Compositions comprising compounds having retinol-like activity and an n-acetyl compound

Abstract

Provided are skincare compositions comprising: a compound having retinol-like activity and an N-acetyl compound selected from the group consisting of N-aldosamines, N-acetylated amino acids and combinations thereof. Also provided are methods for treating skin comprising topically applying these compositions. Also provided are skincare compositions comprising 3-(4- farnesyloxyphenyl)-propionic acid; and a derivative of an aminosugar selected from the group consisting of N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-glucosamine, N-acetyl- galactosamine and N-acetyl-mannosamine, and combinations thereof, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

Description

[0001] COMPOSITIONS COMPRISING COMPOUNDS HAVING RETINOL-LIKE ACTIVITY AND AN N- ACETYL COMPOUND

[0002] FIELD

[0003] The present invention generally relates to compositions suitable for use on skin and particularly compositions comprising compounds having retinol-like activity and an N-acetyl compound.

[0004] BACKGROUND

[0005] The human skin is subject to certain aging processes, some of which are attributable to intrinsic processes (e.g. chronoaging) and some of which are attributable to exogenous factors (e.g. photoaging). In addition, temporary or even lasting changes to the skin can occur, such as acne, greasy or dry skin, keratoses, rosacea, light-sensitive, inflammatory, erythematous, and allergic or autoimmune -reactive reactions, such as dermatosis and photodermatosis.

[0006] The consequences of the above-mentioned ageing processes can include thinning of the skin, weaker interlacing of epidermis and dermis, and a reduction in the number of cells and the supplying blood vessels. These consequences are often undesirable, and individuals suffering from these issues will look to topical treatments to address them.

[0007] Retinoids have been used for treating skin conditions caused by intrinsic aging, exogenous factors, acne or skin diseases. However, despite the beneficial effects of retinoid treatment, its benefits are limited due to skin irritation of retinoids. These side effects can restrict the use of retinoids, and particularly so for individuals having sensitive skin.

[0008] To date, the search for alternative compounds to replace retinoids, and particularly for individuals having sensitive skin, has produced limited success in treating skin conditions associated with aging, such as skin atrophy, acne, photo-aging, and in reducing the appearance of wrinkles, fine lines, stretch marks, or cellulite.

[0009] Accordingly, there is a continued need for alternatives to traditional products. SUMMARY

[0010] Accordingly, one aspect of the invention pertains to a skincare composition comprising: a compound of Formula I: wherein:

[0011] Ri is selected from the group consisting of Ci - C20 alkyl, C2 - C20 alkenyl, C2 - C20 alkynyl, and C3 - Cs cycloalkyl or aryl;

[0012] R2 is selected from the group consisting of hydrogen, hydroxyl, Ci - Ce alkyl, C2 - Ce alkenyl, C2 - Ce alkynyl, C3 - Cs cycloalkyl or aryl, -OCi - Ce alkyl, -OC2 - Ce alkenyl, -OC2 - Ce alkynyl, -OC3 - Cs cycloalkyl or aryl, thiol, -SCi - Ce alkyl, -SC2 - Ce alkenyl, -SC2 - Ce alkynyl, -SC3 - Cs cycloalkyl or aryl, -NR4C1 - Ce alkyl, - NR4C2 - Ce alkenyl, -NR4C2 - Ce alkynyl, and -NR4C3 - Cs cycloalkyl or aryl;

[0013] R3 is selected from -CO2H, -CO2R4 or an isosteric equivalent of a carboxy group, wherein R is Ci - Ce alkyl, C2 - Ce alkenyl, C3 - Cs cycloalkyl or aryl; and

[0014] Y is -(CH2-CH2)-, -(CH=CH)-, or -(C=C)-; or a cosmetically acceptable salt thereof; and an N-acetyl compound selected from the group consisting of N-aldosamines, N- acetylated amino acids and combinations thereof.

[0015] The skincare composition of claim 1, wherein Ri is selected from the group consisting of C5 - Cie alkyl, C5 - Cie alkenyl, and C5 - Cie alkynyl; R2 is selected from the group consisting of hydrogen, hydroxyl, -OCi - Ce alkyl, -OC2 - Ce alkenyl, -OC2 - Ce alkynyl, -OC3 - Cs cycloalkyl; R3 is selected from -CO2H, -CO2R4 wherein R4 is Ci - Ce alkyl, or an isosteric equivalent of a carboxy group; and Y is -(CH2-CH2)- or -(CH=CH)-.

[0016] The skincare composition of claim 1 or 2, wherein Ri is selected from the group consisting of C5 - Cie alkenyl; and R2 is selected from the group consisting of hydrogen or -OCi - C3 alkyl. The skincare composition of any of claims 1-3, wherein the compound of Formula I is selected from the group consisting of 3-(4-farnesyloxyphenyl)-propionic acid, 3-(4-farnesyloxy-3- hydroxyphenyl)- propionic acid, 3-(4-farnesyloxy-3-methoxyphenyl)-propionic acid, ethyl esters thereof, and combinations of two or more thereof.

[0017] In one or more embodiments, the compound of Formula I comprises 3-(4-farnesyloxyphenyl)- propionic acid. In some embodiments, the concentration of the compound of Formula I is present in an amount ranging from about 0.00001% to 10 %, by total weight of the composition. In one or more embodiments, the skincare composition comprises a botanical extract comprising the compound of Formula I. In one or more embodiments, the botanical extract comprises an extract of a plant of the genus Acronychia. In one or more embodiments, said botanical extract is an extract of Acronychia acidula. In some embodiments, the botanical extract is present in an amount ranging from about 0.00001% to about 5% by total weight of the composition. In one or more embodiments, the N-acetyl compound comprises a derivative of an aminosugar. In further embodiments, the derivative of an aminosugar is selected from the group consisting of N-acetyl- ribosamine, N-acetyl-arabinosamine, N-acetyl-glucosamine, N-acetyl-galactosamine and N- acetyl-mannosamine, and combinations thereof. In one or more embodiments, the derivative of an aminosugar comprises N-acetyl-glucosamine. In one or more embodiments, wherein the composition further comprises an ingredient selected from the group consisting of surfactants, chelating agents, emollients, humectants, conditioners, preservatives, opacifiers, fragrances, and combinations of two or more thereof. In some embodiments, the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product. In one or more embodiments, the compound of Formula I is comprises 3- (4-farnesyloxyphenyl)-propionic acid, and the N-acetyl compound comprises N-acetyl- glucosamine.

[0018] Any of the embodiments described can be combined in any suitable combination. For example, in one or more embodiments, the skincare composition comprises: from about 0.001 wt.% to about 1 wt.% of 3-(4-farnesyloxyphenyl)-propionic acid by total weight of the composition; and from about 0.05 wt.% to about 6 wt.% of a derivative of an aminosugar is selected from the group consisting of N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl- glucosamine, N-acetyl-galactosamine and N-acetyl-mannosamine, and combinations thereof by total weight of the composition, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

[0019] Another aspect of the invention pertains to a method for treating skin comprising topically applying any of the compositions described herein. In one or more embodiments, the method is a method for treating signs of aging, treating acne, smoothing skin texture, or brightening the skin. In one or more embodiments, the method is a method of increasing CRABP2 expression.

[0020] DETAILED DESCRIPTION

[0021] It is believed that one skilled in the art can, based on the description herein, utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

[0022] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Also, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference.

[0023] Unless otherwise indicated, percentages used to express amounts of ingredients are percentage by weight (referred to as “weight %,” “wt%”, “% by weight” or “% (WAV)”). Similarly, weight ratios used to express relative proportions of ingredients are also determined using percentage by weight (i.e., weight ratios are calculated by dividing the percentage by weight of one ingredient by another). Unless stated otherwise, all ranges are inclusive of the endpoints, e.g., “from 4 to 9” includes the endpoints 4 and 9. As used herein, a composition that is “essentially free” or “substantially free” of an ingredient means the composition that has about 2% or less of that ingredient by weight based on the total weight of the composition. Preferably, a composition that is essentially free of an ingredient has about 1% or less, more preferably about 0.5% or less, more preferably about 0.1% or less, more preferably about 0.05 or less, more preferably about 0.01% or less by weight based on the total weight of composition of the ingredient. In certain more preferred embodiments, a composition that is essentially free of an ingredient is free of the ingredient, i.e. has none of that ingredient in the composition.

