Polymeric surface coatings

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.

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 haemocompatible. Surfaces may thus be rendered suitable 
for prolonged contact with living tissues and body fluids and with 
protein-containing solutions. 
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 compatibility 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, circulatory-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; 
(b) be capable of being coated onto surfaces without being degraded or 
adversely changed; 
(c) have the requisite mechanical and permeability properties required for 
the specific function of the device for which they are intended; 
(d) be sterilisable without adverse changes in, for example, permeability 
and mechanical or surface properties; 
(e) not be damaged or degraded by the biological environment; 
(f) not be carcinogenic. 
In applications involving direct contact with blood further restrictions 
exist. Materials should not: 
(g) induce significant platelet adhesion; 
(h) interfere with the normal clotting mechanism; or 
(i) cause any significant damage to the cellular elements or soluble 
components of the blood. 
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 suitably 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 such as some polymethanes which are thought to adsorb 
albumin preferentially from blood. All of these however have had 
limitations. 
We have now devised new film-forming polymers which can be used to coat 
surfaces. It has been found that these copolymers may be used to provide 
stable coatings on a wide variety of surfaces including, polyethylene, 
PVC, steel and poly(imide). The invention also provides physiadsorbable 
polymers which when used to coat surfaces, do not swell, to any 
significant extent, in aqueous environments; in some situations swelling 
in aqueous environments can reduce the stability of coatings of 
physiadsorbable polymers on surfaces. 
The polymers which contain zwitterionic groups, mimic the zwitterionic 
structure of phospholipids such as phosphatidylcholine and sphingomyelin 
which are the major components of the outer membrane of all living cells. 
In this way the present invention seeks to provide a biocompatible surface 
on a coated substrate at which the deposition of proteins and cells at the 
substrate is minimised when the coated substrate comes into contact with a 
protein-containing solution or biological fluid. 
In addition a variety of ligands may be attached to the polymers of the 
present invention when coated onto a substrate. Alternatively ligands may 
be attached to the polymers prior to coating on a substrate, e.g. when the 
polymer is in solution. The polymers of the present invention may 
therefore provide a means of attachment of such ligands. The term ligand 
includes, but is not limited to, specific binding agents such as 
immunoglobulins and associated fragments thereof such as those useful for 
affinity separation and diagnostic applications, photosensitive and 
chemisensitive moieties such as those useful for detector and sensor 
applications and therapeutic agents useful for clinical applications. 
Other ligands include peptide fragments which may be chemically linked to 
a polymer of the invention, such as fragments which induce cell attachment 
and may therefore be used to allow the polymers of the present invention 
to provide cell seeding. 
The present invention provides a polymer of one or more radical 
polymerisable, preferably ethylenically unsaturated, 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. Such coatings bind to surfaces with good adhesion and are not 
removable in the environment in which the coated surfaces are used, e.g. 
in use as a coating on a blood-contacting surface. 
Groups bearing a centre of permanent positive charge can be cationic but 
are most preferably zwitterionic. Such zwitterionic groups mimic the 
structure of the head groups of phospholipids in cells. Without wishing to 
be limited by this theory, it is thought that the presence of such groups 
at a surface renders the surface more biocompatible. 
The extent to which a polymer renders a surface biocompatible may be 
assessed as a combination of factors such as reduction in the extent to 
which the surface causes blood platelet activation, protein adsorption, 
(for instance as judged by absorption of fibrinogen from human plasma) and 
reaction with C-reactive protein which is caused by the presence on the 
surface of isolated zwitterionic, e.g. phosphate ammonium ester groups. 
Preferably the polymers of the invention when coated onto a substrate, 
provide a reduction in platelet activation of at least 70%, more 
preferably at least 90%, as assessed by the assay described hereinafter 
compared to an untreated substrate. It is also preferred that the polymers 
of the invention, when coated onto a substrate, provide a reduction in 
fibrinogen absorption of at least 60% as assessed by the assay described 
hereinafter and a protein index of less than 1.5.times.10.sup.-3 compared 
to an untreated substrate. The protein index is defined as the ratio of 
the absorbance due to C-reative protein measured in the assay described 
hereinafter to the reduction in fibrinogen adsorption. 
The nature of the groups capable of binding the polymer to a surface will 
be selected depending upon the nature of the surface which it is intended 
to coat with the polymer. Where the surface is hydrophobic, groups capable 
of being physisorbed at the surface may be used to bind the polymer to the 
surface. Where the surface is hydrophilic and bears functional groups then 
groups which are capable of reacting with surface functional groups to 
form covalent bonds may be used to bind the polymer to the surface. Where 
the surface is charged then groups bearing ionic charge may be used to 
bind the polymer to the surface by ionic interactions. 
Polymers of the invention may therefore bind to a surface by physisorption, 
covalent or ionic bonding depending upon the precise nature of the 
surface. In certain cases it may be possible to use two of these binding 
mechanisms in combination. 
The groups capable of stably binding the polymer to a surface may be 
present in the same monomer as the groups bearing a centre of permanent 
positive charge, or they may be in separate monomer species which are 
copolymerised to provide the polymer of the invention. 
It will be understood that throughout, where a group is referred to as 
capable of binding a polymer to a surface this is intended to mean stably 
binding. 
Where a hydrophobic surface is to be coated, alkyl groups of 6 or more 
carbon atoms, or fluoroalkyl groups, optionally having one or more etheric 
oxygen atoms interrupting the carbon chain, and optionally containing one 
or more carbon-carbon double or triple bonds, or siloxane groups, 
preferably containing from 1 to 50, more preferably 5 to 30, silicon 
atoms, may be used as the pendant groups capable of binding the polymer to 
a surface. Such groups are capable of forming strong secondary valence 
interactions with a surface, and being physisorbed at a hydrophobic 
surface, i.e. adsorbed without formation of a covalent interaction. 
In one embodiment the present invention therefore provides a polymer 
obtainable by 
(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 
(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. 
Such a polymer may be a copolymer comprising residues of a radical 
polymerisable, preferably ethylenically unsaturated, comonomer containing 
a group bearing a centre of permanent positive charge and of a radical 
polymerisable, preferably ethylenically unsaturated comonomer containing, 
in addition to the radical polymerisable moiety, an alkyl group of 6 or 
more carbon atoms which 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. 
Alternatively such a polymer may comprise or consist of residues of a 
radical polymerisable, preferably ethylenically unsaturated, monomer 
containing a group bearing a centre of permanent positive charge and an 
alkyl group of 6 or more carbon atoms which 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. 
In this embodiment, preferably the polymer is a copolymer comprising 
residues of a comonomer containing a physisorbable group and a comonomer 
containing a group bearing a centre of permanent positive charge. 
It is also preferred that the physisorbable group is an alkyl or 
fluoroalkyl group optionally containing one or more carbon-carbon double 
or triple bonds. Such a group may contain one or more etheric oxygen 
atoms, but in an especially preferred embodiment does not contain any 
etheric oxygen atoms. 
In one embodiment, where the physisorbable group is an alkyl or fluoroalkyl 
group, optionally containing one or more etheric oxygen atoms, this group 
does not contain any carbon-carbon double or triple bonds. 
Where a hydrophilic surface having functional groups is to be coated, 
groups capable of covalently binding the polymer to the surface may be 
incorporated into the polymer as pendant groups. 
Thus according to an alternative embodiment, the invention provides a 
polymer obtainable by: 
(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 
(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. 
Such a polymer may be a copolymer comprising residues of a radical 
polymerisable, preferably ethylenically unsaturated, comonomer containing 
a group bearing a centre of permanent positive charge and a radical 
polymerisable, preferably ethylenically unsaturated, comonomer bearing a 
reactive group and is capable of covalently binding to a surface. 
Alternatively, such a polymer may comprise or consist of residues of a 
radical polymerisable, preferably ethylenically unsaturated, monomer 
containing a group bearing a centre of permanent positive charge and a 
reactive group capable of covalently binding to a surface. 
In this embodiment, preferably the polymer is a copolymer comprising 
residues of a comonomer containing a group bearing a centre of permanent 
positive charge and a comonomer containing a reactive group capable of 
covalently binding to the surface. 
Where a surface bearing an ionic charge is to be coated, ionic groups, 
capable of binding the polymer to the surface by ionic interactions, may 
be incorporated into the polymer of the invention as pendant groups. 
According to a third embodiment, the invention therefore provides a polymer 
obtainable by: 
(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 
(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. 
Such a polymer may be a copolymer comprising residues of a radical 
polymerisable, preferably ethylenically unsaturated, comonomer containing 
a group bearing a centre of permanent positive charge, and residues of a 
comonomer containing an ionic group capable of binding to a surface by 
ionic interaction. 
Alternatively such a polymer may comprise or consist of residues of a 
radical polymerisable, preferably ethylenically unsaturated, monomer 
containing a group bearing a centre of permanent positive charge and an 
ionic group capable of binding to a surface by ionic interaction. 
In this embodiment, preferably the polymer is a copolymer comprising 
residues of a comonomer containing a group bearing a centre of permanent 
positive charge and residues of a comonomer containing an ionic group 
capable of binding to a surface by ionic interaction. 
Optionally, in any of the above embodiments, the polymers also comprise 
residues of one or more diluent and/or crosslinkable monomers. 
The invention also provides a process for producing such a polymer which 
comprises polymerising such monomers and a process for coating a surface 
with such a polymer, for instance a process comprising the steps of (a) 
polymerising such monomers to form the polymer and (b) coating the surface 
with the polymer so formed. Optionally, the process further comprises 
attaching a ligand to the polymer either in solution before coating the 
surface, or, more preferably when coated on the surface. 
In a specific embodiment the invention further provides such polymers 
containing residues of a crosslinkable monomer, which are uncrosslinked, 
when either coated on a surface or not coated on a surface and such 
polymers which are crosslinked when coated on a surface. The invention 
further provides a process of crosslinking such polymers when coated on a 
surface. 
As yet a further feature, the present invention provides certain new 
monomers useful in producing the polymers of the invention. 
Monomers and comonomers which may be used in the polymers of the invention 
will now be described in more detail. 
It is to be understood that throughout the specification (alk)acrylate, 
(alk)acrylic and (alk)acrylamide mean acrylate or alkacrylate, acrylic or 
alkacrylic and acrylamide or alkacrylamide respectively. Preferably unless 
otherwise stated alkacrylate, alkacrylic and alkacrylamide groups contain 
from 1 to 4 carbon atoms in the alkyl group thereof and are most 
preferably methacrylate, methacrylic or methacrylamide groups. Similarly 
(meth)acrylate, (meth)acrylic and (meth)acrylamide shall be understood to 
mean acrylate or methacrylate, acrylic or methacrylic and acrylamide or 
methacrylamide respectively. 
Monomers Bearing A Centre of Permanent Positive Charge. 
The monomer (or comonomer) bearing the centre of permanent positive charge 
can either be cationic or, more preferably zwitterionic. In the latter 
case the monomer includes within its structure not only a centre of 
permanent positive charge but also a centre of negative charge. Typically 
the centre of permanent positive charge is provided by a quaternary 
nitrogen atom. 
Preferred comonomers which bear a centre of positive charge are of general 
formula (I) 
EQU 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 positive charge or if Y contains a terminal 
carbon atom bonded to B, a valence bond; 
X is a group bearing a centre of permanent positive charge, preferably a 
zwitterionic group and 
Y is an ethylenically unsaturated polymerisable group selected from 
##STR1## 
wherein: R is hydrogen or a C.sub.1 -C.sub.4 alkyl group; 
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 
K is a group --(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.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. 
The proviso on whether B may be a valence bond ensures that the centre of 
permanent positive charge in X is not directly bonded to a heteroatom, 
such as an oxygen or nitrogen atom in Y. 
Preferred monomers containing a group bearing a centre of permanent 
positive charge are therefore of general formula (II) or (III). 
##STR2## 
where R, A, B, K and X are as defined with reference to formula (I). 
Preferably in the compounds of formula (II) R is hydrogen, methyl, or 
ethyl, more preferably methyl, so that (II) is an acrylic acid, 
methacrylic acid or ethacrylic acid derivative. 
In the compounds of formula (III) K may be a valence bond and B a group, K 
may be a group and B a valence bond, both K and B may be groups, or K and 
B may together be a valence bond. Preferably B is a group where K is a 
valence bond. 
Where K is a group then preferably p is from 1 to 6, more preferably 1,2 or 
3 and most preferably p is 1. When K.is a group --(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 -- or --(CH.sub.2).sub.p NR.sup.2 C(O)N.sup.2 -- then 
R.sup.2 is preferably hydrogen, methyl or ethyl, more preferably hydrogen. 
In the compounds of formula (III) preferably the vinyl group is para to the 
group --K--B--X. 
Preferably B is: 
an alkylene group of formula --CR.sup.3.sub.2).sub.a --, wherein the groups 
--CR.sup.3.sub.2)-- are the same or different, and in each group 
--CR.sup.3.sub.2)-- 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; 
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 
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 
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. 
Preferred groups B include alkylene, oxaalkylene and oligo-oxaalkylene 
groups of up to 12 carbon atoms optionally containing one or more fluorine 
atoms. Where the polymer is not intended for coating a hydrophobic 
surface, and therefore is not intended to be bound by physiosorption to a 
surface, then preferably B is an alkylene, oxaalkylene or 
oligo-oxaalkylene group which does not contain any fluorine atoms. 
In compounds of formula (III) it is preferred that K and B contain up to 12 
carbon atoms in total. 
Preferred groups X containing a centre of permanent positive charge, are 
the groups of formula (IVA), (IVB), (IVC), (IVD), (IVE) and (IVF) as 
defined below: monomers containing such groups may be used in combination 
with further monomers containing groups capable of binding to a surface, 
to provide a copolymer of the invention. Of these groups of formula 
(IVB)-(IVF) and especially (IVC) are particularly preferred. 
In addition, groups of formula (VA), (VB) and (VC) are preferred as 
monomers containing both a centre of permanent positive charge and an 
alkyl, fluoroalkyl or siloxane group capable of binding to a surface by 
physisorption. 
The groups of formula (IVA) are: 
EQU --N.sup..sym. (R.sup.5).sub.3 Z.sup..sym. (IVA) 
where the groups R.sup.5 are the same or different and each is hydrogen or 
C.sub.1-4 alkyl and Z is a counter ion. 
Preferably the groups R.sup.5 are all the same. It is also preferable that 
at least one of the groups R.sup.5 is methyl, and more preferable that all 
the groups R.sup.5 are methyl. 
The counterion Z.sup.- present in the compounds of formula (II) or (III) 
containing a group of formula (IVA) is such that the compounds are neutral 
salts. The counterion may be exchanged with ions in physiological fluids 
and thus the specific nature of the counterion is not critical in the 
present invention. However, physiologically acceptable counterions are 
preferred. Suitable physiologically acceptable counterions include halide 
anions, such as chloride or bromide ions, other inorganic anions such as 
sulphate, phosphate and phosphite and organic anions such as aliphatic 
mono-, di- or tri-carboxylate anions containing from 2 to 25 carbons atoms 
and optionally bearing one or more hydroxyl groups e.g. acetate, citrate 
and lactate. 
When X is a group of formula (IVA), preferably B is a group of formula 
--CR.sup.3.sub.2)-- or --(CR.sup.3.sub.2).sub.2 --, eg. --(CH.sub.2)-- or 
--(CH.sub.2 CH.sub.2)--. 
The groups of formula (IVB) are: 
##STR3## 
where the groups R.sup.6 are the same or different and each is hydrogen or 
C.sub.1-4 alkyl and d is from 2 to 4. 
Preferably the groups R.sup.6 are the same. It is also preferable that at 
least one of the groups R.sup.6 is methyl, and more preferable that the 
groups R.sup.6 are both methyl. 
Preferably d is 2 or 3, more preferably 3. 
When X is a group of formula (IVB) preferably B is a group of formula 
--(CR.sup.3.sub.2)-- or --(CR.sup.3.sub.2).sub.2 --, eg. --(CH.sub.2)-- or 
--(CH.sub.2 CH.sub.2)--. 
