Claims
- 1. A method of treating tissue damage in a mammal selected from the myocardial tissue, tissue(s) of the vascular tree, and tissue(s) of organs dependent on the vascular tree, comprising subjecting said mammal to, and/or administering to said mammal, an amount of an agent or agents effective to lower the copper values content of said tissue(s) and treat said tissue damage.
- 2. A method of claim 1 wherein the patient is a human.
- 3. A method of claim 1 or 2 wherein the patient is not suffering from Wilson's Disease and has an elevated copper values content.
- 4. A method of claim 3 wherein there is at least one copper values status determination.
- 5. A method of claim 2 wherein the agent is trientine or a trientine type copper chelation agent.
- 6. A method of claim 2 wherein the agent is trientine or a trientine type copper chelation agent and the tissue copper values are lowered.
- 7. A method of claim 4 wherein trientine hydrochloride is administered at dosages or a dosage to provide, if parenteral, at least about 120 mg/day in a human patient, and if oral, at least about 600 to at least about 1200 mg/day in a human patient.
- 8. A method of claim 1 wherein the patient is a human being suffering from type 2 diabetes mellitus.
- 9. A method of claim 1 wherein improvement of the tissue repair arises from a restoration of, or substantial restoration, of normal tissue stem cell responses.
- 10. A method of claim 1 wherein the agent(s) is (are) selected from the group consisting of:
trientine (triene), ethylenediaminetetraacetic acid (EDTA), diethylenetriaminetetraacetic acid (DPTA), 2,2,2 tetramine tetrahydrochloride (TETA), 2,3,2 tetramine tetrahydrochloride, D-penicillamine (DPA) 1,4,8,11 tetraazacyclotretradecane (Cyclam), 5,7,7′,12,14,14′ hexamethyl-1,4,8,11 tetraazacyclotretradecane (Cyclam S), Sodium 2,3 dimercaptopropane-1-sulfonate (DMPS), N-acetylpenicillamine (NAPA), D-Penicillamine (PA),′Desferroxamine, 2,3-dimercaptopropanol (BAL), 2,3-dimercaptosuccinic acid (DMSA), trithiomolybdate, 3-7-Diazanonan-1,9-diamin (BE 6184), 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid, 1,4,8,11-tetraazabicyclo [6.6.2]hexadecane, 4,11-bis(N,N-diethyl-amidomethyl)-1,4,8.11-tetraazabicyclo[6.6.2]hexadecane, 4,11-bis(amidoethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane clioquinol, cuprizone, N,N′-diethyldithiocarbamate, zinc acetate, zinc salts, bathocuproinedisulfonic acid; bathocuprinedisulfonate, neocuproine (2,9-dimethyl-1,10-phenanthroline), tetrathiomolybdate, trimetazidine, triethylene tetramine tetrahydrochloride, 2,3,2-tetraamine, pyridine-2,6-bis(thiocarboxylic acid) or pyrrolidine dithiocarbamate, tetraethylenepentamine, N,N,N′,N-tetrakis(2-pyridylemethyl) ethylenediamine 1,4,7,11-tetraazaundecane tetrahydrochloride, tetraethylenepentamine pentahydrochloride, D-Penicillamine (DPA), 1,10-orthophenanthroline, 3,4-Dihydroxybenzoic acid, 2,2′-bicinchinonic acid, diamsar, 3,4′,5, trihydroxystilbene (resveratrol), mercaptodextran, o-phenanthroline, disulfiram (antabuse), sar, calcium trisodium diethylenetriaminepentaacetate (salt of cpd above), and methimazole (1-methyl-2-thiolimidazole).
- 9. A method of claim 1 wherein the agent (agents) is (are) a zinc salt (zinc salts).
- 10. A method of claim 1 wherein said damage is from any one or more of (i) disorders of the heart muscle (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.
- 11. A method of claim 1 wherein the patient is suffering from and/or is predisposed to heart failure.
- 12. A method of claim 11 wherein the patient is suffering from type 2 diabetes mellitus.
- 13. The use of a compound (a) which itself in vivo or (b) which has at least one metabolite in vivo that is (i) a copper chelator or (ii) otherwise reduces available copper values for the production of a pharmaceutical composition or dosage unit able to reduce the level of copper in a mammal thereby to elicit by a lowering of copper values in a mammalian patient an improvement of tissue repair of damaged tissue selected from that of the myocardium, the vascular tree and organs dependent on the vascular tree.
- 14. The use of claim 13 wherein the damage is that which has arisen from a disease selected from the group consisting of (i) disorders of the heart muscle (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.
