Compositions and devices of poly-4-hydroxybutyrate

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.

We claim: 
     
         1 . A composition comprising poly-4-hydroxybutyrate polymer, the composition having at least one property selected from the group consisting of:
 (i) a nitrogen content of 40 ppm or less; (ii) a carbon content of 55.81%±0.5%;   (iii) a hydrogen content of 7.02%±0.3% as determined by elemental combustion analysis, and (iv) a lipid content of less than 100 ppm.   
     
     
         2 . The composition of  claim 1  wherein the composition has a residual solvent content of less than 5 ppm. 
     
     
         3 . The composition of  claim 1  wherein the composition 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%. 
     
     
         5 . The composition of  claim 1  wherein the composition has a heavy metal content of less than 20 ppm. 
     
     
         6 . The composition of  claim 1  wherein the composition has a sulfur content of less than 50 ppm. 
     
     
         7 . The composition of  claim 1  wherein the composition is produced by washing a biomass comprising the polymer with ethanol. 
     
     
         8 . The composition of  claim 7  wherein the biomass is washed with at least 4 grams of ethanol per gram of biomass. 
     
     
         9 . The composition of  claim 7  wherein the biomass is derived from a microorganism. 
     
     
         10 . The composition of  claim 9  wherein the microorganism is  Escherichia Coli  K12. 
     
     
         11 . The composition of  claim 7  wherein the polymer is extracted from the ethanol washed biomass with a solvent. 
     
     
         12 . The composition of  claim 11  wherein the polymer is precipitated from the solvent with a non-solvent for the polymer, harvested, and dried. 
     
     
         13 . The composition of  claim 11  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. 
     
     
         14 . The composition of  claim 12  wherein the non-solvent for the polymer is an alcohol, aqueous alcohol, or water. 
     
     
         15 . The composition of  claim 14  wherein the non-solvent for the polymer is aqueous ethanol. 
     
     
         16 . The composition of  claim 15  wherein the non-solvent for the polymer comprises ethanol, and ethanol is used to wash the biomass. 
     
     
         17 . The composition of  claim 1  wherein the composition is used to form a medical device with a pyrogen level of less than 20 endotoxin units per device. 
     
     
         18 . A medical device formed according to  claim 17  wherein the device is sterilized with cold ethylene oxide gas, gamma-irradiation, or electron beam irradiation. 
     
     
         19 . The medical device of  claim 18  wherein the device is used for soft or hard tissue repair, regeneration or replacement. 
     
     
         20 . The medical device of  claim 19  wherein the device is an implant for soft or hard tissue repair, regeneration or replacement. 
     
     
         21 . The composition of  claim 1  wherein the composition is used as a coating on a medical device. 
     
     
         22 . The medical device of  claim 18  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, including coronary, cardiovascular, peripheral, ureteric, urethral, urology, gastroenterology, nasal, ocular, or neurology stents and stent coatings, stent graft, cardiovascular patch, catheter balloon, vascular closure device, intracardiac septal defect repair device, including but not limited to atrial septal defect repair devices and 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 (including devices for use with breast implants), breast reduction device (including 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.