Polymeric surface coatings

• US 5,648,442 A
• Filed: 03/07/1994
• Issued: 07/15/1997
• Est. Priority Date: 07/05/1991
• Status: Expired due to Term

• Current Assignee: Biocompatibles Incorporated (Boston Scientific Corporation)
• Original Assignee: Biocompatibles Incorporated (Boston Scientific Corporation)
• Inventors: Stratford, Peter W., Jones, Stephen A., Bowers, Roderick W. J.
• Primary Examiner(s): Zitomer, Fred
• Application Number:
  US08/175,348
• Time in Patent Office: 1,226 Days
• Field of Search: 526/278, 526/328.5, 526/310, 526/312, 526/277, 427/387
• US Class Current: 526/277
• 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

Polymers of one or more radical polymerizable monomers which polymer has pendant groups bearing a center of permanent positive charge and other pendant groups capable of stably binding the polymer to a surface are useful in the treatment of surfaces to render them biocompatible. The polymers may contain pendant groups which bind the polymer to a surface by physisorption, covalent bonding or ionic interactions. Additionally reactive groups in the polymer may serve as points for attachment of ligands to the polymer when coated on a surface.

Claims

1. A process comprising the steps of coating a substrate with a coating composition consisting of a solvent and a polymer dissolved or dispersed in the solvent and drying the composition to leave a coating of the polymer on the substrate whereby the biocompatibility of the coating is improved, said polymer being formed by copolymerizing i) a zwitterionic monomer of formula I'"'"' ##STR21## wherein:

R is hydrogen or a C_1-4 alkyl group;

A is --O-- or ---NR¹ -- where R¹ is selected from the group consisting of hydrogen, a C_1-4 -alkyl group and BX where B and X are defined below;

B is selected from the group consisting of an alkylene --(CR³₂)_a wherein the groups --(CR³₂)-- are the same or different and in each group (CR³₂) the groups R³ are the same or different and each group R³ is hydrogen or a C_1-4 -alkyl and a is 1 to 12;

an alkoxyalkyl group having 1 to 6 carbon atoms in each alkyl moiety; and

an oligooxaalkylene group --c(CR⁴₂)_b -- where the groups --(CR⁴₂)-- are the same or different and in each group --(CR⁴₂)-- the groups R⁴ are the same or different and each R⁴ is hydrogen or a C_1-4 -alkyl, b is 1 to 6 and C is 2 to 11; and

X is an ammonium phosphate ester zwitterionic group;

with

ii) a comonomer of 7 formula VI'"'"' ##STR22## wherein R¹⁴ is hydrogen or a C_1-4 alkyl;

A¹ is --O-- or --NR¹⁵ --, where R¹⁵ is selected from the group consisting of hydrogen, a C_1-4 group and Q; and

Q is a straight or branched alkyl group containing 6 to 24 carbon atoms.

2. A process according to claim 1 in which B is an alkylene group --(CR³₂)_a in which each R³ is hydrogen and a is 1 to 6.

3. A process according to claim 1 in which A is O.

4. A process according to claim 1 in which A'"'"' is O.

5. A process according to claim 3 in which A'"'"' is O.

6. A process according to claim 1 in which Q is an alkyl group having at least 12 carbon atoms.

7. A process according to claim 5 in which Q is an alkyl group having at least 12 carbon atoms.

8. A process according to claim 1 in which the molar ratio of zwitterionic monomer of formula I'"'"' to comonomer of formula VI'"'"' is in the range (10:

90)-(50;

50).

9. A process according to claim 7 in which molar ratio of zwitterionic monomer of the formula I'"'"' to comonomer of formula VI'"'"' is in the range (10:

90)-(50;

50).

10. A process according to claim 7 in which the molecular weight of the polymer is in the range of 20,000 to 1 million.

11. A process according to claim 1 in which the substrate is formed from a material selected from the group consisting of polyethylene, polypropylene, polytetrafluoroethylene, polyvinylchloride and steel.

12. A process according to claim 9 in which the substrate is formed from a material selected from the group consisting of polyethylene, polypropylene, polytetrafluoroethylene, polyvinylchloride and steel.

13. A process according to claim 10 in which the solvent comprises an alcohol.

14. A process according to claim 11 in which the solvent comprises an alcohol.

38. A process according to claim 1, wherein in the comonomer of formula I'"'"', X is a group of formula IVB ##STR28## where the groups R⁶ are the same or different and each is hydrogen or C_1-4 alkyl and d is from 2 to 4;

a group of formula IVC ##STR29## where the groups R⁷ are the same or different and each is hydrogen or C_1-4 alkyl, and e is from 1 to 4;

a group of formula IVD;

##STR30## wherein the groups R⁸ are the same or different and each is hydrogen or C_1-4 alkyl, R^8a is hydrogen or a group --C(O)B¹ R^8b where R^8b is hydrogen or methyl, B¹ is a valence bond or straight or branched alkylene, oxaalkylene or oligo-oxaalkyalene group, and f is from 1 to 4; and

if B is other than a valence bond z is 1 and if B is a valence bond Z is 0, if X is directly bonded to an oxygen or nitrogen atom and otherwise Z is 1;

a group of formula IVE;

##STR31## wherein the groups R⁹ are the same or different and each is hydrogen or C_1-4 alkyl, R^9a is hydrogen or a group --C(O)B² R^9b, where R^9b is hydrogen or methyl, B² is a valence bond or a straight or branched alkylene, oxaalkylene or oligo-axaalkylene group, and g is from 1 to 4; and

if B is other than a valence bond Z is 1 and if B is a valence bond Z is 0 if X is directly bonded to an oxygen or nitrogen atom and otherwise Z is 1;

or

a group of formula IVF;

##STR32## wherein the groups R¹⁰ are the same or different and each is hydrogen or C_1-4 alkyl, R^10a is hydrogen or a group --C(O)B³ R^10b where R^10b is hydrogen or methyl, B³ is a valence bond or a straight or branched alkylene, oxaalkylene or oligo-axaalkylene group, and h is from 1 to 4; and

if B is other than a valence bond Z is 1 and if B is a valence bond Z is 0 if X is directly bonded to the oxygen or nitrogen and otherwise Z is 1.

39. A process according to claim 1 in which e is 2 and each R⁷ is methyl.

40. A polymerization process according to claim 1, wherein the molar ratio of Formula I'"'"' zwitterionic monomer to Formula VI'"'"' comonomer is in a range of 10:

90 to 50;

50.

41. A polymerization process according to claim 1, wherein the molar ratio of Formula I'"'"' zwitterionic monomer to Formula VI'"'"' comonomer is about 1:

2.

42. A polymerization process according to claim 1, wherein the molar ratio of Formula I'"'"' zwitterionic monomer to Formula VI'"'"' comonomer is about 1:

4.

15. A polymerization process comprising copolymerizing

i) a zwitterionic monomer of formula I'"'"' ##STR23## wherein:

R is hydrogen or a C_1-4 alkyl group;

A is --O-- or --NR¹ -- where R¹ is selected from the group consisting of hydrogen, a C_1-4 -alkyl group and BX where B and X are defined below;

B is selected from the group consisting of an alkylene group --(CR³₂)_a wherein the groups --(CR³₂)-- are the same or different and in each group (CR³₂) the groups R³ are the same or different and each group R³ is hydrogen or a C_1-4 -alkyl and a is 1 to 12;

an alkoxyalkyl group having 1 to 6 carbon atoms in each alkyl moiety; and

an oligooxaalkylene group --c(CR⁴₂)_b -- where the groups --(CR⁴₂)-- are the same or different and in each group --(CR⁴₂)-- the groups R⁴ are the same or different and each R⁴ is hydrogen or a C_1-4 -alkyl, b is 1 to 6 and C is 2 to 11; and

X is an ammonium phosphate ester zwitterionic group;

with

ii) a comonomer of 7 formula VI'"'"' ##STR24## wherein R¹⁴ is hydrogen or a C_1-4 alkyl;

A¹ is --O-- or --NR¹⁵ --, where R¹⁵ is selected from the group consisting of hydrogen, a C_1-4 group and Q; and

Q is a straight or branched alkyl group containing 6 to 24 carbon atoms.

16. A polymerisation process according to claim 15 in which the solvent comprises an alkanol containing from 1 to 4 carbon atoms.

17. A polymerisation process according to claim 15 in which the solvent is selected from the group consisting of mixtures of tetrahydrofuran and methanol and mixtures of propan-2-ol and ethyl acetate.

18. A polymerisation process according to claim 15 comprising recovering the polymer from the process by precipitating the polymer out of the said solvent by adding the solution of the said polymer in said solvent to a non-solvent for the polymer.

19. A polymerisation process according to claim 15 in which B is an alkylene group of the formula --(CR³₂)_a in which each R³ is hydrogen and a is 1 to 6.

20. A polymerisation process according to claim 15 in which A is O.

21. A polymerisation process according to claim 15 in which X is a group of formula IVC ##STR25## where the groups R⁷ are the same or different and each is hydrogen or C_1-4 -alkyl and e is 1 to 5.

22. A polymerisation process according to claim 21 in which e is 2 and each R⁷ is methyl.

23. A polymerisation process according to claim 15 in which A'"'"' is O.

24. A polymerisation process according to claim 20 in which A'"'"' is O.

25. A polymerisation process according to claim 20 in which is an alkyl group having at least 12 carbon atoms.

26. A polymerisation process according to claim 24 in which Q is an alkyl group having at least 12 carbon atoms.

27. A polymerisation process according to claim 25 in which the molar ratio of zwitterionic monomer of formula I'"'"' to comonomer of formula VI'"'"' is in the range (10:

90)-(50;

50).

28. A polymerisation process according to claim 27 in which the molecular weight of the polymer is in the range 20,000 to 1 million.

29. A polymer formed by copolymerising monomers consisting of:

i) a zwitterionic monomer of formula I" ##STR26## wherein R is hydrogen or methyl,

a is 1 to 6

e is 1 to 4

each R⁷ is lower alkyl, and

ii) a comonomer of formula VI" ##STR27## R¹⁴ is hydrogen or methyl;

Q is an alkyl group having 12 to 24 carbon atoms,

said polymer having a molecular weight in the range 20,000 to 1 million, the molar ratio of the zwitterionic monomer of formula I" to the comonomer of formula VI" being in the range (5;

95) to (50;

50).

31. A polymer according to claim 29 in which e is 2.

32. A polymer according to claim 31 in which a is 2.

33. A polymer according to claim 32 in which R¹⁴ is methyl.

34. A polymer according to claim 29 in which Q is selected from the group consisting of a dodecyl group, a n-octadecyl group and a n-hexadecyl group.

35. A polymer according to claim 33 in which Q is selected from the group consisting of a dodecyl group, a n-octadecyl group and a n-hexadecyl group.

36. A polymer according to claim 29 in which the molar ratio is in the range (1:

2) to (1;

4).

37. A polymer according to claim 35 in which the molar ratio is in the range (1:

2) to (1;

4).

30. A polymer according to claim 30 in which each R⁷ is methyl.