Combination

Abstract

The present invention provides a combination comprising at least two of the following: (i) an insulin modulator, (ii) an immunosuppressive agent and (iii) an aldosterone antagonist, for instance a combination comprising at least two of (i) exenatide, or a functional derivative or analogue thereof, or a pharmaceutically acceptable salt thereof; (ii) cyclosporine, or a functional derivative or analogue thereof, or a pharmaceutically acceptable salt thereof; and (iii) potassium canrenoate, or a functional derivative or analogue thereof. Said combinations are suitable for cardioprotection and for treating and/or preventing ischemia and/or reperfusion injury. Further aspects of the invention relate to pharmaceutical products and pharmaceutical compositions comprising said combinations according to the invention, and methods of treatment using the same.

1 . A combination comprising an insulin modulator, wherein the insulin modulator is exenatide or a pharmaceutically acceptable salt thereof, and an aldosterone antagonist, wherein the aldosterone antagonist is potassium canrenoate. 
     
     
         2 - 11 . (canceled) 
     
     
         12 . A combination according to  claim 1  which comprises at least one further active pharmaceutical ingredient (API) selected from a beta blocker, a renin-angiotensin inhibitor, a statin (HMG-CoA reductase inhibitor), an inhibitor of platelet activation or aggregation, a phosphodiesterase-3 inhibitor, a calcium sensitizer, an antioxidant and an anti-inflammatory agent. 
     
     
         13 . A pharmaceutical composition comprising a combination according to  claim 1  and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         14 . The pharmaceutical composition according to  claim 13  in a form suitable for parenteral administration. 
     
     
         15 . (canceled) 
     
     
         16 . A pharmaceutical product comprising an insulin modulator, wherein the insulin modulator is exenatide, or a pharmaceutically acceptable salt thereof; and an aldosterone antagonist, wherein the aldosterone antagonist is potassium canrenoate. 
     
     
         17 - 33 . (canceled) 
     
     
         34 . A method of treating and/or preventing one or more of ischemia and/or reperfusion injury, ischemic stroke, cardiac arrest, acute myocardial infarction, neonatal asphyxia and cardiogenic shock, or for providing cardioprotection against cardiotoxic drugs, said method comprising simultaneously, sequentially or separately administering to a subject in need thereof, the following components: an insulin modulator, wherein the insulin modulator is exenatide, or a pharmaceutically acceptable salt thereof; and an aldosterone potassium canrenoate. 
     
     
         35 - 37 . (canceled) 
     
     
         38 . The method according to  claim 34  wherein the ischemia and/or reperfusion injury is ischemia and/or reperfusion injury of the brain, heart, lung, or kidney. 
     
     
         39 . The method according to  claim 34  wherein the components are administered parenterally. 
     
     
         40 . The method according to  claim 34  wherein the components are administered during reperfusion. 
     
     
         41 . The method according to  claim 34  wherein the components are administered before reperfusion. 
     
     
         42 . The method according to  claim 34  wherein the components are administered after reperfusion. 
     
     
         43 . The method according to  claim 34  which comprises simultaneously administering the components to said subject. 
     
     
         44 - 61 . (canceled) 
     
     
         62 . The pharmaceutical composition according to  claim 13  in a form suitable for intravenous administration 
     
     
         63 . The pharmaceutical product according to  claim 16 , wherein the components are formulated for simultaneous administration. 
     
     
         64 . The pharmaceutical product according to  claim 16 , wherein the components are formulated for sequential administration. 
     
     
         65 . The pharmaceutical product according to  claim 16 , wherein the components are formulated for separate administration. 
     
     
         66 . The method according to  claim 34 , wherein the ischemia is myocardial ischemia. 
     
     
         67 . The method according to  claim 34 , wherein the reperfusion injury is myocardial reperfusion injury or acute myocardial infarction. 
     
     
         68 . The method according to  claim 34 , wherein the components are administered intravenously. 
     
     
         69 . A pharmaceutical product comprising an insulin modulator, wherein the insulin modulator is exenatide, or a functional derivative or analogue, or a pharmaceutically acceptable salt thereof; and an aldosterone antagonist, wherein the aldosterone antagonist is potassium canrenoate, or a functional derivative or analogue thereof. 
     
     
         70 . The pharmaceutical product according to  claim 69 , wherein the exenatide functional derivative or analogue is selected from lixisenatide, albiglutide, liraglutide, taspoglutide and dulaglutide (LY2189265). 
     
     
         71 . A method of treating and/or preventing one or more of ischemia and/or reperfusion injury, ischemic stroke, cardiac arrest, acute myocardial infarction, neonatal asphyxia and cardiogenic shock, or for providing cardioprotection against cardiotoxic drugs, said method comprising simultaneously, sequentially or separately administering to a subject in need thereof; a pharmaceutical product of  claim 69 .