Compositions and devices of poly-4-hydroxybutyrate

Patent metadata

Field	Value
Publication number	US-9290612-B2
Application number	US-201313801393-A
Country	US
Kind code	B2
Filing date	Mar 13, 2013
Priority date	Mar 13, 2013
Publication date	Mar 22, 2016
Grant date	Mar 22, 2016

Abstract

Compositions of P4HB with high purity have been developed. The compositions are prepared by washing P4HB biomass prior to solvent extraction, and precipitating P4HB from solution. The same solvent is preferably used to wash the P4HB biomass, and as a non-solvent to precipitate the polymer from a P4HB solvent solution. The highly pure P4HB compositions are suitable for preparing implants. The implants may be used for the repair of soft and hard tissues.

First claim

We claim:

1. A composition comprising poly-4-hydroxybutyrate (P4HB) polymer, the composition having: (i) residual lipid, wherein the lipid content, is less than 100 ppm (measured as palmitic acid), as determined by gas chromatography analysis after butanolysis, and relative to a standard measured under the same conditions.

2. The composition of claim 1 wherein the composition comprises residual solvent, wherein the residual solvent content, is less than 5 ppm as determined by head space gas chromatography-mass spectrometry (GC-MS).

3. The composition of claim 1 wherein the polymer has a 4-hydroxybutyrate content in the poly-4-hydroxybutyrate of 99.7%±2% by weight as determined by gas chromatography.

4. The composition of claim 1 wherein the composition has a residue on ignition of less than 0.2% as determined by the method of the United States Pharmacopeia (USP) <281>.

5. The composition of claim 1 wherein the composition comprises residual heavy metal, wherein the residual heavy metal content, is less than 20 ppm as determined by the method of the USP <231>, residual sulfur, wherein the residual sulfur content, is less than 50 ppm as determined by plasma optical emission spectroscopy; a hydrogen content of 7.02%±0.3% as determined by elemental combustion analysis or combinations thereof.

6. The composition of claims 1 wherein the composition is produced by washing a biomass comprising the polymer with ethanol.

7. The composition of claim 6 wherein the biomass is washed with at least 4 grams of ethanol per gram of biomass.

8. The composition of claim 6 wherein the biomass is derived from a microorganism.

9. The composition of claim 8 wherein the microorganism is Escherichia Coli K12.

10. The composition of claim 6 wherein the polymer is extracted from the ethanol washed biomass with a solvent.

11. The composition of claim 10 wherein the polymer is precipitated from the solvent with a non-solvent for the polymer, harvested, and dried.

12. The composition of claim 10 wherein the solvent is selected from the group consisting of methylene chloride, chloroform, tetrahydrofuran, acetone, dioxane, ethyl acetate, dimethylene carbonate, dimethyl sulfoxide, dimethyl formamide, methyl ethyl ketone, butyl acetate, butyl propionate and diethyl carbonate.

13. The composition of claim 11 wherein the non-solvent for the polymer is an alcohol, aqueous alcohol, or water.

14. The composition of claim 13 wherein the non-solvent for the polymer is aqueous ethanol.

15. The composition of claim 14 wherein the non-solvent for the polymer comprises ethanol, and ethanol is used to wash the biomass.

16. A medical device comprising residual pyrogen, wherein the pyrogen level is less than 20 endotoxin units per device as determined by the limulus amebocyte lysate assay the medical device comprising a poly-4-hydroxybyturate (P4HB) polymer composition having: residual lipid, wherein the residual lipid content is less than 100 ppm (measured as palmitic acid), as determined by gas chromatography analysis after butanolysis, and relative to a standard measured under the same conditions.

17. The medical device of claim 16 wherein the device is sterilized with cold ethylene oxide gas, gamma-irradiation, or electron beam irradiation.

18. The medical device of claims 17 wherein the device is used for soft or hard tissue repair, regeneration or replacement.

