System and Method For Treating Atheroma Formation

Patent metadata

Field	Value
Publication number	US-2018235919-A1
Application number	US-201615548829-A
Country	US
Kind code	A1
Filing date	Feb 5, 2016
Priority date	Feb 6, 2015
Publication date	Aug 23, 2018
Grant date	—

Abstract

A method for treating or preventing atherosclerosis is disclosed by administering to a mammal a TMAO producing agent Administering a pharmaceutically effective amount of a TMAO producing agent increases trimethylamine N-oxide levels. Increased trimethylamine N-oxide levels have been found to reduce athero lesions.

First claim

1 . A method for treating artherio lesions comprising:
administering to a mammal a TMAO producing agent, the TMAO producing agent comprising a compound that, when ingested or injected, forms a TMAO in the body of the mammal, the TMAO producing agent being administered to the mammal in a pharmaceutically effective amount to increase TMAO levels in the blood of the mammal.

2 . A method as defined in claim 1 , further comprising the step of monitoring levels of TMAO in the blood of the mammal during periodic administration of the TMAO producing agent.

3 . A method as defined in claim 2 , further comprising the step of adjusting the amount of TMAO producing agent administered to the mammal based upon the levels of TMAO monitored in the blood in order to increase or decrease the amount of TMAO in the blood.

4 . A method as defined in claim 1 , wherein the TMAO producing agent comprises a carnitine, such as L-carnitine or D-camitine.

5 . A method as defined in claim 1 , wherein the TMAO producing agent comprises a choline or a betaine.

6 . (canceled)

7 . A method as defined in claim 1 , wherein the TMAO producing agent comprises a mixture of at least two TMAO producing agents selected from the group consisting of a carnitine, a choline, and a betaine.

8 . A method as defined in claim 1 , wherein the TMAO producing agent comprises a TMAO precursor.

9 . A method as defined in claim 1 , wherein the TMAO producing agent comprises a TMAO analog.

10 . A method as defined in claim 1 , wherein the TMAO producing agent is ingested by the mammal.

11 . A method as defined in claim 1 , wherein the TMAO producing agent is injected into the mammal.

12 . A method as defined in in claim 1 , wherein the TMAO producing agent is administered to a mammal afflicted with or at risk of developing atherosclerosis or a disorder associated with or mediated by atherosclerosis.

13 . A method as defined in claim 1 , wherein the TMAO producing agent is administered to a mammal afflicted with a peripheral vascular disease.

14 . A method as defined in claim 1 , wherein the TMAO producing agent is administered to the mammal at a dose of greater than 50 mg/kg.

15 . A method as defined in claim 1 , wherein the TMAO producing agent is administered to the mammal once or twice a day.

16 . A method as defined hi claim 1 , wherein the mammal comprises a human patient.

17 . A method as defined in claim 1 , wherein the mammal comprises a feline or canine.

18 . A system or kit for treating a mammal inflicted with atherosclerosis or a disorder associated with or mediated by atherosclerosis comprising:
multiple doses of a TMAO producing agent, the TMAO producing agent comprising a compound that chemically converts into trimethylamine when ingested or injected, each dose being sufficient to increase TMAO levels in the blood of the mammal; and an article that facilitates monitoring TMAO levels in a blood sample taken from the mammal.

19 . A system or kit as defined hi claim 18 , wherein the TMAO producing agent comprises a camitine, a choline or a betaine.

20 . (canceled)

21 . (canceled)

22 . A system or kit as defined in claim 18 , wherein each dose of the TMAO producing agent is greater than 150 mg/kg, based on the mammal to be treated.

23 . (canceled)

24 . A system or kit as defined in claim 18 , wherein the article comprises a blood collection device or a TMAO assay device.

25 . (canceled)

26 . A process for detecting analyte levels in a plasma sample, the analyte comprising TMAO, a TMAO precursor, or a TMAO analog, the process comprising:
producing at least two working standard mixtures comprising known but varied concentrations of an unlabeled analyte and known, fixed concentrations of an isotope-labeled analyte; analyzing said working standard mixtures and creating a correlation between the concentration of an analyte versus a comparison of analysis of the non-labeled analyte to the isotope-labeled analyte; producing at least one plasma sample solution comprising plasma sample, water, and a known, fixed concentration of the isotope-labeled analyte; producing a plasma blank solution comprising plasma blank, water, and a known, fixed concentration of the isotope-labeled analyte; producing at least one spiked plasma sample comprising plasma blank, a known, varied concentration of the unlabeled analyte, and a known, fixed concentration of the isotope-labeled analyte; analyzing said plasma sample solution, said plasma blank solution, and said at least one spiked plasma sample and determining the concentration of the analyte in the plasma sample solution by comparing the analysis of the analyte in plasma sample to the isotope-labeled internal standard to the reference.

27 . (canceled)

28 . (canceled)

29 . (canceled)

Assignees

• Lonza Ag

Inventors

• Bellamine Aouatef
• Williamson Yuping Vivian

Classifications

• 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

• G01N33/49

  Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)} · CPC title

• A61K31/205 Primary

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

• G01N2560/00

  Chemical aspects of mass spectrometric analysis of biological material · CPC title

• A61K31/14

  Quaternary ammonium compounds, e.g. edrophonium, choline (betaines A61K31/205) · CPC title