6-substituted pyrimidine 3-oxides for promoting pigmentation of the skin/hair

Abstract

Pigmentation of human skin and/or hair is promoted by administering to individuals in need of such treatment, advantageously topically, an effective tyrosinase activity-stimulating amount of at least one 6-substituted pyrimidine 3-oxide having the structural formula (I): in which R 1 and R 2 , which may be identical or different, are each a hydrogen atom or a C 1 -C 12 alkyl radical; and R 3 and R 4 , which may be identical or different, are each a C 1 -C 12 alkyl radical or, when taken together, form a heterocycle with the nitrogen atom from which they depend, with the proviso that, when R 3 and R 4 , taken together, form a piperidino ring, then at least one of the radicals R 1 or R 2 must be other than a hydrogen atom.

What is claimed is:  
     
         1 . A regimen for promoting pigmentation of the skin and/or hair, comprising administering to an individual in need of such treatment an effective tyrosinase activity-stimulating amount of at least one 6-substituted pyrimidine 3-oxide having the structural formula (I):  
       
         
           
           
               
               
           
         
       
       in which R 1  and R 2 , which may be identical or different, are each a hydrogen atom or a C 1 -C 12  alkyl radical; and R 3  and R 4 , which may be identical or different, are each a C 1 -C 12  alkyl radical or, when taken together, form a heterocycle with the nitrogen atom from which they depend, with the proviso that, when R 3  and R 4 , taken together, form a piperidino ring, then at least one of the radicals R 1  or R 2  must be other than a hydrogen atom.  
     
     
         2 . The regimen as defined by  claim 1 , comprising topically administering said at least one 6-substituted pyrimidine 3-oxide.  
     
     
         3 . The regimen as defined by  claim 1 , comprising systemically administering said at least one 6-substituted pyrimidine 3-oxide.  
     
     
         4 . The regimen as defined by  claim 1 , said at least one 6-substituted pyrimidine 3-oxide comprising 
 2,4-bis-methylamino-6-dimethylaminopyrimidine 3-oxide,    2,4-bis-ethylamino-6-dimethylaminopyrimidine 3-oxide,    2,4-bis-propylamino-6-dimethylaminopyrimidine 3-oxide,    2,4-bis-propylamino-6-piperidinopyrimidine 3-oxide,    2-amino-4-methylamino-6-piperidinopyrimidine 3-oxide,    2-amino-4-propylamino-6-piperidinopyrimidine 3-oxide,    2-amino-4-hexylamino-6-piperidinopyrimidine 3-oxide,    2-amino-4-benzylamino-6-piperidinopyrimidine 3-oxide,    2-amino-4-(2-hydroxyethylamino)-6-piperidinopyrimidine    3-oxide, 2-amino-4-propylamino-6-dimethylaminopyrimidine    3-oxide, 2-amino-4-butylamino-6-dimethylaminopyrimidine    3-oxide, or 2-amino-4-isopropylamino-6-dimethylaminopyrimidine 3-oxide.    
     
     
         5 . The regimen as defined by  claim 1 , said at least one 6-substituted pyrimidine 3-oxide comprising 
 2-amino-4-propylamino-6-dimethylaminopyrimidine 3-oxide,    2-amino-4-methylamino-6-piperidinopyrimidine 3-oxide,    2,4-bis-propylamino-6-dimethylaminopyrimidine 3-oxide,    2,4-bis-propylamino-6-piperidinopyrimidine 3-oxide,    2,4-bis-methylamino-6-dimethylaminopyrimidine 3-oxide,    or 2,4-bis-ethylamino-6-dimethylaminopyrimidine 3-oxide.    
     
     
         6 . The regimen as defined by  claim 1 , comprising coadministering to said individual at least one substrate of at least one enzyme exhibiting tyrosinase activity.  
     