[0024] As used herein, “cosmetically / dermatologically acceptable” means that the ingredients which the term describes are suitable for use in contact with tissues (e.g., the skin or hair) without undue toxicity, incompatibility, instability, irritation, allergic response, and the like. As will be recognized by one of skill in the art, cosmetically / dermatologically acceptable salts are acidic / anionic or basic / cationic salts.

[0025] As used herein, the term “safe and effective amount” means an amount of the compound, extract or of the composition sufficient to induce the desired effect, but low enough to avoid serious side effects. The safe and effective amount of the compound, extract, or composition will vary with e.g. the age, health and environmental exposure of the end user, the duration and nature of the treatment, the specific extract, ingredient, or composition employed, the particular pharmaceutically-acceptable carrier utilized, and like factors.

[0026] As used herein, the term “about” refers to within 5% weight, within 4% weight, within 3% weight, within 2.5% weight, within 2% weight, or within 1% weight of a disclosed value.

[0027] In general, IUPAC nomenclature rules are used herein and according to the following term definitions.

[0028] The term “substituted,” refers to a core molecule in which one or more hydrogen atoms have been replaced with that amount of substituents allowed by available valences. Substitution is not limited to the core molecule, but may also occur on a substituent radical, whereby the radical becomes a linking group. The term “independently selected” refers to two or more substituents that may be selected from a substituent variable group, wherein the selected substituents may be the same or different.

[0029] The term “dependently selected” refers to one or more substituent variables that are specified in an indicated combination for substitution in a core molecule (e.g. variables that refer to groups of substituents appearing in a tabular list of compounds).

[0030] Acceptable salts from inorganic bases include, for example, sodium or potassium salts, and the like. Acceptable salts from organic bases include, for example, salts formed with primary, secondary, or tertiary amines, and the like.

[0031] One aspect of the invention pertains to a skincare composition comprising:

[0032] (a) a compound of Formula I: wherein:

[0033] Ri is selected from the group consisting of Ci - C20 alkyl, C2 - C20 alkenyl, C2 - C20 alkynyl, and C3 - C8cycloalkyl or aryl;

[0034] R2 is selected from the group consisting of hydrogen, hydroxyl, Ci - Ce alkyl, C2 - Ce alkenyl, C2 - Ce alkynyl, C3 - C8cycloalkyl or aryl, -OCi - Ce alkyl, -OC2 - Ce alkenyl, - OC2 - C6alkynyl, -OC3 - C8cycloalkyl or aryl, thiol, -SCi - C6alkyl, -SC2 - C6alkenyl, -SC2 - Ce alkynyl, -SC3 - C8cycloalkyl or aryl, -NR4C1 - Ce alkyl, -NR4C2 - Ce alkenyl, -NR4C2 - Ce alkynyl, and -NR4C3 - C8cycloalkyl or aryl;

[0035] R3 is selected from -CO2H, -CO2R4 or an isosteric equivalent of a carboxy group, wherein R is Ci - Ce alkyl, C2 - Ce alkenyl, C3 - C8cycloalkyl or aryl; and Y is -(CH2-CH2)-, -(CH=CH)-, or -(C=C)-; or a cosmetically acceptable salt thereof; and

[0036] (b) an N-acetyl compound. Such compositions have been shown to exhibit synergy in a variety of respects compared to the ingredients alone.

[0037] Compound of Formula I

[0038] In one or more embodiments, Ri is selected from the group consisting of C5 - Ci6 alkyl, C5 - Ci6 alkenyl, and C5 - Ci6 alkynyl; R2 is selected from the group consisting of hydrogen, hydroxyl, - OCi - Ce alkyl, -OC2 - Ce alkenyl, -OC2 - Ce alkynyl, -OC3 - Cs cycloalkyl; R3 is selected from -CO2H, -CO2R4 wherein R4 is Ci - Ce alkyl, or an isosteric equivalent of a carboxy group; and Y is -(CH2-CH2)- or -(CH=CH)- (or a cosmetically acceptable salt thereof). In some embodiments, Ri is selected from the group consisting of C5 - Cie alkenyl; and R2 is selected from the group consisting of hydrogen or -OCi - C3 alkyl. In one or more embodiments, the compound of Formula I is selected from the group consisting of 3-(4-farnesyloxyphenyl)-propionic acid, 3-(4- farnesyloxy-3-hydroxyphenyl)- propionic acid, 3-(4-farnesyloxy-3-methoxyphenyl)-propionic acid, ethyl esters thereof, and combinations of two or more thereof. In one or more embodiments, the compound of the above Formula I is 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester. In preferred embodiments, the compound of Formula I is comprises 3-(4- farnesyloxyphenyl)-propionic acid. The 3-(4-farnesyloxyphenyl)-propionic acid and / or its ethyl ester can be synthesized using conventional organic synthesis processes.

[0039] The compound of Formula I may be present in an amount ranging from about 0.00001% to 10 %, or about 0.0001 to about 10%, or about 0.001 to about 5%, or about 0.001% to about 1%, or about 0.01% to about 3%, about 0.01% to about 1%, about 0.01% to about 0.5%, or about 0.005% to about 1.5%, or about 0.005% to about 0.06%, or about 0.009% to about 0.06%, or about 0.009% to about 0.03% by total weight of the composition.

[0040] Compounds according to Formula I can also be obtained from natural sources. For example, a compound according to Formula I may be found in a botanical extract. Accordingly, the composition may comprise a botanical extract comprising the compound of Formula I. In one or more embodiments, the botanical extract is an extract of a plant of the genus Acronychia. In further embodiments, the botanical extract is an extract of Acronychia acidula (also known as lemon aspen). In one or more embodiments, at least one compound of the above Formula I is present in the extract of Acronychia at a concentration equal to or greater than about 0.01 to about 30%, or about 0.1% to about 30%, or about 0.1 to about 20%, or about 1% to about 20%, or about 1% to about 10%, or about 1.5% to about 9%, or about 3% to about 9%, by weight of the Acronychia extract. In further embodiments, the extract of Acronychia acidula comprises 3-(4-farnesyloxyphenyl)-propionic acid in a concentration ranging from about 1% to about 10% by total weight of the extract.

[0041] Suitable extracts may be obtained using conventional methods including, but not limited to, direct extraction of material from the biomass by grinding, macerating, pressing, squeezing, mashing, centrifuging, and / or processes such as cold percolation, agitation / distillation, microwave assisted extraction, supercritical / subcritical CO2 compressed gas extraction with or without polar modifiers, pressurized solvent extraction, accelerated solvent extraction, pressurized or normal hot water extraction, surfactant assisted pressurized hot water extraction, oil extraction, membrane extraction, Soxhlet extraction, the gold finger distillation / extraction and / or processes disclosed, for example, in US Pat. Nos. 7442391, 7473435, and 7537791 to Integrated Botanical Technologies, LLC, incorporated herein by reference, and the like, or by other methods such as solvent extraction, and the like.

[0042] Any of a variety of solvents including polar solvents, non-polar solvents, or combinations of two or more thereof may be used in methods comprising solvent extraction. Suitable polar solvents include polar inorganic solvents such as water and the like, polar organic solvents such as alcohols and corresponding organic acids, for example Ci-Cs alcohols including methanol, ethanol, propanol, butanol, and the like and organic acids, including acetic acid, formic acid, propanoic acid, and the like, polyols and glycols, including Ci-Cs polyols / glycols and the like, and combinations of two or more thereof. Suitable non-polar solvents include non-polar organic solvents such as alkanes, including Ci-Cs alkanes, cycloalkanes, including Ci-Cs alkanes, alkyl ethers, including Ci-Cs alkyl ethers, Petroleum ethers, ketones, including Ci-Cs ketones, methylene chloride, ethyl acetate, xylene, toluene, chloroform, vegetable oil, mineral oil and the like. In another embodiment extraction may be obtained by non-polar solvents described above or supercritical fluid extraction with or without a polar modifier such as Ci-Cs alcohols, water, Ci-Cs polyols / glycols or Ci-Cs organic acids.

[0043] In one or more embodiments, the extract comprises an extract of Acronychia acidida. In some embodiments, the extract of the invention comprises a combination of polar and non-polar extracts of Acronychia acidula fruit. In another embodiment, the extract of the invention comprises alcoholic or glycolic extracts of Acronychia acidula fruit.

