Contrast agents

Abstract

The present invention provides contrast agents for use in diagnostic ultrasound studies comprising microbubbles of gas or a gas precursor encapsulated by non-proteinaceous crosslinked or polymerised amphiphilic moieties.

1 . Contrast agents for use in diagnostic ultrasound studies comprising microbubbles of gas or a gas precursor encapsulated by non-proteinaceous crosslinked or polymerised amphiphilic moieties.  
     
     
         2 . Contrast agents as claimed in  claim 1  in the form of gas-filled microballoons.  
     
     
         3 . Contrast agents as claimed in  claim 1  or  claim 2  containing biodegradable linkages selected from amide, imide, imine, ester, anhydride, acetal, carbamate, carbonate, carbonate ester and disulphide groups.  
     
     
         4 . Contrast agents as claimed in  claim 3  containing biodegradable crosslinking groups.  
     
     
         5 . Contrast agents as claimed in  claim 4  wherein the biodegradable crosslinking groups include units of formula  
       —(Y) n .CO.O.C(R 1 R 2 ).O.CO.(Z) n — 
       (where Y and Z, which may be the same or different, are —O—, —S— or —NR3—; R 1  and R 2 , which may be the same or different, are hydrogen atoms or carbon-attached monovalent organic groups or together represent a carbon-attached divalent organic group; R3 is a hydrogen atom or an organic group; and the symbols n, which may be the same or different, are zero or 1).  
     
     
         6 . Contrast agents as claimed in  claim 1  or  claim 2  obtained from polymerisable amphiphilic moieties containing unsaturated lipophilic chains.  
     
     
         7 . Contrast agents as claimed in  claim 6  wherein the unsaturated lipophilic chains are oleyl or linoleyl groups or contain diacetylene groupings or acryloyl or methacryloyl groupings.  
     
     
         8 . Contrast agents as claimed in any of the preceding claims wherein the hydrophilic portion of the amphiphile contains one or more groups selected from quaternary ammonium, hydroxyl, carboxy, carboxylate ion, amide, phosphate, sulphate and sulphonate.  
     
     
         9 . Contrast agents as claimed in  claim 8  wherein the hydrophilic portion of the amphiphile is the triglyceryl moiety of a phospholipid, an iodinated X-ray contrast agent, a carbohydrate, or a choline, ethanolamine, serine or glycerol residue.  
     
     
         10 . Contrast agents as claimed in any of  claims 1  to  7  wherein the hydrophilic portion of the amphiphile is an optionally etherified polyoxyethylene glycol residue.  
     
     
         11 . Contrast agents as claimed in  claim 10  wherein the amphiphile is tetraethylene glycol mono-12-(methacryloyloxy)dodecanoate.  
     
     
         12 . Contrast agents as claimed in  claim 10  wherein the amphiphile is polyethylene glycol (550) methyl ether 12-(methacryloyloxy)dodecanoate.  
     
     
         13 . Contrast agents as claimed in  claim 10  wherein the amphiphile is polyethylene glycol (2000) methyl ether 12-(methacryloyloxy)dodecanoate.  
     
     
         14 . Contrast agents as claimed in  claim 10  wherein the amphiphile is tetraethylene glycol mono-16-(methacryloyloxy)hexadecanoate.  
     
     
         15 . Contrast agents as claimed in  claim 10  wherein the amphiphile is polyethylene glycol. (350) methyl ether 16-(methacryloyloxy)hexadecanoate.  
     
     
         16 . Contrast agents as claimed in  claim 10  wherein the amphiphile is tetraethylene glycol mono-12-(acryloyloxy)dodecanoate.  
     
     
         17 . Contrast agents as claimed in any of the preceding claims further containing an inorganic particulate stabiliser.  
     
     
         18 . A process for the preparation of a contrast agent as claimed in  claim 1  which consists of forming a fluid dispersion of vesicles comprising a gas or gas precursor encapsulated by amphiphilic material and thereafter crosslinking or polymerising said amphiphilic material.  
     
     
         19 . A process as claimed in  claim 11  wherein the fluid dispersion is prepared by sonication to generate an oil-in-water emulsion in which a volatile hydrocarbon is encapsulated by the amphiphilic material and said volatile hydrocarbon is partially or completely removed from the vesicles after crosslinking or polymerisation of the amphiphilic material.