JP6892299B2 - Medical device parts and medical devices - Google Patents

Description

The present invention relates to medical device members and medical devices.

In medical treatment using medical devices such as conventional blood bags and extracorporeal circulation circuits for heart-lung machines, the polymer materials used in many medical devices do not have blood compatibility, so anticoagulants are used when using medical devices. The combined use of is indispensable.
In addition, when biological components such as blood cells and proteins are adsorbed on the surface of a polymer material and denatured, it causes blood coagulation, which not only causes adverse effects such as thrombosis and inflammatory reaction in the body, but also blood coagulation leads to deterioration of the material. Therefore, adsorption and denaturation of biological components on the surface of polymer materials is one of the important issues to be solved.
With the progress of medical technology, the opportunities for polymer materials to come into contact with living tissues and blood are increasing, and the blood compatibility of polymer materials has become a big problem.

Recently, in the fields of drug discovery development and medical treatment, drug evaluation using cells, regenerative medicine in which tissue cells are cultured and applied to medical treatment, and technological development in related fields are being actively carried out. In the development of cell culture vessels, which is one of these research tools, collagen, polystyrene and methyl methacrylate are generally effective as suitable materials, and polystyrene has advantages in low cytotoxicity, economy and workability. In the current cell culture, polystyrene treated with hydrophilicity is widely used.
However, although cell growth and proliferation are observed in a culture vessel made of such members, it is not possible to form cells having a three-dimensional structure that is advantageous for maintaining cell function, and the cultured cells are removed from the vessel. There is a potential problem that the cells cannot be detached and must be peeled off with a scrubber or the like when collecting, which damages the cells.

In order to solve these problems, material development aiming at the realization of excellent biocompatible polymer materials and research on materials related to surface treatment of the surface of a member in direct contact with a living body have been carried out.

Polyethylene oxide (hereinafter abbreviated as PEG) has been disclosed as a biocompatible polymer material that has been studied in particular (see, for example, Patent Documents 1 and 2). PEG has high hydrophilicity and low antigenicity, and has been conventionally used as a nonionic surfactant, a plasticizer, a pharmaceutical base material, and the like. However, while PEG has excellent blood compatibility, it is water-soluble, so that it must be used as a copolymer or composition with other polymers when used as a pharmaceutical material. Is also limited.

Further, in the study on the surface treatment of the surface of the member in direct contact with the living body, for example, when a material having a methacryloxyethyl phosphorylcholine having a phospholipid polar group as a component is treated on the surface of the base material, cells such as lymphocytes appear on the surface. Since it does not adhere at all, its use as a surface treatment agent for various medical products such as cell culture substrates, artificial lymphocytes, and stents is being studied (see Patent Document 3).
Further, since methoxyethyl acrylate is also a polymer material having biocompatibility, it has been studied as a surface treatment agent for many medical devices including artificial heart-lung machines (see Patent Document 4).
However, since these materials are used in the form of treating the surface of the base material, there are problems in medical application such as defects due to uneven treatment and expression of biotoxicity due to elution of uncured monomers.

In addition, in drug discovery development and regenerative medicine using the above-mentioned cells, in the remarkable progress of cell culture technology development, research on cell culture using culture vessels made of various materials and related technology development are being carried out. (See, for example, References 5 and 6). However, in the future, biocompatibility such as toxicity of container materials for culturing cells may become a problem at the stage of practical application such as clinical and medical applications.

Furthermore, in the drug evaluation using cells and the sterilization process of medical instruments in the field of regenerative medicine in which tissue cells are cultured and applied to medical treatment, the above-mentioned polystyrene container has a glass transition temperature of 100 ° C. and is widely used. It cannot be applied to high pressure steam sterilization at 121 ° C.

Japanese Unexamined Patent Publication No. 09-29019 Japanese Patent No. 5831666 International Publication No. 2009/081870A1 Pamphlet International Publication No. 2011/083815A1 Pamphlet International Publication No. 2015/129837A1 Pamphlet Japanese Unexamined Patent Publication No. 2010-45980

An object of the present invention is to provide a medical device member which is made of a biocompatible material that does not exhibit hemolytic toxicity and has excellent heat resistance of the member, and a medical device made of the same.

（式（１）中、Ｒ^１〜Ｒ^４は、フッ素、フッ素を含有する炭素数１〜１０のアルキル基、フッ素を含有する炭素数１〜１０のアルコキシ基、またはフッ素を含有する炭素数２〜１０のアルコキシアルキル基である。Ｒ^１〜Ｒ^４は互いに同一であっても異なっていてもよい。また、Ｒ^１〜Ｒ^４は互いに結合して環構造を形成していてもよい。）
（２）
（１）に記載の医療器具用部材において、
上記フッ素含有環状オレフィンポリマーが上記一般式（１）で表される構造単位［Ａ］と下記一般式（２）で表される繰り返し構造単位［Ｂ］とを含有し、そのモル比［Ａ］／［Ｂ］が９０／１０〜１０／９０である医療器具用部材。

（式（２）中、Ｒ^５〜Ｒ^８は、フッ素、フッ素を含有する炭素数１〜１０のアルキル基、フッ素を含有する炭素数１〜１０のアルコキシ基、またはフッ素を含有する炭素数２〜１０のアルコキシアルキル基である。Ｒ^５〜Ｒ^８は互いに同一であっても異なっていてもよい。また、Ｒ^５〜Ｒ^８は互いに結合して環構造を形成していてもよい。）
（３）
蛍光波長２００ｎｍ以上１０００ｎｍ以下、および励起波長２００ｎｍ以上１０００ｎｍ以下の全領域において蛍光を発しないことを特徴とする請求項１または２に記載の医療器具用部材。
（４）
上記部材が、上記フッ素含有環状オレフィンポリマーと、光硬化性化合物と、光硬化開始剤と、を含むフッ素含有環状オレフィンポリマー組成物により構成されることを特徴とし、かつ、上記フッ素含有環状オレフィンポリマー組成物中における上記フッ素含有環状オレフィンポリマーと上記光硬化性化合物の質量比（上記フッ素含有環状オレフィンポリマー／上記光硬化性化合物）が、９９．９／０．１〜３０／７０である（１）から（３）のいずれか一つに記載の医療器具用部材。
（５）
（１）から（４）のいずれか一つに記載の医療器具用部材であって、
上記フッ素含有環状オレフィンポリマーの固体粘弾性測定における１２０℃の貯蔵弾性率（Ｅ´）が１×１０^６〜１×１０^１０Ｐａであることを特徴とする医療器具用部材。
（６）
（１）から（５）のいずれか一つに記載の医療器具用部材を備える医療器具であって、
当該医療器具は、血液に直接接する、カテーテル、血液バッグ、ステント、または人工心肺用の体外外循環回路である、医療器具。 The present invention is shown below.
(1)
A medical device component that constitutes an extracorporeal circulation circuit for a catheter, blood bag, stent, or heart-lung machine that comes into direct contact with blood.
The member is composed of a fluorine-containing cyclic olefin polymer containing a structural unit represented by the following general formula (1), and is calculated from the absorbance at a wavelength of 576 nm, which is the maximum UV absorption of oxygenated hemoglobin in a hemolytic toxicity test. A member for a medical device, which is made of a biocompatible material having a hemolysis rate of 0% or more and 2% or less.

(In the formula (1), R ^{1 to} R ⁴ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{1 to} R ⁴ may be the same or different from ^{each other, and R 1 to} R ⁴ may be bonded to each other to form a ring structure.)
(2)
In the medical device member described in (1),
The fluorine-containing cyclic olefin polymer contains a structural unit [A] represented by the general formula (1) and a repeating structural unit [B] represented by the following general formula (2), and the molar ratio [A] thereof. / [B] is a member for medical devices in which 90/10 to 10/90.

In the formula (2), R ^{5 to} R ⁸ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{5 to} R ⁸ may be the same or different from ^{each other, and R 5 to} R ⁸ may be bonded to each other to form a ring structure.)
(3)
The medical device member according to claim 1 or 2, wherein the member does not emit fluorescence in the entire region having a fluorescence wavelength of 200 nm or more and 1000 nm or less, and an excitation wavelength of 200 nm or more and 1000 nm or less.
(4)
The member is characterized by being composed of a fluorine-containing cyclic olefin polymer composition containing the fluorine-containing cyclic olefin polymer, a photocurable compound, and a photocuring initiator, and the fluorine-containing cyclic olefin polymer. The mass ratio of the fluorine-containing cyclic olefin polymer to the photocurable compound in the composition (the fluorine-containing cyclic olefin polymer / the photocurable compound) is 99.9 / 0.1 to 30/70 (1). ) To (3). The member for medical equipment according to any one of (3).
(5)
The member for a medical device according to any one of (1) to (4).
A member for a medical device, wherein the storage elastic modulus (E') at 120 ° C. in the solid viscoelasticity measurement of the fluorine-containing cyclic olefin polymer is 1 × 10 ⁶ to 1 × 10 ^{10 Pa.}
(6)
A medical device including the member for the medical device according to any one of (1) to (5) .
The medical device is a catheter, blood bag, stent, or extracorporeal circulation circuit for heart-lung machine that is in direct contact with blood .

