Cosmetic compositions containing quinones and their topical use on skin and hair

Abstract

Described are compositions containing quinones that show activity in enhance DNA repair and/or prevent damage to DNA and/or upregulate genes associated with wound healing. The quinones are thymoquinone, lapachol, myrtucommulone C, or mixtures thereof, and can be formulated into cosmetic compositions for topical administration to a subject in need thereof. The cosmetic compositions can also include sunscreens, surfactants, sunless tanning agents, desquamation agents, antiperspirants, colorants, preservatives and mixtures; and a cosmetically acceptable carrier. The compositions should find use in methods for treating the signs of ageing in mammals, dermatitis and wound healing via topical application to a site in need thereof, such as the skin or hair of the mammals or a wound site.

1 . A cosmetic composition comprising:
 a) a quinone having the structural formula:   
       
         
           
           
               
               
           
         
       
       or mixtures thereof, in amounts ranging from 0.001% to 50% by weight of the composition;
 b) a cosmetic functioning component selected from the group consisting of sunscreens, surfactants, sunless tanning agents, desquamation agents, antiperspirants, colorants, preservatives and mixtures thereof in amounts ranging from 0.0001% to 50% by weight of the composition; and 
 c) a cosmetically acceptable carrier; 
 wherein R1, R2, R3, R4, R5, R6, R7, and R8 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, unsubstituted C2-C10 alkenyl, substituted C2-C10 alkenyl, hydroxyl, thiol, halogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic; and 
 wherein R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, and R23 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, hydroxyl, ═O, substituted C1-C10 carbonyl, or unsubstituted C1-C10 carbonyl, thiol, halogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic. 
 
     
     
         2 . The cosmetic composition of  claim 1 , wherein:
 (a) R1, R2, R3, R4, R5, R6, R7, and R8 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, unsubstituted C2-C10 alkenyl, or substituted C2-C10 alkenyl; and   wherein R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, and R23 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, hydroxyl, ═O, substituted C1-C10 carbonyl, or unsubstituted C1-C10 carbonyl;   (b) for Formula I, R2 and R4 are each hydrogen;   (c) wherein for Formula II, R5, R6, R7, and R8 are independently hydrogen, C1-C10 alkyl, or substituted C1-C10 alkyl; and/or   (d) for Formula III, R9 is substituted C1-C10 carbonyl.   
     
     
         3 . (canceled) 
     
     
         4 . The cosmetic composition of  claim 32 , wherein for Formula I, R1 and R3 are independently unsubstituted C1-C10 alkyl, or substituted C1-C10 alkyl; and optionally, wherein for Formula I, R1 is substituted C1-C5 alkyl; R3 is methyl, and R2 and R4 are each hydrogen. 
     
     
         5 . (canceled) 
     
     
         6 . The cosmetic composition of  claim 4 , wherein Formula I is 
       
         
           
           
               
               
           
         
       
     
     
         7 . (canceled) 
     
     
         8 . The cosmetic composition of  claim 7 , wherein: (a) for Formula II, R5, R6, R7, and R8 are hydrogene; (b) wherein for Formula II, R1 and R2 are independently unsubstituted C2-C10 alkenyl, substituted C2-C10 alkenyl, C1-C10 alkyl, substituted C1-C10 alkyl, or hydroxyl; and/or (c) for Formula II, R1 and R2 are independently unsubstituted C2-C10 alkenyl, substituted C2-C10 alkenyl, or hydroxyl. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The cosmetic composition of  claim 8 , wherein for Formula II, R1 is substituted C2-C10 alkenyl, and R2 is hydroxyl. 
     
     
         12 . The cosmetic composition of  claim 11 , wherein Formula II is 
       
         
           
           
               
               
           
         
       
     
     
         13 . (canceled) 
     
     
         14 . The cosmetic composition of  claim 2 , wherein for Formula III, R10 is hydroxyl. 
     
     
         15 . The cosmetic composition of  claim 14 , wherein for Formula III, X is carbon (C) or CH, Y is carbon (C), Z is hydroxyl, the dashed line between X and Y is a bond, and the dashed line between Y and Z is absent. 
     
     
         16 . The cosmetic composition of  claim 15 , wherein for Formula III,
 (a) R17 is hydroxyl;   (b) R11, R12, R13, R14, R15, R16, R18, R19, R20, R21, R22, and R23 are independently hydrogen, substituted C1-C10 alkyl, or unsubstituted C1-C10 alkyl;   (c) R11, R12, R13, R14, R20, R21, R22, and R23 are unsubstituted C1-C10 alkyl; and R15, R16, R18, and R19 are independently hydrogen or substituted C1-C10 alkyl;   (d) R11, R12, R13, R14, R20, R21, R22, and R23 are unsubstituted C1-C5 alkyl; and R15 and R18 are hydrogen, R16 and R19 are substituted C1-C5 alkyl; and/or   (e) R11, R12, R13, R14, R20, R21, R22, and R23 are methyl; R15 and R18 are hydrogen.   
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . The cosmetic composition of  claim 16 , wherein for Formula III, R11, R12, R13, R14, R20, R21, R22, and R23 are methyl; R15 and R18 are hydrogen. 
     
