# US 9,750,765 B2 · Reactive oxidative species generating materials and methods of use

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,750,765 B2
- Document ID: US9750765B2
- Status: Granted
- Kind: B2
- Application number: 15/377,084
- Filed: 2016-12-13
- Published: 2017-03-30
- Granted: 2017-09-05
- Earliest claimed: 2012-08-31
- Assignees: W. L. Gore & Associates, Inc.
- Applicants: W. L. Gore & Associates, Inc.
- Inventors: Tiffany J. Brown; Adam S. Lafleur; Kenneth Mazich; Jeffrey C. Towler; Ji Zhang
- Web page: https://patentgrep.com/patent/US9750765B2

## CPC

- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61K 31/765: Polymers containing oxygen
- A61K 33/40: Peroxides
- A61L 2/081: Gamma radiation
- A61L 2/082: X-rays
- A61L 2/087: Particle radiation, e.g. electron-beam, alpha or beta radiation
- A61L 27/34: Macromolecular materials
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/58: Materials at least partially resorbable by the body
- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- A61L 31/10: Macromolecular materials
- A61L 31/14: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 31/148: {Materials at least partially resorbable by the body}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61L 2103/15: Laboratory, medical or dentistry appliances, e.g. catheters or sharps
- A61L 2400/18: Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Materials capable of delivering stabilized free radicals to targeted treatment sites. The materials comprise semi-crystalline, hydrolytically degradable polymers that are subjected to ionizing radiation to create stabilized free radicals therein. Upon exposure to oxygen containing aqueous media, the materials generate reactive oxidative species which are useful in biological processes.

## Claims

### Claim 1

A biocompatible device capable of releasing superoxide, said biocompatible device comprising:
a substrate; and
a biocompatible material comprising a first semi-crystalline, hydrolytically degradable polymeric material and a second semi-crystalline hydrolytically degradable polymeric material,
wherein the first and second polymeric materials have each been subjected to ionizing radiation at a dose rate less than about 50 kGy and sterilized by non-ionizing radiation methods,
wherein said biocompatible material is in contact with at least a portion of said substrate,
wherein an initial burst of reactive oxidative species production and a subsequent sustained period of reactive oxidative species production occurs upon contacting the biocompatible material with an oxygen-containing aqueous media, and
wherein the first polymeric material and the second polymeric material have been subjected to different doses of ionizing radiation.

### Claim 2

A biocompatible device capable of releasing superoxide, said biocompatible device comprising:
a substrate; and
a biocompatible material comprising a first semi-crystalline, hydrolytically degradable polymeric material and a second semi-crystalline hydrolytically degradable polymeric material,
wherein the first polymeric material and second polymeric material have been subjected to different doses of ionizing radiation while maintained in an inert atmosphere,
wherein said biocompatible material is in contact with at least a portion of said substrate.

### Claim 3 (depends on 2)

The biocompatible device of claim 2, wherein the first and second polymeric materials enables multi-phasic generation of reactive oxidative species upon contact with an aqueous media.

### Claim 4 (depends on 2)

The biocompatible device of claim 2, wherein an initial burst of reactive oxidative species production and a subsequent sustained period of reactive oxidative species production occurs upon contacting the first and second polymeric materials with an aqueous media.

### Claim 5 (depends on 2)

The biocompatible device of claim 2, wherein the first polymeric material has a different hydrolytic degradation rate than the second polymeric material.

### Claim 6 (depends on 2)

The biocompatible device of claim 2, wherein the first polymeric material has a different degree of crystallinity than the second polymeric material.

### Claim 7 (depends on 2)

The biocompatible device of claim 2, wherein the first and second polymeric materials each comprise stabilized free radicals.

### Claim 8 (depends on 2)

The biocompatible device of claim 2, wherein the first polymeric material comprises stabilized free radicals and the second polymeric material does not contain stabilized free radicals.

### Claim 9 (depends on 2)

The biocompatible device of claim 2, wherein the first polymeric material comprises a different amount of stabilized free radicals than the second polymeric material.

### Claim 10 (depends on 2)

The biocompatible device of claim 2, wherein the first and second polymeric materials have different reactive oxidative species generation profiles.

### Claim 11 (depends on 2)

The biocompatible device of claim 2, wherein at least one of the first and second polymeric materials is bioabsorbable.

### Claim 12 (depends on 11)

The biocompatible device of claim 11, wherein the bioabsorbable polymer is selected from poly(dioxanone), poly(glycolide), poly(lactide) poly(ε-caprolactone), poly(anhydrides) such as poly(sebacic acid), poly(hydroxyalkanoates) such as poly(3-hydroxybutyrate), copolymers of any of these and combinations thereof.

### Claim 13 (depends on 2)

The biocompatible device of claim 2, wherein the first and second polymeric materials have each been subjected to the ionizing radiation at a dose rate less than about 50 kGy.

### Claim 14 (depends on 2)

The biocompatible device of claim 2, wherein the first and second polymeric materials have each been subjected to ionizing radiation at a total dose from about 30 kGy to about 50 kGy.

### Claim 15 (depends on 2)

The biocompatible device of claim 2, wherein the biocompatible material further comprises at least one therapeutically active agent.

### Claim 16 (depends on 2)

The biocompatible device of claim 2, wherein the first and second polymeric materials have been sterilized by a non-ionizing radiation method.

### Claim 17 (depends on 1)

The biocompatible device of claim 1, wherein the first and second biocompatible materials enables multi-phasic generation of reactive oxidative species upon contact with an aqueous media.

### Claim 18 (depends on 1)

The biocompatible device of claim 1, wherein the first polymeric material has a different hydrolytic degradation rate than the second polymeric material.

### Claim 19 (depends on 1)

The biocompatible device of claim 1, wherein the first polymeric material has a different degree of crystallinity than the second polymeric material.

### Claim 20 (depends on 1)

The biocompatible device of claim 1, wherein the first and second polymeric materials each comprise stabilized free radicals.

### Claim 21 (depends on 1)

The biocompatible device of claim 1, wherein the first polymeric material comprises stabilized free radicals and the second polymeric materials does not contain stabilized free radicals.

### Claim 22 (depends on 1)

The biocompatible device of claim 1, wherein the first polymeric material comprises a different amount of stabilized free radicals than the second polymeric material.

### Claim 23 (depends on 1)

The biocompatible device of claim 1, wherein the first and second polymeric materials have different reactive oxidative species generation profiles.

### Claim 24 (depends on 1)

The biocompatible device of claim 1, wherein at least one of said first and second polymeric materials is bioabsorbable.

### Claim 25 (depends on 24)

The biocompatible device of claim 24, wherein the bioabsorbable polymer is selected from poly(dioxanone), poly(glycolide), poly(lactide) poly(ε-caprolactone), poly(anhydrides) such as poly(sebacic acid), poly(hydroxyalkanoates) such as poly(3-hydroxybutyrate), copolymers of any of these and combinations thereof.

### Claim 26 (depends on 1)

The biocompatible device of claim 1, wherein the polymeric material has been subjected to the ionizing radiation at a total dose from about 30 kGy to about 50 kGy.

### Claim 27 (depends on 1)

The biocompatible device of claim 1, wherein the biocompatible material further comprises at least one therapeutically active agent.