Treatment and prevention of cardiovascular disease and thrombosis

Patent metadata

Field	Value
Publication number	US-10064830-B2
Application number	US-201715605437-A
Country	US
Kind code	B2
Filing date	May 25, 2017
Priority date	Jun 11, 2012
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

Provided herein are compositions for the treatment and/or prevention of cardiovascular disease (CVD), and methods of application and use thereof. In particular, the present invention provides treatment and/or prevention of cardiovascular disease with compounds that inhibit the production of TMA in the gut, such as 3,3-dimethyl-1-butanol (DMB) or other compounds represented by Formula I or as shown in FIGS. 20 - 23.

First claim

We claim:

1. A method for inhibiting the conversion of choline to trimethyl amine comprising:
administering to a subject a composition comprising a compound represented by one of the following two structures:

 such that said compound inhibits conversion of choline to trimethyl amine in said subject, and
wherein said subject has or is suspected of having cardiovascular disease and/or thrombosis.

2. The method of claim 1 , wherein said subject has been determined to have increased platelet aggregation.

3. The method of claim 1 , wherein said subject has been determined to have an elevated TMAO level and/or an elevated TMA level.

4. The method of claim 1 , wherein said administering is under conditions such that at least one symptom of said cardiovascular disease and/or said thrombosis is reduced or eliminated.

5. The method of claim 1 , further comprising administering a probiotic, a prebiotic, and/or fiber to said subject.

6. The method of claim 1 , wherein said composition is co-administered with one or more agents which provide therapy for cardiovascular disease.

7. The method of claim 6 , wherein said one or more agents comprises one or more antibiotics that target gut flora.

8. The method of claim 1 , further comprising, prior to said administering, a step of identifying said subject as having increased platelet aggregation and/or elevated TMAO or TMA levels.

9. The method of claim 8 , wherein said identifying comprises viewing results of a platelet aggregation assay performed on a sample from said subject which shows increased platelet aggregation.

10. The method of claim 8 , wherein said identifying comprises viewing results of a TMA or TMAO assay performed on a sample or exhaled breath from said subject which show elevated TMA or TMAO levels.

Assignees

• Cleveland Clinic Found

Inventors

• Hazen Stanley L
• Levison Bruce
• Wang Zeneng

Classifications

• A61K31/66

  Phosphorus compounds · CPC title

• A61K31/663

  Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid · CPC title

• A61K31/133

  having hydroxy groups, e.g. sphingosine · CPC title

• A61K31/22

  of acyclic acids, e.g. pravastatin · CPC title

• A61K31/205

  Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine · CPC title