Implantable thromboresistant valve

• US 20070027535A1
• Filed: 07/27/2006
• Published: 02/01/2007
• Est. Priority Date: 07/28/2005
• Status: Abandoned Application

• Current Assignee: Cook Incorporated (Cook Group Incorporated), MED Institute, Inc. (Cook Group Incorporated)
• Original Assignee: Cook Incorporated (Cook Group Incorporated)
• Inventors: Agnew, Charles, Case, Brian, Paul, Ram, Purdy, James
• Application Number:
  US11/494,424
• Publication Number:
  US 20070027535A1
• Time in Patent Office: Days
• US Class Current: 623/2.180
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• CPC Class Codes: A61F 2/2418 Scaffolds therefor, e.g. support stents
• CPC Class Codes: A61F 2/2475 Venous valves
• CPC Class Codes: A61F 2220/0008 Fixation appliances for connecting prostheses to the body
• CPC Class Codes: A61F 2220/0016 with sharp anchoring protrusions, e.g. barbs, pins, spikes
• CPC Class Codes: A61F 2220/005 using adhesives
• CPC Class Codes: A61F 2220/0058 soldered or brazed or welded
• CPC Class Codes: A61F 2220/0075 sutured, ligatured or stitched, retained or tied with a rope, string, thread, wire or cable
• CPC Class Codes: A61F 2230/0054 V-shaped
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 33/12 Polypeptides, proteins or derivatives thereof , e.g. degradation products thereof
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

Medical devices for implantation within a body vessel comprising a thromboresistant material are provided. The thromboresistant material preferably comprises a biocompatible polyurethane, a remodelable material, a bioactive agent or any combination thereof. The medical device can be a prosthetic valve comprising a thromboresistant material. The medical device can also comprise a support frame with one or more valve leaflets attached to the support frame.

Claims

1. An implantable valve comprising:

a valve leaflet comprising a biocompatible polyurethane and a growth factor.

2. The valve of claim 1, where the growth factor is selected from the group consisting of:

FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, VEGF A, VEGF B, VEGF C, VEGF D, VEGF E, PIGF, PDGF, EGF, IFN-ALPHA, IFN-BETA, IFN-GAMMA, TGF-ALPHA, and TGF-BETA.

3. The valve of claim 1, where the valve leaflet further comprises a remodelable material.

4. The valve of claim 3, where the remodelable material is selected from the group consisting of:

small intestine submucosa (SIS), renal capsule matrix (RCM) and urinary bladder matrix (UBM).

5. The valve of claim 3, where the valve leaflet comprises a first layer comprising the remodelable material and a second layer comprising the biocompatible polyurethane in contact with the remodelable material.

6. The valve of claim 3, where the valve leaflet comprises a first layer comprising the biocompatible polyurethane comprising an adhesion promoting body vessel contact region including a remodelable material in contact with a portion of the biocompatible polyurethane.

7. The valve of claim 1, where the valve leaflet comprises a free edge moveable between an open position and a closed position in response to fluid flow contacting the valve surface.

8. The valve of claim 1, where the valve leaflet further comprises a thromboresistant bioactive agent.

9. The valve of claim 8, where the thromboresistant bioactive agent is selected from the group consisting of:

thrombin, Factor Xa, Factor VIIa, glycoprotein IIb/IIIa, thromboxane A2, ADP-induced glycoprotein Ib/IIIa, plasminogen activators, thrombin activatable fibrinolysis inhibitor (TAFI) inhibitors, heparin, low molecular weight heparin, covalent heparin, synthetic heparin salts, coumadin, bivalirudin (hirulog), hirudin, argatroban, ximelagatran, dabigatran, dabigatran etexilate, D-phenalanyl-L-poly-L-arginyl, chloromethy ketone, dalteparin, enoxaparin, nadroparin, danaparoid, vapiprost, dextran, dipyridamole, omega-3 fatty acids, vitronectin receptor antagonists, DX-9065a, CI-1083, JTV-803, razaxaban, BAY 59-7939, and LY-51,7717, eftibatide, tirofiban, orbofiban, lotrafiban, abciximab, aspirin, ticlopidine, clopidogrel, cilostazol, dipyradimole, sodium nitroprussiate, nitroglycerin, S-nitroso, alfimeprase, alteplase, anistreplase, reteplase, lanoteplase, monteplase, tenecteplase, urokinase, streptokinase, endothelial progenitor cells, phosphorylcholine, phosphatidylcholine, and endothelial cells.

