Methods of orienting multifilament yarn and monofilaments of poly-4-hydroxybutyrate and copolymers thereof

Patent metadata

Field	Value
Publication number	US-9555155-B2
Application number	US-201514964985-A
Country	US
Kind code	B2
Filing date	Dec 10, 2015
Priority date	Dec 11, 2014
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

Abstract

Resorbable multifilament yarns and monofilament fibers including poly-4-hydroxybutyrate and copolymers thereof with high tenacity or high tensile strength have been developed. The yarns and fibers are produced by cold drawing the multifilament yarns and monofilament fibers before hot drawing the yarns and fibers under tension at temperatures above the melt temperature of the polymer or copolymer. These yarns and fibers have prolonged strength retention in vivo making them suitable for soft tissue repairs where high strength and strength retention is required. The multifilament yarns have tenacities higher than 8.1 grams per denier, and in vivo, retain at least 65% of their initial strength at 2 weeks. The monofilament fibers retain at least 50% of their initial strength at 4 weeks in vivo. The monofilament fibers have tensile strengths higher than 500 MPa. These yarns and fibers may be used to make various medical devices for various applications.

First claim

We claim:

1. A multifilament yarn or monofilament fiber comprising a 4-hydroxybutyrate polymer or copolymer wherein the yarn has one or more properties selected from the group consisting of: a tenacity greater than 8.1 grams per denier but less than 12 grams per denier; an elongation to break of between 10% to 30%; and a denier per filament between 1.7 and 9.0, and wherein the monofilament fiber has one or more properties selected from the group consisting of: a tensile strength between 500 MPa and 1,500 MPa; a Young's Modulus of less than 2 GPa and an elongation to break of 15% to 120%,
wherein the multifilament yarn or monofilament fiber is produced by a method comprising (a) spinning a multifilament yarn or monofilament fiber comprising a 4-hydroxybutyrate polymer or copolymer, and (b) cold drawing the multifilament yarn or monofilament fiber, wherein the multifilament yarn or monofilament fiber is hot drawn after cold drawing at a temperature above the melt temperature of the polymer or copolymer, wherein the monofilament fiber is cold drawn with an orientation ratio of 3 to 4, and then hot drawn in one or more subsequent draws; or,
wherein the multifilament yarn or monofilament fiber is produced by a method comprising: (a) producing the polymer with a recombinant E. coli cell culture, (b) extracting and purifying the polymer from the biomass, (c) spinning the multifilament yarn or monofilament fiber from the polymer, (d) cold drawing the multifilament yarn or monofilament fiber, (e) hot drawing the multifilament yarn or monofilament fiber after cold drawing at a temperature above the melt temperature of the polymer or copolymer, and (f) optionally relaxing and/or annealing the multifilament yarn or monofilament fiber, wherein the multifilament yarn or monofilament fiber is biocompatible.

2. The monofilament fiber of claim 1 , wherein the fiber has been allowed time to crystallize before drawing.

3. The monofilament yarn of claim 1 , wherein the yarn has been oriented in a multi-stage orientation process.

4. The multifilament yarn of claim 3 , wherein the yarn is cold drawn in the first stage of the multi-stage orientation process.

5. The monofilament fiber of claim 1 , wherein the monofilament fiber has been drawn at a temperature below 50° C., before being drawn at a temperature above the melt temperature of the fiber.

