# US 11,896,734 B2 · Surgical mesh implants containing poly(butylene succinate) and copolymers thereof

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- Number: US 11,896,734 B2
- Document ID: US11896734B2
- Status: Granted
- Kind: B2
- Application number: 16/290,735
- Filed: 2019-03-01
- Published: 2019-09-05
- Granted: 2024-02-13
- Earliest claimed: 2018-03-01
- Assignees: Tepha, Inc.
- Applicants: Tepha, Inc.
- Inventors: Simon F. Williams; Said Rizk; David P. Martin
- Web page: https://patentgrep.com/patent/US11896734B2

## CPC

- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61F 2/0045: {Support slings}
- A61F 2/0063: {Implantable repair or support meshes, e.g. hernia meshes}
- A61F 2/12: Mammary prostheses
- A61L 17/06: At least partially resorbable materials
- A61L 17/105: {Polyesters not covered by A61L17/12}
- A61L 17/12: Homopolymers or copolymers of glycolic acid or lactic acid
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61L 27/58: Materials at least partially resorbable by the body
- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- A61L 31/146: {Porous materials, e.g. foams or sponges}
- A61L 31/148: {Materials at least partially resorbable by the body}
- C08L 65/00: Compositions of macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain (C08L7/00 - C08L57/00, C08L61/00 take precedence); Compositions of derivatives of such polymers
- C08L 67/00: Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain (of polyester-amides C08L77/12; of polyester-imides C08L79/08); Compositions of derivatives of such polymers
- D02G 3/045: {all components being made from artificial or synthetic material}
- D02G 3/448: {Yarns or threads for use in medical applications (D02G3/449 takes precedence; surgical suture materials A61L17/00)}
- D02G 3/449: {Yarns or threads with antibacterial properties (filaments containing agents inhibiting growth of microorganisms D01F1/103)}
- A61F 2002/0068: {having a special mesh pattern}
- A61F 2220/0016: with sharp anchoring protrusions, e.g. barbs, pins, spikes
- A61F 2240/002: Designing or making customized prostheses
- A61F 2250/0067: Means for introducing or releasing pharmaceutical products into the body
- A61L 17/005: {containing a biologically active substance, e.g. a medicament or a biocide}
- A61L 27/48: with macromolecular fillers
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61L 2300/404: Biocides, antimicrobial agents, antiseptic agents
- A61L 2300/416: Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
- A61L 2430/04: for mammary reconstruction
- A61L 2430/34: for soft tissue reconstruction
- A61L 2430/38: for reconstruction of the spine, vertebrae or intervertebral discs
- D10B 2331/04: polyesters, e.g. polyethylene terephthalate [PET]
- D10B 2401/063: high strength
- D10B 2509/04: Sutures
- 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)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- D02G: CRIMPING OR CURLING FIBRES, FILAMENTS, THREADS, OR YARNS; YARNS OR THREADS
- D10B: INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES

## Abstract

Resorbable implants comprising poly(butylene succinate) and copolymers thereof have been developed. The implants are preferably sterilized, and contain less than 20 endotoxin units per device as determined by the limulus amebocyte lysate (LAL) assay, and are particularly suitable for use in procedures where prolonged strength retention is necessary, and can include one or more bioactive agents. The implants may be made from fibers and meshes of poly(butylene succinate) and copolymers thereof, or by 3d printing, and the fibers may be oriented. Coverings and receptacles made from forms of poly(butylene succinate) and copolymers thereof have also been developed for use with cardiac rhythm management devices and other implantable devices. These coverings and receptacles may be used to hold, or partially/fully cover, devices such as pacemakers and neurostimulators. The coverings and receptacles are made from meshes, webs, lattices, non-wovens, films, fibers, and foams, and contain antibiotics such as rifampin and minocycline.

