween 80, Laureth-4, Laureth-23, Ceteth-10, Ceteth-20, Oleth-5, Oleth-10, KCS20, KRH40, Poloxamer 124, Poloxamer 182, Poloxamer 188, Poloxamer 407, Span20, Span60, Span80, Span83. PEG8 stearate, PEG40 stearate, sodium hyaluronate, gellan gum, hydroxyethyl cellulose, hydropropyl cellulose, and Noveon AA-1 polycarbophil. In some embodiments, the composition comprises a carrier comprising the at least one compound having at least one cosmetic effect, water, glycerin, and PEG400. In some embodiments, the carrier comprises 50-75% by weight of water; 10-30% by weight of glycerin; and 10-30% by weight of PEG400. In some embodiments, the carrier comprises about 56% by weight of water; about 23% by weight of glycerin; and about 21% by weight of PEG400. In some embodiments, the carrier comprises from 1 to 100 mg / ml of the at least one compound having at least one cosmetic effect. In some embodiments, the at least one compound having at least one cosmetic effect is doxycycline and the least one surfactant and / or at least one polymer is Tween 20. In some embodiments, the composition comprises 5-15 mL of propylene glycol; 0.1-2.0 % weight / volume of doxycycline hyclate, based on a volume of propylene glycol; and 5-15 % eight volume of Tween 20. based on a volume of propylene glycol. In some embodiments, the composition comprises about 10 mL of propylene glycol; about 1% weight / volume of doxycycline hyclate, based on a volume of propylene glycol; and about 10% weight / volume of Tween 20, based on a volume of propylene glycol. In some embodiments, the at least one compound having at least one cosmetic effect is doxycycline and the least one surfactant and / or at least one polymer is PEG-8 stearate. In some embodiments, the composition comprises 1-10 mL water; 5-15 mL of propylene glycol; and 1-5 % weight / volume of PEG-8 stearate, based on a combined volume of water and propylene glycol. In some embodiments, the composition comprises about 5 mL water; about 10 mL of propylene glycol; and about 2 % weight / volume of PEG-8 stearate, based on a combined volume of water and propylene glycol. In some embodiments, the at least one compound having at least one301685781.1cosmetic effect is doxycycline and the least one surfactant and / or at least one polymer is Poloxamer 188. In some embodiments, the composition comprises 5-15 mL of propylene glycol; 0 1 -2 % weight / volume of doxycycline hyclate, based on a volume of propylene glycol; and 0.01-1 % weight / volume of Tween 20, based on a volume of propylene glycol. In some embodiments, the composition comprises about 10 mL of propylene glycol; about 1% weight / volume of doxycycline hyclate, based on a volume of propylene glycol; and about 0.1% weight / volume of Tween 20, based on a volume of propylene glycol. In some embodiments, the at least one compound having at least one cosmetic effect is doxycycline and the least one surfactant and / or at least one polymer comprises Tween 20 and Poloxamer 188. In some embodiments, the composition comprises 5-15 mL of propylene glycol, 0.1-2 % weight / volume of doxycycline hyclate, based on a volume of propylene glycol: 5-15 % weight / volume of Tween 20. based on a volume of propylene glycol; and 0.01-1 % weight / volume of Poloxamer 188, based on a volume of propylene glycol. In some embodiments, the composition comprises about 10 mL of propylene glycol; about 1% weight / volume of doxycycline hyclate, based on a volume of propylene glycol; about 10 % weight / volume of Tween 20, based on a volume of propylene glycol; and about 0.1 % weight / volume of Poloxamer 188, based on a volume of propylene glycol.

[0011] In some embodiments, a composition as disclosed herein comprises an effective amount of at least one ingredient capable of improving a skin condition; wLerein the at least one ingredient capable of improving a skin condition is selected from the group consisting of tannic acid, gallic acid, ellagic acid, niacinamide, resveratrol, doxycycline, curcumin, and zoledronic acid. In some embodiments, the at least one ingredient capable of improving a skin condition is capable of reducing collagen degradation; reducing elastin degradation; reducing hyaluronic acid degradation; maintaining or increasing collagen expression; increasing elastin expression; increasing hyaluronic acid production; increasing skin matrix production; inhibiting at least one enzyme responsible for degradation of extracellular matrix; reducing skin wrinkles; and / or reducing premature ageing. In some embodiments, the composition comprises tannic acid and resveratrol. In some embodiments, the composition comprises tannic acid and doxycycline. In some embodiments, the composition comprises tannic acid and curcumin. In some embodiments, the composition comprises tannic acid and niacinamide. In some embodiments, the composition comprises tannic acid and zoledronic acid. In some embodiments, the composition comprises tannic acid, resveratrol, and zoledronic acid. In some301685781.1 - 4 -embodiments, the composition comprises tannic acid, gallic acid, and ellagic acid. In some embodiments, the composition comprises tannic acid and gallic acid.

[0012] In some embodiments, a composition as disclosed herein comprises a carrier comprising water, glycerin, PEG400, and at least one of tannic acid, gallic acid, ellagic acid, niacinamide, resveratrol, doxycycline, curcumin, and zoledronic acid. In some embodiments, the carrier comprises 50-75% by weight of water; 10-30% by weight of glycerin; and 10-30% by weight of PEG400. In some embodiments, the carrier comprises about 56% by weight of water; about 23% by weight of glycerin; and about 21% by weight of PEG400. In some embodiments, the carrier comprises from 1 to 100 mg / ml of the at least one compound having at least one cosmetic effect.

[0013] In some embodiments, the composition comprises one or more of: ascorbic acid, rapamycin, hypoxanthine, nicotinamide, zeaxanthin, theobromine, Oleth-10, tween 20, dimethyl sulfoxide, hydroxyapatite, and N-acetyl cysteine. In some embodiments, the composition comprises one or more of: waler. glycerin, hyaluronate sodium. Tween 60, Span 80, dimethicone, glyceryl monooleate, cetyl alcohol, Poloxamer 188, glycery] stearate, isopropyl myristate, cocoa butter, Ceteth-10, PEG-400, PEG-40 stearate, and PEG-8 stearate. In some embodiments, the composition comprises resveratrol, tannic acid, hyaluronate sodium, Tween 60, Span 80, dimethicone, glyceryl monooleate, and cetyl alcohol. In some embodiments, the composition comprises resveratrol, tannic acid, hyaluronate sodium. Poloxamer 188. glyceryl stearate, cetyl alcohol, isopropyl myristate, and cocoa butter. In some embodiments, the composition comprises resveratrol, tannic acid, hyaluronate sodium, Oleth-10, Ceteth-10, dimethicone, glyceryl stearate, and cetyl alcohol. In some embodiments, the composition compnses resveratrol, tannic acid, zoledronic acid, hyaluronate sodium, Oleth-10, Ceteth-10, dimethicone, glyceryl stearate, and cetyl alcohol. In some embodiments, the composition comprises resveratrol, tannic acid, PEG-40 stearate, PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cetyl alcohol. In some embodiments, the composition comprises resveratrol, tannic acid, zoledronic acid. PEG-40 stearate, PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cety l alcohol.

[0014] In some embodiments, the composition comprises 2 to 10 % by weight of cetyl alcohol: 2 to 10 % by tveight of dimethicone; 2 to 10 % by weight of glyceryl monooleate; 0.1 to 2 % by weight of ’Tween 60; 0.1 to 2 % by weight of Span 80; and 0.1 to 2 % by weight of hyaluronate sodium; and 75 to 95 % by weight of a carrier comprising 2 to 8 mg / ml of resveratrol: 75 to 125 mg / ml of tannic acid; 50-75% by weight of water; 10-30% by weight of301685781.1 - 5 -glycerin; and 10-30% by weight of PEG400. In some embodiments, the composition comprises 45-50 % by weight of water: 12-18 % by weight of glycerin; 12-18 % by weight of PEG 400; 5-10 % by weight of tannic acid; 0.01-0.1 % by weight of resveratrol; 0.5-1.5 % by weight of Tween 60; 0 1-1 % by weight of sodium hyaluronate; 1-5 % by weight of dimethicone; 1-5 % by weight of glyceryl monooleate; 1-5 % by weight of cetyl alcohol; and 0.5-1.5 % by weight of Span 80.

[0015] In some embodiments, the composition comprises 2 to 10 % by weight of dimethicone; 2 to 10 % by weight of isopropyl myristate; 0.1 to 2 % by weight of Pol oxamer 188; 0.1 to 2 % by weight of Tween 20; 0.1 to 2 % by weight of cetyl alcohol; 0.1 to 2 % by ■weight of cocoa butter; 0.1 to 2 % by weight of glyceryl stearate; and 0.1 to 2 % by weight of sodium hyaluronate; and 70 to 95 % by weight of a carrier comprising 1 to 10 mg / ml of resveratrol: 50 to 150 mg / ml of tannic acid; 50-75% by weight of water; 10-30% by weight of glycerin; and 10-30% by weight of PEG400. In some embodiments, the composition comprises 45-50 % by weight of water: 12-18 % by weight of glycerin; 12-18 % by weight of PEG 400; 5-10 % by weight of tannic acid; 0,01-0.1 % by weight of resveratrol; 0.5-1.5 % by weight of Poloxamer 88; 0.5-1.5 % by weight of Tween 20; 0.1-1 % by weight of sodium hyaluronate; 6-10 % by weight of dimethicone; 0.5-1 5 ° / o by weight of glyceryl stearate: 0.5-5 % by weight of cetyl alcohol; 5-10 % by weight of isopropyl myristate; and 0.5-5% by weight of cocoa butter.

[0016] In some embodiments, the composition comprises 2 to 10 % by weight of dimethicone; 2 to 10 % by weight of isopropyl myristate; 0.1 to 2 % by weight of Poloxamer 188; 0.1 to 2 % by weight of Tween 20; 0, 1 to 2 % by weight of cetyl alcohol; 0.1 to 2 % by weight of cocoa butter; 0.1 to 2 % by weight of glyceryl stearate: 0.1 to 2 % by weight of sodium hyaluronate; and 0.01-0.1 % by weight of resveratrol: and 70 to 95 % by weight of a carrier comprising 1 to 10 mg / ml of resveratrol; 1 to 10 mg / ml of zoledronic acid; 50 to 150 mg / ml of tannic acid; 50-75% by weight of water; 10-30% by weight of glycerin; and 10-30% by weight of PEG400. In some embodiments, the composition comprises 45-50 % by weight of water; 12-18 % by weight of glycerin; 12-18 % by weight of PEG 400; 5-10 % by weight of tannic acid: 0.01-0.1 % by weight of resveratrol; 0.5-1 5 % by weight of Poloxamer 88; 0.5-1.5 % by weight of Tween 20; 0.1-1 % by weight of sodium hyaluronate; 6-10 % by weight of dimethicone; 0.5-1.5 % by weight of glyceryl stearate; 0.5-5 % by weight of cetyl alcohol; 5-10 % by weight of isopropyl mysritate; 0.5-5% by weight of cocoa butter; and 0.01-0.1 % by weight of zoledronic acid.301685781.1 - 6 -

[0017] In some embodiments, the composition comprises 2 to 10 % by weight of dimethicone: 0.1 to 2 % by weight of Oleth-10; 0.1 to 2 % by weight of Ceteth-10; 0.1 to 2 % by weight of cetyl alcohol; 0.1 to 2 % by -weight of glyceryl stearate; and 0.1 to 2 % by weight of hyaluronate sodium; and 85 to 95 % by weight of a carrier comprising 1 to 10 mg / ml of resveratrol; 50 to 150 mg / ml of tannic acid; 50-75% by w eight of water; 10-30% by weight of glycerin, and 10-30% by weight of PEG400. In some embodiments, the composition comprises 40-60 % by weight of water: 15-20 % by weight of glycerin; 15-20 % by weight of PEG 400; 1-10 % by weight of dimethicone; 5-10 % by weight of tannic acid: 0.5-1.5 % by weight of glyceryl stearate; 0.5-5 % by weight of cetyl alcohol; 0.5-1.5 % by weight of Oleth-10; 0.5-1.5 % by weight of Ceteth-10; 0.1-1 % by eight of sodium hyaluronate; and 0.01-0.1 % by weight of resveratrol.

[0018] In some embodiments, the composition comprises 2 to 10 % by weight of dimethicone; 0.1 to 2 % by weight of Oleth-10: 0.1 to 2 % by weight of Ceteth-10; 0.1 to 2 % by weight of cetyl alcohol; 0.1 to 2 % by weight of glyceryl stearate; and 0.1 to 2 % by weight of hyaluronate sodium; and 85 to 95 % by weight of a carrier comprising 1 to 10 mg / ml of resveratrol; 1 to 10 mg / ml of zoledronic acid; 50 to 150 mg / ml of tannic acid; 50-75% by¬ weight of water; 10-30% by weight of glycerin; and 10-30% by weight of PEG400. In some embodiments, the composition comprises 40-60 % by weight of -water; 15-20 % by weight of glycerin; 15-20 % by weight of PEG 400; 1-10 % by -weight of dimethicone; 5-10 % by weight of tannic acid; 0.5-1.5 % by weight of glyceryl stearate; 0.5-5 % by weight of cetyl alcohol; 0.5-1.5 % by weight of Oleth-10; 0.5-1.5 % by weight of Ceteth-10; 0.1-1 % by weight of sodium hyaluronate; 0.01-0.1 % by weight of resveratrol: and 0.01-0.1 % by weight of zoledronic acid.

[0019] In some embodiments, the composition comprises 2 to 10 % by weight of dimethicone; 0.1 to 2 % by weight of PEG-8 stearate; 0.1 to 2 % by weight of PEG-40 stearate; 0.1 to 2 % by weight of cetyl alcohol; 0.1 to 2 % by w eight of hyaluronate sodium; and 0,1 to 2 % by weight of glycery l stearate; and 85 to 95 % by weight of a carrier comprising 1 to 10 mg / ml of resveratrol; 50 to 150 mg / ml of tannic acid; 50-75% by weight of water; 10-30% by weight of glycerin; and 10-30% by weight of PEG400. In some embodiments, the composition comprises 40-60 % by weight of water; 15-20 % by weight of glycerin; 15-20 % by weight of PEG 400; 1-10 % by weight of dimethicone; 5-10 % by weight of tannic acid; 0.5-1.5 % byweight of glycery 1 stearate; 0.5-1.5 % by weight of cetyl alcohol; 0.5-1.5 % by w eight of PEG-301685781.1 - 7 -40 stearate: 0.5-1.5 % by weight of PEG-8 stearate: 0.1-1 % by weight of sodium hyaluronate; and 0.01-0.1 % by weight of resveratrol.

[0020] In some embodiments, the composition comprises 2 to 10 % by weight of dimethicone; 0.1 to 2 % by weight of PEG-8 stearate; 0, 1 to 2 % by weight of PEG-40 stearate; 0.1 to 2 % by weight of cetyl alcohol; 0.1 to 2 % by weight of sodium hyaluronate: and 0.1 to 2 % by weight of glyceryl stearate; and 85 to 95 % by weight of a carrier comprising 1 to 10 mg / ml of resveratrol; 1 to 10 mg / rnl of zoledronic acid; 50 to 150 mg / ml of tannic acid; 50- 75% by weight of water; 10-30% by weight of glycerin; and 10-30% by weight of PEG400. In some embodiments, the composition comprises 40-60 % by weight of water; 15-20 % by weight of glycerin; 15-20 % by weight of PEG 400; 1-10 % by weight of dimethicone; 5-10 % by weight of tannic acid; 0.5-1.5 % by weight of glyceryl stearate; 0.5-1.5 % by weight of cetyl alcohol; 0.5-1.5 % by weight of PEG-40 stearate; 0.5-1.5 % by weight of PEG-8 stearate; 0.1- 1 % by weight of sodium hyaluronate; 0.01-0.1 % by weight of resveratrol; and 0. 1-0.1 % by weight of zoledronic acid.

[0021] Tn some embodiments, a method of treating cancer in a subject comprises administering to the subject a therapeutically7effective amount of a composition comprising tannic acid and resveratrol. In some embodiments, the cancer is squamous cell carcinoma. In some embodiments, the composition inhibits expression of at least one of p53, STAT1, a matrix metalloproteinase, elastase, and hyaluronidase. In some embodiments, the composition inhibits phosphorylation of SI' ATI and / or STAT3. In some embodiments, the composition inhibits Akt-mTOR signaling. In some embodiments, the composition inhibits the formation of cyclobutene pyrimidine dimers. In some embodiments, the composition is administered orally, intraadiposally, intraarterially, intraarticularly, intracranially, intradermally, intralesionally, intramuscularly, intraperitoneally, intrapleurally, mtranasally. intraocularally, intrapericardially, intraprostaticaly, intrarectally, intrathecally, intratumorally, intraumbilically, intravaginally, intravenously, intravesicularlly, intr vitreally, liposomally, locally, mucosally. orally, parenterally, rectally, subconjunctival, subcutaneously, sublingually, topically, transbuccally. transdermally, vaginally. in cremes, in lipid compositions, via a catheter, via a lavage, via continuous infusion, via infusion, via inhalation, via injection, via local delivery’, via localized perfusion, bathing target cells directly, or any combination thereof.

[0022] In some embodiments, a method for protecting a subject’s skin from ultraviolet radiation comprises applying a sunscreen composition comprising at least one compound301685781.1 - 8 -selected from the group consisting of tannic acid, resveratrol, doxycycline, curcumin, and zoledronic acid and at least one surfactant and / or at least one polymer is selected from the group consisting of Tween 20, Tween 40, Tween 60, Tween 80, Laureth-4, Laureth-23, Ceteth- 10, Ceteth-20, Oleth-5, Oleth-10, KCS20, KRH40, Poloxamer 124, Poloxamer 182, Poloxamer 188, Poloxamer 407, Span20, Span60, Span80, Span83, PEG8 stearate, PEG40 stearate, sodium hyaluronate, gellan gum, hydroxyethyl cellulose, hydropropyl cellulose, and Noveon AA-1 polycarbophil to the subject's skin,

[0023] A “disease"’ is defined as a pathological condition of a body part, an organ, or a system resulting from any cause, such as infection, genetic defect, or environmental stress. A “health-related condition” is defined herein to refer to a condition of a body part, an organ, or a system that may not be pathological, but for which treatment is sought. Examples include conditions for which cosmetic therapy is sought, such as skm wrinkling, skin blemishes, and the like. The disease can be any disease, and non-limiting examples include hyperproliferative diseases such as cancer and premalignant lesions, wounds, and infections.

[0024] As used herein, the term “treating” is defined as the application or administration of a therapeutic agent, i.e., a compound useful within the invention (alone or in combination with another pharmaceutical agent), to a patient who has a disease or disorder, a symptom of a disease or disorder or the potential to develop a disease or disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, am eh orate, improve or affect the disease or disorder, the symptoms of the disease or disorder, or the potential to develop the disease or disorder. As used herein, the term “preventing” is defined as administration of the compositions, compounds or formulations of the invention to prevent or delay the onset of the symptoms, complications, or biochemical indicia of a disease, condition, or disorder (e.g., cancer).

[0025] As used herein, the term “cosmetic effect” refers to an effect that improves a condition of the skm, wherein the improvement in the condition of skin is a reduction in collagen degradation, a reduction in elastin degradation, a reduction in hyaluronic acid degradation, a preservation or increase in collagen expression, an increase in elastin expression, an increase in hyaluronic acid production, an increase in skin matrix production, inhibition of least one enzyme responsible for degradation of extracellular matrix, a reduction in skin wrinkling, and / or a reduction in premature ageing301685781.1 - 9 -

[0026] A "therapeutically effective amount’’ of a substance / molecule may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the substance / molecule to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the substance / molecule are outweighed by the therapeutically beneficial effects. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically but not necessarily, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount.

