1. Field of the Invention
The present invention relates to new polymers, processes for producing them and processes for coating surfaces with them. The invention also provides improved processes for producing certain monomers and to certain new monomers used to obtain the polymers. The polymers are useful for coating surfaces of devices and materials which come into contact with protein-containing solutions and biological fluids, and rendering the surfaces bio- and haemocomaptible. Surfaces may thus be rendered suitable for prolonged contact with living tissues and body fluids and with protein-containing solutions.
2. Description of Related Art
Materials used in the manufacture of separation substrates and devices, blood contacting devices contact and intraocular lenses, and other devices which are used in contact with protein-containing or biological fluids must be selected on the basis of acceptable physical and mechanical properties and compatability with the protein-containing or biological fluid. For any given application of these materials it is usually difficult to optimise all of these considerations simultaneously and a compromise must be reached often resulting in less than optimal performance. For example, major biological problems are often encountered with materials which have otherwise optimal mechanical and physical properties. These problems often manifest themselves as undesirable deposition of biological components and in particular proteinaceous material. This protein adsorption results in blood clot formation in blood-contacting materials, the adsorption of tear components onto contact lenses resulting in deposit formation, formation of deposits on intraocular lenses and in separation media it results in blockage and failure of separation devices. Such effects lead to significant loss in operational performance and often complete rejection and failure of devices.
In the case of medical devices, for example prostheses and components of blood dialysis equipment, it is common practice to employ biocompatible polymers to form at least the surface of the devices to discourage protein adsorption. However, these materials are not perfect and reaction with the living tissues still remains a problem; for example surface-induced thrombosis is still a major difficulty, particularly where large quantities of blood are contacted with a foreign surface such as in artificial lungs and kidneys. Formation of a clot in an artificial organ has a number of adverse or even catastrophic effects including occlusion of the blood pathway in the extracorporeal system, or embolism if the clot breaks off the artificial surface and lodges in a host blood vessel. Dialysis membranes, heart valves, circulator-assist devices, blood substitutes and artificial lungs all share this problem.
It is known that materials for use as biocompatible coatings should ideally:
(a) be capable of reproducible manufacture as pure materials; PA1 (b) be capable of being coated onto surfaces without being degraded or adversely changed; PA1 (c) have the requisite mechanical and permeability properties required for the specific function of the device for which they are intended; PA1 (d) be sterilisable without adverse changes in, for example, permeability and mechanical or surface properties; PA1 (e) not be damaged or degraded by the biological environment; PA1 (f) not be carcinogenic. PA1 (g) induce significant platelet adhesion; PA1 (h) interfere with the normal clotting mechanism; or PA1 (i) cause any significant damage to the cellular elements or soluble components of the blood. PA1 (i) copolymerising a radical polymerisable, preferably an ethylenically unsaturated, comonomer containing a group bearing a