According to the present invention, there is provided a medical device member or medical device which is made of a biocompatible material that does not exhibit hemolytic toxicity, has excellent heat resistance of the member, and is used in a form in which blood or living cells are in direct contact with each other. be able to.

It is a figure which shows the UV absorbance spectrum in the hemolytic toxicity test of the film-like member described in Example 1. FIG.

Hereinafter, the present invention will be described based on the embodiments. In addition, in this specification, "~" represents the following from the above unless otherwise specified.

(Members for medical equipment)
The materials of the members constituting the medical device in the present embodiment are shown below.
The hemolysis rate is calculated from the absorbance at a wavelength of 576 nm, which is the maximum UV absorption of oxygenated hemoglobin in a hemolysis toxicity test, which is composed of a fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1). It is a biocompatible material characterized by being 0% or more and 2% or less.

（式（１）中、Ｒ^１〜Ｒ^４は、フッ素、フッ素を含有する炭素数１〜１０のアルキル基、フッ素を含有する炭素数１〜１０のアルコキシ基、またはフッ素を含有する炭素数２〜１０のアルコキシアルキル基である。Ｒ^１〜Ｒ^４は互いに同一であっても異なっていてもよい。また、Ｒ^１〜Ｒ^４は互いに結合して環構造を形成していてもよい。）

(In the formula (1), R ^{1 to} R ⁴ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{1 to} R ⁴ may be the same or different from ^{each other, and R 1 to} R ⁴ may be bonded to each other to form a ring structure.)

Hereinafter, the medical device according to the present embodiment will be described in detail.
The member constituting the medical device in the present embodiment is a fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1), preferably a structural unit [A] represented by the general formula (1). A fluorine-containing cyclic olefin polymer containing the repeating structural unit [B] represented by the general formula (2), or a composition containing the fluorine-containing cyclic olefin polymer, for example, a film, a sheet, a fiber, or an injection. It is a molded product such as a molded product, and is a molded product coated with another material or composited with an inorganic material such as metal or an organic material such as resin.

For example, medical devices composed of the members of the present embodiment include members such as catheters, blood bags, stents, extracorporeal circulation circuits for heart-lung machines, plates, petri dishes, dishes, flasks, and tubes.

In any medical device, a fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1) of the present embodiment, or a general formula (1), at least in direct contact with blood or living cells. ), A fluorine-containing cyclic olefin polymer containing the structural unit [A] represented by the general formula (2), and a composition containing the fluorine-containing cyclic olefin polymer. By using the members, it is possible to construct a medical device that does not generate biotoxic components that induce blood coagulation, inflammatory reaction, proliferation of living cells, cell mutation, death and the like.

According to the guidelines for biological safety testing of medical devices (Ministry of Health, Labor and Welfare, Pharmaceutical and Food Safety Bureau, Yakushokuki No. 0301-20), biological for risk assessment of biological adverse effects (toxic hazards) In the concept of safety, items for evaluating the biological safety of substances are set according to the part that comes into contact with the human body and the usage pattern of the medical device used.
Among them, the blood compatibility test and the cytotoxicity evaluation are the main evaluation items and are indicators of the safety of the members constituting the medical device. For example, in the hemolytic toxicity test of the blood compatibility test, an index (also shown as grade) indicating five levels of safety is set in the hemolysis rate indicating the degree of destruction of red blood cells by the eluate from the subject. Among these, a hemolysis rate of 2% or less is positioned as a non-hemolysis grade, and is regarded as an index showing high safety required for catheters, blood bags, stents, extracorporeal circulation circuits for artificial heart-lung machines, and the like.

A fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1) of the present embodiment, or a repetition represented by the structural unit [A] represented by the general formula (1) and the general formula (2). In a hemolytic toxicity test of a member composed of a fluorine-containing cyclic olefin polymer containing the structural unit [B] and a composition containing the fluorine-containing cyclic olefin polymer, from the absorbance at a wavelength of 576 nm, which is the maximum UV absorption of oxygenated hemoglobin. The calculated hemolysis rate is preferably 0% or more and 2% or less, more preferably 0% or more and 1.5% or less, and further preferably 0% or more and 1% or less. This makes it possible to prevent blood contamination from the member and prevent blood clot formation and blood degeneration that causes an inflammatory reaction. Further, by using a medical device having at least a surface in direct contact with living cells made of the medical device member of the present embodiment, it is possible to carry out culturing for a long period of time without causing cell death or mutation.

Here, the hemolytic toxicity test will be described. The test is conducted in accordance with ISO10993 "Biological Evaluation of Medical Devices". Extraction of toxic substances from, for example, film or sheet-like members constituting medical instruments has an area defined by the thickness of the subject (for 1 mL of the extract, a sample having a thickness of 0.5 mm or less is 6 cm ² ). The test piece shredded in (area) is placed in a heating container and heated using, for example, an extract such as phosphate buffered physiological saline. Next, anticoagulant-treated blood is added to the extract, incubated at 37 ° C., the test solution is centrifuged, and the supernatant solution is collected as a test sample.
The absorbance used to calculate the hemolysis rate is determined by a UV spectrophotometer. The absorbance of the test sample is measured, the absorbance at a wavelength of 576 nm, which is the maximum absorption of oxygenated hemoglobin, is measured, and the hemolysis rate is calculated by the following formula (2). In the formula (2), the absorbance of the positive control solution is the absorbance of the sample prepared by changing the above extract into distilled water for injection (see FIG. 1), and the negative control solution is the extraction of toxic substances from the subject. It is the absorbance of the extract used in.

In the application for medical devices, for example, cardiovascular medical devices such as artificial blood vessels and coronary stents may be evaluated in animals at the time of clinical application for functional confirmation. Such functional tests include confirming that the drug can be used safely at the site of application, and the risk assessment of thrombosis is often an important endpoint. In the application for medical devices, the hematological toxicity test of the present embodiment can be applied as one item of the functional test if the reliability of the test is ensured and the risk evaluation of thrombosis is performed appropriately. ..

Regarding the cytotoxicity evaluation method, according to ISO10993 "Biological evaluation of medical equipment", it is determined that mammalian cells are used for evaluation, and the cell types are L929 cells (mouse) and BALB / 3T3 cells (mouse). ) And V79 cells (Chinese hamsters) are defined as test cells. Further, as a test method, there are a method using an extract of the material and a method by direct contact and indirect contact between the material and cells, and the type of medium used is, for example, 10% bovine serum D-MEM medium is recommended. Has been done.

In the present embodiment, mouse BALB / 3T3 cells are cultured using 10% calf serum D-MEM medium by a method in which members and cells are in direct contact with each other, and the proliferative nature of the cell growth process is not attenuated. Autofluorescence associated with the death of the cells is not observed, and the metabolic function of the drug is maintained. From these embodiments, the safety of the medical device composed of the members of the present embodiment as a biocompatible material was confirmed from the viewpoint of cytotoxicity evaluation.

(Fluorine-containing cyclic olefin polymer used for members constituting medical devices)
The fluorine-containing cyclic olefin polymer used for the members constituting the medical device in the present embodiment contains a structural unit represented by the following general formula (1).

（式（１）中、Ｒ^１〜Ｒ^４は、フッ素、フッ素を含有する炭素数１〜１０のアルキル基、フッ素を含有する炭素数１〜１０のアルコキシ基、またはフッ素を含有する炭素数２〜１０のアルコキシアルキル基である。Ｒ^１〜Ｒ^４は互いに同一であっても異なっていてもよい。また、Ｒ^１〜Ｒ^４は互いに結合して環構造を形成していてもよい。）

(In the formula (1), R ^{1 to} R ⁴ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{1 to} R ⁴ may be the same or different from ^{each other, and R 1 to} R ⁴ may be bonded to each other to form a ring structure.)