[0027] An “individual” or “subject” is a mammal. Mammals include, but are not limited to, domesticated animals (e g, cows, sheep, cats, dogs, and horses), primates (e.g., humans and non- human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the individual or subject is a human.

[0028] By “reduce or inhibit” is meant the ability to cause an overall decrease of 20%, 30%, 40%, 50%. 60%, 70%, 75%, 80%. 85%, 90%, 95%, or greater. Reduce or inhibit can refer to inhibition of the activity of an enzyme, reduction in the symptoms of a disorder being treated, the presence or size of metastases, or the size of the primary tumor.

[0029] It is specifically contemplated that any limitation discussed with respect to one embodiment of the invention may apply to any other embodiment of the invention. Furthermore, any composition of the invention may be used in any method of the invention, and any method of the invention may be used to produce or to utilize any composition of the invention.

[0030] The use of the term “or” in the claims is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternative are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.” Ute phrase “and / or” means “and” or “or”. To illustrate, A. B, and / or C includes: A alone, B alone, C alone, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B, and C. In other words, “and / or” operates as an inclusive or.

[0031] The terms “comprise” (and any form of comprise, such as “comprises” and “comprising”), “have” (and any form of have, such as “has” and “having”), “include” (and any form of include, such as “includes” and “includi ng”) and “contain” (and any form of contain, such as “contains” and “containing”) are open-ended linking verbs. As a result, the methods301685781.1 - 10 -and systems of the present invention that '‘comprises,” “has,” “includes” or “contains” one or more elements possesses those one or more elements, but is not limited to possessing only those one or more elements. Likewise, an element of a method or system of the present invention that “comprises,” “has,” “includes” or “contains” one or more features possesses those one or more features, but is not limited to possessing only those one or more features.

[0032] Any method or system of the present invention can consist of or consist essentially of — rather than comprise / include / contain / have — any of the described elements and / or features and / or steps. Thus, in any of the claims, the term "consisting of7or “consisting essentially of” can be substituted for any of the open-ended linking verbs recited above, m order to change the scope of a given claim from what it would otherwise be using the open- ended linking verb.

[0033] Throughout this application, the term “about” is used to indicate that a value includes the standard deviation of error for the device and / or method being employed to determine the value.

[0034] The term “substantially7’ is defined as being largely but not necessarily wholly what is specified (and include wholly what is specified) as understood by one of ordinary- skill in the art. In any disclosed embodiment, the term “substantially” may be substituted with “within [a percentage] of7what is specified, where the percentage includes 0.1, 1, 5, and 10 percent.

[0035] As used herein, in the specification, “a” or “an” may mean one or more, unless clearly indicated otherwise. As used herein, in the claim(s), when used in conjunction with the word “comprising.77the words “a77or “an” may mean one or more than one. As used herein “another” may mean at least a second or more.

[0036] Other objects, features and advantages of the present invention will become apparent from the folloyving detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.301685781.1 - 11 -BRIEF DESCRIPTION OF THE DRAWINGS

[0037] FIG. 1 MMP-1 inhibition screen. All compounds used at 50 pg / ml concentration (combinations were 25 pg / ml for each compound dissolved in appropriate solvent (water or DMSO)).

[0038] FIG. 2 Total collagen content obtained after treatment of human dermal fibroblasts with compounds and combinations of compounds obtained from MMP inhibition screens. All compounds used at 50 pg / ml concentration (combinations were 25 pg / ml for each compound dissolved in appropriate solvent (water or DMSO)).

[0039] FIG. 3 MMP-1 inhibition screen using compounds obtained from previous MMP inhibition screens where additional combinations were evaluated. All compounds used at 50 pg / ml concentration (combinations were 25 pg / ml for each compound dissolved in appropriate solvent (water or DMSO)).

[0040] FIG. 4 Effect of tannic acid concentration on inlii bition of MMP-1 activity compared to enzyme control (no inhibition), using the colorimetric MMP1 Inhibitor Screening Assay Kit, ab 139443 (Abeam).

[0041] FIG. 5 Effect of combinations of compounds identified in screening (versus vehicle controls and single compound controls) on collagen production in normal human dermal fibroblasts (NHDF). The horizontal line indicates the threshold (the detected collagen level of the controls (media)) for increased collagen production.

[0042] FIG. 6 Effect of compounds and combinations on hyaluronidase activity using a hyaluronidase screening assay. Compounds were tested at 250 pg / mL, except for RESTAZA (5: 100:5) that was tested at 374 pg / mL and Tretinoin at 10 pg / mL. owing to its lower solubility in 5% DMSO (v / v) in water.

[0043] FIG. 7 Composition of emulgels (EG) prepared and tested in the high-throughput screenings (H I’S). 60 mg of each surfactant was used in the emulgel formulations. In addition, the polymers were added assuming a 6mL total volume.

[0044] FIG. 8 Compositions of emulsions (EE) developed and tested in the UTS method using excised human skin.

[0045] FIG. 9 Surfactants (1% w / v) in WGP that increase permeation of compounds across human skin. Individual compounds (resveratrol, tannic acid, and zoledronic acid) and301685781.1 - 12 -combinations thereof, are shown where permeation enhancement ratios (ER) are greater than control or more than 20 times control (tannic acid alone) (student's t-test, p<0.05).

[0046] FIGS. 10A-10C Surfactant screening. Enhancement ratio (ER) of tannic acid across dermatomed human skin (all skin layers) (A). ER of resveratrol across dermatomed human skin (B) ER of zoledronic acid across dermatomed human skin (C).

[0047] FIG. 11 Gels formulation effects on the permeability of compounds across human skin relative to controls (vehicle, WGP without polymer) for the Individual compounds (resveratrol, tannic acid, and zoledronic acid) and combinations thereof. Polymers increasing ER ratio greater than control are indicated by an ‘V (student’s l-test, p<0.05).

[0048] FIGS. 12A-12C Gel formulation screening in dermatomed human skin. Enhancement ratio (ER) of tannic acid (TA) across dermatomed human skin (A) ER of resveratrol (RES) across dermatomed human skin (B). ER of zoledronic acid (ZA) across dermatomed human skin (C) * = p<0.05, student’s t-test

[0049] FIG. 13 Formulations with high epidermal permeability compared to control vehicle (p<0.01, Student’s t-test)

[0050] FIGS. 14A-14C Human epi ermal membrane permeability of tannic acid (A), resveratrol (B), and zoledronic acid (C). * = p<0.01, student’s t-test.

[0051] FIG. 15 Formulations with lower dermal permeability’ (p<0.05, Student’s t- test). The “x’‘ indicates formulations with lower dermal permeability' relative to control.

[0052] FIGS. 16A-16C Enhancement ratio (permeability of formulation relative to control) across the dermis layer of tannic acid (A), resveratrol (B), and zoledronic acid (C).

[0053] FIG. 17 Formulations with higher epidermal permeability and lower dermal permeability. The “x" indicates formulations with higher epidermal permeability and lower dermal permeability relative to control.

[0054] FIG. 18 Sum of enhancement ratios of resveratrol and tannic acid (RESTA) across the epidermis layer (permeability of formulation relative to control). * = p<0.05.

[0055] FIG. 19 Sum of enhancement ratios of resveratrol and tannic acid (RESTA) across the dermis layer (permeability of formulation relative to control). *:::p<0.05.10056] FIG. 20 Surfactants and gels with low permeability' through the skin and high epidermal permeability.301685781.1 - 13 -

[0057] FIGS. 21A-21B Measured amounts (ug) of tannic acid (A) and resveratrol (B) that permeated across the skin for various formulations.

[0058] FIGS.22A-22B Amount of TA (pg / mg of skin) in the epidermis (A) and dermis (B) in dermatomed human skin after 16 hours of treatment with selected formulations. Oneway ANOVA, Tukey’s, *p<0.05. ** p<0.005, ***p<0.001, ****p<0.0001.

[0059] FIGS. 23A-23B Amount of Res (pg / mg of skin) in the epidermis (A) and dermis (B) in dermatomed human skin after 16 hours of treatment with selected formulations. One-way ANOVA, Tukey’s, *p<0.05. ** p<0,005, ***p<0.001, ****p<0.0001.

[0060] FIGS. 24A-24B Amount of RES (left) and TA (right) (pg / mg of skin) in the stratum comeum (tape stripped) after 16 hours of treatment with selected formulations. Oneway ANOVA, Tukey’s, *p<0.05. ** p<0.005. ***p<0.001, ****p<0.0001.

[0061] FIG. 25 Schematic depicting the steps taken to formulate Emulsion 4 (EE4).

[0062] FIG. 26 Schematic depicting steps that may be taken to formulate any emulsion where the mixture of surfactants are added to the oil phase.

[0063] FIG. 27 Schematic depicting steps that may be taken to formulate an emulsion where the polymer is added at the end after cooling down the emulsion.

[0064] FIG. 28 Schematic depicting steps that may be taken to formulate an emulsion that involves adding the oil phase to the water phase.

[0065] FIGS. 29A-29B Diagram depicting treatment schedule of mice in experiments on prevention of photocarcinogenesis (A). Table that includes results of photocarcinogenesis prevention experiments (B),

[0066] FIGS. 30A-30B Measurement of elastase, MMP-1, hyaluronidase 1 and hyaluronidase 2 expression in response to no treatment, placebo, and tannic + resveratrol in epidermis (A) and dermis (B). Hyaluronidase 1 and hyaluronidase 2 inhibition is visible at 24 hours after EE4 application (TR) when compared to placebo and no treatment control,

[0067] FIGS. 31A-31D MMP-1 (A), elastase (B), hyaluronidase 1 (C), and hyaluronidase 2 (D) inhibition is visible at 24 hours after EE4 application (TR) when compared to placebo and no treatment control indicating that our formulation can be used for avoiding skin aging and possible tumor initiation and progression effects.301685781.1 - 14 -

[0068] FIGS. 32A-32D RESTA formulation (EE4) decreased SUV -induced p53 expression. When EE4 was administered, p53 expression decreased at both 6 and 24 hours when compared to the placebo formulation and to no treatment control (mice exposed to UV without any treatment)

[0069] FIGS. 33A-33D Phosphorylation at tyrosine residue (Y701) of STAT1 decreased after treatment with EE4 after 24h compared to the placebo formulations and control and it was similar to mice that were not treated with UV and received no formulation. p-STATl (S727) was decreased in both the treatment (EE4) and non-UV induced control when compared to no treatment control and to the placebo formulation. This indicates that the ability of EE4 to inhibit or decrease the phosphorylation of STATl. STAT1 expression was also decreased after 24 hours of EE4 treatment when compared to no treatment control and placebo formulation.

[0070] FIGS.34A-34D Phosphorylation at serine residue (S727) of STAT3, a protein that is active in various human malignancies, decreased after 24 hours of treatment with RESTA when compared to no treatment control and to placebo.

[0071] FIGS. 35A-35C RESTA EE4 formulation inhibits SUV-induced Akt-mTOR signaling.

[0072] FIGS.36A-36D Epidermal thickness of mice treated with formulation EE4. (A) Male mice at 6 hows post-treatment. (B) Female mice at 6 hours post-treatment. (C) Male mice at 24 hours post-treatment. (D) Female mice at 25 hours post-treatment. Epidermal thickness in treated mice is lower when compared to placebo and untreated control at both 6 and 24 hows denoting possible photoprotection effect.

[0073] FIGS. 37A-37B Staining of epidermis to visualize thickness (A). Epidermal thickness was significantly reduced in mice treated with RESTA formulation when compared to control mice given no RESTA formulation (B).

[0074] FIGS. 38A-38B Ki-67 staining (A). Ceil proliferation was significantly decreased in mice treated with RESTA formulation when compared to the control mice exposed to UV (B).

[0075] FIGS.39A-39B Cyclobutane Pyrimidine Dimer (CPD) staining in female mice, 24 h post-treatment. CPDs are DNA lesions present that are formed after UV exposure (A). RESTA significantly inhibited the formation of CPD dimers and was similar to mice not exposed to UV treatment (B).301685781.1 - 15 -

[0076] FIGS. 40A-40C Doxycycline hyclate permeation across and into human skin. Doxycycline hyclate concentration (pg / mL) in the receptor fluid / across the skin (One sample t-test relative to Ipg / mL; * =p<0.05, **=p<0.01, ***=p<0.001, ****=p<0.0001) (A). Amount of doxycycline hyclate in the epidermis (pg / mg skin) (One sample t-test relative to 0 pg / mg of skin; *=p<0.05. **=p<0.01) (B). Amount of doxycycline hyclate in the dermis (pg / mg skin) (One sample t-test relati ve to 0 pg / mg of skin; *==p<0.05, **==p<0.01 ) (C).DETAILED DESCRIPTION

[0077] Disclosed herein are methods and compositions that enable skin permeation and retention of compounds that have anti-aging effects, compounds that can be used for the treatment or prevention of skin cancer, and for sunscreen activity. Combinations of compounds that improve or maintain the skin matrix production and concurrently inhibit the skin matrix degradation enzy mes were discovered and formulated into novel compositions that ensure epidermal permeability', i.e. when applied topically, these compounds will permeate and reach the target tissue within the skin. These novel compositions were determined to significantly increase skin targeting, compound retention, and / or permeability of the individual compounds and the combinations of compounds The formulations disclosed herein can be used to prevent and potentially reverse premature skin aging. They may also be used in treating and preventing skin cancer as they prevent tumor initiation and progression.

[0078] Delivering drugs to and across the skin can be divided in two main modalities: topical and transdermal drug delivery'. Topical drug delivery' pertains to delivering drug to the surface of the skin or to the epidermis and dermis layer, while avoiding systemic absorption. Transdermal drag delivery involves delivery' of drugs across the skin and into the systemic circulation. The importance of skin retention is to maximize effects of drags in the skin, for dermatological diseases and application and minimize off-target and potentially dangerous side-effects. The term “retention” as used herein refers to allowing drugs to permeate through the stratum corneum and retained inside the epidermis and dermis, while minimizing systemic absorption across the whole skin. This has been an issue in the use of corticosteroids in the pediatric population where systemic absorption can cause growth problems and adrenal dysfunction in children. Similarly, some sunscreens exhibit enhanced permeation, which results in systemic absorption of sunscreen components, and potential risk of endocrine disruption, and dermatological diseases involving disruption of stratum corneum function.301685781.1 - 16 -Thus, topical formulations that target the skin and minimize systemic effects are needed and rarely carefully explored.

[0079] Another important thing to note is that, from a regulatory point of view, cosmetics do not need to exhibit permeability' into the skin. Rather, the majority of the cosmetic studies only show the effect of a compound at the cellular level but completely disregard the delivery', permeation and retention of those compounds to the target site where those compounds should enhance collagen production and inhibit degradation enzymes. For example, many current cosmetic products do not demonstrate delivery to the dermis and the base of the viable epidermis, where matrix metalloproteinases (MMPs ) are present and where collagen and other extracellular matrix proteins are produced. In order to examine permeability and systemic absorption, the formulations / compositions disclosed herein were examined for their ability to enter the stratum comeuni and remain m the skin (viable epidermis and demiis) while minimizing permeation across the skin / systemic absorption. High-throughput formulation screening methods employing excised human skin were employed to assess the permeability and retention of active compounds included in the formulations.Ingredients

[0080] Polyethylene glycol 400 (PEG 400) is a polymer of ethylene oxide that is used as a solvent in pharmaceutical and cosmetic preparations.

[0081] Tween is a class of non-ionic surfactants used in personal care applications to compatibilize and solubilize oily and water-based components. Tween compositions are polyethylene sorbitols that are esterified with fatty’ acids. Examples of Tween compositions employed herein include Tween 20, Tween 40, Tween 60, Tween 65, Tween 80, and Tween 85.

[0082] Span refers to a series of surfactant compositions that are used as emulsifiers and dispersing agents in personal care compositions. Span compositions are based on fatty7acid esters of sorbitol. Non-limiting examples of Span compositions include Span20, Span60, Span80, and Span83. Other sorbitans could also be used,

[0083] Laureth refers to a family of non-ionic surfactants, emulsifiers, and solubilizers. The chemical structure of Laureth-4 comprises lauryl alcohol conjugated to 4 units of ethylene oxide. The chemical structure of Laureth-23 comprises lauryl alcohol conjugated to 23 units of ethylene oxide.301685781.1 - 17 -

[0084] Ceteth refers to a family of surfactants, emulsifying agents, and cleansing agents. Ceteth- 10 is a polyethylene glycol ether of cetyl alcohol that includes 10 ethylene oxide units attached to the cetyl alcohol chain. Ceteth-20 s a polyethylene gl col ether of cet l alcohol that includes 20 ethylene oxide units attached to the cetyl alcohol chain.

[0085] Oleth refers to a family of surfactants, emulsifying agents, and cleansing agents. Oleth-5 is a polyethylene glycol ether of oleyl alcohol with 5 ethylene oxide units attached to the oleyl alcohol chain. Oleth-10 is a polyethylene glycol ether of oleyl alcohol with 10 ethylene oxide units attached to the oleyl alcohol chain.

[0086] KCS20 is a polyethylene glycol ether of cetearyl alcohol. KCS 20 is a non¬ ionic emulsifier used in the manufacture of oil / water emulsions. KCS 10 is also referred to as polyoxy 1 20 cetostearyl ether, Kolliphor CS1. and Ceteareth-20.

[0087] KRH40, also known as Cremophor RH 40, is a non-iomc solubilizer and emulsify ing agent that is obtained by reacting hydrogenated castor oil with ethylene oxide. The primary constituents are glyceryl polyethylene glycol oxystearate and fatty acid glyceryl polyglyceryl esters.

[0088] Poloxamer refers to a family of nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene (poly(propylene oxide)) flanked by two hydrophilic chains of polyoxyethylene (poly(ethylene oxide)). Poloxamers are commonly named with the leter P (for poloxamer) followed by three digits: the first two digits multiplied by 100 give the approximate molecular mass of the polyoxypropvlene core, and the last digit multiplied by 10 gives the percentage polyoxyethylene content (e.g. P407 = poloxamer with a polyoxypropvlene molecular mass of 4000 g / mol and a 70% polyoxyethylene content). Examples of poloxamers used herein include Poloxamer 124, Poloxamer 182. Poloxamer 188, and Poloxamer 407.

[0089] PEG stearates are polyethylene glycol esters of stearic acid that are used as emulsifiers, cleansing agents, and emollients. The number included in the PEG stearate corresponds to the average length of the PEG chain. Examples of PEG stearates used herein include PEGS stearate and PEG40 stearate.

[0090] Sodium hyaluronate refers to the sodium salt of hyaluronic acid. Sodium hyaluronate is a surfactant and a humectant that attracts moisture and helps the skin retain water balance.301685781.1 - 18 -

[0091] Gellan gum is a polysaccharide made of repeating units of P-1, 3-d-glucose, p- 1, 4-D glucuronic acid, and a-1. 4-L-rhamnose. Gellan gum is a thickening and gelling agent that is used as an emulsifier to help ingredients blend and stay blended.

[0092] Hydroxyethyl cellulose is a polysaccharide derivative with gel thickening, emulsifying, bubble-forming, water-retaining, and stabilizing properties. Hydroxyethyl cellulose is a polysaccharide that includes a cellulose backbone with 2-hydroxy ethyl ether units on some of the hydroxyl groups.

