Hydrolytically-and proteolytically-stable polycarbonate polyurethane silicone copolymers

• US 5,863,627 A
• Filed: 08/26/1997
• Issued: 01/26/1999
• Est. Priority Date: 08/26/1997
• Status: Expired due to Term

• Current Assignee: Cardiotech International
• Original Assignee: Cardiotech International
• Inventors: Edwards, Alan, Szycher, Michael, Dempsey, Donald
• Primary Examiner(s): Short, Patricia A.
• Application Number:
  US08/920,062
• Time in Patent Office: 518 Days
• Field of Search: 528/26, 528/28, 525/453, 525/459, 525/464, 264/184, 264/209.2, 623/1, 623/12, 428/36.8, 428/36.9
• US Class Current: 428/36.8
• 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 18/12 using two or more compounds having active hydrogen in the first polymerisation step
• CPC Class Codes: C08G 18/3225 Polyamines
• CPC Class Codes: C08G 18/44 Polycarbonates
• CPC Class Codes: C08G 18/61 Polysiloxanes
• CPC Class Codes: C08G 18/778 silicon
• CPC Class Codes: C08G 18/8108 having only one isocyanate or isothiocyanate group
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device
• CPC Class Codes: Y10T 428/1386 Natural or synthetic rubber or rubber-like compound containing
• CPC Class Codes: Y10T 428/139 Open-ended, self-supporting conduit, cylinder, or tube-type article

Abstract

A biocompatible, biodurable polycarbonate polyurethane with internal polysiloxane segments and devices made therefrom.

Claims

1. A biodurable polycarbonate polyurethane block copolymer comprising

(a) a polycarbonate glycol internal segment;

(b) a polyurethane internal segment;

(c) a polydialkylsiloxane internal segment;

(d) di(C_1-6 alkyl)amino or C_1-6 hydroxyalkyl terminating segments;

(e) cyclo(C_5-7 alkane)diamino internal segments; and

(f) C_2-4 alkylene diamino internal segments;

wherein said segments are linked by urethane, urea, and C--Si--C moieties, said block copolymer being devoid of hydrolytically unstable Si--O--C linkages and being substantially devoid of ether linkages.

2. A biodurable polycarbonate polyurethane block copolymer, obtained from reactants comprising

(a) an aromatic or aliphatic diisocyanate;

(b) a polycarbonate diol;

(c) a difunctional polydialkylsiloxane having a viscosity between 15 and 70 centistokes;

(d) two chain extenders independently selected from C_2-8 diamines and C_2-8 diols, wherein said diamines and diols are cyclic, straight chain, or branched, and at least one chain extender is cyclic or branched; and

(e) a C_2-6 alkanol or di(C_2-6 alkyl) amine chain terminator, or mixture thereof;

wherein said block copolymer is devoid of hydrolytically unstable Si--O--C linkages and substantially devoid of ether linkages.

3. A copolymer of claim 2 wherein said diisocyanate is selected from 4,4-diphenyl methane diisocyanate, phenyl diisocyanate, toluene diisocyanate, isophorone diisocyanate, m-trimethylxylylene diisocyanate, p-trimethylxylylene diisocyanate, and methylene bis (4-cyclohexyl isocyanate).

4. A copolymer of claim 3 wherein said diisocyanate is selected from 4,4-diphenyl methane diisocyanate and methylene bis (4-cyclohexyl isocyanate).

5. A copolymer of claim 2 wherein said polycarbonate is polyethylene carbonate having a molecular weight between 500 and 5000 Daltons.

6. A copolymer of claim 5 wherein said polycarbonate has a molecular weight between 1000 and 3000 Daltons.

7. A copolymer of claim 2 wherein the molar ratio of polycarbonate to isocyanate groups is between 55:

100 and 65;

100.

8. A copolymer of claim 2 wherein said chain extenders are selected from ethylene glycol, 1,3-propylene glycol, 1,4-butane diol, 1,5-pentane diol, 1,6-hexane diol, 1,4-cyclohexane diol, and 1,4-isophorone diol.

9. A copolymer of claim 2 wherein said chain extenders are selected from ethylene diamine, 1,3-propylene diamine, 1,4-butane diamine, 1,5-pentane diamine, 1,6-hexane diamine, 1,4-cyclohexane diamine, and 1,4-isophorone diamine.

10. A copolymer of claim 8 wherein said chain extenders are selected from 1,3-cyclohexane diol and ethylene glycol.

11. A copolymer of claim 9 wherein said chain extenders are selected from 1,3-cyclohexane diamine and ethylene diamine.

12. A copolymer of claim 2 wherein the molar ratio of said at least one branched or cyclic chain extender to isocyanate groups is between 3.1:

100 and 5.5;

100.

13. A copolymer of claim 12 wherein the molar ratio of said at least one branched or cyclic chain extender to isocyanate groups is about 4.9:

100.

14. A copolymer of claim 2 wherein the molar ratio of a chain extender to isocyanate groups is between 38:

100 and 48;

100.

