Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...
Reexamination Certificate
1999-01-27
2001-09-25
Wu, David W. (Department: 1713)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Mixing of two or more solid polymers; mixing of solid...
C525S260000, C525S263000, C525S283000, C525S308000, C526S319000, C424S450000
Reexamination Certificate
active
06294614
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a modified polymer containing a poly(2-hydroxyethyl(meth)acrylate) segment in the molecule as a hydrophilic polymer chain and the use thereof, particularly to the use as a medical material.
BACKGROUND ART
Poly(2-hydroxyethyl methacrylate) (hereinafter referred to as polyHEMA in some case) has been evaluated as a polymer which is relatively excellent in biological affinity or biocompatibility, and ABA type block copolymer containing HEMA segment in the molecule is further proposed for a biocompatible medical material (for example, refer to Japanese Patent Application Laid-open No. Sho 55-50028). Moreover, the specific applications of such block copolymer as the medical material, for example, the applications to an artificial blood vessel (Japanese Patent Application Laid-open Nos. Sho 58-175553, 60-31762, 60-34451), a medical suture (Japanese Patent Application Laid-open No. Sho 60-31761), and the like are proposed, and another ABA type block copolymer is also proposed (e.g., Japanese Patent Application Laid-open Nos. Sho 61-236831, 60-232166).
The former group of publications describe the block copolymer in which segment B is a segment derived from polyalkylene oxide having isocyanate groups on opposite terminal ends, and segment A is a segment derived from a)-hydroxyalkyl acrylate. Japanese Patent Application Laid-open No. Sho 61-236831 describes the block copolymer in which segment B is a segment derived from polystyrene having isocyanate groups on opposite terminal ends, and segment A is a segment derived from polyhexyl acrylate.
Moreover, the latter Japanese Patent Application Laid-open No. Sho 60-232166 describes ABA type block copolymer composed of blocks A and B which are both hydrophobic blocks but differ from each other in hydrophobic degree. Additionally, the block A is derived from (meth)acrylic ester having a polyfluoroalkyl group, while the block B contains polystyrene, polybutadiene segments. For these block copolymers, the applications as anticoagulant materials are also proposed.
According to Japanese Patent Application Laid-open No. Sho 55-50028 which belongs to the former group of publications, it is suggested that the block copolymer can form hydrophilic and hydrophobic domains in solution in the state where molecules are getting together, i.e., it can form a micro phase separation structure, so that the biocompatibility can be provided.
As described above, various types of polymers have been developed particularly for medical biocompatible materials, and some of the polymers appear to realize the object of the development to some degree.
However, the conventional material are not necessarily satisfactory for the construction of a blood compatible or biologically compatible surface on various medical devices such as an artificial heart, a dialysis membrane, an artificial lung, a contact lens, a catheter, and the like. Therefore, an object of the present invention is to provide a material superior in blood compatibility or biological compatibility.
DISCLOSURE OF DEVELOPMENT
The present inventors et al. have carried on research under the assumption that if a polymer can be provided in which the mobility of a hydrophilic polymer chain is enhanced separately from the formation of a micro phase separation structure in the solution of a block copolymer (or a copolymer) or the like, a higher resistance may be indicated against the adsorption of, for example, protein in body fluid, platelet in blood, or the like. This is not bound by theory, but if polymer chains having high mobility can be constructed on a certain surface, the adsorption of body fluid components can be expected to be strongly suppressed by the entropy elasticity of the chains as described above.
The present inventors et al. have found that the enlargement of mobility can be achieved by lowering the mobility of either end of the hydrophilic polymer chain by specific means. Specifically, when polyHEMA is used as the hydrophilic polymer chain, by appropriately lowering the mobility of either end thereof, for example, the glass transition temperature (which is, in one view, believed to correspond to the freezing or releasing of polymer chain segment motion or micro-Brownian motion) is remarkably lowered, as compared with a polymer in which such mobility is not lowered. They also found that the strong adsorption suppression against the blood fluid components can be observed as to the polymer.
Therefore, according to the present invention, there is provided a modified polymer containing a poly(2-hydroxyethyl(meth)acrylate) segment as a hydrophilic polymer chain in the molecule,
(A) a) one or two said segments being bonded to a hydrophobic polymer chain at either end thereof,
b) a plurality of said segments as a graft chain being bonded to a main polymer at either end thereof, or
c) said segment being bonded to a bulky lipid residue at either end thereof, and
(B) a glass transition temperature being about 45° C. or less.
There is also provided a biologically compatible polymer composition which is prepared from solution or dispersion liquid containing the modified polymer.
There is further provided the use of the modified polymer for manufacturing a biologically compatible polymer composition such as a medical device or apparatus or covering the surface thereof.
DESCRIPTION OF SPECIFIC MODE OF THE INVENTION
The term “(meth)acrylate” for use in the present specification means either methacrylate or acrylate.
The term “medical device or apparatus” for use in the present specification conceptually includes an artificial heart, a dialysis membrane, an artificial lung, an artificial blood vessel, a contact lens, a catheter, and all articles for use in contact with human body fluid or tissue.
The modified polymer of the present invention includes any polymer, as long as it contains a poly(2-hydroxyethyl(meth)acrylate) segment as a hydrophilic polymer chain in the molecule, the mobility of the poly(2-hydroxyethyl(meth)acrylate) segment is significantly strengthened by appropriately suppressing the mobility of either end of the segment, and its glass transition temperature is about 45° C. or less.
A modified polymer is represented as such preferable polymer in general formula (I):
In the above formula, B denotes a polymer segment derived from either end or both ends living polymer selected from the group consisting of poly(&agr;-methyl-substituted or non-substituted styrene), poly(substituted or non-substituted styrene), polylactide, poly(alkyl(meth)acrylate), poly(dinene) and a living polymer of a copolymer thereof, obtained using an anionic polymerization catalyst,
R denotes a hydrogen atom or a methyl group,
m and n independently denote a certain integer of 10 to 500, and
a broken line denotes that the linked poly(2-hydroxyethyl(meth)acrylate) segment exists or does not exist.
For B, the substituting group in poly(&agr;-methyl substituted or non-substituted styrene) and poly(substituted or non-substituted styrene) may include any group that can be substituted on a benzene ring of styrene and that can achieve the object of the present invention. Examples of the substituting group include C
1-6
alkyl, e.g., methyl, ethyl; isopropyl halide or silylated C
1-6
low-class alkyl, e.g., trifluoromethyl, bis (trimethylsilyl)methyl; halogen atom, e.g., chlorine atom, fluorine atom. Additionally, in the present specification, the terms “low-class alkyl” and “C1-6 alkyl” are exchangeably used, and include, for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-hexyl, and the like.
In general, the polymer segment with B derived from the both ends living polymer can preferably be obtained using styrene and its derivative as monomers and using Na-naphthalene as the anionic polymerization catalyst. For example, 2-hydroxyethyl(meth)acrylate with a hydroxyl group protected is applied as further monomer to the formed both ends living polymer to continue anionic polymerization reaction. Subsequently, when a protecting group is detached from the hydro
Ito Hotaka
Kataoka Kazunori
Kato Masao
Nagasaki Yukio
Okano Teruo
Davis & Bujold P.L.L.C.
K. K. Vayu
Wu David W.
Zalukaeva Tanya
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