- 15. The use of claim 13 or 14 wherein the compound is selected from the group consisting of:
trientine (triene), ethylenediaminetetraacetic acid (EDTA), diethylenetriaminetetraacetic acid (DPTA), 2,2,2 tetramine tetrahydrochloride (TETA), 2,3,2 tetramine tetrahydrochloride, D-penicillamine (DPA) 1,4,8,11 tetraazacyclotretradecane (Cyclam), 5,7,7′,12,14,14′ hexamethyl-1,4,8,11 tetraazacyclotretradecane (Cyclam S), Sodium 2,3 dimercaptopropane-1-sulfonate (DMPS), N-acetylpenicillamine (NAPA), D-Penicillamine (PA),′Desferroxamine, 2,3-dimercaptopropanol (BAL), 2,3-dimercaptosuccinic acid (DMSA), trithiomolybdate, 3-7-Diazanonan-1,9-diamin (BE 6184), 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid, 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane, 4,11-bis(N,N-diethyl-amidomethyl)-1,4,8.11-tetraazabicyclo[6.6.2]hexadecane, 4,11-bis(amidoethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane melatonin, clioquinol, cupnzone, N,N′-diethyldithiocarbamate, zinc acetate, zinc salts, bathocuproinedisulfonic acid; bathocuprinedisulfonate, neocuproine (2,9-dimethyl-1,10-phenanthroline), tetrathiomolybdate, trimetazidine, triethylene tetramine tetrahydrochloride, 2,3,2-tetraamine, pyridine-2,6-bis(thiocarboxylic acid) or pyrrolidine dithiocarbamate, tetraethylenepentamine, N,N,N′,N-tetrakis(2-pyridylemethyl) ethylenediamine 1,4,7,11-tetraazaundecane tetrahydrochloride, tetraethylenepentamine pentahydrochloride, D-Penicillamine (DPA), 1,10-orthophenanthroline, 3,4-Dihydroxybenzoic acid, 2,2′-bicinchinonic acid, diamsar, 3,4′,5, trihydroxystilbene (resveratrol), mercaptodextran, o-phenanthroline, disulfiram (antabuse), sar, calcium trisodium diethylenetriaminepentaacetate (salt of cpd above), and methimazole (1-methyl-2-thiolimidazole).
- 16. The use of claim 13 wherein the compound is trientine or a trientine-type copper chelation agent.
- 17. The use of claim 13 which includes one or more pharmaceutically acceptable excipients, diluents and/or carriers.
- 18. A dosage unit resulting from the use of claim 13.
- 19. A method of treating a mammalian subject at risk of developing, with suspected or with actual tissue disease to the myocardium, the vascular tree and/or organs dependent on the vascular tree, which method comprises the step of administering to the subject one or more agents capable of decreasing the copper values content, whereby tissue repair in said subject is enhanced.
- 20. A method of claim 19 wherein said subject is not suffering from Wilson's Disease and has an elevated copper values content.
- 21. The method of claim 19 wherein said subject is a human.
- 22. A method of any of claims 19, 20 or 21 wherein the agent(s) is (are) a chelator (chelators) of copper.
- 23. A method of any of claims 19, 20 or 21 wherein the agent(s) has (have) an affinity for copper over that of iron.
- 24. A method of treating a mammalian subject at risk of developing, with suspected or with actual tissue disease to the myocardium, the vascular tree and/or organs dependent on the vascular tree, which method comprises or includes the steps of:
determining the copper status of the subject, and if the copper status of a subject is elevated yet the patient is not suffering from Wilson's Disease, subjecting the patient to and/or administering to the subject one or more agents capable of decreasing the subject's copper values content, whereby tissue repair in said subject is enhanced.
- 25. A method of claim 23 which involves continual evaluating or monitoring of the copper status of the subject.
- 26. A method of claim 23 or 24 wherein the determination of the copper status is by reference to extra cellular copper values.
- 27. A method of claim 23 wherein the decreasing of the subject's copper values content is from an elevated status being that typical of the copper values status of a human patient suffering from type 2 diabetic mellitus over that of a non-diabetic.
- 28. A method of claim 23 which includes the step of diagnosing and/or evaluating or monitoring hypertension.
- 29. A method of claim 23 which includes the step of diagnosing alcoholism.
- 30. A method of claim 23 which includes the step of diagnosing and/or evaluating or monitoring a glucose mechanism abnormality of the patient.
- 31. A method of claim 29 wherein the abnormality is type 2 diabetes mellitus, impaired glucose tolerance and/or impaired fasting glucose.
- 32. A method of claim 23 which includes the step of diagnosing and/or evaluating or monitoring macrovascular, microvascular, toxic and/or metabolic damage in the patient.
- 32. A method of claim 23 wherein the damage is that of any one or more of:
(i) disorders of the heart muscle (cardiomyopathy or myocarditis) such as idiopathic cardiomyopathy, metabolic cardiomyopathy which includes diabetic cardiomyopathy, alcoholic cardiomyopathy, drug-induced cardiomyopathy, ischemic cardiomyopathy, and hypertensive cardiomyopathy, or (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, or (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, or (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.
Priority Claims (2)
Number |
Date |
Country |
Kind |
517725 |
Mar 2002 |
NZ |
|
PCT/NZ03/00042 |
Mar 2003 |
WO |
|
RELATED APPLICATIONS
[0001] This application claims priority from U.S. Provisional Patent Application Serial No. 60/364,382, filed Mar. 12, 2002, New Zealand Provisional Patent Application Serial No. 517725, filed Mar. 12, 2002, and a corresponding PCT application filed on Mar. 10, 2003 (Serial No. NZ/03/00042), the contents of each of which are hereby incorporated in their entirety by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60364382 |
Mar 2002 |
US |