In the general formula (1), R ^{1 to} R ⁴ are fluorine; fluoromethyl group, difluoromethyl group, trifluoromethyl group, trifluoroethyl group, pentafluoroethyl group, heptafluoropropyl group, hexafluoroisopropyl group, heptafluoro. Part or all of hydrogen in alkyl groups such as isopropyl group, hexafluoro-2-methylisopropyl group, perfluoro-2-methylisopropyl group, n-perfluorobutyl group, n-perfluoropentyl group, perfluorocyclopentyl group is replaced with fluorine. Fluorine-containing alkyl groups with 1 to 10 carbon atoms such as alkyl groups; fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, trifluoroethoxy group, pentafluoroethoxy group, heptafluoropropoxy group, hexafluoroisopropoxy Group, heptafluoroisopropoxy group, hexafluoro-2-methylisopropoxy group, perfluoro-2-methylisopropoxy group, n-perfluorobutoxy group, n-perfluoropentoxy group, perfluorocyclopentoxy group and other alkoxy groups A fluorine-containing alkoxy group having 1 to 10 carbon atoms, such as an alkoxy group in which part or all of hydrogen is substituted with fluorine; or a fluoromethoxymethyl group, a difluoromethoxymethyl group, a trifluoromethoxymethyl group, or a trifluoroethoxymethyl group. Group, pentafluoroethoxymethyl group, heptafluoropropoxymethyl group, hexafluoroisopropoxymethyl group, heptafluoroisopropoxymethyl group, hexafluoro-2-methylisopropoxymethyl group, perfluoro-2-methylisopropoxymethyl group, n -Pelfluorobutoxymethyl group, n-perfluoropentoxymethyl group, perfluorocyclopentoxymethyl group and other alkoxyalkyl groups. Part or all of the hydrogen is substituted with fluorine. 10 to 10 alkoxyalkyl groups are exemplified.

Further, R ^{1 to} R ⁴ may be bonded to each other to form a ring structure, or a ring such as perfluorocycloalkyl or oxygen-mediated perfluorocycloether may be formed.

The fluorine-containing cyclic olefin polymer may have only the structural unit represented by the general formula (1), or is a structural unit represented by the general formula (1) and is at least ^{R 1 to} R ^4. One may contain two or more types of structural units that are different from each other.

As a specific example of the fluorine-containing cyclic olefin polymer containing the structural unit represented by the general formula (1) in the present embodiment, poly (1,1,2-trifluoro-2-trifluoromethyl-3,5) -Cyclopentylene ethylene), poly (1,2-difluoro-1-trifluoroethyl-2-trifluoromethyl-3,5-cyclopentylene ethylene), poly (1,2-difluoro-1-perfluoro-iso) -Propyl-2-trifluoromethyl-3,5-cyclopentyleneethylene), poly (1,2-difluoro-1,2-bis (trifluoromethyl) -3,5-cyclopentyleneethylene), poly (1,2-difluoro-1,2-bis (trifluoromethyl) -3,5-cyclopentyleneethylene), poly ( 1,1,2,2,3,3,3a, 6a-octafluorocyclopentyl-4,6-cyclopentyleneethylene), poly (1,1,2,2,3,3,4,5,4,3a, 7a-decafluorocyclohexyl-5,7-cyclopentylene ethylene), poly (1,2-difluoro-1-trifluoromethyl-2-perfluoroethyl-3,5-cyclopentylene ethylene), poly (1-( 1-Trifluoromethyl-2,2,3,3,4,5,5-octafluoro-cyclopentyl) -3,5-cyclopentyleneethylene), poly ((1,1,2-trifluoro-) 2-Perfluorobutyl) -3,5-cyclopentyleneethylene), poly (1,2-difluoro-1-trifluoromethyl-2-perfluorobutyl-3,5-cyclopentyleneethylene), poly (1-fluoro) -1-Perfluoroethyl-2,2-bis (trifluoromethyl))-3,5-cyclopentyleneethylene), poly (1,2-difluoro-1-perfluoropropyl-2-trifluoromethyl) -3, 5-Cyclopentylene ethylene), poly (1,2-difluoro-1-trifluoromethyl-2-perfluorobutyl-3,5-cyclopentylene ethylene), poly (1,2-difluoro-1-trifluoromethyl) -2-Perfluoropentyl-3,5-cyclopentyleneethylene), poly (1,1,3,3,3a, 6a-hexafluorofuranyl-3,5-cyclopentyleneethylene), poly (1,1) , 2-Trifluoro-2-trifluoromethoxy-3,5-cyclopentyleneethylene), poly (1,2-difluoro-1,2-bis (trifluoromethoxy) -3,5-cyclopentyleneethylene) , Poly (1,2-difluoro-1-trifluoromethoxy) -2-Perfluoroethoxy-3,5-cyclopentyleneethylene), poly (1,1,2-trifluoro-2-perfluorobutoxy-3,5-cyclopentyleneethylene), poly (1,2-difluoro-) 1-trifluoromethoxy-2-perfluorobutoxy-3,5-cyclopentylene ethylene), poly (1-fluoro-1-perfluoroethoxy-2,2-bis (trifluoromethoxy) -3,5-cyclopentylene) Ethylene), poly (1,2-difluoro-1-perfluoropropoxy-2-trifluoromethoxy-3,5-cyclopentyleneethylene), poly (1,2-difluoro-1-trifluoromethoxy-2-perfluorobutoxy) -3,5-cyclopentyleneethylene), poly (1,1,2-trifluoro-2-perfluoroheptoxy 3,5-cyclopentyleneethylene), poly (1,2-difluoro-1-trifluoromethoxy), poly (1,2-difluoro-1-trifluoromethoxy) -2-Perfluoropentyl-3,5-cyclopentyleneethylene), poly (1- (2', 2', 2'-trifluoroethoxy) -3,5-cyclopentyleneethylene), poly (1-( 2', 2', 3', 3', 3'-pentafluoropropoxy) -3,5-cyclopentyleneethylene), poly (1- (2', 2', 3', 3', 4', 4', 4', 4'-Heptafluorobutoxy) -3,5-cyclopentyleneethylene), poly (1,2-difluoro-1-trifluoromethoxy-2- (2', 2', 2'-trifluoroethoxy) ) -3,5-Cyclopentylene ethylene), poly (1,1,2-trifluoro-2- (2', 2', 3', 3', 4', 4', 4'-heptafluorobutoxy) ) -3,5-Cyclopentylene ethylene), poly (1,2-difluoro-1-trifluoromethoxy-2- (2', 2', 3', 3', 4', 4', 4'-) Heptafluorobutoxy) -3,5-cyclopentyleneethylene), poly (1-fluoro-1- (2', 2', 2'-trifluoroethoxy) -2,2-bis (trifluoromethoxy))- 3,5-Cyclopentylene ethylene), poly (1,2-difluoro-1- (2', 2', 3', 3', 3'-pentafluoropropoxy) -2-trifluoromethoxy-3,5 -Cyclopentylene ethylene), poly (1,1,2-trifluoro-2- (1', 1', 1'-trifluoro-iso-propoxy) -3,5-cyclopentylene ethyle , Poly (1,2-difluoro-1-trifluoromethoxy-2- (2', 2', 3', 3', 4', 4', 4'-heptafluorobutoxy) -3,5- Cyclopentylene ethylene) and the like.

Further, the fluorine-containing cyclic olefin polymer used for the member constituting the medical device in the present embodiment is a repetition represented by the structural unit [A] represented by the above general formula (1) and the general formula (2). It may contain a structural unit [B]. At that time, the molar ratio [A] / [B] of the structural unit [A] and the structural unit [B] is preferably 90/10 to 10/90, preferably 85/15 to 15/85. More preferably, it is 80/20 to 20/80.

（式（２）中、Ｒ^５〜Ｒ^８は、上記一般式（１）で表される構造単位［Ａ］のＲ^１〜Ｒ^４と同義であり、Ｒ^５〜Ｒ^８は互いに同一であっても異なっていてもよい。また、Ｒ^５〜Ｒ^８は互いに結合して環構造を形成していてもよい。）

(In the formula (2), R ^{5 to} R ^{8 are synonymous with R 1 to} R ⁴ of the structural unit [A] represented by the general formula (1), and R ^{5 to} R ⁸ are the same as each other. R ^{5 to} R ⁸ may be combined with each other to form a ring structure.)

In the general formula (2), R ^{5 to} R ^{8 are synonymous with R 1 to} R ⁴ of the structural unit [A] represented by the general formula (1), and R ^{5 to} R ⁸ are connected to each other to form a ring structure. May form a ring of perfluorocycloalkyl, oxygen-mediated perfluorocycloether, or the like.
The fluorine-containing cyclic olefin polymer may have only the structural unit represented by the general formula (2), or is a structural unit represented by the general formula (2) and has at least ^{R 5 to} R ^8. One may contain two or more types of structural units that are different from each other.