[0044] In one or more embodiments, the extract is a polar extract. In further embodiments, the extract is a polar extract prepared using a polar solvent comprising water, Ci-Cs alcohols, Ci-Cs polyols, or Ci-Cs glycols, or combinations of two or more thereof. In certain embodiments, the extract is extracted using one or more C1-C4 alcohols, C1-C4 polyols, and / or C1-C4 glycols. In one or more embodiments, the extract is prepared using a solvent comprising methanol, ethanol, or a combination thereof with or without presence of water. In further embodiments, the extract is a polar extract extracted from Acronychia acidula fruit using a combination of alcohol and water.

[0045] In one or more embodiments, the extract is a non-polar extract prepared using a non-polar solvent comprising one or more Ci-Cs alkanes, Ci-Cs cycloalkanes, Ci-Cs alkyl ethers, Ci-Cs alkyl esters and / or chloroform, more preferably one or more Ci-Cs alkanes, Ci-Cs alkyl esters and / or chloroform. In further embodiments, the extract is a non-polar extract prepared using hexanes, ethyl acetate, chloroform, or mixtures of two or more thereof. In yet further embodiments, the extract is a non-polar extract prepared using ethyl acetate.

[0046] For example, an extract using the fruit of Acronychia acidula may be prepared by homogenizing the fruit in a blender for 30 seconds with denatured alcohol in equal part to fruit. The pulp can then mixed and stirred for another 24 hours at ambient temperature (22 to 26 degrees C). Additional denatured alcohol may be added as needed to keep the pulp covered well in alcohol. The mixture then can then be gravity filtered, and the resulting filter cake washed with additional amounts of denatured alcohol. The total filtrate then may then be dried under reduced pressure to remove alcohol. The residue can then be freeze dried to obtain dry matter free of extraction solvent and water. The extraction may be repeated on the filter cake a few times with an extract yield of 5-7 % regularly obtained from each extraction. Another example of the preparation of Acronychia acidida fruit extract is as follows: 500gm of freeze-dried fruits of Acronychia acidula may be sliced into approximately 5mm cubes and soaked with 5L of ethanol at a ratio of 1:10 (raw material to solvent) and stirred at room temperature for 12 hours. The suspension may then be filtered and resulting filtrate concentrated under low pressure to afford a concentrate. The concentrate can then further be dried by freeze-drying methods to obtain 325gm of residual material called crude extract (65% yield). A sample of the crude extract, 200gm, can then be taken up in IL ethanol and stirred at room temperature overnight. The mixture may then be filtered and dried at reduced pressure and at low temperature

[0047] The extract may be present in an amount of about 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1, 1.5 or 2 to about 0.00005, 0.0005, 0.005, 0.05, 0.5, 1, 1.5, 2, 2.5, 3, 4 or 5 wt.% by total weight of the composition. In one or more embodiments, the extract is present in an amount of about 0.01 to about 5 wt.% by total weight of the composition. In further embodiments, the extract is present in an amount of about 0.01 to about 3 wt.% by total weight of the composition. In one or more embodiments, the extract is present in an amount of about 0.1 to about 3 wt.% by total weight of the composition. In further embodiments, the extract is present in an amount of about 0.2 to about 2.5 wt.% by total weight of the composition. In one or more embodiments, the extract is present in an amount of about 0.5 to about 2 wt.% by total weight of the composition. In further embodiments, the extract is present in an amount of about 0.5 to about 1.5 wt.% by total weight of the composition. In one or more embodiments, the extract is present in an amount of about 0.1 to about 3 wt.% by total weight of the composition. In further embodiments, the extract is present in an amount of about 0.2 to about 1 wt.% by total weight of the composition. In one or more embodiments, the extract is present in an amount of about 0.25 to about 0.5 wt.% by total weight of the composition. In further embodiments, the extract is present in an amount of about 0.1 to about 1 wt.% by total weight of the composition.

[0048] N-acetyl compound

[0049] As used herein, the term “N-acetyl compound” refers to N-aldosamines, N-acetylated amino acids and related compounds as further discussed below. N-acetyl-aldosamines are N-acetylated aminosugars in which the acetylamino group is preferably located at position 2 of the carbon chain. In accordance with the present invention, the generic structure or formula of N-acetyl-aldosamines may be represented as follows: where n is an integer, preferably 1-19; Ri is selected from the group consisting of CHO, CONH2, and COOR3 ; R2 is selected from the group consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form, having 1 to 19 carbon atoms; and R3 is selected from the group consisting of H, an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms. N-Acetyl-aldosamines may be present as saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form. A typical cyclic form of an N-acetyl-aldosamine is a five member ring (furanose form) or a six member ring (pyranose form).

[0050] The following are some representative N-acetyl-aldosamines and related compounds: N-acetyl- glycerosamine, N-acetyl-erythrosamine, N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl- arabinosamine, N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine, N-acetyl- altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine, N-acetyl-gulosamine, N-acetyl- idosamine, N-acetyl-galactosamine, N-acetyl-talosamine, N-acetyl-glucoheptosamine, N-acetyl- galactoheptosamine, N-acetyl-mannoheptosamine, N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine, N-acetylneuramin Lactose, N-acetyl-glyceraminic acid, N-acetyl- erythrosaminic acid, N-acetyl-threosaminic acid, N-acetyl-ribosaminic acid, N-acetyl- arabinosaminic acid, N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid, N-acetyl- allosaminic acid, N-acetyl-altrosaminic acid, N-acetyl-glucosaminic acid, N-acetyl- mannosaminic acid, N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid, N-acetyl- galactosaminic acid, N-acetyl-talosaminic acid, N-acetyl-heptoglucosaminic acid, N-acetyl- heptogalactosaminic acid, N-acetyl-heptomannosaminic acid, and N-acetyl-N-acetylneuraminic. The amides and esters of the foregoing acid compounds also are contemplated by the present invention. Examples of five and six member ring forms are 2-acetamido-2-deoxy-D- ribofuranoside, 2-acetamido-2-deoxy-D-ribopyranoside, 2-acetamido-2-deoxy-D-glucofuranosid e, 2-acetamido-2-deoxy-D-glucopyranoside, 2-acetamido-2-deoxy-D-galactofuranoside and 2- acetamido-2-deoxy-D-galactopyranoside.

[0051] N-acetylamino acids are N-acetyl derivatives of amino acids. In accordance with the present invention, the generic structure or formula of N-acetylamino acids and related compounds may be represented as follows: where Ri is H, or an alkyl or aralkyl group having 1 to 14 carbon atoms; n is an integer, preferably from 0 to 5; R2 is OH, NH2 or OR3 ; and R3 is an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms; the alkyl, aralkyl or aryl group may be saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form; and in addition Ri may carry OH, SH, SCH3, C00H, NH2 CONH2, guanidine or heterocyclic group; the H attached to a carbon atom may be substituted by I, F, Cl, Br or alkoxyl group having 1 to 9 carbons. N-Acetylamino acids may be present as isomeric or non-isomeric, as a free acid, salt, lactone, amide or ester form.

[0052] The following are some representative N-acetylamino acids and related compounds: N-acetyl- glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl- serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-cysteine, N-acetyl-methionine, N-acetyl- aspartic acid, N-acetyl-asparagine, N-acetyl-glutamic acid, N-acetyl-glutamine, N-acetyl- arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N- acetyl-tryptophan, N-acetyl-proline, N-acetyl-P-alanine, N-acetyl-taurine, N-acetyl-r- aminobutanoic acid, N-acetyl-hydroxyproline, N-acetyl-canavanine, N-acetyl-hydroxylysine, N- acetyl-cycloserine, N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline, N-acetyl- homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline, N-acetylethionine, N-acetyl- methoxinine, N-acetyl-P-aminoisobutanoic acid, N-acetyl-homocysteine, N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine, N-acetyl-homotryptophan, N-acetyl-5- hydroxytryptamine (N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine, N-acetyl- citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa, N-acetyl-3-iodotyrosine, N-acetyl-3,5- diiodotyrosine, N-acetyl-3,5,3'-triiodothyronine, N-acetyl-thyroxine, N-acetyl-creatine, N-acetyl- creatinine, N-acetyl-cystine and N-acetyl-homocystine.

