Preparation and uses of obeticholic acid

Patent metadata

Field	Value
Publication number	US-9732116-B2
Application number	US-201514947492-A
Country	US
Kind code	B2
Filing date	Nov 20, 2015
Priority date	Jun 19, 2012
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

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.

First claim

The invention claimed is:

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%.

Assignees

• Intercept Pharmaceuticals Inc

Inventors

• Steiner André
• Waenerlund Poulsen Heidi
• Jolibois Emilie
• Rewolinski Melissa
• Gross Ralf
• Sharp Emma
• Dubas-Fisher Fiona
• Eberlin Alex

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P31/14

  for RNA viruses · CPC title