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 .- 20 . (canceled)
21 . A tablet comprising non-crystalline obeticholic acid in the amount of about 1 mg to about 25 mg wherein the non-crystalline obeticholic acid comprises less than 1% of chenodeoxycholic acid.
22 . The tablet of claim 21 , wherein the non-crystalline obeticholic acid further comprises not more than 0.15% of 6β-ethylchenodeoxycholic acid.
23 . The tablet of claim 21 , wherein the non-crystalline obeticholic acid comprises less than about 0.5% of chenodeoxycholic acid.
24 . The tablet of claim 23 , wherein the non-crystalline obeticholic acid comprises less than about 0.3% of chenodeoxycholic acid.
25 . The tablet of claim 24 , wherein the non-crystalline obeticholic acid comprises less than about 0.2% of chenodeoxycholic acid.
26 . The tablet of claim 21 , wherein the non-crystalline obeticholic acid further comprises not more than 0.15% of 3α(3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oyloxy)-7α-hydroxy-6α-ethyl-5β-cholan-24-oic acid.
27 . The tablet of claim 21 , wherein the non-crystalline obeticholic acid further comprises not more than 0.15% of 6β-ethylchenodeoxycholic acid and not more than 0.15% of 3α(3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oyloxy)-7α-hydroxy-6α-ethyl-5β-cholan-24-oic acid.
28 . The tablet of claim 27 , wherein the non-crystalline obeticholic acid comprises less than about 0.5% of chenodeoxycholic acid.
29 . The tablet of claim 28 , wherein the non-crystalline obeticholic acid comprises less than about 0.3% of chenodeoxycholic acid.
30 . The tablet of claim 29 , wherein the non-crystalline obeticholic acid comprises less than about 0.2% of chenodeoxycholic acid.
31 . The tablet of claim 21 , wherein the non-crystalline obeticholic acid comprises less than about 0.05% of 6β-ethylchenodeoxycholic acid, and less than about 0.05% of 3α(3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oyloxy)-7α-hydroxy-6α-ethyl-5β-cholan-24-oic acid.
32 . The tablet of claim 31 , wherein the non-crystalline obeticholic acid comprises less than about 0.3% of chenodeoxycholic acid.
33 . The tablet of claim 32 , wherein the non-crystalline obeticholic acid comprises less than about 0.2% of chenodeoxycholic acid.
34 . A tablet comprising non-crystalline obeticholic acid wherein the non-crystalline obeticholic acid comprises one or more compound selected from 6β-ethylchenodeoxycholic acid, chenodeoxycholic acid, and 3α(3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oyloxy)-7α-hydroxy-6α-ethyl-5β-cholan-24-oic acid, wherein 6β-ethylchenodeoxycholic acid is present in an amount between about 0% and not more than 0.05%, chenodeoxycholic acid is present in an amount between about 0% and not more than 0.2%, and 3α(3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oyloxy)-7α-hydroxy-6α-ethyl-5β-cholan-24-oic acid is present in an amount between about 0% and not more than 0.05%.
35 . The tablet of claim 21 , wherein the non-crystalline obeticholic acid is in the amount of about 25 mg.
36 . The tablet of claim 21 , wherein the non-crystalline obeticholic acid is in the amount of about 10 mg.
37 . A method for treating NASH comprising administering to a subject in need thereof a tablet comprising non-crystalline obeticholic acid in the amount of about 1 mg to about 25 mg wherein the non-crystalline obeticholic acid comprises less than 1% of chenodeoxycholic acid.
38 . The method of claim 37 , wherein the non-crystalline obeticholic acid comprises less than about 0.2% of chenodeoxycholic acid.
39 . The method of claim 37 , wherein the non-crystalline obeticholic acid is in the amount of about 25 mg.
40 . The method of claim 37 , wherein the non-crystalline obeticholic acid is in the amount of about 10 mg.