# US 8,771,720 B2 · Medical device comprising polyhydroxyalkanoate having pyrogen removed using oxidizing agent

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- Number: US 8,771,720 B2
- Document ID: US8771720B2
- Status: Granted
- Kind: B2
- Application number: 13/545,663
- Filed: 2012-07-10
- Published: 2012-12-27
- Granted: 2014-07-08
- Earliest claimed: 1997-05-12
- Assignees: Metabolix, Inc.
- Applicants: Simon F. Williams; David P. Martin; Tillman Gerngross; Daniel M. Horowitz
- Inventors: Simon F. Williams; David P. Martin; Tillman Gerngross; Daniel M. Horowitz
- Web page: https://patentgrep.com/patent/US8771720B2

## CPC

- C12P 7/625: Polyesters of hydroxy carboxylic acids
- A61B 42/00: Surgical gloves; Finger-stalls specially adapted for surgery; Devices for handling or treatment thereof
- A61K 47/593: {Polyesters, e.g. PLGA or polylactide-co-glycolide}
- A61K 47/6957: {the form being a device or a kit, e.g. stents or microdevices}
- A61L 15/26: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof {(A61L15/225 takes precedence)}
- A61L 17/10: containing macromolecular materials
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/34: Macromolecular materials
- A61L 29/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- C08G 63/06: derived from hydroxycarboxylic acids
- C08G 63/6852: {derived from hydroxy carboxylic acids}
- C08G 63/6882: {derived from hydroxy carboxylic acids}
- C08G 63/912: {derived from hydroxycarboxylic acids}
- C12N 5/0068: {General culture methods using substrates (for specific animal cell type C12N5/06)}
- A61B 17/06166: {Sutures (suture materials A61L17/00; manufacture of artificial threads D01D; treatment of threads D06M)}
- C12N 2533/30: Synthetic polymers
- Y10S 977/775: Nanosized powder or flake, e.g. nanosized catalyst
- Y10T 428/139: Open-ended, self-supporting conduit, cylinder, or tube-type article
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. The PHAs are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone, other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.

## Claims

### Claim 1

A biocompatible medical device comprising
a polyhydroxyalkanoate polymer which is prepared using a process which introduces a pyrogen into the polyhydroxyalkanoate, wherein the pyrogen is removed from the polyhydroxyalkanoate using an oxidizing agent under conditions effective to produce a pyrogen level of less than 20 endotoxin units (EU) per device.

### Claim 2 (depends on 1)

The device of claim 1 wherein the device is in a form selected from the group consisting of stents, coatings on prosthetic devices, sutures, staples, and tubing.

### Claim 3 (depends on 1)

The device of claim 1 wherein the device is in a form selected from the group consisting of tissue regeneration devices, cell culture devices, vascular grafts, wound dressings, and cell or tissue coatings.

### Claim 4 (depends on 1)

The device of claim 1 wherein the device is in a form selected from the group consisting of drug, diagnostic or prophylactic delivery devices.

### Claim 5 (depends on 1)

The device of claim 1 wherein the device is a porous membrane.

### Claim 6 (depends on 1)

The device of claim 1 wherein the device comprises a material selected from the group consisting of therapeutic, prophylactic and diagnostic agents.

### Claim 7 (depends on 6)

The device of claim 6 wherein the device comprises a therapeutic agent selected from the group consisting of peptides, proteins, nucleic acids, saccharides, polysaccharides, lipids, synthetic drug molecules, and imaging agents.

### Claim 8 (depends on 1)

The device claim 1 wherein the device is formulated for administration to a mucosal surface.

### Claim 9 (depends on 1)

The device of claim 1 wherein the polyhydroxyalkanoate is a homopolymer, polymer blend or copolymer.

### Claim 10 (depends on 1)

The device of claim 1 wherein molecules are bound to the polymer, and the molecules are selected from the group consisting of molecules which are bioactive, molecules which can be detected, targeting molecules, and molecules affecting charge, lipophilicity or hydrophilicity of the polymer.

### Claim 11 (depends on 1)

The device of claim 1 wherein the device is for tissue engineering further comprising cells seeded onto or within the device.

### Claim 12 (depends on 1)

The device of claim 1 wherein the device is formed into a bone prosthesis.

### Claim 13 (depends on 1)

The device of claim 1 further comprising structural and adhesive materials to form a bone cement.

### Claim 14 (depends on 1)

The device of claim 1 in the form of a heart prosthetic selected from the group consisting of heart valves, heart leaflets, and heart anulus.

### Claim 15 (depends on 1)

The device of claim 1 in the form of a periodontal graft.

### Claim 16 (depends on 1)

The device of claim 1 in the form of a pericardial patch.