The groups of formula (IVC) are: 
##STR4## 
where the groups R.sup.7 are the same or different and each is hydrogen or 
C.sub.1-4 alkyl, and e is from 1 to 4. 
Preferably the groups R.sup.7 are the same. It is also preferable that at 
least one of the groups R.sup.7 is methyl, and more preferable that the 
groups R.sup.7 are all methyl. 
Preferably e is 2 or 3, more preferably 2. 
When X is a group of formula (IVC) preferably B is a group of formula 
--(CR.sup.3.sub.2)-- or --(CR.sup.3.sub.2).sub.2 --, eg. --(CH.sub.2)-- or 
--(CH.sub.2 CH.sub.2)--. 
The groups of formula (IVD) are: 
##STR5## 
wherein the groups R.sup.8 are the same or different and each is hydrogen 
or C.sub.1-4 alkyl, R.sup.8a is hydrogen or, more preferably, a group 
--C(O)B.sup.1 R.sup.8b where R.sup.8b is hydrogen or methyl, preferably 
methyl, B.sup.1 is a valence bond or straight or branched alkylene, 
oxaalkylene or oligo-oxaalkalyene 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. 
Preferably the groups R.sup.8 are the same. It is also preferable that at 
least one of the groups R.sup.8 is methyl, and more preferable that the 
groups R.sup.8 are all methyl. 
Preferably f is 1 or 2, more preferably 2. 
Preferably B.sup.1 is: 
a valence bond; 
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; 
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 
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. 
Preferred groups B.sup.1 include a valence bond and alkylene, oxaalkylene 
and oligo-oxaalkylene groups of up to 12 carbon atoms. 
Preferably B and B.sup.1 are the same. 
When X is a group of formula (IVD) preferably B is a group of formula 
--[(CR.sup.4.sub.2 CR.sup.4.sub.2).sub.c O.sub.b ]CR.sup.4.sub.2 
CR.sup.4.sub.2 --, eg. --(CH.sub.2 CH.sub.2 O).sub.c (CH.sub.2 
CH.sub.2)--. 
The groups of formula (IVE) are: 
##STR6## 
wherein the groups R.sup.9 are the same or different and each is hydrogen 
or C.sub.1 -C.sub.4 alkyl, R.sup.9a is a hydrogen or, more preferably, a 
group --C(O)B.sup.2 R.sup.9b, R.sup.9b is hydrogen or methyl, preferably 
methyl, B.sup.2 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. 
preferably the groups R.sup.9 are the same. It is also preferable that at 
least one of the groups R.sup.9 is methyl, and more preferable that the 
groups R.sup.9 are all methyl. 
Preferably g is 1 or 2, more preferably 2. 
Preferably B.sup.2 is: 
a valence bond; 
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; 
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 
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. 
Preferred groups B.sup.2 include a valence bond and alkylene, oxalkylene 
and oligo-oxalkylene groups of up to 12 carbon atoms. 
Preferably B and B.sup.2 are the same. 
When X is a group of formula (IVE) preferably B is a group of formula 
--[(CR.sup.4.sub.2 CR.sup.4.sub.2).sub.b O]CR.sup.4.sub.2 CR.sup.4.sub.2 
--, eg. --(CH.sub.2 CH.sub.2 O).sub.c CH.sub.2 CH.sub.2 --. 
The groups of formula (IVF) are: 
##STR7## 
wherein the groups R.sup.10 are the same or different and each is hydrogen 
or C.sub.1-4 alkyl, R.sup.10a is hydrogen or, more preferably, a group 
--C(O)B.sup.3 R.sup.10b where R.sup.10b is hydrogen or methyl, preferably 
methyl, B.sup.3 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. 
Preferably the groups R.sup.10 are the same. It is also preferable that at 
least one of the groups R.sup.10 is methyl, and more preferable that the 
groups R.sup.10 are all methyl. 
Preferably h is 1 or 2, more preferably 2. 
Preferably B.sup.3 is: 
a valence bond; 
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.3c 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; 
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 
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. 
Preferred groups B.sup.3 include a valence bond and alkylene, oxaalkylene 
and oligo-oxaalkylene groups of up to 12 carbon atoms. 
Preferably B and B.sup.3 are the same. 
When X is a group of formula (IVF) preferably B is a group of formula 
--[(CR.sup.4.sub.2 CR.sup.4.sub.2).sub.b O].sub.c CR.sup.4.sub.2 
CR.sup.4.sub.2 --, eg. --(CH.sub.2 CH.sub.2 O).sub.c CH.sub.2 CH.sub.2 --. 
Further groups bearing a centre of permanent positive charge are of formula 
(VA), (VB) and (VC). These groups also contain an alkyl or fluoroalkyl 
group capable of binding to a surface by physisorption. Monomers 
containing such a group are therefore particularly suitable for use in the 
polymers of the invention, optionally without separate comomoners 
containing a group capable of binding to a hydrophobic surface by 
physisorption. 
The groups of formula (VA) are: 
##STR8## 
wherein the groups R.sup.11 are the same or different and each is hydrogen 
or C.sub.1-4 alkyl, R.sup.11a is either 
(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.vv 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; 
(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; i 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. 
Preferably the groups R.sup.11a are the same. It is also preferable that at 
least one of the groups R.sup.11 is methyl, and more preferable that the 
groups R.sup.11 are all methyl. 
Preferably i is 1 or 2, more preferably 2. 
Where R.sup.11a is a siloxane group as defined in (a) above, each group 
(CR.sup.11b.sub.2) may be the same or different, preferably the same, and 
preferably each group R.sup.11b is hydrogen. Preferably ww is from 2 to 4, 
and is most preferably 3 when vw is 0 or 2 when vw is 1. Each group 
(SiR.sup.11c.sub.2) may be the same or different, preferably the same, and 
preferably each group R.sup.11c is methyl. Preferably w is from 4 to 29. 
Preferably the group R.sup.11a is a group --C(O)B.sup.4 R.sup.11d as 
defined above. In such a case, preferably B.sup.4 is: 
a valence bond; 
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 6 to 18; 
an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms and 
optionally one or more fluorine atoms in each alkyl moiety, or 
an oligo-oxalkylene 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. 
When B.sup.4 is a group --[(CR.sup.4d.sub.2).sub.bd O].sub.cd -- wherein 
all the groups R.sup.4d are hydrogen and in all the groups 
--[(CR.sup.4d.sub.2).sub.bd O]-- bd is 2, the residues of the monomer of 
formula (VA) are not able to form strong secondary valence interactions 
with hydrophobic surfaces. Whilst residues of such monomers may be 
included in the polymers of the invention, it is usually also necessary to 
include residues of monomers which are capable of forming strong secondary 
valence interactions if such interactions are to bind a polymer to a 
surface. 
Monomers which have groups containing oligo(higher alkylene) oxide moieties 
can be used to provide strong secondary valence interactions, so can 
monomers which contain oligo alkylene oxide moieties in which at least 50, 
preferably 70, more preferably 90 mol % of individual alkylene oxide units 
contain 3 or more carbon atoms. Thus, for instance a mixed oligo(ethylene 
oxide/propylene oxide) side chain could be used provided that there are 
more propylene oxide units than ethylene oxide units. 
When B.sup.4 is a group --[(CR.sup.4.sub.2).sub.bd O].sub.cd -- then 
preferably bd is 2 in only 50, preferably 70, more preferably 90 mole % or 
less of the residues --[CR.sup.4d.sub.2).sub.bd O]--. 
When the group --B.sup.4 --R.sup.11a is a group capable of forming strong 
secondary valence interactions with a surface, then monomers containing a 
group (VA) may be particularly suitable for use as monomers containing a 
group bearing a centre of permanent positive charge and an alkyl or 
fluoroalkyl group optionally containing one or more etheric oxygen atoms. 
Preferably, in such a case --B.sup.4 --R.sup.11a is an alkyl group 
optionally containing one or more etheric oxygen atoms and preferably 6 or 
more carbon atoms or a fluoroalkyl group optionally containing one or more 
etheric oxygen atoms and preferably 6 or more carbon atoms. 
In one embodiment B and B.sup.4 may be the same. 
The groups of formula (VB) are: 
##STR9## 
wherein the groups R.sup.12 are the same or different and each is hydrogen 
or C.sub.1 -C.sub.4 alkyl, R.sup.12a is either 
(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.u R.sub.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 
(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, 
j 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. 
Preferably the groups R.sup.12 are the same. It is also preferable that at 
least one of the groups R.sup.12 is methyl, and more preferable that the 
groups R.sup.12 are all methyl. 
Preferably J is 1 or 2, more preferably 2. 
Where R.sup.12a is a siloxane group as defined in (a) above, each group 
(CR.sup.12b.sub.2) may be the same or different, preferably the same, and 
preferably each group R.sup.12b is hydrogen. Preferably uu is from 2 to 4, 
and is most preferably 3 when tu is 0 or 2 when tu is 1. Each group 
(Sir.sup.12c.sub.2) may be the same or different, preferably the same, and 
preferably each group R.sup.12c is methyl. Preferably tt is from 4 to 29. 
Preferably the group R.sup.12a is a group --C(O)B.sup.4 R.sup.12d as 
defined above. In such a case, preferably B.sup.5 is: 
a valence bond; 
an alkylene group of formula --(CR.sup.3e.sub.2).sub.ae --, 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; 
an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms and 
optionally one or more fluorine atoms in each alkyl moiety; or 
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. 
When B.sup.5 is a group --[(CR.sup.4e.sub.2).sub.be O].sub.ce -- wherein 
all the groups R.sup.4e are hydrogen and in all the groups 
[CR.sup.4e.sub.2).sub.be O] be is 2, the residues of the monomer of 
formula (VB) are not able to form strong secondary valence interactions 
with hydrophobic surfaces. Whilst residues of such monomers may be 
included in the polymers of the invention, it is also necessary to include 
residues of monomers which are capable of forming such strong secondary 
valence interactions if such interactions are to bind a polymer to a 
surface. Monomers which have groups containing oligo(higher alkylene) 
oxide moieties can be used to provide the necessary strong secondary 
valence interactions, so can monomers which contain oligo alkylene oxide 
moieties in which at least 50, preferably 70, more preferably 90 mol % of 
individual alkylene oxide units contain 3 or more carbon atoms. Thus, for 
instance a mixed oligo(ethylene oxide/propylene oxide) side chain could be 
used provided that there are more propylene oxide units than ethylene 
oxide units. 
When B.sup.5 is a group --[(CR.sup.4c.sub.2).sub.be O].sub.ce -- then 
preferably be is 2 in only 50, preferably 70, more preferably 90 mole % or 
less of the residues --[(CR.sup.4b.sub.2).sub.be O]--. 
When the group --B.sup.5 --R.sup.12a is a group capable of forming strong 
secondary valence interactions with a surface, then monomers containing a 
group (VB) may be particularly suitable for use as monomers containing a 
group bearing a centre of permanent positive charge and an alkyl or 
fluoroalkyl group optionally containing one or more etheric oxygen atoms. 
Preferably, in such a case --B.sup.5 --R.sup.12a is an alkyl group 
optionally containing one or more etheric oxygen atoms and preferably 6 or 
more carbon atoms or a fluoroalkyl group optionally containing one or more 
etheric oxygen atoms and preferably 6 or more carbon atoms. 
In one embodiment B and B.sup.5 may be the same. 
The groups of formula (VC) are: 
##STR10## 
wherein the groups R.sup.13 are the same or different and each is hydrogen 
or C.sub.1-4 alkyl, R.sup.13a is either 
(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 
(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 
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. 
Preferably the groups R.sup.13 are the same. It is also preferable that at 
least one of the groups R.sup.13 is methyl, and more preferable that the 
groups R.sup.13 are all methyl. 
Preferably k is 1 or 2, more preferably 2. 
Where R.sup.13a is a siloxane group as defined in (a) above, each group 
(CR.sup.13b.sub.2) may be the same or different preferably the same and 
preferably each group R.sup.13a is hydrogen. Preferably ss is from 2 to 4, 
and is most preferably 3 when rs is 0 or 2 when rs is 1. Each group 
(SiR.sup.13c.sub.2) may be the same, or different, preferably the same, 
and preferably each group R.sup.13c is methyl. Preferably rr is from 4 to 
29. 
Preferably the group R.sup.13a is a group --C(O)B.sup.6 R.sup.13d as 
defined above. In such a case, preferably B.sup.6 is: 
a valence bond; 
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.sup.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; 
an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms and 
optionally one or more fluorine atoms in each alkyl moiety; or 
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. 
When B.sup.6 is a group --[(CR.sup.4f.sub.2).sub.bf O].sub.cf -- wherein 
all the groups R.sup.4f are hydrogen and in all the groups 
[(CR.sup.4c.sub.2).sub.bf O] bf is 2, the residues of the monomer of 
formula (VC) are not able to form strong secondary valence interactions 
with hydrophobic surfaces. Whilst residues of such monomers may be 
included in the polymers of the invention, it is also necessary to include 
residues of monomers which are capable of forming such strong secondary 
valence interactions if such interactions are to bind a polymer to a 
surface. Monomers which have groups containing oligo(higher alkylene) 
oxide moieties can be used to provide the necessary strong secondary 
valence interactions, so can monomers which contain oligo alkylene oxide 
moieties in which at least 50, preferably 70, more preferably 90 mol % of 
individual alkylene oxide units contain 3 or more carbon atoms. Thus, for 
instance a mixed oligo(ethylene oxide/propylene oxide) side chain could be 
used provided that these are more propylene oxide units then ethylene 
oxide units. 
When B.sup.6 is a group --[(CR.sup.4f.sub.2).sub.bf O].sub.cf -- then 
preferably bf is 2 in only 50, preferably 70, more preferably 90 mol % or 
less of the residues --[(CR.sup.4f.sub.2).sub.bf O--. 
When the group --B.sup.6 --R.sup.13a is a group capable of forming strong 
secondary valence interactions with a surface, then monomers containing a 
group (VC) may be particularly suitable for use as monomers containing a 
group bearing a centre of permanent positive charge and an alkyl or 
fluoroalkyl group optionally containing one or more etheric oxygen atoms. 
Preferably, in such a case --B.sup.6 --R.sup.13a is an alkyl group 
optionally containing one or more etheric oxygen atoms and preferably 6 or 
more carbon atoms or a fluoroalkyl group optionally containing one or more 
etheric oxygen atoms and preferably 6 or more carbon atoms. 
In one embodiment B and B.sup.6 may be the same. 
Particular examples of preferred monomers bearing a group containing a 
centre of permanent positive charge are 
2(methacryloyloxy)ethyl-2'(trimethylammonium)ethyl phosphate inner salt 
and 1[4(4'-vinylbenzyloxy)butane]-2"(trimethylammonium)ethyl phosphate 
inner salt. 
Monomers bearing a group containing a centre of permanent positive charge, 
such as those of formula (II) and (III) may be prepared by conventional 
techniques using known reactions, for example using a suitable substituted 
alkyl (alk)acrylate or suitable substituted styrene as precursor. Examples 
of suitable substituted alkyl (alk)acrylates include 
dimethylaminoethyl(meth)acrylate and 2-hydroxyethyl(meth)acrylate. 
Monomers of formula (II) or (III) containing a group of formula (IVA) may 
be prepared by known methods. Monomers containing a group of formula (IVB) 
or (IVC) may be prepared as described in Reference Example 1 to 3 or by 
analogous known methods. 
Monomers of formula (II) or (III) containing a group of formula (IVD) in 
which R.sup.8a is --C(O)B.sup.1 R.sup.8b may be prepared by selective 
acylation of glycerophosphorylcholine or analogues thereof at the primary 
hydroxyl group with an activated acid derivative such as an acid anhydride 
O(C(O)B.sup.1 R.sup.8b).sub.2 or an acid halide R.sup.8b B.sup.1 COHal 
where B.sup.1 and R.sup.8b are as defined above and Hal is halogen, 
followed by acylation of the secondary hydroxyl group with an appropriate 
acylating agent, for example methacryloyl chloride. Purification, for 
example by column chromatography on a suitable support, may be performed 
after each acylation or after the second acylation only. Suitable 
activated acid derivatives include acid anhydrides, acid halides, reactive 
esters and imidazolides. The acylations may be performed in a suitable 
anhydrous, aprotic solvent, for example N,N-dimethylformamide, optionally 
in the presence of a suitable non-nucleophilic base, for example 
triethylamine. 
