Biocompatibles Limited

Biocompatibles UK Limited

University College London

Biccompatibles Limited

Stephen A Jones

Peter William Stratford

Roderick W Bowers

Michael John Driver

Roderick William Jonathon Bowers

Stephen Alexander Charles

Peter W Straford

Andrew Victor Graham Muir

Steven Rimmer

Andrew Lennard Lewis

Sean Leo Willis

Lee Rowan

Jeremy Colin Russell

Richard Paul Redman

Vincent James O'Byrne

Bruce Duncan Samuel Allan

Roderick William Bowers

David Michael Grey

John Charles Stedman

Stephen Rimmer

Samantha Ryan

Roderick W J Bowers

A novel class of polymers obtainable by copolymerising a monomer mixture comprising (i) hydrophilic monomer of general formula (I) Y&#x2014;B&#x2014;X; (ii) styrene or a substituted styrene, a monomer or mixture of monomers which when polymerized form a polymer with a Tg lower than the Tg of a homopolymer of monomer (I) and lower than the Tg of a homopolymer of monomer (ii); and a monomer having a crosslinkable group is described. The invention also relates to a method for producing such polymers, implants coated with the polymers and methods for forming the same.

Polymer

A biocompatibilizing process in which a substrate having a surface which bears substrate pendant functional groups is biocompatibilized by coating it with a coating composition containing a polymer formed from a radical polymerizable monomers including a radical polymerisable zwitterionic monomer and a radical polymerizable monomer containing a reactive group to form a polymer having zwitterionic groups and pendant reactive groups and the said pendant reactive groups are reacted to form covalent bonds with said substrate pendant functional group and thereby form a stable coating of polymer on the said surface.

Polymeric surface coatings

A polymer is formed of ethylenically unsaturated monomers including a zwitterionic monomer, an aromatic monomer and a cross-linking monomer. Preferably the crosslinking monomer includes at least one a group containing compound and at least one aliphatic group containing compound. The polymer is water-swellable and a hydrogen has optical and mechanical properties rendering it suitable for use as an intraocular refractive device such as an intraocular lens.

Crosslinked polymers and refractive devices formed therefrom

A biocompatibilising process in which a substrate having a surface which bears substrate pendant functional groups is biocompatibilised by coating it with a coating composition containing a polymer formed from a radical polymerisable monomers including a radical polymerisable zwitterionic monomer and a radical polymerisable monomer containing a reactive group to form a polymer having zwitterionic groups and pendant reactive groups and the said pendant reactive groups are reacted to form covalent bonds with said substrate pendant functional group and thereby form a stable coating of polymer on the said surface.

Cross-linked copolymers which are obtainable by polymerising a neutral diluent monomer or monomers, a monomer or monomers bearing a center of permanent positive charge, and a bifunctional and/or trifunctional cross-linking agent, are suitable for use in contact lenses. Process for producing them by copolymerization, contact lens material comprising them, contact lenses made of them and processes for producing contact lenses from them.

Contact lens material

Cross-linked copolymers which are obtainable by polymerizing a neutral diluent monomer or monomers, a monomer or monomers bearing a center of permanent positive charge, and a bifunctional and/or trifunctional cross-linking agent, are suitable for use in contact lenses. Process for producing them by copolymerization, contact lens material comprising them, contact lenses made of them and processes for producing contact lenses from them.

The biocompatibility of various polymers are improved by blending with them a polymer including a zwitterionic group. The zwitterionic group is usually an ammonium phosphate ester zwitterionic group and the polymer containing it may be produced by the free radical polymerisation 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. Preferred blends are of copolymers of 2-(methacryloyloxyethyl)-2&prime;-(trimethylammonium)ethyl phosphate inner salt with higher alkyl(meth)acrylate, blended with olefin polymers and/or with rubber latices. The products may be used in medical devices in which they come into contact with bodily fluids, especially blood, plasma, serum and/or tear film.

Polymeric blends with zwitterionic groups

A non-crosslinked biocompatible polymer is formed from a radical polymerisable ethylenically unsaturated zwitterionic monomer containing a sulpho-betaine zwitterionic group and a radical polymerisable ethylenically unsaturated comonomer containing a hydrophobic group selected from C,-alkyl, C,-fluoroalkyl and siloxane groups. Suitable copolymers are of N,N-dimethyl ammonium-N-propylsulphonate-N-ethyl methacrylate and dodecylmethacrylate. The polymer may be used to coat substrates to render them biocompatible, especially hemocompatible. The hydrophobic groups render the polymer particularly suitable for coating hydrophobic substrates.

A biocompatibilizing process in which the surface of a material in need of being biocompatibilized is coated with a copolymer formed by radical polymerization of ethylenically unsaturated monomers comprising a zwitterionic monomer having a sulphobetaine group and a comonomer having a group selected for providing a stable coating of polymer on the said surface. The comonomer may have a hydrophobic group for binding to oppositely charged ionic groups at the surface or a reactive group for forming a covalent bond with functional groups at the surface and/or for forming cross-links in the polymer coating.

Biocompatibilizing process

A glaucoma filtration implant is constituted by a generally tubular body section having an oblong external diameter formed of a continuous convex curve. The device preferably has flow resistance structure provided by a portion of the internal lumen having a reduced diameter. The flow resistance structure may have a length of up to 5000 &mgr;m and a diameter in the range 15 to 50 &mgr;m, the diameter being selected so as to achieve a pressure drop along the flow resistance structure in the range 5 to 15 mm Hg. The internal conduit for liquid flow also may include a removable flow inhibitor, which can be removed after implantation by a laser, such as an ophthalmic YAG laser. The device is made of biocompatible materials.

Device for use in the eye

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.

A non-crosslinked polymer having pendant zwitterionic groups and pendant functional groups can be coated from a coating composition onto a surface having pendant coreactive functional groups and, after coating, may be cured so that covalent bonds are formed between the coreactive functional groups on the polymer and the surface. Alternatively the polymer can be crosslinked after coating, by formation of covalent intermolecular cross-links between coreactive pendant functional groups on the polymer. The zwitterionic pendant groups preferably have, as the anion, a phosphate ester group, and as the cation, a quaternary ammonium group. The polymer coating is stable and provides improved biocompatibility, especially haemocompatibility.

Polymers of one or more radical polymerisable 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 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.

Polymers of one or more radical polymerisable 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.

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Middlesex, United Kingdom

Stephen A Jones