HYDROGEL IMPLANTS WITH VARYING DEGREES OF CROSSLINKING

• US 20110293688A1
• Filed: 05/24/2011
• Published: 12/01/2011
• Est. Priority Date: 05/27/2010
• Status: Active Grant

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Covidien LP (Medtronic Plc)
• Inventors: Lavigne, Kevin, Bennett, Steven, Mast, Nathaniel, Skalla, Walter
• Granted Patent: US 8,734,824 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 26/0014 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The present disclosure relates to a hydrogel composition and methods of using the same. The hydrogel composition may include precursors that react with each other upon contact as well as precursors that react upon contact with an initiator. In embodiments, the resulting hydrogels may have varying levels of crosslinking with both denser and less dense regions.

Claims

1. A mesh implant comprising:

a filamentous substrate; and

a film coating on at least a portion of the filamentous substrate, the film coating comprising a freeze-dried composition comprising an initiated precursor comprising at least one vinyl group, in combination with a first hydrogel comprising a first reactive precursor comprising a multi-arm polyether possessing electrophilic groups, and a second reactive precursor comprising nucleophilic groups,

wherein the first hydrogel can be re-hydrated to releasably attach the mesh to tissue, and the initiated precursor can be exposed to an initiator to form a second hydrogel securely affixing the mesh to tissue.

2. The mesh implant of claim 1, wherein the first hydrogel is rehydrated upon contact with a fluid selected from the group consisting of saline, body fluids, and combinations thereof.

3. The mesh implant of claim 1, wherein the first reactive precursor, comprises a core selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, and combinations thereof, and wherein the second reactive precursor comprises a core comprising a component selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, polyvinyl alcohol, poly(vinyl pyrrolidinone), poly(amino acids), dextran, chitosan, alginates, carboxymethylcellulose, oxidized cellulose, hydroxyethylcellulose, hydroxymethylcellulose, hyaluronic acid, albumin, collagen, casein, gelatin, and combinations thereof.

4. The mesh implant of claim 1, wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.

5. The mesh implant of claim 1, wherein the initiated precursor is selected from the group consisting of acrylic acid, methacrylic acid, phosphorylcholine containing monomers, furanone functional vinyl monomers, potassium sulfopropyl acrylate, potassium sulfopropyl methacrylate, n-vinyl pyrrolidone, hydroxyethyl methacrylate, vinyl monomers having a high refractive index, siloxane functional vinyl compounds, polyethylene glycol-silicone co-monomers having vinyl groups, tris acrylate, pyrrole, liquid crystalline vinyl monomers, liquid crystalline vinyl polymers, and combinations thereof.

6. The mesh implant of claim 1, further comprising an initiator selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.

7. The mesh implant of claim 6, wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.

8. The mesh implant of claim 1, further comprising a bioactive agent.

9. The mesh implant of claim 1, wherein the first hydrogel has a modulus of from about 10 kPa to about 50 kPa, and the second hydrogel has a modulus of from about 60 kPa to about 200 kPa.

10. A method of attaching mesh to tissue comprising:

contacting a mesh comprising an initiated precursor comprising at least one vinyl group with a first reactive precursor comprising a multi-arm polyether possessing electrophilic groups, and a second reactive precursor comprising nucleophilic groups;

contacting the mesh to tissue;

allowing the first reactive precursor and the second reactive precursor to react to form a first hydrogel; and

contacting the initiated precursor with an initiator to form a second hydrogel, wherein the second hydrogel secures the mesh to the tissue.

11. The method of claim 10, wherein the first reactive precursor comprises a core selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, and combinations thereof, and wherein the second reactive precursor comprises a core comprising a component selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, polyvinyl alcohol, poly(vinyl pyrrolidinone), poly(amino acids), dextran, chitosan, alginates, carboxymethylcellulose, oxidized cellulose, hydroxyethylcellulose, hydroxymethylcellulose, hyaluronic acid, albumin, collagen, casein, gelatin, and combinations thereof.

12. The method of claim 10, wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.

13. The method of claim 10, wherein the initiated precursor is selected from the group consisting of acrylic acid, methacrylic acid, phosphorylcholine containing monomers, furanone functional vinyl monomers, potassium sulfopropyl acrylate, potassium sulfopropyl methacrylate, n-vinyl pyrrolidone, hydroxyethyl methacrylate, vinyl monomers having a high refractive index, siloxane functional vinyl compounds, polyethylene glycol-silicone co-monomers having vinyl groups, tris acrylate, pyrrole, liquid crystalline vinyl monomers, liquid crystalline vinyl polymers, and combinations thereof.

14. The method of claim 10, wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.

15. The method of claim 14, wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.

16. The method of claim 10, wherein the first hydrogel, the second hydrogel, or both, further comprises a bioactive agent.

17. The method of claim 10, further comprising allowing the first hydrogel to form prior to allowing the second hydrogel to form.

18. The method of claim 10, wherein the first hydrogel and the second hydrogel form an interpenetrating network.

19. The method of claim 10, wherein the first hydrogel has a modulus of from about 5 kPa to about 20 kPa, and the second hydrogel has a modulus of from about 50 kPa to about 500 kPa.

20. The method of claim 10, wherein the first hydrogel degrades over a period of from about 1 day to about 7 days, and the second hydrogel degrades over a period of at least about 6 months.

21. The method of claim 20, wherein the first hydrogel degrades more quickly than the second hydrogel, thereby forming spaces permitting tissue in-growth, vascularization, and combinations thereof.

22. The method of claim 10, wherein the first hydrogel is formed prior to initiating the initiated precursor to form the second hydrogel.

23. The method of claim 10, wherein the second hydrogel is formed prior to forming the first hydrogel.

24. The method of claim 10, wherein the first reactive precursor is present in the first hydrogel in an amount from about 10% to about 30% and the second reactive precursor is present in the first hydrogel in an amount from about 70% to about 90%.

25. The method of claim 10, wherein the first reactive precursor is present in the first hydrogel in an amount from about 70% to about 90% and the second reactive precursor is present in the first hydrogel in an amount from about 10% to about 30%.

26. The method of claim 10, wherein the first hydrogel permits adherence and re-adherence of the mesh to the tissue surface for at least 10 minutes before the second hydrogel is formed.