Aromatic polyenic compounds and pharmaceutical/cosmetic compositions comprised thereof

Abstract

Novel pharmaceutically/cosmetically-active aromatic polyenic compounds have the structural formula (I): and are useful for the treatment of a wide variety of disease states, whether human or veterinary, for example dermatological, rheumatic, respiratory, cardiovascular, bone and ophthalmological disorders, as well as for the treatment of mammalian skin and hair conditions/disorders.

What is claimed is:  
     
       1. An aromatic polenic  polyenic compound having the structural formula (I):                    
       in which R 1  is a —CH 3  radical, a radical —CH 2 —O—R 9 , a radical —CH 2 —O—CO—R 10 , or a radical —CO—R 11 , wherein R 9 , R 10 , and R 11  are as defined below; R 2  is a hydrogen atom or a lower alkyl radical having 1 to 6 carbon atoms; R 3  is a hydrogen atom or a lower alkyl radical having 1 to 6 carbon atoms; R 5  is a hydrogen atom or a lower alkyl radical having 1 to 6 carbon atoms; R 7  and R 8  independently are each (i) a hydrogen atom, (ii) a linear or branched alkyl radical having from 1 to 20 carbon atoms, (iii) a cycloaliphatic radical selected from the group consisting of 1-methylcyclohexyl and 1-adamantyl, (iv) a radical —O—CH 2 —O—CH 2 —CH 2 —O—CH 3 , (v) a radical —O—R 13 , or (vi) a radical —S(O) n R 13 , wherein R 13  and n are as defined below, R 4  and R 6  together form, with the carbon atoms from which they depend and with the adjacent benzene ring, a naphthalene ring, and at least one of R 7  and R 8  has the above definition (ii) or (iii); R 9  is a hydrogen atom or a lower alkyl radical having 1 to 6 carbon atoms; R 10  is a lower alkyl radical having 1 to 6 carbon atoms; R 11  is (a) a hydrogen atom, (b) a lower alkyl radical having 1 to 6 carbon atoms, (c) a radical of formula:                    
       in which R′ and R″ independently are each a hydrogen atom, a lower alkyl radical having 1 to 6 carbon atoms, a mono- or polyhydroxyalkyl radical respectively having 2 to 3 carbon atoms or 3 to 6 carbon atoms containing 2 to 5 hydroxyl groups, or an optionally substituted phenyl radical which if substituted, is substituted with at least one halogen atom, hydroxyl or nitro group, or (d) a radical —OR 12 , wherein R 12  is a hydrogen atom, a linear or branched alkyl radical having from 1 to 20 carbon atoms, an alkenyl radical having 2 to 5 carbon atoms and at least one site of ethylenic unsaturation, a mono- or polyhydroxyalkyl radical respectively having 2 to 3 carbon atoms or 3 to 6 carbon atoms and 2 to 5 hydroxyl groups, or an optionally substituted phenyl or radical  benzyl radical or pheneyl  phenyl radical wherein, if substituted, are substituted by at least one halogen atom, hydroxyl or nitro functional group; R 13  is a hydrogen atom or a linear or branched alkyl radical having from 1 to 20 carbon atoms; and n is an integer equal to 0, 1 or 2; or a pharmaceutically/cosmetically acceptable salt or optical or geometric isomer thereof. 
     
     
       2. An aromatic polyenic compound as defined by  claim 1 , comprising a pharmaceutically acceptable salt thereof. 
     
     
       3. An aromatic polyenic compound as defined by  claim 1 , wherein formula (I), the lower alkyl radical substituents are selected from the group consisting of methyl, ethyl, isopropyl, butyl, tert-butyl and hexyl radicals. 
     
     
       4. An aromatic polyenic compound as defined by  claim 1 , wherein formula (I), the linear or branched alkyl radical substituents having from 1 to 20 carbon atoms are selected from the group consisting of methyl, ethyl, propyl, 2-ethylhexyl, octyl, dodecyl, hexadecyl and octadecyl radicals. 
     
     
       5. An aromatic polyenic compound as defied by  claim 1 , wherein formula (I), the monohydroxyalkyl radical substituents are selected from the group consisting of 2-hydroxypropyl and 3-hydroxypropyl radicals. 
     
     
       6. An aromatic polyenic compound as defined by  claim 1 , wherein formula (I), the polyhydroxyalkyl radical substituents are selected from the group consisting of 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl, 2,3,4,5-tetrahydroxypentyl and pentaerythritol radicals. 
     
     
       7. An aromatic polyenic compound selected from the group consisting of trans-7-[3-(1-adamantyl)-4-hydroxyphenyl]-3,7-dimethyl-2,4,6-heptatrienoic acid; ethyl trans-7-[3-(1-adamantyl)-4-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrienoate; trans-7-[-3-(1-adamantyl)-4-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrienoic acid; (2Z,4E,6E)-7-[3-(1-adamantyl)-4-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrienoic acid; trans-5-[-7-(1-adamantyl)-6-methoxyethoxymethoxy-2-naphthyl]-3-methyl-2,4,-pentadienoic acid; trans-5-[-7-(1-adamantyl)-6-hydroxy-2-naphthyl]-3-methyl-2,4-pentadienoic acid; trans-5-[-7-(1-adamantyl)-6-methoxy-2-naphthyl]-3-methyl-2,4-pentadienoic acid; trans-5-[-7-(1-adamantyl)-6-propyloxy-2-naphthyl]-3-methyl-2,4-pentadienoic acid; trans-7-[3-(1-methylcyclohexyl)-4-hydroxy-phenyl]-3,7-dimethyl]-2,4,6-heptatrienoic acid; (2Z,4E,6E)-7-[3-(1-methylcyclohexyl)-4-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrienoic acid; trans-7-[3-(1-adamantyl)-4-isopropyloxy-phenyl]-3,7-dimethyl-2,4,6-heptatrienoic acid; trans-7-[3-(1-adamantyl)-4-methoxyethoxymethoxyphenyl]-3,7-dimethyl-2,4,6-heptatrienoic acid; trans-7-[3-(1-adamantyl)-4-methoxyphenyl]-7-methyl-2,4,6-heptatrienoic acid; trans-7-[3-(1-adamantyl)-4-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrien-1-ol; trans-7-[3-(1-adamantyl)-4-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrien-1-al; trans-N-ethyl-7-[3-(1-adamantyl)-4-methoxy-phenyl]-3,7-dimethyl-2,4,6-heptatrienecarboxamide; trans-N-4-hydroxphenyl-7-[3-(1-adamantyl)-4-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrienecarboxamide; trans-7-(3-tert-butyl-4-methoxyethoxymethoxy-phenyl)-3,7-dimethyl-2,4,6-heptatrienoic acid; ethyl trans-7-(3-tert-butyl-4-hydroxyphenyl)-3,7-dimethyl-2,4,6-heptatrienoate; ethyl trans-7-(3-tert-butyl-4-methoxyphenyl)-3,7-dimethyl-2,4,6-heptatrienoate; and ethyl trans-7-[4-(1-adamantyl)-3-methoxyphenyl]-3,7-dimethyl-2,4,6-heptatrienoate. 
     
     
       8. An aromatic polyenic compound as defined by  claim 2 , which is an alkali or alkaline earth metal, zinc or amine salt. 
     
     
       9. An aromatic polyenic compound as defined by  claim 1 , wherein formula (I), at least one of the following definitions exist: 
       R 1  is a radical —CO—R 11 ; or  
       R 7  is the adamantyl radical.  
     
     
       10. A pharmaceutical composition of matter, comprising a therapeutically effective amount of an aromatic polyenic compound as defined by  claim 1 , or pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       11. The pharmaceutical composition as defined by  claim 10 , further comprising a retinoid compound, a D vitamin, a corticosteroid, an anti-free radical agent, an α-hydroxy or α-keto acid as ion channel blocker, or combination thereof. 
     
