Hydrogel Implants with Varying Degrees of Crosslinking

• US 20120049689A1
• Filed: 08/31/2011
• Published: 03/01/2012
• Est. Priority Date: 05/27/2010
• Status: Active Grant

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Covidien LP (Medtronic Plc)
• Inventors: Bennett, Steven, Mast, Nathaniel, Lavigne, Kevin, Skalla, Walter, Sargeant, Timothy, Stopek, Joshua, Banerjee, Saumya, Desai, Arpan
• Granted Patent: US 8,754,564 B2
• Time in Patent Office: Days
• US Class Current: 310/216.092
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08J 2371/02 Polyalkylene oxides
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08J 3/246 Intercrosslinking of at least two polymers

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 method of in situ hydrogel formation in a body lumen comprising:

introducing a first reactive precursor comprising electrophilic groups, a second reactive precursor comprising nucleophilic groups, and an initiated precursor comprising at least one vinyl group into a body lumen;

permitting the first reactive precursor and the second reactive precursor to react to form a first hydrogel capable of adhering to the lumen; and

exposing the initiated precursor to an initiator to form a second crosslinked hydrogel,

wherein the first hydrogel and the second hydrogel form a composite hydrogel composition.

2. The method of claim 1, wherein the first reactive precursor, the second reactive precursor, or both, comprise 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.

3. The method of claim 1, wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.

4. The method 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.

5. The method of claim 1, wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.

6. The method of claim 5, wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.

7. The method of claim 1, wherein the first hydrogel, the second hydrogel, or both, further comprises a bioactive agent.

8. The method of claim 1, wherein the body lumen comprises a region between an animal'"'"'s stomach and small intestine.

9. The method of claim 8, wherein the first reactive precursor, the second reactive precursor, and the initiated precursor are introduced into the lumen by way of an endoscopic device.

10. The method of claim 9, wherein the initiator is introduced into the lumen by the endoscopic device.

11. The method of claim 8, wherein the composite hydrogel forms a gastric sleeve.

12. The method of claim 1, wherein the body lumen comprises a blood vessel.

13. The method of claim 12, wherein the first reactive precursor, the second reactive precursor, and the initiated precursor are introduced into the lumen on the surface of a balloon.

14. The method of claim 13, wherein the balloon comprises a UV transparent material, and wherein the initiator comprises UV light.

15. The method of claim 12, wherein the composite hydrogel forms a stent.

16. The method of claim 1, wherein the hydrogel is selectively exposed to the initiator to initiate selective crosslinking of the initiated precursor.

17. The method of claim 16, wherein the hydrogel is selectively exposed to the initiator by means of a mask which only permits discrete areas of the hydrogel to be exposed to the initiator.

18. A kit comprising:

a first reactive precursor comprising electrophilic groups, a second reactive precursor comprising nucleophilic groups, and an initiated precursor comprising at least one vinyl group;

an initiator to initiate crosslinking of the initiated precursor; and

a device for introducing the first reactive precursor, the second reactive precursor, the initiated precursor, and the initiator to a body lumen.

19. The kit of claim 18, further comprising an initiator mask to selectively expose the initiated precursor to the initiator.

20. The kit of claim 18, wherein the first reactive precursor, the second reactive precursor, or both, comprise 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.

21. The kit of claim 18, wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.

22. The kit of claim 18, 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.

23. The kit of claim 18, wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.

24. The kit of claim 23, wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.

25. The kit of claim 18, wherein the device comprises an endoscope.

26. The kit of claim 18, wherein the device comprises a balloon catheter.