Treatment of fibrosis using FXR ligands

Patent metadata

Field	Value
Publication number	US-9498484-B2
Application number	US-8100205-A
Country	US
Kind code	B2
Filing date	Mar 14, 2005
Priority date	Mar 12, 2004
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

The present invention relates to a method for inhibiting fibrosis that occurs in an organ where the farnesoid X receptor (FXR) is expressed. This method involves the step of administering a high potency, activating ligand of FXR in an effective amount to a patient who is not suffering from a cholestatic condition. The invention also provides pharmaceutical compositions containing an effective amount of an FXR ligand and kits for dispensing the pharmaceutical compositions.

First claim

What is claimed is:

1. A method of treating liver fibrosis in a human not suffering from a cholestatic condition, comprising the steps of selecting a human who is not suffering from a cholestatic condition and administering to the human 6-ethyl-chenodeoxycholic acid at a daily dose of 5-500 mg orally.

2. The method of claim 1 , wherein the cholestatic condition is defined as having abnormally elevated serum levels of alkaline phosphatase, γ-glutamyl transpeptidase (GGT), and 5′ nucleotidase.

3. The method of claim 2 , wherein the cholestatic condition is further defined as presenting with at least one clinical symptom.

4. The method of claim 3 , wherein the symptom is itching (pruritus).

5. The method of claim 1 , wherein the cholestatic condition is selected from the group consisting of primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced cholestasis, hereditary cholestasis, and intrahepatic cholestasis of pregnancy.

6. The method of claim 1 , wherein the human is not suffering from a cholestatic condition associated with a disease or condition selected from the group consisting of primary liver and biliary cancer, metastatic cancer, sepsis, chronic total parenteral nutrition, cystic fibrosis, and granulomatous liver disease.

7. The method of claim 1 , wherein the human has liver fibrosis associated with a disease selected from the group consisting of hepatitis B; hepatitis C; parasitic liver diseases; post-transplant bacterial, viral and fungal infections; alcoholic liver disease (ALD); non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); liver diseases induced by methotrexate, isoniazid, oxyphenistatin, methyldopa, chlorpromazine, tolbutamide, or amiodarone; autoimmune hepatitis; sarcoidosis; Wilson's disease; hemochromatosis; Gaucher's disease; types III, IV, VI, IX and X glycogen storage diseases; α 1 -antitrypsin deficiency; Zellweger syndrome; tyrosinemia; fructosemia; galactosemia; vascular derangement associated with Budd-Chiari syndrome, veno-occlusive disease, or portal vein thrombosis; and congenital hepatic fibrosis.

8. A method of treating non-alcoholic steatohepatitis in a human not suffering from a cholestatic condition, comprising the steps of selecting a human who is not suffering from a cholestatic condition and administering to the human 6-ethyl-chenodeoxycholic acid at a daily dose of 5-500 mg orally.

Assignees

• Fiorucci Stefano
• Pellicciari Roberto
• Pruzanski Mark
• Intercept Pharmaceuticals Inc

Inventors

• Fiorucci Stefano
• Pellicciari Roberto
• Pruzanski Mark

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P31/10

  Antimycotics · CPC title