     
       12. The pharmaceutical composition as defined by  claim 10 , selected from the group consisting of a tablet, a capsule, a syrup, a dragee, a suspension, an elixir, a solution, a powder, granules, an emulsion , microspheres, nanospheres, lipid vesicles, polymeric vesicles, and a composition for injection. 
     
     
       13. The pharmaceutical composition as defined by  claim 10 , selected from the group consisting of an ointment, a cream, a milk, a salve, an impregnated pad, a gel, a spray, or a lotion. 
     
     
       14. The pharmaceutical composition as defined by  claim 10 , for topical administration. 
     
     
       15. The pharmaceutical composition as defined by  claim 10 , for systemic administration. 
     
     
       16. The pharmaceutical composition as defined by  claim 10 , comprising from 0.001% to 5% by weight of said aromatic polyenic compound, or salt or isomer thereof. 
     
     
       17. A cosmetic composition of matter, comprising a cosmetically effective amount of an aromatic polyenic compound as defined by  claim 1 , or cosmetically acceptable salt or isomer thereof, and a commercially acceptable vehicle, carrier or diluent therefor. 
     
     
       18. The cosmetic composition as defined by  claim 17 , which is selected from the group consisting of a cream, a milk, a lotion, a gel, an ointment, microspheres, nanospheres, lipid vesicles, polymeric vesicles, a soap, and a shampoo. 
     
     
       19. The cosmetic composition as defined by  claim 17 , comprising from 0.001% to 3% by weight of said aromatic polyenic compound, or salt or isomer thereof. 
     
     
       20. The cosmetic composition as defined by  claim 17 , further comprising a compound selected from the group consisting of retinoid compound, a D vitamin a corticosteroid, an anti-free radical agent, an α-hydroxy or α-keto acid an ion channel blocker, and combinations thereof. 
     
     
       21. The pharmaceutical composition as defined by  claim 10 , further comprising a compound selected from the group consisting of a wetting agent, a depigmenting agent, a moisturizing agent, an emollient, an antiseborrhoeic or anti-acne agent, an antibiotic, an antifungal agent, a hair regrowth promoter, a non-steroidal anti-inflammatory agent, a carotenoid, an anti-psoriatic agent, 5,8,11,14-eicosatetraynoic or 5,8,11-eicosatrynoic acid or ester or amide thereof, and combinations thereof. 
     
     
       22. The pharmaceutical composition as defined by  claim 10 , further comprising a compound selected from the group consisting of a taste- or flavor-enhancing agent, a preservative, a stabilizer, a moisture regulating agent, a pH regulating agent, an osmotic pressure modifying agent, an emulsifying agent, a UV-A or UV-B screening agent, an antioxidant, and combinations thereof. 
     
     
       23. The cosmetic composition by  claim 17 , further comprising a compound selected from the group consisting of a wetting agent, a depigmenting agent, a moisturizing gent, an emollient, an antiseborrhoeic or antiacne agent, an antibiotic, an antifungal agent, a hair regrowth promoter, a non-steroidal anti-inflammatory agent, a carotenoid, an anti-psoriatic agent, 5,8,11,14-eicosatetraynoic or 5,8,11-eicosatrynoic acid or ester or amide thereof, and combinations thereof. 
     
     
       24. The cosmetic composition as defined by  claim 17  further comprising a compound selected from the group consisting of a taste- or flavor-enhancing agent, a preservative, a stabilizer, a moisture regulating agent, a pH regulating agent, an osmotic pressure modifying agent, an emulsifying agent, a UV-A or UV-B screening agent, an antioxidant, and combinations thereof. 
     
