Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Processes of preparing a desired or intentional composition...
Reexamination Certificate
2000-04-14
2002-05-28
Szekely, Peter (Department: 1714)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Processes of preparing a desired or intentional composition...
C523S106000, C523S331000, C523S340000, C524S510000, C524S515000, C524S521000, C524S523000, C524S547000, C525S183000, C525S217000
Reexamination Certificate
active
06395800
ABSTRACT:
The present invention relates to new polymeric materials, especially suitable for use in biomedical applications, processes for their production, articles formed from such materials and processes for modifying the physical and biological properties of plastic materials. The medical device industry frequently employs a range of thermoplastic, elastomeric and thermoset materials in medical devices. Many of these polymers were originally developed as engineering materials and their physical and mechanical properties reflect this. Thus a plastic may be employed as a medical device because it posseses physical and mechanical properties suitable for use in a biological environment. However, until recently little attention was paid to the biological properties of these materials. This has resulted in a number of problems with current device materials as a result of adverse biological reactions. Silicone rubbers have been shown to leach toxic silicones when implanted, polyurethanes have been found to degrade by macrophage attack and natural rubbers have caused severe allergic reactions. In addition, PVC, a widely used polymer for medical devices, often contains large quantities of the plasticiser bis-(2-ethylhexyl)phthalate and many studies now show this to be toxic. It is clear, therefore, that many materials possess properties which render them unsuitable for use in biological applications.
Previous attempts to prepare biocompatible materials have mimicked the surface of platelet cells which under normal circumstances exist in the blood without causing any adverse reactions. These cell membranes comprise a phospholipid bilayer with the phosphorylcholine group dominating the external membrane surface. It is believed this outer surface avoids adverse reaction with other biological components. Lipids containing phosphorylcholine groups have been coated on to the surface of device materials and bloodclotting studies showed that they rendered the surface more biocompatible (J A Hayward & D Chapman, Biomaterials, Vol. 5, 135, 1984). These phospholipids have also been used as plasticisers in commercial polymers and have again improved the biocompatibility of the base material (WO-A-87/02684). However these two approaches nevertheless possess disadvantages.
Coating the surface of a finished device has a number of problems, one being the difficulty in coating devices with complex shapes or multiple components; in practice a multi-component device can be impossible to coat. In addition the degree of biocompatibility is dependent on the quality of the coating and how strongly it is bound to the surface; thus defects or scratches in the coating will reduce its effectiveness. The use of a lipid as a plasticiser goes some way to overcome these problems, but the lipid is free to move through the material and can eventually leach out of the system. This can again lead to a reduction in the level of biocompatibility. The lipid also has in addition no mechanical strength and can therefore only be used to soften the base polymer.
We have now devised new blended polymeric materials which seek to overcome these disadvantages. The blends combine the desirable physical and/or mechanical properties of an engineering polymer with the biocompatible properties of a polymer bearing pendant zwitterionic, for example phosphoryl choline, groups.
The present invention accordingly provides a polymer blend comprising:
(A) a polymer bearing zwitterionic pendant groups; and
(B) a polymer having desirable mechanical and/or physical properties.
The extent to which a polymer bearing zwitterionic pendant groups (A) renders a further polymer biocompatible in a blend may be assessed as a combination of factors such as reduction in the extent to which the blend causes blood platelet activation and protein adsorption, (for instance as judged by absorption of fibrinogen from human plasma).
(A) Polymer Bearing Zwitterionic Pendant Groups
The polymer bearing zwitterionic pendant groups may be either a homopolymer or a copolymer. Preferably it is a polymer of residues of one or more radically polymerisable monomers, more preferably ethylenically unsaturated monomers. Preferably the polymer bears zwitterionic pendant groups by virtue of one of the starting monomers from which it is produced carrying such a group. Instead the zwitterionic group may be introduced onto a preformed polymer, for instance by reactions such as are disclosed in EP-A-0157469, WO-A-9113639, WO-A-9207858 or WO-A-9305081. The polymer may be a condensation polymer, for instance a polyurethane or a polyester. Again the zwitterionic group is present on the polymer either by incorporation as a pendant group on one of the starting monomers or by post-reaction of a preformed polymer. Polyurethanes are described in WO-A-8602933 and WO-A-89305081 and polyesters and described in WO-8800956.
Preferably the zwitterionic group is a group X as defined below.
Preferably the polymer is a copolymer of a comonomer containing a zwitterionic group and a comonomer containing an alkyl, usually a hydrophobic group, a reactive functional group, or an ionic group. The presence of residues of such comonomers may serve to improve the compatability of the polymer (A) for the polymer (B) in the blend of the present invention. Copolymers containing residues of a comonomer which contain a hydrophobic group are particularly preferred.
As examples of comonomers containing as hydrophobic groups, mention may be made of comonomers containing as pendant groups alkyl groups 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 ones. Alternatively such comonomers may contain as pendant groups siloxane groups, preferably containing from 1 to 50, more preferably 5 to 30, silicon atoms.
The nature of such hydrophobic groups may be chosen for comparability with polymer (B). For example comonomers containing a hydrophobic fluoroalkyl group are particularly suitable for blending with fluoropolymer such as polyvinylidene fluoride (PVDF).
Alternatively, the polymer may comprise residues of a monomer containing both a zwitterionic group and such a hydrophobic group.
Preferably, such a hydrophobic group is an alkyl or fluoroalkyl group, optionally containing one or more carbon-carbon double or triple bonds. More preferably, the hydrophobic group does not contain any ethylenic unsaturation.
Alternatively, or in addition, such copolymers may further comprise residues of a comonomer containing a reactive functional group or an ionic group. Such reactive groups may serve to crosslink the copolymer (A) and/or bind the copolymer (A) to the polymer (B) having desirable physical and/or mechanical properties. In addition such reactive groups may provide reactive moieties at the surface of the blend. Use of a comonomer of containing ionic groups may serve to improve the miscability of the polymer (A) with polymer (B) where polymer (B) itself bears ionically charged groups.
In addition, the polymer (A) may further comprise residues of one or more diluent comonomers.
Monomers and comonomers of ethylenically unsaturated monomers which may be used in the preferred polymers (A) 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.
A.1. Monomers Containing a Zwitterionic Group
Preferred comonomers which contain a zwitterionic group are of general formula (I)
Y—B—X (I)
wherein B is a straight or branched alkylene
Jones Stephen Alister
Rimmer Steven
Stratford Peter William
LandOfFree
Polymeric blends with zwitterionic groups does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polymeric blends with zwitterionic groups, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polymeric blends with zwitterionic groups will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2904639