US 5,645,883 A · Zwitterionic materials

Abstract

The present invention provides materials which comprise a surface having pendant zwitterionic groups Z comprising, as anion, a phosphate, sulphonate, carboxylate or phosphate-ester group or a phosphate ester group in which one or more of the ester oxygen atoms is replaced by --S--, --NH-- or by a valence bond and, as cation, an ammonium, phosphonium or sulphonium moiety, provided that where the anion is a phosphate-ester group or derivative thereof or sulphonate and the cation is a trialkyl quaternary ammonium group (the alkyl groups each containing from 1 to 4 carbon atoms) and the group linking the anion and cation moieties is an alkylene group, the alkylene group, contains at least 5, preferably at least 6, and more preferably at least 7, carbon atoms. The materials have improved biocompatibility for instance as evidenced by reduced protein deposition and reduced platelet activation.

A method for preparing a coated substrate, comprising the steps (a) and (b) of

(a) coating onto a surface of a substrate a solution or dispersion in a solvent of a polymer formed by polymerizing a monomer selected from compounds of formula (XII) and (XIII):
##STR24## said polymer being obtained by copolymerizing a polymerizable comonomer containing a zwitterionic group Z and a second comonomer containing a group that binds the copolymer to a surface, or by polymerizing a polymerizable monomer containing both a zwitterionic group Z and a group that binds the polymer to a surface,
wherein in formula (XII) and (XIII):
R.sup.11 is hydrogen or a C.sub.1 -C.sub.4 alkyl group;
L is --O-- or --NR.sup.12 -- wherein R.sup.12 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl, and --B--Z.sup.B, wherein B and Z.sup.B are as defined below:
K is selected from the group consisting of --(CH.sub.2).sub.p OC(O)--, --(CH.sub.2).sub.p C(O)O--, --(CH.sub.2).sub.p OC(O)O--, --(CH.sub.2).sub.p NR.sup.13 --, --(CH.sub.2).sub.p NR.sup.13 C(O)--, --(CH.sub.2).sub.p C(O)NR.sup.13 --, --(CH.sub.2).sub.p NR.sup.13 C(O)O--, --(CH.sub.2).sub.p OC(O)NR.sup.13 --, --(CH.sub.2).sub.p NR.sup.13 C(O)NR.sup.13 -- wherein the R.sup.13 groups are the same or different, --(CH.sub.2).sub.p O--, --(CH.sub.2).sub.p SO.sub.3 --, and a covalent bond, wherein p is from 1 to 12 and R.sup.13 is hydrogen or a C.sub.1 -C.sub.4 alkyl;
B is selected from the group consisting of a covalent bond, straight and branched alkylene, oxaalkylene and oligo-oxaalkylene groups, each containing up to 12 carbon atoms, and each optionally containing one or more fluorine atoms;
and
Z.sup.B is a zwitterionic group selected from the group consisting of Z and groups of formulae XIV, XV and XVI
wherein Z is a group of formula (II) ##STR25## wherein:
X.sup.1 and X.sup.2, which are the same or different, are selected from the group consisting of --O, --S--, --NH--, and a covalent bond;
and
W.sup.+ is a cationic group selected from the group consisting of --W.sup.1 --N.sup.+ R.sup.3.sub.3, --W.sup.1 --P.sup.+ R.sup.3a.sub.3, --W.sup.1 --S.sup.+ R.sup.3a.sub.2 and --W.sup.1 --Het.sup.+, wherein
W.sup.1 is selected from the group consisting of an alkylene having at least 5 carbon atoms, and optionally containing one or more ethylenically unsaturated double or triple bonds, a disubstituted-aryl, an aryl alkylene, an alkylene aryl alkylene, a disubstituted cycloalkyl, an alkylene cycloalkyl, a cycloalkyl alkylene, and an alkylene cycloalkyl alkylene, any one of which optionally contains one or more fluorine substituents and/or one or more functional groups,
the R.sup.3 groups are the same or different, and each is hydrogen or an alkyl having from 1 to 4 carbon atoms, wherein two of the R.sup.3 groups are optionally bonded together with the nitrogen atom to which they are attached to form a heterocyclic ring containing from 5 to 7 atoms, or the three R.sup.3 groups are optionally bonded together with the nitrogen atom to which they are attached to form a fused ring structure containing from 5 to 7 atoms in each ring, and optionally one or more of the R.sup.3 groups is substituted by a hydrophilic functional group,
the R.sup.3a groups are the same or different and each is R.sup.3 or --OR.sup.3, where R.sup.3 is as defined above;
and
Het is selected from the group consisting of an aromatic nitrogen-containing ring, an aromatic phosphorus-containing ring, and an aromatic sulphur-containing ring,
(ii) formula (XIV) ##STR26## wherein:
R.sup.14 is hydrogen or a group of formula --C(O)B.sup.1 R.sup.14a wherein R.sup.14a is hydrogen or methyl;
B.sup.1 is selected from the group consisting of a covalent bond, straight and branched alkylene, oxaalkylene and oligo-oxaalkalyene;
if B is a covalent bond and K is other than a covalent bond, z is 0, and otherwise, when B is a covalent bond, z is 1;
Z is as defined above,
(iii) formula (XV) ##STR27## wherein R.sup.14, B.sup.1, z, and Z are as defined above, and (iv) formula (XVI) ##STR28## wherein R.sup.14, B.sup.1, z, and Z are as defined above;
and (b) evaporating the solvent to obtain a coating of said polymer on the surface of said substrate.

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Zwitterionic materials

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Zwitterionic materials

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Abstract

Claims24