     
       25. An aromatic polyenic compound having the structural formula ( I ) :                     
         in which R   1    is a —CH   3    radical, a radical —CH   2   —O—R   9   , a radical —CH   2   —O—CO—R   10   , or a radical —CO—R   11   , wherein R   9   , R   10   , and R   11    are as defined below; R   2    is a hydrogen atom or a lower alkyl radical; R   3    is a hydrogen atom or a lower alkyl radical; R   4  is a hydrogen atom; R 5    is a hydrogen atom or a lower alkyl radical; R   6    is a hydrogen atom, a linear or branched alkyl radical having from  1  to  20  carbon atoms, a radical —O—CH   2   —O—CH   2   —CH   2   —O—C   3    or a radical —O—R   13   , wherein R   13    is as defined below; R   7    and R   8    independently are each  ( i )  a hydrogen atom,  ( ii )  a linear or branched alkyl radical having from  1  to  20  carbon atoms,  ( iii )  a cycloaliphatic radical,  ( iv )  a radical —O—CH   2   —O—CH   2   —CH   2   —O—CH   3   ,  ( v )  a radical —O—R   13   , or  ( vi )  a radical —S ( O ) n   R   13   , wherein R   13    and n are as defined below, and at least one of R   7    and R   8    has the above definition  ( ii )  or  ( iii ) ; R   9    is a hydrogen atom or a lower alkyl radical; R   10    is a lower alkyl radical; R   11    is  ( a )  a hydrogen atom,  ( b )  a lower alkyl radical, or  ( c )  a radical of formula:                     
         in which R′ and R″ independently are each a hydrogen atom, a lower alkyl radical, a mono -  or polyhydroxyalkyl radical, or an optionally substituted phenyl radical, or  ( d )  a radical —OR   12   , wherein R   12    is a hydrogen atom, a linear or branched alkyl radical having from  1  to  20  carbon atoms, an alkenyl radical, a mono -  or polyhydroxyalkyl radical, or an optionally substituted aryl or aralkyl radical; R   13    is a hydrogen atom or a linear or branched alkyl radical having from  1  to  20  carbon atoms; and n is an integer equal to  0 ,  1  or  2 ; or a pharmaceutically/cosmetically acceptable salt or optical or geometric isomer thereof.   
     
     
       26. An aromatic polyenic compound as defined by  claim 25 , comprising a pharmaceutically acceptable salt thereof. 
     
     
       27. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , the lower alkyl radical substituents are selected from the group consisting of methyl, ethyl, isopropyl, butyl, tert - butyl and hexyl radicals.   
     
     
       28. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , the linear or branched alkyl radical substituents having from  1  to  20  carbon atoms are selected from the group consisting of methyl, ethyl, propyl,  2   - ethylhexyl, octyl, dodecyl, hexadecyl and octadecyl radicals.   
     
     
       29. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , the monohydroxyalkyl radical substituents are selected from the group consisting of  2   - hydroxypropyl and  3   - hydroxypropyl radicals.   
     
     
       30. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , the polyhydroxyalkyl radical substituents are selected from the group consisting of  2 , 3   - dihydroxypropyl,  2 , 3 , 4   - trihydroxybutyl,  2 , 3 , 4 , 5   - tetrahydroxypentyl and pentaerythritol radicals.   
     
     
       31. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , the aryl radical substituents are selected from the group consisting of phenyl radicals optionally substituted by at least one halogen atom, or a hydroxyl or nitro functional group.   
     
     
       32. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , the aralkyl radical substituents are selected from the group consisting of benzyl and phenethyl radicals optionally substituted by at least one halogen atom, or a hydroxyl or nitro functional group.   
     
     
       33. An aromatic polyenic compound as defined by  claim 25 , wherein formula ( I ) , the alkenyl radical substituents have from  2  to  5  carbon atoms.   
     
     
       34. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , the cycloaliphatic radical substituents are selected from the group consisting of  1   - methylcyclohexyl and  1   - adamantyl radicals.   
     
     
       35. An aromatic polyenic compound as defined by  claim 26 , which in selected from the group consisting of an alkali or alkaline earth metal, zinc or amine salt. 
     
