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 method for treating endometriosis comprising: 
 administering to a female of child bearing age a combination of:    (a) 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    (b) ethinyl estradiol or a pharmaceutically acceptable salt thereof.    
     
     
         2 . The method according to  claim 1 , 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.  
     
     
         3 . The method according to  claim 1 , 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.  
     
     
         4 . The method of  claim 1  wherein said 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or pharmaceutically acceptable salt thereof is administered in a dose of about 0.01 mg/day to about 1000 mg/day.  
     
     
         5 . The method of  claim 1  wherein said 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or pharmaceutically acceptable salt thereof is administered in a dose of about 1 mg/day to about 600 mg/day.  
     
     
         6 . The method of  claim 1  wherein said 1-[4-(2-Azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol or pharmaceutically acceptable salt thereof is administered in a dose of about 1 mg/day to about 150 mg/day.  
     
     
         7 . The method of  claim 1  wherein said ethinyl estradiol or pharmaceutically acceptable salt thereof is administered in a dose of about 1 μg to 0.3 mg/day.  
     
     
         8 . The method of  claim 1  wherein said ethinyl estradiol or pharmaceutically acceptable salt thereof is administered in a dose of about 2 μg to 0.15 mg/day.  
     
     
         9 . A pharmaceutical composition comprising: 
 (a) a pharmaceutically effective amount 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    (b) a pharmaceutically effective amount of ethinyl estradiol or a pharmaceutically acceptable salt thereof.