Imageable polymers

Patent metadata

Field	Value
Publication number	US-10098972-B2
Application number	US-201414916472-A
Country	US
Kind code	B2
Filing date	Sep 5, 2014
Priority date	Sep 6, 2013
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

This invention relates to imageable polymers, particularly those comprising poly vinylalcohol and to methods for making them as well as to embolic microspheres comprising the polymers. The microspheres are imageable during embolization procedures and can be loaded with drugs or other therapeutic agents to provide an imageable drug delivery system.

First claim

The invention claimed is:

1. Microspheres comprising:
a hydrogel polymer comprising a polyvinyl alcohol polymer cross-linked with 2-acrylamido-2-methylpropanesulfonic acid; and
a radiopaque species coupled with 1,3 diol groups of the polyvinyl alcohol polymer through a cyclic acetal group, wherein the radiopaque species comprises one or more covalently bound halogens.

2. The microspheres according to claim 1 wherein the halogen is selected from iodine and bromine.

3. The microspheres according to claim 2 wherein the radiopaque species comprises an iodinated or brominated phenyl group.

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

5. The microspheres according to claim 1 having a mean diameter from 10 to 2000 μm.

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

7. The microspheres according to claim 1 wherein the hydrogel polymer has a net charge at pH 7.4.

8. The microspheres according to claim 1 comprising a structure of the general formula I

wherein X is a group substituted by one or more halogens and J is a group of the formula —CH 2 — or is a bond.

9. The microspheres according to claim 8 wherein X is a group of the formula

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 C 1-6 alkylene, C 1-6 alkoxylene or C 1-6 alkoxyalkylene;
Hal is 1,2,3 or 4 covalently attached radiopaque halogens.

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

11. A composition according to claim 10 wherein the therapeutic agent is electrostatically held in the hydrogel polymer and elutes from the hydrogel polymer in electrolytic media.

12. The microspheres according to claim 1 wherein the polyvinyl alcohol polymer comprises polyvinyl alcohol modified with N-acryloyl-aminoacetaldehyde dimethylacetal cross-linked with 2-acrylamido-2-methylpropanesulfonic acid.

Assignees

• Biocompatibles Uk Ltd
• Biocompatibles Uk Ltd

Inventors

• Hohn Stéphane
• Lewis Andrew Lennard

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/0442 Primary

  Polymeric X-ray contrast-enhancing agent comprising a halogenated group · CPC title

• A61K31/44

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title

• A61L2430/36

  for embolization or occlusion, e.g. vaso-occlusive compositions or devices · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title