[0093] Hydroxypropyl cellulose is a polysaccharide derivative with gel thickening, emulsifying, bubble-forming, water-retaining, and stabilizing properties. Hydroxypropyl cellulose is a polysaccharide that includes a cellulose backbone with 2 -hydroxypropyl ether units on some of the hydroxyl groups.

[0094] Noveon AA-1 polycarbophi] is a high molecular weight acrylic acid polymer crosslinked with divinyl glycol. Noveon AA-1 polycarbophil is a thickener and rheology modifier, and suspension and emulsion stabilizer used in semisolids and gels, solutions and suspensions.

[0095] Cetyl alcohol is a mixture of aliphatic alcohols composed mainly of 1-hexadecanol. It is a waxy solid material used as an emollient, emulsifying agent and stiffening agent since it increases the consistency of topical products. Related substances include cetostearyl alcohol which include cetyl alcohol and stearyl alcohol being used as an emulsifying and co-emulsifying agent and as a stiffening agent.

[0096] Dimethicone is a polydimethylpolysiloxane used as an oily solvent or vehicle, anti-foaming agent, and emollient. Related substances include cyclomethicone (dimethylcyclopolvsiloxane), simethicone, silicone oil, cyclopentasyloxane.

[0097] Isopropyl myristate (1 -methylethyl tetradecanoate) is an oleaginous vehicle, solvent, and emollient that can also have penetration enhancement activity. It is a relatively non-greasy emollient that is used in topical and transdermal compositions. Related substances include isopropyl palmitate and isopropyl stearate.

[0098] Dimethyl isosorbide (DMI) is a solvent capable of dissolving lipophilic and hydrophilic compounds. It is used in water-based and oil-based formulations andis also known as a permeation enhancer.301685781.1 - 19 -

[0099] Cocoa butter is also known as theobroma oil, oleum cacao, and Oleum theobromatis. It is a natural fat extracted from cocoa beans that is normally used as a suppository base. It is composed of a mixture of unsaturated and saturated fatty acids and triglycerides.Amounts of Ingredients

[0100] It is contemplated that the compositions of the present invention can include any amount of the ingredients discussed in this specification. The compositions can also include any number of combinations of additional ingredients described throughout this specification (e.g., pigments, or additional cosmetic or pharmaceutical ingredients). The concentrations of the ingredients within the compositions can vary. In non-limiting embodiments, for example, the composition can independently comprise, consist essentially of, or consist of, in their final form, for example, at least about 0.0001%, 0.0002%, 0.0003%, 0.0004%. 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%, 0.0010%, 0.0011%, 0.0012%, 0.0013%, 0.0014%, 0.0015%, 0.0016%, 0.0017%, 0.0018%. 0.0019%, 0.0020%. 0.0021%, 0.0022%, 0.0023%, 0.0024%, 0.0025%, 0.0026%, 0.0027%, 0.0028%, 0.0029%, 0.0030%. 0.0031%, 0.0032%, 0.0033%, 0.0034%. 0.0035%, 0.0036%, 0.0037%, 0.0038%, 0 0039%, 0.0040%, 0.0041%, 0.0042%, 0.0043%, 0.0044%, 0.0045%, 0.0046%, 0.0047%, 0.0048%, 0.0049%, 0.0050%, 0.0051%, 0.0052%, 0.0053%, 0.0054%. 0.0055%, 0.0056%, 0.0057?% 0.0058%, 0.0059%, 0.0060%, 0.0061?% 0.0062%, 0.0063%. 0.0064%, 0.0065?% 0.0066%, 0.0067%. 00068%, 0.0069%.0.0070?% 0.0071?% 00072%, 0.0073%, 0.0074%, 0.0075?% 0.0076?% 0.0077%, 00078%, 0.0079°% 0.0080?% 0.0081?% 0.0082%, 0.0083%, 0.0084%, 0.0085?% 0.0086?% 0.0087?% 00088%, 0.0089?% 0.0090?% 0.0091?% 0.0092%, 0.0093%, 0.0094?% 0.0095%, 0.0096?% 0.0097%. 0.0098%, 0.0099?% 0.0100?% 0.0200°% 0.0250%, 0.0275%, 0.0300%, 0.0325?% 0.0350%. 0.0375%, 0.0400%, 0.0425%, 0.0450%, 0.0475%, 0.0500%, 0.0525%. 0.0550%, 0.0575%, 0.0600%, 0.0625%, 0.0650?% 0.0675?% 0.0700?% 0.0725%, 0.0750%, 0.0775%, 0.0800?% 0.0825%, 0.0850%, 0.0875%, 0.0900?% 0.0925%, 0.0950%, 0.0975%, 0.1000%, 0.1250?% 0.1500?% 0.1750%. 0.2000%, 0.2250%, 0.2500?% 0.2750?% 0.3000%, 0.3250%, 0.3500%, 0.3750?% 0.4000%, 0.4250%, 0.4500?% 0.4750%, 0.5000?% 0.5250%, 0.0550%, 05750%. 0.6000?% 0.6250?% 0.6500?% 0.6750%, 0.7000%, 0.7250?% 0.7500%, 0.7750?% 0.8000%. 0.8250%, 0.8500°% 0.8750%, 09000%, 0.9250%, 0.9500%, 0.9750%, 1.0%, 1.1?% 1.2%, 1.3?% 1.4?% 1.5%, 1.6%, 1.7%, 1.8%, 1.9?% 2.0%, 2.1%, 2.2?% 2.3?% 2.4?% 2.5?% 2.6?% 2.7?% 2.8?% 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 34%, 3.5?% 3.6%, 3.7?% 3.8%. 3.9?% 4.0?% 4.1%, 42?% 4.3%, 44?% 4.5?% 46%, 4.7%, 4.8%, 4.9%, 5 0%, 5.1?% 5.2%, 5.3?%301685781.15.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 6.0%, 6.1%, 6.2%, 6.3%, 6.4%, 6.5%, 6.6%, 6.7%, 6.8%, 6.9?% 7.0%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, 8.0%, 8.1%, 8.2%, 8.3%, 8.4%, 8.5%, 8.6%, 8.7%, 8.8%, 8.9%, 90%, 9.1%, 9.2%. 9.3%. 9.4%. 9.5%.9.6%. 9.7%, 9.8%, 9.9%. 10%, 11%, 12%, 13%, 14?% 15%, Wo, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%, 60%, 65%, 70%, 75 %, 80%. 85?% 90%, 95?% or 99% or any range derivable therein, of at least one of the ingredients that are mentioned throughout the specification and claims. In non-limiting aspects, the percentage can be calculated by weight or volume of the total composition. A person of ordinary skill in the art would understand that the concentrations can vary depending on the addition, substitution, and / or subtraction of ingredients in a given composition.Vehicles

[0101] The compositions of the present invention can include or be incorporated into all types of vehicles and carriers. The vehicle or carrier can be a pharmaceutically or dermatologically acceptable vehicle or carrier. Non-limiting examples of vehicles or carriers include water, glycerin, alcohol, oil, a silicon containing compound, a silicone compound, and wax. Variations and other appropriate vehicles will be apparent to the skilled artisan and are appropriate for use in the present invention In certain aspects, the concentrations and combinations of the compounds, ingredients, and agents can be selected in such a way that the combinations are chemically compatible and do not form complexes which precipitate from the finished product.Structure

[0102] The compositions of the present invention can be structured or formulated into a variety of different forms. Non-limiting examples include emulsions (e.g., water-in-oil, water-in-oil-in- water, oil-in-water, sili cone-in-water, water-in-silicone, oil-in-water-in-oil, oil-in- water-in-silicone emulsions, and emulgels), creams, lotions, solutions (including aqueous, non¬ aqueous, and hydro-alcoholic), anhydrous bases (such as lipsticks and powders), gels, masks, scrubs, body butters, peels, suspensions, and ointments. Compositions may also be incorporated into skin patches and intradermal dosage forms such as injections. Variations and other structures will be apparent to the skilled artisan and are appropriate for use in the present invention.301685781.1Additional Ingredients

[0103] In addition to the combinations of ingredients disclosed by the inventors, the compositions can also include additional ingredients such as cosmetic ingredients, pharmaceutical active ingredients, and inactive ingredients. Non-limiting examples of these additional ingredients are included below.

[0104] Cosmetic ingredients - The CTFA International Cosmetic Ingredient Dictionary’ and Handbook (2004 and 2008) describes a wide variety of non-limiting cosmetic ingredients that can be used in the context of the present invention. Examples of these ingredient classes include: fragrance agents (artificial and natural; e.g., gluconic acid, phenoxyethanol, and triethanolamine), dyes and color ingredients (e.g., Blue 1, Blue 1 Lake. Red 40, titanium dioxide, D& C blue no. 4, D& C green no. 5, D& C orange no. 4, D& C red no. 17, D& C red no.33, D& C violet no. 2, D& C yellow no. 10, and D& C yellow no. 11), flavoring agents / aroma agents (e g., Stevia rebaudiana (sweetleaf) extract, and menthol), adsorbents, lubricants, solvents, moisturizers (including, e.g., emollients, humectants, film formers, occlusive agents, and agents that affect the natural moisturization mechanisms of the skin), water-repellants, UV absorbers (physical and chemical absorbers such as para-aminobenzoic acid (‘TABA”) and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.), essential oils, other oils, vitamins (e.g., B, D, E, and K), trace metals (e.g., zinc, calcium and selenium), anti-irritants (e.g., steroids and non-steroidal anti-inflammatories), botanical extracts (e.g., Aloe ver a, chamomile, cucumber extract. Ginkgo biloba. ginseng, and rosemaiy). anti-microbial agents, antioxidants (e.g., BHT and tocopherol), chelating agents (e.g.. disodium EDTA and tetrasodium EDTA), preservatives (e.g., methylparaben and propylparaben), stabilizers, pH adjusters (e.g., sodium hydroxide and citric acid), absorbents (e.g., aluminum starch octenylsuccinate, kaolin, com starch, oat starch, cyclodextrin, talc, and zeolite), skm bleaching and lightening agents (e.g., hydroquinone and niacinamide lactate), humectants (e.g.. sorbitol, urea, methyl gluceth-20, saccharide isomerate, and mannitol), exfoliants, waterproofing agents (e.g., magnesium / aluminum hydroxide stearate), skin conditioning agents (e.g., aloe extracts, allantoin, bisabolol, ceramides, dimethicone, hyaluronic acid, biosaccharide gum-1, ethylhexylglycerin, pentylene glycol, hydrogenated polydecene, octyldodecyl oleate, and dipotassium glycyrrhizate). Non-limiting examples of some of these ingredients are provided in the following subsections.301685781.1 - 22 -

[0105] UV absorption and or reflecting agents - UV absorption and / or reflecting agents that can be used in combination with the compositions of the present invention include chemical and physical sunblocks. Non-limiting examples of chemical sunblocks that can be used include para-aminobenzoic acid (PABA), PABA esters (glyceryl PABA, amyldimethyl PABA and octyldimethyl PABA), butyl PABA, ethyl PABA, ethyl dihydroxypropyl PABA, benzophenones (oxybenzone, sulisobenzone, benzophenone, and benzophenone- 1 through 12), cinnamates (octyl methoxycinnamate (octinoxate), isoamyl p-methoxycinnamate, octylmethoxy cinnamate, cinoxate, diisopropyl methyl cinnamate, DE A-methoxy cinnamate, ethyl diisopropylcinnamate, glyceryl octanoate dimethoxycinnamate and ethyl methoxycinnamate), cinnamate esters, salicylates (homomethyl salicylate, benzyl salicylate, glycol salicylate, isopropylbenzyl salicylate, etc ), anthranilates, ethyl urocanale, homosalate, octisalate, dibenzoylmetliane derivatives (e.g., avobenzone), octociylene, octyl triazone, digalloyl trioleate, glyceryl aminobenzoate, lawsone with dihydroxyacetone, ethylhexyl triazone, dioctyl butamido triazone, benzylidene malonate polysiloxane, terephthalylidene dicamphor sulfonic acid, disodium phenyl dibenzimidazole tetrasulfonate, diethylammo hydroxybenzoyl hexyl benzoate, bis diethylamino hydroxybenzoyl benzoate, bis ben zoxazoyl phenyl ethylhexylimino triazine, drometrizole trisiloxane, methylene bis- benzotriazolyl tetramethylbutylphenol, and bis-ethylhexyloxyphenol methoxyphenyltriazine, 4-methylbenzyhdene camphor, and isopentyl 4-methoxycmnamate. Non-limiting examples of physical sunblocks include, kaolin, talc, petrolatum and metal oxides (e.g., titanium dioxide and zinc oxide).

[0106] Moisturizing agents - Non-limiting examples of moisturizing agents that can be used with the compositions of the present invention include amino acids, chondroitin sulfate, di glycerin, erythritol, fructose, glucose, glycerin, glycerol polymers, glycol, 1,2,6-hexanetnol, honey, hyaluronic acid, hydrogenated honey, hydrogenated starch hydrolysate, inositol, lactitol, maltitol, maltose, mannitol, natural moisturizing factor, PEG-15 butanediol, polyglyceryl sorbitol, salts of pyrrolidone carboxylic acid, potassium PCA, propylene glycol, saccharide isomerate, sodium glucuronate, sodium PCA, sorbitol, sucrose, trehalose, urea, and xylitol.

[0107] Other examples include acetylated lanolin, acetylated lanolin alcohol, alanine, algae extract. Aloe barbadensis, Aloe barbadensis extract, Aloe barbadensis gel. Althea officinalis extract, apricot (Primus armeniaca) kernel oil, arginine, arginine aspartate, Arnica montcma301685781.1extract, aspartic acid, avocado (Persea gratissima) oil, barrier sphingolipids, butyl alcohol, beeswax, behenyl alcohol, beta-sitosterol, birch (Betula alba) bark extract, borage Borago officinalis) extract, butcherbroom (Ruscus aculeatus) extract, butylene glycol, Calendula officinalis extract, Calendula officinalis oil, candelilla (Euphorbia ceriferd) wax, canola oil, caprylic / capric triglyceride, cardamom (Elettaria cardamomum) oil, carnauba (Copernicia cerifera) wax, carrot (Daucus carota sativa) oil. castor (Ricinus communis) oil, ceramides, ceresin, cetearetb-5, ceteareth-12. ceteareth-20, cetearyl octanoate, ceteth-20, ceteth-24, cetyl acetate, cetyl octanoate, cetyl palmitate, chamomile (Anthemis nobilis) oil, cholesterol, cholesterol esters, cholesteryl hydroxystearate, citric acid, clary’ (Salvia sclarea) oil, cocoa (Theobroma cacao) butter, coco-caprylate / caprate, coconut (Cocos nucifera) oil, collagen, collagen amino acids, com (Zea mays) oil. fatly acids, decyl oleate, dimethicone copolyol, dimethiconol, di octyd adipate, dioctyl succinate, dipentaery thrity 1 hexacapry late / hexacaprate, DNA, erythritol, ethoxydiglycol, ethyl linoleate. Eucalyptus globulus oil, evening primrose (Oenothera biennis) oil, fatty acids, Geranium maculatum oil, glucosamine, glucose glutamate, glutamic acid, glyceretli-26, glycerin, glycerol, glyceryl distearate, glyceryl hydroxystearate, glyceryl laurate, glyceryl linoleate, glyceryl myristate, glyceryl oleate, glyceryl stearate, glyceryl stearate SE, glycine, glycol stearate, glycol stearate SE, glycosaminoglycans, grape (Vitis vinifera) seed oil, hazel Corylus americand) nut oil, hazel (Corylus avellana) nut oil, hexylene glycol, hyaluronic acid, hybrid safflower (Carthamus tinctorius) oil, hydrogenated castor oil, hydrogenated coco-glycerides, hydrogenated coconut oil, hydrogenated lanolin, hydrogenated lecithin, hydrogenated palm glyceride, hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenated tallow’ glyceride, hydrogenated vegetable oil, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin, hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline, isocety 1 stearate, isocetyl stearoyl stearate, isodecyl oleate, isopropyl isostearate, isopropyl lanolate. isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearamide DEA, isostearic acid, isostearyl lactate, isostearyl neopentanoate, jasmine (Jasminum officinale) oil jojoba (Buxus chinensis) oil, kelp, kukui (Aleurites moluccana) nut oil, lactamide MEA, laneth-16, laneth-10 acetate, lanolin, lanolin acid, lanolin alcohol, lanohn oil, lanolin wax, lavender (Lavandula angustifolia) oil, lecithin, lemon (Citrus medica limonum) oil, linoleic acid, linolenic acid. Macadamia ternifolia nut oil, maltitol, matncaria (Chamomilla recutita) oil, methyl glucose sesquistearate, methylsilanol PCA, mineral oil, mink oil, mortierella oil, myristyl lactate, myristyl myristate, myristyl propionate, neopentyl glycol di caprylate / dicaprate, octyldodecanol, octyldodecyl myristate, octyldodecyl stearoyl stearate, octyl hydroxystearate, octyl palmitate, octyl301685781.1salicylate, octyl stearate, oleic acid, olive (Olea europaea) oil, orange (Citrus aurantium dulcis) oil. palm (Elaeis guineensis) oil, palmitic acid, pantethine. panthenol, panthenyl ethyl ether, paraffin, PC A, peach (Prunus per ica) kernel oil, peanut (Aracn' is hypogaea) oil, PEG-8 C12- 18 ester, PEG-15 cocamine, PEG-150 distearate, PEG-60 glycer I isostearate, PEG-5 glyceryl stearate, PEG-30 glyceryl stearate, PEG- 7 hydrogenated castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil. PEG-20 methyl glucose sesquistearate, PEG-40 sorbitan peroleate. PEG-5 soy sterol. PEG-10 soy sterol, PEG-2 stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG-40 stearate, PEG-50 stearate, PEG- 100 stearate, PEG- 150 stearate, pentadecalactone, peppermint (Mentha piperita) oil, petrolatum, phospholipids, plankton extract, poly amino sugar condensate, poly glyceryl -3 diisostearate, polyquatemium-24, polysorbate 20. polysorbate 40, polysorbate 60, polysorbate 80. polysorbate 85, potassium myristate, potassium palmitate, propylene glycol, propylene glycol dicaprylate / dicaprate, propylene glycol dioctanoate, propylene glycol dipelargonate, propylene glycol laurate, propylene glycol stearate, propylene glycol stearate SE, PVP, pyridoxine dipalmitate, retinol, retinyl palmitate, rice (Oiyza saliva) bran oil, RN A, rosemary (Rosmarinus officinalis) oil, rose oil, safflower (Carthamus tinctorius) oil, sage (Salvia officinalis) oil. sandalwood (Santalum album) oil, serine, serum protein, sesame (Sesamum indicum) oil, shea butter (Butyrospermum parkii), silk powder, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, sodium palmitate, sodium PCA, sodium polyglutamate, soluble collagen, sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan sesquioleate, sorbitan stearate, sorbitol, soybean (Glycine soja) oil, sphingolipids, squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxy dimethicone, stearoxytrimethylsilane, stearyl alcohol, slearG glycyrrhetmate. stearyl heptanoate, stearyl stearate, sunflower (Helianthus annuus) seed oil, sweet almond (Prunus amygdahts dulcis) oil, synthetic beeswax, tocopheryl acetate, tocopheryl linoleate, tribehenin, tridecyl neopen tan oate, tridecyl stearate, triethanolamine, tristearin, urea, vegetable oil. water, waxes, wheat (Triticum vulgare) germ oil, and ylang (Cananga odorata) oil.

