US2004167114A1PendingUtilityA1

Zinc ionophores as therapeutic agents

56
Priority: Jun 23, 1999Filed: Jan 16, 2004Published: Aug 26, 2004
Est. expiryJun 23, 2019(expired)· nominal 20-yr term from priority
Inventors:Henry Fliss
A61K 31/44A61K 31/47A61K 31/145A61K 31/325A61K 31/405A61K 31/555A61K 31/355A61K 31/27A61K 31/40A61K 31/315A61K 31/07
56
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Claims

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

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method of treating apoptosis comprising administering to a subject in need thereof a pharmaceutically effective amount of a zinc ionophore and a pharmaceutically acceptable carrier.  
     
     
         2 . The method of  claim 1 , wherein the zinc ionophore comprises zinc pyrithione, 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-Diiodo-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 μg 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 μg per kg of body weight to about 600 μg per kg of body weight.  
     
     
         9 . The method of  claim 1 , wherein the zinc ionophore is administered intravenously, intramuscularly, subcutaneously, intracerebroventricularly, orally or topically.  
     
     
         10 . A method of treating the harmful effects of injurious agents selected from the group consisting of oxidants, TNFα, neurotoxins, and radiation comprising administering to a subject in need of such protection an effective amount of a zinc ionophore and a pharmaceutically acceptable carrier.  
     
     
         11 . The method of  claim 10 , wherein the zinc ionophore comprises zinc pyrithione, heterocyclic amines, dithiocarbamates and Vitamins.  
     
     
         12 . The method of  claim 11 , wherein the zinc ionophore is zinc pyrithione.  
     
     
         13 . The method of  claim 11 , wherein said heterocyclic amine comprises 5,7-Diiodo-8-hydroxyquinoline and 8-Hydroxyquinoline.  
     
     
         14 . The method of  claim 11 , wherein said dithiocarbamate comprises pyrrolidine dithiocarbamate, zinc-diethyldithiocarbamate, disulfiram and zinc-dimethyldithiocarbamate.  
     
     
         15 . The method of  claim 11 , wherein said vitamin is selected from the group consisting of Vitamin E and Vitamin A.  
     
     
         16 . The method of  claim 10 , wherein the effective amount of a zinc ionophore ranges from about 0.005 μg per kg of body weight to about 5.0 mg per kg of body weight.  
     
     
         17 . The method of  claim 16 , wherein the effective amount of a zinc ionophore ranges from about 0.2 μg per kg of body weight to about 600 μg per kg of body weight.  
     
     
         18 . The method of  claim 10 , wherein the zinc ionophore is administered intravenously, intramuscularly, subcutaneously, intracerebroventricularly, orally or topically.  
     
     
         19 . A pharmaceutical composition comprising a zinc ionophore and a pharmaceutically acceptable carrier.  
     
     
         20 . A method of treating ischemia comprising administering to a subject in need thereof an effective amount of a zinc ionophore and a pharmaceutically acceptable carrier.  
     
     
         21 . The method of  claim 20 , wherein the zinc ionophore comprises zinc pyrithione, heterocyclic amines, dithiocarbamates and Vitamins.  
     
     
         22 . The method of  claim 21 , wherein the zinc ionophore is zinc pyrithione.  
     
     
         23 . The method of  claim 21 , wherein said heterocyclic amine comprises of 5,7-Diiodo-8-hydroxyquinoline and 8-Hydroxyquinoline.  
     
     
         24 . The method of  claim 21 , wherein said dithiocarbamate comprises of pyrrolidine dithiocarbamate, zinc-diethyldithiocarbamate, disulfiram and zinc-dimethyldithiocarbamate.  
     
     
         25 . The method of  claim 21 , wherein said vitamin is selected from the group consisting of Vitamin E and Vitamin A.  
     
     
         26 . The method of  claim 20 , wherein the effective amount of a zinc ionophore ranges from about 0.005 μg per kg of body weight to about 5.0 mg per kg of body weight.  
     
     
         27 . The method of  claim 26 , wherein the effective amount of a zinc ionophore ranges from about 0.2 μg per kg of body weight to about 600 μg per kg of body weight.  
     
     
         28 . 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.  
     
     
         29 . The method of  claim 28 , wherein the zinc ionophore comprises of zinc pyrithione, heterocyclic amines, dithiocarbamates and Vitamins.  
     
     
         30 . The method of  claim 29 , wherein the zinc ionophore is zinc pyrithione.  
     
     
         31 . The method of  claim 29 , wherein said heterocyclic amine comprises 5,7-Diiodo-8-hydroxyquinoline and 8-Hydroxyquinoline.  
     
     
         32 . The method of  claim 29 , wherein said dithiocarbamate comprises pyrrolidine dithiocarbamate, zinc-diethyldithiocarbamate, disulfiram and zinc-dimethyldithiocarbamate.  
     
     
         33 . The method of  claim 29 , wherein said vitamin is selected from the group consisting of Vitamin E and Vitamin A.  
     
     
         34 . The method of  claim 28 , wherein the effective amount of a zinc ionophore ranges from about 0.005 μg per kg of body weight to about 5.0 mg per kg of body weight.  
     
     
         35 . The method of  claim 24 , wherein the effective amount of a zinc ionophore ranges from about 0.2 μg per kg of body weight to about 600 μg per kg of body weight.  
     
     
         36 . 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.  
     
     
         37 . The method of  claim 36 , wherein the zinc ionophore comprises zinc pyrithione, heterocyclic amines, dithiocarbamates and Vitamins.  
     
     
         38 . The method of  claim 37 , wherein the zinc ionophore is zinc pyrithione.  
     
     
         39 . The method of  claim 37 , wherein said heterocyclic amine is selected from the group consisting of 5,7-Diiodo-8-hydroxyquinoline and 8-Hydroxyquinoline.  
     
     
         40 . The method of  claim 37 , wherein said dithiocarbamate is selected from the group consisting of pyrrolidine dithiocarbamate, zinc-diethyldithiocarbamate, disulfiram and zinc-dimethyldithiocarbamate.  
     
     
         41 . The method of  claim 37 , wherein said vitamin is selected from the group consisting of Vitamin E and Vitamin A.  
     
     
         42 . The method of  claim 36 , wherein the effective amount of a zinc ionophore ranges from about 0.005 μg per kg of body weight to about 5.0 mg per kg of body weight.  
     
     
         43 . The method of  claim 32 , wherein the effective amount of a zinc ionophore ranges from about 0.2μg per kg of body weight to about 600 μg per kg of body weight.  
     
     
         44 . An anti-epileptic composition comprising a zinc ionophore and a pharmaceutically acceptable carrier.  
     
     
         45 . 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.

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