Medical devices comprising ionically and non-ionically crosslinked polymer hydrogels having improved mechanical properties

• US 6,060,534 A
• Filed: 07/11/1996
• Issued: 05/09/2000
• 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: Thompson, Samuel A., Ronan, John M.
• Primary Examiner(s): MERRIAM, ANDREW EDWIN
• Application Number:
  US08/679,609
• Time in Patent Office: 1,398 Days
• Field of Search: 523/113, 523/105, 524/28, 524/916, 424/422, 424/78.17, 536/3, 623/1, 604/264, 525/903
• 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:

exposing a polymer composition to crosslinking conditions such that both ionic and non-ionic crosslinks are formed, thereby forming a crosslinked hydrogel;

shaping the crosslinked hydrogel to form a shaped, crosslinked hydrogel; and

selectively removing one or more ionic crosslinks from the shaped, crosslinked hydrogel.

2. The method of claim 1, wherein the step of exposing to crosslinking conditions includes providing a crosslinking agent comprising a source of ions.

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

4. The method of claim 1, wherein the shaped medical device is selected from the group consisting of stents, catheters, cannulas, plugs, constrictors, and biological encapsulants.

5. The method of claim 1, wherein non-ionic crosslinks are formed prior to forming ionic crosslinks.

6. The method of claim 1, wherein ionic crosslinks are formed prior to forming non-ionic crosslinks.

7. The method of claim 1, wherein the non-ionic crosslinks are covalent crosslinks.

8. The method of claim 1, wherein the polymer comprises one or a mixture of polymers, selected from the group consisting of polyhydroxyethylmethacrylate, polyvinyl alcohol, polyacrylamide, poly(N-vinylpyrolidone), polyethylene oxide, hydrolyzed polyacrylonitrile, polyacrylic acid, polymethacrylic acid, polyethylene amine, alginic acid, pectinic acid, carboxy methyl cellulose, hyaluronic 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.

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

10. The method of claim 1, wherein the crosslinking conditions comprise providing a crosslinking agent selected from the group consisting of carboxyl, hydroxy, epoxy, halogen, and amino functional groups.

11. The method of claim 1, wherein the crosslinking agent is selected from the group consisting of glutaraldehyde, epichlorohydrin, dianhydrides, and diamines.

12. The method of claim 11, wherein the crosslinking agent is glutaraldehyde.

13. The method of claim 8, wherein the polymer comprises alginic acid.

14. The method of claim 13, wherein the alginic acid comprises an ester of a C₂ to C₄ alkylene glycol.

15. The method of claim 14, wherein the alkylene glycol is propylene glycol.

16. The method of claim 8, wherein the polymer comprises a mixture of alginic or pectinic acid and polyvinylalcohol.

17. The method of claim 1, wherein the shaped medical device is in the form of a cylindrical, hollow tube.

18. The method of claim 5, wherein the step of selective removing occurs prior to the step of forming non-ionic crosslinks.

19. The method of claim 1, wherein the step of shaping occurs after ionic crosslinks are formed but before the non-ionic crosslinks are formed.

20. The method of claim 1, wherein the step of shaping occurs after the non-ionic crosslinks are formed but before the ionic crosslinks are formed.

21. The method of claim 1, wherein the step of shaping occurs after both ionic and non-ionic crosslinks are formed.

22. The method of claim 1, wherein the step of selective removing occurs in the body.

23. The method of claim 1, wherein the step of selective removing is done by using a stripping agent.

24. The method of claim 23, 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.