As a specific example of the fluorine-containing cyclic olefin polymer containing the structural unit represented by the general formula (2) in the present embodiment, poly (3,3,4-trifluoro-4-trifluoromethyl-7,9) -Tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-trifluoroethyl-4-trifluoromethyl-7,9-tricyclo [4.3.0] .1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-perfluoro-iso-propyl-4-trifluoromethyl-7,9-tricyclo [4.3.0.1 ^2,5 ] de crab Ren ethylene), poly (3,4-difluoro-3,4-bis (trifluoromethyl) -7,9-tricyclo [4.3.0.1 ^{2, 5]} de crab Ren ethylene), poly (3, 4-Difluoro-3-trifluoromethyl-4-perfluoroethyl-7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly (3- (3-trifluoromethyl-2,) 2,3,3,4,5,5-octafluoro-cyclopentyl) -7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly ((3,3,4) -Trifluoro-2-perfluorobutyl) -7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-trifluoromethyl-4-perfluorobutyl) 7,9 tricyclo [4.3.0.1 ^{2, 5]} de crab Ren ethylene), poly (3-fluoro-3-perfluoroethyl-4,4-bis (trifluoromethyl)) - 7,9 tricyclo [4.3.0.1 ^{2, 5]} de crab Ren ethylene), poly (3,4-difluoro-3-perfluoropropyl-4- trifluoromethyl) -7,9-tricyclo [4.3.0. 1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-trifluoromethyl-4-perfluorobutyl-7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene) , Poly (3,4-difluoro-3-trifluoromethyl-4-perfluoropentyl-7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly (3,3,4- trifluoro-4-trifluoromethoxy-7,9-tricyclo [4.3.0.1 ^{2, 5]} de crab Ren ethylene), poly (3,4-difluoro-3,4-bis (trifluoperazine Lomethoxy) -7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-trifluoromethoxy-4-perfluoroethoxy-7,9-tricyclo [ 4.3.0.1 ^2,5 ] decanylene ethylene), poly (3,3,4-trifluoro-2-perfluorobutoxy-7,9-tricyclo [4.3.0.1 ^2,5 ] deca Niren'echiren), poly (3,4-difluoro-3-trifluoromethoxy-4-perfluoro-butoxy-7,9-tricyclo [4.3.0.1 ^{2, 5]} de crab Ren ethylene), poly (3-fluoro -3-Perfluoroethoxy-4,4-bis (trifluoromethoxy) -7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-perfluoro) Propoxy-4-trifluoromethoxy-7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-trifluoromethoxy-4-perfluorobutoxy-7) , 9-Tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), Poly (3,3,4-trifluoro-3-perfluoroheptoxy-7,9-tricyclo [4.3.0. 1 ^2,5 ] decanylene ethylene), poly (3,4-difluoro-3-trifluoromethoxy-4-perfluoropentyl-7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene) , Poly (3- (4', 4', 4'-trifluoroethoxy) -7,9-tricyclo [4.3.0.1 ^2,5 ] decanylene ethylene), Poly (1- (2', 2', 3', 3', 3'-pentafluoropropoxy) -3,5-cyclopentyleneethylene), poly (1- (2', 2', 3', 3', 4', 4', 4'-Heptafluorobutoxy) -3,5-cyclopentyleneethylene), poly (1,2-difluoro-1-trifluoromethoxy-2- (2', 2', 2'-trifluoroethoxy) -3 , 5-Cyclopentylene ethylene), poly (1,1,2-trifluoro-2- (2', 2', 3', 3', 4', 4', 4'-heptafluorobutoxy) -3 , 5-Cyclopentylene ethylene), poly (1,2-difluoro-1-trifluoromethoxy-2- (2', 2', 3', 3', 4', 4', 4'-heptafluorobutoxy) ) -3,5-Cyclopentylene ethylene ), Poly (1-fluoro-1- (2', 2', 2'-trifluoroethoxy) -2,2-bis (trifluoromethoxy))-3,5-cyclopentyleneethylene), poly (1) , 2-Difluoro-1- (2', 2', 3', 3', 3'-pentafluoropropoxy) -2-trifluoromethoxy-3,5-cyclopentyleneethylene), poly (1,1,1 2-Trifluoro-2- (1', 1', 1'-trifluoro-iso-propoxy) -3,5-cyclopentyleneethylene), poly (1,2-difluoro-1-trifluoromethoxy-2) -(2', 2', 3', 3', 4', 4', 4'-heptafluorobutoxy) -3,5-cyclopentyleneethylene) and the like.

A fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1) as a member for a medical device of the present embodiment, or a structural unit [A] represented by the general formula (1) and a general formula (2). The fluorine-containing cyclic olefin polymer containing the repeating structural unit [B] represented by) ^{has fluorine in the substituents of R 1 to} R ⁴ or R ^{5 to} R ⁸ , or all of which contain fluorine and have 1 carbon number. It is an alkyl group of 10 to 10, an alkoxy group having 1 to 10 carbon atoms, and an alkoxyalkyl group having 2 to 10 carbon atoms. As a result, the fluorine atom of the substituent forms a hydrogen bond due to a relatively strong intermolecular interaction, so that the storage elastic modulus (E') in the solid viscoelasticity measurement as an index of the thermal deformation temperature of the member is within an appropriate range. Can be adjusted to. Further, the same effect can be realized by a fluorine-containing cyclic olefin polymer obtained by copolymerization with the repeating structural unit [B] having a bulky cyclic structure represented by the general formula (2).
The storage elastic modulus (E') in the solid viscoelasticity measurement as an index of the thermal deformation temperature is the storage elastic modulus (E') at 120 ° C., which is the temperature condition of high-pressure steam sterilization, and is preferably 1 × 10 ⁶ to 1. It is 1 × 10 ¹⁰ Pa, more preferably 1 × 10 ^{6 to} 7 × 10 ⁹ Pa, and even more preferably 1 × 10 ^{6 to} 5 × 10 ⁹ Pa.

High-pressure steam sterilization is an effective sterilization method that is simple and inexpensive to operate in the field of drug discovery using cells or regenerative medicine. According to the Guidelines for Guarantee of Sterilization in Medical Fields 2015 (Japan Medical Equipment Society), heat sterilization at 121 ° C for 15 minutes ^{is usually the standard for killing spores of thermostable bacteria at a level of 10-12 or less.} It has been adapted.
A fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1) of the present embodiment, or a repetition represented by the structural unit [A] represented by the general formula (1) and the general formula (2). By setting the storage elastic modulus (E') at 120 ° C. in the solid viscoelasticity measurement of the fluorine-containing cyclic olefin polymer containing the structural unit [B] within the above range, it is carried out under the conditions of 121 ° C. and 15 minutes. In high-pressure steam sterilization, it is possible to provide a member as a medical device having sufficient heat resistance that does not cause thermal deformation.

The molecular weight of the fluorine-containing cyclic olefin polymer in the present embodiment is, for example, 5 in polystyrene-equivalent weight average molecular weight (Mw) measured by gel permeation chromatography (GPC) at a sample concentration of 3.0 to 9.0 mg / ml. It is preferably from 1,000 to 1,000,000, more preferably from 10,000 to 300,000. By setting this weight average molecular weight (Mw) to the above lower limit value or more, a member in a good state in which cracks due to external stress do not occur, especially in a molded product adapted to an operating part such as bending. Can be obtained more reliably. Further, by setting the weight average molecular weight (Mw) to be equal to or lower than the above upper limit value, it is possible to have fluidity that facilitates melt molding.
Furthermore, by setting the polystyrene-equivalent weight average molecular weight (Mw) in the above range, the storage elastic modulus (E') at 120 ° C., which is the temperature condition for high-pressure steam sterilization, is preferably 1 × 10 ⁶ to 1 × 10. It can be reliably adjusted to the range of ¹⁰ Pa, more preferably 1 × 10 ^{6 to} 7 × 10 ⁹ Pa, and even more preferably 1 × 10 ^{6 to} 5 × 10 ^{9 Pa.}

The molecular weight distribution (Mw / Mn), which is the ratio of the weight average molecular weight (Mw) to the number average molecular weight (Mn), is preferably 1.3 to 5.0, preferably 1.5 to 4.5. It is more preferable to set it to 1.7 to 4.0, and it is particularly preferable to set it to 1.7 to 4.0. By setting this molecular weight distribution (Mw / Mn) to the above lower limit value or more, the toughness of the film or molded product produced by various molding methods such as the solution casting method and the melt molding method is improved, and cracks caused by external stress are generated. The occurrence of cracks can be suppressed more effectively. On the other hand, by setting the molecular weight distribution (Mw / Mn) to the above upper limit or less, it is possible to suppress the elution of particularly low molecular weight components such as oligomers, and to prepare a member made of a biocompatible material that does not show hemolytic toxicity. A medical device composed of the member can be preferably obtained.

The glass transition temperature (Tg) of the fluorine-containing cyclic olefin polymer by differential scanning calorimetry is preferably 50 to 300 ° C, more preferably 80 to 280 ° C, and even more preferably 100 to 250 ° C. .. When the glass transition temperature is in the above range, the fluorine-containing cyclic olefin polymer of the present embodiment has a characteristic heat resistance, and the storage elastic modulus (E') of solid viscoelasticity at 120 ° C. is preferably 1 × 10 ⁶ to 1. It is 1 × 10 ¹⁰ Pa, more preferably 1 × 10 ^{6 to} 7 × 10 ⁹ Pa, still more preferably 1 × 10 ^{6 to} 5 × 10 ⁹ Pa, and high-pressure steam sterilization can be applied. In addition, medical or living cells and cells that can maintain their shape under the usage environment, have excellent fluidity with respect to heating temperature in melt molding, have good production stability, and have excellent hue were used. A medical device made of the members of the present embodiment for inspection can be preferably obtained.

