Combination therapy with nitrated lipids and inhibitors of the renin-angiotensin-aldosterone system

• US 10,010,532 B2
• Filed: 10/23/2015
• Issued: 07/03/2018
• Est. Priority Date: 08/19/2011
• Status: Active Grant

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Yang, Tianxin
• Primary Examiner(s): TRAN, MY CHAU T
• Application Number:
  US14/921,880
• Publication Number:
  US 20160045476A1
• Time in Patent Office: 984 Days
• Field of Search: 514 25, 514381
• 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 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present technology provides compositions and methods for treating chronic kidney disease, end-stage renal disease, or diabetic nephropathy. The compositions comprise a nitrated lipid and an inhibitor of the renin-angiotensin-aldosterone system. The methods comprise administering a nitrated lipid in combination with an inhibitor of the renin-angiotensin-aldosterone system to a subject in need thereof, in an amount effective to treat diabetic nephropathy, chronic kidney disease, and/or end-stage renal disease. The use of a nitrated lipid with an inhibitor of the renin-angiotensin-aldosterone system exhibits a synergistic effect in treating chronic kidney disease and diabetic nephropathy.

Claims

1. A method of treating hypertensive nephropathy in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a nitrated lipid, an inhibitor of the renin-angiotensin-aldosterone system, and a pharmaceutically acceptable carrier, excipient, adjuvant, or a combination thereof.

2. The method of claim 1, wherein the inhibitor of the renin-angiotensin-aldosterone system is selected from the group consisting of an angiotensin converting enzyme inhibitor, a renin inhibitor, an angiotensin receptor antagonist, and a combination thereof.

3. The method of claim 1, wherein the nitrated lipid comprises a monounsaturated fatty acid, polyunsaturated fatty acid, or a combination thereof.

4. The method of claim 1, wherein the nitrated lipid comprises a nitro-oleic acid, a nitro-linoleic acid, or a combination thereof.

5. The method of claim 1, wherein the nitrated lipid is selected from the group consisting of 9-nitrooleic acid, 10-nitrooleic acid, and a combination thereof.

6. The method of claim 2, wherein the angiotensin converting enzyme inhibitor is selected from the group consisting of enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, zofenopril, fosinopril, and captopril.

7. The method of claim 2, wherein the renin inhibitor is selected from the group consisting of aliskiren, remikiren, or renin siRNA.

8. The method of claim 2, wherein the angiotensin receptor antagonist is selected from the group consisting of losartan, valsartan, telmisartan, irbesartan, azilsartan, olmesartan, candesartan, or eprosartan.

9. The method of claim 2, wherein the nitrated lipid is nitro-oleic acid and the inhibitor of the renin-angiotensin aldosterone system is an angiotensin converting enzyme inhibitor.

10. The method of claim 1, wherein the nitrated lipid is 10-nitrooleic acid and the inhibitor of the renin-angiotensin-aldosterone system is losartan.