19. The medical device of claim 18 wherein the device is an implant for soft or hard tissue repair, regeneration or replacement.

20. The composition of claim 1 wherein the composition is used as a coating on a medical device.

21. The medical device of claim 17 wherein the device is selected from the group: suture, barbed suture, braided suture, monofilament suture, hybrid suture of monofilament and multifilament fibers, braids, ligatures, knitted or woven meshes, knitted tubes, catheters, monofilament meshes, multifilament meshes, patches, wound healing device, bandage, wound dressing, burn dressing, ulcer dressing, skin substitute, hemostat, tracheal reconstruction device, organ salvage device, dural substitute, dural patch, nerve guide, nerve regeneration or repair device, hernia repair device, hernia mesh, hernia plug, device for temporary wound or tissue support, tissue engineering scaffold, guided tissue repair/regeneration device, anti-adhesion membrane, adhesion barrier, tissue separation membrane, retention membrane, sling, device for pelvic floor reconstruction, urethral suspension device, device for treatment of urinary incontinence, device for treatment of vesicoureteral reflux, bladder repair device, sphincter muscle repair device, injectable particles, injectable microspheres, bulking or filling device, bone marrow scaffold, clip, clamp, screw, pin, nail, medullary cavity nail, bone plate, interference screw, tack, fastener, rivet, staple, fixation device for an implant, bone graft substitute, bone void filler, suture anchor, bone anchor, ligament repair device, ligament augmentation device, ligament graft, anterior cruciate ligament repair device, tendon repair device, tendon graft, tendon augmentation device, rotator cuff repair device, meniscus repair device, meniscus regeneration device, articular cartilage repair device, osteochondral repair device, spinal fusion device, device for treatment of osteoarthritis, viscosupplement, stent, stent coatings, stent graft, cardiovascular patch, catheter balloon, vascular closure device, intracardiac septal defect repair device, atrial septal defect repair devices, PFO (patent foramen ovale) closure devices, left atrial appendage (LAA) closure device, pericardial patch, vein valve, heart valve, vascular graft, myocardial regeneration device, periodontal mesh, guided tissue regeneration membrane for periodontal tissue, ocular cell implant, imaging device, cochlear implant, embolization device, anastomosis device, cell seeded device, cell encapsulation device, controlled release device, drug delivery device, plastic surgery device, breast lift device, mastopexy device, breast reconstruction device, breast augmentation device, devices for use with breast implants, breast reduction device, devices for removal, reshaping and reorienting breast tissue, devices for breast reconstruction following mastectomy with or without breast implants, facial reconstructive device, forehead lift device, brow lift device, eyelid lift device, face lift device, rhytidectomy device, thread lift device to lift and support sagging areas of the face, brow and neck, rhinoplasty device, device for malar augmentation, otoplasty device, neck lift device, mentoplasty device, cosmetic repair device, and device for facial scar revision.

22. The medical device of claim 21 , wherein the stent is selected from the group consisting of a coronary, cardiovascular, peripheral, ureteric, urethral, urology, gastroenterology, nasal, ocular and neurology stent.

23. The composition of claim 1 , having at least one property selected from the group consisting of: a nitrogen content of 40 ppm as determined by the Kjedahl method of nitrogen analysis, residual sulfur, wherein the residual sulfur content, is less than 50 ppm as determined by plasma optical emission spectroscopy; a hydrogen content of 7.02%±0.3% as determined by elemental combustion analysis or combinations thereof, and a carbon content of 55.81%±0.5% as determined by elemental combustion analysis.

24. The composition of claim 1 , wherein the P4HB is made

Assignees

• Tepha Inc

Inventors

• Martin David P
• Guo Kai
• Williams Simon F

Classifications

• A61L31/06

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)} · CPC title

• A61L29/085

  Macromolecular materials · CPC title

• C08G63/90

  Purification; Drying · CPC title

• A61L29/06

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• C08G63/06 Primary

  derived from hydroxycarboxylic acids · CPC title