     
         7 . The regimen as defined by  claim 6 , said at least one substrate comprising tyrosine or derivative thereof, or 3,4-dihydroxy-α-phenylalanine (DOPA).  
     
     
         8 . A cosmetic/pharmaceutical composition of matter suited for promoting pigmentation of the skin and/or hair, comprising an effective tyrosinase activity-stimulating amount of at least one 6-substituted pyrimidine 3-oxide having the structural formula (I):  
       
         
           
           
               
               
           
         
       
       in which R 1  and R 2 , which may be identical or different, are each a hydrogen atom or a C 1 -C 12  alkyl radical; and R 3  and R 4 , which may be identical or different, are each a C 1 -C 12  alkyl radical or, when taken together, form a heterocycle with the nitrogen atom from which they depend, with the proviso that, when R 3  and R 4 , taken together, form a piperidino ring, then at least one of the radicals R 1  or R 2  must be other than a hydrogen atom, formulated into a cosmetically/pharmaceutically acceptable vehicle, diluent or carrier therefor.  
     
     
         9 . The cosmetic/pharmaceutical composition as defined by  claim 8 , further comprising at least one substrate of at least one enzyme exhibiting tyrosinase activity.  
     
     
         10 . The cosmetic/pharmaceutical composition as defined by  claim 9 , said at least one substrate comprising tyrosinase or derivative thereof, or 3,4-dihydroxy-α-phenylalanine.  
     
     
         11 . The cosmetic/pharmaceutical composition as defined by  claim 8 , comprising from 0.01% to 20% by weight of said at least one 6-substituted pyrimidine 3-oxide.  
     
     
         12 . The cosmetic/pharmaceutical composition as defined by  claim 11 , comprising from 0.1% to 10% by weight of said at least one 6-substituted pyrimidine 3-oxide.  
     
     
         13 . The cosmetic/pharmaceutical composition as defined by  claim 8 , comprising from 1% to 30% by weight of said at least one 6-substituted pyrimidine 3-oxide.  
     
     
         14 . The cosmetic/pharmaceutical composition as defined by  claim 13 , comprising from 2% to 15% by weight of said at least one 6-substituted pyrimidine 3-oxide.  
     
     
         15 . The cosmetic/pharmaceutical composition as defined by  claim 8 , comprising a solution, dispersion, lotion, serum, emulsion, milk, cream, gel, microcapsules, microparticles, vesicle dispersion, mousse, aerosol, shampoo, dyeing formulation, permanent-wave, syrup, granules, tablets or soap.  
     
     
         16 . The cosmetic/pharmaceutical composition as defined by  claim 8 , further comprising an oil, wax, emulsifier and/or co-emulsifier.  
     
     
         17 . The cosmetic/pharmaceutical composition as defined by  claim 8 , further comprising at least one active agent selected from among antibacterial agents, antiparasitic agents, antifungal agents, antiviral agents, anti-inflammatory agents, antipruriginous agents, anaesthetics, keratolytic agents, anti-free-radical agents, antiseborrhoeic agents, antidandruff agents, antiacne agents and/or agents for reducing skin differentiation and/or proliferation and/or pigmentation, and extracts of plant or bacterial origin.  
     
     
         18 . The cosmetic/pharmaceutical composition as defined by  claim 8 , further comprising at least one active agent promoting regrowth and/or retarding loss of hair, and/or at least one active agent decreasing differentiation and/or proliferation.  
     
     
         19 . The cosmetic/pharmaceutical composition as defined by  claim 8 , further comprising at least one hydrophilic or lipophilic gelling agent, hydrophilic or lipophilic additive, preservative, antioxidant, solvent, fragrance, filler, UV-screening agent, odor absorber or colorant or dyestuff.  
     
     
         20 . A kit comprising at least two separate compartments, at least one of which comprising at least one 6-substituted pyrimidine 3-oxide as defined in  claim 1 , and at least one of which comprising at least one substrate of at least one enzyme exhibiting tyrosinase activity.