Prevention and treatment of oxidative stress disorders by gluthathione and phase II detoxification enzymes

• US 8,709,406 B2
• Filed: 11/06/2012
• Issued: 04/29/2014
• Est. Priority Date: 12/18/2001
• Status: Expired due to Term

• Current Assignee: Brassica Foundation for Chemoprotection Research, Inc.
• Original Assignee: Brassica Foundation for Chemoprotection Research, Inc.
• Inventors: Gao, Xiangqun, Dinkova-Kostova, Albena T., Talalay, Paul
• Primary Examiner(s): Saidha, Tekchand
• Application Number:
  US13/670,161
• Publication Number:
  US 20130157965A1
• Time in Patent Office: 539 Days
• Field of Search: 424/94.4, 435/183
• US Class Current: 424/94.4
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/26 Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
• CPC Class Codes: A61K 31/7024 Esters of saccharides
• CPC Class Codes: A61P 17/18 Antioxidants, e.g. antiradicals preparations for protection against sunlight A61Q17/00
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention generally relates to the field of treating oxidative stress disorders by administering a pharmaceutically effective amount of a compound that elevates the intracellular levels of glutathone or intracelluar levels of at least one Phase II detoxification enzyme in animal tissue. The present invention also relates to the field of protecting a subject from oxidative stress disorders by administering a pharmaceutically effective amount of a compound that elevates the intracellular levels of glutathone or intracelluar levels of at least one Phase II detoxification enzyme in the subject. The present invention also relates to a pharmaceutical composition useful for the treatment of oxidative stress disorders.

Claims

1. A method of treating a subject in need of treatment of an oxidative stress disorder, said method comprising administering to said subject a composition comprising an effective amount of a compound that elevates intracellular levels of glutathione or intracelluar levels of at least one Phase IT detoxification enzyme in diseased tissue of said subject, wherein said oxidative stress disorder is selected from the group consisting of Alzheimer'"'"'s Disease and aging.

2. The method of claim 1, wherein said compound is selected from the group consisting of an isothiocyanate and a glucosinolate.

3. The method of claim 2, wherein said isothiocyante is sulforaphane.

4. The method of claim 1, wherein said Phase IT detoxification enzyme is selected from the group consisting of UDP-glucuronosyltransferases, sulfotransferases, phenol-O-methyltransferase, catechol-O-methyltransferase, histamine N-methyltransferase, nicotinamide N-methyltransferase, thiopurine methyltransferase, thiol methyltransferase, N-acetyltransferases, O-acetyltransferases, acyl-CoA synthetases, acyl-CoA:

amino acid N-acyltransferases, aminoacyl-tRNA synthetases, glutathione synthetases, gamma glutamylcysteine synthetases, glutathione S-transferases, quinone reductases, heme oxygenases, rhodaneses, glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase.

9. The method of claim 1, wherein the composition is administered orally, nasally, parenterally, intrasystemically, intraperitoneally, topically, bucally, or as an oral or nasal spray.

10. The method of claim 1, wherein the composition further comprises a carrier or excipient and is formulated as a lotion, a cream, a gel or an ointment for topical administration.

11. The method of claim 10, wherein the composition is administered to the skin.

5. A method of protecting a subject from an oxidative stress disorder, said method comprising administering to said subject a composition comprising an effective amount of a compound that elevates intracellular levels of glutathione or intracellular levels of at least one Phase II detoxification enzyme in diseased tissue of said subject, wherein said oxidative stress disorder is selected from the group consisting of Alzheimer'"'"'s Disease and aging.

6. The method of claim 5, wherein said compound is selected from the group consisting of an isothiocyanate and a glucosinolate.

7. The method of claim 6, wherein said isothiocyanate is sulforaphane.

8. The method of claim 5, wherein said Phase II detoxification enzyme is selected from the group consisting of UDP-glucuronosyltransferases, sulfotransferases, phenol-O-methyltransferase, catechol-O-methyltransferase, histamine N-methyltransferase, nicotinamide N-methyltransferase, thiopurine methyltransferase, thiol methyltransferase, N-acetyltransferases, O-acetyltransferases, acyl-CoA synthetases, acyl-CoA:

amino acid N-acyltransferases, aminoacyl-tRNA synthetases, glutathione synthetases, gamma glutamylcysteine synthetases, glutathione S-transferases, quinone reductases, heme oxygenases, rhodaneses, glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase.

12. The method of claim 5, wherein the composition is administered orally, nasally, parenterally, intrasystemically, intraperitoneally, topically, bucally, or as an oral or nasal spray.

13. The method of claim 5, wherein the composition further comprises a carrier or excipient and is formulated as a lotion, a cream, a gel or an ointment for topical administration.

14. The method of claim 13, wherein the composition is administered to the skin.