Examples of the use form of the member in the present embodiment include members constituting medical devices such as catheters, blood bags, stents, extracorporeal circulation circuits for heart-lung machines, plates, petri dishes, dishes, flasks, and tubes.

(Method for Producing Fluorine-Containing Cyclic Olefin Polymer)
Next, a method for producing the fluorine-containing cyclic olefin polymer will be described.
By using a member for a medical device made of a fluorine-containing cyclic olefin polymer obtained by the production method described below for at least a member in direct contact with blood or living cells of the medical device, blood contamination is prevented and a thrombus is formed. It is possible to obtain a medical device that does not cause blood degeneration that causes an inflammatory reaction and that does not cause cell death for a long period of time, and that makes contact with living cells containing blood.

Specifically, the cyclic olefin monomer represented by the following general formula (3) is chain-transfer polymerized by a ring-opening metathesis polymerization catalyst, and the olefin portion of the main chain of the obtained polymer is hydrogenated to form a fluorine-containing cyclic. Olefin polymers can be synthesized.

（式（３）中、Ｒ^１〜Ｒ^４は、一般式（１）のＲ^１〜Ｒ^４と同義である。また、Ｒ^１〜Ｒ^４は互いに結合して環構造を形成していてもよい。）

(In the formula ^(3), R 1 to R ⁴ have the same meanings as ^R 1 to R ⁴ in the general formula (1). ^Moreover, also form an R 1 to R ⁴ are bonded to each other to form a ring structure Good.)

Further, by copolymerizing the cyclic olefin monomer represented by the following general formula (4) with the cyclic olefin monomer represented by the above general formula (3) and hydrogenating the olefin portion of the main chain of the obtained polymer. , Fluorine-containing cyclic olefin polymers can also be synthesized.

（式（４）中、Ｒ^５〜Ｒ^８は、一般式（２）のＲ^５〜Ｒ^８と同義である。また、Ｒ^５〜Ｒ^８は互いに結合して環構造を形成していてもよい。）

(In the formula ^(4), R 5 to R ⁸ have the same meanings as ^R 5 to R ⁸ of general formula (2). ^Moreover, even if R 5 to R ⁸ are connected to form a ring structure Good.)

In addition, a monomer other than the cyclic olefin monomer represented by the general formulas (3) and (4) may be contained as long as the effect of the present embodiment is not impaired.

Here, when synthesizing the fluorine-containing cyclic olefin polymer of the present embodiment, the monomers represented by the general formulas (3) and (4) may be used in an amount of 90 to 100% by mass based on the total amount of the compounds contributing to the polymerization. It is preferable to use 95 to 100% by mass, and even more preferably 98 to 100% by mass.

A fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1) of the present embodiment or a repeating structure represented by the structural unit [A] represented by the general formula (1) and the general formula (2). In the fluorine-containing cyclic olefin polymer containing the unit [B], the double bond of the main chain is hydrogenated after ring-opening metathesis polymerization of the monomer represented by the general formula (3) or / and the general formula (4). It is a (hydrogenated) fluorine-containing polymer. For ring-opening metathesis polymerization, a Schrock catalyst is preferably used, and a Grubbs catalyst may be used, whereby the polymerization catalytic activity for polar monomers can be enhanced, and an industrially excellent production method can be realized. These ring-opening metathesis polymerization catalysts may be used alone or in combination of two or more. It is also possible to use a ring-opening metathesis polymerization catalyst consisting of a combination of a classical organic transition metal complex, a transition metal halide or a transition metal oxide, and Lewis acid as a co-catalyst.

Further, when performing ring-opening metathesis polymerization, an olefin or diene can be used as a chain transfer agent in order to control the molecular weight and its distribution. As the olefin, for example, α-olefins such as ethylene, propylene, 1-butene, 1-pentene, 1-hexene and 1-octene, or fluorine-containing olefins thereof can be used. Furthermore, silicon-containing olefins such as vinyltrimethylsilane, allyltrimethylsilane, allyltriethylsilane, and allyltriisopropylsilane, or fluorine and silicon-containing olefins thereof can also be used as the chain transfer agent. Examples of the diene include non-conjugated diene such as 1,4-pentadiene, 1,5-hexadiene, and 1,6-heptadiene, or fluorine-containing non-conjugated diene thereof. These olefins, fluorine-containing olefins or dienes may be used alone or in combination of two or more.

Further, the ring-opening metathesis polymerization of the monomer may be carried out without a solvent or with a solvent. When a solvent is used, the solvent includes ethers such as tetrahydrofuran, diethyl ether, dibutyl ether, dimethoxyethane or dioxane; esters such as ethyl acetate, propyl acetate or butyl acetate; aliphatic hydrocarbons such as pentane, hexane or heptane. Hydrogens; aliphatic cyclic hydrocarbons such as cyclopentane, cyclohexane, methylcyclohexane, dimethylcyclohexane or decalin; fluorine-containing aliphatic cyclic hydrocarbons such as perfluorohexane and perfluorocyclodecalin; or perfluoro-2-butyl tetrahydrofuran and the like Fluorine-containing ethers can be used. These may be used alone or in combination of two or more.

In ring-opening metathesis polymerization of a monomer, the concentration of the monomer in the monomer solution is preferably 5 to 100% by mass, preferably 10 to 60% by mass, although it depends on the reactivity of the monomer and the solubility in the polymerization solvent. Is more preferable. The reaction temperature is preferably -30 to 150 ° C, more preferably 30 to 100 ° C. The reaction time is preferably 10 minutes to 120 hours, more preferably 30 minutes to 48 hours. Further, the reaction can be stopped with aldehydes such as butyraldehyde, ketones such as acetone, alcohols such as methanol, and deactivators such as water to obtain a solution of the polymer.

The catalyst for hydrogenating the double bond portion of the main chain of the polymer obtained by ring-opening metathesis polymerization can be either a homogeneous metal complex catalyst or a heterogeneous metal-supporting catalyst as long as it can hydrogenate. There may be. Among these, a heterogeneous metal-supported catalyst capable of easily separating the catalyst is preferable, and examples thereof include activated carbon-supported palladium, alumina-supported palladium, activated carbon-supported rhodium, alumina-supported rhodium, activated carbon-supported ruthenium, and alumina-supported ruthenium. Can be mentioned. These catalysts may be used alone or in combination of two or more. Particularly preferred is an activated carbon-supported catalyst. By using this activated carbon-supporting catalyst, metal components derived from the above-mentioned polymerization catalyst and hydrogenation catalyst are removed, there is no hemolytic toxicity to blood or living cells in direct contact, and a fluorine-containing ring as a biocompatible material. Olefin polymers can be produced.

The solvent used for hydrogenation is not particularly limited as long as it dissolves the polymer and the solvent itself is not hydrogenated. For example, ethers such as tetrahydrofuran, diethyl ether, dibutyl ether and dimethoxyethane; ethyl acetate. , Esters such as propyl acetate or butyl acetate; aliphatic hydrocarbons such as pentane, hexane, heptane; aliphatic cyclic hydrocarbons such as cyclopentane, cyclohexane, methylcyclohexane, dimethylcyclohexane, decalin; perfluorohexane, perfluorocyclo Fluorine-containing aliphatic cyclic hydrocarbons such as decalin; fluorine-containing ethers such as perfluoro-2-butyl tetrahydrofuran and the like can be mentioned. These may be used alone or in combination of two or more.

In the hydrogenation reaction of the olefin portion of the main chain, the hydrogen pressure is preferably 10 MPa at normal pressure, more preferably 0.5 to 8 MPa, and particularly preferably 2 to 5 MPa. The reaction temperature is preferably 0 to 200 ° C, more preferably room temperature to 150 ° C, and particularly preferably 50 to 100 ° C. The embodiment of the hydrogenation reaction is not particularly limited, and for example, a method in which the catalyst is dispersed or dissolved in a solvent, a method in which the catalyst is packed in a column or the like, and a polymer solution is circulated as a stationary phase is used. Can be mentioned.

Further, in the hydrogenation treatment of the olefin portion of the main chain, even if the polymerization solution of the polymer before the hydrogenation treatment is precipitated in a poor solvent to isolate the polymer and then dissolved in the solvent again and the hydrogenation treatment is performed, the polymerization is carried out. The hydrogenation treatment may be carried out with the above hydrogenation catalyst without isolating the polymer from the solution, and there is no particular limitation.

The hydrogenation rate of the olefin portion of the polymer is preferably 80% or more, preferably 90 to 100%, and even more preferably 95 to 100%. When the hydrogenation rate is set to the above lower limit or higher, deterioration due to light absorption and oxidation due to heating during molding are suppressed in the olefin portion, and the adhesiveness with the members constituting the medical device is improved. It can be good. In addition, residual double bonds can interfere with the observation of growing cells under a fluorescence microscope.