     
       36. An aromatic polyenic compound as defined by  claim 25 , where in formula ( I ) , at least one of the following definitions is satisfied:    
       
         R 
         1  
         is a radical —CO—R 
         11 
         ;  
       
       
         R 
         7  
         is the adamantyl radical; and  
       
       
         R 
         6  
         is a hydrogen atom or a linear or branched alkyl radical having from  1  to  20  carbon atoms. 
       
     
     
       37. A pharmaceutical composition of matter, comprising a therapeutically effective amount of an aromatic polyenic compound as defined by  claim 25 , or pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       38. The pharmaceutical composition as defined by  claim 37 , further comprising a compound selected from the group consisting of a retinoid compound, a D vitamin, a corticosteroid, an anti- free radical agent, an α - hydroxy or α - keto acid, an ion channel blocker, and combinations thereof.   
     
     
       39. The pharmaceutical composition as defined by  claim 37 , which is in a pharmaceutically acceptable form selected from the group consisting of a tablet, a capsule, a syrup, a dragee, a suspension, an elixir, a solution, a powder, granule, an emulsion, microsphere, nanosphere, lipid vesicle, polymeric vesicle, and an injectable composition. 
     
     
       40. The pharmaceutical composition as defined by  claim 37 , which is in a pharmaceutically acceptable form selected from the group consisting of an ointment, a cream, a milk, a salve, an impregnated pad, a gel, a spray, and a lotion. 
     
     
       41. The pharmaceutical composition as defined by  claim 37 , which is suitable for topical administration. 
     
     
       42. The pharmaceutical composition as defined by  claim 37 , which is suitable for systemic administration. 
     
     
       43. The pharmaceutical composition as defined by  claim 37 , comprising from  0 . 001 %  to  5   %  by weight of said aromatic polyenic compound, or salt or isomer thereof.   
     
     
       44. A cosmetic composition of matter, comprising a cosmetically effective amount of an aromatic polyenic compound as defined by  claim 25 , or cosmetically acceptable salt or isomer thereof, and a cosmetically acceptable vehicle, carrier or diluent therefor. 
     
     
       45. The cosmetic composition as defined by  claim 44 , which is in a cosmetically acceptable form selected from the group consisting of a cream, a milk, a lotion, a gel, an ointment, microsphere, nanosphere, lipid vesicle, polymeric vesicle, a soap, or a shampoo. 
     
     
       46. The cosmetic composition as defined by  claim 44 , comprising from  0 . 001 %  to  3   %  by weight of said aromatic polyenic compound, or salt or isomer thereof.   
     
     
       47. The cosmetic composition as defined by  claim 44 , further comprising a compound selected from the group consisting of a retinoid compound, a D vitamin, a corticosteroid, an anti- free radical agent, an α - hydroxy or α - keto acid or derivative thereof, an ion channel blocker, and combinations thereof.   
     
     
       48. The pharmaceutical composition as defined by  claim 37 , further comprising an additional compound selected from the group consisting of a wetting agent, a depigmenting agent, a moisturizing agent, an emollient, an antiseborrhoeic or antiacne agent, an antibiotic, an antifungal agent, a hair regrowth promoter, a non- steroidal anti - inflammatory agent, a carotenoid, an anti - psoriatic agent,  5 , 8 , 11 , 14   - eicosatetraynoic or  5 , 8 , 11   - eicosatrynoic acid or ester or amide thereof, and combinations thereof.   
     
     
       49. The pharmaceutical composition as defined by  claim 37 , further comprising an additional compound selected from the group consisting of a taste-  or flavor - enhancing agent, a preservative, a stabilizer, a moisture regulating agent, a pH regulating agent, an osmotic pressure modifying agent, an emulsifying agent, a UV - A or UV - B screening agent, an antioxidant, and combinations thereof.   
     
     
       50. The cosmetic composition by  claim 44 , further comprising an additional compound selected from the group consisting of a wetting agent, a depigmenting agent, a moisturizing gent, an emollient, an antiseborrhoeic or antiacne agent, an antibiotic, an antifungal agent, a hair regrowth promoter, a non- steroidal anti - inflammatory agent, a carotenoid, an anti - psoriatic agent,  5 , 8 , 11 , 14   - eicosatetraynoic or  5 , 8 , 11   - eicosatrynoic acid or an ester or an amide thereof, and combinations thereof.   
     