[0108] Antioxidants - Additional antioxidants can be used in combination with ascorbic acid and vitamin E. Non-limiting examples of antioxidants that can be used include acetyl cysteine, ascorbic acid derivatives like ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, l-bnlyl hydroquinone, cysteine, cysteine HC1, diamylhydroquinone, di-t-butylhydroquinone, dicetyl thiodipropionate, dioleyl tocopheryl methylsilanol, disodium ascorbyl sulfate, distearyl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, esters of301685781.1ascorbic acid, ethyl ferulate, ferulic acid, gallic acid esters, hydroquinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanol ascorbate, natural botanical anti-oxidants such as green tea or grape seed extracts, nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid, potassium ascorbyl tocopheryl phosphate, potassium sulfite, propyl gallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium thioglycol ate, sorbityl furfural, thiodiglycol. thiodiglycolamide, thiodiglycolic acid, thioglycolic acid, thiolactic acid, thiosalicylic acid, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18, tocophereth-50, tocophersolan, tocopheryl acetate, tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate, tris(nonylphenyl)phosphite, tannic acid, gallic acid, ellagic acid, and other tannins.

[0109] Structuring and stiffening agents - In other non-limiting aspects, the compositions of the present invention can include a structuring agent. Structuring agents, in certain aspects, assist in providing rheological characteristics to the composition that contribute to stability. In other aspects, structuring agents can also function as an emulsifier or surfactant Non-limiting examples of structuring agents include stearic acid, palmitic acid, stearyl alcohol, cety l alcohol, behenyl alcohol, stearic acid, palmitic acid, the polyethylene glycol ether of stearyl alcohol having an average of about 1 to about 21 ethylene oxide units, the polyethylene glycol ether of cetyl alcohol having an average of about 1 to about 5 ethylene oxide units, and mixtures thereof,

[0110] Emulsifiers - Emulsifiers can reduce the interfacial tension between phases and improve the formulation and stability of an emulsion. The emulsifiers can be nonionic, cationic, anionic, and zwitterionic emulsifiers (See McCutcheon's (1986); U. S. Pat. Nos.5,011,681; 4,421,769; 3,755,560) Non-limiting examples include esters of glycerin, esters of propylene glycol, fatty7acid esters of polyethylene glycol, fatty7acid esters of polypropylene gly col, esters of sorbitol, esters of sorbitan anhydrides, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatly acid amides, acyl lacty laics. soaps, TEA stearate. DEA oleth-3 phosphate, polyethylene glycol 20 sorbitan monolaurate (poly sorbate 20), polyethy lene glycol 5 soya sterol, steareth-2, steareth-20, steareth-21, ceteareth-20, ceteary 1 glucoside, cetearyi alcohol, Cl2-13 pareth-3, PPG-2 methyl glucose ether distearate, PPG-5-ceteth-20, bis-PEG / PPG-20 / 20 dimethicone, ceteth-10, polysorbate 80, cetyl phosphate, potassium cetyl301685781.1 - 26 -phosphate, diethanolamine cetyl phosphate, polysorbate 60, glyceryl stearate, PEG- 100 stearate, arachidyl alcohol, arachidyl glucoside, and mixtures thereof.

[0111] Silicone containing compounds - In non-limiting aspects, silicone containing compounds include any member of a family of polymeric products whose molecular backbone is made up of alternating silicon and oxygen atoms with side groups attached to the silicon atoms. By varying the -Si-O- chain lengths, side groups, and crosslinking, silicones can be synthesized into a wide variety of materials. They can vary in consistency from liquid to gel to solids. The silicone containing compounds that can be used in the context of the present invention include those described in this specification or those known to a person of ordinary skill in the art. Non-limiting examples include silicone oils (e.g., volatile and non-volatile oils), gels, and solids In certain aspects, the silicon containing compounds includes a silicone oils such as a polyorganosiloxane. Non-limiting examples of polyorganosiloxanes include dimethicone, cyclomethicone. polysilicone-11, phenyl trimetliicone, trimethylsilylamodimethicone, stearoxytriinethylsilane, or mixtures of these and other organosiloxane materials in any given ratio in order to achieve the desired consistency and application characteristics depending upon the intended application (e.g., to a particular area such as the skin, hair, or eyes). A "‘volatile silicone oil’" includes a silicone oil have a low heat of vaporization, i.e. normally less than about 50 cal per gram of silicone oil. Non-limiting examples of volatile silicone oils include: cyclomethi cones such as Dow Coming 344 Fluid. Dow Coming 345 Fluid, Dow Coming 244 Fluid, and Dow Coming 245 Fluid, V olatile Silicon 7207 (Union Carbide Corp., Danbury, Conn.); low viscosity dimethicones, i.e. dimethicones having a viscosity of about 50 cst or less (e.g.. dimethicones such as Dow Coming 200-0.5 cst Fluid). The Dow Coming Fluids are available from Dow Coming Corporation, Midland, Michigan. Cyclomethicone and dimethicone are described in the Third Edition of the CTFA Cosmetic Ingredient Dictionary (incorporated by reference) as cyclic dimethyl polysiloxane compounds and a mixture of fully methylated linear siloxane polymers end-blocked with trimethylsiloxy units, respectively. Other non-limiting volatile silicone oils that can be used in the context of the present invention include those available from General Electric Co., Silicone Products Div., Waterford, N. Y. and SWS Silicones Div of Stauffer Chemical Co., Adrian, Michigan.

[0112] Exfoliating agents - Exfoliating agents include ingredients that remove dead skin cells on the skin's outer surface. These agents may act through mechanical, chemical, and / or301685781.1other means. Non-limiting examples of mechanical exfoliating agents include abrasives such as pumice, silica, cloth, paper, shells, beads, solid crystals, solid polymers, etc. Non-limiting examples of chemical exfoliating agents include acids and enzyme exfoliants. Acids that can be used as exfoliating agents include, but are not limited to, glycolic acid, lactic acid, citric acid, alpha hydroxy acids, beta hy droxy acids, etc. Other exfoliating agents known to those of skill in the art are also contemplated as being useful within the context of the present invention.

[0113] Essential oils - Essential oils include oils derived from herbs, flowers, trees, and other plants. Such oils are typically present as tiny droplets between the plant’s cells, and can be extracted by several method known to those of skill in the art (e.g.. steam distilled, enfleurage (i.e., extraction by using fat), maceration, solvent extraction, or mechanical pressing) When these types of oils are exposed to air they tend to evaporate (i.e., a volatile oil). As a result, many essential oils are colorless, but with age they can oxidize and become darker. Essential oils are insoluble in water and are soluble in alcohol, ether, fixed oils (vegetal), and other organic solvents. Typical physical characteristics found in essential oils include boiling points that vaty from about 160° to 240° C and densities ranging from about 0.759 to about 1.096.

[0114] Essential oils typically are named by the plant from which the oil is found. For example, rose oil or peppermint oil are derived from rose or peppermint plants, respectively. Non-limiting examples of essential oils that can be used in the context of the present invention include sesame oil, macadamia nut oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary' oil, coriander oil, thyme oil, pimento berries oil. rose oil, anise oil, balsam oil. bergamot oil. rosewood oil. cedar oil. chamomile oil, sage oil, clary sage oil. clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil. geranium oil. ginger oil, grapefruit oil, jasmine oil, juniper oil. lavender oil, lemon oil, lemongrass oil, lime oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, orange oil. patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil. rose otto oil, rosemary oil, sandalwood oil, spearmint oil, spikenard oil, vetiver oil, wintergreen oil, or ylang. Other essential oils known to those of skill in the art are also contemplated as being useful w ithin the context of the present invention.

[0115] Oils and oil-based ingredients - Oils and oil-based ingredients include oil ingredients that are natural, synthetic or semi -synthetic and that can act as that can be solvents, co-solvents, or permeation enhancers and retarders that make a two-phase system or a singlephase system. Non-limiting examples include castor oil, safflower oil, sunflower oil, soybean301685781.1 - 28 -oil, olive oil, sesame seed oil, medium-chain triglycerides, isopropyl palmitate, isopropyl myristate, isopropyl stearate, cholesterol and relative compounds, paraffin, ethylhexylpalmitate, lanolin and its derivatives, lanolin oil, lanolin alcohol, jojoba oil, argan oil, shea butter, almond oil, sweet almond oil, apricot kernel oil, coconut oil, linseed oil, macadamia oil, rapeseed oil, rosehip oil, shea butter, wheat germ oil, avocado oil, mango seed butter, mineral oil, parafin, petroleum jelly, dimethicone, cyclopentasiloxane, caprylic / capric triglycerides, fatty acids and esters, stearic acid, oleic acid, caprylic acid, glyceryl stearate, cetyl alcohol, stearyl alcohol, cetearyl alcohol, cetostearyl alcohol, grape seed oil, hemp seed oil, pumpkin seed oil, evening primrose oil, squalene, squalane, esters of fatty alcohols, and cetyl palmitate. Non-limiting examples of silicone oils include dimethicone, cyclopentasiloxane, trimethyl siloxylsilicate, phenyl trimethicone, and cyclohexasiloxane. Non-limiting examples of ester oils include isopropyl myristate, isopropyl palmitate, cetearyl / ethylhexanoate, caprylic / capric triglycerides, and ethylhexyl palmitate. Non-limiting examples of synthetic esters of fatty alcohols include cetyl palmitate, stearyl stearate, and glyceryl starate. Non-limiting examples of synthetic triglycerides include caprylic / capric triglyceride, and medium chain triglycerides. Non-limiting examples of alkyl esters include C12-C15 alkyl benzoate, and coco-caprylate / caprate. Non-limiting examples of hydrocarbon oils include mineral oil (paraffinum liquidum), petrolatum and petroleum jelly. Non-limiting examples of poly olefin oils include poly butene, and polyisobutene. Non-limiting examples of emollients include polyethylene glycol derivatives and dimethiconol.

[0116] Waxes and butters - Waxes and butters include lipids that are solid at room temperature. Non-limiting examples of waxes and butters include beeswax, carnauba wax, rice bran wax, tribehenm. sorbitol / sebacic acid copolymer behenate, lanolin cera, shea butter, cocoa butter, mango butter, beeswax, candelia wax, emulsifying waxes, and microcrystalline wax.

[0117] Thickening agents - Thickening agents, including thickener or gelling agents, include substances which that can increase the viscosity of a composition. Thickeners includes those that can increase the viscosity of a composition without substantially modifying the efficacy of the active ingredient within the composition. Thickeners can also increase the stability of the compositions of the present invention. In certain aspects of the present invention, thickeners include hydrogenated poly isobutene, trihydroxystearin, ammonium acryloyldimethyltaurate / vp copolymer, or a mixture of them. Non-limiting examples of additional thickening agents that can be used in the context of the present invention include301685781.1carboxylic acid polymers, crosslinked polyaciylate polymers, polyacrylamide polymers, polysaccharides, and gums. Examples of carboxylic acid polymers include crosslinked compounds containing one or more monomers derived from acry lic acid, substituted acrylic acids, and salts and esters of these acrylic acids and the substituted acry lic acids, wherein the crosslinking agent contains two or more carbon-carbon double bonds and is derived from a polyhydric alcohol (see U. S. Pat. Nos. 5,087,445; 4,509,949; 2,798,053; CTF A International Cosmetic Ingredient Dictionary', Fourth edition. 1991, pp. 12 and 80). Examples of commercially’ available carboxylic acid polymers include carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of sucrose or pentaerythritol (e.g., CARBOPOL ™ 900 series from B. F. Goodrich).00118] Polymers -Non-limiting examples of polyacrylamide polymers (including nonionic polyacrylamide polymers including substituted branched or unbranched polymers) include polyacrylamide, isoparaffin and laureth-7, multi-block copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids. Non-limiting examples of crosslinked polyaciylate polymers include cationic and nonionic polymers Examples are described in U. S Pat. Nos. 5,100,660; 4,849,484; 4.835,206; 4,628.078; 4,599,379).

[0119] Polysaccharides - Non-limiting examples of polysaccharides include cellulose, carboxymethyl hydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, methyl hydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Another example is an alky l substituted cellulose where the hydroxy groups of the cellulose polymer is hydroxy alkylated (preferably hydroxy ethylated or hydroxypropylated) to form a hydroxyalkylated cellulose which is then further modified with a CIO -C30 straight chain or branched chain alkyl group through an ether linkage. Typically these polymers are ethers of C10-C30 straight or branched chain alcohols with hydroxyalkylcelluloses. Other useful polysaccharides include scleroglucans comprising a linear chain of (1-3) linked glucose units with a (1-6) linked glucose every three units.

[0120] Gums - Non-limiting examples of gums that can be used with the present invention include acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxy propyl tri monium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium301685781.1 - 30 -alginate, potassium carrageenan, propylene glycol alginate, alginate sodium, sclerotium gum, sodium carboxymethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum. acacia gum, pectin, and mixtures thereof.

[0121] Preservatives - Non-limiting examples of preservatives that can be used in the context of the present invention include quaternary ammonium preservatives such as polyquaternium-1 and benzalkonium halides (e.g., benzalkonium chloride (" BAC”) and benzalkonium bromide), parabens (e.g., methylparabens and propylparabens), phenoxyethanol, benzyl alcohol, chlorobutanol, phenol, sorbic acid, thimerosal, or combinations thereof.

[0122] Emollients - Useful emollients include the following: (a) silicone oils and modifications thereof such as linear and cyclic polydimethylsiloxanes; amino, alkyl, alkylaryl, and aryl silicone oils; (b) fats and oils including natural fats and oils such as jojoba, soybean, sunflower, rice bran, avocado, almond, olive, sesame, persic, castor, coconut, mink oils; cacao fat; beef tallow, lard; hardened oils obtained by hydrogenating the aforementioned oils; and synthetic mono, di and triglycerides such as myristic acid glyceride and 2 -ethylhexanoic acid glyceride; (c) waxes such as carnauba, spermaceti, beeswax, lanolin, and derivatives thereof; (d) hydrophobic plant extracts; (e) hydrocarbons such as liquid paraffins, vaseline, microcrystalline wax, ceresin, squalene, pnstan and mineral oil; ( f) higher fatty acids such as lauric, myristic, palmitic, stearic, behenic, oleic, linoleic, linolenic, lanolic, isostearic, arachidonic and poly unsaturated fatty acids (PUFA); (g) higher alcohols such as laury l, cetyl, stearyl, oleyl, behenyl, cholesterol and 2-hexydecanoI alcohol; (h) esters such as cetyl octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, glycerol monostearate, glycerol distearate, glycerol tristearate, alkyl lactate, alkyl citrate and alkyl tartrate; (i) essential oils and extracts thereof such as mentha, jasmine, camphor, white cedar, bitter orange peel, ryu, turpentine, cinnamon, bergamot, citrus unshiu. calamus, pine, lavender, bay. clove, hiba, eucalyptus, lemon, starflower, thyme, peppermint, rose, sage, sesame, ginger, basil, juniper, lemon grass, rosemary', rosewood, avocado, grape, grapeseed, myrrh, cucumber, watercress, calendula, elder flower, geranium, linden blossom, amaranth, seaweed, ginko, ginseng, carrot, guarana. tea tree, jojoba, comfrey, oatmeal, cocoa, neroli. vanilla, green tea, penny royal, aloe vera. menthol, cineole, eugenol, citral, Citronelle, borneol, linalool, geraniol, evening primrose, camphor, thymol, spirantol, penene, limonene and terpenoid oils; (j) lipids301685781.1 - 31 -such as cholesterol, ceramides, sucrose esters and pseudo-ceramides as described in European Patent Specification No. 556,957; (k) vitamins, minerals, and skin nutrients such as vitamins A, E, and K; vitamin alkyl esters, including vitamin C alkyl esters; magnesium, calcium, and milk; (1) sunscreens such as octyl methoxyl cinnamate (Parsol MCX) and butyl methoxy benzoylmethane (Parsol 1789); (1) phospholipids; (m) polyhydric alcohols such as glycerine and propylene glycol; and polyols such as polyethylene glycols; (n) antiaging compounds such as alpha hydroxy acids, beta hydroxy acids: and (o) mixtures of any of the foregoing components, and the like.

[0123] Tackifiers - Examples of suitable tackifiers, include, but are not limited to. aliphatic hydrocarbon resins, aromatic modified aliphatic hydrocarbon resms, hydrogenated polycyclopentadiene resins, poly cyclopentadiene resins, gum rosins, gum rosin esters, wood rosins, wood rosin esters, tall oil rosins, tall oil rosin esters, polyterpenes, aromatic modified polyterpenes, terpene phenolics, aromatic modified hydrogenated poly cyclopentadiene resins, hydrogenated aliphatic resin, hydrogenated aliphatic aromatic resins, hydrogenated terpenes and modified terpenes, hydrogenated rosin acids, hydrogenated rosin esters, polyisoprene, partially or fully hydrogenated polyisoprene, polybutenediene, partially or fully hydrogenated poly butenediene, and the like. As is evidenced by some of the cited examples, the tackifier may¬ be fully or partially hydrogenated. The tackifier may also be non-polar. (Non-polar meaning that the tackifier is substantially free of monomers having polar groups. Preferably, the polar groups are not present, however, if they are present, they are preferably present in an amount of up to about 5% by weight, preferably up to about 2% by weight, and more preferably up to about 0.5% by weight.).

[0124] Colorants - The compositions of the present invention also contain at least one cosmetically acceptable colorant such as a pigment or dyestuff. Examples of suitable pigments include, but are not limited to, inorganic pigments, organic pigments, lakes, pearlescent pigments, iridescent or optically variable pigments, and mixtures thereof. A pigment should be understood to mean inorganic or organic, white or colored particles. Said pigments may optionally be surface-treated within the scope of the present invention but are not limited to treatments such as silicones, perfluorinated compounds, lecithin, and amino acids.

[0125] Surfactants - Surfactants useful as the surfactant components in the compositions of the present invention include nonionic, anionic, cationic, and amphoteric (zwitterionic) surfactants and may be used in combination with each other.301685781.1

[0126] pH adjustors - The pH adjustors, include inorganic and organic acids and bases and in particular aqueous ammonia, citric acid, phosphoric acid, acetic acid, sodium hydroxide, lactic acid, levulinic acid, glycolic acid, tartaric acid, malic acid, pyrrolidonecarboxylic acid (PC A), succinic acid, citric acid, glutamic acid, 2-amino-2-methyl-l -propanol (AMP), and triethanolamine (TEA).

[0127] Reducing agents - Suitable reducing agents include, but are not limited to, thiourea, salts (such as sodium salts) of thiosulfate, sulfite, bisulfite, metabisulfite, borohydride, and hypophosphite, ascorbic acid and salts, esters, and derivatives thereof (e.g., ascorbyl palmitate and ascorbyl polypeptide), and tocopherols and salts, esters, and derivatives thereof (e.g., tocopherol acetate). Other reducing agents are listed on pages 1655 -56 of the INCI Handbook.