## Claims

### Claim 1

A surgical mesh implant comprising a polymeric composition, wherein the polymeric composition comprises a 1,4-butanediol unit and a succinic acid unit, wherein: (a) under physiological conditions in vivo: the weight average molecular weight of the polymeric composition decreases 3% to 15% over a 4-week time period, the weight average molecular weight of the polymeric composition decreases 20% to 35% over a 12-week time period, or the percent mass loss of the surgical mesh implant is between 0% and 5% over a 12-week period, or (b) the burst strength of the surgical mesh implant decreases less than 20% at 4 weeks, or less than 35% at 12 weeks; and wherein the surgical mesh implant is sterile.

### Claim 2 (depends on 1)

The surgical mesh implant of claim 1, wherein the surgical mesh implant has one or more of the following: (i) an areal density of 5 g/m2 to 800 g/m2, (ii) a suture pullout strength of at least 10 N, (iii) pores with a diameter of at least 10 μm, (iv) a burst strength greater than 0.1 kPa, (v) a Taber stiffness of at least 0.01 Taber stiffness units, (vi) knitted fibers, woven fibers, crocheted fibers or braided fibers, (vii) monofilament fibers, (viii) multifilament fibers, and (ix) a degradation rate in phosphate buffered saline at 37° C. wherein the weight average molecular weight of the surgical mesh implant decreases between 10% and 30% over a 12-week time period.

### Claim 3 (depends on 2)

The surgical mesh implant of claim 2, wherein the fibers have one or more of the following properties: (i) orientation, (ii) a tensile strength between 400 MPa and 1,200 MPa, (iii) a tenacity between 4 grams/denier and 14 grams/denier, (iv) a Young's Modulus between 600 MPa and 3.0 GPa, (v) an elongation to break of 10% to 50%, (vi) a diameter between 10 μm and 1 mm, (vii) a melting temperature between 100° C. and 150° C., and (viii) a degradation rate in phosphate buffered saline at 37° C. wherein the weight average molecular weight of the fibers decreases between 10% and 25% over a 12-week time period.

### Claim 4 (depends on 2)

The surgical mesh implant of claim 2, wherein the surgical mesh implant has a burst strength of greater than 0.1 kPa, and/or wherein the Young's modulus of the fibers is at least 600 MPa.

### Claim 5 (depends on 4)

The surgical mesh implant of claim 4, wherein the fibers are prepared by melt extrusion from the polymeric composition, and the weight average molecular weight of the extruded fibers is not less than 80% of the weight average molecular weight of the polymeric composition prior to extrusion.

### Claim 6 (depends on 4)

The surgical mesh implant of claim 4, wherein the mesh has one or more of the following properties: an areal density of 5 g/m2 to 800 g/m2, a suture pullout strength of at least 10 N, and pores with a diameter of at least 10 μm.

### Claim 7 (depends on 4)

The surgical mesh implant of claim 4, wherein the monofilament fibers have been stretched to orient the fibers and increase the stiffness of the mesh, and wherein the Young's Modulus of the fibers is at least 600 MPa.

### Claim 8 (depends on 7)

The surgical mesh implant of claim 7, wherein the Young's Modulus of the fibers is less than 3 GPa.

### Claim 9 (depends on 8)

The surgical mesh implant of claim 8, wherein the fibers have been oriented with an orientation ratio of at least 6.0.

### Claim 10 (depends on 7)

The surgical mesh implant of claim 7, wherein the fibers have a diameter between 10 μm and 1 mm.

### Claim 11 (depends on 4)

The surgical mesh implant of claim 4, wherein the fibers have one or more of the following properties: (i) a tensile strength between 400 MPa and 1,200 MPa, (ii) a tenacity between 4 grams/denier and 12 grams/denier, (iii) a Young's Modulus of less than 3.0 GPa, (iv) an elongation to break of 10% to 50%, (v) a diameter between 10 μm and 1 mm, and (vi) a melting temperature between 100° C. and 150° C.

### Claim 12 (depends on 4)

The surgical mesh implant of claim 4, wherein the weight average molecular weight of the extruded fibers is not less than 85%.

### Claim 13 (depends on 2)

The surgical mesh implant of claim 2, wherein the fibers have a melting temperature between 105° C. and 120° C.

### Claim 14 (depends on 2)

The surgical mesh implant of claim 2, wherein the Young's modulus of the fibers is at least 800 MPa.