10. The valve of claim 1, where the biocompatible polyurethane comprises a first layer comprising a base polymer and about 0.5% to about 5% of a surface modifying additive;

a. where the surface modifying additive comprises polydimethylsiloxane and the reaction product of diphenylmethane diisocyanate and 1,4-butanediol; and

b. where the base polymer is a polyetherurethane urea comprising polytetramethylene oxide and the reaction product of 4,4′

-diphenylmethane diisocyanate and ethylene diamine.

11. The implantable valve of claim 1, where the valve leaflet has a thickness of between about 0.0001 inch and about 0.0050 inch.

12. The valve of claim 1, where the implantable valve further comprises a support frame and where the valve leaflet is attached to at least a portion of the support frame.

19. The valve of claim 1, where the growth factor is selected from the group consisting of:

FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, VEGF A, VEGF B, VEGF C, VEGF D, VEGF E, PIGF, PDGF, EGF, IFN-ALPHA, IFN-BETA, IFN-GAMMA, TGF-ALPHA, and TGF-BETA.

13. An implantable valve comprising a radially expandable support frame and two or more flexible valve leaflets comprising a biocompatible polyurethane, where each leaflet comprises a flexible leaflet free edge and at least two edges defining an adhesion promoting body vessel contact region and attached to the support frame, at least two of the leaflet free edges forming a valve orifice defined by at least two opposable flexible leaflet free edges, the valve orifice permitting fluid to flow in a first direction through the implantable valve when each valve leaflet is in the open position, each leaflet free edge being moveable in response to fluid flow contacting the leaflet free edge, and each adhesion promoting body vessel contact region comprising a second layer comprising a material selected from the group consisting of:

a remodelable material, a growth factor, a bioactive agent and a porous biocompatible polyurethane.

14. The valve of claim 13, where the biocompatible polyurethane comprises a first layer comprising a base polymer and about 0.5% to about 5% of a surface modifying additive;

a. where the surface modifying additive comprises polydimethylsiloxane and the reaction product of diphenylmethane diisocyanate and 1,4-butanediol; and

b. where the base polymer is a polyetherurethane urea comprising polytetramethylene oxide and the reaction product of 4,4′

-diphenylmethane diisocyanate and ethylene diamine.

15. The valve of claim 13, where the porous biocompatible polyurethane comprises a first layer comprising a base polymer and about 1% to about 5% of a surface modifying additive and a pore size of between about 10 μ

m and about 500 μ

m;

a. where the surface modifying additive comprises polydimethylsiloxane and the reaction product of diphenylmethane diisocyanate and 1,4-butanediol; and

b. where the base polymer is a polyetherurethane urea comprising polytetramethylene oxide and the reaction product of 4,4′

-diphenylmethane diisocyanate and ethylene diamine.

16. The implantable valve of claim 13, where the adhesion promoting body vessel contact region comprises a porous biocompatible polyurethane having a void-to-volume ratio, preferably from about 0.40 to about 0.90.

17. The implantable valve of claim 13, where the implantable valve comprises two leaflets.

18. The valve of claim 13, where the thromboresistant bioactive agent is selected from the group consisting of:

thrombin, Factor Xa, Factor VIIa, glycoprotein IIb/IIIa, thromboxane A2, ADP-induced glycoprotein IIb/IIIa, plasminogen activators, thrombin activatable fibrinolysis inhibitor (TAFI) inhibitors, heparin, low molecular weight heparin, covalent heparin, synthetic heparin salts, coumadin, bivalirudin (hirulog), hirudin, argatroban, ximelagatran, dabigatran, dabigatran etexilate, D-phenalanyl-L-poly-L-arginyl, chloromethy ketone, dalteparin, enoxaparin, nadroparin, danaparoid, vapiprost, dextran, dipyridamole, omega-3 fatty acids, vitronectin receptor antagonists, DX-9065a, CI-1083, JTV-803, razaxaban, BAY 59-7939, and LY-51,7717, eftibatide, tirofiban, orbofiban, lotrafiban, abciximab, aspirin, ticlopidine, clopidogrel, cilostazol, dipyradimole, sodium nitroprussiate, nitroglycerin, S-nitroso, alfimeprase, alteplase, anistreplase, reteplase, lanoteplase, monteplase, tenecteplase, urokinase, streptokinase, endothelial progenitor cells, phosphorylcholine, phosphatidylcholine, and endothelial cells.

20. An implantable valve comprising:

a valve leaflet comprising a biocompatible polyurethane and an extracellular matrix material comprising at least one growth factor.