Nitrated-fatty acids modulation of type II diabetes

Patent metadata

Field	Value
Publication number	US-9186408-B2
Application number	US-201414244741-A
Country	US
Kind code	B2
Filing date	Apr 3, 2014
Priority date	Aug 1, 2007
Publication date	Nov 17, 2015
Grant date	Nov 17, 2015

Abstract

Nitro oleic acid and related metabolites are agonists of PPAR-γ. Surprisingly, nitro oleic acid is a more potent agonist of PPAR-γ, relative to nitro linoleic acid. Thus, nitro oleic acid and its metabolites, as well as their pharmaceutically acceptable salts and prodrug forms, are candidate therapeutics for the treatment of type-2 diabetes, which results from insulin resistance accompanying the improper functioning of PPAR-γ.

First claim

What is claimed is:

1. A method for controlling weight gain, comprising the steps of:
administering to a subject in need thereof a pharmaceutical composition comprising an active agent selected from nitro oleic acid and a metabolite of nitro oleic acid, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable excipient, carrier, or combination thereof; and
repeating the step of administering at least once.

2. The method of claim 1 , further comprising, after the administering step, monitoring said subject for a change relating to weight gain.

3. The method of claim 1 , further comprising, after at least one repetition of the administering step, monitoring said subject for a change relating to weight gain.

4. The method of claim 1 , wherein the active agent is nitro oleic acid.

5. The method of claim 1 , wherein the administering step is carried out by oral administration or intravenous drip.

6. The method of claim 1 , wherein the pharmaceutical composition is formulated as a solution, suspension, solid, or emulsion.

7. The method of claim 1 , wherein the pharmaceutical composition further comprises one or more thickeners, diluents, solvents, buffers, preservatives, surface active agents, excipients, and combinations thereof.

8. The method of claim 1 , wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

9. The method of claim 8 , wherein the one or more therapeutic agents are selected from the group consisting of cytokines, and regulators of growth factors.

10. The method of claim 1 , wherein the nitro oleic acid comprises a single regioisomer of nitro oleic acid or both regioisomers of nitro oleic acid.

11. The method of claim 1 , wherein the pharmaceutically acceptable salt comprises a salt formed by the reaction of nitro oleic acid with an inorganic base selected from the group consisting of sodium hydroxide, ammonium hydroxide, potassium hydroxide, monoalkyl amine, dialkyl amine, trialkyl amine, aryl amine, substituted ethanolamine, and combinations thereof.

12. The method of claim 1 , wherein the prodrug comprises a methyl or ethyl ester of nitro oleic acid.

13. The method of claim 1 , wherein the pharmaceutical composition further comprises one or more agents to maintain osmolarity selected from the group consisting of sedum chloride, Ringer's dextrose, lactated Ringer's solution, fluid and nutrient replenishers, and combinations thereof.

14. The method of claim 1 , wherein the subject is afflicted with type 2 diabetes.

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

Assignees

• Univ Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Freeman Bruce A
• Schopfer Francisco J

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K31/20

  having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids · CPC title

• A61K31/201 Primary

  having one or two double bonds, e.g. oleic, linoleic acids · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title