### Claim 15 (depends on 2)

The surgical mesh implant of claim 2, wherein the Young's modulus of the fibers is at least 1 GPa.

### Claim 16 (depends on 2)

The surgical mesh implant of claim 2, wherein the Young's modulus of the fibers is at least 1.5 GPa.

### Claim 17 (depends on 2)

The surgical mesh implant of claim 2, wherein the Young's modulus of the fibers is at least 2 GPa.

### Claim 18 (depends on 1)

The surgical mesh implant of claim 1, wherein the polymeric composition used to prepare the mesh further comprises one or more of: (a) a second diacid unit, a second diol unit, 1,3-propanediol, ethylene glycol, 1,5-pentanediol, glutaric acid, adipic acid, terephthalic acid, malonic acid, and oxalic acid (b) a hydroxycarboxylic acid unit, and (c) a branching agent, a cross-linking agent, chain extender agent, and reactive blending agent, wherein the branching agent, cross-linking agent, or chain extender unit is selected from one or more of the following: malic acid, maleic acid, fumaric acid, trimethylol propane, trimesic acid, citric acid, glycerol propoxylate, and tartaric acid.

### Claim 19 (depends on 1)

The surgical mesh implant of claim 1, wherein the polymeric composition comprises:
a. succinic acid-1,4-butanediol-malic acid copolyester;
b. succinic acid-1,4-butanediol-citric acid copolyester;
c. succinic acid-1,4-butanediol-tartaric acid copolyester;
d. succinic acid-1,4-butanediol-malic acid copolyester further comprising citric acid, tartaric acid, or a combination thereof;
e. succinic acid-adipic acid-1,4-butanediol-malic acid copolyester;
f. succinic acid-adipic acid-1,4-butanediol-citric acid copolyester;
g. succinic acid-adipic acid-1,4-butanediol-tartaric acid copolyester; or
h. succinic acid-adipic acid-1,4-butanediol-malic acid copolyester further comprising citric acid, tartaric acid, or combinations thereof.

### Claim 20 (depends on 1)

The surgical mesh implant of claim 1, wherein the polymeric composition: (i) excludes urethane bonds, and (ii) is not prepared with a diisocyanate.

### Claim 21 (depends on 20)

The surgical mesh implant of claim 20, wherein the polymeric composition: (i) comprises 1 ppm to 500 ppm of one or more of: silicon, titanium and zinc; (ii) excludes tiny or (iii) is not a blend of two or more polymers.

### Claim 22 (depends on 1)

The surgical mesh implant of claim 1, wherein the polymeric composition has a melt temperature between 100° C. and 150° C.

### Claim 23 (depends on 1)

The surgical mesh implant of claim 1, wherein the surgical mesh is a knitted mesh, a woven mesh, a crocheted mesh, a monofilament mesh, a multifilament mesh, a weft knit mesh, a warp knit mesh, a plug, a hernia plug, a void filler, an inguinal hernia plug, and (i) has a three-dimensional shape that can be temporarily deformed, or (ii) has an outwardly curving exterior and an inwardly curving interior.

### Claim 24 (depends on 23)

The surgical mesh implant of claim 23, wherein the surgical mesh further comprises an anti-adhesion layer, barbs, hooks, self-anchoring tips, micro-grips, fleece, reinforcement, and a reinforced outer edge or border.

### Claim 25 (depends on 1)

The surgical mesh implant of claim 1, further comprising a plasticizer, nucleant, coating, dye, medical marker, bioactive agent, therapeutic agent, diagnostic agent, prophylactic agent, contrast agent, radiopaque marker, radioactive substance, anti-adhesion agent, hyaluronic acid, antibiotic, rifampin, minocycline, collagen, hydroxyapatite, or an absorbable polymer comprising one or more of the following monomers: glycolic acid, lactic acid, trimethylene carbonate, p-dioxanone, ε-caprolactone, 4-hydroxybutyric acid, and 3-hydroxybutyric acid.

