Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Polymers from only ethylenic monomers or processes of...
Reexamination Certificate
2001-09-26
2003-07-08
Pezzuto, Helen L. (Department: 1713)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Polymers from only ethylenic monomers or processes of...
C526S259000, C526S265000, C526S303100, C526S307000, C526S320000
Reexamination Certificate
active
06590054
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a copolymer that can be used as an antithrombotic surface treating agent and to an antithrombotic surface treating agent comprising such a copolymer. Also, the present invention relates to a medical apparatus and tool the surface of which is treated with the antithrombotic surface treating agent described above and to a method for producing such a medical apparatus or tool.
2. Description of the Related Art
Recently, studies on medical materials utilizing various polymer materials has been in progress and their application to blood filters, membranes for dialyzer, membranes for blood plasma separator, catheters, membranes for oxygenator, artificial blood vessels, membranes for preventing accretion, artificial skin or the like is expected. In this case, synthetic materials that are foreign materials to organisms are used in contact with tissues or blood in the organism so that the medical material must have biocompatibility.
Where a medial material is used as a material to be contacted with blood, the following three elements are important items of its biocompatibility: (a) inhibition of the blood coagulation system, (b) inhibition of the adhesion and activation of platelets, and (c) inhibition of activation of the complement system.
In particular, where it is used as a material to be contacted with blood only for a relatively short time, such as a medical material for extracorporeal circulation (for example, dialyzer, membrane of blood plasma separator, etc.), generally an anticoagulating agent such as heparin or sodium citrate is simultaneously used. Accordingly, the inhibition of activation of platelets and complement system as in (b) and (c) described above are important problems.
Regarding (b) the inhibition of the adhesion and activation of platelets above, it has been reported that a surface with micro phase separation or a hydrophilic surface, in particular a gelled surface having bonded thereon a water-soluble polymer is superior but a hydrophobic surface such as a surface of polypropylene is inferior (see, for example, Trans. Am. Soc. Artif. Intern. Organs, Vol. XXXIII, p. 75-84 (1987) and Polymers and Remedy, Mita Publishing Association, p. 73 (1989)).
Although the surface having a micro phase separation structure can exhibit good blood compatibility by controlling it to a suitable phase separation state, the conditions under which such a phase separation state can be made are limited and the material finds a limited application. The gelled surface having bonded thereon a water-soluble polymer can inhibit the adhesion of platelets. However, the platelets activated on the surface of the material and fine thrombi are returned into the body, which frequently causes the problem of extraordinary variation of blood cells (platelets).
Tsuruta et al. have proposed a polymer having a basic nitrogen containing functional group and a nitrogen content of 0.05 to 3.5% by weight as a surface to which platelets hardly adhere (Japanese Patent Application Laid-open Nos. 60-119955, 60-119956, and 60-119957). However, the polymer is based on HEMA (2-hydroxyethyl methacrylate) so that a problem arises that the activation of complement system takes place.
On the other hand, regarding (c) activation of the complement system, it is known that the surface of material having a hydroxyl group, such as cellulose or ethylene-vinyl alcohol copolymer, shows a high activity but a hydrophobic surface such as the surface of polypropylene shows a weak activity (see, for example,
Artificial Organs
16(2), p. 1045-1050 (1987)).
Therefore, use of materials based on cellulose and vinyl alcohol, respectively in for example membranes for artificial organs causes the problem of activation of the complement system. On the contrary, use of hydrophobic surfaces such as the surface of polyethylene causes the problem of adhesion and activation of platelets.
Furthermore, where the medical material is used as a material to be contacted with blood for a relatively long time as in the case of an artificial blood vessel, it must be a material having affinity for the tissues (cells) in an organism in addition to the above 3 items so that neoplastic tunica intima formation and neogenesis and regeneration of tissues in the organism can take place suitably. The material for an artificial blood vessel includes, for example, ultra fine polyester fiber (Artificial Organs 19(3), p. 1287-1291 (1990)). The ultra fine polyester fiber is one of medical materials that utilize recognition of foreign matter by the organism, cure of wounds by biophylaxis, and self-to-self tissue regeneration, and is currently used mainly as an artificial blood vessel.
However, a prolonged application of the artificial blood vessel to microvessels causes the problem of their occlusion.
Moreover, for medial materials that contact tissues or fluid in the organism as well as blood, for example, membrane for preventing accretion and implanting material, which are implanted in the organism for a long period of time, or wound covering material used in contact with wounded portion (site where the skin is peeled and damaged to expose the tissue in the organism), a surface that is recognized by the organism as a foreign matter in few occasions and is readily peeled off from the organism (no accreting surface) is necessary.
However, in the case of silicone, polyurethane and polytetrafluoroethylene used as the above-described material, no satisfactory properties have been obtained yet since the tissue in the organism coalesce with the surface of the material or the recognition of it as a foreign matter by the organism is too intense.
Therefore, no polymer surface that satisfies simultaneously the biocompatibilities required for medical materials used in contact with the tissues in the organism or blood, such as inhibition of adhesion and activation of platelets, inhibition of activation of complement system and affinity for the tissues in the organism, has been obtained yet.
On the contrary, the present inventors have found that specified alkoxyalkyl (meth)acrylate polymer is excellent in antithrombosis and further in biocompatibility and proposed as a medical material (Japanese Patent Application Laid-open No. Hei 4-152952 (Japanese Patent No. 2806510) and Japanese Patent Application Laid-open No. Hei 5-262656).
However, the surface treated with these polymers is hydrophobic so that its application is limited and cannot be used for a variety of uses.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a copolymer that is superior in antithrombotic property and further biocompatibility to the conventional medical materials and can be used as a medical material having high hydrophilicity.
Another object of the present invention is to provide a surface treating agent comprising such a copolymer.
Still another object of the present invention is to provide a medical apparatus having a surface treated with such an antithrombotic surface treating agent.
Yet another object of the present invention is to provide a method for producing such a medical apparatus.
The present inventors have made extensive studies with a view to solving the above problems and as a result they have found that a copolymer comprising a specified alkoxyalkyl (meth)acrylate and a monomer having a basic functional group copolymerizable with the specified monomer as monomer components and having a specified molar ratio of one to the other has antithrombotic property equivalent to or higher than and hydrophilicity higher than the conventional alkoxyalkyl (meth)acrylate homopolymer or the like. The present invention is based on this discovery.
That is, in accordance with a first embodiment of the present invention, there is provided a copolymer comprising a monomer of formula (1) below and a monomer having a basic functional group copolymerizable with the monomer as monomer components, wherein molar ratio of the monomer of formula (1) to the monomer having a basic functional group is 85/15
Irie Yukiko
Ochiai Shoji
Tanaka Masaru
Tokunaga Norifumi
Pezzuto Helen L.
Terumo Kabushiki Kaisha
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