[0053] The above N-acetylamino acids and related N-acetyl compounds may be present as a free acid, salt, lactone, amide or ester form. Examples of these compounds include N-acetyl-cysteine ammonium salt, N-acetyl-homocysteine thiolactone, N-acetyl-L-cystine methyl ester, N-acetyl- L-tryosinamide, N-acetyl-L-tryosine ethyl ester, N-acetyl-serine amide, N-acetylglycine methyl ester, N-acetylglycinamide, and N-acetyl-tryptophan methyl, ethyl, propyl or isopropyl esters.

[0054] The related N-acetyl compounds may also include dimers and oligomers formed from N- acetylamino acids with 2 to 5 monomer units. Examples include N-acetylglycylglycine and its amide and esters, N-acetylglycyl-leucine its amide and esters, N-acetylglycyltryptophan, N- acetylglycyl-glutamic acid and its amide and esters, N-acetyltryosyl-phenylalanine and its amide and esters, N-acetylglycyl-lysine and its amide and esters, N-acetylleucyl-glycine and its amide and esters, N-acetylglycyl-glycyl-glycine and its amide and esters, N-acetylglycyl-lysyl- hydroxyproline and its amide and esters.

[0055] N-Acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds which are useful for topical treatment of skin, nail and hair changes associated with intrinsic and / or extrinsic aging and extrinsic factors include, inter alia, N-acetyl-aldosamines which are derivatives of aminosugars and include N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-glucosamine, N-acetyl- galactosamine and N-acetyl-mannosamine, and N-acetylamino acids which are N-acetyl derivatives of amino acids and include N-acetyl-glucine, N-acetyl-proline, N-acetyl-lysine, N- acetyl-arginine and N-acetyl-tryptophan. In one or more embodiments, the N-acetyl compound comprises a derivatives of an aminosugar. In further embodiments, the derivative of an aminosugar is selected from the group consisting of N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-glucosamine, N-acetyl-galactosamine and N-acetyl-mannosamine, and combinations thereof. In further embodiments, derivative of an aminosugar comprises N-acetyl-glucosamine.

[0056] The N-acetyl compound may be present in amounts ranging from about 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1, 1.5 or 2 to about 0.05, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 wt% by total weight of the composition. In one or more embodiments, the N-acetyl compound may be present in amounts ranging from about 0.001 to about 10 wt%. In further embodiments, the N-acetyl compound may be present in amounts ranging from about 0.01 to about 8 wt%. In one or more embodiments, the N-acetyl compound may be present in amounts ranging from about 0.05 to about 6 wt%. In further embodiments, the N-acetyl compound may be present in amounts ranging from about 2 to about 4 wt%. In one or more embodiments, the N-acetyl compound may be present in amount of about 2 wt%. In one or more embodiments, the N-acetyl compound may be present in amounts of about 4 wt%.

[0057] In embodiments where the N-acetyl compound comprises N-acetyl-glucosamine, the N-acetyl- glucosamine may be present in amounts ranging from about 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1, 1.5 or 2 to about 0.05, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 wt% by total weight of the composition. In one or more embodiments, the N-acetyl compound may be present in amounts ranging from about 0.001 to about 10 wt%. In further embodiments, the N-acetyl compound may be present in amounts ranging from about 0.01 to about 8 wt%. In one or more embodiments, the N-acetyl compound may be present in amounts ranging from about 0.05 to about 6 wt%. In further embodiments, the N-acetyl compound may be present in amounts ranging from about 2 to about 4 wt%. In one or more embodiments, the N-acetyl compound may be present in amount of about 2 wt%. In one or more embodiments, the N-acetyl compound may be present in amounts of about 4 wt%.

[0058] In one or more embodiments, the compound of Formula I is comprises 3-(4-farnesyloxyphenyl)- propionic acid, and the N-acetyl compound comprises N-acetyl-glucosamine, and wherein the 3- (4-farnesyloxyphenyl)-propionic acid and gluconolactone are present in a weight ratio of about 1:25 to about 1:300, or about 1:50 to about 1:250, or about 1:55 to about 1:239, or about 1:50 to about 1 :60, or about 1 : 100 to about 1 : 120, or about 1 : 110 to about 1 : 130, or about 1 :220 to about 1:250.

[0059] Methods

[0060] Another aspect of the invention pertains to a method for treating skin, the method comprising topically applying to skin a composition in accordance with one or more embodiments of the invention. As used herein, “treatment” or “treating” means the amelioration, prophylaxis, or reversal of a condition, disease, or disorder, or at least one discernible symptom thereof. In one embodiment, “treatment” or “treating” refers to an amelioration, prophylaxis, or reversal of at least one measurable physical parameter related to the condition, disease, or disorder being treated, not necessarily discernible in or by the subject being treated. In another embodiment, “treatment” or “treating” refers to inhibiting or slowing the progression of a condition, disease, or disorder, either physically, e.g., stabilization of a discernible symptom, physiologically, e.g., stabilization of a physical parameter, or both. In another embodiment, “treatment” or “treating” refers to delaying the onset of a condition, disease, or disorder.

[0061] The compositions / compounds described herein may be used in treating skin for treating acne, treating the signs of aging (e.g., wrinkles), improving skin barrier function and / or lightening skin. In one or more embodiments, said treatment is for a subject who has a condition or a history of a condition selected from the group consisting of atopic dermatitis, rosacea, seborrheic dermatitis, psoriasis, dry skin, flaky skin.

[0062] Compositions of the present invention are suitable for treating or preventing signs of skin aging. As used herein “signs of skin aging” include the presence of lines and wrinkles, loss of elasticity, uneven skin, and blotchiness. In a particularly preferred embodiment, the sign of aging is the presence of lines and wrinkles and / or loss of elasticity.

[0063] Compositions of the invention are suitable for improving the texture of skin or improving the firmness of skin, or any of the conditions / symptoms described below.

[0064] As used herein, “improving the texture of skin” means the smoothing of the surface of the skin to remove either bumps or crevasses on the skin surface. As used herein, “improving the firmness of skin” means the enhancing of the firmness or elasticity of the skin, preventing the loss of firmness or elasticity of skin, or preventing or treating sagging, lax and loose skin.

[0065] As used herein, “loss of elasticity” includes loss of elasticity or structural integrity of the skin or tissue, including but not limited to sagging, lax and loose tissue. The loss of elasticity or tissue structure integrity may be a result of a number of factors, including but not limited to disease, aging, hormonal changes, mechanical trauma, environmental damage, or the result of an application of products, such as a cosmetics or pharmaceuticals, to the tissue.

[0066] As used herein, “uneven skin” means a condition of the skin associated with diffuse or mottled pigmentation, which may be classified as hyperpigmentation, such as post-inflammatory hyperpigmentation .

[0067] As used herein, “blotchiness” means a condition of the skin associated with redness or erythema.

[0068] As used herein, “age spots” means a condition of the skin associated with discrete pigmentation, e.g., small areas of darker pigmentation that may develop on the face as well as the hands.

[0069] Signs of skin aging also include the presence of diminished skin thickness, and abnormal or diminished synthesis of collagen, glycosaminoglycans, proteoglycans, elastin, or glycoproteins including fibronectin. In one embodiment, the sign of aging is selected from the abnormal or diminished synthesis of collagen, glycosaminoglycans, proteoglycans, elastin, or glycoproteins including fibronectin. In another embodiment, the sign of skin aging is diminished synthesis of collagen or elastin.

[0070] Examples of skin aging that may be treated by topical use of the compositions of this invention include, but are not limited to, wrinkles on the skin. As used herein, the term “wrinkle” includes fine line, fine wrinkles, coarse wrinkles, cellulite, scars, and stretch marks. Examples of wrinkles include, but are not limited to, fine lines around the eyes (e.g., “crow’s feet”), forehead and cheek wrinkles, frown-lines, and laugh-lines around the mouth.

[0071] As used herein, "topical use" and “topically applying” means directly laying on or spreading on the skin, hair, or nail, e.g., by use of the hands or an applicator such as a wipe or sponge. The compositions are also suitable for treating or preventing acne. As used herein, “acne” refers to disorders resulting from the actions of hormones and other substances on the sebaceous glands and hair follicles, typically leading to clogged pores and the formation of inflammatory or noninflammatory lesions on the skin. Specifically, it relates to blemishes, lesions, or pimples, pre- emergent pimples, blackheads, and / or whiteheads. As used herein, a “pre-emergent pimple” is an inflamed follicle that is not visually apparent on the surface of the skin with the naked eye (e.g., as a lesion).

[0072] The compositions of the invention are also suitable for treating or preventing rosacea. As used herein, “rosacea” means skin with persistent erythema with or without papules, pustules, or nodules.

