Preparation and Uses of Obeticholic Acid

Abstract

The present invention relates to obeticholic acid: or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.

1 - 13 . (canceled) 
     
     
         14 . A crystalline form of obeticholic acid, wherein the crystalline form is selected from the group consisting of D, F, G, and I. 
     
     
         15 . The crystalline form of  claim 14 , wherein the crystalline form is Form D and characterized by an X-ray diffraction pattern including peaks at about 4.4, 5.2 and 7.5 degrees 2-Theta. 
     
     
         16 . The crystalline form of  claim 15 , wherein the crystalline form is characterized by an X-ray diffraction pattern including peaks at about 9.5, 12.3, 14.5, 15.9, and 16.8 degrees 2-Theta. 
     
     
         17 . The crystalline form of  claim 14 , wherein the crystalline form is Form F and characterized by an X-ray diffraction pattern including peaks at about 8.0, 13.2, and 13.8 degrees 2-Theta. 
     
     
         18 . The crystalline form of  claim 17 , wherein the crystalline form is characterized by an X-ray diffraction pattern including peaks at about 9.9, 10.5, 15.7, 16.0 and 17.5 degrees 2-Theta. 
     
     
         19 . The crystalline form of  claim 14 , wherein the crystalline form is Form G and characterized by an X-ray diffraction pattern including peaks at about 12.9 and 13.4 degrees 2-Theta. 
     
     
         20 . The crystalline form of  claim 19  wherein the crystalline form is characterized by an X-ray diffraction pattern including peaks at about 7.9, 12.3, 14.5, 16.9 and 23.1 degrees 2-Theta. 
     
     
         21 . The crystalline form of  claim 14 , wherein the crystalline form is Form I and characterized by an X-ray diffraction pattern including a peak at about 7.2 degrees 2-Theta. 
     
     
         22 . The crystalline form of  claim 21  wherein the crystalline form is characterized by an X-ray diffraction pattern including peaks at about 13.9, 14.5, 17.4, 19.2 and 22.8 degrees 2-Theta. 
     
     
         23 . The crystalline form of  claim 15 , wherein the crystalline form is obtained from the recrystallization of obeticholic acid from methyl isobutyl ketone. 
     
     
         24 . The crystalline form of  claim 17 , wherein the crystalline form is obtained from the recrystallization of obeticholic acid from nitromethane. 
     
     
         25 . The crystalline form of  claim 19 , wherein the crystalline form is obtained from the recrystallization of obeticholic acid from acetonitrile. 
     
     
         26 . The crystalline form of  claim 21 , wherein the crystalline form is obtained from the recrystallization of obeticholic acid from acetonitrile/water mixture.