Bioprosthetic Heart Valve With Polyphosphazene

• US 20080086205A1
• Filed: 10/10/2007
• Published: 04/10/2008
• Est. Priority Date: 10/10/2006
• Status: Active Grant

• Current Assignee: Celonova Biosciences, Inc. (Boston Scientific Corporation)
• Original Assignee: Celonova Biosciences, Inc. (Boston Scientific Corporation)
• Inventors: Denk, Roman, Fritz, Ulf, Gordy, Thomas, Ung, Neng
• Granted Patent: US 7,922,764 B2
• Time in Patent Office: Days
• US Class Current: 623/2.42
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3645 Connective tissue
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/40 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 85/02 containing phosphorus

Abstract

This disclosure encompasses a bioprosthetic heart valve having a polyphosphazene polymer such as poly[bis(trifluoroethoxy)phosphazene], which exhibits improved antithrombogenic, biocompatibility, and hemocompatibility properties. A method of manufacturing a bioprosthetic heart valve having a polyphosphazene polymer is also described.

Claims

1. A bioprosthetic heart valve comprising a biological tissue and a polyphosphazene represented by formula (I):

2. The bioprosthetic heart valve of claim 1, wherein at least one of R¹ to R⁶ is an alkoxy group substituted with at least one fluorine atom.

3. The bioprosthetic heart valve of claim 1, wherein the polyphosphazene is poly[bis(trifluoroethoxy)phosphazene].

4. The bioprosthetic heart valve of claim 1, wherein the polyphosphazene is coated, diffused, impregnated, grafted, or any combination thereof, into or onto the biological tissue.

5. The bioprosthetic heart valve of claim 1, wherein the polyphosphazene is coated onto the biological tissue at a thickness of from about 1 nm to about 100 μ

m.

6. The bioprosthetic heart valve of claim 1, wherein the polyphosphazene has an average molecular weight of about 10 to about 13 million Daltons.

7. The bioprosthetic heart valve of claim 1, wherein the biological tissue comprises at least one of a mammalian heart valve, a mammalian pericardium, or a mammalian vascular graft.

8. A method of manufacturing a bioprosthetic heart valve, comprising

providing a biological tissue;

and

contacting the biological tissue with a polyphosphazene of formula (I);

 

wherein

n is 2 to ∞

; and

R¹ to R⁶ are groups which are each selected independently from alkyl, aminoalkyl, haloalkyl, thioalkyl, thioaryl, alkoxy, haloalkoxy, aryloxy, haloaryloxy, alkylthiolate, arylthiolate, alkylsulphonyl, alkylamino, dialkylamino, heterocycloalkyl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof, or heteroaryl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof.

9. The method of claim 8, wherein the polyphosphazene is coated, diffused, impregnated, grafted, or any combination thereof into or onto the biological tissue.

10. The method of claim 8, wherein at least one of R¹ to R⁶ is an alkoxy group substituted with at least one fluorine atom.

11. The method of claim 8, wherein the polyphosphazene is poly[bis(trifluoroethoxy)phosphazene].

12. The method of claim 8, wherein the biological tissue comprises at least one of a mammalian heart valve, a mammalian pericardium, or a mammalian vascular graft.

13. The method of claim 8, further comprising

combining the polyphosphazene, a fixing agent, a surfactant, and a polyphosphazene soluble organic solvent to form a polyphosphazene solution prior to contacting the biological tissue with the polyphosphazene solution.

14. The method of claim 13, wherein the polyphosphazene is poly[bis(trifluoroethoxy)phosphazene].

15. The method of claim 13, wherein the fixing agent is selected from formaldehyde, glutaraldehyde, or a combination thereof.

16. The method of claim 13, wherein the surfactant is selected from a polysorbate, a poloxamer, glycerol, polyethylene imines, chitosans, polyallylamines, polyvinyl pyrrolidone, PVP, DEAE dextran, or a combination thereof.

17. A method of improving the antithrombogenic, biocompatibility, or hemocapatibility properties of a bioprosthetic heart valve, comprising:

contacting the bioprosthetic heart valve with a polyphosphazene of formula (I);

 

wherein

n is 2 to ∞

; and

R¹ to R⁶ are groups which are each selected independently from alkyl, aminoalkyl, haloalkyl, thioalkyl, thioaryl, alkoxy, haloalkoxy, aryloxy, haloaryloxy, alkylthiolate, arylthiolate, alkylsulphonyl, alkylamino, dialkylamino, heterocycloalkyl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof, or heteroaryl comprising one or more heteroatoms selected from nitrogen, oxygen, sulfur, phosphorus, or a combination thereof;

wherein the polyphosphazene is coated, diffused, impregnated, grafted, or any combination thereof, into or onto the bioprosthetic heart valve.

18. The method of claim 17, wherein the polyphosphazene is coated onto the bioprosthetic heart valve at a thickness of from about 1 nm to about 100 μ

m.

19. The method of claim 17, wherein at least one of R¹ to R⁶ is an alkoxy group substituted with at least one fluorine atom.

20. The method of claim 17, wherein the polyphosphazene is a poly[bis(trifluoroethoxy)phosphazene]

21. The method of claim 17, wherein the polyphosphazene has a molecular weight of about 10 to about 13 million Daltons.

22. The method of claim 17, further comprising

combining the polyphosphazene, a fixing agent, a surfactant, and a polyphosphazene soluble organic solvent to form a polyphosphazene solution prior to contacting the bioprosthetic heart valve with the polyphosphazene solution;

wherein the polyphosphazene is a poly[bis(trifluoroethoxy)phosphazene];

the fixing agent is selected from formaldehyde, glutaraldehyde, or a combination thereof; and

the surfactant is selected from a polysorbate, a poloxamer, glycerol, or a combination thereof.

23. A bioprosthetic heart valve comprising a mammalian heart valve and a poly-[bis(trifluoroethoxy)phosphazene].

24. A method of making a bioprosthetic heart valve comprising

providing a mammalian heart valve;

and

contacting the mammalian heart valve with a poly[bis(trifluoroethoxy)-phosphazene];

wherein the poly[bis(trifluoroethoxy)phosphazene] is coated, diffused, impregnated, grafted, or any combination thereof, into or onto the mammalian heart valve.