Imageable polymers

Patent metadata

Field	Value
Publication number	US-9895452-B2
Application number	US-201414478213-A
Country	US
Kind code	B2
Filing date	Sep 5, 2014
Priority date	Sep 6, 2013
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

The present invention relates to hydrogels comprising 1,2-diol or 1,3-diol groups acetalized with a radiopaque species of one or more covalently bound radiopaque halogens which are imageable during embolization therapy. The invention further relates to methods of making radiopaque polymers and radiopaque hydrogel microspheres to provide an imageable drug delivery system.

First claim

The invention claimed is:

1. Microspheres comprising a polymer formed from an acrylamido polyvinyl alcohol-co-acrylamido-2-methylpropane sulfonate hydrogel polymer, the polymer having a structure of formula I or II

wherein X is formula III:

wherein Z is a linking group, or is absent, such that the phenyl group is bonded to the cyclic acetal;
if Z is present, then Z is selected from the group consisting of C 1-6 alkylene, C 1-6 alkoxylene or C 1-6 alkoxyalkylene;
Hal is 1,2,3 or 4 covalently attached radiopaque iodines; and
J is —CH 2 — or a bond.

2. The microspheres according to claim 1 wherein the hydrogel polymer comprises greater than 10% iodine by dry weight.

3. The microspheres according to claim 1 wherein the microspheres have a mean diameter size range of from 10 to 2000 μm.

4. The microspheres according to claim 1 having a mean radiopacity of 500 HU or greater.

5. The microspheres according to claim 1 wherein the hydrogel polymer has a net charge at physiological pH.

6. A composition comprising the microspheres according to claim 1 and a therapeutic agent wherein the therapeutic agent is absorbed into the hydrogel polymer.

7. A composition according to claim 6 wherein the therapeutic agent is electrostatically held in the hydrogel polymer and elutes from the hydrogel polymer in electrolytic media.

8. The microspheres according to claim 1 for use in embolization of a blood vessel.

9. A composition according to claim 6 for use in embolization of a blood vessel.

10. The microspheres according to claim 1 , wherein the hydrogel polymer comprises an iodinated aromatic group comprising 1, 2, 3, or 4 covalently bound iodines.

11. The microspheres according to claim 10 , wherein the aromatic group comprises a phenyl group covalently attached 1, 2, 3, or 4 iodines.

12. A composition according to claim 6 , wherein the therapeutic agent is selected from doxorubicin, epirubicin, sorafenib, sunitinib, vandetinib, miriplatin, topotecan and irinotecan.

Assignees

• Biocompatibles Uk Ltd

Inventors

• Hohn Stephane
• Lewis Andrew Lennard

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/0419

  Microparticles, microbeads, microcapsules, microspheres, i.e. having a size or diameter higher or equal to 1 micrometer · CPC title

• C08F8/18

  Introducing halogen atoms or halogen-containing groups · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• A61K49/048

  Microparticles, microbeads, microcapsules, microspheres, i.e. having a size or diameter higher or equal to 1 micrometer · CPC title