Chemoembolisation

Abstract

A composition for chemoembolotherapy of solid tumours comprises particles of a water-insoluble water-swellable synthetic anionic polymer and, absorbed therein an anthracycline. Suitably the polymer is a poly(vinyl alcohol) based polymer and the drug is doxorubicin.

What is claimed is: 
     
         1 . A composition comprising microspheres having a matrix of water-swellable water-insoluble polymer and, absorbed in the matrix, a water-soluble therapeutic agent, wherein the polymer has an overall anionic charge at a pH in the range 6 to 8, wherein the particles, when swollen to equilibrium in water have particle sizes in the range 40-1500 μm, wherein the therapeutic agent is an anthracycline compound having at least one amine group, and wherein the polymer is a polymer of ethylenically unsaturated monomers including anionic monomer and di- or higher-functional cross-linking monomer in amounts to obtain polymer having an anionic charge at a level of 1 to 10 meq/g. 
     
     
         2 . A composition according to  claim 1  in which the anion is a carboxylate, carbonate, sulphonate, sulphate, nitrate, phosphonate or phosphate group. 
     
     
         3 . A composition according to  claim 1  wherein the anion is a carboxylate group. 
     
     
         4 . A composition according to  claim 1  wherein the anion is a sulphonate group. 
     
     
         5 . A composition according to  claim 1  in which the anthracycline is a 20 compound of the general formula II 
       
         
           
           
               
               
           
         
       
     
     
         6 . A composition according to  claim 5  wherein the compound of general formula II is doxorubicin. 
     
     
         7 . A composition according to  claim 1  wherein the particles are swollen with and suspended in an aqueous liquid. 
     
     
         8 . A composition according to  claim 7  further comprising an imaging agent. 
     
     
         9 . A composition according to  claim 8  wherein the imaging agent is a radiopaque agent. 
     
     
         10 . A composition according to  claim 1  wherein the particles are in the form of a pumpable slurry comprising particles swollen with aqueous liquid. 
     
     
         11 . A composition according to  claim 10 , which is filled into a storage container and is sterile. 
     
     
         12 . A composition according to  claim 11  wherein the storage container is a syringe. 
     
     
         13 . A composition according to  claim 1  which is substantially dry. 
     
     
         14 . Process for producing a composition according to  claim 1  comprising the steps:
 providing microspheres of a water-swellable, water-insoluble polymer, wherein the polymer has an overall anionic charge at a pH in the range 6 to 8, wherein the microspheres, when swollen to equilibrium in water have particle sizes in the range 40-1500 μm and wherein the water-swellable water insoluble polymer is a polymer of ethylenically unsaturated monomers including anionic monomer and di- or higher-functional cross-linking monomer in amounts such that it has an anionic charge at a level of 1 to 10 meq/g; and 
 contacting the microspheres with a solution of an anthracycline having at least one amine group in the presence of water; and
 absorbing anthracycline into the matrix of the polymer. 
 
 
     
     
         15 . Process according to  claim 14  in which the contacting is carried out by suspending the microspheres in an aqueous solution of the anthracycline. 
     
     
         16 . Process according to  claim 15  comprising the further step of recovering the microspheres of polymer with anthracycline absorbed in the matrix from the suspension. 
     
     
         17 . A process according to  claim 16  comprising the further step of drying the microspheres. 
     
     
         18 . A process according to  claim 17  wherein the drying is freeze-drying. 
     
     
         19 . A method of embolising a solid tumour comprising the steps of mixing a composition according to  claim 1  with a contrast agent and administering the mixture into a blood vessel of a patient to embolise the solid tumour. 
     
     
         20 . A method of embolising a solid tumour comprising the steps of administering a composition according to  claim 7  into a blood vessel of a patient to embolise the solid tumour.