[0073] The compositions of the invention are also suitable for reducing epidermal hyperkeratinzation. Accordingly, the composition may be used for treatment or prevention of conditions characterized by hyperkeratinzation, such as acne or warts.

[0074] In one or more embodiments, one or more of the methods described herein modify the expression of one or more biomarkers. For example, in one or more embodiments, the method may be a method of increasing CRABP2, HAS2, or HBEGF expression in skin.

[0075] The embodiments described herein may be combined in any suitable combination. For example, an exemplary embodiment pertains to a method of treating acne, signs of aging and / or lightening skin, the method comprising applying to the skin a composition comprising: a. from about 0.001 wt.% to about 1 wt.% of 3-(4-farnesyloxyphenyl)-propionic acid by total weight of the composition; and b. from about 0.05 wt.% to about 6 wt.% of a derivative of an aminosugar is selected from the group consisting of N-acetyl-ribosamine, N-acetyl-arabinosamine, N- acetyl-glucosamine, N-acetyl-galactosamine and N-acetyl-mannosamine, and combinations thereof by total weight of the composition.

[0076] In further embodiments, the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product. The 3-(4- farnesyloxyphenyl)-propionic acid may be chemically synthesized, naturally occurring in a

[0077] Y1 botanical extract, or chemically synthesized and added to a botanical extract. In one or more embodiments, the applying step comprises applying to the skin a composition comprising a botanical extract, wherein the botanical extract is an extract of a plant of the genus Acronychia. In further embodiments, the botanical extract is an extract of Acronychia acidula. In yet further embodiments, the extract is a polar extract. In one or more embodiments, the extract is present in an amount of about 0.1 to about 3 wt.% by total weight of the composition. In further embodiments, the extract is present in an amount of about 0.4 to about 1.5 wt.% by total weight of the composition.

[0078] The compositions described herein may be applied to any skin in need of treatment on the human body. For example, application may be made to any one or more of the skin of the face, neck, chest, back, arms, axilla, hands and / or legs. In certain preferred embodiments, the method comprises applying a composition according to one or more embodiments of the invention to skin of the face.

[0079] Any suitable method of applying the extract to the skin in need may be used in accordance with the present invention. For example, the extract may be applied directly from a package to the skin in need, by hand to the skin in need, or may be transferred from a substrate such as a wipe, sponge or mask, or a combination of two or more thereof. In other embodiments, the extract may be applied via a dropper, tube, roller, spray, patch or added to a bath or otherwise to water to be applied to the skin, and the like.

[0080] In one or more embodiments, the methods of the present invention further comprise the step of leaving the composition in contact with the skin for period of time. For example, in certain preferred embodiments after application, the compound is left in contact with the skin for a period of about 15 minutes or greater. In certain more preferred embodiments, the extract is left in contact with the skin for about 20 minutes or greater, more preferably about 1 hour or greater.

[0081] In some embodiments, the method of the present invention comprises a regimen comprising applying the composition to skin multiple times over a selected period of time. For example, in certain embodiments, the present invention provides a method of treating signs of aging comprising applying to skin in need of antiaging a composition in accordance with one or more embodiments of the invention once or twice daily for at least 12 weeks, preferably at least 8 weeks and more preferably for at least 2 weeks.

[0082] Compositions

[0083] Any suitable carrier may be used in the compositions of the present invention. Preferably, for a skin care composition, the carrier is a cosmetically-acceptable carrier. As will be recognized by those of skill in the art, cosmetically-acceptable carriers comprise carriers that are suitable for use in contact with the body, in particular the skin for antiaging applications, without undue toxicity, incompatibility, instability, irritation, allergic response, and the like. A safe and effective amount of carrier is from about 50% to about 99.999%, preferably from about 80% to about 99.9%, more preferably from about 95% to about 99.9%, most preferably from about 98% to about 99.8% of the composition. The carrier can be in a wide variety of forms. For example, emulsion carriers, including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions, are useful herein. These emulsions can cover a broad range of viscosities, e.g., from about 100 cP to about 200,000 cP. Examples of suitable cosmetically-acceptable carriers include cosmetically-acceptable solvents and materials for cosmetic solutions, suspensions, lotions, creams, serums, essences, gels, toners, sticks, sprays, ointments, liquid washes and soap bars, shampoos, hair conditioners, pastes, foams, mousses, powders, shaving creams, wipes, patches, strips, powered patches, microneedle patches, bandages, hydrogels, film-forming products, facial and skin masks, makeup, liquid drops, and the like. These product types may contain several types of cosmetically- acceptable carriers including, but not limited to solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids, liposomes, other encapsulation technologies and the like. In one or more embodiments, the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

[0084] The following are non-limitative examples of such carriers. Carriers can be formulated by those of ordinary skill in the art. In one embodiment, the carrier contains water. In a further embodiment, the carrier may also contain one or more aqueous or organic solvents. Examples of organic solvents include, but are not limited to: dimethyl isosorbide; isopropylmyristate; surfactants of cationic, anionic and nonionic nature; vegetable oils; mineral oils; waxes; gums; synthetic and natural gelling agents; alkanols; glycols; and polyols. Examples of glycols include, but are not limited to, glycerin, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, capryl glycol, glycerol, butanediol and hexanetriol, and copolymers or mixtures thereof. Examples of alkanols include, but are not limited to, those having from about 2 carbon atoms to about 12 carbon atoms (e.g., from about 2 carbon atoms to about 4 carbon atoms), such as isopropanol and ethanol. Examples of polyols include, but are not limited to, those having from about 2 carbon atoms to about 15 carbon atoms (e.g., from about 2 carbon atoms to about 10 carbon atoms) such as propylene glycol. The organic solvents may be present in the carrier in an amount, based upon the total weight of the carrier, of from about 1 percent to about 99.99 percent (e.g., from about 20 percent to about 50 percent). Water may be present in the carrier (prior to use) in an amount, based upon the total weight of the carrier, of from about 5 percent to about 95 percent (e.g., from about 50 percent to about 90 percent). Solutions may contain any suitable amounts of solvent, including from about 40 to about 99.99%. Certain preferred solutions contain from about 50 to about 99.9%, from about 60 to about 99%, from about 70 to about 99%, from about 80 to about 99%, or from about 90 to 99%.

[0085] A lotion can be made from such a solution. Lotions typically contain at least one emollient in addition to a solvent. Lotions may comprise from about 1% to about 20% (e.g., from about 5% to about 10%) of an emollient(s) and from about 50% to about 90% (e.g., from about 60% to about 80%) of water. As used herein, "emollients" refer to materials used for the prevention or relief of dryness, as well as for the protection of the skin or hair. Examples of emollients include, but are not limited to, those set forth in the International Cosmetic Ingredient Dictionary and Handbook, eds. Wenninger and McEwen, pp. 1656-61, 1626, and 1654-55 (The Cosmetic, Toiletry, and Fragrance Assoc., Washington, D.C., 7th Edition, 1997) (hereinafter “ICI Handbook”).

[0086] Another type of product that may be formulated from a solution is a cream. A cream typically contains from about 5% to about 50% (e.g., from about 10% to about 20%) of an emollient(s) and from about 45% to about 85% (e.g., from about 50% to about 75%) of water.

[0087] Yet another type of product that may be formulated from a solution is an ointment. An ointment may contain a simple base of animal, vegetable, or synthetic oils or semi-solid hydrocarbons. An ointment may contain from about 2% to about 10% of an emollient(s) plus from about 0.1% to about 2% of a thickening agent(s).

[0088] The compositions useful in the present invention can also be formulated as emulsions. If the carrier is an emulsion, from about 1% to about 10% (e.g., from about 2% to about 5%) of the carrier contains an emulsifier(s). Emulsifiers may be nonionic, anionic or cationic. Examples of emulsifiers include, but are not limited to, those set forth in the ICI Handbook, pp.1673- 1686.

[0089] Lotions and creams can be formulated as emulsions. Typically such lotions contain from 0.5% to about 5% of an emulsifier(s), while such creams would typically contain from about 1% to about 20% (e.g., from about 5% to about 10%) of an emollient(s); from about 20% to about 80% (e.g., from 30% to about 70%) of water; and from about 1% to about 10% (e.g., from about 2% to about 5%) of an emulsifier(s).