Alternatively, the primary alcohol group in glycerophosphoryl choline or an 
analogue thereof may be blocked by reaction with a suitable protecting 
group reagent, for example t-butyldimethylsilyl chloride, under standard 
conditions and the secondary hydroxy group then treated with an acylating 
agent such as methacryloyl chloride. The t-butyldimethylsilyl protecting 
group may be removed by treatment with a dilute organic or mineral acid, 
for example p-toluene sulphonic acid, hydrochloric acid or with 
tetra-butylammonium fluoride. The deblocked primary hydroxyl group may 
then be treated with an activated acid derivative such as an acid 
anhydride O(C(O)B.sup.1 R.sup.8b).sub.2 or acid halide R.sup.8b B.sup.1 
COHal where B.sup.1 and R.sup.8b are as defined above, and Hal is halogen. 
Analogues of glycerophosphorylcholine (compounds of formual (II) or (III) 
containing a group (IVD) where R.sup.8a is hydrogen) may be prepared by 
reaction of phosphorus oxychloride with a bromoalcohol in an inert aprotic 
solvent, such as dichloromethane, to give a 
bromoalkylphosphorodichloridate. The dichloro derivative thus produced may 
then be treated with an appropriately protected glycerol derivative, for 
example 2,2-dimethyl 1,3-dioxolane-4-methanol, in the presence of a base, 
for example triethylamine, followed by acid hydrolysis to give a 
bromoalkylphosphoroglycerol derivative. This may then be treated with an 
amine NR.sup.8.sub.3, where R.sup.8 is as defined above, for example 
trimethylamine, to generate the glycerophosphorylcholine analogue. This 
preparation is depicted in the following scheme. 
##STR11## 
where R.sup.8 and f are as defined in relation to groups of formula (IVD). 
Monomers of formula (II) or (III) containing a group of formula (IVE) in 
which R.sup.9a is --C(O)B.sup.2 R.sup.9b may be prepared by the selective 
acylation of glycerophosphorylcholine or an analogue thereof at the 
primary hydroxyl group with for example, methacryloyl chloride followed by 
reaction at the secondary hydroxyl group using an activated acid 
derivative, such as an acid halide O(C(O)B.sup.2 R.sup.9b).sub.2 or an 
acid halide R.sup.96 B.sup.2 COHal, where B.sup.2 and R.sup.9b are as 
defined above and Hal is halogen. The intermediates and final products may 
be purified, as necessary using column chromatography. Optionally, 
protecting group strategy, similar to that outlined above in relation to 
production of monomers containing a group of formula (IVD) may be 
employed. 
Monomers of formula (II) or (III) containing a group of formula (IVF) may 
be prepared in an analogous manner to monomers containing groups of 
formula (IVD) or (IVE). 
Monomers of formula (II) or (III) containing a group of formula (VA), (VB) 
or (VC) may be prepared by direct analogy with methods described for 
monomers containing groups of formula (IVD), (IVE) and (IVF) respectively. 
Comonomers capable of stably binding a polymer to a surface 
In the polymer of the invention, where the group bearing a centre of 
permanent positive charge and group capable of stably binding the polymer 
to a surface are not present in the residue of the same monomer, the 
polymer comprises residues of comonomer containing a group capable of 
stably binding a polymer to a surface as well as the residues of the 
comonomer containing a group bearing a centre of permanent positive 
charge. Optionally, where the monomer containing a group bearing a centre 
of permanent positive charge also contains a group capable of stably 
binding the polymer to a surface, further groups capable of stably binding 
to a surface may be provided by additional comonomer residues containing a 
group capable of binding the polymer to a surface. 
As has already been mentioned, the nature of the group capable of binding 
to a surface, and therefore the nature of the comonomers containing such 
groups, will depend upon the nature of the surface which is to be coated 
with the polymer. The various types of such comonomers will now be 
described. 
It Will be appreciated that in some circumstances it may be desirable to 
use a combination of different comonomers containing groups capable of 
binding to a surface. Preferably a comonomer of type a), b) and/or c) as 
defined below or a combination of such comonomers is used, more preferably 
only one of comonomer types a), b) and c) is used. 
a) Comonomers containing an alkyl, fluoroalkyl or siloxane group 
The comonomers containing an alkyl, fluoroalkyl or siloxane group, which 
are suitable for providing binding to a hydrophobic surface, are 
comonomers containing an alkyl group of 6 or more carbon atoms which group 
optionally contains one or more etheric oxygen atoms and optionally one or 
more carbon-carbon double or triple bonds or a fluoroalkyl group, 
preferably of 6 or more carbon atoms, which group optionally contains one 
or more etheric oxygen atoms and optionally one or more carbon-carbon 
double or triple bonds, or containing a siloxane group, containing up to 
50 silicon atoms, preferably in a linear chain. 
Preferably the alkyl or fluoroalkyl groups contains up to 24 carbon atoms, 
for instance up to 18 carbon atoms, or containing a siloxane group, 
containing up to 50 silicon, preferably in a linear chain. Preferred 
comonomers containing an alkyl, fluoroalkyl or siloxane group are those of 
general formula (VI) 
EQU Y.sup.1 --Q (VI) 
where Y.sup.1 is an ethylenically unsaturated polymerisable group selected 
from 
##STR12## 
where R.sup.14 is hydrogen or C.sub.1 -C.sub.4 alkyl, 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; 
K.sup.1 is a group --(CH.sub.2).sub.l OC(O)--, --(CH).sub.l C(O)O--, 
--(CH.sub.2).sub.l OC(O)O--, --(CH.sub.2).sub.l NR.sup.16 --, 
--(CH.sub.2).sub.l NR.sup.16 C(O)--, --(CH.sub.2).sub.1 C(O)NR.sup.16 --, 
--(CH.sub.2).sub.l NR.sup.16 C(O)O--, --(CH.sub.2).sub.l OC(O)NR.sup.16 
--, --(CH.sub.2).sub.l NR.sup.16 C(O)NR.sup.16 -- (in which the groups 
R.sup.16 are the same or different), --(CH.sub.2).sub.l O--, 
--(CH.sub.2).sub.l SO.sub.3 --, a valence bond and l is from 1 to 12 and 
R.sup.16 is hydrogen or a C.sub.1 -C.sub.4 alkyl group; and 
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 
(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. 
Preferred comonomers of formula (VI) bearing a group Q include those of 
formula (VII) and (VIII): 
##STR13## 
wherein: R.sup.14, A', K.sup.1 and Q are as defined in relation to formula 
(VI). 
Preferably in the compounds of formula (VII) R.sup.14 is hydrogen methyl or 
ethyl, more preferably methyl so that the compound of formula (VII) is 
preferably an acrylic acid, methacrylic acid or ethacrylic acid 
derivative. 
In the compounds of formula (VIII) K.sup.l may for instance be a valence 
bond. Where K.sup.l is a group then preferably l is from 1 to 6, more 
preferably 1, 2 or 3 and most preferably l is 1. When K.sup.l is a group 
--(CH.sub.2).sub.l NR.sup.16 --, --(CH.sub.2).sub.l OC(O)NR.sup.16 --, 
--(CH.sub.2).sub.l NR.sup.16 C(O)O--, --(CH.sub.2).sub.l NR.sup.16 C(O)--, 
--(CH.sub.2).sub.l C(O)NR.sup.16 -- or --(CH.sub.2).sub.l NR.sup.16 
C(O)NR.sup.16 -- then R.sup.16 is preferably hydrogen, methyl or ethyl, 
more preferably hydrogen. 
In the compounds of formula (VIII), preferably the vinyl group is para to 
the group --K.sup.l --Q. 
Preferably Q is an alkyl or fluoroalkyl group optionally containing one or 
more etheric oxygen atoms and optionally one or more carbon-carbon double 
or triple bonds. More preferably Q is: 
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; 
an alkoxyalkyl having 1 to 12 carbon atoms in each alkyl moiety; 
unsubstituted or substituted by one or more fluorine atoms; or 
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 o is from 1 to 
12. 
When Q is a group --[(CR.sup.18.sub.2).sub.n O].sub.o 
(CR.sup.18.sub.2).sub.n R.sup.18 wherein all the groups R.sup.18 are 
hydrogen and in all the groups --[(CR.sup.18.sub.2).sub.n O]-- n is 2 the 
group of formula Q is not able to form strong secondary valence 
interactions with hydrophobic surfaces. Whilst residues of monomers 
containing such a group may be included in the polymers of the invention, 
it is also necessary to include residues of monomers which are capable of 
forming such strong secondary valence interactions if such interactions 
are to bind a polymer to a surface. Monomers which have groups containing 
oligo(higher alkylene) oxide moieties can be used to provide monomers 
which contain oligo alkylene oxide moieties in which at least 50 mol % of 
individual alkylene oxide units contain 3 or more carbons atoms. Thus, for 
instance a mixed oligo(ethylene oxide/propylene oxide) side chain could be 
used provided that there are more propylene oxide units than ethylene 
oxide units. 
Where Q is an (oligo-alkoxy)-alkyl group containing residues 
--[(CR.sup.18.sub.2).sub.n O]-- wherein n is 2, then preferably n is 2 in 
no more than 50 mol % of the residues --[(CR.sup.18.sub.2).sub.n O]--. 
Alternatively, Q may be a group in which one or more of the alkyl or 
alkylene moieties in such an alkyl, alkoxyalkyl or (oligoalkoxy) alkyl 
group is replaced by a corresponding alkenyl, alkynyl, alkenylene or 
alkynylene moiety. 
Preferred groups Q include alkyl, alkoxyalkyl and (oligoalkoxy)alkyl groups 
optionally containing one or more carbon-carbon double or triple bonds of 
8 or more, more preferably 10 or more, even more preferably 12 or more, 
for instance 14 or more, such as 16 or more carbon atoms. Such groups may 
contain one or more fluorine atoms and be therefore fluoroalkyl 
derivatives. Preferably however, such groups do not contain any fluorine 
atoms. 
Particularly preferred groups are straight chain alkyl or fluoroalkyl 
groups optionally containing one or more carbon-carbon double or triple 
bonds. 
Where Q is a siloxane group, each group --(CR.sup.16a.sub.2)-- may be the 
same or different, preferably the same, and preferably each group 
R.sup.16a is hydrogen. Preferably qq is from 2 to 4, and is most 
preferably 3. Each group --(SiR.sup.16b.sub.2)-- may be the same or 
different, preferably the same, and preferably each group R.sup.16b is 
methyl. Preferably pp is from 4 to 29. Preferred comonomers where Q is a 
siloxane group are those of formula (VII). 
In one specific embodiment the group Q does not contain any ethylenic 
unsaturation, i.e. any carbon-carbon double or triple bonds. 
Particular examples of comonomers containing an alkyl, fluoroalkyl or 
siloxane group include: n-dodecyl methacrylate, octadecyl methacrylate, 
hexadecyl methacrylate, 1H,1H,2H,2H-heptadecafluorodecyl methacrylate, 
p-octyl styrene, p-dodecyl styrene and monomethacryloxypropyl terminated 
siloxanes. n-Dodecyl methacrylate is particularly preferred. 
Comonomers containing a physisorbable alkyl or fluoroalkyl, which does not 
contain a carbon-carbon double or triple bond, or a siloxane group such as 
those of formulae (VII) and (VIII) are commercially available or may be 
prepared by conventional techniques using known reactions. 
In a second specific embodiment of such comonomers, the group Q does 
contain ethylene unsaturation, i.e. one or more carbon-carbon double or 
triple bonds. Such comonomers may for example contain a vinylic, 
divinylic, acetylenic or diacetylenic moiety. Comonomers containing 
acetylenic rather than vinylic unsaturation are in general preferred, 
especially those containing a single acetylenic group. 
Comonomers which contain such an ethylenic unsaturated group are capable of 
providing crosslinking between linear polymer claims once the polymer is 
coated onto a substrate, as well as binding to the substrate by 
physisorption. Such crosslinking may improve the stability of the coating 
and is typically formed by irradiation, for example with UV-or 
gamma-radiation. The crosslinking of such groups may be employed either 
alone or in addition to the use of a comonomer containing a reactive group 
as a crosslinkable comonomer as described below. 
Particularly preferred crosslinkable comoners capable of binding to a 
substrate by physisorption are those of formula (VIIA) and (VIIIA). 
##STR14## 
in which R.sup.14, A' and K.sup.1 are as hereinbefore defined and QQ is an 
alkynyl group containing 6 or more carbon atoms and one or two, preferably 
one, carbon-carbon triple bonds provided that the acetylenic moieties are 
not directly bonded to A' or K.sup.l. 
The present invention provides, as a further feature, comonomers of formula 
(VIIA) and (VIIIA). 
Amongst such comonomers it is preferred that QQ is a group containing from 
6 to 24 carbon atoms, preferably 8 or more, more preferably 10 or more, 
even more preferably 12 or more, for instance 14 or more, such as 16 or 
more carbon atoms. 
It is also preferred that the group QQ does not contain a terminal 
acetylenic moiety, i.e. a group --C.tbd.CH. 
A particularly preferred group QQ is 7-dodecynyl and a specific example of 
a compound of formula (VIIA) containing such a group is dodec-7-yn-l-ol 
methacrylate. 
The compound of formula (VIIA) and (VIIIA) and other comonomers of formula 
(VII) and (VIII) containing an ethylenically unsaturated physisorable 
group Q, may be prepared by anology with known methods. Their preparation 
is illustrated by Reference Example 5. 
b) Comonomers bearing a reactive group 
Preferred comonomers, which are suitable for providing binding to a 
hydrophilic surface having functional groups, contain a reactive group 
capable of covalently binding to a surface and are of general formula (IX) 
EQU Y.sup.2 --Q.sup.1 (IX) 
where Y.sup.2 is an ethylenically unsaturated polymerisable group selected 
from 
##STR15## 
where R.sup.19 is hydrogen or C.sub.1 -C.sub.4 alkyl, 
K.sup.2 is a group --(CH.sub.2).sub.q OC(O)--, --(CH).sub.q C(O)O--, 
--(CH.sub.2).sub.q OC(O)O--, --(CH.sub.2).sub.q NR.sup.20 --, 
--(CH.sub.2).sub.q NR.sup.20 C(O)--, --(CH.sub.2).sub.q C(O)NR.sup.20 --, 
--(CH.sub.2).sub.q NR.sup.20 C(O)O--, --(CH.sub.2).sub.q OC(O)NR.sup.20 
--, --(CH.sub.2).sub.q NR.sup.20 C(O)NR.sup.20 -- (in which the groups 
R.sup.20 are the same or different), --(CH.sub.2).sub.q O--, or 
--(CH.sub.2).sub.q SO.sub.3 --, or a valence bond and q is from 1 to 12 
and R.sup.20 is hydrogen or a C.sub.1 -C.sub.4 alkyl group; and 
Q.sup.1 is a reactive group capable of reacting to provide covalent binding 
to a surface. 
Preferred comonomers of formula (IX) bearing a reactive group Q.sup.1 
include those of formula (X) and (XI) defined below. 
The compounds of formula (X) are: 
##STR16## 
wherein: R.sup.19 is as defined with reference to formula (X), and Q.sup.2 
is a reactive group. 
Preferably in the compounds of formula (X) R.sup.19 is hydrogen, methyl or 
ethyl, more preferably methyl, so that the compound of formula (X) is 
preferably an acrylic acid, methacrylic acid or ethacrylic acid 
derivative. 
Preferably Q.sup.2 is hydrogen, or more preferably --OH or a group of the 
formula: 
EQU --T--B.sup.7 --Q.sup.3 
where 
T is --O--, or --NR.sup.21 -- where R.sup.21 is hydrogen, C.sub.1 -C.sub.4 
alkyl or a group --B.sup.7 --Q.sup.3 ; 
B.sup.7 is a valence bond or, more preferably, a straight or branched 
alkylene, oxaalkylene or oligo-oxaalkylene chain; and 
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. 
