Polymeric surface coatings

• US 20040176556A1
• Filed: 03/10/2004
• Published: 09/09/2004
• Est. Priority Date: 07/05/1991
• Status: Active Grant

• 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
• Granted Patent: US 7,160,953 B2
• Time in Patent Office: Days
• 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

A biocompatibilising process in which a substrate having a surface which bears substrate pendant functional groups is biocompatibilised by coating it with a coating composition containing a polymer formed from a radical polymerisable monomers including a radical polymerisable zwitterionic monomer and a radical polymerisable 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 process in which a substrate having a surface which bears substrate pendant functional groups is coated with a coating composition containing a polymer formed from a radical polymerisable monomers including a radical polymerisable zwitterionic monomer and a radical polymerisable 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, and wherein

said zwitterionic monomer has the general formula I

Y-B-X 

 

(I)

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 IVB, IVC, IVD, IVE and IVF in which group IVB has the formula

wherein the groups R⁶ are the same or different and each is hydrogen or C_1-4 alkyl and d is from 2 to 4;

group IVC has the formula

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;

group IVD has the formula

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)B¹R^8b wherein R^8b is hydrogen or methyl, B¹ is a valence bond or straight or branched alkylene, oxaalkylene or oligo-oxaalkyene 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;

group IVE has the formula

wherein the groups R⁹ are the same or different and each is hydrogen or C₁-C₄ alkyl, R^9a is hydrogen or a group —

C(O)B²R^9b, wherein R^9b is hydrogen or methyl, B² is a valence bond or a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene 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; and

group IVF has the formula

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)B³R^10b wherein R^10b is hydrogen or methyl, B³ is a valence bond or a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene 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; and

Y is an ethylenically unsaturated polymerisable group selected from

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)_pOC(O)—

, —

(CH₂)_pC(O)O—

, —

(CH₂)_pOC(O)O—

, —

(CH₂)_pNR²—

, —

(CH₂)_pNR²C(O)—

, —

CH₂)_pC(O)NR²—

, —

(CH₂)_pNR²C(O)O—

, —

(CH₂)OC(O)NR²—

, —

(CH₂)_pNR²C(O)NR²—

, (in which the groups R² are the same or different) —

(CH₂)_pO—

, —

(CH₂)_pSO₃—

, 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

said radical polymerisable monomer containing reactive groups has the formula general formula (XII)

Y²-B⁷-Q³ 

 

(XII)

where Y² is an ethylenically unsaturated polymerisable group selected from

where R²⁶ is hydrogen or C₁-C₄ alkyl;

T is —

O—

or NR²⁷—

, wherein R²⁷ is hydrogen or a C₁-C₄ alkyl group or R²⁷ is a group -B⁷Q³;

B⁷ is a valence bond a straight or branched alkylene oxaalkylene or oligo-oxaalkylene group;

K² is a group —

(CH₂)_qOC(O)—

, —

(CH)_qC(O)O—

, —

(CH₂)_qOC(O)O—

, —

(CH₂)_qNR²⁰—

, —

(CH₂)_qNR²⁰C(O)—

, —

(CH₂)_qC(O)NR²⁰—

, —

(CH₂)NR²⁰C(O)O—

, —

(CH₂)_qOC(O)NR²⁰—

, —

(CH₂)_qNR²⁰C(O)NR²⁰—

(in which the groups R²⁰ are the same or different), —

(CH₂)_qO—

, or —

(CH₂)_qSO₃—

, or a valence bond and q is from 1 to 12 and R²⁰ is hydrogen or a C₁-C₄ alkyl group; and

Q³ is a reactive group selected from the group consisting of aldehyde groups;

silane and siloxane groups containing one or more substituents selected from halogen atoms and C_1-4-alkoxy groups;

hydroxyl;

amino;

carboxyl;

epoxy;

—

CHOHCH₃Hal (in which Hal is selected from chlorine, bromine and iodine atoms);

succinimido;

tosylate;

triflate;

imidazole carbonyl amino;

optionally substituted triazine groups;

aceloxy;

mesylate;

carbonyl di(cyclo)alkyl carbodiimidoyl; and

oximino.

2. A process according to claim 1 in which Q³ is selected from the group consisting of aldehyde, reactive silane and siloxane amino, epoxy, CHOHCH Hal (in which Hal is halogen), succimimido, tosylate, triflate, imidazolecarbonyl amino and optionally substituted triazine groups.

3. A process according to claim 1 in which the surface pendant groups are selected from the group consisting of hydroxyl, carboxyl and amine groups.

4. A process according to claim 1 in which the polymer is formed from 2-(methacryloyloxyethyl) -2′

-(trimethylammonium) ethyl phosphate inner salt and 2-aminoethylmethacrylate and in which the covalent bonding of the pendant amino group is to a surface having pendant carboxylate groups is achieved through the formation of an amide linkage.

5. A process according to claim 1 in which the said radical polymerisable monomers include a comonomer of the general formula VI

Y′

-Q 

 

(VI)

where Y′

is an ethylenically unsaturated polymerisable group selected from

6. A process according to claim 5 in which

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

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

9. A process 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 process 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 process 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 process according to claim 9 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 20% by weight diluent monomer.

13. A process 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.

14. A biocompatibilising process in which a substrate having a surface which bears substrate pendant functional groups is biocompatibilised by coating it with a coating composition containing a polymer formed from a radical polymerisable monomers including a radical polymerisable zwitterionic monomer and a radical polymerisable 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.

15. A process according to claim 14 in which the zwitterionic group is a group X selected from groups IVB, IVC, IVD, IVE and IVF in which group IVB has the formula

16. A process according to claim 14 in which the pendant functional group on the polymer is a group Q³ selected from the group consisting of aldehyde groups;

silane and siloxane groups containing one or more substituents selected from halogen atoms and C_1-4-alkoxy groups;

hydroxyl;

amino;

carboxyl;

epoxy;

—

CHOHCH₂Hal (in which Hal is selected from chlorine, bromine and iodine atoms);

succinimido;

tosylate;

triflate;

imidazole carbonyl amino;

optionally substituted triazine groups;

aceloxy;

mesylate;

carbonyl di(cyclo)alkyl carbodiimidoyl; and

oximino.

17. A process according to claim 15 in which the pendant functional group on the polymer is a group Q³ selected from the group consisting of aldehyde groups;

silane and siloxane groups containing one or more substituents selected from halogen atoms and C_1-4-alkoxy groups;

hydroxyl;

amino;

carboxyl;

epoxy;

—

CHOHCH₂Hal (in which Hal is selected from chlorine, bromine and iodine atoms);

succinimido;

tosylate;

triflate;

imidazole carbonyl amino;

optionally substituted triazine groups;

aceloxy;

mesylate;

carbonyl di(cyclo)alkyl carbodiimidoyl; and

oximino.

18. A process according to claim 16 in which the pendant functional group is selected from the group consisting of aldehyde, reactive silane and siloxane amino, epoxy, CHOHCH₂Hal (in which Hal is halogen), succimimido, tosylate, triflate, imidazolecarbonyl amino and optionally substituted triazine groups.

19. A process according to claim 17 in which the pendant functional group is selected from the group consisting of aldehyde, reactive silane and siloxane amino, epoxy, CHOHCH₂Hal (in which Hal is halogen), succimimido, tosylate, triflate, imidazolecarbonyl amino and optionally substituted triazine groups.

20. A process according to claim 14 in which the surface pendant groups are selected from the group consisting of hydroxyl, carboxyl and amine groups.

21. A process according to claim 14 in which the zwitterionic group is a group of formula IVC