After hydrogenation, the method for obtaining the polymer from the polymer solution, particularly when a heterogeneous metal-supporting catalyst such as activated carbon-supported palladium or alumina-supported palladium is preferably used, is not particularly limited, and is, for example, filtration, centrifugation, or decantation. A method of obtaining a catalyst-free polymer solution by a method such as filtration and discharging the reaction solution into a poor solvent under stirring, a method of precipitating the polymer by a method such as steam stripping in which steam is blown into the reaction solution, or a method of precipitating the polymer. Examples thereof include a method of evaporating and removing the solvent from the reaction solution by heating or the like.

When the hydrogenation reaction is carried out using a heterogeneous metal-supporting catalyst, the polymer can be obtained by the above method after filtering the synthetic solution and filtering the metal-supporting catalyst. Preferably, in order to obtain a polymer solution containing no catalyst as a member constituting a medical device, the solution obtained by roughly removing the catalyst component may be filtered to obtain the polymer by the method described above. In particular, it is preferable to microfilter the catalyst component, and the opening of the filtration filter is preferably 10 μm to 0.05 μm, particularly preferably 10 μm to 0.10 μm, and further preferably 5 μm to 0.10 μm. Is.

A fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1) or a structural unit [A] represented by the general formula (1) used for producing a member constituting the medical device of the present embodiment. The molded product (member) made of the fluorine-containing cyclic olefin polymer containing the repeating structural unit [B] represented by the general formula (2) does not emit autofluorescence from the member. As a result, the medical device on which the member made of the material is mounted can be used as a medical tube for drawing the drug into the living body, for example, marking the drug by fluorescence from outside the body, or autofluorescence of the cell used for determining the life or death of the cell. It can be widely used for observation. At that time, the applicable fluorescence wavelength is preferably a wavelength of 200 to 1000 nm, more preferably 220 to 900 nm, and further preferably 250 to 800 nm. Further, the excitation wavelength of fluorescence applicable to the above fluorescence wavelength is preferably a wavelength of 200 to 1000 nm, more preferably 220 to 900 nm, and further preferably 250 to 800 nm. By being able to adapt to a wide range of fluorescence wavelengths from ultraviolet to near infrared and the excitation wavelength of fluorescence, it can be applied to many types of drugs and cells, and can be used in a wide range of fields as medical instruments.

(Fluorine-containing cyclic olefin polymer composition used for members constituting medical devices)
The member according to the present embodiment may be composed of a fluorine-containing cyclic olefin polymer composition containing a fluorine-containing cyclic olefin polymer, a photocurable compound, and a photocuring initiator.
In the fluorine-containing cyclic olefin polymer composition of the present embodiment, the fluorine-containing cyclic olefin polymer represented by the general formula (1) of the present embodiment or the structural unit [A] represented by the general formula (1) and the general formula. The mass ratio of the fluorine-containing cyclic olefin polymer containing the repeating structural unit [B] represented by (2) to the photocurable compound (fluorine-containing cyclic olefin polymer / photocurable compound) is 99.9 / 0. It is preferably 1 to 30/70, more preferably 99.9 / 0.1 to 35/65, and even more preferably 99.9 / 0.1 to 40/60.
Examples of the photocurable compound include a ring-opening polymerizable compound capable of cationically polymerizable, a compound having a reactive double bond group, and the like. Preferably, from the viewpoint of suppressing deformation of the member due to volume shrinkage after curing when coated and used, compatibility with a fluorine-containing cyclic olefin polymer, and safety to a living body, ring-opening polymerization property capable of cationic polymerization is possible. The compound is selected.

The ring-opening polymerizable compound capable of cationically polymerizable and the compound having a reactive double-bonding group may have one reactive group in one molecule, or may have a plurality of reactive groups. Further, in the photocurable compound, compounds having different reactive groups may be mixed and used at an arbitrary ratio. Further, as the photocurable compound, a compound having a reactive double bond group and a ring-opening polymerizable compound that can be cationically polymerized may be mixed at an arbitrary ratio.

Among the photocurable compounds, the cationically polymerizable ring-opening polymerizable compounds include, for example, cyclohexene epoxide, dicyclopentadiene oxide, limonendioxide, 4-vinylcyclohexenedioxide, and 3,4-epoxycyclohexylmethyl-3'. , 4'-epoxycyclohexanecarboxylate, di (3,4-epoxycyclohexyl) adipate, (3,4-epoxycyclohexyl) methyl alcohol, (3,4-epoxy-6-methylcyclohexyl) methyl-3,4-epoxy -6-Methylcyclohexanecarboxylate, ethylene-1,2-di (3,4-epoxycyclohexanecarboxylic acid) ester, (3,4-epoxycyclohexyl) ethyltrimethoxysilane, phenylglycidyl ether, dicyclohexyl-3,3' -Diepoxide, 1,7-octadiene diepoxy, bisphenol A type epoxy resin, halogenated bisphenol A type epoxy resin, bisphenol F type epoxy resin, o-, m-, p-cresol novolac type epoxy resin, phenol novolac type epoxy Resins, polyglycidyl ethers of polyhydric alcohols, alicyclic epoxy resins such as 3,4-epoxycyclohexenylmethyl-3', 4'-epoxycyclohexene carboxylate, or epoxy compounds such as glycidyl ether of hydrogenated bisphenol A. Epoxy compounds can be mentioned.

In addition, 3-methyl-3- (butoxymethyl) oxetane, 3-methyl-3- (pentyloxymethyl) oxetane, 3-methyl-3- (hexyloxymethyl) oxetane, 3-methyl-3- (2-ethyl) Hexyloxymethyl) oxetane, 3-methyl-3- (octyloxymethyl) oxetane, 3-methyl-3- (decaniloxymethyl) oxetane, 3-methyl-3- (dodecaniloxymethyl) oxetane, 3-methyl -3- (phenoxymethyl) oxetane, 3-ethyl-3- (butoxymethyl) oxetane, 3-ethyl-3- (pentyloxymethyl) oxetane, 3-ethyl-3- (hexyloxymethyl) oxetane, 3-ethyl -3- (2-ethylhexyloxymethyl) oxetane, 3-ethyl-3- (octyloxymethyl) oxetane, 3-ethyl-3- (decanyroxymethyl) oxetane, 3-ethyl-3- (dodecaniloxy) Methyl) oxetane, 3- (cyclohexyloxymethyl) oxetane, 3-methyl-3- (cyclohexyloxymethyl) oxetane, 3-ethyl-3- (cyclohexyloxymethyl) oxetane, 3-ethyl-3- (phenoxymethyl) oxetane , 3,3-dimethyloxetane, 3-hydroxymethyloxetane, 3-methyl-3-hydroxymethyloxetane, 3-ethyl-3-hydroxymethyloxetane, 3-ethyl-3-phenoxymethyloxetane, 3-n-propyl- 3-Hydroxymethyloxetane, 3-isopropyl-3-hydroxymethyloxetane, 3-n-butyl-3-hydroxymethyloxetane, 3-isobutyl-3-hydroxymethyloxetane, 3-sec-butyl-3-hydroxymethyloxetane, 3-tert-Butyl-3-hydroxymethyloxetane, 3-ethyl-3- (2-ethylhexyl) oxetane, etc. Other compounds having two or more oxetanyl groups include bis (3-ethyl-3-oxetanylmethyl) ether (3-ethyl-3-oxetanylmethyl) ether ( 3-Ethyl-3 {[(3-ethyloxetane-3-yl) methoxy] methyl} oxetane), 1,2-bis [(3-ethyl-3-oxetanylmethoxy)] ethane, 1,3-bis [( 3-Ethyl-3-oxetanylmethoxy)] propane, 1,3-bis [(3-ethyl-3-oxetanylmethoxy)]-2,2-dimethyl-propane, 1,4-bis (3-ethyl-3-3) Oxetane methoxy) butane, 1,6-bis (3) -Ethyl-3-oxetanylmethoxy) hexane, 1,4-bis [(3-methyl-3-oxetanyl) methoxy] benzene, 1,3-bis [(3-methyl-3-oxetanyl) methoxy] benzene, 1, 4-bis {[(3-methyl-3-oxetanyl) methoxy] methyl} benzene, 1,4-bis {[(3-methyl-3-oxetanyl) methoxy] methyl} cyclohexane, 4,4'-bis {[ (3-Methyl-3-oxetanyl) methoxy] methyl} biphenyl, 4,4'-bis {[(3-methyl-3-oxetanyl) methoxy] methyl} bicyclohexane, 2,3-bis [(3-methyl-) 3-Oxetanyl) methoxy] bicyclo [2.2.1] heptane, 2,5-bis [(3-methyl-3-oxetanyl) methoxy] bicyclo [2.2.1] heptane, 2,6-bis [(3-methyl-3-oxetanyl) methoxy] bicyclo [2.2.1] heptane 3-Methyl-3-oxetanyl) methoxy] bicyclo [2.2.1] heptane, 1,4-bis [(3-ethyl-3-oxetanyl) methoxy] benzene, 1,3-bis [(3-ethyl-) 3-Oxetanyl) methoxy] benzene, 1,4-bis {[(3-ethyl-3-oxetanyl) methoxy] methyl} benzene, 1,4-bis {[(3-ethyl-3-oxetanyl) methoxy] methyl} Cyclohexane, 4,4'-bis {[(3-ethyl-3-oxetanyl) methoxy] methyl} biphenyl, 4,4'-bis {[(3-ethyl-3-oxetanyl) methoxy] methyl} bicyclohexane, 2 , 3-Bis [(3-ethyl-3-oxetanyl) methoxy] bicyclo [2.2.1] heptane, 2,5-bis [(3-ethyl-3-oxetanyl) methoxy] bicyclo [2.2.1] ] Heptane, 2,6-bis [(3-ethyl-3-oxetanyl) methoxy] bicyclo [2.2.1] oxetane compounds such as heptane can be mentioned. These may be used alone or in combination of two or more.

