Contrast agents

Abstract

Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful as efficacious contrast agents. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.

1 - 79 . (canceled)  
     
     
         80 . A process for the preparation of a reconstitutable contrast agent comprising the steps of: 
 i) dispersing gas in an aqueous medium containing a membrane-forming lipid to form a lipid-stabilised gas microbubble dispersion; and    ii) lyophilising said dispersion to yield a dried lipid-containing product.    
     
     
         81 . A process as claimed in  claim 80 , wherein the gas employed in step (i) is a fluorinated low molecular weight hydrocarbon.  
     
     
         82 . A process as claimed in  claim 81 , wherein said hydrocarbon is perfluorinated.  
     
     
         83 . A process as claimed in  claim 80 , wherein the gas employed in step (i) is sulphur hexafluoride.  
     
     
         84 . A process as claimed in  claim 80 , wherein the lipid-containing aqueous medium employed in step (i) further contains one or more additives selected from the group consisting of viscosity enhancers and solubility aids for the lipid.  
     
     
         85 . A process as claimed in  claim 84 , wherein said one or more additives are selected from the group consisting of alcohols and polyols.  
     
     
         86 . A process as claimed in  claim 84 , wherein said one or more additives includes a polyethyleneglycol.  
     
     
         87 . A process as claimed in  claim 80 , wherein the membrane-forming lipid comprises at least one phospholipid.  
     
     
         88 . A process as claimed in  claim 80 , wherein the membrane-forming lipid consists essentially of phospholipid and predominantly comprises molecules which individually have an overall net charge.  
     
     
         89 . A process as claimed in  claim 80 , further comprising the step of washing the lipid-stabilised dispersion formed in step (i) prior to step (ii).  
     
     
         90 . A process as claimed in  claim 80 , further comprising the step of size fractionating the lipid-stabilised dispersion formed in step (i) prior to step (ii).  
     
     
         91 . A process as claimed in  claim 80 , further comprising the step of adding one or more of the group consisting of a cryoprotectant, a lyoprotectant, and a bulking agent to the lipid-stabilised dispersion formed in step (i) prior to step (ii).  
     
     
         92 . A process as claimed in  claim 91 , wherein at least one of said cryoprotectant, said lyoprotectant, and said bulking agent is selected from the group consisting of alcohols, polyols, aminoacids, carbohydrates and polyglycols.  
     
     
         93 . A process as claimed in  claim 91 , wherein at least one of said cryoprotectant, said lyoprotectant, and said bulking agent is a physiologically tolerated sugar.  
     
     
         94 . A process as claimed in  claim 91 , wherein at least one of said cryoprotectant, said lyoprotectant, and said bulking agent is selected from the group consisting of t-butanol, glycerol, glycine, sucrose, mannitol, trehalose, glucose, lactose, cyclodextrins and polyethyleneglycol.  
     
     
         95 . A reconstitutable contrast agent obtained by a process as claimed in  claim 80.