Preparation and uses of obeticholic acid
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. A crystalline form of obeticholic acid characterized by an X-ray powder diffraction pattern comprising peaks at 9.5, 12.5 and 16.7±0.2 degrees 2-theta.
2. A crystalline form of obeticholic acid characterized by an X-ray powder diffraction pattern set forth in FIG. 5 .
3. The crystalline form of claim 1 characterized by a differential scanning calorimetry thermogram having an endothermic peak at about 98±2° C.
4. The crystalline form of claim 1 characterized by a differential scanning calorimetry thermogram pattern set forth in FIG. 6 .
5. The crystalline form of claim 1 characterized by a thermo-gravimetric analysis thermogram pattern set forth in FIG. 6 .
6. The crystalline form of claim 1 having a purity of greater than about 96%.
7. The crystalline form of claim 6 having a purity of greater than about 98%.
8. The crystalline form of claim 1 having a total of less than about 4% of one or more impurities selected 6-ethylursodeoxycholic acid, 3α-hydroxy-6α-ethyl-7-cheto-5β-cholan-24-oic acid, 6β-ethylchenodeoxycholic acid, 3α,7α-dihydroxy-6-ethyliden-5β-cholan-24-oic acid, chenodeoxycholic acid, and 3α(3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oyloxy)-7α-hydroxy-6α-ethyl-5β-cholan-24-oic acid.
9. The crystalline form of claim 8 , wherein the total percentage of impurities is less than about 3.8%.
10. The crystalline form of claim 9 , wherein the total percentage of impurities is less than about 3.6%.