Chemoembolisation

1. A composition comprising substantially dry microspheres having a matrix of cross-linked water-swellable water-insoluble polymer comprising poly (vinyl alcohol) and, a water-soluble therapeutic agent which is not covalently attached to the matrix, wherein the polymer has an overall anionic charge at a pH in the range 6 to 8, wherein the anionic charge is at a level of 1 to 10 meq/g, wherein themicrospheres, when swollen to equilibrium in water, have particle sizes in the range 40-1500 μm, and wherein the therapeutic agent is an anthracycline compound having at least one amine group.

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 3 , wherein the polymer has pendant anionic groups selected from carboxylate, carbonate, sulphonate, sulphate, nitrate, phosphonate and phosphate groups.

5. A composition according to claim 4 , wherein the anion is selected from carboxylate and sulphonate groups.

6. A composition according to claim 5 , wherein the anion is a sulphonate group.

7. A composition according to claim 1 wherein the anion is a sulphonate group.

8. A composition according to claim 1 in which the anthracycline is a compound of the general formula II

9. A composition according to claim 8 wherein the compound of general formula II is doxorubicin.

10. A composition according to claim 1 wherein the microspheres are swollen with and suspended in an aqueous liquid.

11. A composition according to claim 10 further comprising an imaging agent.

12. A composition according to claim 11 wherein the imaging agent is a radiopaque agent.

13. A composition according to claim 10 wherein the particles are in the form of a pumpable slurry comprising particles swollen with aqueous liquid.

14. A composition according to claim 13 , which is filled into a storage container and is sterile.

15. A composition according to claim 14 wherein the storage container is a syringe.

16. A method of embolising a solid tumor comprising the steps of administering a composition according to claim 10 into a blood vessel of a patient to embolise the solid tumor.

17. Process for producing a composition according to claim 1 comprising the steps:

providing microspheres of a water-swellable, water-insoluble polymer comprising poly (vinyl alcohol), 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 anionic charge is 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 and drying the microspheres.

18. Process according to claim 17 in which the contacting is carried out by suspending the microspheres in an aqueous solution of the anthracycline.

19. Process according to claim 18 comprising the further step of recovering the microspheres of polymer with anthracycline absorbed in the matrix from the suspension.

20. A process according to claim 17 wherein the drying is freeze-drying.

21. A method of embolising a solid tumor 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 tumor.

22. A method according to claim 21 wherein the tumor is hepatocellular carcinoma.

23. A method according to claim 22 wherein the tumor is hepatocellular carcinoma.

24. A composition according to claim 1 , wherein the level of anion in the polymer matrix is in the range 0.1-10 meq/g.

25. A composition according to claim 1 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.