Examples of the photocuring initiator for curing the above-mentioned monomer of the present embodiment include a photocation initiator that generates a cation by irradiation with light, a photoradical initiator that generates a radical by irradiation with light, and the like. The amount of the photocurable initiator used is preferably 0.05 parts by mass or more, and more preferably 0.1 to 10 parts by mass with respect to 100 parts by mass of the photocurable compound.

The type of photocurable initiator and the amount used for the photocurable compound are suitably selected according to the purpose of use as a medical device composed of a member composed of the fluorine-containing cyclic olefin polymer composition of the present embodiment.

Among the photocuring initiators, the photocation initiator that generates a cation by irradiation with light is not particularly limited as long as it is a compound that initiates cationic polymerization of the above-mentioned cationically polymerizable ring-opening polymerizable compounds by irradiation with light. However, for example, a compound that photoreacts with an onium salt with an anion paired with an onium cation to release Lewis acid is preferable.

Specific examples of onium cations include diphenyliodonium, 4-methoxydiphenyliodonium, bis (4-methylphenyl) iodonium, bis (4-tert-butylphenyl) iodonium, bis (dodecylphenyl) iodonium, triphenylsulfonium, and diphenyl. -4-thiophenoxyphenyl sulfonium, bis [4- (diphenyl sulfonio) -phenyl] sulfide, bis [4- (di (4- (2-hydroxyethyl) phenyl) sulfonio) -phenyl] sulfide, η ^5- Examples thereof include 2,4- (cyclopentagenyl) [1,2,3,4,5,6-η- (methylethyl) benzene] -iron (1+). In addition to the onium cation, perchlorate ion, trifluoromethanesulfonic acid ion, toluenesulfonic acid ion, trinitrotoluenesulfonic acid ion and the like can be mentioned. Further, these photocation initiators may be used alone or in combination of two or more.

On the other hand, specific examples of anions include tetrafluoroborate, hexafluorophosphate, hexafluoroantimonate, hexafluoroarsenate, hexachloroantimonate, tetra (fluorophenyl) borate, tetra (difluorophenyl) borate, and tetra (trifluoro). Phenyl) borate, tetra (tetrafluorophenyl) borate, tetra (pentafluorophenyl) borate, tetra (perfluorophenyl) borate, tetra (trifluoromethylphenyl) borate, tetra [di (trifluoromethyl) phenyl)] borate, etc. Can be mentioned. Further, these photocation initiators may be used alone or in combination of two or more.

Specific examples of the photocation initiators that are more preferably used include, for example, Irgacure 250 (manufactured by BASF), Irgacure 290 (manufactured by BASF), Irgacure 784 (manufactured by BASF), and Esacure 1064 (manufactured by Lamberty). ), WPI-124 (manufactured by Wako Pure Chemical Industries, Ltd.), CYRAURE UVI 6990 (manufactured by Union Carbite Japan), CPI-100P (manufactured by Sun Appro), PHOTO INITIOTOR 2074 (manufactured by Solbay Japan), ADEKA PUTMER SP-172 (Made by ADEKA), ADEKA PTMER SP-170 (manufactured by ADEKA), ADEKA PTMER SP-152 (manufactured by ADEKA), ADEKA PTMER SP-150 (manufactured by ADEKA) and the like. In addition, these photocation initiators may be used alone or in combination of two or more.

Further, if necessary, other known components as a third component, for example, an antiaging agent, a leveling agent, a wettability improving agent, a surfactant, a modifier such as a plasticizer, an ultraviolet absorber, an antiseptic, and an antibacterial agent. Stabilizers such as agents, photosensitizers, silane coupling agents, etc. may be added, but since the biocompatible material of the present embodiment is a material that does not have hemolytic toxicity, the third component should be used as much as possible. If you don't need to put it in, you don't need it.

In the cured form of the fluorine-containing cyclic olefin polymer composition of the present embodiment, the photocurable compound can form a three-dimensional network structure and the surface hardness can be modified to be hard. Therefore, it is possible to improve the scratch resistance when the member of the present embodiment is mounted on a medical device or the like, and it can be conveniently used in the medical field.

(Manufacturing method of medical device parts)
The member constituting the medical device in the present embodiment is a fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1), or a structural unit [A] represented by the general formula (1) and a general member. A member produced from a fluorine-containing cyclic olefin polymer containing the repeating structural unit [B] represented by the formula (2) or a composition containing the fluorine-containing cyclic olefin polymer, and is an inorganic material such as a metal. , And a member composited with an organic material such as a resin, and the form is not particularly limited.

Other materials used for compounding include metal materials such as nickel, iron, stainless steel, germanium, titanium and silicon, inorganic materials such as glass, quartz and alumina, polyimide, polyamide, polyester, polycarbonate, polyphenylene ether and polyphenylene sulfide. Examples thereof include resin materials such as polyacrylate, polymethacrylate, epoxy resin and silicone resin, and carbon materials such as diamond, graphite and carbon fiber.

Examples of the method for producing a member constituting a medical device by a melt molding method include a method in which the fluorine-containing cyclic olefin polymer exemplified above is heated and melted by a melt kneader and formed into a film through a T-die. In the production of melt-extruded film by T-die, for example, a cyclic olefin polymer containing an additive is charged into an extruder, and the temperature is preferably 50 ° C. to 200 ° C. higher than the glass transition temperature, more preferably 80. It is melt-kneaded at a high temperature of ° C. to 150 ° C., extruded from a T-die, fed by a cooling roll, and processed into a winding film.

Further, in the melt molding method, it is also possible to process the molten resin into a tube shape by providing a desired tubular die at the resin outlet of the extruder, extruding the molten resin, and feeding the resin by a take-up machine to cool the resin. Furthermore, the resin extruded from the tubular die is sandwiched between molds, air is blown from the air extraction port of the mold to inflate the resin, and after cooling, the resin is separated from the mold by blow molding to form a flask shape or the like. You can also process things.

As a method for producing a member constituting a medical device by injection molding, the fluorine-containing cyclic olefin polymer exemplified above is heated and melted by a melt-kneader and filled in a mold via a plunger or a screw, which is desired. A method of obtaining a member having a shape can be mentioned. The temperature at which the resin used at this time is melted is higher than the above-mentioned glass transition temperature, and the injection pressure is preferably in the range of 1 MPa to 100 MPa, more preferably 5 MPa to 90 MPa, and further preferably 10 MPa to 80 MPa. The injection rate is preferably selected in consideration of the shape of the molded product or the productivity.

Further, when molding by injection molding, a member made of, for example, metal or resin is filled (inserted) in advance in the mold, and the heat-melted resin is passed through a plunger or a screw. An insert molding method may be used in which the mold is filled and the metal or resin and the fluorine-containing cyclic olefin polymer of the present embodiment are integrally molded in a desired shape.

In any molding method such as melt extrusion molding method, injection molding method, insert molding method, etc., UV absorbers, antioxidants, flame retardants, antistatic agents, colorants, etc., as long as the effects of the present embodiment are not impaired. Additives may be added.

Other methods include film and sheet molding by a solution casting method. A fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1), preferably a structural unit [A] represented by the general formula (1) and a repeating structural unit represented by the general formula (2) [ The fluorine-containing cyclic olefin polymer containing B] or the fluorine-containing cyclic olefin polymer composition is liquefied using an organic solvent, coated on an inorganic material such as the above-mentioned metal, or an organic material such as a resin, and dried. When the fluorine-containing cyclic olefin polymer composition is used, the photocurable compound can be cured by UV irradiation to prepare a coated composite member.
In any case, the film or sheet-like member of the present embodiment can be obtained by peeling from the coating substrate made of the above-mentioned inorganic material such as metal or organic material such as resin.

