Dodecafluoropentane emulsion as a stroke and ischemia therapy

Abstract

The present invention provides methods and combinations for reducing the infarct volume in a tissue of a subject undergoing ischemia or at risk of developing ischemia.

What is claimed is: 
     
         1 . A method for reducing the infarct volume in a tissue of a subject undergoing ischemia resulting from an ischemic event, the method comprising administering an effective amount of a composition comprising a perfluorocarbon emulsion, wherein the perfluorocarbon has a boiling point below about 100° C. to the subject, wherein the infarct volume is reduced without resolving the ischemic event. 
     
     
         2 . The method of  claim 1 , (a) wherein the composition comprising a perfluorocarbon emulsion is administered (i) in a time ranging from immediately after the start of the ischemic event to 24 hours after the onset of symptoms and (ii) at more than one time point and/or (b) wherein a composition of about 1% to about 5% w/v of perfluorocarbon emulsion is administered to the subject in an amount of about 0.01 ml/kg to about 1 ml/kg of the subject. 
     
     
         3 . The method of  claim 1 , wherein the composition comprising a perfluorocarbon emulsion is administered intravenously by a method selected from a group consisting of a bolus administration, continuous administration and a combination of a bolus and continuous administration. 
     
     
         4 . The method of  claim 1 , wherein the subject is administered a perfluorocarbon wherein the perfluorocarbon is DDFPe and the DDFPe is administered alone or in combination with a second agent selected from the group consisting of an anticoagulant, thrombolytic agent, which may include tPA, and oxygen inhalation. 
     
     
         5 . The method of  claim 1 , wherein the composition comprising a perfluorocarbon emulsion improves the oxygenation of the tissue such that the infarct volume is reduced without increasing incidence of brain hemorrhage. 
     
     
         6 . The method of  claim 1 , further comprising resolving the ischemic event. 
     
     
         7 . The method of  claim 1 , wherein the ischemic event is selected from a group consisting of stroke, hypotension and hypoxia. 
     
     
         8 . The method of  claim 1 , wherein the ischemic event is a stroke, the perfluorocarbon is DDFPe, and the composition is administered intravenously via at least one bolus injection. 
     
     
         9 . A method for improving tissue oxygenation and/or neuroprotection in a subject at risk for ischemic tissue damage, the method comprising administering an effective amount of a composition comprising a perfluorocarbon emulsion to the subject prior to a medical procedure that results in the subject being at high risk of ischemic tissue damage. 
     
     
         10 . The method of  claim 9 , wherein the medical procedure is selected from the group consisting of cardiac surgery, open surgery, orthopedic surgery, and skeletal surgery, angioplasty, stenting, device implantation, and ablations. 
     
     
         11 . The method of  claim 9 , wherein a composition of about 1% to about 5% w/v of perfluorocarbon emulsion is administered to the subject in an amount of about 0.01 ml/kg to about 1 ml/kg of the subject at more than one time point during and/or after the medical procedure. 
     
     
         12 . The method of  claim 9 , wherein the composition comprising a perfluorocarbon emulsion is administered intravenously by a method selected from a group consisting of a bolus administration, continuous administration and a combination of a bolus and continuous administration. 
     
     
         13 . The method of  claim 9 , wherein the subject is administered a perfluorocarbon wherein the perfluorocarbon is DDFPe and the DDFPe is administered alone or in combination with a second agent selected from the group consisting of an anticoagulant, thrombolytic agent, which may include tPA, and oxygen inhalation. 
     
     
         14 . The method of  claim 9 , wherein the composition comprising a perfluorocarbon emulsion improves the oxygenation of the tissue such that the infarct volume is reduced without increasing incidence of brain hemorrhage. 
     
     
         15 . The method of  claim 9 , wherein the ischemic tissue damage is neural ischemic tissue damage. 
     
     
         16 . A method for decreasing infarct size resulting from intracranial brain hemorrhage, the method comprising administering an effective amount of a composition comprising a perfluorocarbon emulsion to the subject in need of treatment for intracranial brain hemorrhage. 
     
     
         17 . The method of  claim 16 , (a) wherein the composition comprising a perfluorocarbon emulsion is administered in a time ranging from prior to the start of the intracranial brain hemorrhage to 24 hours after the onset of symptoms and (ii) at more than one time point and/or (b) wherein a composition of about 1% to about 5% w/v of perfluorocarbon emulsion is administered to the subject in an amount of about 0.01 ml/kg to about 1 ml/kg of the subject. 
     
     
         18 . The method of  claim 16 , wherein the composition comprising a perfluorocarbon emulsion is administered intravenously by a method selected from a group consisting of a bolus administration, continuous administration and a combination of a bolus and continuous administration. 
     
     
         19 . The method of  claim 16 , wherein the perfluorocarbon is DDFPe. 
     
     
         20 . A combination, the combination comprising a composition comprising a perfluorocarbon emulsion and a thrombolytic agent. 
     
     
         21 . The combination of  claim 20 , the combination comprising a composition comprising a perfluorocarbon emulsion and tPA, wherein the perfluorocarbon is DDFPe.