Patient oxygenation using stabilized fluorocarbon emulsions

Abstract

Storage stable fluorocarbon emulsions having a continuous aqueous phase and a discontinuous fluorocarbon phase, in which the fluorocarbon phase comprises a major amount of a first fluorocarbon or fluorocarbon mixture, and a minor amount of a second fluorocarbon or fluorocarbon mixture, in which the second fluorocarbon has a molecular weight greater than that of the first fluorocarbon and the second fluorocarbon includes a lipophilic moiety in its structure, whereby the second fluorocarbon serves to promote particle size stability in the emulsion while simultaneously providing favorably short organ retention times when administered to animals in vivo.

What is claimed is:  
     
         1 . A method for delivering oxygen using a stabilized emulsion to a patient in need thereof comprising the steps of; 
 intravenously administering to said patient a therapeutically effective amount of a fluorocarbon emulsion comprising an emulsifying agent, a continuous aqueous phase and a discontinuous phase wherein said discontinuous phase comprises from about 60% to about 99.9% w/w of perfluorooctyl bromide and from about 0.1% to about 40% by weight of one or more second lipophilic fluorocarbons wherein each second fluorocarbon has a critical solution temperature in hexane at least 10° C. lower than that of a fully fluorinated analog compound.    
     
     
         2 . The method of  claim 1  wherein said administering is by injection.  
     
     
         3 . The method of  claim 1  wherein said second fluorocarbon has an in vivo half-life of less than about 4 weeks.  
     
     
         4 . The method of  claim 1  wherein said second fluorocarbon comprises a lipophilic moiety selected from the group consisting of Br, Cl, I, H, CH 3  and a saturated or unsaturated hydrocarbon chain of 2 or 3 carbon atoms.  
     
     
         5 . The method of claim I wherein said second fluorocarbon comprises a fluorinated compound having a molecular weight greater than about 110 Daltons.  
     
     
         6 . The method of  claim 1  wherein said second fluorocarbon is perfluorodecyl bromide.  
     
     
         7 . The method of  claim 6  wherein said emulsifying agent comprises a phospholipid.  
     
     
         8 . The method of  claim 7  wherein said phospholipid comprises from about 0.1% to about 10% w/v.  
     
     
         9 . The method of  claim 8  wherein said perfluorodecyl bromide comprises from about 0.1% to about 5% w/w of said discontinuous phase.  
     
     
         10 . A method for oxygenating a patient in need thereof comprising the steps of: 
 intravenously administering to said patient a therapeutically effective amount of a fluorocarbon emulsion comprising an emulsifying agent, a continuous aqueous phase and a discontinuous phase wherein said discontinuous phase comprises from about 10% to about 99.9% w/w of a first fluorocarbon and from about 0.1% to about 10% by weight of one or more second fluorocarbons having a molecular weight between about 140 to about 700 Daltons wherein the molecular weight of each second fluorocarbon is greater than that of said first fluorocarbon and wherein each second fluorocarbon has a critical solution temperature in hexane at least 10° C. lower than that of a fully fluorinated analog compound.    
     
     
         11 . The method of  claim 10  wherein said first fluorocarbon is selected from the group consisting of perfluoromethylbicyclo (3, 3, 1) nonane, perfluorodimethyl bicyclononane, perfluoro-2, 2, 4, 4-tetramethylpentane, perfluorotripropylamine, bis(F-butyl) ethene, (F-isopropyl) (F-hexyl) ethene, perfluoromethyladamantane, perfluorodimethyladamantane, F-N-methyldecahydro-isoquinoline, F-4-methyloctahydroquinolidizine, perfluorooctyl bromide, perfluorodecalin and combinations thereof.  
     
     
         12 . The method of  claim 10  wherein said first fluorocarbon is perfluorooctyl bromide.  
     
     
         13 . The method of  claim 10  wherein said first fluorocarbon is pefluorodecalin.  
     
     
         14 . The method of  claim 10  wherein said emulsifying agent comprises a fluorinated surfactant.  
     
     
         15 . The method of  claim 10  wherein said discontinuous fluorocarbon phase comprises from about 90% to about 99% w/w of said first fluorocarbon and from about 1% to about 10% of said second fluorocarbon.  
     
     
         16 . The method of  claim 15  wherein said emulsifying agent comprises a phospholipid.