Preferably B.sup.7 is: 
an alkylene group of formula --(CR.sup.22.sub.2).sub.r --, wherein the 
groups --(CR.sup.22.sub.2)-- are the same or different, and in each group 
--(CR.sup.22.sub.2)13 the groups R.sub.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; 
an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each 
alkyl moiety; or 
an oligo-oxaalkylene group of formula --[(CR.sup.23.sub.2).sub.s O].sub.t 
(CR.sup.23.sub.2).sub.s -- where the groups --(CR.sup.22.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. 
Preferred groups B.sup.7 include alkylene, oxaalkylene and 
oligo-oxaalkylene groups of up to 12 carbon atoms. 
Where Q.sup.3 is a silane or siloxy group, preferably B.sup.7 is an 
alkylene group of 1 to 6, preferably 2 to 4, more preferably 3 carbon 
atoms. 
Particular examples of the group B.sup.7 are --CH.sub.2 --, --CH.sub.2 
CH.sub.2 -- and --(CH.sub.2).sub.6 --. 
The compounds of formula (XI) are: 
##STR17## 
wherein K.sup.2 is as defined in relation to formula (IX) and; 
B.sup.8 is a straight of branched alkylene, oxaalkylene or 
oligo-oxaalkylene chain and 
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. 
In the compounds of formula (XI) preferably the vinyl group is para to the 
group --K.sup.2 --B.sup.8 --Q.sup.4. 
K.sup.2 may for instance be a valence bond. Where K.sup.2 is a group then 
preferably q is from 1 to 6, more preferably 1,2 or 3 and most preferably 
q is 1. When K.sup.2 is a group --(CH.sub.2).sub.q NR.sup.20 --, 
--(CH.sub.2).sub.q OC(O)NR.sup.20 --, --(CH.sub.2).sub.q NR.sup.20 
C(O)O--, --(CH.sub.2).sub.q NR.sup.20 C(O)--, --(CH.sub.2).sub.q 
C(O)NR.sup.20 -- or --(CH.sub.2).sub.q NR.sup.20 C(O)NR.sup.20 -- then 
R.sup.20 is preferably hydrogen, methyl or ethyl, more preferably 
hydrogen. 
Preferably B.sup.8 is: 
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; 
an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each 
alkyl moiety; or 
an oligo-oxaalkylene group of formula --[(CR.sup.25.sub.2).sub.y 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. 
Preferred groups B.sup.8 include alkylene, oxaalkylene and 
oligo-oxaalkylene groups of up to 12 carbon atoms. In one embodiment 
B.sup.8 and K.sup.2 contain together up to 12 carbon atoms. 
Particular examples of comonomers bearing a reactive group include 
chloromethylstyrene, methacrylic acid, 2-aminoethylmethacrylate, 
2,3-epoxypropyl methacrylate, 3-chloro-2-hydroxypropylmethacrylate, 
2-methacryloyloxy-ethyl dichlorotriazine, 
3-chloro-2-hydroxy-propylmethacrylamide and glycidyl methacrylate and 
reactive methacrylate esters containing the group HetC(O)O-- in which 
(Het) is a heterocyclic ring, for example benzotriazole or imidazole and 
reactive methacrylate esters containing a group R.sup.16 OC(O)-- in which 
R.sup.16 is a succinimido or pentafluorophenyl group. 
Particularly preferred comonomers bearing reactive groups are 
2-aminoethyl-methacrylate and 3-chloro-2-hydroxypropylmethacrylate. 
Comonomers bearing a reactive group capable of binding covalently to a 
surface, such as those of formula (X) or (XI), are commercially available 
or may be prepared by conventional techniques using known reactions. 
Comonomers of formula (X), which are dichlorotriazine monomers may be 
prepared in known manner for example by reacting a substituted 
hydroxy-alkyl(alk)acrylate or aminoalkyl(alk)acrylate with 
trichlorotriazine in a suitable solvent and in the presence of a base. 
Comonomers of formula (XI) which are reactive methacrylate esters in which 
the ester groups contains an imidazole group may be prepared in known 
manner by reacting a substituted hydroxyalkyl(alk)acrylate (e.g. 
2-hydroxyethyl(meth)acrylate), polyethylene-oxide(meth)acrylate or 
polypropyleneoxide (meth)acrylate with 1,1-carbonyl-diimidazole in a dry 
solvent. Analogous known methods may be used to prepare succinimido and 
pentafluorophenyl methacrylate esters of formula (X), by reaction with a 
reactive ester, acid halide or acid anhydride. 
Where comonomers containing a reactive group are used to bind a copolymer 
to a surface by covalent bonding, it will be appreciated that not all of 
the reactive groups need necessarily bind to surface reactive groups and 
that groups not so bound may participate in other chemistry. Such groups 
may in particular provide points for the attachment of moieties such as 
ligands to the polymer, when coated onto a substrate. 
Comonomers containing a reactive group, such as compounds of formula (X) 
and (XI) may be used as comonomers containing crosslinkable groups, which 
react with other crosslinkable groups, rather than a monomer which bind 
covalently to a surface. 
Where comonomers containing a reactive group are used to provide such 
crosslinkable groups then the crosslinkable groups and/or the 
copolymerisation conditions will be chosen so that they will not crosslink 
when the comonomers are copolymerised; thus the polymerisation product 
will be an uncrosslinked linear copolymer which may be subsequently 
crosslinked after coating the copolymer onto a surface so as to improve 
the stability of the coating. When such crosslinking between linear 
polymer chains is employed the crosslinkage may be formed either between 
two such crosslinkable groups or between a crosslinkable group and a 
non-inert group in a diluent comonomer residue (defined later). Such a 
crosslinkage may be formed either by direct reaction of the groups forming 
the crosslinkage or by reaction of these groups with a reactive bridging 
molelcule for example a reactive gas, such as ammonia. 
Residues of such comonomers may therefore be present in polymers which are 
designed to coat hydrophobic surfaces and containing residues of a monomer 
containing a group bearing a centre of permanent positive charge which is 
of formula (VA), (VB) or (VC) or a comonomer containing an alkyl, 
fluoroalkyl or siloxane group, which is of formula (VII) or (VIII). 
Similarly residues of such comonomers may also be present in polymers 
designed to bind to a surface by ionic interaction and which contains 
residues of a compound of formula (XIII) or (XIV) as defined below. 
Preferred reactive comonomers which are used to crosslink the comonomer, 
rather than provide covalent binding to the surface, are those of formula 
(X) or (XI) in which Q.sup.2, or Q.sup.4 contains a crosslinkable 
cinnamyl, epoxy, --CHOHCH.sub.2 Hal (in which Hal is a halogen atom), 
methylol, silyl, an ethylenically unsaturated crosslinkable group, such as 
an acetylenic, diacetylenic, vinylic or divinylic group, or an 
acetoacetoxy or chloroalkyl sulfone, preferably chloroethyl sulphone, 
group. 
Particular examples of comonomers bearing a group capable of crosslinking 
include methacrolein, cinnamyl methacrylate, 2,3-epoxypropyl methacrylate, 
3-chloro-2-hydroxypropyl methacrylate, hydroxymethyl methacrylamide, 
3-(trimethoxysilyl)propyl methacrylate, 2-acetoacetoxyethyl methacrylate, 
3-(vinylbenzyl)-2-chloroethyl sulfone. 
When a polymer of the invention, containing crosslinkable groups, is coated 
on a substrate the polymer is in substantially uncrosslinked form. After 
coating, crosslinking of crosslinkable groups may be performed to increase 
the strength and stability of the polymer coating. 
c) Comonomers bearing an ionic group 
Preferred comonomers bearing an ionic group capable of binding to a surface 
by ionic interaction are of general formula (XII) 
EQU Y.sup.2 --B.sup.9 --Q.sup.5 (XII) 
where Y.sup.2 is an ethylenically unsaturated polymerisable group selected 
from 
##STR18## 
where R.sup.26 is hydrogen or C.sub.1 -C.sub.4 alkyl; 
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 ; 
B.sup.9 is a valence bond, a straight or branched alkylene, oxaalkylene or 
oligo-oxaalkylene group; 
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 B.sup.9) and x is from 1 to 12 and R.sup.28 is hydrogen or a C.sub.1 
-C.sub.4 alkyl group; 
Q.sup.5 is an ionic group capable of binding to a surface by ionic 
interaction. 
Preferred comonomers of formula (XII) are therefore those of formula (XIII) 
and (XIV): 
##STR19## 
wherein: R.sup.26, A", B.sup.9, K.sup.3 and Q.sup.5 are as defined in 
relation to formula (XII). 
Preferably in the compounds of formula (XIII) R.sup.26 is hydrogen, methyl 
or ethyl, more preferably methyl, so that the compound of formula (XIII) 
is preferably an acrylic acid, methacrylic acid or ethacrylic acid 
derivative. 
In the compounds of formula (XIV), K.sup.3 may for instance be a valence 
bond. Where K.sup.3 is a group then x is preferably from 1 to 6, more 
preferably 1, 2 or 3 and most preferably x is 1. When K.sup.3 is a group 
--(CH.sub.2).sub.x NR.sup.26 --, --(CH.sub.2).sub.x OC(O)NR.sup.26 --, 
--(CH.sub.2).sub.x NR.sup.26 C(O)O--, --(CH.sub.2).sub.x NR.sup.26 C(O)--, 
--(CH.sub.2).sub.x C(O)NR.sup.26 -- or --(CH.sub.2).sub.x NR.sup.26 
C(O)NR.sup.26 -- then R.sup.26 is preferably hydrogen, methyl or ethyl, 
more preferably hydrogen. 
In the compounds of formula (XIV) preferably the vinyl group is para to the 
group --K.sup.3 --B.sup.8 --Q.sup.4. 
Preferably B.sup.9 is: 
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; 
an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms in each 
alkyl moiety; or 
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. 
Preferred groups B.sup.9 include alkylene, oxaalkylene and 
oligo-oxaalkylene groups of up to 12 carbon atoms. 
Particular examples of the group B.sup.9 are --CH.sub.2 --, --CH.sub.2 
CH.sub.2 -- and --(CH.sub.2).sub.6 --. 
The group Q.sup.5 may be either anionic or cationic depending upon the 
surface to be coated. Where the surface has a cationic surface charge, the 
group Q.sup.5 will be anionic and may for example be a carboxylate, 
sulphonate, hydrogenphosphate or phosphate group. Where the surface has an 
anionic surface charge, the group Q.sup.5 will be cationic and may for 
example by a group --NR.sup.31.sub.3.sup..sym. in which each group 
R.sup.31 is the same or different, and is hydrogen or alkyl of 1 to 6 
carbon atoms two of which groups R.sup.31 may together from a heterocyclic 
ring containing from 5 to 7 atoms, preferably hydrogen or methyl, a group 
N.sup..sym. Het, where Het is an unsaturated heterocyclic group such as 
pyridyl, substituted or unsubstituted by one or more alkyl groups of 1 to 
4 carbon atoms or a group --PR.sup.32.sub.3.sup..sym. in which each group 
R.sup.32 is the same or different and is hydrogen or alkyl of 1 to 6 
carbons atoms, two of which groups R.sup.31 may together form a 
heterocyclic ring containing from 5 to 7 atoms, preferably methyl. 
Particular examples of comonomers bearing an ionic group include acrylic 
acid, methacrylic acid, 2-sulfoethyl methacrylate, 2-methacryloyloxyethyl 
phosphate, p-styrene sulfonic acid, 
2-(methacryloyloxyethyl)trimethylammonium chloride, 3-aminopropyl 
methacrylamide, vinylbenzyl trimethylammonium chloride. 
Comonomers bearing a group capable of binding a polymer to a surface by 
ionic interaction, such as those of formula (XIII) and (XIV) are 
commercially available or may be prepared by conventional techniques using 
known reactions. 
Diluent Comonomers 
In addition to a) the residues of monomers containing a group bearing a 
centre of permanent positive charge or b) the residues of comonomers 
containing a group bearing a centre of permanent positive charge and 
comonomers which are capable of binding to a surface, the polymers of the 
present invention may comprise residues of a diluent comonomer. 
Such diluent comonomers may be used to give the polymer the desired 
physical and mechanical properties. They may be of any known conventional 
radical polymerisable, preferably ethylenically unsaturated, type 
compatible with other comonomer(s). 
Particular examples of diluent comonomers include alkyl(alk)acrylate 
preferably containing 1 to 4 carbon atoms in the alkyl group of the ester 
moiety, such as methyl (alk)acrylate; a dialkylamino alkyl(alk)acrylate, 
preferably containing 1 to 4 carbon atoms in each alkyl moiety of the 
amine and 1 to 4 carbon atoms in the alkylene chain, e.g. 
2-(dimethylamino)ethyl (alk)acrylate; an alkyl (alk) acrylamide preferably 
containing 1 to 4 carbon atoms in the alkyl group of the amide moiety; a 
hydroxyalkyl (alk)acrylate preferably containing from 1 to 4 carbon atoms 
in the hydroxyalkyl moiety, e.g. a 2-hydroxyethyl (alk)acrylate; or a 
vinyl monomer such as an N-vinyl lactam, preferably containing from 5 to 7 
atoms in the lactam ring, for instance vinyl pyrrolidone; styrene or a 
styrene derivative which for example is substituted on the phenyl ring by 
one or more alkyl groups containing from 1 to 6, preferably 1 to 4, carbon 
atoms, and/or by one or more halogen, such as fluorine atoms, e.g. 
(pentafluorophenyl)styrene. 
Other suitable diluent comomers include polyhydroxyl, for example sugar, 
(alk)acrylates and (alk)acrylamides in which the alkyl group contains from 
1 to 4 carbon atoms, e.g. sugar acrylates, methacrylates, ethacrylates, 
acrylamides, methacrylamides and ethacrylamides. Suitable sugars include 
glucose and sorbitol. Particularly suitable diluent comonomers include 
methacryloyl glucose or sorbitol methacrylate. 
Further diluents which may be mentioned specifically include polymerisable 
alkenes, preferably of 2-4 carbon atoms, eg. ethylene, dienes such as 
butadiene, alkylene anhydrides such as maleic anhydride and 
cyano-substituted alkylenes, such as acrylonitrile. 
Diluent comonomers may be obtained by conventional known methods. 
Of the above diluent comonomers some are inert and act simply to modify the 
physical and mechanical properties of copolymers containing them. Others, 
and in particular the hydroxyalkyl(alk)acrylates and polyhydroxyl 
(alk)acrylates have a reactive role in addition to simply modifying 
physical and mechanical properties. Such comonomers contain functional 
groups, such as hydroxyl groups, which may react with a crosslinking group 
or may react with reactive groups in other molecules to attach them to the 
copolymer. 
It will also be appreciated that alkyl(alk)acrylates containing 6 or more 
carbon atoms in the alkyl group may be regarded as either diluent 
comonomers or comonomers capable of binding a polymer to a surface by 
physisorption. In particular it should be noted that a copolymer which 
contains such a diluent comonomer and a reactive comonomer capable of 
reacting at a surface to provide covalent binding to a surface may be used 
to coat a hydrophilic surface, the reactive comonomer providing binding to 
the surface and the diluent modifying physical and mechanical properties. 
However, such a copolymer may also be to coat hydrophobic surfaces, in 
which the "diluent" monomer will act as a comonomer capable of binding to 
the surface by physisorption and the comonomer capable of covalent binding 
will act as a crosslinkable comonomer. 
According to a feature of the present invention polymers of the invention 
may be prepared by: 
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 
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. 
Any conventional technique may be used for polymerisation, typically 
thermal or photochemical polymerisation. Where comonomers capable of 
producing crosslinking in the coated polymer film are present, the 
polymerisation condition are set such that crosslinking does not occur 
during polymerisation. Thus, for example, actinic radiation would not be 
used to prepare a polymer containing a comonomer which can form crosslinks 
by exposure to actinic radiation. 
For thermal polymerisation a temperature from 40.degree. to 100.degree. C., 
typically 50.degree. to 80.degree. C. is used. For photochemical 
polymerisation actinic radiation such as gamma, U.V., visible, or 
microwave radiation may be used. Typically U.V. radiation of wavelength 
200 to 400 nm is used. 
The polymerisation is generally performed in a reaction medium, which is 
for instance a solution or dispersion using as a solvent for example 
acetonitrile, dimethyl formamide, chloroform, dichloromethane, ethyl 
acetate, dimethyl sulphoxide, dioxan, benzene, toluene, tetrahydrofuran, 
or where the polymer does not contain groups which react with protic 
solvents, water or an alkanol containing from 1 to 4 carbon atoms, e.g. 
methanol, ethanol or propan-2-ol. Alternatively, a mixture of any of the 
above solvents may be used. 
The polymerisation may be carried out in the presence of one or more 
polymerisation initiators, such as benzoyl peroxide, 
2,2'-azo-bis(2-methylpropionitrile) or benzoin methyl ether. Other 
polymerisation initiators which may be used are disclosed in "Polymer 
Handbook", 3rd edition, Ed. J. Brandrup and E. H. Immergut, Pub. 
Wiley-Interscience, New York, 1989. 
Generally the copolymerisation is performed for 1 to 72 hours, preferably 8 
to 48, for instance 16 to 24 hours, and under an inert atmosphere of for 
example nitrogen or argon. The polymer is generally purified by dialysis, 
precipitation in a non-solvent (e.g. diethyl ether or acetone) or 
ultrafiltration. The resulting polymer is generally dried under vacuum, 
eg. for 5 to 72 hours and has a molecular weight from 10,000 to 10 
million, preferably from 20,000 to 1 million. 
The precise proportion and nature of the various comonomers used to prepare 
a copolymer according to the present invention comprising residues of a 
comonomer containing a group bearing a centre of permanent positive charge 
and a comonomer containing a group capable of stably binding the polymer 
to a surface may be adjusted to provide a copolymer which is particularly 
suitable for coating a particular surface. Thus the proportion of 
comonomer containing a group capable of stably binding the polymer to a 
surface may be adapted to provide efficient physisorption at a particular 
hydrophobic surface, to correspond to the number of functional groups at a 
particular surface or to provide efficient binding by ionic interaction 
with a particular surface. Similarly the proportion of the comonomer 
containing a group bearing a centre of permanent positive charge and of 
diluent and/or crosslinkable comonomer may be adapted to provide the 
desired biocompatibility and physical and mechanical properties. It will 
be appreciated that to obtain the desired combination of properties more 
than one type of comonomer containing a group bearing a centre of 
permanent positive charge, comonomer containing a group capable of stably 
binding the polymer to a surface or crosslinkable and/or diluent comonomer 
may be used. 
Similarly, in polymers comprising residues of a monomer containing a group 
bearing a centre of permanent positive charge and a group capable of 
stably binding the polymer to a surface, the nature of these groups may be 
adjusted to provide the desired biocompatibility and efficient binding at 
a particular surface, as well as desired physical and mechanical 
properties. Where, in addition, a diluent and/or crosslinkable comonomer 
is used the nature of the diluent and/or crosslinkable comonomer and the 
proportions of the comonomers may be likewise adjusted. It will again be 
appreciated that to obtain the desired combination of properties more than 
one type of monomer containing a group bearing a centre of permanent 
positive charge and a group capable of stably binding the polymer to a 
surface and/or more than one type of crosslinkable and/or diluent 
comonomer may be used. 
The monomer composition which is subjected to polymerisation to provide a 
polymer according to the invention comprises a minimum of 0.01%, 
preferably 1%, more preferably 5% by weight of monomer or monomers 
containing a group bearing a centre of permanent positive charge and a 
maximum of 99.9%, preferably 99%, more preferably 95% by weight of other 
monomer or monomers. Such other monomer or monomers may be a monomer or 
monomers containing a group capable of stably binding the polymer to a 
surface, a diluent monomer or monomers and/or a crosslinkable monomer or 
monomers. 
The monomer composition further comprises a minimum of 0.01%, preferably 
1%, more preferably 5% by weight of monomer or monomers containing a group 
capable of stably binding the polymer to a surface and a maximum of 99.9%, 
preferably 99%, more preferably 95% by weight of other monomer or 
monomers. Such other monomer or monomers may be a monomer or monomers 
containing a group bearing a centre of permanent positive charge, a 
diluent monomer or monomers and/or a crosslinkable monomer or monomers. 
It will be appreciated that where at least some of the monomer or monomers 
containing a group bearing a centre of permanent positive charge also 
contains a group capable of stably binding the polymer to a surface, at 
least a proportion of the content of both these groups is provided by the 
same monomer. In such a case the polymer may be a homopolymer of a monomer 
containing both these groups. 
Where the polymer is to bind to a surface by physisorption then preferably 
the monomer composition comprises no more than 95%, more preferably no 
more than 90% and even more preferably no more than 80% by weight of 
monomer or monomers containing an alkyl, fluoroalkyl or siloxane group 
which is capable of binding the polymer to a surface by physisorption and 
which does not also contain a group bearing a centre of permanent positive 
charge, the balance of the composition being monomer or monomers 
containing a group bearing a centre of permanent positive charge, diluent 
monomer or monomers and/or crosslinkable monomer or monomers. Such a 
composition typically comprises up to 50% by weight of diluent comonomer 
or comonomers. Where diluent comonomer is present, it preferably comprises 
at least 1%, more preferably 5%, by weight of the total comonomer 
composition. Where present, crosslinkable comonomer or comonomers 
generally comprise from 0.1% to 20% by weight of the total comonomer 
composition. 
Where different comonomers are used to provide the centre of permanent 
positive charge and the physisorption, then preferably the molar ratio in 
the copolymer of comonomer residues bearing a centre of permanent positive 
charge to comonomer residues containing an alkyl, fluoroalkyl or siloxane 
group capable of binding the polymer to a surface by physisorption is from 
5:95 to 80:20, more preferably 10:90 to 50:50. In addition the copolymer 
preferably comprises from 5% to 50%, more preferably 10% to 25%, by mole 
residues of diluent monomer and/or from 0.1 to 20%, more preferably 1% to 
10%, by mole residues of crosslinkable comonomer, provided that where 
residues of both diluent and crosslinkable comonomer are present, they do 
not exceed in combination 50%, preferably 35% by mole. 
Where the polymer is to bind covalently to a surface then preferably the 
monomer composition comprises no more than 25%, more preferably up to 20% 
and even more preferably up to 15% by weight of monomer or monomers 
containing a group capable of binding the polymer to a surface covalently 
and which does not also contain a group bearing a centre of permanent 
positive charge; the balance of the composition being monomer or monomers 
containing a group bearing a centre of permanent positive charge, and 
optionally diluent monomer or monomers. Such a composition typically 
comprises up to 95%, preferably to 90%, by weight of diluent comonomer or 
comonomers. Where diluent comonomer is present, it preferably comprises at 
least 5%, more preferably 10%, by weight of the total comonomer 
composition. 
Preferably the molar ratio in the copolymer of comonomer residues bearing a 
centre of permanent positive charge to comonomer residues containing a 
reactive group capable of binding the polymer to a surface by covalent 
bonding is from 5:95 to 95:5, more preferably 50:50 to 90:10. In addition, 
the copolymer preferably comprises from 5% to 50%, more preferably 10% to 
25%, by mole residues of diluent monomer and/or from 0.1% to 20%, more 
preferably 1% to 10%, by mole residues of crosslinkable comonomer, 
provided that where residues of both diluent and crosslinkable comonomer 
are present, they do not exceed in combination 50%, preferably 35% by 
mole. 
Where the polymer is to bind to a surface by ionic interaction, then 
preferably the molar ratio in the copolymer of comonomer residues bearing 
a centre of permanent positive charge to comonomer residues containing an 
ionic group capable of binding the polymer to a surface by ionic 
interactions is from 5:95 to 95:5, more preferably 50:50 to 90:10. In 
addition, the copolymer preferably comprises from 5% to 50%, more 
preferably 10% to 25%, by mole residues of diluent monomer and/or from 
0.1% to 20%, more preferably 1% to 10%, by mole residues of crosslinkable 
comonomer, provided that where residues of both diluent and crosslinkable 
comonomer are present, they do not exceed in combination 50%, preferably 
35% by mole. 
In addition the monomer or comonomer composition may comprise further 
components such as a polymerisation initiator, chain transfer agent, acid, 
base, surfactant, emulsifier or catalyst of conventional type each in an 
amount from 0.1% to 5%, typically from 0.2% to 3% and preferably about 
0.5%, by weight each relative to the total weight of the monomers. 
As a further feature the present invention provides a process for 
biocompatibilising a surface which comprises coating the surface with a 
polymer according to the present invention. Various types of surfaces may 
be coated depending upon the nature of the groups in the polymer capable 
of binding it to the surface. 
Polymers containing residues of monomers containing alkyl, fluoroalkyl or 
siloxane groups capable of binding the polymer to a surface by 
physisorption are particularly suitable for coating hydrophobic surfaces, 
e.g. polyethylene, polypropylene and polytetrafluoroethylene (PTFE) 
surfaces; fluorine containing polymers of the invention being particularly 
suited to coating PTFE surfaces. 
Hydrophilic surfaces may be rendered hydrophobic and suitable for coating 
with such polymers by known methods (see for example "Chemical Reactions 
of Polymers" Ed. E. M. Fettes, 1964, Interscience, London). 
Treatment with such a polymer is generally carried out by coating the 
surface with a solution, dispersion (including a microdispersion) of the 
polymer, generally in an alcoholic, aqueous, organic or halogenated 
solvent or a mixture thereof, e.g. methanol, ethanol, dichloromethane or 
freon. The treatment is generally carried out at ambient or elevated 
temperature, such as from 5.degree. to 60.degree. C. 
In one specific embodiment of the invention, the copolymer is coated onto 
the substrate in the form of a microdispersion for example a 
microemulsion. 
After coating the polymer may be crosslinked if it contains the residues of 
crosslinkable comonomer by known method for crosslinking the specific 
crosslinkable groups which are present. Crosslinking may, for instance, be 
introduced thermally, using actinic radiation, using reactive gases for 
example ammonia by changing the pH, using difunctional additives or by 
using activation chemistries for example by known methods as described in 
"Methods in Enzymology, volume 135, Immobilised Enzymes and Cells, part 
B", Ed. K. Mosbach, Academic Press Inc, New York, 1987. This activation 
may be performed on the dry coating, in the cases of thermal radiation or 
gas treatment. Alternatively for cases where the pH needs to be changed or 
additives need to be included, activation may be performed on the coated 
material in a solution which does not remove the coating. 
Surfaces having functional groups such as hydroxyl, carboxyl or amino 
groups are particularly suitable for treatment with polymers according to 
the invention comprising residues of monomer containing a group capable of 
binding the polymer to a surface covalently. 
Where necessary the surface of the substrate may be functionalised prior to 
treatment. For surfaces which do not have functional groups it is 
necessary to introduce these groups at the surface before treatment with 
the polymer. This can be effected by known etching or derivatising 
techniques, such as plasma discharge, which introduce the appropriate 
surface functionality (see for example "Chemical Reactions of Polymers" 
Ed. E. M. Fettes, 1964, Interscience, London). 
In certain cases it is also necessary to activate functional groups at the 
surface of the substrate and/or the reactive groups of the polymer of the 
invention. This may be achieved by known means using a known activating 
agent for example a carbodiimide such as 
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. Other suitable activating 
agents are disclosed in "Methods in Enzymology", supra. It will be 
appreciated that corresponding methods of activation of groups on a 
polymer may also be used to attach moieties, such as ligands to the 
polymer when coated on a substrate. 
Treatment with such a polymer is generally carried out by treating the 
surface with a solution of the polymer, generally an alcoholic, aqueous 
alcoholic or aqueous solution. The treatment is generally carried out at a 
temperature from -5.degree. to 50.degree. C., for from 0.1 to 24 hours and 
at a pH from 2 to 13. 
Surfaces having ionic groups such as carboxyl, sulphonate, phosphate, 
ammonium or phosphonium groups are particularly suitable for treatment 
with polymers according to the invention comprising residues of monomer 
containing a group capable of binding the polymer to ionic interaction. 
Where necessary the surface of the substrate may be functionalised prior to 
treatment. For surfaces which do not have ionic groups it is necessary to 
introduce these groups at the surface before treatment with the polymer. 
This can be effected by known etching or derivatising techniques, such as 
plasma discharge, which introduce the appropriate surface functionality 
(see for example "Chemical Reactions of Polymers" Ed. E. M. Fettes, 1964, 
Interscience, London) 
Treatment with such a polymer is generally carried out by treating the 
surface with a solution of the polymer, generally an alcoholic, aqueous 
alcoholic or aqueous solution. Treatment is generally carried out at a 
temperature from -5.degree. to 50.degree. C., for from 0.1 to 24 hours and 
at a pH from 2 to 13. 
Materials may be coated with polymers of the invention by known techniques, 
such as dip-coating, spray-coating, web-coating or spin coating. 
Materials having surfaces coated according to the present invention can be 
used as a construction material for implants or prostheses for the human 
or animal body, particularly where these implants or prostheses are to 
come into direct physical contact with blood and where biocompatibility 
and particularly haemocompatibility are required e.g. in heart valves. 
They can also be used in the construction of membranes and other devices 
that are to be brought into contact with blood or other body fluids on an 
extra-corporeal basis, for example in heart-lung machines or artificial 
kidneys. 
Additionally the polymers of the invention can be used to coat materials 
employed in down stream processing applications e.g. separation membranes 
and process equipment and tubing. In particular the materials of the 
invention can be used to modify the surface properties of biofiltration 
membranes in bioreactors and fermentation systems, where the membranes 
come into direct contact with complex biological solutions containing e.g. 
proteins, polysaccharides, fats and even whole cells. The polymers of the 
invention are particularly useful in reducing membrane fouling by the 
components of a process solution. 
When the polymers of the present invention are used to coat the surface of 
a material which is then used in the construction coat of finished 
devices, it may be necessary to take precautionary steps to ensure that 
the coated surface is not damaged and the effectiveness of the treatment 
reduced before the finished device is produced. 
In addition, the polymers of the present invention can be used to coat 
finished implants, prostheses, membranes, catheters, contact lenses, 
intraocular lenses, and other devices which are coated with a polymer 
according to the present invention to impart biocompatibility to the 
article. 
The invention thus also provides a finished device comprising a surface 
having a coating thereon of a polymer of the present invention.

The present invention will now be further illustrated by the following 
Examples: 
EXAMPLES 
The following assays have been used to evaluate coatings of polymers 
according to the present invention. 
Protein adsorption using an enzyme immunoassay 
The assay determines adsorption of human fibrinogen at a surface. This 
protein is representative of protein which is typically adsorbed at a 
surface. The assay can be readily modified to determine the adsorption of 
other proteins. 
Discs (7 mm in diameter) of untreated material (as controls) and material 
treated with polymer as described below, were prepared and washed with 
phosphate buffered saline (PBS) for at least 10 minutes in the wells of 
microplates. The samples were incubated with human plasma (300 .mu.l) for 
10 minutes and then washed with PBS three times. Each of the test samples 
and each of the control samples were treated with human 
fibrinogen-specific antibody (300 .mu.l) for 30 minutes and again washed 
with PBS three times. As a control for non-specific binding of antibody to 
the samples, each sample was also incubated with non-specific antibody 
(300 .mu.l) for 30 minutes. A conjugate of horseradish peroxidase and a 
second antibody specific to the first antibody (300 .mu.l) was added to 
both the test samples and the controls and incubated for 30 minutes before 
washing. Each of the test samples and the controls were transferred to new 
microplates and a solution of 2,2'-azino-bis(3-ethyl 
benzthiazoline-6-sulphonic acid) (ABTS) in phosphate-citrate buffer (300 
.mu.l, 0.6 mg/ml) added, the reaction was allowed to proceed for 10 
minutes. At this time an aliquot of the mixture (200 .mu.l) was removed 
and added to a solution of citric acid and sodium azide in distilled water 
(20 .mu.l, 0.21 g/ml and 2 mg/ml respectively). The optical density of the 
solutions was measured using a Techgen automated plate reader at 650 nm 
using the ABTS solution as blank. 
In an alternative procedure, rather than using ABTS, each of the samples 
was transferred to wells of new microplates and a solution of o-phenylene 
diamine (OPD) in phosphate-citrate buffer (300 .mu.l, 0.4 mg/ml) added, 
and the reaction was allowed to proceed for 10 minutes. At this time an 
aliquot of the mixture (200 .mu.l) was removed from each well and the 
optical density of the solutions was measured using a Techgen automated 
plate reader at 450 nm using the OPD solution as blank. 
Activated Platelet Study 
Blood was collected from a healthy adult volunteer using the double syringe 
method where the first 5 ml of blood is discarded. The blood was collected 
into tri-sodium citrate (32 g/l) in the proportion of 9 volumes to 1 
volume citrate in plastic tubes. The samples were kept at room temperature 
on a spiral mixer until used. 
Discs (7 mm in diameter) of untreated material as controls and material 
treated with polymers as described below were prepared and placed into the 
wells of a microplate. The samples were incubated with whole fresh 
citrated blood (200 .mu.l) on a rotary mixer for 30 minutes before washing 
in PBS four times. Platelet activation was measured by a proprietary assay 
[Lindon, J. N. et al., Blood, 68, 355 (1986)] and British Patent 
Application No. 91-25721.2]. 
In an alternative procedure half of the test replicates were incubated with 
citrated blood (200 .mu.l) and the remainder were incubated with 
EDTA-treated blood on a phase shaker for 30 minutes before washing in PBS 
four times. Platelet activation was measured in a manner similar to that 
described above for detection of proteins by enzyme immunoassay using 
antibodies against GMP140 to detect the presence of this platelet 
activation marker on the surface of biomaterials. In the presence of EDTA, 
which extracts calcium from inside platelets, activation is inhibited, so 
that incubation with EDTA-treated blood acts as a non-specific control for 
activation, obviating the need for incubation in non-specific antibody. 
C-Reactive protein (CRP) binding assay 
C reactive protein is a protein which binds specifically to isolated 
ammonium phosphate esters groups e.g. phosphoryl choline groups which are 
attached to a surface. 
Discs (7 mm in diameter) of untreated material and material treated with 
polymer as described below, were prepared and washed with HEPES-buffered 
saline (HBS) for a least 10 minutes in the wells of microplates. The 
samples were incubated in quadruplet for 45 minutes in a protein solution 
consisting of bovine serum albumin (BSA) (40 mg/ml) and CRP (0.012 mg/ml) 
in HBS and containing calcium chloride (1 mM). In parallel, identical 
samples (both coated and uncoated) were incubated either in BSA/Ca.sup.2+ 
solution in the absence of CRP, in BSA/CRP/Ca.sup.2+ solution in the 
presence of soluble phosphoryl choline (1.5 mg/ml) or in BSA/CRP solution 
containing EDTA (20 mM) rather than calcium chloride. 
After incubation, all the samples were washed in phosphate buffered saline 
(PBS) three times and then incubated for 1 hour in 300 .mu.l of a 1:100 
dilution of commercially available anti-CRP antibody conjugated with 
horseradish peroxidase. The samples were washed three times in PBS as 
before and transferred to new microplates. A solution of o-phenylene 
diamine (OPD, 0.4 mg/ml) in phosphate-citrate buffer was added and the 
reaction allowed to proceed for ten minutes. At this time an aliquot of 
the mixture (200 .mu.l) in each of the wells was transferred to a new 
well, and the optical density of the solutions measured using a Techgen 
automated plate reader at 450 nm using the OPD solution as a blank. 
A positive control containing isolated phosphoryl choline groups may be 
provided using beaded agarose immobilised with p-aminophenylphosphoryl 
choline. The specificity of CRP binding may be demonstrated by inhibition 
by phosphoryl choline and dependance upon the presence of calcium. 
Example 1 
Preparation of poly(2(methacryloyloxyethyl)-2'trimethylammonium)ethyl 
phosphate inner salt -co-n-dodecyl methacrylate (1:2) 
2(Methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(5.0 g, 0.0170 mole) and n-dodecylmethacrylate (8.55 g, 0.0340 mole) were 
dissolved in methanol/THF (140 ml, 5:9). The solution was stirred (250 
rpm) at 23.degree. C. under a stream of nitrogen (50 ml/min) for 30 
minutes. 2,2'-Azo-bis(2-methylpropionitrile) (0.17 g, 1.02 mmole) was 
added and the flow of nitrogen was reduced to 10 ml/min, the temperature 
was raised to 60.degree. C. This temperature and nitrogen flow rate were 
maintained for 16 hours. 
The mixture was allowed to cool and vacuum filtered. The filtrate was 
collected and the polymer precipitated by dropwise addition to acetone 
(1.21). 
The polymer was isolated by filtration under vacuum under a nitrogen 
atmosphere and finally dried under reduced pressure overnight at room 
temperature. The resulting polymer (9.5 g, 70%) was a fine white powder. 
In an alternative procedure, 
2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(12.06 g, 0.0409 mole) and n-dodecyl methacrylate (20.52 g, 0.0808 mole) 
were dissolved in propan-2-ol (215 ml) and ethyl acetate (85 ml). The 
solution was stirred (250 rpm) at 23.degree. C. under a stream of nitrogen 
(50 ml/min) for 30 minutes, 2,2'-azo-bis(2-methylpropionitrile) (0.0645 g, 
0.39 mmole) was added and the flow of nitrogen was reduced to 10 ml/min, 
the reaction temperature was raised to 60.degree. C. This temperature and 
nitrogen flow rate were maintained for 40 hours. 
The mixture was allowed to cool and vacuum filtered. The filtrate was 
evaporated to dryness using a rotary evaporator and dissolved in 
dichloromethane (120 ml) and methanol (10 ml). The polymer was isolated 
from this mixture by precipitation in acetone (2500 ml), vacuum filtration 
and drying. The polymer was redissolved in dichloromethane (100 ml) and 
methanol (30 ml) and isolated as described above. 
The resulting polymer, obtained in 70-80% yield was a white powder. 
NMR(200 MHz, d, ppm, CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5(s), 0.8-1.0(s) 
IR(cm.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788. 
Elemental Analysis 
______________________________________ 
theory C 64.5, H 9.9, N 1.8, P 3.9 
actual C 59.0, H 10.0, N 1.8, P 3.9 
______________________________________ 
The polymer had a relative viscosity in ethanol: chloroform (50:50) at 
25.degree. C. of 1.13.+-.0.02 (when prepared using methanol: THF as 
solvent) and 1.26.+-.0.02 (when prepared using propan-2-0l: ethylacetate 
as solvent). 
Example 2 
The coating of poly(ethylene) ribbon with 
poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner 
salt -co-n-dodecyl methacrylate (1:2) 
Poly(ethylene) ribbon was washed with ethanol and allowed to dry in the 
air. The poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate 
inner salt -co-n-dodecyl methacrylate) (1:2) (50 mg) was dissolved in 
ethanol/chloroform (5 ml, 40:1) and the poly(ethylene) coated by a one 
stage mechanical dip-coating procedure drawing the ribbon through the 
solution slowly. The coated ribbon was allowed to dry in a dust free 
atmosphere at room temperature. 
The treated poly(ethylene) showed a 65% reduction in protein adsorption as 
compared to the untreated material and a 83% reduction in platelet 
activation (determined using the assay of Lindon et al) as compared to the 
untreated material. 
In the C-reactive protein binding assay, no binding of CRP was observed to 
the treated poly(ethylene). In contrast, CRP binding was observed for a 
positive control. The specificity of this CRP binding was demonstrated by 
the fact that it was inhibited by phosphoryl choline and dependence upon 
the presence of calcium. 
According to an alternative procedure, polyethylene ribbon was washed in 
propan-2-ol and coated with the copolymer dissolved in propan-2-ol (1 g in 
100 ml) at 40.degree. C. using an otherwise analogous manner. 
Example 3 
In an analogous manner to that described in Example 2 steel and PVC 
substrates were coated with 
poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner 
salt -co-n-dodecyl methacrylate (1:2). 
The treated steel samples showed a reduction in protein adsorption of over 
80% compared to untreated samples and the treated PVC samples showed a 
reduction in protein adsorption of over 70% compared to untreated samples 
as measured by the enzyme immunoassay described above. In a further 
determination a sample of stainless steel coated with the polymer showed a 
reduction, compared to untreated material, in protein adsorption of 84% as 
determined by the enzyme immunoassay technique and a reduction of 95% in 
platelet activation as determined by the platelet activiation assay 
described above using anti-GMP140. A further sample of PVC coated with the 
polymer showed a reduction of 87% in protein adsorption and a reduction of 
100% in platelet activation, compared to untreated material, using the 
same assay techniques. 
Example 4 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-n-dodecyl methacrylate 1:4). 
2(Methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(10.00 g, 0.0339 mole) and n-dodecyl methacrylate (35.56 g, 0.1400 mole) 
were dissolved in propan-2-ol (200 ml) and ethyl acetate (200 ml). The 
solution was stirred (250 rpm) at 23.degree. C. under a stream of nitrogen 
(50 ml/min) for 30 minutes. 2,2'-azo-bis-(2-methylpropionitrile) (0.0886 
g, 0.54 mmole) was added and the flow of nitrogen was reduced to 10 
ml/min, the reaction temperature was raised to 60.degree. C. This 
temperature and nitrogen flow rate were maintained for 40 hours. 
The mixture was allowed to cool and vacuum filtered. The filtrate was 
evaporated to dryness using a rotary evaporator and dissolved in 
dichloromethane (130 ml). The polymer was isolated from this mixture by 
precipitation in acetone (2500 ml), vacuum filtration and drying. The 
polymer was redissolved in dichloromethane (120 ml) and methanol (10 ml) 
isolated as before. 
The resulting polymer, obtained in 70-80% yield was a white solid. 
NMR(200 MHz, d, ppm, CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5(s), 0.8-1.0(s) 
IR(cm.sup.-1 KBr disc) 3430, 2929, 2854 1732, 1469, 1246, 1156, 1089, 968, 
788. 
Elemental Anaylsis: 
______________________________________ 
theory C: 68.9, H 10.5, N 1.1, P 2.4 
actual C: 65.5, H 10.8, N 1.1, P 2.4 
______________________________________ 
The polymer had a relative viscosity in ethanol: chloroform (50.50) at 
25.degree. C. of 1.26.+-.0.02. 
Samples of polyethylene, steel and PVC were coated using the methods 
described in Examples 2 and 3. Using the enzyme immunoassay for protein 
adsorption, a greater than 80% reduction in protein adsorption on steel 
and greater than 70% reduction in protein adsorption on PVC were obtained. 
In a further determination, a sample of stainless steel coated with the 
polymer showed a reduction of 80% in protein adsorption (determined by the 
enzyme immunoassay described above) and a reduction of 95% in platelet 
activation (determined by the platelet activation assay described above 
using anti-GMP 140), compound to untreated material. A sample of PVC 
coated with the polymer showed a reduction of 70% in protein adsorption 
and 100% in platelet activation compound to untreated material using the 
same assay techniques. 
Example 5 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-1H, 1H, 2H,2H,heptadecafluorodecyl methacrylate 
(2:1) 
2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(1.0 g, 0.0034 mole) and 1H, 1H, 2H, 2H-heptadecafluorodecyl methacrylate 
(0.90 g, 0.0017 mole) were dissolved in methanol (10 ml) and 
tetrahydrofuran (10 ml). The solution was stirred (250 rpm) at 23.degree. 
C. under a stream of nitrogen (50 ml/min) for 30 minutes. 
2,2'-azo-bis(2-methylpropionitrile) (0.0167 g, 0.10 mmole) was added and 
the flow of nitrogen was reduced to 10 ml/min, the reaction temperature 
was raised to 60.degree. C. This temperature and nitrogen flow rate were 
maintained for 16 hours. 
The mixture was allowed to cool and vacuum filtered. The filtrate was 
evaporated to dryness using a rotary evaporator and dissolved in 
dichloromethane (10 ml) and methanol (10 ml). The polymer was isolated 
from this mixture by precipitation in acetone (500 ml), vacuum filtration 
and drying. The polymer was redissolved in dichloromethane (10 ml) and 
methanol (10 ml) and isolated as before. The resulting polymer, obtained 
in 70-80% yield was a white powder. 
NMR(200 MHz, d, ppm, CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 2.4-2.7(b), 2.2-1.7(b), 1.2-1.0(b), 0.8-1.0(b) 
The polymer was used to coat a polyvinylidene fluoride microfiltration 
membrane. The resulting coated membrane showed very little flux decline 
during processing with bovine serum albumin (BSA) indicating very little 
protein fouling. The flux change for the treated membrance was from 6000 
to 5000 l/m.sup.2 /hr compared to the flux change for the untreated 
membrane which was from 5000 to 500 l/m.sup.2 /hr. Both measurements were 
taken over a two hour period. 
Example 6 
preparation of poly(2(methacryloyloxyethyl)-2'trimethylammonium)ethyl 
phosphate inner salt-co-n-hexadecyl methacrylate (1:2) 
2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(2.00 g, 6.78 sole) and n-hexadecyl methacrylate (4.21 g, 0.0136 mole) 
were dissolved in propan-2-ol (35.5 ml) and ethyl acetate (14.5 ml). The 
solution was stirred (250 rpm) at 23.degree. C. under a stream of nitrogen 
(50 ml/min) for 30 minutes. 2,2'-azo-bis(2-methylpropionitrile) (0.0168 g, 
0.10 mmole) was added and the flow of nitrogen was reduced to 10 ml/min, 
the reaction temperature was raised to 60.degree. C. This temperature and 
nitrogen flow rate were maintained for 40 house. 
The mixture was allowed to cool and vacuum filtered. The filtrate was 
evaporated to dryness using a rotary evaporator and dissolved in 
dichloromethane (10 ml) and methanol (10 ml). The polymer was isolated 
from this mixture by precipitation in acetone (700 ml), vacuum filtration 
and drying. The polymer was redissolved in dichloromethane (10 ml) and 
methanol (10 ml) isolated as described above. The resulting polymer, 
obtained in 40-60% yield was a white solid. 
NMR(200 MHz, d, ppm, CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5 (s), 0.8-1.0(s) 
IR(cm.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788. 
Example 7 
Preparation of poly(2(methyacryloyloxyethyl)-2(trimethylammonium)ethyl 
phosphate inner salt -co-2-aminoethylmethacrylate) (9:1) 
2(Methacryloyloxyethyl)-2(trimethylammonium)ethyl phosphate inner salt 
(9.96 g, 0.0335 mole) was dissolved in methanol (115 ml). Water (10 ml) 
was added followed by the addition of 2-aminoethylmethacrylate (0.5571 g, 
0.0034 mole). The solution was stirred (250 rpm) at 22.degree. C. under a 
stream of nitrogen (70 ml/min) for 30 minutes. 
2,2'Azo-bis(2-methylpropionitrile) 0.12 g, 0.73 mmole) was added and the 
flow of nitrogen was reduced to 9 ml/min, the temperature was raised to 
60.degree. C. The temperature and nitrogen flow rate were maintained for 
16 hours. 
The mixture was allowed to cool and transferred to centrifuge tubes. The 
samples were centrifuged for 30 minutes at 4000 rpm. The samples were 
combined and the polymer precipitated by dropwise addition to acetone 
(800ml). The acetone was decanted from the polymer and the polymer washed 
with acetone (200 ml). The polymer was isolated by vacuum filtration under 
a nitrogen atmosphere and finally dried in vacuo overnight at room 
temperature. 
IR (cm.sup.-1 ; KBr disc) 3435, 2929, 2096, 1732, 1628, 1245, 1166, 1089, 
970. 
Example 8 
Treatment of poly(acrylic acid) subbed poly(imide) sheets with 
poly(2(methacryloyloxyethyl)-2(trimethylammonium)ethyl phosphate inner 
salt -co-2-aminoethylmethacrylate) (9:1). 
