Treatment of diseases associated with hepatic stellate cell activation using ammonia-lowering therapies

Patent metadata

Field	Value
Publication number	US-10039735-B2
Application number	US-201515527999-A
Country	US
Kind code	B2
Filing date	Nov 23, 2015
Priority date	Nov 24, 2014
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

Disclosed herein are methods of preventing, treating, and delaying the onset or progression of diseases associated with hepatic stellate cells (HSCs), such as non-alcoholic fatty liver disease (NAFLD), fibrosis, and liver cancer, using ammonia-lowering therapies.

First claim

What is claimed is:

1. A method of treating or delaying the onset or progression of a disease associated with hepatic stellate cell (HSC) activation, comprising administering an ammonia-lowering agent to a subject in need thereof, wherein the ammonia-lowering agent comprises ornithine phenylacetate.

2. The method of claim 1 , wherein the administration is oral, intravenous, intraperitoneal, intragastric, or intravascular administration.

3. The method of claim 2 , wherein the administration is intravenous administration.

4. The method of claim 2 , wherein the administration is oral administration.

5. The method of claim 1 , wherein the disease associated with HSC activation is non-alcoholic fatty liver disease (NAFLD).

6. The method of claim 5 , wherein the NAFLD is non-alcoholic steatohepatitis (NASH).

7. The method of claim 5 , wherein the NAFLD is steatosis.

8. The method of claim 1 , wherein the disease associated with HSC activation is liver cancer.

9. The method of claim 1 , wherein the disease associated with HSC activation is a fibrotic condition.

10. The method of claim 9 , wherein the fibrotic condition is liver fibrosis.

11. A method of preventing non-alcoholic fatty liver disease (NAFLD), comprising administering an ammonia-lowering agent to a subject in need thereof.

12. The method of claim 11 , wherein the NAFLD is non-alcoholic steatohepatitis (NASH).

13. The method of claim 11 , wherein the NAFLD is steatosis.

14. The method of claim 11 , wherein the ammonia-lowering agent comprises a magnesium phosphate product (MGP), glycerol phenylbutyrate (GPB), sodium phenylacetate, sodium phenylbutyrate (NaPBA), glutamine, sodium benzoate,L-arabinose, a laxative, an antibiotic, ornithine in combination with at least one of phenylacetate and phenylbutyrate, or any combination thereof.

15. The method of claim 14 , wherein the ammonia-lowering agent comprises ornithine in combination with at least one of phenylacetate and phenylbutyrate.

16. The method of claim 15 , wherein separate pharmaceutically acceptable salts of the ornithine and at least one of phenylacetate and phenylbutyrate are administered to the subject.

17. The method of claim 16 , wherein at least one of phenylacetate and phenylbutyrate is administered as a sodium phenylacetate or sodium phenylbutyrate.

18. The method of claim 15 , wherein the ornithine is administered as a free monomeric amino acid or physiologically acceptable salt thereof.

19. The method of claim 15 , wherein the ornithine and phenylacetate is administered as ornithine phenylacetate.

20. The method of claim 11 , wherein the administration is oral, intravenous, intraperitoneal, intragastric, or intravascular administration.

21. The method of claim 20 , wherein the administration is intravenous administration.

22. The method of claim 20 , wherein the administration is oral administration.

Assignees

• Ucl Business Plc

Inventors

• Jalan Rajiv
• Mookerjee Rajeshwar Prosad
• Rombouts Krista
• Andreola Fausto
• De Chiara Francesco
• Thomsen Karen Louise

Classifications

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61P1/10

  Laxatives · CPC title

• A61K31/198

  Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) · CPC title