IP Library Patent Application 13935882
Patent Application
App. No. 13/935,882

ORGAN PRECONDITIONING, ARREST, PROTECTION, PRESERVATION AND RECOVERY (2)

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Patent No.
US None
App. No.
13/935,882
Abstract

The present invention relates to a method for reducing electrical disturbance of a cell's resting membrane potential comprising administering an effective amount of a composition comprising an effective amount of a local anaesthetic and of one or more of a potassium channel opener, an adenosine receptor agonist, an anti-adrenergic, a calcium antagonist, an opioid, an NO donor and a sodium hydrogen exchange inhibitor.

Claims (25)

1 - 25 . (canceled)

26 . A method for reducing electrical disturbance of a cell's resting membrane potential comprising administering to the cell an effective amount of a composition comprising an effective amount of (i) a local anaesthetic; and (ii) at least one of a potassium channel opener, an adenosine receptor agonist, an anti-adrenergic, a calcium antagonist, an opioid, an NO donor and a sodium hydrogen exchange inhibitor, said composition further comprising a physiological potassium concentration.

27 . A method for reducing damage to a cell, tissue or organ following ischaemia comprising administering to the cell, tissue or organ an effective amount of a composition comprising an effective amount of (i) a local anesthetic; and (ii) at least one of a potassium channel opener, an adenosine receptor agonist, an anti-adrenergic, a calcium antagonist, an opioid, an NO donor and a sodium hydrogen exchange inhibitor, said composition further comprising a physiological potassium concentration.

28 . A method for preconditioning a cell or tissue during ischaemia or reperfusion comprising administering an effective amount of a composition comprising an effective amount of (i) a local anesthetic; and (ii) at least one of a potassium channel opener, an adenosine receptor agonist, an anti-adrenergic, a calcium antagonist, an opioid, an NO donor and a sodium hydrogen exchange inhibitor, said composition further comprising a physiological potassium concentration.

29 . A method for reducing damage to a cell, organ or tissue before, during and following a surgical or clinical intervention comprising administering to the cell, organ or tissue an effective amount of a composition comprising an effective amount of (i) a local anaesthetic; and (ii) at least one of a potassium channel opener, an adenosine receptor agonist, an anti-adrenergic, a calcium antagonist, an opioid, an NO donor and a sodium hydrogen exchange inhibitor, said composition further comprising a physiological potassium concentration.

30 . A method according to claim 27 wherein the anti-adrenergic is selected from beta-blockers and alpha(1)-adrenoceptor-antagonists.

31 . A method according to claim 27 wherein the opioid is selected from enkephalins, endorphins and dynorphins.

32 . A method according to claim 27 wherein the opioid is a delta opioid receptor agonist.

33 . A method according to claim 27 wherein the calcium antagonist is selected from Amlodipine, nifedipine, nicardipine, nimodipine, nisoldipine, lercanidipine, telodipine, angizem, altiazem, bepridil, amlodipine, felodipine, mibefradil, isradipine, cavero, Bay K 8644(L-type)(1,4-dihydro-26-dimethyl-5-nitro-[2(trifluoromethyl)phenyl]-3-pyridine carboxylic acid (methyl ester)), calciseptine (L-type), omega-conotoxin GVIA (N-type), omega-conotoxin MVIIC (Q-type), cyproheptadine HCI, dantrolene sodium, diltiazem HCI (L-type), filodipine, flunarizine HCI (Ca2+/Na+), fluspirilene (L-type), HA-1077 2HCI(1-(5 isoquinolinyl sulphonyl) homo piperazine.HCI), isradipine, loperamide HCI, manoalide, niguldipine HCI (L-type), nitrendipine (L-type), pimozide (L- and T-type), ruthenium red, ryanodine (SR channels), taicatoxin, verapamil HCI (L-type), Azelnidipine (L-type) methoxy-verapamil HCI (L-type), YS-035 HCI (L-type) N[2(3,4-dimethoxyphenyl)ethyl]-3,4-dimethoxy N-methyl benzene ethaneamine HCI) and calcium antagonists with AV blocking actions.

34 . A method according to claim 27 wherein the NO donor is either nitric-oxide synthase independent or nitric-oxide synthase dependent.

35 . A method according to claim 27 wherein the sodium hydrogen exchange inhibitor is selected from the group consisting of amiloride, cariporide, eniporide, triamterene and EMD 84021, EMD 94309, EMD 96785, and T-162559.

36 . A method according to claim 27 wherein the cell is a myocyte, endothelial cell, smooth-muscle cell, neutrophil, platelet and other inflammatory cells, or the tissue is heart tissue or vasculature, or the organ is a heart.

37 . A method according to claim 27 wherein the composition further comprises one or more of an antioxidant, ionic magnesium, an impermeant and a metabolic substrate.

38 . A method according to claim 27 wherein the composition has been oxygenated.

39 . A method according to claim 27 comprising administering the composition as part of a medicament including the composition and a pharmaceutically acceptable carrier, diluent, adjuvant, and/or excipient.

40 . A method according to claim 39 wherein the medicament has concentrations of one or more of sodium, calcium and chloride lower than physiological concentrations.

41 . A method according to claim 27 wherein the composition is at a temperature of profound hypothermia (0 to 4 degrees Celsius), moderate hypothermia (5 to 20 degrees Celsius), mild hypothermia (20 to 32 degrees Celsius) or normothermia (32 to 38 degrees Celsius).

42 . A method according to claim 27 wherein the components of the medicament or composition are combined before administration or when the components are administered substantially simultaneously or co-administered.

43 . A method according to claim 30 , wherein the alpha(1)-adrenoceptor-antagonist is prazosin.

44 . A method according to claim 30 , wherein the beta-blocker is selected from esmolol, atenolol, metoprolol and propranolol.

45 . A method according to claim 31 , wherein the opioid is an enkephalin which targets delta, alpha and/or mu receptors.

46 . A method according to claim 31 , wherein the opioid is DPDPE.

47 . A method according to claim 33 , wherein the calcium antagonist is verapamil.

48 . A method according to claim 34 , wherein the nitric-oxide synthase independent NO donor is selected from nitroprusside, nitro-glycerine, flurbiprofen or its NO-donating derivative, HCT1026 (2-fluoro-a-methyl[1,1 1 -biphenyl]-4-acetic acid and 4-(nitrooxy)butyl ester.

49 . A method according to claim 30 , wherein the nitric-oxide synthase dependent NO-donor is regulator calcium calmodulin and L-arginine.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2014
From: DOBSON, GEOFFREY PHILLIP
To: GLOBAL CARDIAC SOLUTIONS PTY LTD
Reel/Frame 033374/0620 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2014
From: HIBERNATION THERAPEUTICS LTD
To: HIBERNATION THERAPEUTICS GLOBAL LTD
Reel/Frame 033375/0319 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2014
From: HIBERNATION THERAPEUTICS GLOBAL LTD
To: HIBERNATION THERAPEUTICS, A KF LLC
Reel/Frame 033375/0359 →
CHANGE OF NAME Recorded Jul 23, 2014
From: GLOBAL CARDIAC SOLUTIONS PTY LTD
To: HIBERNATION THERAPEUTICS LTD
Reel/Frame 033390/0915 →