[0090] Single emulsion skin care preparations, such as lotions and creams, of the oil-in-water type and water-in-oil type are well-known in the art and are useful in the subject invention. Multiphase emulsion compositions, such as the water-in-oil-in-water type or the oil-in-water-in-oil type, are also useful in the subject invention. In general, such single or multiphase emulsions contain water, emollients, and emulsifiers as essential ingredients.

[0091] The compositions of this invention can also be formulated as a gel (e.g., an aqueous, alcohol, alcohol / water, or oil gel using a suitable gelling agent(s)). Suitable gelling agents for aqueous and / or alcoholic gels include, but are not limited to, natural gums, acrylic acid and acrylate polymers and copolymers, and cellulose derivatives (e.g., hydroxymethyl cellulose and hydroxypropyl cellulose). Suitable gelling agents for oils (such as mineral oil) include, but are not limited to, hydrogenated butylene / ethylene / styrene copolymer and hydrogenated ethylene / propylene / styrene copolymer. Such gels typically contains between about 0.1% and 5%, by weight, of such gelling agents.

[0092] The compositions of the present invention can also be formulated into a solid formulation (e.g., a wax-based stick, soap bar composition, powder, or wipe). The composition of the present invention can also be combined with a solid, semi-solid or dissolvable substrate (eg., a wipe, mask, pad, glove or strip).

[0093] The compositions of the present invention may further comprise any of a variety of additional cosmetically active agents, although they are preferably formulated to account for use on skin. Examples of suitable additional active agents include: additional skin lightening agents, darkening agents, anti-acne agents, shine control agents, antimicrobial agents such as anti-yeast agents, anti-fungal, and anti-bacterial agents, anti-inflammatory agents, anti-parasite agents, external analgesics, sunscreens, photo-protectors, antioxidants, keratolytic agents, detergents / surf actants, moisturizers, nutrients, vitamins, energy enhancers, anti-perspiration agents, astringents, deodorants, hair removers, hair growth enhancing agents, hair growth delaying agents, firming agents, hydration boosters, efficacy boosters, anti-callous agents, agents for skin conditioning, anti-cellulite agents, fluorides, teeth whitening agents, anti-plaque agents, and plaque-dissolving agents, odor-control agents such as odor masking or pH-changing agents, and the like. Examples of various suitable additional cosmetically acceptable actives include hydroxy acids, benzoyl peroxide, D-panthenol, UV filters such as but not limited to avobenzone (Parsol 1789), bisdisulizole disodium (Neo Heliopan AP), diethylamino hydroxybenzoyl hexyl benzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T 150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysilicone-15 (Parsol SLX), trolamine salicylate, Bemotrizinol (Tinosorb S), benzophenones 1-12, dioxybenzone, drometrizole trisiloxane (Mexoryl XL), iscotrizinol (Uvasorb HEB), octocrylene, oxybenzone (Eusolex 4360), sulisobenzone, bisoctrizole (Tinosorb M), titanium dioxide, zinc oxide, carotenoids, free radical scavengers, spin traps, retinoids and retinoid precursors such as retinol, retinoic acid and retinyl palmitate, ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes, enzyme inhibitors, minerals, hormones such as estrogens, steroids such as hydrocortisone, 2- dimethylaminoethanol, copper salts such as copper chloride, peptides containing copper such as Cu:Gly-His-Lys, coenzyme Q10, amino acids such a proline, vitamins, lactobionic acid, acetyl-coenzyme A, niacin, riboflavin, thiamin, ribose, electron transporters such as NADH and FADH2, and other botanical extracts such as oat, aloe vera, Feverfew, Soy, Shiitake mushroom extracts, and derivatives and mixtures thereof.

[0094] In one or more embodiments, the compositions of the present invention are skin care compositions that comprise at least one skin lightening active agent. Examples of suitable skin lightening active agents include, but are not limited to, tyrosinase inhibitors, melanin-inhibiting agents, melanosome transfer inhibiting agents including PAR-2 antagonists, exfoliants, sunscreens, retinoids, antioxidants, Tranexamic acid, skin bleaching agents, allantoin, opacifiers, talcs and silicas, zinc salts, and the like, and other agents as described in Solano et al. Pigment Cell Res. 2006, 19 (550-571). Examples of suitable tyrosinase inhibitors include but, are not limited to, Vitamin C and its derivatives, Vitamin E and its derivatives, Kojic Acid, Arbutin, resorcinols, hydroquinone, Flavones e.g. Licorice flavanoids, Licorice root extract, Mulberry root extract, Dioscorea Coposita root extract, Saxifraga extract and the like, Ellagic acid, Salicylates and derivatives, Fullerene, Hinokitiol, Dioic acid, Magnolignane, combinations of two or more thereof, and the like. Examples of Vitamin C derivatives include, but are not limited to, ascorbic acid and salts, Ascorbic Acid-2-Glucoside, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, and natural extract enriched in Vitamin C. Examples of Vitamin E derivatives include, but are not limited to, alpha-tocopherol, beta, tocopherol, gammatocopherol, delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, delta- tocotrienol and mixtures thereof, tocopherol acetate, tocopherol phosphate and natural extracts enriched in Vitamin E derivatives. Examples of resorcinol derivatives include, but are not limited to, resorcinol, 4-substituted resorcinols like 4-alkylresorcinols such as 4-butyresorcinol (rucinol), 4-hexylresorcinol, phenylethyl resorcinol, l(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy- 3-methylphenyl)-Propane and the like and natural extracts enriched in resorcinols. Examples of salicylates include, but are not limited to, salicylic acid, acetylsalicylic acid, 4-methoxysalicylic acid and their salts. In certain preferred embodiments, the tyrosinase inhibitors include a 4- substituted resorcinol, a Vitamin C derivative, or a Vitamin E derivative. In more preferred embodiments, the tyrosinase inhibitor comprises Phenylethyl resorcinol, 4-hexyl resorcinol, or ascorbyl-2-glucoside.

[0095] Examples of suitable melanin-degradation agents include, but are not limited to, peroxides and enzymes such as peroxidases and ligninases. In certain preferred embodiments, the melanininhibiting agents include a peroxide or a ligninase.

[0096] Examples of suitable melanosome transfer inhibiting agents including PAR-2 antagonists such as soy trypsin inhibitor or Bowman-Birk Inhibitor, Vitamin B3 and derivatives such as Niacinamide, Essential soy, Whole Soy, Soy extract. In certain preferred embodiments, the melanosome transfer inhibiting agents includes a soy extract or niacinamide. Examples of exfoliants include, but are not limited to, alpha-hydroxy acids such as lactic acid, glycolic acid, malic acid, tartaric acid, citric acid, or any combination of any of the foregoing, beta-hydroxy acids such as salicylic acid, polyhydroxy acids such as lactobionic acid and gluconic acid, and mechanical exfoliation such as microdermabrasion. In certain preferred embodiments, the exfoliant include glycolic acid or salicylic acid.

[0097] Examples of sunscreens include, but are not limited to, avobenzone (Parsol 1789), bisdisulizole disodium (Neo Heliopan AP), diethylamino hydroxybenzoyl hexyl benzoate (Uvinul A Plus), ecamsule (Mexoryl SX), methyl anthranilate, 4-aminobenzoic acid (PABA), cinoxate, ethylhexyl triazone (Uvinul T 150), homosalate, 4-methylbenzylidene camphor (Parsol 5000), octyl methoxycinnamate (Octinoxate), octyl salicylate (Octisalate), padimate O (Escalol 507), phenylbenzimidazole sulfonic acid (Ensulizole), polysilicone- 15 (Parsol SLX), trolamine salicylate, Bemotrizinol (Tinosorb S), benzophenones 1-12, dioxybenzone, drometrizole trisiloxane (Mexoryl XL), iscotrizinol (Uvasorb HEB), octocrylene, oxybenzone (Eusolex 4360), sulisobenzone, bisoctrizole (Tinosorb M), titanium dioxide, zinc oxide, and the like.

[0098] Examples of retinoids include, but are not limited to, vitamin A, retinol, retinaldehyde, retinoic acid, retinyl palmitate, tretinoin, tazarotene, bexarotene and adapalene. In certain preferred embodiments, the retinoid is retinol. Nevertheless, in one or more embodiments, the composition is essentially free of retinoids or retinoid precursors; and in further embodiments, is free of retinoids or retinoid precursors.