     
         21 . The cosmetic composition of  claim 20 , wherein for Formula III, R16 and R19 are isopropyl. 
     
     
         22 . The cosmetic composition of  claim 11 , wherein Formula III is 
       
         
           
           
               
               
           
         
       
     
     
         23 . The cosmetic composition of 1, wherein UV irradiated samples of the quinone or cosmetic composition formulated with the quinone exhibit, in testing against a CUL4A bio target, a reduction in DNA damage relative to a UV irradiated control of at least 10%, as measured by % cyclobutane pyrimidine dimer (CPD) formed in a test cell. 
     
     
         24 . The cosmetic composition according to  claim 1 , wherein:
 (a) the sunscreens are selected from the group consisting of 2-ethylhexyl p-methoxycinnamate, 4,4′-t-butyl methoxydibenzoylmethane, octylsalicylate, tetraphthalylidene dicamphor sulfonic acid, benzophenone-3, microfine titanium dioxide, microfine zinc oxide and mixtures thereof;   (b) the surfactants are selected from the group selected consisting of anionic, nonionic, cationic, and amphoteric type;   (c) the sunless tanning agents are dihydroxy acetone;   (c) the desquamation agents are selected from the group consisting of glycolic acid, lactic acid, salicylic acid, retinoic acid, retinol and mixtures thereof, and including salt forms thereof;   (d) the antiperspirants are selected from the group consisting of metal sails of aluminum, zinc, zirconium and zirconium aluminum mixtures of sulfates, chlorides, chlorohydroxides, tetrachlorohydrex glycinates, alums, formates, lactates, benzyl sulfonates, succinates, and phenol sulfonates;   (e) the colorants are selected from pigments and dyes; and/or   (f) the preservatives are selected from the group consisting of methylchloroisothiazolinone and methylisothiazolinone combinations, phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroacetate and benzyl alcohol.   
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A method for treating a site in need thereof in mammals selected from the group consisting of aging skin, dermatitis and a wound site, comprising topically applying to the skin or hair of the mammals a cosmetic composition comprising a quinone having the structural formula: 
       
         
           
           
               
               
           
         
       
       or mixtures thereof in amounts ranging from 0.001% to 10% by weight of the cosmetic composition,
 wherein R1, R2, R3, R4, R5, R6, R7, and R8 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, unsubstituted C2-C10 alkenyl, substituted C2-C10 alkenyl, hydroxyl, thiol, halogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic; and 
 wherein R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, and R23 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, hydroxyl, ═O, substituted C1-C10 carbonyl, or unsubstituted C1-C10 carbonyl, thiol, halogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic, 
 wherein the composition is effective to: 
 (a) inhibit cullin 4 A (CUL4A) ubiquitin ligase, 
 (b) upregulate expression of one or more genes selected from the group consisting of interleukin-6 (IL-6), fibroblast growth factor (FGF), GPHR, ADAM17 and VEGF; 
 (c) down regulate expression of Smad3 or 
 (d) combinations thereof. 
 
     
     
         32 . The method according to  claim 31  wherein the skin shows signs of ageing selected from the group consisting of fine lines and wrinkles; lack of skin firmness; reduction of skin luminescence; lack of skin smoothness; lack of skin elasticity; formation of age spots; blotching; sallowness; uneven pigmentation; spider veins; thinning and loss of hair; lack of hair lustre or shine; and hair with split ends. 
     
     
         33 . A method of enhancing DNA repair, the method comprising contacting DNA with a composition comprising a quinone having the structural formula: 
       
         
           
           
               
               
           
         
       
       or mixtures thereof,
 wherein the quinone is present in amounts ranging from 0.001% to 50% by weight of the composition; 
 wherein R1, R2, R3, R4, R5, R6, R7, and R8 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, unsubstituted C2-C10 alkenyl, substituted C2-C10 alkenyl, hydroxyl, thiol, halogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic; and 
 wherein R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, and R23 are independently hydrogen, unsubstituted C1-C10 alkyl, substituted C1-C10 alkyl, hydroxyl, ═O, substituted C1-C10 carbonyl, or unsubstituted C1-C10 carbonyl, thiol, halogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic. 
 
     
     
         34 . The method of  claim 31 , wherein site selected from the group consisting of a cut, burn, skin ulcer, sore, dermatitis and diabetic ulcer. 
     
     
         35 . The method of  claim 31  wherein the composition comprises 
       
         
           
           
               
               
           
         
       
     
     
         36 . The method of  claim 31  wherein myrtucummolone c is present between a, 40%:60% and a 60% to 40% mixture the diastereomers.