Zinc ionophores as therapeutic agents

• US 6,495,538 B2
• Filed: 01/12/2001
• Issued: 12/17/2002
• Est. Priority Date: 06/23/1999
• Status: Expired due to Fees

• Current Assignee: ZINC Therapeutics Canada Incorporated
• Original Assignee: ZINC Therapeutics Canada Incorporated
• Inventors: Fliss, Henry
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US09/759,091
• Publication Number:
  US 20010036939A1
• Time in Patent Office: 704 Days
• Field of Search: 514/458, 514/725, 514/188, 514/476
• US Class Current: 514/188
• CPC Class Codes: A61K 31/07 Retinol compounds, e.g. vitamin A retinoic acids A61K31/203
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/315 Zinc compounds
• CPC Class Codes: A61K 31/325 Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof thiurams A61K31/145
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol

Abstract

The present invention provides methods and compositions comprising one or more zinc ionophores for protecting tissue from the harmful effects of apoptosis in patients in need thereof. Concentrations of zinc-pyrithione and diethyldithiocarbamate in the picomolar to nanomolar range have a strong protective effect against apoptosis.

Claims

1. A method of treating seizures comprising administering to a subject in need of thereof an effective amount of a zinc ionophore and a pharmaceutically acceptable carrier.

2. The method of claim 1, wherein the zinc ionophore comprises of zinc pyrithone, heterocyclic amines, dithiocarbamates and Vitamins.

3. The method of claim 2, wherein the zinc ionophore is zinc pyrithione.

4. The method of claim 2, wherein said heterocyclic amine comprises 5,7-Diiode-8-hydroxyquinoline and 8-Hydroxyquinoline.

5. The method of claim 2, wherein said dithiocarbamate comprises pyrrolidine dithiocarbamate, zinc-diethyldithiocarbamate, disulfiram and zinc-dimethyldithiocarbamate.

6. The method of claim 2, wherein said vitamin is selected from the group consisting of Vitamin E and Vitamin A.

7. The method of claim 1, wherein the effective amount of a zinc ionophore ranges from about 0.005 μ

g per kg of body weight to about 5.0 mg per kg of body weight.

8. The method of claim 7, wherein the effective amount of a zinc ionophore ranges from about 0.2 μ

g per kg of body weight to about 600 μ

g per kg of body weight.

9. A method of treating conditions caused by apoptosis comprising administering to a subject in need thereof an effective amount of a zinc ionophore and a pharmaceutically acceptable carrier.

10. The method of claim 9, wherein the zinc ionophore comprises zinc pyrithione, heterocyclic amines, dithiocarbamates and Vitamins.

11. The method of claim 10, wherein the zinc ionophore is zinc pyrithione.

12. The method of claim 10, wherein said heterocyclic amine is selected from the group consisting of 5,7-Diiodo-8-hydroxyquinoline and 8-Hydroxyquinoline.

13. The method of claim 10, wherein said dithiocarbamate is selected from the group consisting of pyrrolidine dithiocarbamate, zinc-diethyldithiocarbamate, disulfiram and zinc-dimethyldithiocarbamate.

14. The method of claim 10, wherein said vitamin is selected from the group consisting of Vitamin E and Vitamin A.

15. The method of claim 9, wherein the effective amount of a zinc ionophore ranges from about 0.005 μ

g per kg of body weight to about 5.0 mg per kg of body weight.

16. The method of claim 15, wherein the effective amount of a zinc ionophore ranges from about 0.2 μ

g per kg of body weight to about 600 μ

g per kg of body weight.

17. An anti-epileptic composition comprising a zinc ionophore and a pharmaceutically acceptable carrier.

18. A method of preventing seizures comprising administering to a subject in need thereof an effective amount of a zinc ionophore and a pharmaceutically acceptable carrier.

19. The method of claim 18, wherein the zinc ionophore comprises zinc pyrithione, heterocyclic amines, dithiocarbamates and Vitamins.

20. The method of claim 19, wherein the zinc ionophore is zinc pyrithione.

21. The method of claim 19, wherein said heterocyclic amine comprises 5,7-Diiodo-8-hydroxyquinoline and 8-Hydroxyquinoline.

22. The method of claim 19, wherein said dithiocarbamate comprises pyrrolidine dithiocarbamate, zinc-diethyldithiocarbamate, disulfiram and zinc-dimethyldithiocarbamate.

23. The method of claim 19, wherein said vitamin is selected from the group consisting of Vitamin E and Vitamin A.

24. The method of claim 18, wherein the effective amount of a zinc ionophore ranges from about 0.005 μ

g per kg of body weight to about 5.0 mg per kg of body body weight.

25. The method of claim 24, wherein the effective amount of a zinc ionophore ranges from about 0.2 μ

g per kg of body weight to about 600 μ

g per kg of body weight.

26. The method of claim 18, wherein the zinc ionophore is administered intravenously, intramuscularly, subcutaneously, intracerebroventricularly, orally or topically.