[0099] Examples of antioxidants include, but are not limited to, water-soluble antioxidants such as sulfhydryl compounds and their derivatives (e.g., sodium metabisulfite and N-acetyl-cysteine, glutathione), lipoic acid and dihydrolipoic acid, stilbenoids such as resveratrol and derivatives, lactoferrin, and ascorbic acid and ascorbic acid derivatives (e.g., ascobyl-2-glucoside, ascorbyl palmitate and ascorbyl polypeptide). Oil-soluble antioxidants suitable for use in the compositions of this invention include, but are not limited to, butylated hydroxytoluene, retinoids (e.g., retinol and retinyl palmitate), tocopherols (e.g., tocopherol acetate), tocotrienols, and ubiquinone. Natural extracts containing antioxidants suitable for use in the compositions of this invention, include, but not limited to, extracts containing flavonoids and isoflavonoids and their derivatives (e.g., genistein and diadzein), extracts containing resveratrol and the like. Examples of such natural extracts include grape seed, green tea, pine bark, feverfew, parthenolide-free feverfew, oat extracts, pomelo extract, wheat germ extract, Hesperidin, Grape extract, Portulaca extract, Licochalcone, chaicone, 2,2 ’-dihydroxy chaicone, Primula extract, propolis, and the like.

[0100] The additional cosmetically active agent may be present in a composition in any suitable amount, for example, in an amount of from about 0.0001% to about 20% by weight of the composition, e.g., about 0.001% to about 10% such as about 0.01% to about 5%. In certain preferred embodiments, in an amount of 0.1% to 5% and in other preferred embodiments from 1% to 2%.

[0101] A variety of other materials may also be present in the compositions of the present invention. These include, for example, chelating agents, humectants, opacifiers, conditioners, preservatives, fragrances and the like. The compositions may include surfactants, for example, those selected from the group consisting of anionic, non-ionics, amphoteric, cationic, or a combination of two or more thereof.

[0102] The compositions of the present invention may also contain chelating agents (e.g., EDTA) and preservatives (e.g., parabens). Examples of suitable preservatives and chelating agents are listed in pp. 1626 and 1654-55 of the ICI Handbook. In addition, the compositions useful herein can contain conventional cosmetic adjuvants, such as colorants such as dyes and pigments, opacifiers (e.g., titanium dioxide), and fragrances.

[0103] In certain preferred embodiments, the present invention comprises applying a compound or composition of the invention via a substrate comprising such material. Any suitable substrate may be used in the present invention. Examples of suitable substrates and substrate materials are disclosed, for example, in U.S. Published Application Nos. 2005 / 022683 and 2009 / 0241242 which are incorporated herein by reference in their entirety. In certain preferred embodiments, the substrate is a wipe or a facial mask.

[0104] The composition and products containing such compositions of this invention may be prepared using methodology that is well known by an artisan of ordinary skill.

[0105] EXAMPLES

[0106] EXAMPLE 1: LEMON ASPEN AND ACETYL GLUCOSAMINE COMPOSITIONS Compositions were prepared by adding purified water to a suitable sized beaker. Mixing was started using a propeller mixing blade and the water was heated to 70-75°C. Acetyl glucosamine (NAG) was added when appropriate according to the tables below. Sepimax Zen™ was slowly added into the main batch and mixed until fully hydrated and free of visible particles, with the mixing speed increased as needed. Next, the glycerin was added and mixed until homogeneous. The mixture was reheated to 70-75°C, then chlorphenesin, emulsifier, dimethicones, and Sepiplus™ 400 were added one at a time and mixed until uniform and free of undissolved particles. The batch was cooled to below 40°C and then the phenoxyethanol and ethylhexylglycerin was added and mixed until uniform. Cooling continued to 25-30°C while the solution was mixed at moderate speed. Lemon aspen (LA) was added as appropriate per the tables below and mixed until homogeneous. Water was added q.s. and the pH was adjusted with sodium hydroxide. The solution was mixed until uniform and allowed to cool to room temperature. Acronychia Acidula Fruit Extract (30% extract in carrier) acquired from Southern Cross Botanicals Pty Ltd., Knockrow NSW, Australia. Acronychia Acidula Fruit extract as used in the examples typically contains between about 1% and 10% 3-(4-farnesyloxyphenyl)- propionic acid (FOPA) by weight of the active extract, with the tested extract containing about 1.11% 3-(4-farnesyloxyphenyl)-propionic acid by weight of the extract raw material (30% Acronychia Acidula Fruit extract in a mixture of water, butylated hydroxytoluene and polysorbate 20). This corresponds to a final concentration of 0.0167 wt. % FOPA in samples containing 0.5 wt.% Acronychia Acidula extract raw material and 0.0363 wt.% FOPA in samples containing 1 wt.% Acronychia Acidula extract raw material. The weight ratio of FOPA to NAG for Examples 5-8 corresponds 1:119.76, 1:239.52, 1:110.19, 1:55.10, respectively.

[0107] Comparative Examples:

[0108] . Mixture of Xiameter PMX-200 Silicone Fluid 50 cs; Xiameter PMX-1503 Fluid; Dows EL-9241 DM Si leone Elastomer Blend . Olivem 1000 MB . Equapell . 30% Lemon Aspen Extract in carrier (1.11 % FOPA) . Mixture of Sepiplus 400; Sepimax Zen

[0109] Inventive Examples

[0110] 1. Mixture of Xiameter PMX-200 Silicone Fluid 50 cs; Xiameter PMX-1503 Fluid.. Dowsil EL-9241 DM Silicone Elastomer Blend

[0111] 2. Olivem 1000 MB

[0112] 3. Equapell

[0113] 4. 30% Lemon Aspen Extract in carrier (1.1 1 % FOPA)

[0114] 5. Mixture of Sepiplus 400; Sepimax Zen

[0115] EXAMPLE 2: Bioactivity Assay of CRABP2, HBEGF, IL8, and HAS3 in Whole Tissue Human Skin Explants

[0116] Abdominal skin samples were obtained from human adults undergoing abdominoplasty surgery. Informed consent was obtained from each patient, and all experimental steps were approved by an institutional review board (IRB). Subcutaneous fat was carefully removed and skin biopsies of 10 mm diameter size were prepared under sterile conditions and acclimated in DMEM / F12 (1: 1) medium, 2% heat-inactivated fetal bovine serum, 10 pg / mL insulin, 10 ng / mL hydrocortisone, 10 ng / mL EGF, lx Antibiotic-Antimycotic (AB AM) under a 5% CO2 humidified atmosphere overnight. Skin explants were treated topically with 4p L of each formulation for 48 hours.

[0117] At the end of the 48h incubation, the skin biopsies were cut in half and either half of the skin biopsies or the two-halves were each lysed in 600 pL lysis buffer, consisting of 100 parts RLT buffer (RNA purification kit, sold under the tradename RNEASY Mini kit, Qiagen, Valencia, CA), to one part 2-mercaptoethanol inside a reinforced tube with screw cap and o-ring closure, and ceramic beads in the tube for tissue grinding (sold under the tradename PRECELLYS CKMix50-R, Bertin Corp, Rockville, MD). The tubes were shaken 40 seconds at 6300 rpm. RNA was extracted from the solutions using the RNEASY Mini Kit (Qiagen, Valencia, CA) according to manufacturer’s instructions and RNA was eluted in 25 pL RNase- free water.

[0118] Reverse transcription (RT) was performed using the Applied Biosystems High Capacity Reverse Transcription Kit (ThermoFisher Scientific, Bridgewater, NJ). Gene expression assays sold under the tradename TAQMAN for cellular retinoic acid binding protein 2 (CRABP2), heparin-binding epidermal growth factor (HbEGF), hyaluronic acid 15 synthase 3 (HAS3), interleukin-8 (IL8), TATA box binding protein (TBP), and master mix sold under the tradename BIORAD (BIORAD, Hercules, CA) . qPCR analysis was performed using the BIORAD iTaq universal probes supermix, and run on a real time PCR system sold under the tradename QUANTSTUDIO 7 Flex System (ThermoFisher Scientific, Bridgewater, NJ). The expression of these genes was normalized against the expression of the human TBP “housekeeping” genes. These “housekeeping” genes are widely used controls for normalizing specific gene expression levels because of their invariant expression across tissues, cells, and experimental treatments. The method for normalization involves measuring the expression of an internal reference or "housekeeping" gene, which takes into account the potential error of RNA / cDNA loading, and variation of reverse transcription efficiency. The fold changes were calculated in comparison to the untreated or vehicle controls and two-tailed two-sample Student t-tests (Microsoft Office Excel 2007; Microsoft, Redmond, WA, USA) were performed. Results are shown as Average Fold Change over Untreated.

