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

• US 10,227,713 B2
• Filed: 12/05/2016
• Issued: 03/12/2019
• Est. Priority Date: 12/11/2014
• Status: Active Grant

• Current Assignee: Tepha Incorporated (Becton, Dickinson & Co)
• Original Assignee: Tepha Incorporated (Becton, Dickinson & Co)
• Inventors: Ganatra, Amit, Felix, Fabio, Shah, Bhavin, Bernasconi, Matthew, Rizk, Said, Martin, David P., Williams, Simon F.
• Primary Examiner(s): Dickinson, Paul W
• Application Number:
  US15/368,922
• Publication Number:
  US 20170081784A1
• Time in Patent Office: 827 Days
• CPC Class Codes: A61L 17/105 Polyesters not covered by A61L17/12
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: B29C 55/005 characterised by the choice of materials
• CPC Class Codes: B29K 2073/00 Use of other polymers having oxygen as the only hetero atom in the main chain, as moulding material
• CPC Class Codes: B29K 2673/00 Use of other polymers having oxygen as the only hetero atom in the main chain, for preformed parts, e.g. for inserts
• CPC Class Codes: B29L 2031/731 Filamentary material, i.e. comprised of a single element, e.g. filaments, strands, threads, fibres cables B29L2031/707
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: D01D 5/08 Melt spinning methods D01D5/0023 takes precedence
• CPC Class Codes: D01F 6/625 derived from hydroxy-carboxylic acids, e.g. lactones
• CPC Class Codes: D01F 8/14 with at least one polyester as constituent
• CPC Class Codes: D02G 3/04 Blended or other yarns or threads containing components made from different materials
• CPC Class Codes: D04C 1/12 Cords, lines, or tows
• CPC Class Codes: D10B 2331/04 polyesters, e.g. polyethylene terephthalate [PET]
• CPC Class Codes: D10B 2331/041 derived from hydroxy-carboxylic acids, e.g. lactones
• CPC Class Codes: D10B 2401/063 high strength
• CPC Class Codes: D10B 2509/04 Sutures
• CPC Class Codes: D10B 2509/08 Hernia repair mesh

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.

Claims

1. A multifilament yarn or monofilament fiber comprising a 4-hydroxybutyrate polymer or copolymer

wherein the yarn has a tenacity greater than 8.1 grams per denier but less than 12 grams per denier;

and one or more properties selected from the group consisting of;

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 a tensile strength between 800 MPa and 1,500 MPa and a minimum knot pull tensile strength greater than 0.25 kgf; and

one or more properties selected from the group consisting of;

a Young'"'"'s Modulus of less than 2 GPa and an elongation to break of 15% to 120%.

2. A method for preparing the multifilament yarn or a monofilament fiber of claim 1, wherein the method comprises:

(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.

3. The method of claim 2, wherein the multifilament yarn is cold drawn with an orientation ratio of 2 to 6, and then hot drawn in one or more subsequent draws to yield a yarn with a tenacity of at least 8.1 grams per denier.

4. The method of claim 3, further comprising relaxing and/or annealing the fiber.

5. The method of claim 2, wherein the multifilament yarn or monofilament fiber are spun from a polymer or copolymer with a weight average molecular weight between 50 kDa and 1,200 kDa measured by gel permeation chromatography relative to polystyrene.

6. The method of claim 2, wherein the monofilament fiber has an elongation to break between 15% and 120%.

7. The multifilament yarn of claim 1, wherein the yarn has a tenacity greater than 10 grams per denier.

8. The multifilament yarn of claim 1, wherein the yarn has been oriented in a multi-stage orientation process, wherein the yarn is hot drawn in at least one stage.

9. The multifilament yarn of claim 8, wherein the yarn is cold drawn in the first stage of the multi-stage orientation process.

10. The multifilament yarn of claim 1, wherein the retained breaking load of the yarn decreases less than 65% after implantation for two weeks.

11. The multifilament yarn or monofilament fiber of claim 1, further comprising an additive wherein the additives are plasticizers, nucleants, compatibilizers, porogens, radiolabelled substances, imaging agents, radiopaque markers, contrast agents, dyes, bioactive agents, absorbable polymers, natural polymers, and synthetic polymers.

12. The multifilament yarn or monofilament fiber of claim 1, wherein the weight average molecular weight of the 4-hydroxybutyrate polymer or copolymer is between 50 kD and 1,200 kD.

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

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

15. The multifilament yarn of claim 14, wherein the yarn is cold drawn in the first stage of the multi-stage orientation process.

16. 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.

17. The multifilament yarn or monofilament fiber of claim 1 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.

18. 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 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.

19. The device of claim 18, wherein the device is sterile and/or biocompatible.

20. The device of claim 18, wherein the device has been sterilized by ethylene oxide, electron beam irradiation or gamma irradiation and/or contains less than 20 endotoxin units.

21. The device of claim 20, 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.

22. The device of claim 21 wherein the mesh can withstand a burst pressure of at least 0.1 kPa.

23. The device of claim 18, wherein the device is a braid or tape with 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.

24. The device of claim 18, wherein the device is a braid, with a diameter less than 0.8 mm, and a breaking load greater than 22 kgf, or a tape with a thickness less than 0.52 mm and a width less than 3.75 mm, and a breaking load greater than 35 kgf.

