EMBOLIZATION DEVICE CONSTRUCTED FROM EXPANSILE POLYMER

• US 20070299464A1
• Filed: 06/15/2007
• Published: 12/27/2007
• Est. Priority Date: 06/15/2006
• Status: Active Grant

• Current Assignee: Microvention Incorporated (Terumo Corporation)
• Original Assignee: Microvention Incorporated (Terumo Corporation)
• Inventors: Constant, Michael, Tran, Terrance, Cruise, Gregory
• Granted Patent: US 8,377,091 B2
• Time in Patent Office: Days
• US Class Current: 606/192
• CPC Class Codes: A61B 17/12113 within an aneurysm
• CPC Class Codes: A61B 17/1214 Coils or wires
• CPC Class Codes: A61B 17/12145 having a pre-set deployed three-dimensional shape methods of manufacturing A61B2017/00526
• CPC Class Codes: A61B 17/12154 having stretch limiting means
• CPC Class Codes: A61B 17/12168 having a mesh structure A61B17/1214 takes precedence
• CPC Class Codes: A61B 17/1219 expandable in contact with liquids
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 31/00 Materials for other surgical articles , e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices shape or structure of stent-grafts A61F2/07, of stents A61F2/82, of surgical gloves A61B42/00, of surgical drapes A61B46/00, of occluding devices A61B17/12022
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• 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: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Devices for the occlusion of body cavities, such as the embolization of vascular aneurysms and the like, and methods for making and using such devices. The devices may be comprised of novel expansile materials, novel infrastructure design, or both. The devices provided are very flexible and enable deployment with reduced or no damage to bodily tissues, conduits, cavities, etceteras.

Claims

1. A device for implantation in an animal comprising:

a hydrogel having ionizable functional groups wherein said hydrogel comprises at least one macromer, further wherein said hydrogel is environmentally-responsive, and further wherein said hydrogel has an unexpanded bending resistance of about 0.1 mg to about 85 mg.

2. A device according to claim 1 wherein said macromer has a molecular weight of about 400 grams/mole to about 35,000 grams/mole.

3. A device according to claim 1 wherein said hydrogel comprises polyethers, polyurethanes, derivatives thereof, or combinations thereof.

4. A device according to claim 1 wherein said with ionizable functional groups comprise basic groups.

5. A device according to claim 4 wherein said basic groups comprise an amine, derivatives thereof, or combinations thereof.

6. A device according to claims 5 wherein said basic functional groups can be deprotonated at pHs greater than the pKa or protonated at pHs less than the pKa of said functional groups.

7. A device according to claim 1 wherein said with ionizable functional groups comprise acidic groups.

8. A device according to claim 7 wherein said acidic groups comprise a carboxylic acid, derivatives thereof, or combinations thereof.

9. A device according to claim 8 wherein said acidic functional groups can be protonated at pHs less than the pKa or de-protonated at pHs greater than the pKa of said functional groups.

10. A device according to claim 1 wherein said hydrogel comprises vinyl, acrylates, acrylamides, methacrylates, derivatives thereof, or combinations thereof.

11. A device according to claim 1 wherein said macromer comprises poly(ethylene glycol), derivatives thereof, or combinations thereof.

12. A device according to claim 1 wherein said macromer comprises poly(ethylene glycol) di-acrylamide, poly(ethylene glycol) di-acrylate, poly(ethylene glycol) dimethacrylate, derivatives thereof, or combinations thereof.

13. A device according to claim 12 wherein said macromer comprises poly(ethylene glycol) di-acrylamide.

14. A device according to claim 1 wherein said hydrogel is substantially free of acrylamide.

15. A device according to claim 1 wherein said macromer is cross-linked with at least one ethylenically unsaturated compound.

16. A device according to claim 1 wherein said macromer is cross-linked with N,N′

-methylenebisacrylamide, derivatives thereof, or combinations thereof.

17. A device according to claim 1 wherein said hydrogel is polymerized using a polymerization initiator selected from N,N,N′

,N′

-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2′

-azobis(2-methylpropionamidine) dihydrochloride, derivatives thereof, or combinations thereof.

