Methods of making drug loaded microfiber sutures for ophthalmic application

• US 10,471,172 B2
• Filed: 12/12/2016
• Issued: 11/12/2019
• Est. Priority Date: 05/04/2012
• Status: Active Grant

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Kashiwabuchi, Fabiana Kimie, Hanes, Justin, Mao, Hai-Quan, McDonnell, Peter John, Xu, Qingguo, Zhang, Shuming, Parikh, Kunal S.
• Primary Examiner(s): Tentoni, Leo B
• Application Number:
  US15/375,472
• Publication Number:
  US 20170087271A1
• Time in Patent Office: 1,065 Days
• Field of Search: 264 10, 26421112, 264234, 264464, 264465, 264466, 264484
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: B29C 48/022 characterised by the choice of material
• CPC Class Codes: B29C 48/142 using force fields, e.g. gravity or electrical fields B29C48/9165 takes precedence
• CPC Class Codes: B29C 48/147 after the die nozzle
• CPC Class Codes: B29K 2067/046 PLA, i.e. polylactic acid or polylactide
• CPC Class Codes: B29K 2105/0035 Medical or pharmaceutical agents
• CPC Class Codes: B29K 2995/0056 Biocompatible, e.g. biopolymers or bioelastomers
• CPC Class Codes: B29K 2995/006 Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible
• CPC Class Codes: B29L 2031/7546 Surgical equipment
• CPC Class Codes: D01D 5/0007 Electro-spinning non-woven fabrics produced by electro-spinning D04H1/728
• CPC Class Codes: D01D 5/0038 the fibre formed by solvent evaporation, i.e. dry electro-spinning
• CPC Class Codes: D01D 5/0046 the fibre formed by coagulation, i.e. wet electro-spinning
• CPC Class Codes: D01D 5/0076 characterised by the collecting device, e.g. drum, wheel, endless belt, plate or grid D01D5/0046 takes precedence
• CPC Class Codes: D02G 3/448 Yarns or threads for use in medical applications D02G3/449 takes precedence; surgical suture materials A61L17/00

Abstract

Ophthalmic suture materials made from biocompatible and biodegradable polymers with high tensile strength for use in drug delivery, methods of making them, and method of using them for ocular surgery and repair have been developed. The suture materials are made from a combination of a biodegradable, biocompatible polymer and a hydrophilic biocompatible polymer. In a preferred embodiment the suture materials are made from a poly(hydroxyl acid) such as poly(1-lactic acid) and a polyalkylene oxide such as poly(ethylene glycol) or a polyalkylene oxide block copolymer. The sutures entrap (e.g., encapsulate) one or more therapeutic, prophylactic or diagnostic agents and provide prolonged release over a period of at least a week, preferably a month.

Claims

1. A method of making a suture between about 10 microns and about 100 microns in diameter and having a tensile strength between about 700 MPa and about 2.5 GPa comprising one or more fibers, comprising

extruding a jet onto a spinning device, wherein the jet comprises an electrically charged solution comprising a biodegradable, biocompatible hydrophobic polymer and a hydrophilic polymer, and optionally one or more therapeutic, diagnostic, or prophylactic agents in a solvent,

and drying the jet to form fibers,

wherein the amount of the hydrophilic polymer is between about 1 and about 10% by weight of the finished fiber.

2. The method of claim 1, wherein the spinning device contains another solvent capable of extracting the solvent of the jet upon contact.

3. The method of claim 1, wherein the spinning device has an angular velocity in the range between 20 to 40 rotations per minute or permits a travel distance between 20 and 40 centimeters per second.

4. The method of claim 1, wherein the jet is dried by evaporating the solvent in a vacuum chamber.

5. The method of claim 1, wherein the suture is in the form of a braided or multifiber suture.

6. The method of claim 1, wherein the suture has a diameter between about 20 μ

m and 90 μ

m.

7. The method of claim 1, wherein the suture has a diameter between 20 μ

m and 60 μ

m.

8. The method of claim 1, wherein the suture has a tensile strength between 1.3 GPa and 2.3 GPa.

9. The method of claim 1, wherein the biodegradable, biocompatible hydrophobic polymer comprises a biodegradable, biocompatible polymer selected from the group consisting of polyhydroxyacids, polyhydroxyalkanoates, polycaprolactones, polyanhydrides, polyesters, hydrophobic polyethers, and copolymers thereof.

10. The method of claim 1, wherein the hydrophilic polymer is selected from the group consisting of a poly(alkylene glycol), a polysaccharide, poly(vinyl alcohol), polypyrrolidone, a polyoxyethylene block copolymer, or a copolymers thereof.

11. The method of claim 10, wherein the amount of the hydrophilic polymer is between about 2% and about 5% by weight of the finished fibers.

12. The method of claim 1, wherein the solution comprises one or more therapeutic agents selected from the group consisting of anti-glaucoma agents, anti-angiogenesis agents, anti-infective agents, anti-inflammatory agents, growth factors, immunosuppressant agents, anti-allergic agents, and combinations thereof.

13. The method of claim 12, wherein the anti-infective agent is levofloxacin.

14. The method of claim 1, wherein the solution comprises one or more therapeutic, diagnostic, or prophylactic agents providing sustained release over at least seven days after placement.

15. The method of claim 9, wherein the amount of the biodegradable, biocompatible polymer is between about 75% and about 85% by weight of the finished fibers.

16. The method of claim 1, wherein the amount of the therapeutic, prophylactic, or diagnostic agent is between about 0.1% and about 50% by weight of the finished fibers.