[0128] Fragrances - The compositions disclosed herein may optionally include a fragrance. Examples of possible fragrances include natural oils or naturally derived materials, and synthetic fragrances such as hydrocarbons, alcohols, aldehydes, ketones, esters, lactones, ethers, nitriles, and polyfunctionals. Non-limiting examples of natural oils include the following: basil (Ocimum basilicutn) oil, bay (Pimento acris) oil, bee balm (Monarda didyma) oil, bergamot (Citrus aurantium bergamia) oil, cardamom (Elettaria cardamomum) oil, cedarwood (Cedrus atlantica) oil, chamomile (Anthemis nobilis) oil, cinnamon (Cinnamomum cassia) oil, citronella (Cymbopogon nardus) oil, clan- (Salvia sclarea) oil, clove (Eugenia caryophyllus) oil, cloveleaf (Eufenia caryophyllus) oil, Cyperus esculentus oil, cypress (Cupressus sempeni rens) oil. Eucalyptus citriodora oil, geranium maculatum oil, ginger (Zingiber officinale) oil, grapefruit (Citrus grandis) oil, hazel (Corylus avellana) nut oil, jasmine (Jasminum officinale) oil. Juniperus communis oil, Juniperus oxycedrus tar, Juniperus virginiana oil, kiwi (Actinidia chinensis) water, lavandin (Lavandula hybrida) oil, lavender (Lavandula angustifolia) oil, lavender (Lavandula angustifolia) water, lemon (Citrus medica limonum) oil, lemongrass (Cymbopogon schoenanthus) oil, lime (Citrus aurantifolia) oil, linden (Tilia cordata) oil, linden (Tilia cordata) water, mandarin orange (Citrus nobilis) oil, nutmeg (Myristica fragrans) oil, orange (Citrus aurantium dulcis) flower oil, orange (Citrus aurantium dulcis) oil, orange (Citrus aurantium dulcis) water, patchouli (Pogostemon cablin) oil, peppermint (Menthe piperita) oil, peppermint (Menthe peperita) water, rosemary (Rosmarinus officinalis) oil. rose oil, rose (Rosa damascena) extract, rose (Rosa multiflora) extract, rosewood (Aniba rosaeodora) extract, sage (Salvia officinalis) oil. sandalwood (Santalum album) oil, spearmint (Menthe viridis) oil, tea tree (Melaleuca alternifolia) oil, and301685781.1 - 33 -ylang (Cananga odorata) oil. Some non-limiting examples of synthetic hydrocarbon fragrances include caryophyllene, p-farnesene. limonene, a-pinene, and, p-pinene. Some non-limiting examples of synthetic alcohol fragrances include bacdanol, citronellol, linalool, phenethyl alcohol, and a-terpineol (R=H). Some non-limiting examples of synthetic aldehyde fragrances include 2 -methyl undecanal, citral, hexyl cinnamic aldehyde, isocy col citral, lilial, and 10- undecenal. Some non-limiting examples of synthetic ketone fragrances include cashrneran, a- ionone. isocyclemone E, koavone, muscone, and tonalide. Some non-limiting examples of synethetic ester fragrances include benzyl acetate. 4-t-butylcvclohexyl acetate (cis and trans), cedryl acetate, cyclacet, isobornyl acetate, and a-terpinyl acetate (R=acetyl). Some non¬ limiting examples of synthetic lactone fragrances include coumarin, jasmine lactone, muskalactone, and peach aldehyde. Some non-limiting examples of synthetic ether fragrances include ambroxan, anther, and galaxolide. Some non-limiting examples of synthetic nitrile fragrances include cmnamonitrile and gernonitrile. Finally, some non-limiting examples of synthetic polyfunctional fragrances include amyl salicylate, isoeugenol, hedione, heliotropine, lyral, and vanillin.

[0129] Foaming agents - The foaming agents include, for example, sodium lauryl sulfate, sodium lauroyl sarcosine, sodium alkyl sulfosuccinates, sodium coconut oil fatty acid monoglycerol sulfonates, sodium a-olefm sulfonates. N-acylamino acid salts such as N-acyl glutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, maltitol fatty acid esters, sucrose fatty acid esters, polyglycerol fatty acid esters, fatty’ acid diethanolamides, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil and polyoxyethylene fatty acid esters. These foaming agents are usable either alone or in combination of two or more of them.

[0130] Tanning agents - Suitable tanning agents include, without limitation, alpha-hydroxy aldehydes and ketones, glyceraldehyde and related alcohol aldehydes, various indoles, imidazoles and derivatives thereof, and various approved pigmentation agents. Other suitable tanning agents include, without limitation, methyl glyoxal, glycerol aldehyde, erythrulose, alloxan, 2,3-dihydroxysuccindialdehyde, 2,3-dimethoxysuccindialdehyde. 2-amino-3-hy droxy -s uccindi aldehyde and 2-benzy lamino-3 -hy droxy s uccindi aldehyde.

[0131] Astringents - Suitable astringents include, without limitation, aluminum citrate, aluminum lactate, extracts of birch, extracts of coffee, extracts of evening primrose, extracts of grape, extracts of henna, extracts of ivy, extracts of lemon, extracts of witch hazel. Ammonium301685781.1 - 34-and Potassium Alum, Aluminum Triphosphate, Aluminum Glycinate and Aluminum Phenolsulfate, Alcloxa, Aklioxa, Aluminum Stearate, Aluminum Sulfate and Aluminum Citrate, Sodium Aluminum Phosphate, Sodium Alum, Sodium Aluminum Chlorohydroxy Lactate, Calcium Lactate, Calcium Chloride. Calcium Sulfate Hydrate, Sodium Aluminum Lactate, Zinc Acetate, Zinc Chloride, Zinc Sulfate, Zinc Lactate, Zinc Zeolite, Zinc Phenolsulfonate, and combinations thereof. What is meant by an extract is either the whole fruit, bean, and / or plant or select constituents of such fruit, bean, and / or plant.

[0132] Antiseptics - Suitable antiseptics include, without limitation, methyl, ethyl, propyl, or butyl ester of p-oxybenzoic acid, phenoxyethanol, o-phenylphenol, dehydroacetic acid, or salts thereof, p-cresol, m-cresol, o-chlor-m-xylenol. peppermint oil, Echinacea, bloodroot, cayenne, tea tree oil. wild bergamont, chaparral, stinging metal, bay, myrrh, rhatany bark, toothache tree, calendula, chamomile, mupirocin, neomycin sulfate, bacitracin, polymyxin B, 1-ofloxacin, tetracyclines (chlortetracycline hydrochloride, oxytetracycline hy drochloride and tetrachcy cline hydrochori de), clindamycin phsphate, gentamicin sulfate, benzalkonium chloride, benzethonium chloride, hexylresorcinol, methylbenzethoniura chloride, phenol, quaternary ammonium compounds, triclocarbon, triclosan, and tea tree oil.

[0133] Deodorants and Antiperspirants - Suitable antiperspirants and deodorants include, without limitation, zinc salts such as zinc sulfate and zinc chloride, glycinates such as aluminum zirconium glycinate, aluminum chlorohydrate, aluminum zirconium tetrachlorohydrex, zinc carbonate, orthophenylphenol, and quaternary ammonium compounds such as dimethyl benzyl ammonium chloride and hexamethonium chloride.

[0134] Tighteners - Examples of skin lighteners include, without limitation, hydroquinone, kojic acid, licorice and / or its derivatives, ascorbic acid and / or its derivatives, arbutin, bearberry extract. Glycyrrhiza glabra and its derivatives, Chlorella vulgaris extract, perilla extract, coconut fruit extract, niacinamide, resveratrol, tannic acid, and / or other depigmenting agents.

[0135] Biocides - Examples of biocides include, without limitation, triclosan, 3,4,4'- trichlorocarbanilide (triclocarban); 3,4,4'-trifhioromethyl-4,4'-dichlorocarbanilide (cloflucarban); 5-chloro-2-methyl-4-isothiazohn-3-one: lodopropynlbulyl carbamate; 8-hydroxyquinoline; 8-hydroxyquinoline citrate; 8-hydroxyquinoline sulfate: 4-chloro-3,5-xylenol(chloroxylenol); 2-bromo-2-nitropropane-1.3-diol; diazolidinyl urea; butoconazole; ny statin; terconazole; nitrofurantoin; phenazopyridine; acyclovir; clortrimazole;301685781.1 - 35 -chloroxylenol; chlorhexidine; miconazole; terconazole; butylparaben; ethylparaben; methylparaben; methylchloroisothiazoline; methylisothiazoline; a mixture of 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin and 3-iodo-2-propynyl butyl carbamate; oxyquinoline; EDTA; tetrasodium EDTA; p-hydroxyl benzoic acid ester; alkyl pyridinum compounds; coco phosphatidyl PG-dimonium chloride; chlorhexidine gluconate; chlorhexidine digluconate; chlorhexidine acetate; chlorhexidine isethionate; chlorhexidine hydrochloride; benzalkonium chloride; benzethonium chloride; polyhexamethylene biguanide; and mixtures thereof.

[0136] Pharmaceutical active agents are also contemplated as being useful with the compositions of the present invention. Non-limiting examples of pharmaceutical active agents include anti-acne agents, agents used to treat rosacea, analgesics, anesthetics, anorectals, antihistamines, anti-inflammatory agents including non-steroidal anti-inflammatory drugs, antibiotics, antifungals, antivirals, antimicrobials, anti-cancer actives, scabicides, pediculicides, antineoplastics, antiperspirants, antipruritics, antipsoriatic agents, antiseborrheic agents, biologically active proteins and peptides, bum treatment agents, cauterizing agents, depigmenting agents, depilatories, diaper rash treatment agents, enzymes, hair growth stimulants, hair growth retardants including DFMO and its salts and analogs, hemostatics, keratolytics, canker sore treatment agents, cold sore treatment agents, photosensitizing actives, skin protectant / barner agents, steroids including hormones and corticosteroids, sunburn treatment agents, sunscreens, transdermal actives, wart treatment agents, wound treatment agents, wound healing agents, etc.Pharmaceutical and Cosmetic Preparations

[0137] In some embodiments, the methods disclosed herein can include the administration of pharmaceutical and / or cosmetic compositions and formulations comprising any of the active components disclosed herein.

[0138] In certain embodiments, the compositions are formulated with a pharmaceutically acceptable carrier. The pharmaceutical compositions and formulations can be administered parenterally, topically, by direct administration into the gastrointestinal tract (e.g., orally or rectally), or by local administration, such as by aerosol or transdermally. The pharmaceutical compositions can be formulated in any way and can be administered in a variety' of unit dosage forms depending upon the condition or disease and the degree of illness, the general medical condition of each patient, the resulting preferred method of administration301685781.1 - 36 -and the like. Details on techniques for formulation and administration of pharmaceuticals are well described in the scientific and patent literature, see, e.g.. Remington: The Science and Practice of Pharmacy, 21st ed., 2005.

[0139] The active compounds can be administered alone or as a component of a pharmaceutical formulation (composition). The compounds may be formulated for administration, in any convenient way for use in human or veterinary medicine. Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.

[0140] Formulations of the compositions include those suitable for intradermal, inhalation, oral / nasal, topical, parenteral, rectal, and / or intravaginal administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient (e.g., resveratrol + tannic acid) which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration, e.g, intradermal or inhalation. Die amount of active ingredient which can be combined with a carrier material to produce a single dosage form w ill generally be that amount of the compound which produces a therapeutic effect.

[0141] Pharmaceutical formulations can be prepared according to any method known to the art for the manufacture of pharmaceuticals. Such drugs can contain sweetening agents, flavoring agents, coloring agents and preserving agents. A formulation can be admixtured with nontoxic pharmaceutically acceptable excipients which are suitable for manufacture. Formulations may comprise one or more diluents, emulsifiers, preservatives, buffers, excipients, etc. and may be provided in such forms as liquids, powders, emulsions, lyophilized powders, sprays, creams, lotions, controlled release formulations, tablets, pills, gels, on patches, in implants, etc.

[0142] Aqueous suspensions can contain an active agent (e.g., zoledronic acid + tannic acid + resveratrol) in admixture with excipients suitable for the manufacture of aqueous suspensions, e.g., for aqueous intradermal injections. Such excipients include a suspending agent, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia, and dispersing or wetting agents such as a naturally occurring phosphatide (e.g..301685781.1 - 37 -lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethylene oxycetanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol (e.g., polyoxyethylene sorbitol mono-oleate), or a condensation product of ethylene oxide with a partial ester derived from fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan mono-oleate). The aqueous suspension can also contain one or more preservatives such as ethyl or n-propyl p-hydroxybenzoate. one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose, aspartame or saccharin. Formulations can be adjusted for osmolarity.1001431 In certain embodiments, oil -based pharmaceuticals are used for administration of the active compounds disclosed herein. Oil-based suspensions can be formulated by suspending an active agent in a vegetable oil. such as arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin; or a mixture of these. See e.g., U. S. Patent No.5,716,928 describing using essential oils or essential oil components for increasing bioavailability and reducing inter- and intra-individual variability of orally administered hydrophobic pharmaceutical compounds (see also U. S. Patent No. 5,858,401). The oil suspensions can contain a thickening agent, such as beeswax, hard paraffin or cetyl alcohol. Sweetening agents can be added to provide a palatable oral preparation, such as glycerol, sorbitol or sucrose. These formulations can be preserved by the addition of an antioxidant such as ascorbic acid. As an example of an injectable oil vehicle, see Minto (1997) J. Pharmacol. Exp. Then 281:93-102,

[0144] In certain embodiments, the pharmaceutical compositions and formulations are in the form of oil-in- water emulsions. The oily phase can be a vegetable oil or a mineral oil, described above, or a mixture of these. Suitable emulsifying agents include naturally-occurring gums, such as gum acacia and gum tragacanth, naturally occurring phosphatides, such as soybean lecithin, esters or partial esters derived from fatty acids and hexitol anhydrides, such as sorbitan mono-oleate, and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan mono-oleate. The emulsion can also contain sweetening agents and flavoring agents, as in the formulation of syrups and elixirs. Such formulations can also contain a demulcent, a preservative, or a coloring agent. In alternative embodiments, these injectable oil-in-water emulsions comprise a paraffin oil, a sorbitan monooleate, an ethoxylated sorbitan monooleate and / or an ethoxylated sorbitan trioleate.301685781.1 - 38 -

[0145] In certain embodiments, the pharmaceutical compositions and formulations are delivered transdermally, including through the use of transdemial patches, by a topical route, formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols.

[0146] In certain embodiments, the pharmaceutical compounds and formulations are lyophilized. Stable lyophilized formulations comprising an inhibitory nucleic acid can be made by lyophilizing a solution comprising a pharmaceutical and a bulking agent, e.g., mannitol, trehalose, raffinose, and sucrose or mixtures thereof. A process for preparing a stable lyophilized formulation can include lyophilizing a solution about 2.5 mg / mL nucleic acid, about 15 mg / mL sucrose, about 19 mg / mL NaCl, and a sodium citrate buffer having a pH greater than 5.5 but less than 6.5. See, e.g., U. S. 20040028670,

[0147] The formulations can be administered for prophylactic and / or therapeutic treatments, in some aspects, the formulations are administered in combination with dermal injections. In certain embodiments, for therapeutic applications, compositions are administered to a subject who is need of reduced triglyceride levels, or who is at risk of or has a disorder described herein, in an amount sufficient to cure, alleviate or partially arrest the clinical manifestations of the disorder or its complications; this can be called a therapeutically effective amount. For example, in certain embodiments, pharmaceutical compositions are administered in an amount sufficient for the prevention or treatment of cancer in a subject.

[0148] The amount of pharmaceutical composition adequate to accomplish this is a therapeutically effective dose. The dosage schedule and amounts effective for this use, i.e., the dosing regimen, will depend upon a variety of factors, including the stage of the disease or condition, the severity of the disease or condition, the general state of the patient's health, the patient's physical status, age and the like. In calculating the dosage regimen for a patient, the mode of administration also is taken into consideration.

[0149] The dosage regimen also takes into consideration pharmacokinetic and dermatokinelic parameters well known in the art, i.e., the active agents' rate of absorption, bioavailability, metabolism, clearance, and the like (see, e.g., Hidalgo-Aragones (1996) J. Steroid Biochem. Mol. Biol. 58:611-617; Groning (1996) Pharmazie 51:337-341; Fotherby (1996) Contraception 54:59-69: Johnson (1995) J Pharm. Sci. 84: 1 144-1 146; Rohatagi (1995) Pharmazie 50:610-613; Brophy (1983) Eur. J. Clin. Pharmacol. 24: 103-108; Remington: The Science and Practice of Pharmacy, 21st ed., 2005). The state of the art allows301685781.1 - 39 -the clinician to determine the dosage regimen for each individual patient, active agent and disease or condition treated. Guidelines provided for similar compositions used as pharmaceuticals can be used as guidance to determine the dosage regiment, i.e., dose schedule and dosage levels, administered practicing the methods are correct and appropriate. Single or multiple administrations of formulations can be given depending on for example: the dosage and frequency as required and tolerated by the patient, the degree and amount of cholesterol homeostasis generated after each administration, and the like. The formulations should provide a sufficient quantity of active agent to effectively treat, prevent or ameliorate conditions, diseases or symptoms, e.g., treat squamous ceil carcinoma.A. Examples

[0150] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention,

[0151] A series of compounds and combinations of compounds were identified that inhibit the endogenous enzymes found in human skin that are responsible for the degradation of the extracellular matrix (e.g. matrix metalloproteinases. MMPs) and at the same time increase collagen, elastin, and other extracellular matrix component production when compared to well-known controls, such as of 0.16-pM (0.062 pg / ml) of Ilomastat (an MMI’-l inhibitor) and 50 mcg / mL of isotretinoin (a prescribed drug product for the treatment of wrinkles and where retinol is derived from). Isotretinoin is commonly recommended by physicians for the treatment of skin aging / wrinkles because it is said to increase collagen production. At the same time, many research publications describe isotretinoin as an MMP inhibitor, avoiding collagen degradation in addition to inducing collagen production. Compounds and combinations of compounds were identified that are able to not only inhibit matrix metalloproteinases but at the same time increase collagen production more strongly when compared to isotretinoin and controls and when used at the same concentration (50 pg / ml).301685781.1 - 40 -

[0152] Fonnulations / compositions that would enter the stratum comeum and remain within the skin (viable epidermis and dermis) while minimizing permeation across the skin / systemic absorption were screened for utilizing excised human skin. These compositions permeate the stratum comeum (surface of the skin) and retain m the viable epidermis / dermis to exert their effects at the target site where fibroblasts, viable keratinocytes and macrophages are found. The targeting of both pathways would enable the treatment and prevention of photocarcinogenesis (skin cancer prevention and treatment) or matrix related conditions including but not limited to skin aging and photoprotection. There are two main pathways associated with skin aging, a decrease in collagen production and an increase in enzymatic degradation. The methods herein assessed effects on both collagen production and enzymatic degradation.Example 1Identification of combinations of compounds for (1) MMP-1 enzyme inhibition and (2) collagen production

[0153] Tannic acid (TA) alone or in combination with other compounds such as resveratrol (RES) or doxycycline (DOX), significantly inhibited MMP-1 activity' and increased collagen production in normal human dermal fibroblasts when compared to a no-treatment control (FIG. 1). Certain combinations such as tannic acid and curcumin inhibit MMP-1 over 100%. Zoledronic acid (ZA) enhanced collagen production by 1.5-fold when compared to ascorbic acid (control). Tannic acid in combination with doxycycline or with resveratrol also inhibited MMP-1 strongly than the control. At the same time resveratrol in combination with tannic acid enhanced collagen production when compared to no treatment. The same was observed with doxycycline (dox) in combination with the inactive ingredient / excipient Oleth-10. The following compounds and combinations resulted in significant MMP-1 inhibition: tannic acid, doxycycline with tannic acid (dox-TA), curcumin with tannic acid (Cu-Ta), resveratrol with tannic acid (RESTA), ascorbic acid, zoledronic acid and Tween 20 (Tw20) - p<0.005 vs enzyme control and tretinoin control. Some compounds that have been used as excipients (inactive ingredients) in pharmaceutical and cosmetic formulations / compositions were found to have an effect on MMP-1 activity.

