Ultrasound contrast agents and methods of making and using them

Abstract

Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain surfactants and, optionally, hydrophilic stabilizers. The surfactants can be in the form of liposomes. The suspensions are obtained by exposing the surfactants to air or a gas before or after admixing with an aqueous phase. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are also disclosed that have advantageous properties.

1 .- 17 . (canceled)  
     
     
         18 . A method for preparing an ultrasound contrast agent comprising the steps of 
 dissolving diarachidoylphosphatidylcholine, dipalmitoylphosphatidic acid and polyethyleneglycol in a tert-butanol solution at 60° C.,    cooling said solution to −45° C.,    lyophilizing said solution to obtain a powder,    transferring said powder to a vial,    closing said vial under vacuum conditions,    introducing sulfur hexafluoride gas into said vial,    introducing saline into said vial,    shaking said vial to dissolve said powder and create stabilized microbubbles comprising said sulfur hexafluoride gas stabilized by diarachidoylphosphatidylcholine and dipalmitoylphosphatidic acid in lamellar or laminar form at the gas/liquid interface.