ANEURYSM OCCLUSION DEVICE CONTAINING BIOACTIVE AND BIOCOMPATIBLE COPOLYMER SHELL AND BIOCOMPATIBLE METALLIC FRAME MEMBER

• US 20090062834A1
• Filed: 04/25/2008
• Published: 03/05/2009
• Est. Priority Date: 04/27/2007
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Xu, Fangmin, Masters, Kristyn S., Moftakhar, Roham, Crone, Wendy C.
• Granted Patent: US 8,425,542 B2
• Time in Patent Office: Days
• US Class Current: 606/191
• CPC Class Codes: A61K 31/75 of ethene
• 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: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 33/0035 using a polymer with positively charged atoms in the polymeric backbone, e.g. ionenes
• CPC Class Codes: C08B 37/0063 Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
• CPC Class Codes: C08B 37/0069 Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08B 37/0075 Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: C08G 18/3206 aliphatic
• CPC Class Codes: C08G 18/4854 Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
• CPC Class Codes: C08G 18/64 Macromolecular compounds not provided for by groups C08G18/42 - C08G18/63
• CPC Class Codes: C08G 18/6484 Polysaccharides and derivatives thereof
• CPC Class Codes: C08G 18/7657 containing two or more aromatic rings
• CPC Class Codes: C08G 18/7671 containing only one alkylene bisphenyl group
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

An endovascular device for occluding a vascular aneurysm is disclosed. The device includes a polymeric shell member that, in one embodiment, may be constructed from a bioactive and biocompatible polyurethane-diol-glycosaminoglycan copolymer, and a biocompatible metallic frame member. The copolymer is sufficiently flexible and strong for endovascular delivery into a vascular aneurysm and for use as a polymeric shell for receiving the biocompatible metallic frame member. The biometallic frame member may include one or more components constructed from a NiTi alloy.

Claims

1. An endovascular medical device comprising:

a polymeric member defining an interior chamber; and

a biocompatible metallic frame member comprising one or more components constructed from a NiTi alloy having a transformation temperature below a patient'"'"'s body temperature, disposed within the interior chamber, and adapted to structurally support the polymeric member.

2. The medical device of claim 1, wherein the polymeric member is constructed from a copolymer comprising the reaction product of a biocompatible urethane and a bioactive polysaccharide.

3. The medical device claim of claim 1, wherein the polymeric member is constructed of a material selected from the group consisting of polyester materials, silicone-based materials and derivatives thereof, polyethylene materials, polytetrafluoroethylene, biocompatible urethanes and derivatives thereof, and combinations thereof.

4. The medical device of claim 2, wherein the bioactive polysaccharide is a bioactive glycosaminoglycan.

5. The medical device of claim 4, wherein the bioactive glycosaminoglycan is a member selected from the group consisting of a suitable salt of hyaluronic acid and a suitable salt of heparin.

6. The medical device of claim 5, wherein the salt of hyaluronic acid is a member selected from the group consisting of a cetylpyridinium salt and a tetrabutylammonium salt, and wherein the salt of heparin is a dimethyldioctadecylammonium salt.

7. The medical device of claims 6, wherein the salt of hyaluronic acid has 5 to 10,000 repeating units, and wherein the dimethyldioctadecylammonium salt of heparin has 5 to 65 repeating units.

8. The medical device of claim 2, wherein the weight content of the bioactive polysaccharide is in the range of about 0.05% to about 30%.

9. The medical device of claim 8, wherein the high and low range endpoints of the weight content of the bioactive polysaccharide are any combination of members selected from the group consisting of 0.05%, 0.1%, 0.33%, 0.66%, 1.3%, 2.0%, 5.4%, 10% and 30%.

10. The medical device of claim 9, comprising the cetylpyridinium salt of hyaluronic acid.

11. The medical device of claim 2, wherein the biocompatible urethane is the reaction product of 4,4′

-methylene-di-(p-phenyl isocyanate) and poly(tetramethylene oxide), and further reacted with 1,4-butanediol, and wherein n=10 to 40.

12. The medical device of claim 2, wherein the biocompatible urethane is the reaction product of 4,4′

-methylene-di-(p-phenyl isocyanate) and poly(tetramethylene oxide), and further reacted with 1,4-butanediol, and wherein n=10 to 40.

13. The medical device of claim 2, wherein the biocompatible urethane is the reaction product of a suitable isocyanate-containing molecule and a suitable poly(C_2-10 alkylene oxide), and further reacted with a suitable C_4-50 diol-containing molecule, wherein n=10 to 40, wherein the C_2-10 alkylene is linear or branched, substituted or un-substituted, and wherein the C_4-50 is linear or branched, substituted or un-substituted.

14. The medical device of claim 1, wherein the polymeric member has a wall thickness in the range of 0.05 to 0.4 mm.

15. The medical device of claim 14, wherein the polymeric member is adapted to substantially conform to a vascular aneurysm.