Poly(imide) samples were placed in the plasma chamber of a plasma barrel 
etcher and evacuated with a pump down to a pressure of 0.001 mbar. Oxygen 
was then allowed to flow into the reactor. The plasma was started with 90 
W forward power and nearly 0 W backward. The pressure was approximately 
0.7 mbar. The plasma was turned on for 5 minutes, then the radio frequency 
generator (13.56 MHz) was switched off at the same time as the flow of 
oxygen stopped. The pressure was allowed to drop and the valve of the 
flask with acrylic acid was opened to let the monomer flow into the 
chamber (100% acrylic acid). The vacuum was decreased to 0.3 mbar. The 
high frequency generator was then started with 30 W forward power and 0 W 
backward power and the polymerisation carried out for 20 minutes. After 
switching off the high frequency generator and closing the valve to the 
acrylic acid, the chamber was evaporated again for another 5 minutes to 
remove all of the excess monomer. 
The poly(acrylic acid) subbed poly(imide) was cut into 4.times.1.5 cm.sup.2 
pieces and washed with distilled water. The squares were then added to a 
1.25% solution (6.3 ml) of 
poly(2(methacryloyloxyethyl)-2(trimethylammonium)ethyl phosphate inner 
salt -co-2-aminoethylmethacrylate (9:1). 
1-Ethyl-3(3-dimethylaminopropyl)carbodiimide (20 g) was then dissolved in 
the solution and the pH then adjusted to 5.0 using hydrochloric acid (0.5 
M). After 1 hour the samples were removed, washed with distilled water and 
allowed to dry. 
Visualisation of platelet activation on a surface 
Blood was collected from a healthy adult volunteer using the double syringe 
method where the first 5 ml of blood is discarded. The blood was collected 
into tri-sodium citrate (32g/l) in the proportion of 9 volumes of blood to 
1 volume citrate in plastic tubes. The samples were kept at room 
temperature on a spiral mixer until used. 
1 cm.sup.2 samples of 
poly(2(methacryloyloxyethyl)-2(trimethylammonium)ethyl phosphate inner 
salt -co-2-aminoethylmethacrylate) (9:1) coated poly(imide) as prepared 
above and of uncoated poly(imide) as a comparison were placed into 1 ml of 
the fresh citrated blood and incubated for 30 minutes on a spiral mixer at 
room temperature. The samples were then washed in phosphate buffered 
saline (PBS,pH7.4) prior to fixing in an aliquot of the following solution 
for 30 minutes. 
2ml 25% w/v glutaraldehyde 
83 ml 0.15M PBS (pH7.4) 
15 ml Saturated picric acid. 
Picric acid increases the preservation of lipid-associated protein. The 
samples were again washed in PBS and then dehydrated using 70% and 100% 
methanol followed by 100% acetone prior to drying in air. Finally samples 
were sputter-coated with a platinum target (20 mAmps for 6.times.30 
seconds) and observed at appropriate magnifications using a scanning 
electron microscope. 
No platelet activation was seen on the coated poly(imide) samples whereas 
gross adhesion activation and aggregation were seen on the uncoated 
sample. The presence of the polymer on the surface was confirmed by the 
use of X-ray photoelectron spectroscopy (XPS). It can thus be seen that 
treatment of polyamide by first coating with a subbing layer of acrylic 
acid to render the surface reactive, and then coating with a copolymer 
according to the present invention substantially removed the haemostatic 
reaction to the polyamide. 
Example 9 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt-co-3-chloro-2-hydroxypropyl methacrylate (1:1) 
2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(7.46 g, 25.3 mmole), 3-chloro-2-hydroxypropyl methacrylate (4.51 g, 25.3 
mmole) and p-toluene sulphonic acid monohydrate (0.1048 g, 0.55 mmole) 
were dissolved in methanol (101 ml). The solution was stirred (250 rpm) at 
23.degree. C. under a stream of nitrogen (50 ml/min) for 30 minutes. 
2,2'-azo-bis(2-methylpropionitrile) (0.0843 g, 0.51 mmole) was added and 
the flow of nitrogen was reduced to 10 ml/min, the reaction temperature 
was raised to 60.degree. C. This temperature and nitrogen flow rate were 
maintained for 16 hours. 
The polymer was isolated from this mixture by precipitation in acetone 
(1500 ml), vacuum filtration and drying. The polymer was redissolved in 
methanol (40 ml) and isolated as before using acetone (1000ml). 
The resulting polymer, obtained in 62% yield was a white solid. 
NMR(200 MHz, d, ppm, CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 4.3-4.0(b), 
3.6-3.8(b), 3.3(s), 1.6-2.4(b), 1.0-1.5(b), 0.7-1.0(b). 
IR(cm.sup.-1, KBr disc) 3416, 2959, 1727, 1655, 1490, 1247, 1165, 1088, 
968, 792, 748. 
Example 10 
Preparation of poly (2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-7 dodecynmethacrylate (1:2) 
The polymer was prepared by a method analogous to that described in 
Examples 4 and 6 using 2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt (8.41 g, 0.0285 mole) and n-dodecynmethacrylate 
(14.31 g, 0.0572 mole) dissolved in propan-2-ol (160 ml) and ethyl acetate 
(60 ml). 
The resulting polymer, obtained in 35% yield was a white powder. 
NMR (100 MHz,d,ppm,CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 2.25(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5 (s), 
0.8-1.0(s) 
IR(cm.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788. 
Elemental Analysis 
______________________________________ 
theory C 65.1 H 9.0 N 1.8 P 3.9 
actual C 54.9 H 8.5 N 1.9 P 4.4 
______________________________________ 
Relative Viscosity (chloroform/ethanol 50:50 , 30.degree. C.) 1.18. 
The polymer may be crosslinked by gamma-irradiation or exposure to UV light 
which renders the polymer insoluble in dichloromethene/methanol. 
A sample of stainless steel treated with the polymer showed a reduction in 
protein adsorption of 68% (determined by the enzyme immunoassay described 
above) and a reduction in platelet activation of 100% (determined by the 
platelet activation assay described above, using anti GMP 140) compared to 
untreated material. A sample of PVC coated with the polymer showed a 
reduction in protein adsorption of 60% compared to untreated material as 
determined by the same assay technique. 
Example 11 
Preparation of poly(2(acryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-n-dodecyl methacrylate) (1:2) 
The polymer was prepared by a method analogous to that described in 
Examples 4 and 6 using 2(acryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt (3.0 g, 0.0107 mole) and n-dodecyl methacrylate (5.42 
g, 0.0214 mole) dissolved in propan-2-ol (53 ml) and ethyl acetate (22 
ml). 
The resulting polymer, obtained in 58% yield was a white solid. 
NMR(100 MHz,d,ppm,CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b),3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5(s), 0.8-1.0(s) 
IR(CM.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788. 
Elemental Analysis 
______________________________________ 
theory C 64.9 H 8.7 N 1.8 P 4.0 
actual C 57.8 H 9.8 N 2.1 P 4.9 
______________________________________ 
A sample of stainless steel treated with the polymer showed a reduction in 
protein adsorption of 53% (determined by the enzyme immunoassay described 
above) and a reduction in platelet activation of 100% (determined by the 
platelet activation assay described above, using anti-GMP140) compared to 
untreated material. A sample of PVC treated with the polymer showed a 
reduction in protein adsorption of 68% and a reduction in platelet 
activation of 100% compared to untreated material determined by the same 
assay techniques. 
Example 12 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-n-hexyl methacrylate ((1:2) 
The polymer was prepared by a method analogous to that described in 
Examples 4 and 6 using 2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt (2.0 g, 0.0068 mole) and n-hexyl methacrylate (2.31 
g, 0.0136 mole) dissolved in propan-2-ol (35.5 ml) and ethyl acetate (14.5 
ml). 
The resulting polymer, obtained in 34% yield was a white solid. 
NMR(100 MHz,d,ppm,CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b),1.2-1.5(s), 0.8-1.0(s) 
IR(cm.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788. 
Elemental Analysis 
______________________________________ 
theory C 58.8 H 8.8 N 2.2 P 4.9 
actual C 47.3 H 7.9 N 2.6 P 5.8 
______________________________________ 
Example 13 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-n-octadecyl methacrylate) (1:2) 
The polymer was prepared by a method analogous to that described in Example 
5 using 2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner 
salt (3.0 g, 0.0102 mole) and n-octadecyl methacrylate (6.90 g, 0.0204 
mole) dissolved in methanol (30 ml) and THF (70 ml). The reaction mixture 
rate was maintained for 40 hours at 60.degree. C. The polymer was isolated 
from this mixture by precipitation in acetone (1200 ml), vacuum filtration 
and drying. The resulting polymer, obtained in 55% yield was a white 
solid. 
NMR(100 MHz,d,ppm, CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5(s), 0.8-1.0(s) 
IR(cm.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788. 
Example 14 
Preparation of poly(2(methacryloyloxyethyl-2'(trimethylammonium)ethyl 
phospate inne salt -co-n-dodecyl methacrylate -co-2 
hydroxyethylmethacrylate) (17:75:8) 
The polymer was prepared by a method analogous to Examples 4 and 6, using 
2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(2.0 g, 0.0068 mole), n-dodecyl methacrylate (7.65 g, 0.0301 mole) and 
2hydroxyethyl methacrylate (0.42 g, 0.0032 mole) dissolved in propan-2-ol 
(70 ml) and ethyl acetate (30 ml). 
The resulting polymer, obtained in 53% yield was a white solid. 
NMR(100 MHz,d,ppm,CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5(s), 0.8-1.0(s). 
IR(cm.sup.-1, KBr disc) 3435, 2925, 2860, 1729, 1468, 1243, 1152, 1089, 
969, 791. 
A coating solution of 
poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phospate inner 
salt -co-n-dodecyl methacrylate -co-2-hydroxyethylmetacrylate) (0.5097 g) 
in propan-2-ol (50 ml) was prepared. Aluminium sheet was washed with 
propan-2-ol, hexane and water and dried, the coating solution (0.5 ml) was 
applied to pieces of the aluminium sheet (7.5 cm.sup.2) by a spin coating 
technique using a spin speed of 1200 rpm. 
Example 15 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-methacrylic acid (7:3) 
The polymer was prepared by a method analogous to that of Examples 4 and 6 
using 2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner 
salt (4.44 g, 0.0149 mole), and methacrylic acid (0.54 g, 0.0063 mole) 
dissolved in propan-2-ol (25 ml) and water (25 ml). The polymer was 
isolated by precipitation in acetone (500 ml), redissolved in methanol (50 
ml) and isolated by precipitation in diethylether (500 ml). 
The resulting polymer, obtained in 30% yield was a white solid. 
NMR(100 MHz,d,ppm,CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5(s), 0.8-1.0(s) 
IR(cm.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788 
This polymer was used to treat cellulose film which had been treated with 
2-aminoethyl methacrylate as follows: 
A section of cellulose dialysis membrane (4.times.6 cm) was taken, and 
placed into a solution of 2-aminopropylmethacrylate (3.34 g) and ceric 
ammonium nitrate (0.05 g) in distilled water (20 ml). The solution was 
deoxygenated with N.sub.2 for 10 minutes, then the vessel was sealed, and 
left at room temperature for 2 hours. The cellulose sample was then 
removed from the solution, then washed extensively in distilled water for 
24 hours. 
The presence of amine hydrochloride moieties on the grafted sample was 
demonstrated by the differential uptake of anionic and cationic dyes 
(Trypton blue and methylene blue respectively). 
Strips of the functionalised cellulose (0.5 cm.times.2 cm) were placed in a 
10% w/w solution of the polymer in water. The samples were left to stand 
at room temperature for 1 hour, then washed extensively in distilled water 
(200 ml) for 2 hours. 
Following the aqueous wash, the treated cellulose was placed into a 
solution of acid molybdate spray reagent and left to stand for 1 hour, 
then removed and washed with distilled water. The presence of phosphate 
groups on the sample was demonstrated by the development of a blue colour. 
Example 16 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-(2-methacryoyloxyethyl trimethylammonium chloride 
(7:3) 
2(Methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
(4.45 g, 0.0151 mole), 2-methacryolyloxyethyl trimethylammonium chloride 
(1.96 g of a 75% aqueous solution, 0.0071 mole) were dissolved in ethanol 
(50 ml). The solution was stirred (250 rpm) at 23.degree. C. under a 
stream of nitrogen (50 ml/min) for 30 minutes. 
2,2'-Azo-bis(2-methylpropionitrile) (0.02 g, 0.122 mole) was added and the 
flow of nitrogen was reduced to 10 ml/min, the reation temperature was 
raised to 60.degree. C. This temperature and nitrogen flow rate were 
maintained for 40 hours. 
The mixture was allowed to cool and filtered under vacuum. The polymer was 
isolated from this mixture by precipitation in diethylether (500 ml), 
vacuum filtration and drying. 
The resulting polymer, obtained in 68% yield was a white solid. 
NMR(100 MHz,d,ppm,CD.sub.3 OD/CDCl.sub.3) 4.2-4.4(b), 3.8-4.2(b), 
3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.5-1.8(b), 1.2-1.5(s), 0.8-1.0(s) 
IR(cm.sup.-1, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 
968, 788. 
The polymer was used to treat cellulose film which had been treated with 
3-sulfopropyl methacrylate potassium salt using the method described in 
Example 15 but using 3-sulfopropyl methacrylate potassium salt (4.92 g) 
rather than 2-aminopropyl methacrylate. 
The presence of sulphate moieties on the grafted sample was demonstrated by 
the differntial uptake of anionic and cationic dyes (Trypton blue and 
methylene blue respectively). 
Strips of the functionalised cellulose (0.5 cm.times.2 cm) were treated 
with a 10% w/w solution of the polymer in water in an analogous manner to 
that described in Example 15 and the presence of phosphate groups was 
demonstrated in the same way. 
Example 17 
Preparation of poly(2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl 
phosphate inner salt -co-n-dodecyl methacrylate (14:86) 
The polymer was prepared by a method analogous to that described in Example 
1 using a comonomer mixture consisting of 
2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
and n-dodecyl methacrylate in a molar ratio of 14:86 using 
propan-2-ol/ethylacetate solvent. 
A PVC substrate was coated with the polymer using a method analogous to 
that described in Example 3. 
Comparative Example 
The fibrinogen adsorption and C-reactive protein binding to PVC substrates 
coated with polymers of the invention in accordance with Examples 3 and 17 
was compared with that for copolymers of 
2(methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate, inner salt 
and butyl methacrylate in a molar ratio of 1:2 (Comparison A) and 14:86 
(Comparison B). The comparison copolymers were prepared by a method 
analogous to that described in Example 1 and coated onto the PVC substrate 
using a method analogous to that described in Example 3. All the 
copolymers were prepared using the procedure described under Example 1 
using a propan-2-ol/ethylacetate solvent. The results are shown in the 
following Table: 
______________________________________ 
Example Comparison 
3 17 A B 
______________________________________ 
Fibrinogen Adsorption 
87 60 82 72 
C-reative Protein 
0.094 0.043 0.101 
0.139 
Protein Index (.times. 10.sup.3) 
1.1 0.7 1.9 1.9 
______________________________________ 
The results were obtained using the assay techniques described above after 
incubation in PBS for 24 hours. The fibrinogen adsorption results are 
expressed as a percentage reduction in optical density relative to 
untreated Polyvinylidene chloride. C-reactive protein results are 
expressed as absorbance due to C-reactive protein; a positive control 
showed CRP binding. Protein index is the ratio of C-reactive protein 
binding to fibrinogen adsorption. 
These results show that in order to obtain a good reduction in protein 
adsorption using copolymers containing butylmethacrylate a high C-reactive 
protein binding must be accepted. In contrast, using longer chain alkyl 
monomers good reduction in protein adsorption and low C-reactive protein 
binding are obtained as well as good adhesion to the substrate and low 
swelling in aqueous environments. 
Copolymers containing comonomers comprising short chain alkyl groups of up 
to 4 carbon atoms as potential physisorbable groups such as butyl 
methacrylate, in smaller molar proportions, exhibit poor adhesion to 
hydrophobic substrates and are subject to high swelling in aqueous 
environments which renders them unsuitable for use in coating surfaces. 
