Nitrated-fatty acids modulation of type II diabetes

• US 9,700,534 B2
• Filed: 10/26/2015
• Issued: 07/11/2017
• Est. Priority Date: 08/01/2007
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Freeman, Bruce A., Schopfer, Francisco J.
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US14/923,265
• Publication Number:
  US 20160045467A1
• Time in Patent Office: 624 Days
• Field of Search: 514560
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/201 having one or two double bonds, e.g. oleic, linoleic acids
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

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.

Claims

1. A method for lowering blood glucose levels, comprising administering a nitro oleic acid, or a metabolite, a pharmaceutically acceptable salt, or prodrug thereof to a subject in need of treatment.

2. The method of claim 1, wherein administering is carried out by a method selected from the group consisting of topical administration, oral administration, inhalation, intravenous drip, subcutaneous injection, intraperitoneal injection, and intramuscular injection.

3. The method of claim 1, further comprising administering one or more therapeutic agents in addition to the nitro oleic acid.

4. The method of claim 3, wherein the one or more therapeutic agents are selected from the group consisting of cytokines, chemokines, and regulators of growth factors.

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

6. The method of claim 1, further comprising administering an anti-microbial agent, an anti-inflammation agent, an anesthetic, or a combination thereof.

7. The method of claim 1, wherein the nitro oleic acid is a salt of 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 a combination thereof.

8. The method of claim 1, wherein the nitro oleic acid is a prodrug selected from the group consisting of a methyl ester of nitro oleic acid or an ethyl ester of nitro oleic acid.

9. The method of claim 1, wherein the nitro oleic acid, metabolite, salt, or prodrug thereof is in a pharmaceutical composition.

10. The method of claim 9, wherein the pharmaceutical composition further comprises sodium chloride, Ringer'"'"'s dextrose, dextrose, lactated Ringer'"'"'s solution, fluid and nutrient replenishers, or a combination thereof.

11. The method of claim 9, wherein the pharmaceutical composition is a solution, suspension, solid, or emulsion.

12. The method of claim 9, wherein the pharmaceutical composition further comprises thickeners, diluents, solvents, buffers, preservatives, surface active agents, excipients, or a combination thereof.