Uses of oxygenated cholesterol sulfates (OCS)

Patent metadata

Field	Value
Publication number	US-10786517-B2
Application number	US-201916368553-A
Country	US
Kind code	B2
Filing date	Mar 28, 2019
Priority date	Dec 24, 2013
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

Methods of preventing and/or treating ischemia, organ dysfunction and/or organ failure, including multiple organ dysfunction syndrome (MODS), and necrosis and apoptosis associated with organ dysfunction/failure, are provided. For instance, the methods involve contacting organ(s) with an oxygenated cholesterol sulfate (OCS), e.g. 5-cholesten-3,25-diol, 3-sulfate (25H-C3S). The organ(s) may be in vivo (e.g. in a patient that is treated with the OCS) or ex vivo (e.g. an organ that has been harvested from a donor and is to be transplanted).

First claim

The invention claimed is:

1. A method of treating acute liver dysfunction or acute liver failure in a subject in need thereof, comprising
administering to the subject an amount of 5-cholesten-3,25-diol, 3-sulfate (25HC3S) or pharmaceutically acceptable salt thereof that is sufficient to treat the acute liver dysfunction or acute liver failure,
wherein the acute liver dysfunction or acute liver failure comprises alcoholic hepatitis, and
wherein the subject has a serum bilirubin level of >1.9 mg/dL prior to treatment.

2. The method of claim 1 , wherein the administering is performed by at least one of orally, subcutaneously, and intramuscularly.

3. The method of claim 1 , wherein the administering is performed intravenously.

4. The method of claim 1 , wherein the administering comprises injection.

5. The method of claim 1 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered in a formulation further comprising a pharmaceutically acceptable carrier.

6. The method of claim 1 , wherein the 25HC3S or pharmaceutically acceptable salt thereof comprises a pharmaceutically acceptable salt of 25HC3S.

7. The method of claim 1 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.001 mg/kg to about 100 mg/kg.

8. The method of claim 1 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.001 mg/kg to about 10 mg/kg.

9. The method of claim 1 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.1 mg/kg to about 10 mg/kg.

10. The method of claim 1 , wherein the administering is performed from once to 3 times per day.

11. The method of claim 3 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.001 mg/kg to about 10 mg/kg.

12. The method of claim 4 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.001 mg/kg to about 10 mg/kg.

13. The method of claim 5 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.001 mg/kg to about 10 mg/kg.

14. The method of claim 6 , wherein the 25HC3S or pharmaceutically acceptable salt thereof is administered at a dose ranging from about 0.001 mg/kg to about 10 mg/kg.

Assignees

• Univ Virginia Commonwealth
• Durect Corp

Inventors

• Ren Shunlin
• Theeuwes Felix
• Brown James E
• Lin Weiqi

Classifications

• A01N1/126

  Physiologically active agents, e.g. antioxidants or nutrients · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K31/575 Primary

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P1/16

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