Medical devices comprising hydrogel polymers having improved mechanical properties

• US 6,368,356 B1
• Filed: 02/25/2000
• Issued: 04/09/2002
• Est. Priority Date: 07/11/1996
• Status: Expired due to Term

• Current Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Madenjian, Arthur R., Ronan, John M., Godshall, Douglas E., Thompson, Samuel A., Zhong, Sheng Ping
• Primary Examiner(s): SZEKELY, PETER A
• Application Number:
  US09/512,698
• Time in Patent Office: 774 Days
• Field of Search: 523/113, 523/105, 524/503, 524/916, 524/28, 524/47, 524/43, 524/44, 524/45, 525/903, 424/78.17, 424/422, 604/264, 623/1.49, 623/23.75, 623/925, 623/926, 623/1.18, 623/1.19
• US Class Current: 623/23.75
• 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 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque
• 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 524/918 Wood patching composition
• CPC Class Codes: Y10S 525/903 Interpenetrating network
• CPC Class Codes: Y10S 623/925 Natural
• CPC Class Codes: Y10S 623/926 Synthetic

Abstract

The invention provides a means of boosting the mechanical performance of shaped shaped medical devices comprising polymer hydrogels, such as stents, so that they may be more easily inserted into or removed from the body. In one aspect, the invention provides shaped medical devices having increased mechanical strength and comprising both ionic and covalent crosslinks. In another aspect, the invention provides a shaped medical device having a heterogeneous polymer composition and a variable dissolution or degradation rate along its length. The shaped medical devices according to the present invention retain their shape and stiffness during insertion into the body and can swell and soften inside the body to enhance patient comfort.

Claims

1. A medical device that does not require a surgical procedure for removal comprising a crosslinkable polymer having ionic crosslinks susceptible to dissolution in vivo, the medical device comprising at least two segments that degrade in vivo at different rates.

2. The medical device of claim 1, wherein the polymer is derived from a polymer precursor selected from the group consisting of hyaluronic acid, heparin, chondroitin sulfate, pectinic acid, a carboxyl-derivatized polysaccharide, a synthetic polymer, and combinations thereof.

3. The medical device of claim 1, wherein the polymer is derived from a polymer precursor selected from the group consisting of polyhydroxy ethyl methacrylate, polyvinyl alcohol, polyacrylamide, poly (N-vinyl pyrrolidone), polyethylene oxide, hydrolyzed polyacrylonitrile, polyacrylic acid, polymethacrylic acid, polyethylene amine, a polysaccharide, and combinations thereof.

4. The medical device of claim 3, wherein the polysaccharide is selected from the group consisting of alginic acid, pectinic acid, carboxymethyl cellulose, hyaluronic acid, chitosan, cationic guar, and cationic starch, including salts, and esters, and combinations thereof.

5. The medical device of claim 1, wherein the device comprises a crosslinkable polymer having non-ionic crosslinks susceptible to hydrolysis in vivo.

6. The medical device of claim 5, wherein the non-ionic crosslinks are reversible covalent crosslinks.

7. The medical device of claim 5, wherein the polymer is crosslinked by a polyfunctional covalent crosslinking agent.

8. The medical device of claim 5, wherein the polymer is crosslinked by a covalent crosslinking agent which is a polyfunctional carbodiimide.

9. The medical device of claim 5, wherein the polymer is crosslinked by a covalent crosslinking agent which is a polyfunctional aziridine crosslinking agent.

10. The medical device of claim 5, wherein the polymer is crosslinked by a covalent crosslinking agent which is a polyisocyanate crosslinking agent.

11. The medical device of claim 5, wherein the polymer is crosslinked by a covalent crosslinking agent which is a glutaraldehyde crosslinking agent.

12. The medical device of claim 1, wherein the device includes a first segment and a second segment each having ionic crosslinks susceptible to dissolution in vivo such that the first segment and the second segment degrade in vivo at different rates.

13. The medical device of claim 12, wherein the first segment has a higher ionic crosslinking content than the second segment.

14. The medical device of claim 12, wherein the first segment has a thinner wall than the second segment.

15. The medical device of claim 12, wherein the first segment comprises a polymer crosslinked with a first ion and the second segment comprises a polymer crosslinked with a second ion.

19. The medical device of claim 12, wherein the first segment and the second segment comprise one or more polymers crosslinked with a high affinity ion and a low affinity ion, and the first segment has a higher concentration of high affinity ion crosslinks and a lower concentration of low affinity ion crosslinks than the second segment.

20. The medical device of claim 1, wherein the device includes a first segment comprising a crosslinkable polymer having ionic crosslinks susceptible to dissolution in vivo and a second segment comprising a crosslinkable polymer having non-ionic crosslinks susceptible to hydrolysis in vivo.

21. The medical device of claim 20, wherein the device includes break point in a relatively straight section of the device proximal to a curved section of the device.

22. The medical device of claim 1, further comprising a segment comprising a non-dissolvable, non-disintegrable polymer.

23. The medical device of claim 22 wherein the non-dissolvable, non-disintegrable polymer is silicone.

24. The medical device of claim 22, wherein the segment comprising the non-dissolvable, non-disintegrable polymer is selected from the group consisting of a string, a mesh, a suture, and a braid.

25. The medical device of claim 1, further comprising a segment comprising a biodegradable polymer.

26. The medical device of claim 25, wherein the biodegradable polymer is selected from the group consisting of the polymers of glycolic acid, ε

-caprolactone, lactic acid and copolymers thereof.

27. The medical device of claim 25, wherein the segment comprising the biogradable polymer is selected from the group consisting of a string, a mesh, a suture, and a braid.

28. The medical device of claim 1, wherein the device is selected from the group consisting of a stent, a catheter, a cannula, a plug, a constrictor, a bone anchor, a plate, a rod, a seed, a capsule, a sheet, and a tube.

29. The medical device of claim 1, wherein the device is a biliary, urinary, or vascular stent.

30. The medical device of claim 1, further comprising at least one pigtail end.

31. The medical device of claim 1, wherein the device is a tissue prosthesis.

32. The medical device of claim 1, further comprising suture material as a filler.

33. The medical device of claim 1, wherein the device is seeded with cells.

34. The medical device of claim 1, further comprising a radiopaque filler.

35. The medical device of claim 34, wherein the radiopaque filler is selected from the group consisting of bismuth sub-carbonate, barium sulfate, bismuth oxychloride, tungsten, bismuth trioxide, tantalum, and combinations thereof.

36. The medical device of claim 1, further comprising an additive for medical treatment selected from the group consisting of an antiseptic, an antibiotic, an anticoagulant, a contraceptive, a nucleic acid, a protein, and a medicine.

37. The medical device of claim 36, wherein the nucleic acid is selected from the group consisting of a gene, a cDNA, a vector, an RNA molecule, an antisense molecule, a ribozyme, and a PNA molecule.

38. The medical device of claim 36, wherein the additive for medical treatment is added to only a portion of the medical device.

16. The medical device of 15, wherein the first ion has a higher electron affinity than the second ion.

17. The medical device of 16, wherein the second ion is selected from the group consisting of Mg²⁺⁺ and Ca²⁺⁺.

18. The medical device of 17, wherein the first ion is selected from the group consisting of Ba²⁺⁺ and Zn²⁺⁺.