Oxidant Scavengers for Treatment of Diabetes or Use in Transplantation or Induction of Immune Tolerance

• US 20110105452A1
• Filed: 11/08/2010
• Published: 05/05/2011
• Est. Priority Date: 01/25/1999
• Status: Active Grant

• Current Assignee: Aeolus Sciences Incorporated, National Jewish Medical and Research Center, University of Colorado System
• Original Assignee: Aeolus Sciences Incorporated, National Jewish Medical and Research Center, University of Colorado System
• Inventors: Crapo, James D., Haskins, Kathryn, Flores, Sonia C., Patel, Manisha, day, Brian J., Gammans, Richard, Piganelli, Jon D., Gill, Ronald G.
• Granted Patent: US 8,470,808 B2
• Time in Patent Office: Days
• US Class Current: 514/185
• CPC Class Codes: A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine hemin, hematin A61K31/555
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• 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 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The present invention relates, in one embodiment, to a method of preventing or treating diabetes using low molecular weight antioxidants. In a further embodiment, the invention relates to a method of protecting and/or enhancing viability of cells/tissues/organs during isolation (harvesting), preservation, expansion and/or transplantation. In yet another embodiment, the present invention relates to a method of inducing immune tolerance. The invention also relates to compounds and compositions suitable for use in such methods.

Claims

1. A method of preventing or treating diabetes, said method comprising administering to a patient in need an effective amount of a compound of formula

2. The method according to claim 1, wherein said compound is complexed with a metal selected from the group consisting of manganese, iron copper, cobalt, nickel and zinc.

3. The method according to claim 2, wherein said metal is manganese.

4. The method according to claim 1, wherein said electronic withdrawing group is alkyl, 2-hydroxyalkyl, methoxyalkyl, halogen, nitro, cyano, trialkylammonium, formyl, amide of carboxylic acid, alkyl ester of carboxylic acid, carboxylic acid, glucuronyl or glyceryl ester of carboxylic acid, 1,2-dihydroxyalkyl, acetyl, vinyl, glycosyl or taurate.

5. The method according to claim 1, wherein each P is hydrogen.

6. The method according to claim 1, wherein each R is C₆ alkyl.

7. The method according to claim 1, wherein said diabetes is type I diabetes or type II diabetes.

8. The method according to claim 1, said compound of formula

9. The method according to claim 8, wherein said diabetes results from death of pancreatic islet cells due to autoimmune disease.

10. The method according to claim 8, wherein said diabetes results from death of pancreatic islet cells due to radical induced toxicity.

11. A method of preventing or treating diabetes specific microvascular disease, said method comprising administering to a patient in need an effective amount of a compound of formula

12. The method according to claim 11, wherein said compound is complexed with a metal selected from the group consisting of manganese, iron copper, cobalt, nickel and zinc.

13. The method according to claim 12, wherein said metal is manganese.

14. The method according to claim 11, wherein said electronic withdrawing group is alkyl, 2-hydroxyalkyl, methoxyalkyl, halogen, nitro, cyano, trialkylammonium, formyl, amide of carboxylic acid, alkyl ester of carboxylic acid, carboxylic acid, glucuronyl or glyceryl ester of carboxylic acid, 1,2-dihydroxyalkyl, acetyl, vinyl, glycosyl or taurate.

15. The method according to claim 11, wherein each P is hydrogen.

16. The method according to claim 11, wherein each R is C₆ alkyl.

17. The method according to claim 11, said compound of formula