2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole and estrogen formulations

Abstract

The present invention relates to new formulations containing one or more estrogens and 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds which are useful as estrogenic agents, as well as pharmaceutical compositions and methods of treatment utilizing these compounds, which have the general structures below:

1 . A pharmaceutical composition comprising a pharmaceutically effective amount of 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol acetate and a pharmaceutically effective amount of conjugated estrogens.  
     
     
         2 . A pharmaceutical composition comprising a pharmaceutically effective amount of 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol hydrochloride and a pharmaceutically effective amount of conjugated estrogens.  
     
     
         3 . A method of treating vasomotor symptoms in a postmenopausal or estrogen deficient woman in need thereof, which comprises administering to said woman an effective amount of a combination of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof and conjugated estrogens.  
     
     
         4 . The method according to  claim 3 , wherein the vasomotor symptom is hot flushes.  
     
     
         5 . The method according to  claim 3 , wherein said pharmaceutically acceptable salt is the acetate salt of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol.  
     
     
         6 . The method according to  claim 3 , wherein said pharmaceutically acceptable salt is the hydrochloride salt of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol.  
     
     
         7 . A method of inhibiting or retarding bone demineralization or treating or inhibiting osteoporosis in a postmenopausal or estrogen deficient woman in need thereof, which comprises administering to said woman an effective amount of a combination of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof and conjugated estrogens.  
     
     
         8 . The method according to  claim 7 , wherein said pharmaceutically acceptable salt is the acetate salt of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol.  
     
     
         9 . The method according to  claim 7 , wherein said pharmaceutically acceptable salt is the hydrochloride salt of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol.  
     
     
         10 . A method of treating or inhibiting menopausal or postmenopausal disorders in a postmenopausal or estrogen deficient woman in need thereof, which comprises administering to said woman an effective amount of a combination of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or a pharmaceutically acceptable salt thereof and conjugated estrogens.  
     
     
         11 . The method according to  claim 10 , wherein said pharmaceutically acceptable salt is the acetate salt of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol.  
     
     
         12 . The method according to  claim 10 , wherein said pharmaceutically acceptable salt is the hydrochloride salt of 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol.