Polymeric surface coatings

• US 7,160,953 B2
• Filed: 03/10/2004
• Issued: 01/09/2007
• Est. Priority Date: 07/05/1991
• Status: Expired due to Fees

• Current Assignee: Biocompatibles Incorporated (Boston Scientific Corporation)
• Original Assignee: Biocompatibles Incorporated (Boston Scientific Corporation)
• Inventors: Stratford, Peter William, Bowers, Roderick William Jonathon, Jones, Stephen Alister
• Primary Examiner(s): Lipman; Bernard
• Application Number:
  US10/795,977
• Publication Number:
  US 20040176556A1
• Time in Patent Office: 1,035 Days
• Field of Search: 525/326.6 526/277,279,307,307.1,307.2,310,312,328.5,347,347.1
• US Class Current: 525/326.6
• CPC Class Codes: C07F 9/091 with hydroxyalkyl compounds with further substituents on alkyl
• CPC Class Codes: C07F 9/65742 non-condensed with carbocyclic rings or heterocyclic rings or ring systems
• CPC Class Codes: C08F 246/00 Copolymers in which the nature of only the monomers in minority is defined

Abstract

A biocompatibilizing process in which a substrate having a surface which bears substrate pendant functional groups is biocompatibilized by coating it with a coating composition containing a polymer formed from a radical polymerizable monomers including a radical polymerisable zwitterionic monomer and a radical polymerizable monomer containing a reactive group to form a polymer having zwitterionic groups and pendant reactive groups and the said pendant reactive groups are reacted to form covalent bonds with said substrate pendant functional group and thereby form a stable coating of polymer on the said surface.

Claims

1. A cross-linked polymer formed by

a) radical polymerisation of radical polymerisable monomers including

i) a zwitterionic monomer having the formula:

Y—

B—

X

wherein

B is a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene chain optionally containing one or more fluorine atoms up to and including perfluorinated chains, or if X contains a carbon-carbon chain between B and the centre of permanent position charge or if Y contains a terminal carbon atom bonded to B, a valence bond;

X is a zwitterionic group selected from groups, IVC, IVD and IVF in which group IVC has the formula

2. A polymer according to claim 1 in which Q³ is selected from the group consisting of aldehyde, silane and siloxane groups containing one or more substituents selected from halogen atoms and C_1-4 alkoxy groups, amino, epoxy, CHOHCH₂Hal (in which Hal is halogen), succinimido, tosylate, triflate, imidazolecarbonyl amino and optionally substituted triazine groups.

3. A polymer according to claim 1 in which the group Q³ is selected from the group consisting of amino, acetylenically unsaturated hydrocarbon groups, 3-chloro-2-hydroxypropyl and 3-trimethyoxy silyl propyl.

4. A polymer according to claim 1 in which the said monomer having a reactive group is selected from the group consisting of 2-aminoethylmethacrylate, 7-dodecynmethacrylate, 3-chloro-2- hydroxypropylmethacrylate and 3-(trimethoxysilyl) propylmethacrylate.

5. A polymer according to claim 1 in which said radical polymerisable monomers include a comonomer having the general formula (VI)

Y¹—

Q 

 

(VI)

where

Y¹ is an ethylenically unsaturated polymerisable group selected from

6. A polymer according to claim 5 in which Y¹ is

7. A polymer according to claim 6 in which the said comonomer is selected from the group consisting of n-dodecyl methacrylate, octadecyl methacrylate, hexadecylmethacrylate, 1H, 1H, 2H, 2H-heptadecafluorodecylmethacrylate, p-octyl styrene, p-dodecyl styrene and monomethacryloyloxypropyl terminated siloxanes.

8. A polymer according to claim 7 in which the said comonomer is dodecyl methacrylate.

9. A polymer according to claim 1 in which the said radical polymerisable monomers include a diluent monomer selected from the group consisting of C_1-4-alkyl(alk)acrylates, N, N-dialkylamino alkyl(alk)acrylates containing 1 to 4 carbon atoms in each N-alkyl group and 1 to 4 carbon atoms in the alkylene group, C_1-4 alkyl(alk)acrylamide, hydroxy C_1-4-alkyl(alk)acrylate, N-vinyl lactam having 5–

7 atoms in the lactam ring, styrene, derivatives of styrene having ring substituents selected from C_1-4 alkyl groups and halogen atoms, polyhydroxyl (alk)acrylates, alkenes, butadiene, maleic anhydride and acrylonitrile.

10. A polymer according to claim 9 in which the diluent monomer is selected from hydroxy C_1-4-alkyl(alk)acrylates and polyhydroxyl(alk)acrylates.

11. A polymer according to claim 1 in which the said radical polymerisable monomers include at least 5% by weight zwitterionic monomer and at least 0.1% by weight monomer having a reactive group.

12. A polymer according to claim 1 in which the said radical polymerisable monomers include at least 5% by weight zwitterionic monomer and 0.1% to 20% by weight monomer having a reactive group.

13. A polymer according to claim 9 in which the said radical zwitterionic monomers include at least 5% by weight, at least 0.1% by weight monomer having a reactive group and 5 to 20% by weight diluent monomer.

14. A polymer according to claim 5 in which the said radical polymerisable monomers include at least 5% by weight zwitterionic monomer, at least 0.1% by weight monomer having a reactive group and 5 to 90% by weight of said comonomer.

15. A polymer according to claim 1 in which said cross-linkage is by direct reaction of groups Q³ with one another.

16. A polymer according to claim 1 in which said cross-linkage is by reaction of groups Q³ with a reactive bridging molecule.

33. A polymer according to claim 1 in which X is said group IVC.

17. A process in which a cross-linkable polymer is cross-linked by forming cross-linkages between reactive groups Q⁵ on the polymer wherein the cross-linkable polymer is formed by

a) radical polymerisation of radical polymerisable monomers including

i) a zwitterionic monomer having the formula:

Y—

B—

X

wherein

B is a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene chain optionally containing one or more fluorine atoms up to and including perfluorinated chains, or if X contains a carbon-carbon chain between B and the centre of permanent position charge or if Y contains a terminal carbon atom bonded to B, a valence bond;

X is a zwitterionic group selected from groups, IVC, IVD and IVF in which

group IVC has the formula

18. A process according to claim 17 in which Q³ is selected from the group consisting of aldehyde, silane and siloxane groups containing one or more substituents selected from halogen atoms and C_1-4 alkoxy groups, amino, epoxy, CHOHCH₂Hal (in which Hal is halogen), succinimido, tosylate, triflate, imidazolecarbonyl amino and optionally substituted triazine groups.

19. A process according to claim 17 in which the group Q³ is selected from the group consisting of amino, acetylenically unsaturated hydrocarbon groups, 3-chloro-2-hydroxypropyl and 3-trimethyoxy silyl propyl.

20. A process according to claim 17 in which the said monomer having a reactive group is selected from the group consisting of 2-aminoethylmethacrylate, 7-dodecynmethacrylate, 3-chloro-2-hydroxypropylmethacrylate and 3-(trimethoxysilyl) propylmethacrylate.

21. A process according claim 17 in which said radical polymerisable monomers include a comonomer having the general formula (VI):

Y¹—

Q 

 

(VI)

where

Y¹ is an ethylenically unsaturated polymerisable group selected from

22. A polymer according to claim 17 in which Y¹ is

23. A process according to claim 22 in which the said comonomer is selected from the group consisting of n-dodecyl methacrylate, octadecyl methacrylate, hexadecylmethacrylate, 1H, 1H, 2H, 2H-heptadecafluorodecylmethacrylate, p-octyl styrene, p-dodecyl styrene and monomethacryloyloxypropyl terminated siloxanes.

24. A process according to claim 23 in which the said comonomer is dodecyl methacrylate.

25. A process according to claim 17 in which the said radical polymerisable monomers include a diluent monomer selected from the group consisting of C_1-4-alkyl(alk)acrylates, N, N-dialkylamino alkyl(alk)acrylates containing 1 to 4 carbon atoms in each N-alkyl group and 1 to 4 carbon atoms in the alkylene group, C_1-4 alkyl(alk)acrylamide, hydroxy C_1-4-alkyl(alk)acrylate, N-vinyl lactam having 5–

7 atoms in the lactam ring, styrene, derivatives of styrene having ring substituents selected from C_1-4 alkyl groups and halogen atoms, polyhydroxyl (alk)acrylates, alkenes, butadiene, maleic anhydride and acrylonitrile.

26. A process according to claim 25 in which the diluent monomer is selected from hydroxy C_1-4-alkyl(alk)acrylates and polyhydroxyl(alk)acrylates.

27. A process according to claim 17 in which the said radical polymerisable monomers include at least 5% by weight zwitterionic monomer and at least 0.1% by weight monomer having a reactive group.

28. A process according to claim 17 in which the said radical polymerisable monomers include at least 5% by weight zwitterionic monomer and 0.1% to 20% by weight monomer having a reactive group.

29. A process according to claim 25 in which the said radical zwitterionic monomers include at least 5% by weight, at least 0.1% by weight monomer having a reactive group and 5 to 20% by weight diluent monomer.

30. A process according to claim 21 in which the said radical polymerisable monomers include at least 5% by weight zwitterionic monomer, at least 0.1% by weight monomer having a reactive group and 5 to 90% by weight of said comonomer.

31. A process according to claim 17 in which said cross-linkage is by direct reaction of groups Q³ with one another.

32. A process according to claim 17 in which said cross-linkage is by reaction of groups Q³ with a reactive bridging molecule.

34. A process according to claim 17 in which X is said group IVC.