25. The medical device of claim 18 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.

26. The medical device of claim 25, 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;

cefprozil;

ceftazidime;

cefotaxime and its sodium salt;

cefadroxil;

ceftazidime and its sodium salt;

cephalexin;

cefamandole nafate;

cefepime and its hydrochloride, sulfate, and phosphate salt;

cefdinir and its sodium salt;

ceftriaxone and its sodium salt;

cefixime and its sodium salt;

cefpodoxime proxetil;

meropenem and its sodium salt;

imipenem and its sodium salt;

cilastatin and its sodium salt;

azithromycin;

clarithromycin;

dirithromycin;

erythromycin and hydrochloride, sulfate, or phosphate salts, ethylsuccinate, and stearate forms thereof, clindamycin;

clindamycin hydrochloride, sulfate, or phosphate salt;

lincomycin and hydrochloride, sulfate, or phosphate salt thereof, tobramycin and its hydrochloride, sulfate, or phosphate salt;

streptomycin and its hydrochloride, sulfate, or phosphate salt;

neomycin and its hydrochloride, sulfate, or phosphate salt;

acetyl sulfisoxazole;

colistimethate and its sodium salt;

quinupristin;

dalfopristin;

amoxicillin;

ampicillin and its sodium salt;

clavulanic acid and its sodium or potassium salt;

penicillin G;

penicillin G benzathine, or procaine salt;

penicillin G sodium or potassium salt;

carbenicillin and its disodium or indanyl disodium salt;

piperacillin and its sodium salt;

ticarcillin and its disodium salt;

sulbactam and its sodium salt;

moxifloxacin;

ciprofloxacin;

ofloxacin;

levofloxacins;

norfloxacin;

gatifloxacin;

trovafloxacin mesylate;

alatrofloxacin mesylate;

trimethoprim;

sulfamethoxazole;

demeclocycline and its hydrochloride, sulfate, or phosphate salt;

doxycycline and its hydrochloride, sulfate, or phosphate salt;

oxytetracycline and its hydrochloride, sulfate, or phosphate salt;

chlortetracycline and its hydrochloride, sulfate, or phosphate salt;

metronidazole;

dapsone;

atovaquone;

rifabutin;

linezolide;

polymyxin B and its hydrochloride, sulfate, or phosphate salt;

sulfacetamide and its sodium salt;

clarithromycin; and

silver ions, salts, and complexes.

27. A method of using the device of claim 18 comprising implanting the device in the body of a patient in need thereof.

28. The method of claim 27, wherein the device is implanted using an open procedure, arthroscopic procedure, laparoscopic procedure, or delivered from a preconfigured delivery unit that may or may not be under tension.

29. The method of claim 27, wherein the device is a suture anchor, bone anchor, soft suture anchor, suture, tape, mesh or patch, and is preloaded for delivery.

30. The method of claim 27 wherein the device is used in orthopedic surgery, ligament and tendon repairs, Bankart lesion repair, SLAP lesion repair, acromion-clavicular repair, capsular shift/capsulolabral reconstruction, deltoid repair, Labral repair of the shoulder, Capsular/Labral Repairs of the Hip, rotator cuff tear repair, biceps tenodesis, foot and ankle medial/lateral repair and reconstruction, mid- and forefoot repair, Hallux valgus reconstruction, metatarsal ligament/tendon repair and reconstruction, Achilles tendon repair, ulnar or radial collateral ligament reconstruction, lateral epicondylitis repair, biceps tendon reattachment, knee extra-capsular repair, iliotibial band tenodesis, patellar tendon repair, vastus medialis obliquus (VMO) advancement, knee joint capsule closure, hand and wrist collateral ligament repair, scapholunate ligament reconstruction, tendon transfers in phalanx, volar plate reconstruction, acetabular labral repair, anterior ligament repair, spinal repair, fracture fixation, cardiovascular surgery, general surgery, gastric surgery, bowel surgery, abdominoplasty, plastic, cosmetic and reconstructive surgery, forehead lifting, brow lifting, eyelid lifting, facelift, neck lift, breast lift, lateral canthopexy, elevation of the nipple, breast reconstruction, breast reduction, breast augmentation, mastopexy, pelvic floor reconstruction, cystocele and rectocele repair, low anterior resection, urethral suspension, obstetrics and gynecological surgery, Nissen Fundoplication, myomectomy, hysterectomy, sacrolpopexy, cesarean delivery, hernia repair, general soft tissue approximation and ligation, wound closure reduction of wide scars, wound hernia repair, hemostasis, anastomosis, abdominal closure, laparoscopic procedures, partial nephrectomy, and implantation of cardiac rhythm management (CRM) devices, including pacemakers, defibrillators, generators, neurostimulators, ventricular access devices, infusion pumps, devices for delivery of medication and hydration solutions, intrathecal delivery systems, pain pumps, and other devices to provide drugs or electrical stimulation to a body part.

31. The multifilament yarn of claim 1, wherein the yarn has a denier per filament between 1.7 and 6.

32. The monofilament fiber of claim 16, wherein the monofilament fiber has been drawn at a temperature below 45°

C. before being drawn at a temperature above the melt temperature of the fiber.

33. The device of claim 24, wherein the device is a braid, with a diameter less than 0.7 mm, and a breaking load greater than 24 kgf, or a tape with a thickness less than 0.52 mm and a width less than 3.75 mm, and a breaking load greater than 60 kgf.

34. The device of claim 33, wherein the tape has a breaking load of up to 80 kgf.

37. The monofilament or multifilament of claim 1, comprising a 4-hydroxybutyrate homopolymer.

38. The monofilament or multifilament of claim 1, wherein the fiber is spun from a polymer with a weight average molecular weight between 100 kDa and 1,200 kDa measured by gel permeation chromatography relative to polystyrene.

35. 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.

36. The monofilament of claim 35, wherein the tensile strength is between 900 MPa and 1,500 MPa.