IP Library Granted Patent US 10,166,244
Granted Patent B2
US 10,166,244 · App. 15/369,056 · Granted Jan 1, 2019

Targeting NC

Inventor: J. Marc Simard (Baltimore, MD)
Assignees: University of Maryland, Baltimore; The United States of America as Represented by the Department of Veteran Affairs
A61K31/57G01N33/6872A61K31/427A61K31/565A61K38/00
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Quick Facts
Patent No.
US 10,166,244
App. No.
15/369,056
Granted
Jan 1, 2019
Kind
B2
Abstract

The present invention concerns protection of an organ or tissue outside of the central nervous system following an ischemic episode. In particular aspects, the invention concerns organ preservation for transplantation, angina pectoris, kidney reperfusion injury, and so forth. In specific embodiments, the organ is subjected to an inhibitor of an NC Ca-ATP channel that is regulated by SUR1. Exemplary inhibitors include sulfonylurea compounds, such as glibenclamide, for example.

Claims (19)

1. A method of treating or reducing ischemic damage in a subject comprising administering an inhibitor of an NC Ca-ATP channel that is a SUR1 antagonist and/or a TRPM4 antagonist as a loading bolus dose followed by a constant infusion of a maintenance dose, wherein the bolus dose is 30-90 times the amount of the maintenance dose.

2. The method of claim 1 , wherein the SUR1 antagonist is glibenclamide (glyburide), tolbutamide, acetohexamide, chlorpropamide, tolazimide, glipizide, gliquidone, repaglinide, nateglinide, meglitinide, gliclazide, glimepiride, repaglinide, nateglinide, mitiglinide, a pharmaceutically salt thereof, or an active metabolite thereof.

3. The method of claim 1 , wherein the TRPM4 antagonist is selected from the group consisting of flufenamic acid, mefanimic acid, niflumic acid, and antagonists of VEGF, MMP, NOS, TNFα, NFkB, and/or thrombin.

4. The method of claim 1 , wherein said inhibitor is delivered by intravenous, subcutaneous, intramuscular, intracutaneous, intragastric or oral administration.

5. The method of claim 1 , wherein the inhibitor is administered prior to an ischemic episode, concurrent with an ischemic episode, or both.

6. The method of claim 1 , wherein the inhibitor is administered following an ischemic episode.

7. The method of claim 1 , wherein the method further comprises delivering the inhibitor directly to the organ or tissue.

8. The method of claim 1 , wherein the method further comprises delivering the inhibitor to the subject prior to extraction of an organ or tissue, during extraction of the organ or tissue, or both.

9. The method of claim 1 , wherein the method further comprises delivering the inhibitor to an organ or tissue prior to extraction of the respective organ or tissue from the subject, delivering the inhibitor to the organ or tissue during extraction of the respective organ or tissue from the subject, delivering the inhibitor to the organ or tissue subsequent to extraction of the respective organ or tissue from the subject, or a combination thereof.

10. The method of claim 1 , wherein the method further comprises delivering the inhibitor to a recipient of an organ or tissue prior to transplantation of the respective organ or tissue into the recipient, during transplantation of the respective organ or tissue into the recipient, and/or after transplantation of the respective organ or tissue into the recipient.

11. The method of claim 1 , wherein the ischemic damage is related to organ preservation for transplantation, angina pectoris, or kidney reperfusion injury.

12. The method of claim 1 , wherein the method further comprises delivery of an additional therapeutic agent.

13. The method of claim 12 , wherein the additional therapeutic agent comprises an antacid, an immunosuppressant, an antiviral compound, an antibacterial compound, an antifungal compound, or a combination or mixture thereof.

14. The method of claim 12 , wherein the additional therapeutic agent comprises anti-thymocyte globulin, basiliximab, methylprednisolone, tacrolimus, mycophenolate mofetil, prednisone, sirolimus, rapamycin, azathioprine, or a mixture thereof.

15. The method of claim 1 , wherein SUR1 antagonist is administered to the subject in a dosage of less than 3.5 mg per day.

16. The method of claim 1 , wherein the SUR1 antagonist is administered to the subject at a dosage of less than 0.8 mg/kg body weight within a 24 hour period.

17. The method of claim 1 , wherein the maintenance dose is administered as a constant infusion.

18. The method of claim 1 , wherein the maintenance dose is administered for six or more hours.

19. The method of claim 1 , wherein the maintenance dose is administered for twenty-four or more hours.

Assignments (3)
ASSIGNMENT OF A JOINT UNDIVIDED RIGHT, TITLE AND INTEREST Recorded Feb 2, 2017
From: UNIVERSITY OF MARYLAND, BALTIMORE
To: THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS
Reel/Frame 041592/0063 →
CONFIRMATORY LICENSE Recorded Jan 11, 2017
From: UNIVERSITY OF MARYLAND BALTIMORE
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 040940/0636 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 10, 2017
From: SIMARD, J. MARC
To: UNIVERSITY OF MARYLAND, BALTIMORE
Reel/Frame 040938/0326 →
Continuity (6)
Continuation 12522444
Provisional Application 61012613 · Dec 10, 2007
Provisional Application 60952396 · Jul 27, 2007
Provisional Application 60923378 · Apr 13, 2007
Provisional Application 60880119 · Jan 12, 2007
Related Publication 20170296555A1 · Oct 19, 2017