[0119] CRABP2 Expression CRABP2 is well-established in literature as a highly sensitive marker of retinoid bioactivity and potency, and has been associated with conferring skin anti-aging benefits. As can be seen from the above results, Ex. 5 (0.5% LA and 2% NAG), Ex. 6 (0.5% LA and 4% NAG), Ex. 7 (1% LA and 2% NAG), and Ex. 8 (1% LA and 4% NAG) all had a statistically significant improvements over Ex. 1 placebo for CRABP2. Ex. 4 (4% NAG) did not result in an increase in CRABP2. Ex. 6 (0.5% LA and 4% NAG) surprisingly showed a synergistic increase in CRABP2.

[0120] HBEGF Expression

[0121] Heparin-binding epidermal growth factor (HbEGF) is associated with cell proliferation, one of the hallmarks of retinoid bioactivity. Accordingly, this data shows the inventive examples exhibit an increase of retinol-like property, and hence antiaging benefits. As can be seen from the above results, Ex. 6 (0.5% LA and 4% NAG) in particular surprisingly showed a synergistic improvement in HBEGF, and had a statistically significant improvement over Ex.2 (0.5% LA) and Ex. 4 (4% NAG) for HBEGF. Ex. 4 (4% NAG) did not result in an increase in HBEGF.

[0122] HAS3 Expression

[0123] HAS 3, also known as hyaluronic acid synthase 3, encodes for a protein involved in the synthesis of hyaluronic acid. Hyaluronic acid is associated with skin hydration and plumping. Skin plumpness confers antiaging or youthful appearance. Thus upregulation of this gene as seen in the results is also associated with anti-aging and other retinoid behavior. As can be seen from the above results, Ex. 5 (0.5% LA and 2% NAG), Ex. 6 (0.5% LA and 4% NAG), Ex. 7 (1% LA and 2% NAG), Ex. 8 (1% LA and 4% NAG) all had a statistically significant improvement over Ex. 1 placebo for HAS3. In particular, Ex. 6 (0.5% LA and 4% NAG) and Ex. 8 (1% LA and 4% NAG) showed a surprisingly synergistic improvement for HAS3. Additionally, Ex. 6 (0.5% LA and 4% NAG) and Ex. 8 (% LA and 4% NAG) showed statistically significant improvements over Ex. 4 (4% NAG) for HAS3.

[0124] IL8 Expression

[0125] IL-8, is an inflammatory mediator interleukin. Expression of the IL-8 gene is associated with increased inflammation. In general, IL-8 gene expression revealed no significant increases, suggesting that these combinations with enhanced benefits did not result in more irritation. Furthermore, Ex. 7 (1% LA and 2% NAG) and Ex. 8 (1% LA and 4% NAG) showed similar or less IL8 than even the placebo.

Claims

What is claimed is:

1. A skincare composition comprising: a. a compound of Formula I:wherein:Ri is selected from the group consisting of Ci - C20 alkyl, C2 - C20 alkenyl, C2 - C20 alkynyl, and C3 - C8cycloalkyl or aryl;R2 is selected from the group consisting of hydrogen, hydroxyl, Ci - Ce alkyl, C2 - Ce alkenyl, C2 - Ce alkynyl, C3 - C8cycloalkyl or aryl, -OCi - Ce alkyl, -OC2 - Ce alkenyl, - OC2 - C6alkynyl, -OC3 - C8cycloalkyl or aryl, thiol, -SCi - C6alkyl, -SC2 - C6alkenyl, -SC2 - Ce alkynyl, -SC3 - C8cycloalkyl or aryl, -NR4C1 - Ce alkyl, -NR4C2 - Ce alkenyl, -NR4C2 - Ce alkynyl, and -NR4C3 - C8cycloalkyl or aryl;R3 is selected from -CO2H, -CO2R4 or an isosteric equivalent of a carboxy group, wherein R is Ci - Ce alkyl, C2 - Ce alkenyl, C3 - C8cycloalkyl or aryl; and Y is -(CH2-CH2)-, -(CH=CH)-, or -(C=C)-; or a cosmetically acceptable salt thereof; and b. an N-acetyl compound selected from the group consisting of N-aldosamines, N- acetylated amino acids and combinations thereof.

2. The skincare composition of claim 1 , wherein Ri is selected from the group consisting of C5 - Cie alkyl, C5 - Cie alkenyl, and C5 - Cie alkynyl; R2 is selected from the group consisting of hydrogen, hydroxyl, -OCi - Ce alkyl, -OC2 - Ce alkenyl, -OC2 - Ce alkynyl, -OC3 - C8cycloalkyl; R3 is selected from -CO2H, -CO2R4 wherein R is Ci - Ce alkyl, or an isosteric equivalent of a carboxy group; and Y is -(CH2-CH2)- or -(CH=CH)-.

3. The skincare composition of claim 1 or 2, wherein Ri is selected from the group consisting of C5 - Cie alkenyl; and R2 is selected from the group consisting of hydrogen or -OCi - C3 alkyl.

4. The skincare composition of any of claims 1-3, wherein the compound of Formula I is selected from the group consisting of 3-(4-farnesyloxyphenyl)-propionic acid, 3-(4- farnesyloxy-3 -hydroxyphenyl)- propionic acid, 3-(4-farnesyloxy-3-methoxyphenyl)- propionic acid, ethyl esters thereof, and combinations of two or more thereof.

5. The skincare composition of any of claims 1-4, wherein the compound of Formula I comprises 3-(4-farnesyloxyphenyl)-propionic acid.

6. The skincare composition of any of claims 1-5, wherein the concentration of the compound of Formula I is present in an amount ranging from about 0.00001% to 10 %, by total weight of the composition.

7. The skincare composition of any of claims 1-6, wherein the skincare composition comprises a botanical extract comprising the compound of Formula I.

8. The skincare composition of any of claims 1-7, wherein the botanical extract comprises an extract of a plant of the genus Acronychia.

9. The skincare composition of any of claims 1-8, wherein said botanical extract is an extract of Acronychia acidida.

10. The skincare composition of any of claims 1-9, wherein the botanical extract is present in an amount ranging from about 0.00001% to about 5% by total weight of the composition.

11. The skincare composition of any of claims 1-10, wherein the N-acetyl compound comprises a derivative of an aminosugar.

12. The skincare composition of any of claims 1-11, wherein the derivative of an aminosugar is selected from the group consisting of N-acetyl-ribosamine, N-acetyl-arabinosamine, N- acetyl-glucosamine, N-acetyl-galactosamine and N-acetyl-mannosamine, and combinations thereof.

13. The skincare composition of any of claims 1-12, wherein the derivative of an aminosugar comprises N-acetyl-glucosamine.

14. The skincare composition of any of claims 1-13, further comprising an ingredient selected from the group consisting of surfactants, chelating agents, emollients, humectants, conditioners, preservatives, opacifiers, fragrances, and combinations of two or more thereof.

15. The skincare composition of any of claims 1-14, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquidwash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

16. The skincare composition of any of claims 1-15, wherein the compound of Formula I is comprises 3-(4-farnesyloxyphenyl)-propionic acid, and the N-acetyl compound comprises N-acetyl-glucosamine.

17. A method for treating skin comprising topically applying the composition of any of claims 1-16.

18. The method of claim 17, wherein the method is a method for treating signs of aging, treating acne, smoothing skin texture, or brightening the skin.

19. The method of claim 17 or 18, wherein the method is a method of increasing CRABP2 expression.

20. A skincare composition comprising: a. from about 0.001 wt.% to about 1 wt.% of 3-(4-farnesyloxyphenyl)-propionic acid by total weight of the composition; and b. a.from about 0.05 wt.% to about 6 wt.% of a derivative of an aminosugar is selected from the group consisting of N-acetyl-ribosamine, N-acetyl-arabinosamine, N- acetyl-glucosamine, N-acetyl-galactosamine and N-acetyl-mannosamine, and combinations thereof by total weight of the composition, wherein the composition is in the form of a solution, suspension, emulsion, lotion, cream, serum, gel, stick, spray, ointment, liquid wash, soap bar, shampoo, hair conditioner, paste, foam, powder, mousse, shaving cream, hydrogel, or film-forming product.

Images