Compositions and methods of treating abnormal cell proliferation

Abstract

A composition is described comprising a vitamin D analog and a retinoid wherein: (a) the vitamin D analog is capable of binding a vitamin D receptor or being converted in vivo into a compound capable of binding a vitamin D receptor; and (b) the retinoid is selected from the group consisting of retinol in a concentration of at least about 1.0%, a compound in a concentration of at least about 1.0% capable of being converted in vivo into retinol, and a retinoid characterized by having a substitution at the 4-position. Further, methods of treating disorders characterized by abnormal cell-proliferation and/or cell-differentiation are also described.

What is claimed is:  
     
         1 . A method of restoring the natural color of gray hair comprising applying to a scalp with gray hair either simultaneously or at different times: 
 (a) a vitamin D analog capable of binding a vitamin D receptor or being converted in vivo into a compound capable of binding a vitamin D receptor; and    (b) a retinoid selected from the group consisting of retinoid D with an alcohol CH 2 OH terminal side chain, an ester of retinoid D having an ester bond, an ether of retinoid D having an ether bond, and retinoid D where the alcohol CH 2 OH terminal side chain is replaced with an aldehyde CHO terminal side chain, wherein each of the ester bond and the ether bond is formed with the oxygen at the terminal side chain of Retinoid D and wherein retinoid D with the alcohol CH 2 OH terminal side chain has the structure:                          wherein R 1  is selected from the group consisting of                          wherein the keto group at the 4-position is free or protected, or is replaced by a thioketone group which is free or protected or is replaced by C 1-6 -alkylidene group;                          wherein X is selected from the group consisting of hydrogen and C 1-6 -alkyl and Y is selected from the group consisting of C 1-6 -alkyl, hydroxyl, alkoxyl, acyloxyl, halide, azide, sulfhydryl, amine and C 1-6 -alkyl substituted amino and wherein the absolute configuration at the 4-position is independently R or S;                          wherein X 1 , Y 1  are independently selected from the group consisting of hydrogen, C 1-6 -alkyl, hydroxyl, alkoxyl, acyloxyl, halide, azide, sulfhydryl, amine and C 1-6 -alkyl substituted amino and Z 1  is selected from the group consisting of C 1-6 -alkyl, hydroxyl, alkoxyl, acyloxyl, halide, azide, sulfhydryl, amine and C 1-6 -alkyl substituted amino;                          wherein X 2  is selected from the group consisting of hydrogen, C 1-6 -alkyl, hydroxyl, alkoxyl, acyloxyl, halide, azide, sulfhydryl, amine and C 1-6 -alkyl substituted amino and Z 2  is selected from the group consisting of C 1-6 -alkyl, hydroxyl, alkoxyl, acyloxyl, halide, azide, sulfhydryl, amine and C 1-6 -alkyl substituted amino; and                          wherein X 3  and Y 3  are independently selected from the group consisting of hydrogens, C 1-6 -alkyl, hydroxyl, alkoxyl, acyloxyl, halide, azide, sulfhydryl, amine and C 1-6 -alkyl substituted amino so long as X 3  and Y 3  are not both hydrogens.