Preventing and/or treating cardiovascular disease and/or associated heart failure

• US 20060009534A1
• Filed: 09/07/2005
• Published: 01/12/2006
• Est. Priority Date: 03/08/2002
• Status: Active Grant

• Current Assignee: Philera New Zealand Limited
• Original Assignee: Philera New Zealand Limited
• Inventors: Baker, John R., Cooper, Garth J.S.
• Granted Patent: US 8,034,799 B2
• Time in Patent Office: Days
• US Class Current: 514/673
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/30 Copper compounds
• CPC Class Codes: A61K 31/38 having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/45 having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 33/34 Copper; Compounds thereof
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 39/04 Chelating agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

Methods are provided for reducing copper values for, by way of example, treating, preventing or ameliorating tissue damage such as, for example, tissue damage that may be caused by (i) disorders of the heart muscle (for example, cardiomyopathy or myocarditis) such as idiopathic cardiomyopathy, metabolic cardiomyopathy which includes diabetic cardiomyopathy, alcoholic cardiomyopathy, drug-induced cardiomyopathy, ischemic cardiomyopathy, and hypertensive cardiomyopathy, (ii) atheromatous disorders of the major blood vessels (macrovascular disease) such as the aorta, the coronary arteries, the carotid arteries, the cerebrovascular arteries, the renal arteries, the iliac arteries, the femoral arteries, and the popliteal arteries, (iii) toxic, drug-induced, and metabolic (including hypertensive and/or diabetic disorders of small blood vessels (microvascular disease) such as the retinal arterioles, the glomerular arterioles, the vasa nervorum, cardiac arterioles, and associated capillary beds of the eye, the kidney, the heart, and the central and peripheral nervous systems, (iv) plaque rupture of atheromatous lesions of major blood vessels such as the aorta, the coronary arteries, the carotid arteries, the cerebrovascular arteries, the renal arteries, the iliac arteries, the fermoral arteries and the popliteal arteries, (v) diabetes or the complications of diabetes.

Claims

1. A method of treating heart failure in a non-diabetic human subject, comprising administering to the subject a composition comprising a therapeutically effective amount of an agent capable of reducing copper levels in the subject.

2. The method of claim 1, wherein heart failure in the non-diabetic subject is associated with elevated copper levels.

3. The method of claim 1, wherein the copper is copper (II).

4. The method of claim 1, wherein the agent capable of reducing copper levels is a copper chelator.

5. The method of claim 1, wherein the agent capable of reducing copper levels is a copper (II) chelator.

6. The method of claim 5, wherein the affinity of the copper (II) chelator for copper is greater that its affinity for other trace metals.

7. The method of claim 1, wherein the agent capable of reducing copper levels is trientine.

8. The method of claim 1, wherein the agent is selected from a group consisting of 2,3,2 tetramine, D-penicillamine, N-acetylpenicillamine, trithimolybdate, and tetrathimolybdate.

9. The method of claim 1 wherein the copper chelator is selected from a group consisting of a 2,2,2 tetramine hydrochloride salt and a 2,3,2 tetramine hydrochloride salt.

10. The method of any of claims 1-8 or 9, wherein the amount of the agent administered is about 0.1 mg/kg, about 1.0 mg/kg, about 10 mg/kg, or about 100 mg/kg.

11. The method of any of claims 1-8 or 9, wherein the agent is administered in an amount ranging from about 0.001 to about 100 mg/kg/day, from about 0.01 to about 25 mg/kg/day, or from about 0.05 to about 10 mg/kg/day, from about 0.1 to about 5 mg/kg/day, or from about 0.5 to about 5 mg/kg/day.

12. The method of any of claims 1-8 or 9, wherein the agent is administered in an amount ranging from about 0.005 to about 0.05 mg/kg/day, from about 0.05 to about 0.5 mg/kg/day, or from about 0.001 to about 1 mg/kg/day.

13. The method of any of claims 1-8 or 9, wherein the agent is administered in an amount ranging from about 1 to about 1000 milligrams, from one to four times per day.

14. The method of any of claims 1-8 or 9, wherein the composition comprises about 1, 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, 400, 500, 600, 750, 800, 900, or 1000 milligrams of the agent, and is administered from one to four times per day.

15. The method of any of claims 1-8 or 9, wherein the composition is administered orally.

16. The method of claim 15, wherein the composition is in the form of a tablet or capsule.

17. The method of claim 15, wherein the composition is in the form of a long-acting tablet or capsule.

18. The method of any one of claims 1-8 or 9, wherein the agent is administered parenterally.

19. The method of claim 18, wherein the amount of agent administered is from about 0.001 to about 100 mg/kg/day.

20. The method of any of claims 1-8 or 9, wherein the composition is administered intravenously, subcutaneously, transdermally, transmucosally, sublingually, or by an implantable delivery system.

21. The method of claim 1, wherein the composition further comprises one or more zinc salts.

22. The method of claim 21, wherein the zinc salt is selected from the group consisting of zinc acetate, zinc chloride and zinc sulfate, zinc citrate, zinc isocitrate, zinc ketogluterate, zinc succinate, zinc malate, and zinc glucoante.

23. The method of claim 1, further comprising evaluating the copper values status of the subject.

24. The method of claim 23, wherein copper (II) values status is evaluated.

25. The method of claim 1, further comprising monitoring the copper values status of the subject.

26. The method of claim 25, wherein copper (II) values status is monitored.