### Claim 26 (depends on 1)

The surgical mesh implant of claim 1, the surgical mesh implant is selected from the group: wound closure device, patch, wound healing device, device for tissue or suture line reinforcement, tracheal reconstruction device, organ salvage device, dural patch or substitute, nerve regeneration or repair device, hernia repair device, hernia mesh, hernia plug, inguinal hernia plug, device for temporary wound or tissue support, tissue engineering scaffold, guided tissue repair/regeneration device, anti-adhesion membrane or barrier, tissue separation membrane, retention membrane, sling, device for pelvic floor reconstruction, device for treating pelvic organ prolapse, urethral suspension device, device for treatment of urinary incontinence, bladder repair device, void filling device, bone marrow scaffold, ligament repair device or augmentation device, anterior cruciate ligament repair device, tendon repair device or augmentation device, rotator cuff repair device, meniscus repair or regeneration device, articular cartilage repair device, osteochondral repair device, spinal fusion device, cardiovascular patch, vascular closure device, intracardiac septal defect repair device, atrial septal defect repair device, patent foramen ovale closure device, left atrial appendage closure device, pericardial patch, vascular graft, myocardial regeneration device, periodontal mesh, guided tissue regeneration membrane for periodontal tissue, imaging 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, breast implant, facial reconstructive device, forehead lift device, brow lift device, eyelid lift device, face lift device, rhytidectomy device, rhinoplasty device, device for malar augmentation, otoplasty device, neck lift device, mentoplasty device, buttock lift device, cosmetic repair device, device for facial scar revision, and a pouch, holder, cover, enclosure, or casing to partially or fully encase, surround or hold: an implantable medical device, a cardiac rhythm management device, a pacemaker, a defibrillator, a generator, an implantable access system, a neurostimulator, a ventricular access device, an infusion pump, a device for delivery of medication and hydration solution, an intrathecal delivery system, a pain pump, or device that provides drug(s) or electrical stimulation to a body.

### Claim 27 (depends on 1)

The surgical mesh implant of claim 1, wherein the dimensions of the mesh do not shrink by more than 5% of their initial values, or the area occupied by the mesh does not decrease by more than 5%, following implantation in vivo under physiological conditions, for 4 weeks.

### Claim 28 (depends on 1)

The surgical mesh implant of claim 1, wherein the polymeric composition is isotopically enriched.

### Claim 29 (depends on 1)

The surgical mesh implant of claim 1, wherein the surgical mesh has a suture pullout strength of at least 20 N.

### Claim 30 (depends on 1)

The surgical mesh implant of claim 1, wherein the surgical mesh has pores with a diameter of at least 50 μm.

### Claim 31 (depends on 1)

The surgical mesh implant of claim 1, wherein the surgical mesh has pores with a diameter of at least 100 μm.

### Claim 32

A surgical mesh implant comprising a polymeric composition, wherein the polymeric composition comprises a 1,4-butanediol unit and a succinic acid unit, wherein the mesh comprises fibers, wherein the fibers are produced by a method comprising spinning a multifilament or monofilament fiber comprising the polymeric composition, drawing the multifilament or monofilament fiber by an orientation ratio of 6 to 8 in one or more stages at a temperature of 50° C. to 80° C.

### Claim 33 (depends on 32)

The surgical mesh implant of claim 32, wherein the fibers are first drawn with a minimum orientation ratio of 3 to 4 at a temperature of 50° C. to 70° C. in one or more stages, followed by drawing with a minimum orientation ratio of 2 to 3 at a temperature between 60° C. and 80° C. in one or more stages, followed by hot drawing with an orientation ratio higher than 1.0 at a temperature between 70° C. and 80° C.

### Claim 34 (depends on 32)

The surgical mesh implant of claim 32, wherein the method comprises: (i) drying the polymeric composition prior to melt spinning so that the moisture content of the polymeric composition is less than 0.1 wt %, and (ii) hot drawing the fibers in a hot conductive liquid chamber.

### Claim 35 (depends on 32)

The surgical mesh implant of claim 32, wherein the polymeric composition: (i) excludes urethane bonds, and (ii) is not prepared with a diisocyanate.