# US 10,307,493 B2 · Imageable embolic microsphere

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- Number: US 10,307,493 B2
- Document ID: US10307493B2
- Status: Granted
- Kind: B2
- Application number: 14/777,168
- Filed: 2014-03-14
- Published: 2016-02-04
- Granted: 2019-06-04
- Earliest claimed: 2013-03-15
- Assignees: Biocompatible UK Ltd.; National Institutes of Health
- Applicants: Biocompatibles UK Limited; Matthew R. Dreher; Bradford J. Wood; Ayele H. Negussie; Andrew Leonard Lewis; Yiqing Tang
- Inventors: Matthew R. Dreher; Bradford J. Wood; Ayele H. Negussie; Andrew Leonard Lewis; Yiqing Tang
- Web page: https://patentgrep.com/patent/US10307493B2

## CPC

- A61K 49/0442: {Polymeric X-ray contrast-enhancing agent comprising a halogenated group}
- A61K 49/0438: {Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol}
- A61K 49/0476: {Particles, beads, capsules, spheres}
- A61K 49/0485: {Nanoparticles, nanobeads, nanospheres, nanocapsules, i.e. having a size or diameter smaller than 1 micrometer}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C08F 116/06: Polyvinyl alcohol {; Vinyl alcohol}
- C08L 29/04: Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

This invention concerns imageable, radiopaque embolic beads, which are particularly useful for monitoring embolization procedures. The beads comprise iodine containing compounds which are covalently incorporated into the polymer network of a preformed hydrogel bead. The beads are prepared by activating pre-formed hydrogel beads towards nucleophilic attack and then covalently attaching iodinated compounds into the polymer network. The radiopaque beads may be loaded with chemotherapeutic agents and used in methods of embolizing hyperplastic tissue or solid tumors.

## Claims

### Claim 1

A radiopaque hydrogel microsphere comprising functional groups on a preformed crosslinked polyvinyl alcohol (PVA) hydrogel microsphere that have been activated towards nucleophilic substitution reaction with carbonyl diimidazole or carbodiimide, wherein the carbonyl diimidazole or carbodiimide is configured to react with an aromatic iodine containing compound and covalently bind the aromatic iodine containing compound to the hydrogel microsphere.

### Claim 2 (depends on 1)

A radiopaque hydrogel microsphere according to claim 1 wherein the iodine containing compound is an iodinated benzyl or phenyl alcohol or is an iodinated benzoic acid.

### Claim 3 (depends on 1)

A radiopaque hydrogel microsphere according to claim 1 wherein the iodine containing compound is 2,3,5-triiodobenzoic acid.

### Claim 4 (depends on 1)

A radiopaque hydrogel microsphere according to claim 1 in which the hydrogel microsphere has been pre-formed from a polymer which has alcoholic hydroxyl substituents or acylated derivatives thereof.

### Claim 5 (depends on 1)

A radiopaque hydrogel bead microsphere according to claim 1 in which the hydrogel microsphere has been pre-formed from a crosslinked polyvinyl alcohol which has been formed by copolymerizing ethylenically unsaturated polyvinyl alcohol macromer with ethylenically unsaturated comonomer.

### Claim 6 (depends on 1)

A radiopaque hydrogel microsphere according to claim 1 in which the ethylenically unsaturated polyvinyl alcohol macromer comprises pendant ethylenic groups are linked via cyclic acetal linkages with oxygen atoms from adjacent hydroxyl groups, formed by the reaction of N-acrylaminoacetaldehyde dimethyl acetal.

### Claim 7 (depends on 1)

A radiopaque hydrogel microsphere according to claim 1 in which the hydrogel comprises polyvinyl alcohol partially acetalized with N-formylmethyl acrylamide copolymerized with 2-acrylamido-2-methylpropane sulfonate sodium salt.

### Claim 8 (depends on 1)

The radiopaque hydrogel microsphere according to claim 1, further comprising a pharmacologically active agent absorbed within the microsphere.

### Claim 9 (depends on 8)

The radiopaque hydrogel microsphere according to claim 8, wherein the pharmacologically active agent is an antiangiogenic or a chemotherapeutic drug.

### Claim 10 (depends on 8)

The radiopaque hydrogel microsphere according to claim 8, wherein the pharmacologically active agent is doxorubicin.