Ultrasound contrast media, contrast agents containing the media and method

Abstract

The invention relates to injectable media for ultrasonic echography in the form of microbubbles or microballoons comprising at least two biocompatible substances A and B (gaseous at the body temperature) forming a mixture which when in suspension with usual surfactants, additives and stabilisers provides useful ultrasound contrast agents. At least one of the components (B) in the mixture is a gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml per ml of water at standard conditions. The presence of the first component (B) in the contrast medium may vary between 0.5 and 41 volume percent. The other component (A) of the ultrasound contrast media is a gas or a mixture of gases whose molecular weight is below 80 daltons. The second component is present in a proportion of between 59-99.5% by vol., and is preferably chosen from oxygen, air, nitrogen, carbon dioxide or mixtures thereof. Gas mixtures described are found to be very effective as ultrasound contrast media. The invention also comprises a method of making the ultrasound contrast medium, the contrast agent and the ultrasound agent kit.

1 - 24 . (cancelled)  
     
     
         25 . A method of making an ultrasound contrast agent comprising suspending gas filled microbubbles in a physiologically acceptable aqueous carrier comprising film forming saturated phospholipid surfactants present in laminar and/or lamellar form, in which the gas filling the microbubbles is a mixture of at least two biocompatible gases A and B, 
 wherein A is selected from the group consisting of air, oxygen, nitrogen and carbon dioxide,    and B is C 4 F 10 .    
     
     
         26 . The method of  claim 25 , wherein A is air.  
     
     
         27 . The method of  claim 25 , wherein A is nitrogen.  
     
     
         28 . The method of  claim 27 , wherein the saturated phospholipid surfactants are selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidyl linositol, cardiolipin, sphingomyelin and mixtures thereof.  
     
     
         29 . The method of  claim 27 , wherein the saturated phospholipid surfactants comprise phosphatidic acid and phosphatidylcholine.