Surgical mesh implants containing poly(butylene succinate) and copolymers thereof

Patent metadata

Field	Value
Publication number	US-11896734-B2
Application number	US-201916290735-A
Country	US
Kind code	B2
Filing date	Mar 1, 2019
Priority date	Mar 1, 2018
Publication date	Feb 13, 2024
Grant date	Feb 13, 2024

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.

First claim

We 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.

2. 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/m 2 to 800 g/m 2 , (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.

3. 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.

4. 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.

5. 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.

6. The surgical mesh implant of claim 4 , wherein the mesh has one or more of the following properties: an areal density of 5 g/m 2 to 800 g/m 2 , a suture pullout strength of at least 10 N, and pores with a diameter of at least 10 μm.

7. 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.

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

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

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

11. 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.

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

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

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

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

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

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

18. 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.

19. 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.

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

21. 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.

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

23. 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.

24. 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.

25. 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,

Assignees

• Tepha Inc

Inventors

• Williams Simon F
• Rizk Said
• Martin David P

Classifications

• A61L27/18 Primary

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

• A61F2/0045

  Support slings · CPC title

• A61F2/0063

  Implantable repair or support meshes, e.g. hernia meshes · CPC title

• A61F2/12

  Mammary prostheses · CPC title

• A61L17/06

  At least partially resorbable materials · CPC title