centre of permanent positive charge, which is preferably zwitterionic, and a radical polymerisable, preferably an ethylenically unsaturated, comonomer containing a radical polymerisable moiety and an alkyl group of 6 or more carbon atoms, which alkyl group optionally contains one or more etheric oxygen atoms and optionally one or more carbon--carbon double or triple bonds, or a fluoroalkyl group which optionally contains one or more etheric oxygen atoms and optionally one or more carbon--carbon double or triple bonds, or a siloxane group; or PA1 (ii) polymerising a radical polymerisable, preferably ethylenically unsaturated, monomer containing a group bearing a centre of permanent positive charge which is preferably zwitterionic, and an alkyl group of 6 or more carbon atoms, which alkyl group optionally contains one or more etheric oxygen atoms, or a fluoroalkyl group which optionally contains one or more etheric oxygen atoms, or a siloxane group. PA1 (i) copolymerising a radical polymerisable, preferably ethylenically unsaturated, comonomer containing a group bearing a centre of permanent positive charge, which is preferably zwitterionic, and a radical polymerisable, preferably ethylenically unsaturated, comonomer bearing a reactive group capable of covalently binding the polymer to a surface; or PA1 (ii) polymerising a radical polymerisable, preferably ethylenically unsaturated, monomer containing a group bearing a centre of permanent positive charge, which is preferably zwitterionic, and a reactive group capable of covalently binding the polymer to a surface. PA1 (i) copolymerising a radical polymerisable, preferably ethylenically unsaturated, comonomer containing a group bearing a centre of permanent positive charge which is preferably zwitterionic, and a radical polymerisable, preferably ethylenically unsaturated, comonomer bearing an ionic group capable of binding to a surface by ionic interaction; or PA1 (ii) polymerising a radical polymerisable, preferably ethylenically unsaturated, monomer containing a group bearing a centre of permanent positive charge, which is preferably zwitterionic, and an ionic group capable of binding to a surface by ionic interaction. PA1 X is a group bearing a centre of permanent positive charge, preferably a zwitterionic group and PA1 Y is an ethylenically unsaturated polymerisable group selected from ##STR1## PA1 R is hydrogen or a C.sub.1 -C.sub.4 alkyl group; PA1 A is --O-- or --NR.sup.1 -- where R.sup.1 is hydrogen or a C.sub.1 -C.sub.4 alkyl group or R.sup.1 is -B-X where B and X are as defined above; and PA1 K is a group --(CH.sub.2).sub.p OC(O)--, --(CH2).sub.p C(O)O--, --(CH.sub.2).sub.p OC(O)O--, --(CH.sub.2).sub.p NR.sup.2 --,--(CH.sub.2).sub.p NR.sup.2 C(O)--, --(CH.sub.2).sub.p C(O)NR.sup.2 --, --(CH.sub.2).sub.p NR.sup.2 C(O)O--, --(CH.sub.2).sub.p OC(O)NR.sup.2 --, --(CH.sub.2).sub.p NR.sup.2 C(O)NR.sup.2 --, (in which the groups R.sup.2 are the same or different) --(CH.sub.2).sub.p O--, --(CH.sub.2).sub.p SO.sub.3 --, or, optionally in combination with B, a valence bond and p is from 1 to 12 and R.sup.2 is hydrogen or a C.sub.1 -C.sub.4 alkyl group. PA1 an alkylene group of formula --(CR.sup.3.sub.2).sub.a --, wherein the groups --(CR.sup.3.sub.2).sub.a -- are the same or different, and in each group --(CR.sup.3.sub.2).sub.a -- the groups R.sup.3 are the same or different and each group R.sup.3 is hydrogen, fluorine or C.sub.1-4 alkyl or fluroalkyl, preferably hydrogen, and a is from 1 to 12, preferably 1 to 6; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each alkyl moiety, more preferably --CH.sub.2 O(CH.sup.2).sub.4 --; or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.4.sub.2).sub.b O].sub.c (CR.sup.4.sub.2).sub.b -- where the groups --(CR.sup.4.sub.2)-- are the same or different and in each group --(CR.sup.4.sub.2)-- the groups R.sup.4 are the same or different and each group R.sup.4 is hydrogen, fluorine or C.sub.1-4 alkyl or fluoroalkyl, preferably hydrogen, and b is from 1 to 6, preferably 2 or 3 and c is from 2 to 11, preferably 2 to 5; or PA1 if X contains a carbon--carbon chain between B and the centre of permanent positive charge or if Y contains a terminal carbon atom, a valence bond. PA1 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. PA1 a valence bond; PA1 an alkylene group of formula --(CR.sup.3a.sub.2).sub.aa --, wherein the groups --(CR.sup.3a.sub.2)-- are the same or different, and in each group (CR.sup.3a.sub.2)-- the groups R.sup.3a -- are the same or different and each group R.sup.3a -- is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and aa is from 1 to 12, preferably 1 to 6; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each alkyl moiety, more preferably --CH.sub.2 O(CH.sub.2).sub.4 --; or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.4a.sub.2).sub.ba O].sub.ca -- where the groups --(CR.sup.4a.sub.2)-- are the same or different and in each group --(CR.sup.4a.sub.2)-- the groups R.sup.4a are the same or different and each group R.sup.4a is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and ba is from 1 to 6, preferably 2 or 3, and ca is from 1 to 12, preferably 1 to 6. PA1 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. PA1 a valence bond; PA1 an alkylene group of formula --(CR.sup.3b.sub.2).sub.ab --, wherein the groups --(CR.sup.3b.sub.2)-- are the same or different, and in each group --(CR.sup.3b.sub.2)-- the groups R.sup.3b are the same of different and each group R.sup.3b is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and ab is from 1 to 12, preferably 1 to 6; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6, carbon atoms in each alkyl moiety, more preferably --CH.sub.2 O(CH.sub.2).sub.4 --; or PA1 an oligo-oxaalkylene group of formula --(CR.sup.4b.sub.2).sub.bb O].sub.cb -- where the groups --(CR.sup.4b.sub.2)-- are the same or different and in each group --(CR.sup.4b.sub.2)-- the groups R.sup.4b are the same or different and each group R.sup.4b is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and bb is from 1 to 6, preferably 2 or 3, and cb is from 1 to 12, preferably 1 to 6. PA1 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. PA1 a valence bond; PA1 an alkylene group of formula --(CR.sup.3c.sub.2).sub.ac --, wherein the groups --(CR.sup.3c.sub.2)-- are the same or different and in each group (CR.sup.3c.sub.2)-- the groups R.sup.3 l are the same or different and each group R.sup.3c is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and ac is from 1 to 12, preferably 1 to 6; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each alkyl moiety, more preferably --CH.sub.2 O(CH.sub.2).sub.4 --; or PA1 an-oligo-oxaalkylene group of formula --[(CR.sup.4c.sub.2).sub.bc O].sub.cc -- where the groups --(CR.sup.4c.sub.2)-- are the same or different and in each group --(CR.sup.4c.sub.2)-- the groups R.sup.4c are the same or different and each group R.sup.4c is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and bc is from 1 to 6, preferably 2 or 3, and cc is from 1 to 12, preferably 1 to 6. PA1 (a) a group --[C(O)].sub.vw (CR.sup.11b.sub.2).sub.ww (SiR.sup.11c.sub.2) (OSiR.sup.11c.sub.2).sub.w R.sup.11c in which each group R.sup.11b is the same or different and is hydrogen or alkyl of 1 to 4 carbon atoms, each group R.sup.11c is the same or different and is alkyl of 1 to 4 carbon atoms or aralkyl, for example benzyl or phenethyl, vw is 0 or 1, ww is from 0 to 6 with the proviso that vw and