Prosthetic heart valve with surface modification

• US 20010025196A1
• Filed: 12/21/2000
• Published: 09/27/2001
• Est. Priority Date: 09/06/1996
• Status: Active Grant

• Current Assignee: Corcym SRL (LivaNova Plc)
• Original Assignee: Carbomedics Inc. (Snia SpA)
• Inventors: Chinn, Joseph Andrew, Frautschi, Jack R., Phillips, Richard E. Jr.
• Granted Patent: US 6,764,509 B2
• Time in Patent Office: Days
• US Class Current: 623/2.17
• 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: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/34 Macromolecular materials

Abstract

Biocompatible prostheses, specifically, biocompatible heart valves, are described having incorporated therein an effective amount of coating applied thereto to render the valve resistant to in vivo pathologic thrombus formation and in vivo pathologic mineralization. Preferably, the coating is derived from a precursor having the formula:

X-Y-Z

wherein X is a chemically reactive group capable, upon activation, of bonding to the surface of the heart valve; Y is either null or a relatively inert skeletal moiety resistant to cleavage in aqueous physiological fluids; and Z is a functionally active moiety or a biocompatible agent.

Claims

1. A method for reducing mineralization and thrombus formation in a biocompatible polymeric heart valve after implantation, comprising:

coating, prior to implantation, at least a portion of the heart valve with a coating precursor of the formula;

X-Y-Z

wherein X is a chemically reactive group capable, upon activation, of bonding to the surface of the heart valve;

Y is either null or a relatively inert skeletal moiety resistant to cleavage in aqueous physiological fluids; and

Z is a functionally active moiety or a biocompatible agent; and

bonding the precursor to at least a portion of the heart valve, to produce a heart valve with a bonded coating;

wherein the bonded coating is present in an amount effective to reduce mineralization and thrombus formation after implantation.

2. The method of

claim 1

, wherein X is a photochemically reactive group.

3. The method of

claim 2

, wherein X is derived from a compound selected from aryl azides, alkyl azides, acyl azides, azidoformates, sulfonylazides, phosphoryl azides, diazo compounds, diazirines, ketenes, or aromatic ketones.

4. The method of

claim 1

, wherein Y is derived from a compound selected from C₁-C₁₀ alkyldiol or diamine;

polyethyleneoxide (PEO);

amino-substituted PEO (MW=200−

1450);

diamine-terminated PEO (MW=200−

1450);

ε

-amino caproic acid (EAC);

ethylene diamine (ED);

or diaminopropane (DAP).

5. The method of

claim 1

, wherein Z is derived from a compound selected from functionalized C₁-C₁₈ alkylene, functionalized mucopolysaccharides, functionalized polyoxyethylene, functionalized vinyl polymers, or functionalized polypeptides.

6. The method of

claim 1

, wherein X is derived from a substituted benzyl benzoyl having structure I:

wherein R1 is a carboxyl group;

Y is derived from diaminopropane (DAP) or a diamine-terminated amide; and

,

Z is derived from a compound selected from functionalized fatty acids, functionalized hyaluronic acid, functionalized polyoxyethylene, functionalized heparin, or functionalized polyvinylpyrrolidone.

7. The method of

claim 6

, wherein the precursor has the structure II or III:

8. A biocompatible heart valve, comprising:

a stent defining a blood flow path; and

a plurality of polymeric leaflets having applied thereto a surface coating effective to render the heart valve resistant to in vivo pathologic thrombus formation and in vivo pathologic mineralization, wherein the surface coating comprises a fatty acid moiety, a hyaluronic acid moiety, a polyoxyethylene moiety, a heparin moiety, or a vinylpyrrolidone moiety.

9. The biocompatible heart valve of

claim 8

, wherein the polymeric leaflets comprise a polymer selected from siloxane polymers, polydimethylsiloxanes, silicone rubber, polyurethane, polyether urethane, polyester urethane, polyamide, polycarbonate, polyester, polypropylene, polyethylene, polystyrene, polyvinyl chloride, polytetrafluoroethylene, polysulfone, cellulose acetate, polymethylmethacrylate, or poly(ethylene/vinylacetate).

10. The biocompatible heart valve of

claim 9

, wherein the polymer is selected from silicone rubber, polyurethane, polyetherurethane, polyetherurethane/polysiliconeurethane, or epoxy-bisphosphonate-modified polyetherurethane.

11. The biocompatible heart valve of

claim 8

, wherein the surface coating comprises a benzyl benzoyl moiety bonding the surface coating to the polymeric leaflets.

12. The biocompatible heart valve of

claim 8

, wherein the coating is covalently bonded to the polymeric leaflets.

13. The biocompatible heart valve of

claim 8

, wherein the coating is non-covalently bonded to the polymeric leaflets.

14. The biocompatible heart valve of

claim 8

, wherein the surface coating is derived from a precursor of the formula:

X-Y-Z

wherein X is a chemically reactive group capable, upon activation, of bonding to the surface of the heart valve;

Y is either null or a relatively inert skeletal moiety resistant to cleavage in aqueous physiological fluids; and

Z is a fatty acid moiety, a hyaluronic acid moiety, a polyoxyethylene moiety, a heparin moiety, or a vinylpyrrolidone moiety.

15. The biocompatible heart valve of

claim 14

, wherein X is a photochemically reactive group.

16. The biocompatible heart valve of

claim 15

, wherein X is derived from a compound selected from aryl azides, alkyl azides, acyl azides, azidoformates, sulfonylazides, phosphoryl azides, diazo compounds, diazirines, ketenes, or aromatic ketones.

17. The biocompatible heart valve of

claim 14

, wherein Y is derived from a compound selected from C₁-C₁₀ alkyldiol or diamine;

polyethyleneoxide (PEO);

amino-substituted PEO (MW=200−

1450);

diamine-terminated PEO (MW=200−

1450);

ε

-amino caproic acid (EAC);

ethylene diamine (ED);

or diaminopropane (DAP).

18. The biocompatible heart valve of

claim 16

, wherein X is derived from a substituted benzyl benzoyl having structure I:

wherein R1 is a carboxyl group;

Y is derived from diaminopropane (DAP) or a diamine-terminated amide; and

,

Z is derived from a compound selected from functionalized fatty acids, functionalized hyaluronic acid, functionalized polyoxyethylene, functionalized heparin, or functionalized vinylpyrrolidone.

19. The method of

claim 18

, wherein the precursor has the structure II or III: