Polymeric surface coatings

• US 6,087,462 A
• Filed: 05/12/1998
• Issued: 07/11/2000
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: Biocompatibles Incorporated (Boston Scientific Corporation)
• Original Assignee: Biocompatibles Incorporated (Boston Scientific Corporation)
• Inventors: Bowers, Roderick W J, Charles, Stephen A, Jones, Stephen A, Stratford, Peter W
• Primary Examiner(s): Zitomer, Fred
• Application Number:
  US09/076,089
• Time in Patent Office: 791 Days
• Field of Search: 526/277, 526/278, 526/287, 526/288, 526/310, 526/312, 526/320, 526/328.5, 526/332, 526/347.1
• US Class Current: 526/277
• 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 polymerisable monomers which polymer has pendant groups bearing a centre 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 coating composition consisting essentially of (a) a polymer formed by the radical polymerization of monomers consisting essentially of

(i) a zwitterionic monomer of general formula (I):

space="preserve" listing-type="equation">Y--B--X (I)

wherein B is selected from the group consisting of straight and branched alkylene, oxaalkylene and oligo-oxaalkylene chain optionally containing one or more fluorine atoms and a valence bond;

X is a zwitterionic group and

Y is an ethylenically unsaturated polymerisable group selected from ##STR21## wherein;

R is hydrogen or a C₁ -C₄ alkyl group;

A is --O-- or --NR¹ -- where R¹ is hydrogen or a C₁ -C₄ alkyl group or R¹ is --B--X where B and X are as defined above; and

K is a group --(CH₂)_p OC(O), --(CH₂)_p C(O)O--, --(CH₂)_p OC(O)O--, (CH₂)_p NR² --, --(CH₂)_p NR² C(O)--, --(CH₂)_p C(O) NR² --, --(CH₂)_p NR² C(O)O--, --(CH₂)_p OC(O)NR² --, --(CH₂)_p NR² C(O)NR² --(in which the groups R² are the same or different), --(CH₂)_p O--, --(CH₂)_p SO₃ --, or, optionally in combination with B, a valence bond and p is from 1 to 12 and R² is hydrogen or a C1-C4 alkyl group; and

(ii) a hydrophobic comonomer of the general formula formula (VI);

space="preserve" listing-type="equation">Y.sup.1 --Q (VI)

where Y¹ is an ethylenically unsaturated polymerisable group selected from ##STR22## where R¹⁴ is hydrogen or C₁ -C₄ alkyl, A¹ is --O-- or --NR¹⁵ -- where R¹⁵ is hydrogen or a C₁ -C₄ alkyl group or R¹⁵ is a group Q;

K¹ is selected from the group consisting of --(CH₂)₁ OC(O)--, --(CH)₁ C(O)O--, --(CH₂)₁ OC(O)O--, --(CH₂)₁ NR¹⁶ --, --(CH₂)₁ NR¹⁶ C(O)--, --(CH₂)₁ C(O)NR¹⁶ --, --(CH₂)₁ NR¹⁶ C(O)O--, --(CH₂)₁)OC(O)NR¹⁶ --, --(CH₂)₁ NR¹⁶ C(O)NR¹⁶ -- (in which the groups R¹⁶ are the same or different), --(CH₂)₁ O--, --(CH₂)₁ SO₃ --, and a valence bond and l is from 1 to 12 and R¹⁶ is hydrogen or a C₁ -C₄ alkyl group; and

Q is selected from the group consisting of straight and branched alkyl, alkoxyalkyl and (oligo-alkoxy)alkyl chain containing 8 to 24 carbon atoms optionally containing one or more carbon-carbon double or triple bonds; and

(b) a solvent consisting essentially only of alcohol in which the polymer is dispersed.

2. A coating composition according to claim 1 in which the alcohol is selected from methanol, ethanol and isopropanol.

3. A coating composition according to claim 1 in which the polymer is in microdispersion form.

4. A coating composition according to claim 1 in which the polymer has a molecular weight in the range 2×

10⁴ to 10⁶.

5. A coating composition according to claim 1 in which the zwitterionic monomer is a compound of general formula (II) ##STR23## in which R is H or Me;

A is O;

B is alkylene of formula (CH₂)_a where a is in the range 1 to 12, and

X is as defined in claim 1.

6. A coating composition according to claim 5 in which a is in the range 1 to 6.

7. A coating composition according to claim 1 in which X is selected from the group consisting of groups (IVB), (IVC), (IVD), (IVE) and (IVF):

##STR24## 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;

##STR25## 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;

##STR26## wherein the groups R⁸ are the same or different and each is hydrogen or C_1-4 alkyl, R⁸ -- is hydrogen or a group --C(O)B¹ R^8b is hydrogen or methyl, B¹ is selected from the group consisting of a valence bond, and straight and branched alkylene, oxaalkylene and oligo-oxaalkylene 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;

##STR27## wherein the groups R⁹ are the same of different and each is hydrogen or C₁ -C₄ alkyl, R^9a is a hydrogen or a group --C(O) B² R^9b, R^9b is hydrogen or methyl, B² is selected from the group consisting of a valence bond and straight and branched alkylene, oxaalkylene and oligo-oxaalkylene groups, 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;

##STR28## 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 selected from the group consisting of a valence bond and straight and branched alkylene, oxaalkylene or oligo-oxaalkylene groups, 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.

8. A composition according to claim 7 in which X is a group of formula (IVC), in which each R⁷ is the same and is lower alkyl, and in which e is 2 or 3.

9. A composition according to claim 8 in which each R⁷ is methyl.

10. A coating composition according to claim 5 in which X is selected from the group consisting of (IVB), (IVC), (IVD), (IVE) and (IVF):

##STR29## 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;

##STR30## 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;

##STR31## wherein the groups R⁸ are the same or different and each is hydrogen or C_1-4 alkyl, R⁸ -- is hydrogen or a group --C(O)B¹ R^8b where R^8b is hydrogen or methyl, B¹ is selected from the group consisting of a valence bond, and straight and branched alkylene, oxaalkylene and oligo-oxaalkylene group, and f is from 1 to 4; and

if B is other than a valence bone 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;

##STR32## wherein the groups R⁹ are the same or different and each is hydrogen or C_1-4 alkyl, R^9a is a hydrogen or a group --C(O)B² R^9b, R^9b is hydrogen or methyl, B² is selected from the group consisting of a valence bond and straight and branched alkylene, oxaalkylene and oligo-oxaalkylene groups, 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;

##STR33## 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_hu 10b where R^10b is hydrogen or methyl, B³ is selected from the group consisting of a valence bond and straight and branched-alkylene, oxaalkylene or oligo-oxaalkylene groups, 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.

11. A coating composition according to claim 10 in which X is a group of formula (IVC), in which each R⁷ is the same and is lower alkyl, and in which e is 2 or 3.

12. A coating composition according to claim 11 in which each R⁷ is methyl.

13. A coating composition according to claim 1 in which, in the hydrophobic comonomer, Q is an alkyl group of formula (CR¹⁷₂)_m CR¹⁷₃ wherein the groups (CR¹⁷₂) are the same or different, and in each group (CR¹⁷₂) the groups R¹⁷ are the same or different and each group R¹⁷ is hydrogen or C_1-4 alkyl, and m is in the range 5 to 23.

14. A coating composition according to claim 13 in which each group R¹⁷ is hydrogen.

15. A coating composition according to claim 14 in which m is in the range 7 to 23.

16. A coating composition according to claim 15 in which the hydrophobic monomer is selected from n-dodecylmethacrylate, octadecylmethacrylate and hexadecylmethacrylate.

17. A coating composition according to claim 10 in which, in the hydrophobic comonomer, Q is an alkyl group of formula (CR¹⁷₂)_m CR¹⁷₃ wherein the groups (CR¹⁷₂) are the same or different, and in each group (CR¹⁷₂) the groups R¹⁷ are the same or different and each group R¹⁷ is hydrogen or C_1-4 alkyl, and m is in the range 5 to 23.

18. A coating composition according to claim 17 in which each R₁₇ is hydrogen.

19. A coating composition according to claim 18 in which m is in the range 7 to 23.

20. A coating composition according to claim 1 in which the zwitterionic monomer is used in an amount by weight of at least 5% to form the polymer and in which the hydrophobic monomer is used in an amount of at least 5% by weight to form the polymer.

21. A coating composition according to claim 1 in which the polymer is copolymer of 2-(methacryloyloxyethyl)-2-(trimethyl-ammonium)ethyl phosphate inner salt and n-dodecylmethacrylate.

22. A coating composition according to claim 21 in which the monomers are used in a molar ratio in the range 1:

2-14;

86 to form the polymer.

23. A coating composition according to claim 21 in which the solvent is ethanol or isopropanol.

24. A coating composition according to claim 22 in which the solvent is ethanol or isopropanol.