18. A device according to claim 1 wherein said hydrogel is substantially non-resorbable.

19. A method for preparing an environmentally-responsive hydrogel for implantation in an animal comprising:

a) combining at least one ethylenically unsaturated macromer, at least one macromer or monomer comprising at least one ionizable functional group, at least one polymerization initiator, and at least one solvent to prepare a hydrogel;

b) treating said hydrogel to prepare an environmentally-responsive hydrogel that is responsive at physiological conditions.

20. A method according to claim 19 wherein said at least one ionizable functional group comprises an acidic group.

21. A method according to claim 20 wherein said treating comprises incubating said hydrogel in an acidic environment to protonate said acidic groups.

22. A method according to claim 20 wherein said acidic group comprises a carboxylic acid, a derivative thereof, or combinations thereof.

23. A method according to claim 19 wherein said at least one ionizable functional group comprises a basic group.

24. A method according to claim 23 wherein said treating comprises incubating said hydrogel in a basic environment to de-protonate said basic group.

25. A method according to claim 24 wherein said basic group comprise an amine, derivatives thereof, or combinations thereof.

26. A method according to claim 19 wherein said solvent comprises water, ethyl alcohol, or combinations thereof.

27. A method according to claim 26 wherein said solvent comprises water.

28. A method according to claim 19 wherein said at least one macromer or monomer comprising at least one ionizable functional group comprises a vinyl group, an acrylate, a methacrylate, an acrylamide, derivatives thereof, or combinations thereof.

29. A method according to claim 19 wherein said at least one ethylenically unsaturated macromer comprises poly(ethylene glycol), derivatives thereof, or combinations thereof.

30. A method according to claim 19 wherein said at least one ethylenically unsaturated macromer comprises poly(ethylene glycol) di-acrylamide, poly(ethylene glycol) di-acrylate, derivatives thereof, or combinations thereof.

31. A method according to claim 30 wherein said at least one ethylenically unsaturated macromer comprises poly(ethylene glycol) di-acrylamide.

32. A method according to claim 19 wherein said ethylenically unsaturated macromer is at a concentration of about 5% to about 40% by weight.

33. A method according to claim 19 wherein said solvent is at a concentration of about 20% to about 80% by weight.

34. A method according to claim 19 wherein said combining further comprises adding at least one cross-linking agent comprising a compound with a plurality of ethylenically unsaturated moieties.

35. A method according to claim 19 wherein said polymerization initiator comprises a reduction-oxidation polymerization initiator.

36. A method according to claim 19 wherein said polymerization initiator comprises N,N,N′

,N′

-tetramethylethylenediamine, ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides, 2,2′

-azobis(2-methylpropionaminide) dihydrochloride, derivatives thereof, or combinations thereof.

37. A method according to claim 19 wherein said combining further comprises adding a porosigen.

38. A method according to claim 21 wherein said acidic groups are capable of being de-protonated after implantation in an animal.

39. A method according to claim 24 wherein said basic groups are capable of being protonated after implantation in an animal.

40. A method according to claim 19 wherein said ethylenically unsaturated macromer comprises poly(ethylene glycol) di-acrylamide, said at least one macromer or monomer comprising at least one ionizable functional group comprises sodium acrylate, said at least one polymerization initiator comprises ammonium persulfate and N,N,N,′

,N′

tetramethylethylenediamine, and said solvent comprises water.

41. A method according to claim 19 wherein said ethylenically unsaturated macromer has a molecular weight of about 400 grams/mole to about 35,000 grams/mole.

42. A method according to claim 19 wherein said environmentally-responsive hydrogel is substantially non-resorbable.

43. A method according to claim 19 wherein said environmentally-responsive hydrogel is substantially free of acrylamide.

44. A method according to claim 19 wherein said at least one ethylenically unsaturated macromer is non-ionic.

45. A method according to claim 19 wherein said environmentally-responsive hydrogel has an unexpanded bending resistance of from about 0.1 mg to about 85 mg.