6. A medical device comprising the multifilament yarn or the monofilament fiber of claim 1 , wherein the device is a suture, monofilament suture, multifilament suture, braided suture, hybrid suture of monofilament and multifilament fibers, barbed suture, self-retaining suture, braid, ligature, tape, knitted or woven mesh, non-woven mesh, knitted tube, monofilament mesh, multifilament mesh, patch, wound healing device, bandage, wound dressing, burn dressing, ulcer dressing, skin substitute, hemostat, tracheal reconstruction device, organ salvage device, dural substitute, dural patch, 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, suture anchor, soft 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, stent, coronary stent, cardiovascular stent peripheral stent, ureteric stent, urethral stent, urology stent, gastroenterology stent, nasal stent, ocular stent, neurology stent, stent graft, cardiovascular patch, vascular closure device, intracardiac septal defect repair device, atrial septal defect repair device, 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, embolization device, anastomosis device, cell seeded device, controlled release device, drug delivery device, plastic surgery device, breast lift device, mastopexy device, breast reconstruction device, breast augmentation device, breast reduction device, 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/or neck, rhinoplasty device, device for malar augmentation, otoplasty device, neck lift device, mentoplasty device, cosmetic repair device, device for facial scar revision, and enclosures, pouches, holders, covers, clamshells, casings to hold implantable medical devices.

7. The device of claim 6 , wherein the device is sterile and/or biocompatible.

8. The device of claim 6 , wherein the device has been sterilized by ethylene oxide, electron beam irradiation or gamma irradiation and/or contains less than 20 endotoxin units.

9. The device of claim 8 , wherein the device is a mesh produced by a method comprising: (a) knitting or weaving the monofilament fiber or multifilament yarn and (b) packaging and sterilizing the mesh.

10. The device of claim 9 wherein the mesh can withstand a burst pressure of at least 0.1 kPa.

11. The device of claim 6 , wherein the device is a braid or tape with a breaking load between a breaking load greater than 1.0, 10.0, 20.0, 30.0, 40.0, 50.0, 60.0, 70.0 or 80.0 kgf and less than or equal to 85.2 kgf.

12. The device of claim 6 , wherein the device is a braid, with a diameter less than 0.8 mm, and a breaking load between a breaking load greater than 22 kgf and less than or equal to 26.2 kgf, or a tape with a thickness less than 0.52 mm and a width less than 3.75 mm, and a breaking load between 35 kgf and 85.2 kgf.

13. The medical device of claim 6 , further comprising one or more of the following: plasticizer, nucleant, dye, medical marker, bioactive agent, therapeutic agent, antimicrobial agent, diagnostic agent, prophylactic agent, protein, peptide, antibody, polysaccharide, glycoprotein, lipid, lipoprotein, nucleic acid molecule, inorganic or organic synthetic molecule, contrast agent, radiopaque marker, radioactive substance, hyaluronic acid or derivative thereof, collagen, hydroxyapatite, synthetic polymer, natural polymer or one or more absorbable polymers derived from glycolic acid, glycolide, lactic acid, lactide, 1,4-dioxanone, trimethyl carbonate, ε-caprolactone.

14. The medical device of claim 13 , wherein the antimicrobial agent is selected from one or more of the following: rifampin; minocycline and its hydrochloride, sulfate, or phosphate salt; triclosan; chlorhexidine; vancomycin and its hydrochloride, sulfate, or phosphate salt; tetracycline and its hydrochloride, sulfate, or phosphate salt, and derivatives; gentamycin; cephalosporin antimicrobials; aztreonam; cefotetan and its disodium salt; loracarbef; cefoxitin and its sodium salt; cefazolin and its sodium salt; cefaclor; ceftibuten and its sodium salt; ceftizoxime; ceftizoxime sodium salt; cefoperazone and its sodium salt; cefuroxime and its sodium salt; cefuroxime axetil; cefp

Assignees

• Tepha Inc

Inventors

• Ganatra Amit
• Felix Fabio
• Shah Bhavin
• Bernasconi Matthew
• Rizk Said
• Martin David P
• Williams Simon F

Classifications

• D01D5/08

  Melt spinning methods {(D01D5/0023 takes precedence)} · CPC title

• D01F8/14

  with at least one polyester as constituent · CPC title

• B29K2673/00

  Use of other polymers having oxygen as the only hetero atom in the main chain, for preformed parts, e.g. for inserts · CPC title

• A61L31/06

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

• D10B2509/04

  Sutures · CPC title