Example 18 
Polymers from examples 1 and 4 were coated onto PVC tubing and their 
performance assessed in an extracorporeal system using a left heart bypass 
procedure in a calf model. Blood was pumped around the system continuously 
at physiological temperature in the absence of anticoagulant at a rate of 
3.5 litre per minute. Parameters associated with the condition of 
circulating blood were measured throughout the experiments. 
Virtually all the parameters tested gave results which showed that the 
presence of the coated circuit had little or no effect on the blood and 
the physiological function of the animals (typically three identical 
experiments were run on consecutive days and were very reproducible from 
animal to animal). 
In comparison with the above an uncoated circuit cannot be successfully run 
for a continuous 6 hour period without the use of anticoagulant. Also 
blood parameters are very adversely affected in a short period of time. 
Results of protein adsorption tests and macroscopic observation of circuit 
components indicate that both coatings perform at least as well as 
heparinised tubing and that, in areas of the circuit where high turbulence 
in the flow of the blood occurs, fewer clots were found. 
Reference Example 1 
Preparation of 2(methacryloyloxyethyl)-2'(trimethylammonium ethyl phosphate 
inner salt 
The preparation is illustrated by the reaction scheme A which follows. 
a) 2-Chloro-1,3-dioxaphospholane (1) 
In a flask fitted with a pressure equalising dropping funnel, reflux 
condenser (fitted with a CaCl.sub.2, guard tube) and magnetic stirrer, was 
placed a solution of phosphorus trichloride (220 ml; 346.3 g; 2.52 mol) in 
dichloromethane (500 ml). Ethylene glycol (139 ml; 154.7 g, 2.49 mol) was 
then added dropwise via the dropping funnel at such a rate that the 
evolution of HCl did not become too excessive. On the addition of the 
ethylene glycol, the condenser was arranged for distillation, and the 
dichloromethane removed at atmospheric pressure. When the distillate 
temperature reached 60.degree. C. the flask was arranged for vacuum 
distillation using a water pump, Distillation then gave 
2-chloro-1,3-dioxaphospholane (158 ml; 224.5 g; 71.3%) as a colourless 
mobile liquid (which fumes in moist air) b.pt. 36.degree.-40.degree. C./21 
mm Hg. [cf 45.5.degree.-47.degree. C./20 mm Hg, Lucas et al, J. Am. Chem. 
Soc., 72, 5491, (1950)]. 
IR (cm.sup.-1, thin film) 2980, 2905, 1470, 1210, 1005, 930, 813, 770. 
b) 2-Chloro-2-oxo-1,3,2-dioxaphospholane (2) 
In a flask fitted with a magnetic stirrer, reflux condenser (fitted with a 
CaCl.sub.2 guard tube) and sintered glass gas inlet tube, was placed a 
solution of 2-chloro-1,3-2-dioxaphospholane (100.8 g; 0.797 mol) in dry 
benzene (200 ml). The solution was stirred and a steady stream of oxygen 
was bubbled through the solution. The reaction was mildly exothermic, and 
temperature control was achieved by allowing the solvent to reflux. The 
oxygen was passed through the reaction mixture for 6 hours. The solvent 
was removed by rotary evaporation, and the colourless mobile residue 
distilled to give 2-chloro-2-oxo-1,3,2-dioxaphospholane (2) (87.41 g; 77%) 
as a colourless mobile liquid -b.pt 95.degree.-97.degree. C./0.2 mbar 
[c.f. 102.5.degree.-105.degree. C./1 mbar (Edmundson, Chem. Ind. 
(London)), 1828 (1962); 79.degree. C./0.4 mbar (Umeda et al., Makromol. 
Chem. Rapid Commun., 3, 457, (1982)]. 
IR(cm.sup.-1, thin film) 2990, 2910, 1475, 1370, 1310, 1220, 1030, 930, 
865, 830. 
c) 2(2-Oxo-1,3,2-dioxaphospholan-2-yloxy)ethyl methacrylate (3) 
In a flask fitted with a magnetic stirrer, low temperature thermometer, and 
a pressure equalising funnel fitted with a silica gel guard tube, was 
placed a solution of 2-hydroxyethylmethacrylate (20.00 g, 0.154 mol) and 
triethylamine (15.60 g; 0.154 mol) in dry diethyl ether (300 ml). The 
solution was stirred and cooled to between -20.degree. C. and -30.degree. 
C. A solution of freshly distilled 
2-chloro-2-oxo-1,3,2-dioxaphospholane(2) (21.9 g; 0.154 mol) in dry 
diethyl ether (20 ml) was then added dropwise over 30 minutes, the 
temperature being held at -20.degree. C. during the addition. Stirring was 
continued at this temperature for a further 1 hour and then for a further 
hour as the reaction mixture was allowed to warm to room temperature. The 
precipitated triethylamine hydrochloride was removed by filtration, and 
was washed well with dry ether. The ether was removed from the combined 
filtrate and washings by rotary evaporation. The cloudy oil residue was 
then shaken for 5 minutes with dry diethyl ether (50 ml) to precipitate a 
further crop of triethylamine hydrochloride, which was again removed by 
filtration. Removal of the ether on the rotary evaporator gave (3) (34.18 
g; 94.3%) as a colourless viscous oil. 
IR (cm.sup.-1, thin film) 1720, 1640, 1450, 1360, 1310, 1290, 1170, 1030, 
930, 850. 
NMR (CDCl.sub.3 ; 60 MHz, .delta. ppm) 1.95 (s,3H), 4.25-4.70 (m,8H), 5.70 
(m,1H), 6.25 (m,1H). 
Rf 0.9 (SiO.sub.2, eluting with 10% methanol:90% dichloromethane; spot 
visualised with molybdenum blue spray reagent and with iodine vapour). 
d) 2(Methacryloyloxyethyl)-2'(trimethylammonium)ethyl phosphate inner salt 
The phospholane (3) (67.20 g; 0.285 mol) was dissolved in 100 ml of dry 
acetonitrile, and placed in a heavy walled tissue culture bottle. The 
phospholane solution was then treated with a solution of anhydrous 
trimethylamine (25.74 g; 0.436 mol) in dry acetonitrile (100 ml). The 
vessel was then sealed, and placed in a water bath held at 50.degree. C. 
for 30 hours. The vessel was opened, and the solution brought to the boil. 
The solution was filtered whilst hot, and then set aside for 
crystallisation. 
The product was collected by filtration, and most of the solvent removed by 
suction. The wet product was then washed thoroughly with anhydrous ether, 
then dried under reduced pressure, to give (4) as a white amorphous, 
hygroscopic solid (51.16 g; 61%). Evaporation of the mother liquor gave a 
very viscous oil (20.00 g; 23%), from which further product (4) 
crystallised on standing at -20.degree. C. TLC (silica gel plates, eluting 
with methanol/dichloromethane (1:1 v/v)) showed one spot Rf 0.1, which was 
revealed with Dragendorff's reagent, Molybdenum blue spray reagent, and 
iodine vapour. 
IR(cm.sup.-1 1720, 1640, 1320, 1300, 1230, 1170, 970, 750. 
NMR (D.sub.2 O; 60 MHz; .delta. ppm) 2.0 (s,3H), 3.27 (s,9H) 3.60-4.50 (m, 
8H), 5.80, (m,1H) and 6.25 (m,1H). CHN Found: C 42.98%, H 7.88%, N 4.42%, 
P 10.51%. CHN Theory: C 44.75%, H 7.46%, N 4.75%, P 10.51%. 
Reference Example 2 
Synthesis of dimethyl(2-methacroyloxyethyl)-(1(2-sulphopropyl)) ammonium 
betaine inner salt 
2(Dimethylamino)ethylmethacrylate was vacuum distilled and then dissolved 
in 0.1M dichloromethane. To this solution was added an equimolar amount of 
propane sultone. The betaine slowly precipitated out of solution and was 
recovered by filtration and washed with cold dichloromethane. The reaction 
is shown in Reaction Scheme B. 
Reference Example 3 
Preparation of 1[4(4'-vinylbenzyloxy)butane]-2"-(trimethylammonium)ethyl 
phosphate inner salt. 
The synthesis is depicted in Reaction Scheme C. 
4-Hydroxy-1(4'-vinylbenzyloxy)butane (5) 
Butanediol (40 ml; 40.68 g; 0.452 mol) was stirred in a 100 ml round 
bottomed flask, and treated portionwise with potassium butoxide (17.60 g; 
0.144 mol). The initial reaction was exothermic. The reaction mixture was 
stirred for 1.5 hours at room temperature. The resulting cloudy solution 
was then treated with chloromethyl styrene (20.00 g; 0.131 mol). The 
styrene formed an upper, pale green layer, (the colouration being due to 
the presence of inhibitor), whose color darkened considerably on the 
addition of 18-crown-6 (0.49 g; 1.86.times.10.sup.-3 mole). The flask was 
stoppered, protected from light, and stirred for 28 hours at room 
temperature. The mixture was then poured into water (120 ml) and extracted 
with dichloromethane (4.times.50 ml). The combined organic extracts were 
dried (MgSO.sub.4) and evaporated to give viscous yellow oil (932.7 g). 
This oil was distilled from a small amount of CuCl to give a product 
showing some impurities on TLC. The oil was then chromatographed on silica 
gel, initially eluting with dichloromethane/petrol (1:1) to remove the 
impurities. The product was then eluted off the column with ethyl 
acetate/petrol (1:1). Evaporation of the solvent gave a colourless oil, 
which was distilled to give the desired styrylbutyl alcohol as a 
colourless oil b.pt. 150.degree.-152.degree./0.4 mbar. Yield 18.70 g; 
69.2%. 
NMR (60 MHz: CDCl.sub.3) 1.55 (m4H C--CH.sub.2 --C); 3.50 (m, 5H, 1H exch.; 
O--CH.sub.2 --, O--H), 4.45 (s,2H; Ar--CH.sub.2 --), 5.50 (dd, 2H, 
vinylic), 6.75 (dd, vinylic), 7.40 (m, 4H, Ar--H). 
IR 3402, 2938, 2888, 1631, 1602, 1582, 1511, 1480, 1445, 1382, 1320, 1116, 
1063, 920, 907, 827, 801, 716 and 667 cm.sup.-1 
4(2-Oxo-1,2,3-dioxaphospholane-2-yloxyl-1(4'-vinylbenzyloxy)butane (6) 
4-Hydroxy-1(4'-vinylbenzyloxy)butane (5) (10.03 g; 48.69 mmol) and dried 
triethylamine (4.92 g, 48.69 mmol) were dissolved in dry diethyl ether 
(150 ml) and the resulting solution placed in a rigorously dried flask. 
The solution was cooled to -30.degree. C. and 
2-chloro-2-oxo-1,3,2-dioxaphospholane (6.94 g; 48.69 mmol) added dropwise 
over 30 minutes, the temperature being held at -30.degree. C. The reaction 
mixture was then stirred for a further 2 hours, during which time the 
temperature was allowed to rise to 10.degree. C. The mixture was filtered 
and the precipitate washed with dry ether. The filtrate was evaporated 
(20.degree. C./21 mm) to give a cloudy oil. The residue was shaken with 50 
ml of dry ether and refiltered. Evaporation of the filtrate gave the 
product as a viscous yellow oil (13.73 g; 90.4%). 
TLC (eluting with 10% methanol 90% dichloromethane) showed one major spot, 
which stained with acid molybdate reagent (Rf 0.61), IR (thin film) 3458, 
2945, 2917, 2860, 1630, 1602, 1581, 1475, 1419, 1363, 1283, 1103, 1032, 
820, 842, 807, 800, 715, 610 and 421 cm.sup.-1. 
1[4(4'-Vinylbenzyloxy)butane]-2"(trimethylammonium)ethyl phosphate inner 
salt (7) 
Trimethylamine (2.00 g, 33.9 mmol) was distilled into a reaction vessel, 
and frozen with liquid nitrogen. A solution of the 
4(2-oxo-1,3,2-dioxaphospholane-2-yloxy)-1-(4'-vinylbenzyloxy)butane (6) 
(10.00 g, 32.1 mmol) in anhydrous acetonitrile (40 ml) was then added to 
the reaction vessel, which was then sealed and placed in a thermostatted 
water bath (50.degree. C. for 50 hours). The reaction vessel was then 
cooled to room temperature, opened, and the reaction mixture evaporated to 
about half its original volume (21 mm pressure). The concentrated solution 
was then stirred at room temperature, whilst anhydrous ether (200 ml) was 
added dropwise to precipitate the product as a viscous oil. The mixture 
was then left for several hours at -10.degree. C. The product was 
collected by decanting off the supernatent solid. TLC (eluting with 
methanol/dichloromethane 1:1) showed one major spot at Rf 0.01-0.1 which 
stained with both Dragendorffs reagent and acid molybdate. 
Reference Example 4 
Preparation of 2(acryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate 
inner salt 
The synthesis is essentially analogous to that described in Reference 
Example 1 and uses a synthetic strategy analogous to that shown in 
Reaction Scheme A. 
(a) 2-(2-Oxo-1,3,2-dioxaphospholan-2-yloxy)ethyl acrylate 
2-Hydroxyethyl acrylate (11.5 ml, 0.1M) and triethylamine (14.6 ml) in dry 
diethyl ether (250 ml) were cooled to -25.degree. C. under nitrogen as a 
solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.3 g) in dry diethyl 
ether was added over 20 minutes. The mixture was stirred for a further 1 
hour at -20.degree. C. and then allowed to warm to 10.degree. C. over a 
further hour. The precipitate was filtered, washed with ethyl acetate (100 
ml) and the combined filtrate and washings evaporated under reduced 
pressure to give a pale yellow oil (21 g). 
.sup.1 H NMR (200 MHz) d (CD.sub.3 CN) 6.4 (1H,dd), 6.2 (1H, dd), 5.9 
(1H,dd), 4.0-3.6 (8H,complex) ppm. 
(b) 2-(Acryloyloxyethyl)-2'-(trimethylammonium)ethyl phospate, inner salt. 
2-(2-Oxo1,3,2-dioxaphospholan-2yloxy) ethyl acrylate (21 g, 0.095M) in 
acetonitile (50 ml) was treated with a solution of triethylamine (12.1 g) 
in acetonitrile (150 ml) in a pressure reactor at 50.degree. C. for 17 
hours. The mixture was cooled and some of the excess triethylamine removed 
by evaporation under reduced pressure. 
The solid material was filtered under nitrogen, washed with acetonitrile 
(20 ml) and diethylether (50 ml) and then dried under reduced pressure to 
give a colourless oil (12.1 g, 45%). 
.sup.1 H NMR (200 MHz) d (D.sub.2 O) 6.45 (1H,dd,J1.2 and 17.1 Hz), 6.25 
(1H,dd,J1.2 and 10.25 Hz), 6.02 (1H,dd, J1.23 and 10.25 Hz), 4.4 (2H,m), 
4.3 (2H,m), 4.2 (2H,m) 3.6 (2H,m) and 3.2 (9H,s) ppm. 
Reference Example 5 
Dodec-7-yn-1-ol Methacrylate 
To dodec-7-yn-1-ol (25 g) in dichloromethane (60 ml) was added distilled 
triethylamine (14.1 g). The mixture was cooled in an ice bath (0.5.degree. 
C.) and stirred as distilled methacryloyl chloride (16.2 g) in 
dichloromethane (50 ml) was added over 10 minutes. The temperature of the 
reation was allowed to warm to ambient and the mixture stirred for two 
hours. Water (150 ml) was added and the organic layer was removed and 
successively extracted with water (2.times.150 ml) and saturated sodium 
bicarbonate solution (2.times.150 ml), washed with brine (150 ml) and 
dried over anhydrous sodium sulphate. The solvent was removed under 
reduced pressure to give a pale yellow oily liquid which was distilled 
under reduced pressure (0.18 mBar, 106.degree.-110.degree. C.) in the 
presence of copper (1) chloride to give dodec-7-yn-1-ol methacrylate, 17 
g, 50% yield. 
.sup.1 H-NMR (200 MHz,d,ppm,CDCl.sub.3): 0.90 (t,3H), 1.45 (m,10H), 1.70 
(m,2H), 1.95 (s,3H), 2.15 (m,6H), 4.15 (t,2H), 5.55 (s,1H), 6.10 (s,1H). 
##STR20##