Medical devices comprising cross-linked hydrogels having improved mechanical properties

• US 6,184,266 B1
• Filed: 02/02/2000
• Issued: 02/06/2001
• Est. Priority Date: 07/11/1996
• Status: Expired due to Term

• Current Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Thompson, Samuel A., Ronan, John M.
• Primary Examiner(s): Szekely, Peter A.
• Application Number:
  US09/496,709
• Time in Patent Office: 370 Days
• Field of Search: 523/105, 523/113, 524/28, 524/503, 524/916, 525/903, 536/3, 424/78.17, 424/422, 604/264, 623/1
• US Class Current: 523/113
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61M 27/008 pre-shaped, for use in the urethral or ureteral tract
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P
• CPC Class Codes: C08B 37/0084 Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
• CPC Class Codes: C08J 2300/14 Water soluble or water swellable polymers, e.g. aqueous gels
• CPC Class Codes: C08J 3/243 Two or more independent types of crosslinking for one or more polymers
• CPC Class Codes: Y10S 524/916 Hydrogel compositions
• CPC Class Codes: Y10S 525/903 Interpenetrating network
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device

Abstract

Shaped medical devices, e.g. stents, having improved mechanical properties and structural integrity are disclosed. The devices comprise shaped polymeric hydrogels which are both ionically and non-ionically crosslinked and which exhibit improved structural integrity after selective removal of the crosslinking ions. Process for making such devices are also disclosed wherein an ionically crosslinkable polymer is both ionically and non-ionically crosslinked to form a shaped medical device. When implanted in the body, selective in-vivo stripping of the crosslinking ions produces a softer, more flexible implant having improved structural integrity.

Claims

1. A method for forming a shaped medical device, comprising the steps of:

(a) providing a crosslinkable polymer, crosslinking the crosslinkable polymer with at least one non-ionic crosslink, and shaping the crosslinked polymer to form a device having a primary shape; and

(b) deforming the device comprising the primary shape by providing ions and ionically crosslinking the device comprising the primary shape, producing a device having a secondary shape.

2. The method of claim 1, wherein the device having the secondary shape is implanted in the body of a mammal.

3. The method of claim 1 or 2, further comprising after step (b), the step (c) of removing the ions, thereby restoring the device having the secondary shape to its primary shape.

13. The method of claim 1, 4, or 9, wherein the crosslinkable polymer comprises a cationic polymer aid the ions are anions selected from the group consisting of phosphate, citrate, borate, succinate, maleate, adipate, and oxalate ions.

14. The method of claim 1 or 4, wherein the primary shape is the shape of a stent, catheter, plug, constrictor, or biological encapsulant.

16. The method of claim 1, 4, or 9, wherein the non-ionic crosslinks are covalent crosslinks.

17. The method of claim 1, 4, or 9, wherein the crosslinkable polymer comprises one or a mixture of polymers, selected from the group consisting of polyhydroxyethylmethacrylate, polyvinyl alcohol, polyacrylamide, poly (N-vinyl pyrolidone), polyethylene oxide, hydrolyzed polyacrylonitrile, polyacrylic acid, polymethacrylic acid, polyethylene amine, alginic acid, pectinic acid, carboxy methyl cellulose, hyalurcnic acid, heparin, heparin sulfate, chitosan, carboxymethyl chitosan, chitin, pullalan, gellan, xanthan, carboxymethyl starch, carboxymethyl dextran, chondroitin sulfate, cationic guar, cationic starch, and salts and esters thereof.

18. The method of claim 1, 4, or 9, wherein the crosslinkable polymer comprises one or a mixture of cationic polymers selected from the group consisting of chitosan, cationic guar, cationic starch, and polyethylene amine.

19. The method of claim 1, 4, or 9, wherein the crosslinking is performed by providing a crosslinking agent selected from the group consisting of carboxyl, hydroxy, epoxy, halogen, and amino functional groups.

20. The method of claim 1, 4, or 9, wherein the non-ionic crosslinks are formed by providing a crosslinking agent is selected from the group consisting of glutaraldehyde, epichlorohydrin, dianhydrides, and diamines.

21. The method of claim 20, wherein the crosslinking agent is glutaraldehyde.

22. The method of claim 17, wherein the crosslinkable polymer comprises alginic acid.

23. The method of claim 22, wherein said crosslinkable polymer comprises an ester of alginic acid and a C₂ to C₄ alkylene glycol.

24. The method of claim 23, wherein the alkylene glycol is propylene glycol.

25. The method of claim 17, wherein the crosslinkable polymer comprises a mixture of alginic or pectinic acid, and polyvinyl alcohol.

26. The method of claim 1, 4, or 9, wherein the shaped medical device is in the form of a cylindrical, hollow tube.

27. The method of claim 3 or 4, wherein the step of selective removing occurs prior to the step of forming non-ionic crosslinks.

28. The method of claim 3 or 4, wherein the step of selective removing occurs in the body.

29. The method of claim 3 or 4, wherein the step of selective removing is done by using a stripping agent.

30. The method of claim 29, wherein the stripping agent is selected from the group consisting of ethylenediaminetetracetic acid, ethylenediaminetetraacetate, organic phosphates, inorganic phosphates, sodium ions, potassium ions, lithium ions, calcium ions, and magnesium ions.

4. A method for forming a shaped medical device, comprising the steps of:

(a) providing a crosslinkable polymer;

(b) crosslinking the crosslinkable polymer to produce a crosslinked polymer having both ionic and non-ionic crosslinks;

(c) shaping the crosslinked polymer to form a device having a primary shape; and

(d) deforming the primary shape by selectively removing the ionic crosslinks to form a device having a secondary shape.

5. The method of claim 4, further comprising after step (d), the step of re-ionically crosslinking the device having the secondary shape.

6. The method of claim 4, wherein the device having the secondary shape is implanted in the body of a mammal.

7. The method of claim 6, further comprising the step of removing the crosslinking ions, thereby causing the device to revert to its primary shape.

8. The method of claim 4, wherein both the device having the primary shape and the device having the secondary shape comprise a hollow tube and wherein the lumen of the device having the primary shape is larger than the lumen of the device having the secondary shape.

9. A method of changing the shape of a shaped medical device in vivo in the body of a mammal, comprising the steps of:

(a) providing a shaped medical device having at least non-ionic crosslinks; and

(b) providing in vivo a source of ions in and around the device and ionically crosslinking the device.

10. The method of claim 9, wherein the shaped medical device comprises both ionic and non-ionic crosslinks.

11. The method of claim 9, further comprising the step (c) of removing the shaped medical device from the body of the mammal.

12. The method of claim 11, wherein step (b) is performed prior to step (c).

15. The method of claim 9, wherein the shaped medical device has the shape of a stent, catheter, plug, constrictor, or biological encapsulant.