Crystalline and liquid crystalline 25-hydroxy-cholest-5-en-3-sulfate sodium and methods for preparing same
Crystalline and liquid crystalline forms of 25HC3S sodium are described herein. The disclosure includes Forms I, II, III, V, IX, XI, and XIII of 25HC3S sodium and combinations thereof. Pharmaceutical formulations of said forms, or combinations thereof, and methods of treating or preventing disease such as hypercholesterolemia, hypertriglyceridemia, and conditions related to fat accumulation and inflammation (e.g., non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic hepatitis, acute kidney injury (AKI), psoriasis, and atherosclerosis) are further disclosed herein. Methods for preparing 25HC3S are also provided.
1 . A crystalline form of 5-cholesten-3β-25-diol-3-sulphate (25HC3S) sodium, selected from Form I, Form II, Form III, Form V, Form IX, Form XI, Form XIII, a hydrate form and an anhydrate form.
2 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is a crystalline hydrate of crystalline 25HC3S sodium.
3 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is Form I of crystalline 25HC3S sodium.
4 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is Form II of crystalline 25HC3S sodium.
5 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is Form XI of crystalline 25HC3S sodium.
6 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is a crystalline anhydrate of crystalline 25HC3S sodium.
7 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is Form XIII of crystalline 25HC3S sodium.
8 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is Form III of crystalline 25HC3S sodium.
9 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is Form V of crystalline 25HC3S sodium.
10 . The crystalline form of 25HC3S sodium of claim 1 , wherein the crystalline form is Form IX of crystalline 25HC3S sodium.
11 . A method of treating one or more of hypercholesterolemia, hypertriglyceridemia, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic hepatitis, acute kidney injury (AKI), psoriasis, and atherosclerosis, comprising administering to a patient in need thereof an effective amount of a crystalline form of 25HC3S sodium of claim 1 .
12 . The method of claim 11 , wherein the crystalline form of 25HC3S sodium is the hydrate of crystalline 25HC3S sodium.
13 . The method of claim 11 , wherein the crystalline form of 25HC3S sodium is Form I of crystalline 25HC3S sodium.
14 . The method of claim 11 , wherein the crystalline form of 25HC3S sodium is Form II of crystalline 25HC3S sodium.
15 . A pharmaceutical composition comprising a crystalline form of 25HC3S sodium of claim 1 , and at least one pharmaceutically acceptable excipient.
16 . The pharmaceutical composition of claim 15 , wherein the crystalline form of 25HC3S sodium is the hydrate of crystalline 25HC3S sodium.
17 . The pharmaceutical composition of claim 15 , wherein the crystalline form of 25HC3S sodium is Form I of crystalline 25HC3S sodium.
18 . The pharmaceutical composition of claim 15 , wherein the crystalline form of 25HC3S sodium is Form II of crystalline 25HC3S sodium.
19 . A method of treating one or more of hypercholesterolemia, hypertriglyceridemia, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic hepatitis, acute kidney injury (AKI), psoriasis, and atherosclerosis, comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition of 25HC3S sodium of claim 15 .
20 . A composition comprising the crystalline form of 25HC3S sodium of claim 1 , wherein the composition comprises two or more of Form I of 25HC3S sodium, Form II of 25HC3S sodium, Form III of 25HC3S sodium, Form V of 25HC3S sodium, Form IX of 25HC3S sodium, Form XI of 25HC3S sodium, and Form XIII of 25HC3S sodium.