Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Polymers from only ethylenic monomers or processes of...
Reexamination Certificate
2002-04-25
2004-05-18
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...
C526S226000, C526S328000, C526S332000
Reexamination Certificate
active
06737493
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a biocompatible material and a method of manufacturing the same. More specifically, the present invention relates to a biocompatible material, which is usable in a medical apparatus to be contact with blood or any tissue in a living body, and a method of manufacturing such a biocompatible material.
2. Description of the Related Art
In these years, various kinds of medical apparatuses comprised of polymeric materials have been developed and practically used in many fields. For instance, the medical apparatuses include artificial kidneys, oxygenator, plasma-separating films, catheters, artificial blood vessels, artificial joints, artificial skins, and the like. An artificial polymer would be recognized as a foreign substance in the body, causing various kinds of biological defense mechanisms, which are undesirable for living bodies. Therefore, it has been expected to develop a novel material that makes no biological defense reaction. In other words, it has been expected so far to have an excellent biocompatibility or an excellent blood compatibility. In the present situation, it is known that a material having a micro-phase separation structure in which a hydrophilic phase and a hydrophobic phase are separated from one another shows an excellent blood compatibility, especially an excellent blood-platelet compatibility. However, the application of such a material is restricted because such a phase separation with certain dimensions should be generated and the conditions for adjusting such a structure are restricted within their respective narrow ranges. Furthermore, there is another finding in which the blood-platelet compatibility can be expressed by applying a hydro gel such as polyethylene glycol on the surface of the material. However, such a compatibility lasts only a short time, so it can be difficult to keep the compatibility for the long term. Furthermore, it is also known that blood platelets adhere remarkably to the surface of a hydrophobic material made of polypropylene, polyethylene terephthalate, or the like, resulting in the activation of each blood platelet.
In the blood compatibility, with respect to the compatibility to a complement system, significant complement-activating abilities can be found in cellulose, ethylene/vinylalcohol copolymer, and the like. It is known that hydroxyl groups in these polymeric materials cause such an activation. In contrast, it is also known that a hydrophobic material such as polypropylene has a less complement-activating ability (The Journal of Artificial Organs, 16 (2), 1045-1050, 1987).
In JP 04-152952A, polyalkoxyalkyl (meth)acrylate is disclosed as a material that keeps its blood-platelet compatibility, anti-complement activity, and ease of surface modification in balance.
From a view point of maintaining safety, for making this material fit for practical use, a polymer in low molecular weight region of the polymer should be completely removed from the entire material by means of repeated fractional precipitations to prevent any undesired substance of this material from eluting into the blood. Under present circumstances, therefore, the resulting product becomes very expensive.
This can be explained as follows. That is, an alkoxyalkyl (meth)acrylate and its copolymer have one or more alkoxyl groups, so that it has a comparatively high hydrophilicity. Therefore, it becomes water-soluble as its molecular weight becomes smaller. If the polymer is synthesized by means of radical polymerization, its polymerization mechanism would be destined to be resulted in a comparatively wide molecular weight distribution. In other words, it is inevitable that a ratio (Mw/Mn) of dividing the weight-average molecular weight (Mw) by the number-average molecular weight (Mn) will be obtained as a value of 2 to 3 in general. This means a lot of low molecular weight polymer components are included in the resulting polymeric material and impart slight water solubility to the polymeric material. Therefore, if such a polymeric material is directly used as a biocompatible material, there is a fear of causing low molecular weight polymer components to elute into the blood.
For solving this problem, heretofore, synthesized polymers have been put in to practical use after removing low molecular weight polymer components from them by subjecting to repeated cycles of washing and re-precipitation. In this case, each of steps of washing and re-precipitation requires a large quantity of an organic solvent such as hexane or ether, which is expensive and is also exceedingly volatile and flammable. Therefore, it is inevitable that the resulting polymer will be an extremely high cost product. In addition, the use of these organic solvents leads to extremely low working properties. Furthermore, there is another problem in that the evaporated solvent has a deleterious effect on the environment.
SUMMARY OF THE INVENTION
The present invention has been made in view of the above-mentioned problem and it is an object of the present invention to provide a much safer biocompatible medical material at low cost. Specifically, an object of the present invention is to provide a polyalkoxyalkyl (meth)acrylate based biocompatible material at a low price.
The present inventors have paid their attention on anionic polymerization and found that a copolymer with a homopolymer composed of alkoxyalkyl (meth)acrylates that a ratio (Mw/Mn) of a weight-average molecular weight (Mw) to a number-average molecular weight (Mn) is 1 to 1.5, and also weight-average molecular weight (Mw) of 40,000 or more or a copolymer composed of alkoxyalkyl (meth)acrylates and other polymers would result in a substantially water-insoluble polymer. As a result, the present invention has been completed. In other words, the present invention can be attained by the following.
A first aspect of the present invention relates to a biocompatible material comprising a polymer synthesized from monomers by an anionic polymerization, wherein the
polymer has a ratio (Mw/Mn) of a weight-average molecular weight (Mw) to a number-average molecular weight (Mn) in the range of 1.0 to 1.5, in which the weight-average molecular weight is 40,000 or more, and each of the monomers is represented by the following general formula (1):
where R
1
is a hydrogen atom or a methyl group; R
2
is a C
1
-C
4
alkylene group; and R
3
is a C
1
-C
4
alkyl group.
In the biocompatible material according to the present invention, it is preferable that, in the polymerization system, the anionic polymerization proceeds in the presence of a tertiary organic aluminum compound having the structure represented by the following general formula (2):
Al—O—Ar (2)
where Ar is an aromatic ring.
In the biocompatible material of the present invention, it is preferable that R
1
is a hydrogen atom, R
2
is an ethylene group, and R
3
is a methyl group in the above-mentioned general formula (1).
A second aspect of the present invention relates to a method of obtaining a polymer, including performing an anionic polymerization of monomers to obtain a polymer having the ratio (Mw/Mn) of a weight-average molecular weight (Mw) to a number-average molecular weight (Mn) in the range of 1.0 to 1.5, in which the weight-average molecular weight is 40,000 or more, each of the monomers being represented by the following general formula (1):
where R
1
is a hydrogen atom or a methyl group; R
2
is a C
1
-C
4
alkylene group; and R
3
is a C
1
-C
4
alkyl group.
A third aspect of the present invention relates to a polyalkoxyalkyl (meth)acrylate, which is polymerized by an anionic polymerization and is substantially free of a water-soluble component.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Hereinafter, a biocompatible material of the present invention will be described in detail.
The biocompatible material of the present invention is a synthetic polymer to be obtained from alkoxyalkyl (meth)acrylate using an anionic polymerization, which is represented by the general
Anzai Takao
Hamada Kenichi
Ishiura Kazushige
Mochizuki Akira
Shimura Ken-ichi
Burns Doane , Swecker, Mathis LLP
Pezzuto Helen L.
Terumo Kabushiki Kaisha
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