US 6,150,432 AGranted

Polymeric blends with zwitterionic groups

AssigneeBiocompatibles Limited

InventorsStephen Alister Jones, Peter William Stratford, Steven Rimmer

Life of this patent

Estimating the term…

Loading patent…

Abstract

Disclosed is a polymer blend composition and shaped article, and a process of blending and making shaped articles of polymer blends in which the biocompatibility of various polymers is improved by blending with them a polymer including a zwitterionic group. The zwitterionic group is usually an ammonium phosphate ester, preferably a choline, zwitterionic group and the polymer containing it may be produced by the free radical polymerization of ethylenically unsaturated monomers including a monomer bearing the zwitterionic group. Blending of the two polymers may be achieved by dry blending particulate polymers or by mixing the polymers in liquid dispersion or solution followed by removal of the liquid medium. The fibrinogen absorption and/or platelet activation of polymers may be reduced to a value of less than 80% or even less than 60% of the base polymer by introducing amounts of more than 10% or more than 30% of the zwitterionic group containing polymer.

Claims34

Dependent claims

A method of improving the biocompatibility of a polymer, comprising the steps of:

(1) providing a polymer having desirable mechanical and/or physical properties in solution or dispersion in a liquid vehicle to provide a liquid polymer composition;
(2) dispersing or dissolving into the liquid polymer composition a zwitterionic polymer bearing zwitterionic pendant groups to produce a liquid blended composition;
wherein the zwitterionic polymer is formed from a radical polymerisable monomer including zwitterionic monomer of formula (I)
Y--B--X (I)
wherein B is a straight or branched alkylene, an oxaalkylene or an 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 zwitterionic moiety or if Y contains a terminal carbon bonded to B, a valence bond;
X is a zwitterionic group,
Y is an ethylenically unsaturated polymerisable group selected from ##STR22## wherein:
R is hydrogen or a C.sub.1 -C.sub.4 alkyl group;
A is --O-- or --NR'-- 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 selected from the group consisting of:
--(CH.sub.2).sub.p OC(O)--,
--(CH.sub.2).sub.p C(O)--,
--(CH.sub.2).sub.p OC(O)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)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 R.sup.2 groups are the same or different), --(CH.sub.2).sub.p O--, --(CH.sub.2).sub.p SO.sub.3 --, and 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 alkl group;
provided that the cationic moiety of the zwitterionic group is located at a distant end of the pendant X group from the B group;
and
(3) optionally in addition dispersing or dissolving into the liquid polymer composition or into the liquid blended composition at least one additive selected from the group consisting of plasticisers, fillers, colourants, UV absorbers, antioxidants and preservatives, said additives being biocompatible and
(4) removing the liquid vehicle from the liquid blended composition of step (2) or step (3) to provide a solid blend.

21 more elements

A process for producing a blend, comprising the steps of:

providing a preformed polymer (A) bearing zwitterionic pendant groups and a polymer (B) having desirable mechanical and/or physical properties, wherein polymer (A) is more hydrophilic than polymer (B) and polymer (A) and polymer (B) are both in solid particulate form;
and blending polymer (A) and polymer (B) by a technique selected from roll-milling, Banbury mixing, screw extrusion and disk compounding, to form a polymer (A)/polymer (B) blend, the blend having a superior biocompatibility than polymer (B) alone,
wherein the zwitterionic polymer is formed from a radical polymerisable monomer including zwitterionic monomer of formula (I)
Y--B--X (I)
wherein B is a straight or branched alkylene, an oxaalkylene or an 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 zwitterionic moiety or if Y contains a terminal carbon bonded to B, a valence bond;
X is a zwitterionic group,
Y is an ethylenically unsaturated polymerisable group selected from ##STR31## 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 selected from the group consisting of:
--(CH.sub.2).sub.p OC(O)--,
--(CH.sub.2).sub.p C(O)--,
--(CH.sub.2).sub.p OC(O)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)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 R.sup.2 groups are the same or different), --(CH.sub.2).sub.p O--, --(CH.sub.2).sub.p SO.sub.3 --, and 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;
and wherein, in the zwitterionic polymer, X is a zwitterionic group in which the anionic moiety is a phosphate group.

18 more elements

A method of improving the biocompatibility of a polymer, comprising the steps of:

(1) providing a polymer B having desirable mechanical and/or physical properties in solution or dispersion in a liquid vehicle to provide a liquid polymer composition;
(2) dispersing or dissolving into the liquid polymer composition a zwitterionic polymer A bearing zwitterionic pendant groups to produce a liquid blended composition;
(3) optionally in addition dispersing or dissolving into the said liquid polymer composition or into said liquid blended composition at least one additive selected from the group consisting of plasticisers, tillers, colourants, UV absorbers, antioxidants and preservatives, said additives being biocompatible;
and
(4) removing the liquid vehicle from the liquid blended composition of steps (2) or step (3) to provide a solid blend;
in which the zwitterionic polymer A is formed from radical polymerisable monomers including at least 5 mole % zwitterionic monomer of formula (I)
Y--B--X (I)
wherein B is a straight or branched alkylene, an oxaalkylene or an 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 zwitterionic moiety or if Y contains a terminal carbon bonded to B, a valence bond;
X is a zwitterionic group,
Y is an ethylenically unsaturated polymerisable group selected from ##STR34## wherein:
R is hydrogen or a C.sub.1 -C.sub.4 alkyl;
A is --O-- or --NR.sup.1 is a 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 selected from the group consisting of:
--(CH.sub.2).sub.p OC(O)--,
--(CH.sub.2).sub.p C(O)O--,
--(CH.sub.2).sub.p OC(O)O--,
--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)NR.sup.2 C(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 R.sup.2 groups are the same or different), --(CH.sub.2).sub.p O--, --(CH.sub.2).sub.p SO.sub.3 --, and, 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;
and
wherein the solid blend contains at least 10% by weight of said zwitterionic polymer A.

22 more elements

Dependencies are inferred from the claim text.