Microbubble Compositions, Method of Making Same, and Method Using Same

Abstract

A method of forming a plurality of microbubbles, wherein the method disposes in a sealed container comprising a first volume at ambient pressure, a second volume of a mixture comprising one or more microbubble stabilizing materials. The first volume is greater than said second volume. The method further comprises sealing said container, introducing a gas into said sealed container, and shaking the container to form said plurality of microbubbles.

1 - 11 . (canceled) 
     
     
         12 . A contrast agent composition for medical imaging comprising:
 a plurality of microbubbles, wherein each microbubble comprises a shell and a gas bubble encapsulated therein;   wherein:   said gas bubble comprises a gas selected from the group consisting of perfluorobutane, perfluoropentane, and perfluorohexane; and   each of said plurality of microbubbles comprises a diameter less than about 1.25 microns.   
     
     
         13 . The contrast agent of  claim 12 , wherein said gas bubble comprises perfluoropentane. 
     
     
         14 . The contrast agent of  claim 12 , wherein said gas bubble comprises perfluorohexane. 
     
     
         15 . The contrast agent of  claim 12 , wherein said shell comprises dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolaminepolyethylene glycol, and dipalmitoylphosphatidic acid. 
     
     
         16 . The contrast agent of  claim 15 , wherein the ratio of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolaminepolyethylene glycol, and dipalmitoylphosphatidic acid is about 82 mole percent, 10 mole percent, and 8 mole percent, respectively. 
     
     
         17 . The contrast agent of  claim 12 , wherein said shell comprises a fluorosurfactant. 
     
     
         18 . The contrast agent of  claim 17 , wherein said fluorosurfactant is PEG-Telomer B. 
     
     
         19 . A contrast agent composition for medical imaging formed by the process of:
 disposing in a sealed container comprising a first volume at ambient pressure, a second volume of a mixture comprising one or more microbubble stabilizing materials in combination with a liquid having a boiling point less than about 57° C. at 760 mm pressure, wherein said first volume is greater than said second volume;   volatizing said liquid by reducing the pressure in said sealed container; and   shaking the container to form a contrast agent composition comprising a plurality of microbubbles, wherein each of said plurality of microbubbles comprises a diameter less than about 1.25 microns.   
     
     
         20 . The contrast agent composition of  claim 19 , wherein said one or more microbubble stabilizing materials comprise dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolaminepolyethylene glycol, and dipalmitoylphosphatidic acid. 
     
     
         21 . The contrast agent composition of  claim 20 , wherein the ratio of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolaminepolyethylene glycol, and dipalmitoylphosphatidic acid is about 82 mole percent, 10 mole percent, and 8 mole percent, respectively. 
     
     
         22 . The contrast agent composition of  claim 19 , wherein the stabilizing material comprises a fluorosurfactant. 
     
     
         23 . The contrast agent composition of  claim 22 , wherein the fluorosurfactant is PEG-Telomer B. 
     
     
         24 . The contrast agent composition of  claim 19 , wherein said liquid comprises a liquid selected from the group consisting of perfluorobutane, perfluoropentane, and perfluorohexane. 
     
     
         25 . The contrast agent composition of  claim 19 , wherein volatizing comprises reducing the pressure in said sealed container to a pressure of 400 Torr for 20 minutes. 
     
     
         26 . The contrast agent composition of  claim 19 , wherein shaking comprises placing the container on a mechanical shaker set at about 75 Hz for about 45 seconds.