Pharmaceutical compositions for use in the treatment of cardiovascular calcification

Patent metadata

Field	Value
Publication number	US-11382894-B2
Application number	US-201816498807-A
Country	US
Kind code	B2
Filing date	Mar 29, 2018
Priority date	Mar 30, 2017
Publication date	Jul 12, 2022
Grant date	Jul 12, 2022

Abstract

The inventors demonstrate that the phosphatase and hydrolase domains of soluble epoxide hydrolase (sEH) regulate the cardiovascular calcification process and revealed that inhibition of the phosphatase domain of sEH could represent a new pharmacological target in the prevention of cardiovascular calcification. The present invention thus relates to a therapeutically effective amount of an inhibitor of phosphatase activity of soluble epoxide hydrolase for use in a method of treating cardiovascular calcification in a subject in need thereof.

First claim

The invention claimed is:

1. A method of treating cardiovascular calcification in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of phosphatase activity of soluble epoxide hydrolase, wherein the inhibitor of phosphatase activity of soluble epoxide hydrolase is N-acetyl-S-farnesyl-Lcysteine (AFC) or ebselen.

2. The method of claim 1 wherein the cardiovascular calcification is valvular or vascular calcification.

3. The method of claim 1 wherein the subject is elderly and/or has a mineral imbalance disorder.

4. An in vitro method for screening a plurality of test substances to identity those which are useful for the treatment of cardiovascular calcification in a subject in need thereof comprising i) testing each of the test substances for its ability to inhibit the phosphatase activity of soluble epoxide hydrolase and ii) identifying a test substance which inhibits said phosphatase activity as useful for treating cardiovascular calcification in a subject in need thereof.

5. The method of claim 3 , wherein the mineral imbalance disorder is associated with severe renal failure in a subject on hemodialysis, a hemodialysis arteriovenous (AV) graft/shunt, a vein graft, a vascular anastomosis, diabetes, Paget's disease, rheumatoid arthritis, osteoporosis or osteoarthritis.

Assignees

• Inst Nat Sante Rech Med
• Univ Rouen Normandie
• Univ Picardie
• Univ Rouen Centre Hospitalier
• Centre Hospitalier Univ Damiens

Inventors

• Bellien Jeremy
• Six Isabelle
• Mentaverri Romuald
• Kamel Said

Classifications

• G01N2800/32

  Cardiovascular disorders · 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

• A61K31/41 Primary

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C12Q1/42

  involving phosphatase · CPC title