Identification of oleanolic acid and plant extract for glucose-6-phosphate dehydrogenase-related disorders including Bag3opathy

Patent metadata

Field	Value
Publication number	US-12357641-B2
Application number	US-202218046194-A
Country	US
Kind code	B2
Filing date	Oct 13, 2022
Priority date	Oct 13, 2022
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

A method of treating a glucose-6-phosphate dehydrogenase deregulated disorder in a subject in need thereof, the method involving administering a therapeutically effective amount of oleanolic acid or a conjugate salt thereof or prodrug thereof to the subject. The glucose-6-phosphate dehydrogenase deregulated disorder can be BCL2 associated athanogene myofibrillar myopathy, amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, or Alzheimer disease.

First claim

What is claimed is:

1. A method of treating a glucose-6-phosphate dehydrogenase (G6PD) deregulated disorder in a subject in need thereof, the method comprising administering a therapeutically effective amount of oleanolic acid, a pharmaceutically acceptable salt thereof, or a prodrug thereof to the subject, wherein the G6PD deregulated disorder is BCL2 associated athanogene myofibrillar myopathy Bag3opathy).

2. The method of claim 1 , wherein the subject suffers from one or more of severe muscle weakness, cardiomyopathy, and respiratory insufficiency.

3. The method of claim 1 , wherein the oleanolic acid or a pharmaceutically acceptable salt thereof is administered to the subject in the form of a botanical product or an extract thereof.

4. The method of claim 3 , wherein the botanical product comprises one or more of Crataegi fructus, Forsythiae fructus, Prunellae spica, Verbenae herba, Eriobotryae folium, Ligustri lucidi fructus, Kaki calyx, Chaenomelis fructus, Jujubae fructus, Corni fructus , or an extract thereof.

5. The method of claim 3 , wherein the botanical product comprises Chaenomelis fructus or an extract thereof.

6. The method of claim 5 , wherein the Chaenomelis fructus extract is prepared by contacting Chaenomelis fructus with ethanol thereby extracting at least a portion of the oleanolic acid or a pharmaceutically acceptable salt thereof present in the Chaenomelis fructus and forming an ethanol extract comprising oleanolic acid or a pharmaceutically acceptable salt thereof and optionally removing ethanol from the ethanol extract thereby forming the Chaenomelis fructus extract.

7. The method of claim 1 , wherein the subject has a BCL2 Associated Athanogene 3 (BAG3) gene comprising a c.626C>T mutation.

8. The method of claim 1 , wherein the prodrug of oleanolic acid has the chemical formula 2:

or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen, R(C═O)— or RO(C═O)—;
R 2 is hydrogen, alkyl, cycloalkyl, aralkyl, or aryl; and
R for each instance is independently hydrogen, alkyl, aralkyl, aryl, or heterocycloalkyl, wherein at least one R 1 and R 2 is not hydrogen.

9. The method of claim 1 , wherein the subject is a human.

Assignees

• Univ Hong Kong Baptist Univ

Inventors

• Bian Zhaoxiang
• Hung Tao
• Zhao Ling
• Zhong Lidan
• Lin Chengyuan

Classifications

• A61K36/732

  Chaenomeles, e.g. flowering quince · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title