     
       51. The cosmetic composition as defined by  claim 44 , further comprising an additional compound selected from the group consisting of a taste-  or flavor - enhancing agent, a preservative, a stabilizer, a moisture regulating agent, a pH regulating agent, an osmotic pressure modifying agent, an emulsifying agent, a UV - A or UV - B screening agent, an antioxidant, and combinations thereof.   
     
     
       52. The aromatic polyenic compound of  claim 25 , wherein R 6    is hydrogen.   
     
     
       53. The aromatic polyenic compound of  claim 25 , wherein R 6    is a linear or branched alkyl radical having  1  to  20  carbon atoms.   
     
     
       54. The aromatic polyenic compound of  claim 25 , wherein R 6    is a radical —O—C   2   —O—CH   2   —CH   2   —O—CH   3   .   
     
     
       55. The aromatic polyenic compound of  claim 25 , wherein R 6    is an —O—R   13    radical, wherein R   13    is hydrogen or a linear or branched alkyl radical having  1  to  20  carbon atoms.   
     
     
       56. The aromatic polyenic compound of  claim 53 , wherein said linear or branched alkyl radical having  1  to  20  carbon atoms is selected from the group consisting of methyl, ethyl, propyl,  2 - ethylhexyl, octyl, dodecyl, hexadecyl, and octadecyl radicals.   
     
     
       57. The aromatic polyenic compound of  claim 55 , wherein R 13    is selected from the group consisting of methyl, ethyl, propyl,  2   - ethylhexyl, octyl, dodecyl, hexadecyl, and octadecyl radicals.   
     
     
       58. A pharmaceutical composition containing a pharmaceutically effective amount of a compound according to  claim 52 , or a pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       59. A pharmaceutical composition containing a pharmaceutically effective amount of a compound according to  claim 53 , or a pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       60. A pharmaceutical composition containing a pharmaceutically effective amount of a compound according to  claim 54 , or a pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       61. A pharmaceutical composition containing a pharmaceutically effective amount of a compound according to  claim 55 , or a pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       62. A pharmaceutical composition containing a pharmaceutically effective amount of a compound according to  claim 56 , or a pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       63. A pharmaceutical composition containing a pharmaceutically effective amount of a compound according to  claim 57 , or a pharmaceutically acceptable salt or isomer thereof, and a pharmaceutically acceptable vehicle, carrier or diluent therefor. 
     
     
       64. A cosmetic composition containing a cosmetically effective amount of a compound according to  claim 52 , or a pharmaceutically acceptable salt or isomer thereof, and a cosmetically acceptable vehicle, carrier or diluent therefor. 
     
     
       65. A cosmetic composition containing a cosmetically effective amount of a compound according to  claim 53 , or a pharmaceutically acceptable salt or isomer thereof, and a cosmetically acceptable vehicle, carrier or diluent therefor. 
     
     
       66. A cosmetic composition containing a cosmetically effective amount of a compound according to  claim 54 , or a pharmaceutically acceptable salt or isomer thereof, and a cosmetically acceptable vehicle, carrier or diluent therefor. 
     
     
       67. A cosmetic composition containing a cosmetically effective amount of a compound according to  claim 55 , or a pharmaceutically acceptable salt or isomer thereof, and a cosmetically acceptable vehicle, carrier or diluent therefor. 
     
     
       68. A cosmetic composition containing a cosmetically effective amount of a compound according to  claim 56 , or a pharmaceutically acceptable salt or isomer thereof, and a cosmetically acceptable vehicle, carrier or diluent therefor. 
     
     
       69. A cosmetic composition containing a cosmetically effective amount of a compound according to  claim 57 , or a pharmaceutically acceptable salt or isomer thereof, and a cosmetically acceptable vehicle, carrier or diluent therefor.