15. A copolymer of claim 14 wherein the molar ratio of a chain extender to isocyanate groups is about 44:

100.

16. A copolymer of claim 2 wherein said chain terminator has between 2 and 4 carbon atoms.

17. A copolymer of claim 2 wherein said chain terminator is diethyl amine.

18. A copolymer of claim 2 wherein the molar ratio of said chain terminator to isocyanate groups is between 0.1:

100 and 2;

100.

19. A copolymer of claim 2 wherein the molar ratio of said chain terminator to isocyanate groups is about 1.5:

100.

20. A copolymer of claim 2 wherein said siloxane is polydimethylsiloxane.

21. A copolymer of claim 2 wherein said siloxane is a polydi(fluoro-C_1-3 alkyl)siloxane or a poly(C_1-3 alkyl C_1-4 fluoroalkyl)siloxane.

22. A copolymer of claim 21 wherein said siloxane comprises a fluoroalkyl group selected from fluoromethyl, difluoromethyl, trifluoromethyl, 2-perfluoroethyl, and 3-perfluoropropyl.

23. A copolymer of claim 2 wherein said siloxane has a terminating group selected from a C_1-6 aminoalkyl and C_1-6 hydroxyalkyl.

24. A copolymer of claim 23 wherein said terminating group has between 2 and 4 carbon atoms.

25. A copolymer of claim 24 wherein said terminating group is aminopropyl or hydroxypropyl.

26. A polycarbonate polyurethane block copolymer of claim 2, obtained by reacting

(a) 4,4-diphenyl methane diisocyanate or methylene bis (4-cyclohexyl isocyanate);

(b) a polycarbonate diol having a molecular weight between 1000 and 3000 Daltons;

(c) a polydimethylsiloxane having a viscosity between 15 and 70 centistokes;

(d) ethylene diamine and a cyclohexane diamine; and

(e) a dialkylamine having between 2 and 6 carbon atoms.

27. A copolymer of claim 26 wherein said polydimethylsiloxane is terminated with aminopropyl groups.

28. A copolymer of claim 26 wherein said dialkylamine is diethylamine, ethylmethylamine, or ethylpropylamine.

29. A copolymer of claim 26 wherein said diisocyanate is 4,4-diphenyl methane diisocyanate.

30. A copolymer of claim 26 wherein said polycarbonate diol has a molecular weight between 2000 and 3000 Daltons.

31. A copolymer of claim 26 wherein said cyclohexanediamine is 1,3-cyclohexane diamine.

32. A block copolymer of claim 26 wherein the molar proportions are, respectively, within 5% of (a) 100, (b) 59.51, (c) 0.8, (d) 35.0 and 3.9, and (e) 1.5.

33. A block copolymer of claim 26 wherein a test sample of copolymer has no surface cracks visible by SEM to a resolution between 40×

at 400% elongation after being subjected to the Stokes'"'"' test for 6 months.

34. A vascular graft comprising a graft wall base including at least 85% by weight a biodurable polycarbonate polyurethane block copolymer comprising

(a) a polycarbonate glycol internal segment;

(b) a polyurethane internal segment;

(c) a polydialkylsiloxane internal segment;

(d) di(C_1-6 alkyl)amino or C_1-6 hydroxyalkyl terminating segments;

(e) cyclo(C_5-7 alkane)diamino or cyclo(C_5-7 alkane)dihydroxy internal segments; and

(f) C_2-8 alkylene diamino or dihydroxy internal segments;

wherein said segments are linked by urethane, urea, and C--Si--C moieties, said block copolymer being devoid of hydrolytically unstable Si--O--C linkages and being substantially devoid of ether linkages;

said graft wall being an anisotropically microporous single layer with a porosity between 60% and 80% void/volume.

35. A method of making a vascular graft, said method comprising

(a) obtaining a polymer solution comprising

a polar solvent;

a water soluble filler, 10% to 60% by weight;

a surfactant 1% to 10% by weight; and

a polycarbonate polyurethane block copolymer obtained from reactants comprising

(i) an aromatic or aliphatic diisocyanate;

(ii) a polycarbonate diol;

(iii) a difunctional polydialkylsiloxane or polydi(fluoroalkyl)siloxane having a viscosity between 15 and 70 centistokes;

(iv) two chain extenders independently selected from C_2-7 diamines and C_2-8 diols, wherein said diamines and diols are cyclic, straight chain, or branched, and at least one chain extender is cyclic or branched; and

(v) a C_2-6 alkanol or di(C_2-6 alkyl) amine chain terminator, or mixture thereof;

wherein said block copolymer is devoid of hydrolytically unstable Si--O--C linkages and substantially devoid of ether linkages;

(b) contacting said polymer solution with a mandrel surface;

(c) synchronously rotating said mandrel and an extrusion head;

(d) drawing said mandrel through an extrusion head into a coagulant maintained at a temperature less than 55 degrees Centigrade (preferably 40 degrees Centigrade); and