ww are not both 0, and w is from 0 to 49; PA1 (b) a group of formula --C(O)B.sup.4 --R.sup.11d, in which R.sup.11d is hydrogen or methyl, B.sup.4 is a valence bond or straight or branched alkylene, oxaalkylene or oligo-oxaalkalyene group optionally containing one or more fluorine atoms, and containing from 6 to 24, preferably 6 to 18 carbon atoms; PA1 i is from 1 to 4; and PA1 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. PA1 a valence bond; PA1 an alkylene group of formula --(CR.sup.3d.sub.2).sub.ad -- wherein the groups --(CR.sup.3d.sub.2)-- are the same or different, and in each group --(CR.sup.3d.sub.2)-- the groups R.sup.3d are the same or different and each group R.sup.2d is hydrogen, fluorine or C.sub.1-4 alkyl or fluoroalkyl, preferably hydrogen or fluorine, and ad is from 1 to 24, preferably to 18; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms and optionally one or more fluorine atoms in each alkyl moiety, or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.4d.sub.2).sub.bd O].sub.cd -- where the groups --(CR.sup.4d.sub.2)-- are the same or different and in each group --(CR.sup.4d.sub.2)-- the groups R.sup.4d are the same or different and each group R.sup.4d is hydrogen, fluorine or C.sub.1-4, alkyl or fluoroalkyl, preferably hydrogen or fluorine, and bd is from 2 to 6, preferably 3 or 4, and cd is from 1 to 12, preferably 1 to 6. PA1 (a) a group --[C(O)].sub.tu (CR.sup.12b.sub.2).sub.uu (SiR.sup.12c.sub.2) (OSiR.sup.12c.sub.2).sub.tt R.sup.12c in which each group R.sup.12b is the same or different and is hydrogen or alkyl of 1 to 4 carbon atoms, each group R.sup.12c is the same or different and is alkyl of 1 to 4 carbon atoms or aralkyl, for example benzyl or phenethyl, tu is 0 or 1, uu is from 0 to 6, with the proviso that tu and uu are not both 0, and tt is from 0 to 49; or PA1 (b) a group of formula --C(O)B.sup.5 --R.sup.12d, in which R.sup.12d is hydrogen or methyl, B.sup.5 is a valence bond or a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene group optionally containing one or more fluorine atoms and from 6 to 24 carbon atoms, more preferably 6 to 18 carbons atoms, PA1 j is from 1 to 4; and PA1 a valence bond; PA1 an alkylene group of formula --(CR.sup.3e.sub.2).sub.ac --, wherein the groups --(CR.sup.3e.sub.2)-- are the same or different, and in each group --(CR.sup.3e.sub.2)-- the groups R.sup.3e are the same of different and each group R.sup.3e is hydrogen, fluorine or C.sub.1-4 alkyl, or fluoroalkyl, preferably hydrogen or fluorine, and ae is from 1 to 24, preferably 6 to 18; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms and optionally one or more fluorine atoms in each alkyl moiety; or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.4e.sub.2).sub.be O].sub.ce where the groups --(CR.sup.4e.sub.2)-- are the same or different and in each group --(CR.sup.4e.sub.2)-- the groups R.sup.4e are the same or different and each group R.sup.4e is hydrogen, fluorine or C.sub.1-4 alkyl or fluoroalkyl, preferably hydrogen or fluorine, and be is from 2 to 6, preferably 3 or 4, and ce is from 1 to 12, preferably 1 to 6. PA1 (a) a group --[C(O)].sub.rs (CR.sup.13b.sub.2).sub.ss (SiR.sup.13c.sub.2) (oSiR.sup.13c.sub.2).sub.rr R.sup.13c in which each group R.sup.13b is the same or different and is hydrogen or alkyl of 1 to 4 carbon atoms, each group R.sup.13c is the same or different and is alkyl of 1 to 4 carbon atoms or aralkyl, for example benzyl or phenethyl, rs is 0 or 1, ss is from 0 to 6, with the proviso that rs and ss are not both 0, and rr is from 0 to 49; or PA1 (b) a group of formula --C(O)B.sup.6 --R.sup.13d, in which R.sup.13a is hydrogen or methyl, B.sup.6 is a valence bond or a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene group optionally containing one or more fluorine atoms and from 6 to 24, more preferably 6 to 18 carbon atoms and k is from 1 to 4; and PA1 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. PA1 a valence bond; PA1 an alkylene group of formula --(CR.sup.3f.sub.2).sub.af --, wherein the groups --(CR.sup.3f.sub.2)-- are the same or different, and in each group (CR.sup.3f.sub.2)-- the groups R.sup.3f are the same or different and each group R.sub.3f is hydrogen, fluorine or C.sub.1-4 alkyl or fluoroalkyl, preferably hydrogen or fluorine, and is from 1 to 24, preferably 6 to 18; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms and optionally one or more fluorine atoms in each alkyl moiety; or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.4f.sub.2).sub.bf O].sub.cf -- where the groups --(CR.sup.4f.sub.2)-- are the same or different and in each group --(CR.sup.4f.sub.2)-- the groups R.sup.4f are the same or different and each group R.sup.4f is hydrogen, fluorine or C.sub.1-4 alkyl or fluoroalkyl, preferably hydrogen or fluorine, and bf is from 2 to 6, preferably 3 or 4, and cf is from 1 to 12, preferably 1 to 6. PA1 A' is --O-- or --NR.sup.15 -- where R.sup.15 is hydrogen or a C.sub.1 -C.sub.4 alkyl group or R.sup.15 is a group Q; PA1 K.sup.1 is a group --(CH.sub.2).sub.1 OC(O)--, --(CH).sub.1 C(O)O--, --(CH.sub.2).sub.1 OC(O)O--, --(CH.sub.2).sub.1 NR.sup.16 --, --(CH.sub.2).sub.1 NR.sup.16 C(O)--, --(CH.sub.2).sub.1 C(O)NR.sup.16 --, --(CH.sub.2).sub.1 NR.sup.16 C(O)O--, --(CH.sub.2).sub.1 OC(O)NR.sup.16 --, --(CH.sub.2).sub.1 NR.sup.16 C(O)NR.sup.16 --(in which the groups R.sup.16 are the same or different), --(CH.sub.2).sub.1 O--, --(CH.sub.2).sub.1 SO.sub.3 --, a valence bond and 1 is from 1 to 12 and R.sup.16 is hydrogen or a C.sub.1 -C.sub.4 alkyl group; and PA1 Q is (a) a straight or branched alkyl, alkoxyalkyl or (oligo-alkoxy)alkyl chain containing 6 or more, preferably 6 to 24, carbon atoms unsubstituted or substituted by one or more fluorine atoms and optionally containing one or more carbon--carbon double or triple bonds; or PA1 (b) a siloxane group --(CR.sup.16a.sub.2).sub.qq (SiR.sup.16b.sub.2) (OSiR.sup.16b.sub.2).sub.pp R.sup.16b in which each group R.sup.16a is the same or different and is hydrogen or alkyl of 1 to 4 carbon atoms or aralkyl, for example benzyl or phenethyl, each group R.sup.16b is alkyl of 1 to 4 carbon atoms, qq is from 1 to 6 and pp is from 0 to 49. PA1 wherein: PA1 R.sup.14, A', K.sup.1 and Q are as defined in relation to formula (VI). PA1 an alkyl group of formula --(CR.sup.17.sub.2).sub.m CR.sup.17.sub.3 wherein the groups --(CR.sup.17.sub.2)-- are the same or different, and in each group --(CR.sup.17.sub.2)the groups R.sup.17 are the same or different and each group R.sup.17 is hydrogen, fluorine or C.sub.1-4 alkyl or fluoroalkyl and m is from 5 to 23 if Q contains no fluorine atoms or from 1 to 23, preferably 5 to 23, if Q contains one or more fluorine atoms; PA1 an alkoxyalkyl having 1 to 12 carbon atoms in each alkyl moiety; unsubstituted or substituted by one or more fluorine atoms; or PA1 an (oligo-alkoxyl) alkyl group of formula --[(CR.sup.18.sub.2).sub.n O].sub.o (CR.sup.18.sub.2).sub.n R.sup.18 where the groups --(CR.sup.18.sub.2)-- are the same or different and in each group --(CR.sup.18.sub.2)-- the groups R.sup.18 are the same or different and each group R.sup.18 is hydrogen, fluorine or C.sub.1-4 alkyl or fluoroalkyl and n is from 2 to 6, preferably 3 to 4, and 0 is from 1 to 12. PA1 Q.sup.1 is a reactive group capable of reacting to provide covalent binding to a surface. PA1 R.sup.19 is as defined with reference to formula (X), and Q.sup.2 is a reactive group. PA1 B.sup.7 is a valence bond