[0154] A primary screening with additional were tested tor collagen production (FIG.2), Enhanced college production as observed with some of the compounds tested that also exhibited MMP inhibition (Figure 3). These included DMSO, doxycycline (dox), RESTA,301685781.1 - 41 -rapamycin, dox-Oleth-10, ascorbic acid, zoledronic acid, hypoxanthine - p<0.05 vs no treatment (control). A comparator peptide that has purported collagen activity (KTTKS) did not enhance collagen production when used at the same concentration as other tested compounds that we have identified. The assays were repeated with more combinations including the resveratrol-tannic acid-zoledronic acid (RESTAZA) and other potential combinations, including ascorbic acid and niacinamide. RESTAZA includes three compounds resveratrol, tannic acid, and zoledronic acid in the a control vehicle that includes water, glycerin, and PEG 400 at a volume ratio of 3: 1:1. The control vehicle is referred to herein as WGP. TaZa includes a combination of tannic acid and zoledronic acid in the control vehicle. For MMP-1 inhibition, RESTAZA was not different from RESTA. Other combinations of interest identified were: ascorbic acid + tannic acid (TA), nicotinamide + tannic acid or glyoxylic acid (GA), zeaxanthin + TA, hydroxyapatite + TA, N-acetyl-cysteine, and theobromine + TA were identified as combinations effective at inhibiting MMP-1 at the concentrations tested.Example 2Effect of tannic acid concentration on inhibition of MMP-1 activity

[0155] The effect of tannic acid concentration on inhibition of MMP-1 activity compared to enzyme control (no inhibition), was evaluated using the MMP1 Inhibitor Screening Assay Kit (FIG. 4). The effect of tannic acid, on MMP-1 is concentration-dependent.Example 3Eff ect of compounds on collagen production

[0156] The effect of combinations of compounds identified in screening (versus vehicle controls and single compound controls) on collagen production in normal human dermal fibroblasts (NHDF) was examined (FIG. 5). The horizontal line indicates the threshold (the detected collagen level of the controls (media)) for increased collagen production.Example 4Effect of compounds on hyaluronidase activity

[0157] Hyaluronidase can be altered m skin aging. The effect of compounds and combinations on hyaluronidase activity was evaluated using a hyaluronidase screening assay (FIG. 6), Compounds were tested at 250 pg / rnL, except for REST A A (5: 100: 5) that was tested at 374 pg / mL and tretinoin at 10 pg / mL since it is poorly soluble in 5% DMSO (v / v) in water.301685781.1 - 42 -TA inhibited hyaluronidase close to 100% and when compared to tretinoin at the same concentration. Some points show greater than 100% inhibition due to assay variability. For example, tannic acid does not absorb at the same wavelength as the assay methods.Example 5Formulations far skin retention

[0158] Formulations / compositions were examined for their ability7to enter the stratum corneum and remain in the skin (viable epidermis and dermis) while minimizing permeation across the skin / systemic absorption. A high-throughput formulation screening method employing excised human skin was employed to assess the permeability' and retention of compounds. The targeting of both pathways would enable the treatment and prevention of photocarcinogenesis (skin cancer prevention and treatment) or matrix-related conditions including but not limited to skin aging and photoprotection.

[0159] Formulations / compositions for the treatment and prevention of photoaging and photocarcinogenesis were examined. Surfactants were added to the WGP solvent system described above to test the permeation and retention of resveratrol, tannic acid and zoledronic acid across / in the skin. Gels were formulated by using WGP and adding polymer excipients to this system. These gel formulations were assessed for skm permeation and retention of resveratrol, tannic acid and zoledronic acid across / in the skin. Emulgels including the solvent system (WGP) were formulated The emulgels included a polymer to help stabilize and add a more gel-like feeling while retaining the organoleptic properties of a cream, and an oil phase. In addition to emulgels, emulsions were developed following the same general strategy but with less polymer content.

[0160] The emulgel (EG) compositions included in FIG. 7 were prepared and tested in the high-throughput screenings (HTS). 60 mg of each surfactant was used m the emulgel formulations. In addition, the polymers were added assuming a 6 mL total volume. Similarly, the emulsions (EE) depicted in FIG. 8 were prepared and tested in the HTS method using excised human skm. Selected formulations that were homogeneous in appearance that did not immediately phase-separate were tested in human skin samples for permeability7. These studies were conducted in four phases: 1 Permeability through dermatomed human skm containing all skin layers (stratum corneum, viable epidermis, dermis). 2. Formulation effects on permeability were evaluated in studies across separated human skin. This second phase identified formulations that can permeate the epidermis but minimally permeate the dermis. This provides301685781.1 - 43 -information on the ability of the formulations to facilitate skin targeting (i.e. permeate and retain inside the skin) for each compound tested. Permeability was tested in (a) human separated / isolated epidermis (stratum comeum, viable epidermis) layer, and (b) separated / isolated dermis layer. Formulations identified through these experiments can be used with microneedle pretreatment / cotreatment of the skin. Microneedles porate the stratum comeum and give a direct route to compound delivery inside the skin. Thus, identifying formulations that have lower dermis permeability could be used with microneedle delivery' systems. 3. A screen of formulations with the highest amount detected inside the skm (below the stratum comeum), and that did not remain substantially on the surface / stratum corneum, and at the same time presented the lowest amount permeating across the skin were selected for a permeation study with more replicates (n=8). This study helped confirm previous results and was used to select an example formulation for m vivo testing. 4. A single composition was tested in vivo for the prevention of photocarcinogenesis (more specifically squamous cell carcinoma upon UV exposure) using phvtochemicals in combination (resveratrol and tannic acid). MMP. collagen and other matrix related proteins were also measured that can be correlated with skm aging. These studies show positive changes m photocarcinogenesis markers (MMPs, p53, STAT1, STAT3, AKT, epidermal thickness, CPDs, Ki67).

[0161] Multiple permeation screening experiments were performed across a range of formulations including various surfactants, gels, emulsions and with human skin and separated human skin layers to determine which formulations lead to permeation into the skin, also identifying compounds with minimal permeation across the dermis layer of the skin to find the formulations for skin or epidermal-dermal targeting.Example 6Permeability through dermaiomed human skin containing all skin layers (stratum comeum, viable epidermis, dermis).

[0162] Surfactants with high skin permeation of RESTA - Resveratrol, tannic acid and zoledronic acid were dissolved in WGP and 1% (w / v) of surfactant or 1% (w / v) combinations of surfactants (0.5% w / v of each surfactant to a total of 1 % w / v) were added to each formulation to be tested. Those formulations (containing surfactants and combinations of surfactants) were applied on top of dermatomed human skin (with all skm layers) and permeation was measured after 16 hours using high performance liquid chromatography (HPLC) or LC-mass spectrometry' (LC-MS). PBS with 2% Tween 80 was used as the receptor fluid to enable sink conditions for the experiment. Enhancement ratios were calculated for each formulation tested301685781.1 - 44 -when compared to the control (resveratrol, tannic acid and zoledronic acid in WGP) using the following equation: Enhancement Ratio (ER) = sample (area) / av erage control (area) * 100, where area corresponds to the area under the curve for each compound as determined by HPLC or LC-MS.

[0163] For TA in WGP across the human dermatomed skin, after 16 hours, concentrations in the receptor compartment of 2.5 - 5.0 micrograms / mL (average 3 micrograms / mL). As shown in FIG. 4 above. MMP inhibition was tested across the TA concentration range of 0-50 micrograms / mL. All of the surfactants increased permeation of TA compared to the control (Vehicle (WGP) + resveratrol + tannic acid + zoledronic acid (REST AZA in WGP)). For the purposes of selecting excipients and formulations, surfactants that caused an average ER > 20 as high permeation enhancers for tannic acid were selected. Only a few surfactants were able to significantly enhance permeation of resveratrol and zoledronic acid when compared to the control (RESTAZA in WGP) and those are represented in FIG. 9 and indicated by the "‘x”. They are also graphically represented in FIGS 10A-10C.

[0164] Gels with high skin permeation of RESTA - The effects of including polymers the vehicle were used to examine the permeation enhancement (ER) of the compounds. Gels formulation effects on the permeability of compounds across human skin relative to controls (vehicle, WGP without polymer) for the individual compounds (resveratrol, tannic acid, and zoledronic acid) and combinations thereof are depicted in FIG, 11. Polymers increasing ER ratio greater than control are indicated by an '‘x’" (student’s t-test, p<0.05). Gel formulation screening in dermatomed human skin is depicted in FIGS. 12A-12C. FIG. 12A depicts ER of tannic acid (TA) across dermatomed human skin. FIG. 12B depicts ER of resveratrol across dermatomed human skin. FIG. 12C depicts ER of zoledronic acid (ZA) across dermatomed human skin. * = p<0.05, student’s t-test.Example 7Formulations with high epidermal permeability

[0165] Formulation effects on permeability were evaluated in studies across separated human skin. This allowed the identification of formulations that can permeate the epidennis but minimally permeate the dermis. This provides information on the ability of the formulations to facilitate skin targeting (i.e. permeate and retain inside the skin) for each compound tested. Permeability was tested in human separated / isolated epidermis (stratum comeum, viable epidermis) layer and separated / isolated dermis layer. Formulations identified through these301685781.1 - 45 -experiments may also be used with microneedle pretreatment / cotreatment of the skin. Microneedles porate the stratum comeum and give a direct route to compound deliver}- inside the skin. Thus, identifying formulations that have lower dermis permeability could be used with microneedle delivery systems.

[0166] In this screening, human dermatomed skin (all skin layers) was heated at 60 °C for 1 minute and human epidermal membrane was obtained (also known as epidemiis). Different formulations ranging from surfactant mixtures, gels, emulgels, and emulsions containing resveratrol, tannic acid, and zoledronic acid were tested across this skin layer. Resveratrol, tannic acid, and zoledronic acid were added to WGP and this was used as a stock solution to prepare each formulation and as a control as previously described. FIG. 13 shows the formulations that had high epidermal permeability and indicates the statistically higher ER ratios with an£'x”. FIG 14 depicts human epidermal membrane permeability of tannic acid (A), resveratrol (B). and zoledronic acid (C). * = p<0.01, student’s t-test.Example 8Formulations with low dermal permeability

[0167] Formulation effects on dermal permeability were performed on human dermatomed skin. The skin was heated at 60 °C for 1 minute and human dermal membrane was obtained. This screening 'as performed using human dermal membrane instead of whole human skin. FIG. 15 identifies formulations that have the capacity for skin retention, as they exhibit low dermal permeability. Each formulation with the combination of compounds were tested across the human dermis layer only (not whole skin). FIG. 16 depicts enhancement ratios (permeability of formulation relative to control) across the dermis layer of tannic acid (A), resveratrol (B). and zoledronic acid (C).

[0168] Combining the permeability characteristics of the formulations in both epidermal and dermal membranes allowed for the identification of formulations with high epidermal and low' dermal permeability. All complex formulations (emulsions) promoted low-er dermal permeability, and serve as good retention candidate formulations. These were selected for subsequent screenings. EE4 significantly enhanced epidermis permeation of resveratrol compared to the vehicle (REST AZA in WGP) and at the same time showed significantly low er permeability across the dermis. Tannic acid and zoledronic acid also showed lower dermal permeability' and similar epidermal permeability when compared to RESTAZA in WGP.301685781.1 - 46 -

[0169] Enhancement ratios of resveratrol, tannic acid, and zoledronic acid were summed to show the combinatorial effect on enhancement ratios of the drugs in the formulations when compared to the control RESTAZA in WGP. Overall, EE4 enhanced permeability of resveratrol and tannic acid across the epidermis and decreased permeability of those drags across the dermis, showing the retention effect this formulation can cause (FIGS.18 and 19).

[0170] Surfactants with good permeability across the whole skin compared to RESTAZA in WGP showed higher epidermal permeability indicating a higher propensity for epidermal-dermal targeting (FIG. 20).Example 9Comparison of select formulations

[0171] A screen of formulations with the highest amount detected inside the skin (below the stratum corneum). and that did not remain substantially on the surface / stratum comeum, and at the same time presented the lowest amount permeating across the skin were selected for a permeation study with more replicates (n=8). This study helped confirm previous results and was used to select an example formulation for in vivo testing.

[0172] The emulsions with the highest skin-to-receiver ratios and / or higher epidermis to dermis ratios were selected for a final comparison using the high-throughput screening method and dermatomed human skin (n=8 per formulation). The amount of resveratrol and tannic acid that permeated across the skin was measured using LC / MS. The epidermis was separated from the dermis and the stratum comeum was tape-stripped (5 times) to separate it from the viable epidermis. The amount in each skm layer (stratum comeum, viable epidermis, and dermis) was quantified by doing a skin extraction in methanol and using LC / MS. This determined the amount that stayed in each layer and not permeated further. These analyses are different from the analyses above where the permeability through each layer not in each layer was determined.

[0173] FIG. 21 depicts permeability of tannic acid (A) and resveratrol (B) across the human dermatomed skm (all layers intact, compounds measured in receptor fluid). From previous screenings, EE4 was identified as a formulation that would permeate the least. Consequently a student’s t-test was performed and EE4 had the lowest permeability of TA when compared to HA gel, EE8, and EE21 (p<0.05) and the lowest permeability of RES when compared to EE4.2 and EE8. The permeation of the compounds across the skin into the receptor301685781.1 - 47 -was found to be low and at an acceptable level for all formulations. In 16 hours of treatment, for example, less than 1 microgram of TA permeated across the skin from all formulations. Resveratrol permeation was even lower.

[0174] The amounts of TA and RES (pg / mg of skin) in the viable epidermis versus dermis were determined (FIGS. 22-23). MMP are produced by keratinocytes in the basal epidermis and by fibroblasts in the dermis. Therefore, targeting the compounds of interest to the viable epidermis and dermis is essential for ensuring the desired effects of the compounds in the skin. The formulation with highest amount in the epidermis for both drugs (resveratrol and tannic acid) was Emulsion 4. Emulsion 21 on the other hand led to the highest amount of tannic acid in the epidermis layer but a very small amount of resveratrol was found in the epidermis. The same was observed for the dermis layer. Different formulations had different effects depending on the API. Emulsion 4 significantly increased the amount of resveratrol in both epidermis and dermis when compared to all the other formulations. EE4 (an example of a cosmetic serum), EE4.2 - cream (an example of a day / night cream), and EE21 showed the highest levels of TA in the epidermis and dermis. EE4, EE8, and EE4.1 had the highest levels of resveratrol in the epidermis and dermis. These data also show that the amount that gets inside the skin (epidermis and dermis) is enough to have the desired effect as it is higher than the amount tested in cultured fibroblasts (10-50ug / mL).Example 10Amounts of compounds in the stratum corneum

[0175] The amounts of compounds in the stratum corneum layer were determined using the tape stripping method to remove and quantify the drug in this layer (FIG. 24). These results show that for all formulations. RES and TA permeation through the stratum corneum is limited by this barrier and significant amounts remain on / in this layer. Despite this, significant levels of the compounds were observed permeating and relevant concentrations were detected in the epidermis and dermis below the stratum corneum.Example 11Franz cell experiment: EE4 versus placebo

[0176] A 16 hour in vitro permeation study using dermatomed human skin was performed for emulsion 4 (EE4) with samples taken at different timepoints. Results still showed a lower TA amount across the skin (1.1 pg) and higher amount in the skin, mainly at the surface (5.9 pg), followed by epidermis (0.94 pg) and dermis (0.8 pg). Resveratrol301685781.1 - 48 -permeation across the skin was also minimal with higher amounts of the drug inside the skin ( 0.05 pg in the receptor fluid. 1.2 pg in stratum comeum, 0.06 pg in epidermis, and 0.025 pg in dermis). In terms of TA concentrations in the skm, it was determined that an average of 293.7 micrograms / g of skin was obtained in the epidermis layer. In terms of TA concentrations in the skin, it was determined that an average of 12.6 micrograms / g of skin was obtained in the dermis layer. In terms of RES concentrations in the skin, it was determined that an average of 21.6 micrograms / g of skin was obtained in the epidermis layer. In terms of RES concentrations in the skin, it was determined that an average of 0.38 micrograms / g of skin was obtained in the dermis layer.Example 12Exemplary formulations and preparation methods

[0177] An exemplary' RESTA stock solution can be prepared by adding 5 mg / ml of resveratrol (RES) and 100 mg / ml of tannic acid (TA) in a solvent system composed of Water: Glycerin: PEG400 (3:1:1) ratio (WGP). An exemplary RESTAZA stock solution can be prepared by adding 2-5 mg / ml of RES, 2-5 mg / ml of zoledronic acid (ZA), 80-100 mg / ml of tannic acid.

[0178] Exemplary emulsion EE4 can be prepared by combining 85.34 % RESTA stock, 0.3 % sodium hyaluronate, 1.0 % Tween 60, 1.0 % Span 80. 4.02 % dimethicone, 4.02 % glyceryl monooleate, and 4.32 % cetyl alcohol, with all values representing % w / w The EE formulation can be prepared according to the method depicted in FIG. 25. with dimethicone used as the oil phase.

[0179] Exemplary emulsion EE10 can be prepared by combining 91.0 % RESTA or RESTAZA stock, 0,2 % sodium hyaluronate, 1.0 % Oleth-10, 1,0 % Ceteth-10, 5.0 % dimethicone. 0.8 % glyceryl stearate, and 1.0 % cetyl alcohol, with all values representing % w / w. The EE 10 formulation can be prepared according to the method depicted in FIG. 25, with dimethicone used as the oil phase.

[0180] Exemplary emulsion EE 12 can be prepared by combining 91.0 % RESTA or RESTAZA stock, 1.0 % PEG 40-stearate, 0.2 % sodium hyaluronate. 5.0 % dimethicone, 0.8 % glyceryl stearate, and 1.0 % cetyl alcohol, with all values representing % w / w. Tire EE12 formulation can be prepared according to the method depicted in FIG 25, with dimethicone used as the oil phase.301685781.1 - 49 -

[0181] FIG. 26 depicts a method that can be used to prepare any of the formulations disclosed herein. The method involves adding a mixture of surfactants to the oil phase. FIG.27 depicts a method that can be used to prepare any of the formulations disclosed herein. The method involves adding a polymer (e g., HA) at the final stage, subsequent to cooling down the emulsion. FIG. 28 depicts a method that can be used to prepare any of the formulations disclosed herein. The method can be used to prepare exemplary emulsion 12 (EE12) that includes PEG 40-siearate, for example.Example 13Prevention of photocarcinogenesis

[0182] A composition was tested in vivo for the prevention of photocarcinogenesis (more specifically squamous cell carcinoma upon UV exposure) using a combination of resveratrol and tannic acid. MMP. collagen and other matrix related proteins were measured, and these studies showed positive changes in photocarcinogenesis markers (MMPs, p53, STAT1, STATS, AKT, epidermal thickness, CPDs, Ki67).

[0183] Enzj'me expression in epidermis and dermis was inhibited by RESTA formulation (EE4). Upon UV exposure, MMPs, elastases and hyaluronidases get overexpressed and can lead to tumor initiation and promotion. These enzymes are also known to be involved in tumor progression and metastasis. In addition, since MMPs lead to degradation of collagen and elastin and consequently promote skin aging, their inhibition would help prevent those effects. FIG. 29A includes a diagram of photocarcinogenesis prevention experiments on mice. FIG. 29B shows the treatment and control groups used in the photocarcinogenesis prevention experiments.

