Lipid microbubbles and process of making thereof

Abstract

Disclosed is a suspension of gas-filled microbubbles in a physiologically acceptable liquid carrier comprising a lipid mixture of a first lipid having transition temperature of about 41° C. such as DPPC or DPPG, a second lipid having transition temperature of about 55° C. such as DSPC or DSPG, and a PEGylated DSPE such as DSPE-PEG2000, DSPE-PEG3000, or DSPE-CPEG5000, and methods of preparation thereof.

1 . A suspension of gas-filled microbubbles in a physiologically acceptable liquid carrier, said microbubbles comprising (a) a lipid mixture comprising a first lipid having transition temperature of about 41° C., a second lipid having transition temperature of about 55° C., and a PEGylated DSPE, and (b) a biocompatible gas, wherein the ratio of said first lipid is in a range of 40% to 63% by weight in the lipid mixture. 
     
     
         2 . The suspension of  claim 1 , wherein said first lipid is DPPC or DPPG. 
     
     
         3 . The suspension of  claim 1 , wherein the ratio of said first lipid is in a range of 50% to 63% by weight. 
     
     
         4 . The suspension of  claim 1 , wherein the ratio of said first lipid is in a range of 40% to 60% by weight. 
     
     
         5 . (canceled) 
     
     
         6 . The suspension of  claim 1 , wherein said first lipid is DPPC. 
     
     
         7 . The suspension of  claim 1 , wherein said first lipid is DPPG. 
     
     
         8 . The suspension of  claim 1 , wherein said second lipid is DSPC or DSPG. 
     
     
         9 . The suspension of  claim 1 , wherein said PEGylated DSPE is DSPE-PEG2000, DSPE-PEG3000, or DSPE-PEG5000. 
     
     
         10 . The suspension of  claim 1 , wherein the ratio of the PEGylated DSPE is about 10% to about 15% by weight. 
     
     
         11 . The suspension of  claim 1 , wherein the ratio of the PEGylated DSPE is about 12.5% by weight. 
     
     
         12 . The suspension of  claim 1 , wherein said suspension further comprises 1% to 20% of glycerol. 
     
     
         13 . The suspension of  claim 1 , wherein said suspension further comprises about 5% of glycerol. 
     
     
         14 . The suspension of  claim 1 , wherein said gas is selected from the group consisting of perfluorocarbons, SF 6 , Ar and N 2 . 
     
     
         15 . The suspension of  claim 1 , wherein said perfluorocarbons gas is C 3 F 8 , C 4 F 10 , or C 5 F 12 . 
     
     
         16 . A seal vial comprising a suspension of gas-filled microbubbles of  claim 1 . 
     
     
         17 . The seal vial of  claim 16 , wherein said gas is selected from the group consisting of perfluorocarbons gas, SF 6 , Ar and N 2 . 
     
     
         18 . The seal vial of  claim 16 , wherein said first lipid is DPPC or DPPG. 
     
     
         19 . The seal vial of  claim 16 , wherein said second lipid is DSPC or DSPG. 
     
     
         20 . The seal vial of  claim 16 , wherein said PEGylated DSPE is DSPE-PEG2000, DSPE-PEG3000, or DSPE-PEG5000. 
     
     
         21 . The seal vial of  claim 16 , wherein said seal vial further comprises 1% to 20% of glycerol.