or, more preferably, a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene chain; and PA1 Q.sup.3 is a reactive group capable of reacting to provide covalent binding to a surface such as an aldehyde group or a silane or siloxane group containing one or more reactive substituents such as halogen, for example chlorine, or alkoxy, generally containing from 1 to 4 carbon atoms, for example methoxy or ethoxy, or, more preferably Q.sup.3 is a hydroxyl, amino, carboxyl, epoxy, --CHOHCH.sub.2 Hal, (in which Hal is a halogen atom such as chlorine, bromine or iodine) succinimido, tosylate such as 2(N-methylpyridinium) tosylate, triflate, imidazole carbonyl-amino, or an optionally substituted triazine group. PA1 an alkylene group of formula --(CR.sup.22.sub.2).sub.3 --, wherein the groups --(CR.sup.22.sub.2)-- are the same or different, and in each group --(CR.sup.22.sub.2)-- the groups R.sup.22 are the same or different and each group R.sup.22 is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and r is from 1 to 12, preferably 1 to 6; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each alkyl moiety; or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.23.sub.2).sub.s O].sub.1 (CR.sup.23.sub.2).sub.s -- where the groups --(CR.sup.23.sub.2)-- are the same or different and in each group --(CR.sup.23.sub.2)-- the groups R.sup.23 are the same or different and each group R.sup.23 is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and s is from 1 to 6, preferably 2 or 3, and t is from 1 to 11, preferably 1 to 5. PA1 B.sup.8 is a straight of branched alkylene, oxaalkylene or oligo-oxaalkylene chain; and PA1 Q.sup.4 is a reactive group capable of reacting to provide covalent binding to a surface, for example an aldehyde group or a silane or siloxane group containing one or more reactive substituents such as halogen, for example chlorine, or alkoxy, generally containing from 1 to 4 carbon atoms, for example methoxy or ethoxy, or, more preferably, Q.sup.4 is a hydroxyl, amino, carboxyl, epoxy, --CHOHCH.sub.2 Hal, (in which Hal is a halogen atom such as chlorine, bromine or iodine) succinimido, tosylate, triflate, imidazole carbonyl-amino or optionally substituted triazine group. PA1 an alkylene group of formula --(CR.sup.24.sub.2).sub.u --, wherein the groups --(CR.sup.24.sub.2)-- are the same or different, and in each group --(CR.sup.24.sub.2)-- the groups R.sup.24 are the same of different and each group R.sup.24 is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and u is from 1 to 12, preferably 1 to 6; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each alkyl moiety; or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.25.sub.2).sub.v O].sub.w (CR.sup.25).sub.v -- where the groups --(CR.sup.25.sub.2)-- are the same or different and in each group --(CR.sup.25.sub.2)-- the groups R.sup.25 are the same or different and each group R.sup.25 is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and v is from 1 to 6, preferably 2 or 3, and w is from 1 to 12, preferably 1 to 6. PA1 A" is --O-- or --NR.sup.27 --, wherein R.sup.27 is hydrogen or a C.sub.1 -C.sub.4 alkyl group or R.sup.27 is a group -B.sup.9 -Q.sup.5 ; PA1 B.sup.9 is a valence bond, a straight or branched alkylene, oxaalkylene or oligo-oxaalkylene group; PA1 K.sup.3 is a group --(CH.sub.2).sub.x OC(O)--, --(CH).sub.x C(O)O--, --(CH.sub.2).sub.x OC(O)O--, --(CH.sub.2).sub.x NR.sup.28 --, --(CH.sub.2).sub.x NR.sup.28 C(O)--, --(CH.sub.2).sub.x C(O)NR.sup.28 --, --(CH.sub.2).sub.x NR.sup.28 C(O)O--, --(CH.sub.2).sub.x OC(O)NR.sup.28 --, --(CH.sub.2).sub.x NR.sup.28 C(O)NR.sup.28 --(in which the groups R.sup.28 are the same or different), --(CH.sub.2).sub.x O--, --(CH.sub.2).sub.x SO.sub.3 --, a valence bond (optionally in combination with B9) and x is from 1 to 12 and R.sup.28 is hydrogen or a C.sub.1 -C.sub.4 alkyl group; PA1 Q.sup.5 is an ionic group capable of binding to a surface by ionic interaction. PA1 R.sup.26, A.sup.11, B.sup.9, K.sup.3 and Q.sup.5 are as defined in relation to formula (XII). PA1 an alkylene group of formula --(CR.sup.29.sub.2).sub.y --, wherein the groups --(CR.sup.29.sub.2)-- are the same or different, and in each group --(CR.sup.29.sub.2)-- the groups R.sup.29 are the same or different and each group R.sup.29 is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and y is from 1 to 12, preferably 1 to 6; PA1 an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each alkyl moiety; or PA1 an oligo-oxaalkylene group of formula --[(CR.sup.30.sub.2).sub.yy O].sub.xx (CR.sup.30.sub.2).sub.yy -- where the groups --(CR.sup.30.sub.2)-- are the same or different and in each group --(CR.sup.30.sub.2)-- the groups R.sup.30 are the same or different and each group R.sup.30 is hydrogen or C.sub.1-4 alkyl, preferably hydrogen, and yy is from 1 to 6, preferably 2 or 3, and xx is from 1 to 12, preferably 1 to 6. PA1 a) copolymerising a comonomer containing a group bearing a centre of permanent positive charge, preferably a zwitterionic group, a comonomer containing a group capable of stably binding the polymer to a surface and optionally a diluent and/or crosslinkable comonomer; or PA1 b) polymerising a monomer containing a group containing a group bearing a centre of permanent positive charge, preferably a zwitterionic group, and a group capable of stably binding the polymer to a surface and optionally further comonomer containing a group capable of stably binding the polymer to the surface and a diluent and/or a crosslinkable comonomer.
In applications involving direct contact with blood further restrictions exist. Materials should not:
There have been many attempts to prepare biocompatible, and specifically blood compatible (i.e. haemocompatible), surfaces, which do not activate the blood coagulation process and do not promote thrombus formation. Examples of such attempts include the preparation of negatively charged surfaces, such as by use of anionic polymers or suitable oriented electret polymers, preparation of surfaces coated with the natural anticoagulant heparin or synthetic heparin analogues, preparation of surfaces with inherently low surface free energy such as by use of silicone rubber, preparation of albumin-coated surfaces, and preparation of surfaces coated with compounds which are thought to adsorb albumin preferentially from blood. All of these however have had limitations.
In JP-A-03-039309 copolymers of a zwitterionic monomer, 2-(methacryloyloxyethyl)-2'-(trimethylammonium) ethyl phosphate inner salt, and alkyl methacrylates are used to form membranes and to mould to form medical materials. There is a suggestion that the polymers could be dissolved in a solvent and used to modify surfaces of materials.
In U.S. Pat. No. 3,671,502 copolymers of a zwitterionic monomer, which is a sulphobetaine or a carboxybetaine, and a hydroxyalkyl methacrylate comonomer are used as binders for hydrophilic substrates. The polymers are neutral (i.e. uncharged).
In GB-A-1529378 cross-linkable copolymers are formed by copolymerising a zwitterionic monomer, which is a sulphobetaine or a carboxybetaine compound, and a comonomer having a reactive group such as an epoxy group. The polymers are used in thermosetting paints.
In EP-A-293963 copolymers of fluoroalkyl group containing monomers and ionic monomers are produced. The ionic groups provide cross-linking with counterionically charged groups in the polymer or at a surface. The product may be used in a wound dressing.