[0184] RESTA formulation (EE4) decreases SUV-induced p53 expression. The tumor suppressor protein. p53. is involved in DNA repair, cell cycle arrest and apoptosis. P53 is usually overexpressed upon UV exposure which leads to initiation of apoptosis. When EE4 was applied, p53 expression decreased at both 6 and 24 hours when compared to the placebo formulation and to no treatment control (mice exposed to UV without any treatment, FIGS. 30-32).

[0185] STAT1 and STAT3 are involved in skin carcinogenesis. STAT3 is activated following exposure to UVB, is required for tumor initiation and promotion, and also plays a role in malignant progression of skin tumors by regulating angiogenesis and invasion, making STAT3 a critical target for skm carcinogenesis. STAT3 is also involved in the expression of301685781.1 - 50-MMPs In the experimental results depicted m FIG. 33, STAT1 decreased after 24 hours compared to controls. In the case of p-STATl (Y701), RESTA formulation led to a slight decrease of phosphorylated STAT1 in the tyrosine residue after 24 hours compared to the placebo formulations and control, and it was similar to mice that were not treated with UV and received no formulation. p-STATl (S727) was decreased in both the treatment (EE4) and non-UV induced control when compared to no treatment control and to the placebo formulation. This indicates that the ability of EE4 to inhibit or decrease the phosphorylation of STAT1. STAT1 expression w7as also decreased after 24 hours of EE4 treatment when compared to no treatment control and placebo formulation.

[0186] STAT3 is active in various human malignancies. In the experimental results depicted in FIG, 34, STAT3 phosphorylation in the serine residue (S727) decreased after 24 hours of treatment when compared to no treatment control and to the placebo formulation. The RESTA formulation was also found to inhibit SUV-induced Akt-mTOR signaling (FIG. 35). Epidermal thickness on EE4 treated mice was found to be lower in comparison to placebo and untreated control at both 6 and 24 hours (FIG. 36). 'The lower epidermal thickness can be associated with a photoprotective effect.

[0187] Ki-67 staining experiments were performed (FIG. 37), and cell proliferation was significantly decreased in mice treated with RESTA formulation in comparison to control mice exposed to UV. Cyclobutane pyrimidine dimer (CPD) staining experiments were performed (FIG. 38). CPDs are DNA lesions present that are formed after UV exposure. RESTA significantly inhibited the formation of CPD dimers and was similar to mice not exposed to UV treatment.Example 14Analyses of drug retention vehicles

[0188] Different formulations containing doxycycline hyclate were assessed for their ability to retain the drug in the skin. The effect of different surfactants was compared to determine which excipient(s) would lead to higher amount of drug permeating the stratum comeum. retaining into the skin (viable epidermis and dermis) and minimizing systemic absorption / absorption across the skin (into the receptor fluid).

[0189] A series of high-throughput screenings were used to determine the influence of surfactants in doxycycline hyclate permeation in different solvent systems (PG: propylene glycol, W: water, PG: W: propylene glycol in water m a 50:50 ratio. Screen 1: FIG. 40A301685781.1 - 51 -Doxycycline hyclate concentration ( ig / mL) in the receptor fluid / across the skin (One sample t-test relative to lug / mL; *::::p<0.05, **:=p<0.01, ***:::p<0.001, ****==p<0.0001). Screen 2: FIG. 40B Amount of doxycycline hyclate in the epidermis (pg / mg skin) (One sample t-test relative to 0 pg / mg of skin; *=p<0.05, **=p<0.01). Screen 3: FIG, 40C Amount of doxycycline hyclate in the dermis (pg / mg skin) (One sample t-test relative to 0 pg / mg of skin (One sample t-test relative to 0 pg / mg of skin: *=p<0.05, **=p<0.01). The experiments showed that showed that doxycycline in a formulation that included 10% Tween 20 in propylene glycol led to skin retention. PEG-8-stearate in combination with doxycycline hyclate in propylene glycol and water also led to skm retention of the drug. This formulation could be used for dermal retention if a physical method of enhancement (e.g. microneedles) is used, as it did not permeate the stratum comeum. This was further confirmed by using a mass-spec pen.

[0190] Doxycycline exhibited long-term visual stability when used in combination with propylene glycol and Tween 2010%, and for greater than one year than when used without Tween 20. Stability improvements were also observed when Poloxamer 188 was used. Doxycycline solutions exhibited no color change or minima] color change over long storage periods at ambient temperature conditions (-25 °C) when also protected from light. This is in comparison to the solvent system (PG and water) and compared to propylene glycol alone and to other excipients which were not stable at room temperature for a whole year. Doxycycline, like other tetracyclines and related compounds, is ven- unstable in aqueous solutions and somewhat stable in propylene glycol (PG). However, it was observed that doxycycline in PG exhibited discoloration within 1 year, while the doxycycline formulation in PG with Pl 88 had no discoloration or color change and maintained its characteristic bright yellow color.

[0191] The present inventors discovered compounds and combinations of compounds that inhibit enzymes responsible for the degradation of the extracellular matrix (e.g. matrix metalloproteinases as an example) and at the same time increase collagen, elastin, and other extracellular matrix component production. As an example, tannic acid alone or in combination with other compounds such as resveratrol or doxycycline, significantly inhibited MMP-1 activity and increased collagen production in normal human dermal fibroblasts when compared to a no-treatment control. Certain combinations such as tannic acid and curcumin were found to completely inhibit MMP-1 activity. Zoledronic acid enhanced collagen production by 1.5- fold when compared to an ascorbic acid control. Tannic acid in combination with doxycycline or with resveratrol also inhibited MMP-1 more strongly than the control. At the same time resveratrol m combination with tannic acid enhanced collagen production when compared to301685781.1no treatment. The same happened with doxycycline in combination with the inactive ingredient / excipient Oleth- 10.301685781.1 - 53 -

Claims

CLAIMS1. A method for treating skin of a subject in order to improve a condition of the subject’s skin, the method comprising topically applying a composition comprising an effective amount of at least one of tannic acid, gallic acid, ellagic acid, niacinamide, resveratrol, doxycycline, curcumin, and zoledronic acid to the subject’s skin.

2. The method of claim 1, wherein improving a condition of the skin is selected from the group consisting of: reducing collagen degradation; reducing elastin degradation; reducing hyaluronic acid degradation; maintaining or increasing collagen expression; increasing elastin expression; increasing hyaluronic acid production; increasing skin matrix production; inhibiting at least one enzyme responsible for degradation of extracellular matrix; reducing skin wrinkles; and reducing premature ageing.

3. The method of claim 2. wherein the at least one enzyme responsible for degradation of extracellular matrix is selected from the group consisting of elastase, collagenase, hyaluronidase, and a matrix metalloproteinase.

4. The method of claim 3, wherein the matrix metalloproteinase is matrix metall oproteinase- 1.

5. The method of claim 1. wherein the composition comprises tannic acid and resveratrol,6. The method of claim 1, wherein the composition comprises tannic acid and doxycycline.

7. The method of claim 1, wherein the composition comprises tannic acid and curcumin.

8. The method of claim 1, wherein the composition compnses tannic acid and niacinamide.

9. The method of claim 1, wherein the composition comprises tannic acid and zoledronic acid.301685781.1 - 54 -10. The method of claim 1, wherein the composition comprises tannic acid, resveratrol, and zoledronic acid.

11. The method of claim 1, wherein the composition comprises tannic acid, gallic acid, and ellagic acid.

12. The method of claim 1, wherein the composition comprises tannic acid and gallic acid.

13. The method of claim 1, wherein the composition comprises a carrier comprising water, glycerin, PEG400. and at least one of tannic acid, gallic acid, ellagic acid, niacinamide, resveratrol, doxycycline, curcumin, and zoledronic acid.

14. The method of claim 13, wherein the carrier comprises:50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400.

15. The method of claim 13, wherein the carrier comprises:about 56% by weight of w ater;about 23% by weight of glycerin; andabout 21% by weight of PEG400.

16. The method of claim 13. wherein the carrier comprises from 1 to 100 mg / ml of the at least one compound having at least one cosmetic effect.

17. The method of claim 1, wherein the composition comprises one or more of: ascorbic acid, rapaniycin. hypoxanthine, nicotinamide, zeaxantliin, theobromine, Oleth-10, tween 20, dimethyl sulfoxide, hydroxyapatite, and N-acetyl cysteine.

18. The method of claim 1, wherein the composition comprises one or more of: water, glycerin, hyaluronate sodium, Tween 60. Span 80, dimethicone, glyceryl monooleate, cetyl alcohol, Poloxamer 188, glyceryl stearate, isopropyl myristate, cocoa butter, Ceteth-10, PEG-400, PEG-40 stearate, and PEG-8 stearate.301685781.1 - 55 -19. The method of ciaim 1, wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Tween 60, Span 80, dimethicone, glyceryl monooleate, and cetyl alcohol.

20. The method of claim 1, wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Poloxamer 188, glyceryl stearate, cetyl alcohol, isopropyl myristate, and cocoa butter.

21. The method of claim 1, wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Oleth-10, Ceteth-10, dimethicone, glyceryl stearate, and cetyl alcohol.

22. The method of claim 1, wherein the composition comprises resveratrol, tannic acid, zoledronic acid, hyaluronate sodium, Oleth-10, Ceteth-10, dimethicone, gly cetyl stearate, and cetyl alcohol.

23. The method of claim 1, wherein the composition comprises resveratrol, tannic acid, PEG-40 stearate, PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cetyl alcohol.

24. The method of claim 1, wherein the composition comprises resveratrol, tannic acid, zoledronic acid, PEG-40 stearate, PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cetyl alcohol.

25. The method of claim 1, wherein the composition comprises:75 to 95 % by weight of a carrier comprising:2 to 8 mg / ml of resveratrol;75 to 125 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of cetyl alcohol;2 to 10 % by weight of dimethicone:2 to 10 % by weight of glyceryl monooleate;0.1 to 2 % by weight of Tween 60;0.1 to 2 % by weight of Span 80; and301685781.1 - 56 -0.1 to 2 % by weight of hyaluronate sodium.

26. The method of claim 1, wherein the composition comprises:45-50 % by weight of water;12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;0.01-0.1 % by weigh; of resveratrol;0.5-1.5 % by weight of Tween 60;0.1-1 % by weight of sodium hyaluronate;1-5 % by weight of dimethicone;1-5 % by weight of glyceryl monooleate;1-5 % by weight of cetyl alcohol; and0.5-1.5 % by weight of Span 80.

27. The method of claim 1, wherein the composition comprises:70 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;50 to 150 mg / ml of tannic acid;50- 5% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;2 to 10 % by weight of isopropyl myristate;0.1 to 2 % by weight of Poloxamer 188;0.1 to 2 % by weight of Tween 20;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of cocoa butter;0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of sodium hyaluronate.

28. The method of claim 1, wherein the composition compnses:45-50 % by weight of water;301685781.1 - 57 -12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;001-0.1 % by weight of resveratrol;0.5-1.5 % by weight of Poloxamer 88;0.5-1.5 by weight of Tween 20;0.1-1 % by weight of sodium hyaluronate;6-10 % by weight of dimethicone;0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;5-10 % by weight of isopropyl myristate; and0.5-5% by weight of cocoa butter.

29. The method of claim 1, wherein the composition comprises:70 to 95 % by weight of a carrier comprising;1 to 10 mg / ml of resveratrol;1 to 10 mg / ml of zoledronic acid;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;2 to 10 % by weight of isopropyl myristate;0.1 to 2 % by weight of Poloxamer 188;0 1 to 2 % by weight of Tween 20;0.1 to 2 % by weight of cetyl alcohol;0 1 to 2 % by weight of cocoa butter;0.1 to 2 % by w eight of glycery l stearate;0.1 to 2 % by weight of sodium hyaluronate; and0.01-0.1 % by weight of resveratrol.

30. The method of claim 1, wherein the composition comprises:45-50 % by weight of water;301685781.1 - 58 -12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;001-0.1 % by weight of resveratrol;0.5-1.5 % by weight of Poloxamer 88;0.5-1.5 % by weight of Tween 20;0.1-1 % by weight of sodium hyaluronate;6-10 % by weight of dimethicone;0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;5-10 % by weight of isopropyl mysritate;0.5-5% by weight of cocoa butter; and0.01-0.1 % by weight of zoledronic acid.

31. The method of claim 1, wherein the composition comprises:85 to 95 % by weight of a carrier comprising;1 to 10 mg / ml of resveratrol;50 to 1 0 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of Oleth-10;0.1 to 2 % by weight of Ceteth-10,0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of hyaluronate sodium.

32. The method of claim 1, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;301685781.1 - 59 -0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;05-1.5 % by weight of Oleth-10;05-1.5 % by weight of Ceteth-10;0.1-1 % by weight of sodium hyaluronate; and0.01-0.1 % by weight of resveratrol.

33. The method of claim 1, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;1 to 10 mg / ml of zoledronic acid;50 to 1 0 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of Oleth-10;0.1 to 2 % by weight of Ceteth-10;0.1 to 2 % by weight of cetyl alcohol;0, 1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of hyaluronate sodium.

34. The method of claim 1, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;0.5-1.5 % by weight of glyceryl stearate:0.5-5 % by weight of cetyl alcohol;0.5-1.5 % by weight of Oleth-10;0.5- 1.5 % by weight of Ceteth-10;0.1-1 % by weight of sodium hyaluronate;0.01-0.1 % by weight of resveratrol; and301685781.1 - 60 -0.01-0.1 % by weight of zoledronic acid.

35. The method of claim 1, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of PEG-8 stearate;0.1 to 2 % by weight of PEG-40 stearate;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of hyaluronate sodium; and0.1 to 2 % by weight of glyceryl stearate.

36. The method of claim 1, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid:0.5-1.5 % by weight of glyceryl stearate;0.5-1.5 % by weight of cetyl alcohol:0.5-1.5 2 / <> by weight of PEG-40 stearate:0.5-1.5 % by weight of PEG-8 stearate;0.1-1 % by weight of sodium hyaluronate: and0.01-0.1 % by weight of resveratrol.

37. The method of claim 1, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;1 to 10 mg / ml of zoledronic acid;50 to 150 mg / ml of tannic acid;301685781.150-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of PEG-8 stearate;0.1 to 2 % by weight of PEG-40 stearate;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of sodium hyaluronate; and0.1 to 2 % by weight of glyceryl stearate.

38. The method of claim 1, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;0.5-1.5 % by weight of glyceryl stearate;0.5-1.5 % by weight of cetyl alcohol;0.5-1.5 % by weight of PEG-40 stearate;0.5-1.5 % by weight of PEG-8 stearate;0.1-1 % by weight of sodium hyaluronate;0.01-0.1 % by weight of resveratrol; and0.01-0.1 % by weight of zoledronic acid.

39. A topical skin composition comprising an effective amount of at least one ingredient capable of improving a skin condition; wherein the at least one ingredient capable of improving a skin condition is selected from the group consisting of tannic acid, gallic acid, ellagic acid, niacinamide, resveratrol, doxycycline, curcumin, and zoledronic acid.

40. The topical skin composition of claim 39, wherein the at least one ingredient capable of improving a skin condition is capable of reducing collagen degradation; reducing elastin degradation; reducing hyaluronic acid degradation; maintaining or increasing collagen expression: increasing elastin expression; increasing hyaluronic acid production; increasing301685781.1 - 62 -skin matrix production; inhibiting at least one enzyme responsible for degradation of extracellular matrix; reducing skin wrinkles; and / or reducing premature ageing.

41. The composition of claim 39, wherein the composition comprises tannic acid and doxycycline.

42. The composition of claim 39, wherein the composition comprises tannic acid and curcumin.

43. The composition of claim 39, wherein the composition comprises tannic acid and zoledronic acid.

44. The composition of claim 39, wherein the composition comprises tannic acid, resveratrol, and zoledronic acid.

45. The composition of claim 39, wherein the composition comprises tannic acid and niacinamide.

46. The composition of claim 39, wherein the composition comprises tannic acid, gallic acid, and ellagic acid.

47. The composition of claim 39, wherein the composition comprises tannic acid and gallic acid.

48. The composition of claim 39, wherein the composition comprises a carrier comprising water, glycerin, PEG400, and at least one of tannic acid, gallic acid, ellagic acid, niacinamide, resveratrol, doxycycline, curcumin, and zoledronic acid.

49. The composition of claim 48, wherein the carrier comprises:50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400.

50. The composition of claim 48. wherein the carrier comprises:about 56% by weight of water;301685781.1 - 63 -about 23% by weight of glycerin; andabout 21% by weight of PEG400.

51. The composition of claim 48, from 1 to 100 mg / ml of the at least one compound capable of improving a skin condition.

52. The composition of claim 39 wherein the composition comprises one or more of: ascorbic acid, rapamycin, hypoxanthine, nicotinamide, zeaxanthin, theobromine, Olelh-10, tween 20, dimethyl sulfoxide, hydroxyapatite, and N -acetyl cysteine.

53. The composition of claim 39, wherein the composition comprises one or more of: glycerin, hyaluronate sodium, Tween 60, Span 80, dimethicone, glyceryl monooleate, cetyl alcohol, Poloxamer 188, glyceryl stearate, isopropyl myristate, cocoa butter, Ceteth-10, PEG-400, PEG-40 stearate, and PEG-8 stearate.

54. The composition of claim 39, wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Tween 60, Span 80, dimethicone, glyceryl monooleate, and cetyl alcohol.

55. The composition of claim 39, wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Poloxamer 188, glyceryl stearate, cetyl alcohol, isopropyl myristate, and cocoa butter.

56. The composition of claim 39. wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Oleth-10, Ceteth-10, dimethicone, glyceryl stearate, and cetyl alcohol.

57. The composition of claim 39, wherein the composition comprises resveratrol, tannic acid, zoledronic acid, hyaluronate sodium, Oleth-10, Ceteth-10, dimethicone, glyceryl stearate, and cetyl alcohol58. The composition of claim 39, wherein the composition comprises resveratrol, tannic acid, PEG-40 stearate, PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cetyl alcohol.301685781.1 - 64 -59. The composition of claim 39, wherein the composition comprises resveratrol, tannic acid, zoledronic acid, PEG-40 stearate, PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cetyl alcohol.

60. The composition of claim 39, wherein the composition comprises:75 to 95 % by weight of a carrier comprising:2 to 8 mg / ml of resveratrol;75 to 125 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of cetyl alcohol2 to 10 % by weight of dimethicone;2 to 10 % by weight of glyceryl monooleate;0.1 to 2 % by weight of Tween 60;0.1 to 2 % by weight of Span 80; and0.1 to 2 % by weight of hyaluronate sodium.

61. The composition of claim 39, wherein the composition comprises:45-50 % by weight of water;12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;0.01-0.1 % by weight of resveratrol;0.5-1.5 2 / <> by weight of Tween 60;0.1-1 % by weight of hyaluronic acid,1-5 % by weight of dimethicone;1-5 % by weight of glyceryl monooleate;1.5 % by weight of cetyl alcohol; and0.5-1.5 % by weight of Span 80,62. The composition of claim 39, wherein the composition comprises:70 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;301685781.1 - 65 -50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;2 to 10 % by weight of isopropyl myristate;0.1 to 2 % by weight of Poloxamer 188;0.1 to 2 % by weight of Tween 20;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of cocoa butter0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of hyaluronate sodium.

63. The composition of claim 39, wherein the composition comprises:45-50 % by weight of water;12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;0.01-0.1 % by weight of resveratrol;0.5-1.5 % by weight of Poloxamer 88;0.5-1.5 % by weight of Tween 20;0.1-1 % by weight of sodium hyaluronate;6-10 % by weight of dimethicone;0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;5-10 % by weight of isopropyl myristate; and0.5-5% by weight of cocoa butter.