16. The medical device of claim 1, wherein the NiTi alloy comprises in the range of about 49 to about 51 wt. % Ni and in the range of about 51 to about 49 wt. % Ti.

17. The medical device of claim 16, wherein the metallic frame member comprises a single component.

18. The medical device of claim 16, wherein the metallic frame member is in the shape of a coil.

23. The method of claim 17, wherein the glycosaminoglycan is a member selected from the group consisting of a cetylpyridinium salt of hyaluronic acid having 5 to 10,000 repeating units, a tetrabutylammonium salt of hyaluronic acid having 5 to 10,000 repeating units and a dimethyldioctadecylammonium salt of heparin having 5 to 65 repeating units.

24. The method of claim 23, wherein the weight content of the glycosaminoglycan is in the range of about 0.05% to about 30%.

25. The method of claim 24, wherein the high and low range endpoints of the weight content of the bioactive polysaccharide are any combination of members selected from the group consisting of 0.05%, 0.1%, 0.33%, 0.66%, 1.3%, 2.0%, 5.4%, 10% and 30%.

26. The method of claim 17, further comprising:

substantially conforming the polymeric member to the vascular aneurysm, and,

contacting a substantial portion of the metallic frame member with the polymeric member.

19. An endovascular method of occluding a vascular aneurysm comprising:

endovascularly disposing into a vascular aneurysm an elastic hemocompatible polymeric member defining an interior chamber, and,

endovascularly disposing a biocompatible metallic frame member within the interior chamber.

20. The method of claim 19, wherein the metallic frame member comprises one or more components constructed from a biocompatible NiTi alloy having a transformation temperature below a patient'"'"'s body temperature, and wherein the polymeric member is constructed from a copolymer comprising the reaction product of a biocompatible urethane and a bioactive glycosaminoglycan, comprising:

endovascularly threading the NiTi component through a catheter,

threading the NiTi component into the interior chamber, and,

deforming the NiTi component within the interior chamber by heating the component above the transformation temperature,

whereby the component adopts a predetermined form and shape, and,

whereby the component takes the form of the frame adapted to structurally support the polymeric member.

21. The method of claim 19, wherein the biocompatible urethane is the reaction product of 4,4′

-methylene-di-(p-phenyl isocyanate) and poly(tetramethylene oxide), and further reacted with 1,4-butanediol, wherein n=10 to 40.

22. The method of claim 19, wherein the biocompatible urethane is the reaction product of a suitable isocyanate-containing molecule and a suitable poly(C_2-10 alkylene oxide), and further reacted with a suitable C_4-50 diol-containing molecule, wherein n=10 to 40, wherein the C_2-10 alkylene is linear or branched, substituted or un-substituted, and wherein the C_4-50 is linear or branched, substituted or un-substituted.

27. An endovascular medical device comprising:

a polymeric member defining an interior chamber and constructed from an elastic, hemocompatible polymer, and,

a biocompatible metallic frame member comprising one or more components constructed from a NiTi alloy having a transformation temperature below a patient'"'"'s body temperature, disposed within the interior chamber, and adapted to structurally support the polymeric member.

28. The medical device of claim 27, wherein the hemocompatible polymer is a member selected from the group consisting of poly(ethylene glycol), poly(vinyl alcohol), polytetrafluoroethylene, polyethylene terephthalate, poly(hydroxyethyl methacrylate), poly(hydroxyethyl acrylate), a copolymer thereof and a anti-thrombotic modified derivative thereof.

29. The medical device of claim 28, wherein the copolymer is a member selected from the group consisting of poly(ethylene glycol) diacrylate, poly(ethylene glycol) dimethacrylate and acrylated poly(vinyl alcohol).

30. The medical device of claim 28, wherein the anti-thrombotic modified derivative includes the hemocompatible polymer modified by an anti-thrombotic agent selected from the group consisting of heparin, chitosan and a nitric oxide donor molecule.

31. The medical device of claim 28, wherein the anti-thrombotic modified derivative is a member selected from the group consisting of heparin-releasing polyvinylpyrrolidone, heparin-releasing methacrylate, heparin-releasing polyester, nitric oxide-releasing polyester, and nitric oxide-releasing polyvinyl chloride.

32. The medical device of claim 27, wherein the polymeric member has a wall thickness in the range of 0.05 to 0.4 mm.

33. The medical device of claim 27, wherein the polymeric member is adapted to substantially conform to a vascular aneurysm.

34. The medical device of claim 27, wherein the alloy comprises in the range of about 49 to about 51 wt. % Ni and in the range of about 51 to about 49 wt. % Ti.

35. The medical device of claim 34, wherein the metallic frame member comprises a single component.

36. The medical device of claim 35, wherein the metallic frame member is in the shape of a coil.