64. The composition of claim 39, wherein the composition comprises:70 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;1 to 10 mg / ml of zoledronic acid;50 to 150 mg / ml of tannic acid;50-75% by weight of water;301685781.1 - 66 -10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;2 to 10 % by weight of isopropyl myristate;0.1 to 2 % by weight of Poloxamer 188;0.1 to 2 % by weight of Tween 20:0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of cocoa butter0.1 to 2 % by weight of glyceryl stearate;0.1 to 2 % by weight of hyaluronate sodium.

65. The composition of claim 39, wherein the composition comprises:45-50 % by weight of water;12-18 % by weight of glycerin:12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;0.01-0.1 % by weight of resveratrol:0.01-0.1 % by weight of zoledronic acid:0.5-1.5 % by weight of Poloxamer 88;0.5-1.5 % by weight of Tween 20;0.1-1 % by weight of sodium hyaluronate:6-10 % by weight of dimethicone;0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;5-10 % by weight of isopropyl myristate; and0.5-5% by weight of cocoa butter.

66. The composition of claim 39, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol:50 to 150 mg / ml of tannic acid:50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400: and301685781.1 - 67 -2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of Oleth-10;0.1 to 2 % by weight of Ceteth-10;0.1 to 2 % by weight of cetyl alcohol0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of hyaluronate sodium.

67. The composition of claim 39, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;0.5-1.5 % by weight of Oleth-10;0.5-1.5 % by weight of Ceteth-10; and0.1-1 % by weight of sodium hyaluronate.

68. The composition of claim 39, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;1 to 10 mg / ml of zoledronic acid;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin: and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of Oleth-10;0.1 to 2 % by weight of Ceteth-10;0.1 to 2 % by weight of cetyl alcohol0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of sodium hyaluronate.301685781.1 - 68 -69. The composition of claim 39, wherein the composition comprises: 40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;0.5-1.5 % by weight of Oleth-10;0.5-1.5 % by weight of Ceteth-10;0.1-1 % by weight of sodium hyaluronate;0.01-0.1 % by weight of resveratrol; and0.01-0.1 % by weight of zoledronic acid.

70. The composition of claim 39, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;50 to 150 mg / ml of tannic acid;50-75% by weight of water,10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of PEG-8 stearate;0.1 to 2 % by weight of PEG-40 stearate;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of sodium hyaluronate; and0.1 to 2 % by weight of glyceryl stearate.

71. The composition of claim 39, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;301685781.1 - 69 -0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;0.5-1.5 % by weight of PEG-40 stearate;0.5-1.5 % by weight of PEG-8 stearate;0.1-1 % by weight of sodium hyaluronate; and0.01-0.1 % by weight of resveratrol.

72. The composition of claim 39, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;1 to 10 mg / ml of zoledronic acid;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of PEG-8 stearate;0.1 to 2 % by weight of PEG-40 stearate;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of hyaluronate sodium; and0.1 to 2 % by weight of glyceryl stearate.

73. The composition of claim 39, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;0.5-1.5 % by weight of glyceryl stearate:0.5-1.5 % by weight of cetyl alcohol;0.5-1.5 % by weight of PEG-40 stearate:0.5-1.5 % by weight of PEG-8 stearate;0.1-1 % by weight of sodium hyaluronate;0.01-0.1 % by weight of resveratrol; and301685781.1 - 70 -0.01-0.1 % by weight of zoledronic acid.

74. A sunscreen composition comprising the composition of any one of claims 39 to 73.

75. A method for increasing epidermal permeability of at least one topically-applied compound having at least one cosmetic effect, retaining at least one topically-applied compound having at least one cosmetic effect in the dermis while avoiding systemic absorption of the topically-applied compound, and / or increasing an effect of at least one topically -applied compound having at least one cosmetic effect, the method comprising topically applying a composition comprising the at least one compound having at least one cosmetic effect and an effective amount of at least one surfactant and / or at least one polymer.

76. The method of claim 75, wherein the at least one surfactant and / or at least one polymer is selected from the group consisting of Tween 20, Tween 40, Tween 60, Tween 80, Laureth-4. Laureth-23, Ceteth-10, Ceteth-20, Oleth-5, Oleth-10, KCS20, KRH40, Poloxamer 124, Poloxamer 182, Poloxamer 188, Poloxamer 407, Span20, Span60, Span80, Span83, PEG8 stearate, PEG40 stearate, sodium hyaluronate, gellan gum, hydroxyethyl cellulose, hydropropyl cellulose, and Nov eon AA-1 polycarbophil.

77. The method of claim 75, wherein the composition comprises a carrier comprising the at least one compound having at least one cosmetic effect, water, glycerin, and PEG400.

78. The method of claim 77, wherein the carrier comprises:50-75% by weight of water;10-30% by weight of glycerin: and10-30% by weight of PEG400.

79. The method of claim 77, wherein the carrier comprises:about 56% by weight of water;about 23% by weight of glycerin, andabout 21% by weight of PEG400.301685781.1 - 71 -80. The method of claim 77, wherein the carrier comprises from 1 to 100 mg / ml of the at least one compound having at least one cosmetic effect.

81. The method of claim 75, wherein the at least one compound having at least one cosmetic effect is selected from the group consisting of tannic acid, resveratrol, doxycycline, curcumin, and zoledronic acid.

82. The method of claim 75. wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium. Tween 60, Span 80, dimethicone, glyceryl monooleate, and cetyl alcohol.

83. The method of claim 75, wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Pol oxamer 188, glyceryl stearate, cetyl alcohol, isopropyl myristate, and cocoa butter.

84. The method of claim 75, wherein the composition comprises resveratrol, tannic acid, hyaluronate sodium, Oleth-10. Ceteth-10, dimethicone, glyceryl stearate, and cetyl alcohol.

85. The method of claim 75. wherein the composition comprises resveratrol, tannic acid, zoledronic acid, hyaluronate sodium, Oleth-10, Ceteth-10, dimethicone, glyceryl stearate, and cetyl alcohol.

86. The method of claim 75, wherein the composition comprises resveratrol, tannic acid, PEG-40 stearate, PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cetyl alcohol.

87. The method of claim 75, wherein the composition comprises resveratrol, tannic acid, zoledronic acid, PEG-40 stearate. PEG-8 stearate, hyaluronate sodium, dimethicone, glyceryl stearate, and cety l alcohol.

88. The method of claim 75, wherein the composition comprises:75 to 95 % by weight of a carrier comprising:2 to 8 mg / ml of resveratrol;75 to 125 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin: and301685781.1 - 72 -10-30% by weight of PEG400; and2 to 10 % by weight of stearyl alcohol2 to 10 % by weight of dimethicone;2 to 10 % by weight of glyceryl monooleate;0.1 to 2 % by weight of Tween 60;0.1 to 2 % by weight of Span 80: and0.1 to 2 % by weight of hyaluronate sodium89 The method of claim 75. wherein the composition comprises:45-50 % by weight of water;12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;001-0.1 % by w-eight of resveratrol;0.5-1.5 % by weight of Tween 60;0.1-1 % by w-eight of sodium hyaluronate,1-5 % by weight of dimethicone;1-5 % by w eight of glyceryl monooleate;1-5 % by weight of cetyl alcohol; and0.5-1.5 % by weight of Span 80,90. The method of claim 75, wherein the composition comprises:70 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;50 to 150 mg / ml of tannic acid;50-75% by w-eight of aler:10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by eight of dimethicone;2 to 10 % by weight of isopropyl myristate;0 1 to 2 % by weight of Poloxamer 188;0.1 to 2 % by weight of Tw-een 20;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of cocoa butter301685781.1 - 73 -0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of hyaluronate sodium.

91. The method of claim 75, wherein the composition comprises:45-50 % by weight of water;12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;0.01-0.1 % by -weight of resveratrol;0.5-1.5 % by weight of Poloxamer 88;0.5-1.5 % by weight of Tween 20;0.1-1 % by weight of sodium hyaluronate;6-10 % by weight of dimethicone;05-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;5-10 % by w eight of isopropyl my sritate; and0.5-5% by weight of cocoa butter.

92. The method of claim 75, wherein the composition comprises:70 to 95 % by eight of a carrier comprising:1 to 10 mg / ml of resveratrol;50 to 150 mg / ml of tannic acid;1 to 10 mg / ml of zoledronic acid;50-75% by weight of w-ater;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;2 to 10 % by weight of isopropyl myristate;0.1 to 2 % by weight of Poloxamer 188;0.1 to 2 % by weight of Tw een 20;0 1 to 2 % by w-eight of cetyl alcohol;0.1 to 2 % by weight of cocoa butter0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of hyaluronate sodium.301685781.1 - 74 -93. The method of claim 75, wherein the composition comprises: 45-50 % by weight of water;12-18 % by weight of glycerin;12-18 % by weight of PEG 400;5-10 % by weight of tannic acid;0.01-0.1 % by weight of resveratrol,0.01-0.1 % by weight of zoledronic acid;0.5-1.5 % by weight of Poloxamer 88;0.5-1.5 % by weight of Tween 20;0.1-1 % by weight of sodium hyaluronate;6-10 % by weight of dimethicone;0.5-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;5-10 % by weight of isopropyl mysntate; and0.5-5% by weight of cocoa butter.

94. The method of claim 75, wherein the composition comprises:85 to 95 % by 'eight of a carrier comprising:1 to 10 mg / ml of resveratrol;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of Oleth-10;0.1 to 2 % by weight of Ceteth-10;0.1 to 2 % by weight of cetyl alcohol0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of hyaluronate sodium.

95. The method of claim 75, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;301685781.1 - 75 -1-10 % by weight of dimethicone;5-10 % by weight of tannic acid:05- 1.5 % by weight of glyceryl stearate;05-5 % by weight of cetyl alcohol;0.5-1.5 % by weight of Oleth-10;0.5-1.5 by weight of Ceteth-10;0.1-1 % by weight of sodium hyaluronate; and0.01-0.1 % by weight of resveratrol.

96. The method of claim 75, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;1 to 10 mg / ml of zoledronic acid;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of Oleth-10;0.1 to 2 % by weight of Ceteth-10:0.1 to 2 % by weight of cetyl alcohol0.1 to 2 % by weight of glyceryl stearate; and0.1 to 2 % by weight of sodium hyaluronate,97. The method of claim 75, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;05-1.5 % by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;0.5-1.5 % by weight of Oleth-10;0.5-1.5 % by weight of Ceteth-10;301685781.1 - 76 -0.1-1 % by weight of sodium hyaluronate;0.01-0.1 % by weight of resveratrol; and0.01-0.1 % by weight of zoledronic acid.

98. The method of claim 75, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 10 mg / ml of resveratrol;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by rveight of dimethicone;0 1 to 2 % by weight of PEG-8 stearate;0.1 to 2 % by weight of PEG-40 stearate;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of hyaluronate sodium: and0.1 to 2 % by weight of glyceryl stearate.

99. The method of claim 75, wherein the composition comprises:40-60 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;0.5-1.5 2 / o by weight of glyceryl stearate;0.5-5 % by weight of cetyl alcohol;0.5 -1.5 % by weight of PEG-40 stearate;0.5-1.5 % by weight of PEG-8 stearate,0.1-1 % by weight of sodium hyaluronate; and0.01-0.1 % by weight of resveratrol.

100. The method of claim 75, wherein the composition comprises:85 to 95 % by weight of a carrier comprising:1 to 1 mg / ml of resveratrol;301685781.1 - 77 -1 to 10 mg / ml of zoledronic acid;50 to 150 mg / ml of tannic acid;50-75% by weight of water;10-30% by weight of glycerin; and10-30% by weight of PEG400; and2 to 10 % by weight of dimethicone;0.1 to 2 % by weight of PEG-8 stearate;0.1 to 2 % by weight of PEG-40 stearate;0.1 to 2 % by weight of cetyl alcohol;0.1 to 2 % by weight of hyaluronate sodium; and0.1 to 2 % by weight of glyceryl stearate.

101. The method of claim 75, wherein the composition comprises:40-6)0 % by weight of water;15-20 % by weight of glycerin;15-20 % by weight of PEG 400;1-10 % by weight of dimethicone;5-10 % by weight of tannic acid;0.5-1.5 % by weight of glyceryl stearate:0.5-1.5 % by weight of cetyl alcohol;0.5 -1.5 % by weight of PEG-40 stearate;0.5-1.5 % by weight of PEG-8 stearate;0.1-1 % by weight of sodium hyaluronate;0.01-0.1 % by weight of resveratrol; and0.01-0.1 % by weight of zoledronic acid.

102. The method of claim 75, wherein the at least one compound having at least one cosmetic effect is doxycycline and the least one surfactant and / or at least one polymer is Tween 20103. The method of claim 102, wherein the composition comprises:5-15 mL of propylene glycol;0.1 -2.0 % weight / volume of doxycycline hy elate, based on a volume of propylene glycol; and5-15 % weight / volume of Tween 20, based on a volume of propylene glycol.301685781.1 - 78 -104. The method of claim 102, wherein the composition comprises:about 10 mL of propylene glycol;about 1% weight / volume of doxycycline hy elate, based on a volume of propylene glycol; andabout 10% weight / volume of Tween 20, based on a volume of propylene glycol.

105. The method of claim 75, wherein the at least one compound having at least one cosmetic effect is doxycycline and the least one surfactant and / or at least one polymer is PEG-8 stearate.

106. The method of claim 105, wherein the composition comprises:1-10 mL water;5-15 mL of propylene glycol; and1-5 % weight / volume of PEG-8 stearate, based on a combined volume of water and propylene glycol.

107. The method of claim 105, wherein the composition comprises:about 5 mL water;about 10 mL of propylene glycol; andabout 2 % weight / volume of PEG-8 stearate, based on a combined volume of water and propylene glycol.

108. The method of claim 75, wherein the at least one compound having at least one cosmetic effect is dox cycline and the least one surfactant and / or at least one polymer is Poloxamer 188.

109. The method of claim 108, wherein the composition comprises:5-15 mL of propylene glycol;0.1 -2 % weight / volume of doxycycline hy elate, based on a volume of propylene glycol;and0.01-1 % weight / volume of Tween 20, based on a volume of propylene glycol.

110. The method of claim 108, wherein the composition comprises:about 10 mL of propylene glycol;about 1% weight / volume of doxycycline hy elate, based on a volume of propylene glycol; and301685781.1 - 79 -about 0,1% weight / volume of Tween 20, based on a volume of propylene glycol.

111. The method of claim 75, wherein the at least one compound having at least one cosmetic effect is doxycycline and the least one surfactant and / or at least one polymer comprises Tween 20 and Poloxamer 188.

112. The method of claim 108, wherein the composition comprises:5-15 mL of propylene glycol;0.1-2 % weight / volume of doxycycline hy elate, based on a volume of propylene glycol; 5-15 % weight / volume of Tween 20, based on a volume of propylene glycol; and 0.01-1 % weight / volume of Poloxamer 188, based on a volume of propylene glycol.

113. The method of claim 108, wherein the composition comprises:about 10 rnL of propylene glycol;about 1% weight / volume of doxycycline hy elate, based on a volume of propylene glycol;about 10 % weight / volume of Tween 20, based on a volume of propylene glycol; and about 0.1 % weight / volume of Poloxamer 188, based on a volume of propylene glycol.

114. A topical skin composition comprising:at least one compound having at least one cosmetic effect; andan effective amount of at least one surfactant and / or at least one polymer; wherein the at least one surfactant and / or at least one polymer is selected from the group consisting of Tween 20, Tween 40, Tween 60, Tween 80, Laureth-4, Laureth-23, Ceteth-10, Ceteth-20, Oleth-5. Oleth-10, KCS20, KRH40. Poloxamer 124, Poloxamer 182, Poloxamer 188, Poloxamer 407, Span20, Span60, Span80, Span83, PEG8 stearate, PEG40 stearate, sodium hyaluronate, gellan gum, hydroxyethyl cellulose, hydropropyl cellulose, and Noveon AA-1 polycarbophil.

115. The topical skin composition of claim 114, wherein the composition is capable of increasing epidermal permeability of the at least one compound having at least one cosmetic effect, retaining the at least one compound having at least one cosmetic effect in the dermis w'hile avoiding systemic absorption of the at least one compound having at least one cosmetic301685781.1 - 80 -effect, and / or increasing an effect of the at least one compound having at least one cosmetic effect.

116. The topical skin composition of claim 114, wherein the at least one compound having at least one cosmetic effect is selected from the group consisting of tannic acid, resveratrol, doxycycline, curcumin, and zoledronic acid.

117. A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising tannic acid and resveratrol.

118. The method of claim 117, wherein the cancer is squamous cell carcinoma.

119. The method of claim 117, wherein the subject is a human patient.

120. The method of claim 117, wherein the composition is administered orally, intraadiposally, intraarterially, intraarticularly, intracranially, intradermally, intralesionally, intramuscularly, intraperitoneally. intrapleurally, intranasally, intraocularally, intrapericardially, intraprostaticaly, intrarectally, intrathecally, intratumorally, intraumbilically, intravaginally, intravenously, intravesicularlly, intravitreally, liposomally, locally, mucosally. orally, parenterally, rectally, subconjunctival, subcutaneously, sublingually, topically, transbuccally, transdermally, vaginally. in cremes, in lipid compositions, via a catheter, via a lavage, via continuous infusion, via infusion, via inhalation, via injection, via local delivery,, via localized perfusion, bathing target cells directly, or any combination thereof.

121. The method of claim 117, wherein the composition inhibits expression of at least one of p53. STAT1, a matrix metalloproteinase, elastase, and hyaluronidase.

122. The method of claim 117, wherein the composition inhibits phosphorylation of STAT1 and / or STAT3.

123. The method of claim 117, wherein the composition inhibits Akt-mTOR signaling.301685781.1 - 81 -124. The method of claim 117, wherein the composition inhibits the formation of cyclobutene pyrimidine dimers.

125. A method for protecting a subject’s skin from ultraviolet radiation, comprising applying a sunscreen composition comprising at least one compound selected from the group consisting of tannic acid, resveratrol, doxycycline, curcumin, and zoledronic acid and at least one surfactant and / or at least one polymer is selected from the group consisting of Tween 20, Tween 40, Tween 60. Tween 80, Laureth-4, Laureth-23, Ceteth-10, Ceteth-20, Oleth-5, Oleth-10, K. CS20, KRH40, Poloxamer 124, Poloxamer 182, Poloxamer 188, Poloxamer 407, Span20, Span60, Span80, Span83, PEG8 stearate, PEG40 stearate, sodium hyaluronate, gellan gum, hydroxyethyl cellulose, hydropropyl cellulose, and Noveon AA-1 polycarbophil to the subject’s skin.

126. A sunscreen composition comprising at least one compound selected from the group consisting of tannic acid, resveratrol, doxycycline, curcumin, and zoledronic acid and at least one surfactant and / or at least one polymer is selected from the group consisting of Tween 20, Tween 40, Tween 60, Tween 80. Laureth-4, Laureth-23, Ceteth-10, Ceteth-20, Oleth-5. Oleth-10, KCS20, KRH40, Poloxamer 124, Poloxamer 182, Poloxamer 188. Poloxamer 407, Span20, Span60, Span 80, Span83, PEG8 stearate, PEG40 stearate, sodium hyaluronate, gellan gum, hydroxyethyl cellulose, hydropropyl cellulose, and Noveon AA-1 polycarbophil.301685781.1

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