Examples of the organic solvent used include fluorine-containing ethers such as perfluoro-2-butyl tetrahydrofuran; ethers such as tetrahydrofuran, dibutyl ether, 1,2-dimethoxyethane and dioxane; ethyl acetate, propyl acetate, butyl acetate and the like. Esters; or ketones such as methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and the like can be mentioned. From these, it can be selected in consideration of solubility and film forming property. Further, these may be used alone or in combination of two or more types. In particular, from the viewpoint of film forming property, a solvent having a boiling point of 70 ° C. or higher under atmospheric pressure is preferable. As a result, it is possible to surely suppress that the evaporation rate becomes too fast, it is possible to suppress the occurrence of unevenness on the film surface, and it is also possible to contribute to the improvement of the film thickness accuracy during film formation.

The heating temperature for removing the solvent used for solution by drying is preferably 50 ° C. to 300 ° C., more preferably 60 ° C. to 280 ° C., and further preferably 70 ° C. to 250 ° C. is there. A multi-step process of changing the heating temperature stepwise may be used. The heating temperature is preferably selected in consideration of the characteristics and productivity of the organic and inorganic materials to be compounded, and the drying time is below the lower limit in consideration of the safety allowed when used as a medical device. It is set in a timely manner while checking the amount of residual solvent.

Further, the integrated light amount represented by the product of the irradiation intensity of light and time used when curing the fluorine-containing cyclic olefin polymer composition is preferably 3 to 3000 mJ / cm ² , and more preferably 5 to 2500 mJ / cm. It is cm ² , and more preferably 10 to 2000 mJ / cm ² . This light irradiation is controlled for each target product and is not particularly limited, but by setting the integrated light amount to the above lower limit value or more, the generation of active species from the photopolymerization initiator is generated. The above is sufficient, and the characteristics of the obtained cured product can be improved. On the other hand, by setting the integrated light amount to the above upper limit value or less, it is possible to contribute to the improvement of productivity. In some cases, it is also preferable to use heating in combination to promote the polymerization reaction. The temperature at which the curable resin is cured by irradiating it with light is usually preferably 0 to 150 ° C, more preferably 0 to 60 ° C.
Further, using the film or sheet-shaped member of the present embodiment obtained by the above method, a molded product such as a cup shape can be processed from a mold made of a desired metal or resin by a heat vacuum forming method. .. The temperature at which the resin used at this time is heated is preferably Tg-30 ° C. to Tg + 30 ° C., more preferably Tg-25 ° C. to Tg + 25 ° C., and even more preferably Tg + 25 ° C., based on the above-mentioned glass transition temperature (Tg). The degree of vacuum is Tg-20 ° C. to Tg + 20 ° C., and the degree of vacuum is preferably in the range of 90 to 0.001 kPa, more preferably 50 to 0.005 kPa, still more preferably 10 to 0.01 kPa, and the shape of the molded product or It is preferably selected in consideration of productivity.

（式（１）中、Ｒ ^１ 〜Ｒ ^４ は、フッ素、フッ素を含有する炭素数１〜１０のアルキル基、フッ素を含有する炭素数１〜１０のアルコキシ基、またはフッ素を含有する炭素数２〜１０のアルコキシアルキル基である。Ｒ ^１ 〜Ｒ ^４ は互いに同一であっても異なっていてもよい。また、Ｒ ^１ 〜Ｒ ^４ は互いに結合して環構造を形成していてもよい。）
２． １．に記載の医療器具用部材において、
前記フッ素含有環状オレフィンポリマーが前記一般式（１）で表される構造単位［Ａ］と下記一般式（２）で表される繰り返し構造単位［Ｂ］とを含有し、そのモル比［Ａ］／［Ｂ］が９０／１０〜１０／９０である医療器具用部材。

（式（２）中、Ｒ ^５ 〜Ｒ ^８ は、フッ素、フッ素を含有する炭素数１〜１０のアルキル基、フッ素を含有する炭素数１〜１０のアルコキシ基、またはフッ素を含有する炭素数２〜１０のアルコキシアルキル基である。Ｒ ^５ 〜Ｒ ^８ は互いに同一であっても異なっていてもよい。また、Ｒ ^５ 〜Ｒ ^８ は互いに結合して環構造を形成していてもよい。）
３． 蛍光波長２００ｎｍ以上１０００ｎｍ以下、および励起波長２００ｎｍ以上１０００ｎｍ以下の全領域において蛍光を発しないことを特徴とする１．または２．に記載の医療器具用部材。
４． 前記部材が、前記フッ素含有環状オレフィンポリマーと、光硬化性化合物と、光硬化開始剤と、を含むフッ素含有環状オレフィンポリマー組成物により構成されることを特徴とし、かつ、前記フッ素含有環状オレフィンポリマー組成物中における前記フッ素含有環状オレフィンポリマーと前記光硬化性化合物の質量比（前記フッ素含有環状オレフィンポリマー／前記光硬化性化合物）が、９９．９／０．１〜３０／７０である１．から３．のいずれか一つに記載の医療器具用部材。
５． １．から４．のいずれか一つに記載の医療器具用部材であって、
前記フッ素含有環状オレフィンポリマーの固体粘弾性測定における１２０℃の貯蔵弾性率（Ｅ´）が１×１０ ^６ 〜１×１０ ^１０ Ｐａであることを特徴とする医療器具用部材。
６． １．から５．のいずれか一つに記載の医療器具用部材を備える医療器具。 Further, depending on the purpose of the medical device, an uneven structure may be formed on the surface of the member constituting the medical device of the present embodiment. Various methods such as screen printing, embossing, submicron imprinting, and nanoimprinting can be applied to the formation of the concavo-convex structure, and the concavo-convex structure is preferably selected according to the shape and size of the concavo-convex structure. In particular, submicron imprint and nanoimprint are preferably used because they have a high degree of freedom in the shape of the concave-convex structure and can be widely applied in size from micro to nano-order.
Hereinafter, an example of the reference form will be added.
1. 1. A member that constitutes a medical device
The member is composed of a fluorine-containing cyclic olefin polymer containing a structural unit represented by the following general formula (1), and is calculated from the absorbance at a wavelength of 576 nm, which is the maximum UV absorption of oxygenated hemoglobin in a hemolytic toxicity test. A member for a medical device, which is made of a biocompatible material having a hemolysis rate of 0% or more and 2% or less.

(In the formula (1), R ^{1 to} R ⁴ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{1 to} R ⁴ may be the same or different from ^{each other, and R 1 to} R ⁴ may be bonded to each other to form a ring structure.)
2. 1. 1. In the medical device parts described in
The fluorine-containing cyclic olefin polymer contains a structural unit [A] represented by the general formula (1) and a repeating structural unit [B] represented by the following general formula (2), and the molar ratio [A] thereof. / [B] is a member for medical devices in which 90/10 to 10/90.

In the formula (2), R ^{5 to} R ⁸ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{5 to} R ⁸ may be the same or different from ^{each other, and R 5 to} R ⁸ may be bonded to each other to form a ring structure.)
3. 3. 1. It is characterized in that it does not fluoresce in the entire region having a fluorescence wavelength of 200 nm or more and 1000 nm or less and an excitation wavelength of 200 nm or more and 1000 nm or less. Or 2. A member for a medical device described in.
4. The member is characterized by being composed of a fluorine-containing cyclic olefin polymer composition containing the fluorine-containing cyclic olefin polymer, a photocurable compound, and a photocuring initiator, and the fluorine-containing cyclic olefin polymer. The mass ratio of the fluorine-containing cyclic olefin polymer to the photocurable compound in the composition (the fluorine-containing cyclic olefin polymer / the photocurable compound) is 99.9 / 0.1 to 30/70. From 3. A member for a medical device according to any one of the above.
5. 1. 1. From 4. A member for a medical device described in any one of the above.
A member for a medical device, wherein the storage elastic modulus (E') at 120 ° C. in the solid viscoelasticity measurement of the fluorine-containing cyclic olefin polymer is 1 × 10 ⁶ to 1 × 10 ^{10 Pa.}
6. 1. 1. From 5. A medical device including the member for the medical device described in any one of the above.

Hereinafter, the present invention will be described with reference to Examples, but the present invention is not limited to these examples. In addition, the polymer analysis value measurement method in the examples, the production conditions and analysis methods of the single-layer film member and the composite sheet member as the biocompatibility material evaluation, the hematological toxicity test method, and the cell culture and the cultured cells carried out as the cytotoxicity evaluation. The evaluation method is as described below.

[Weight average molecular weight (Mw), molecular weight distribution (Mw / Mn)]
Gel permeation chromatography (GPC) is used under the following conditions to determine the weight average molecular weight (Mw) and number average molecular weight (Mn) of a polymer dissolved in tetrahydrofuran (THF) or trifluorotoluene (TFT). , The molecular weight was calibrated and measured by polystyrene standard.
Detector: RI-2031 and 875-UV manufactured by JASCO Corporation, Model 270 manufactured by Viscotec, series-connected column: Shodex K-806M, 804, 803, 802.5, column temperature: 40 ° C., flow rate: 1.0 ml / min , Sample concentration: 3.0-9.0 mg / ml

[Glass-transition temperature]
Using a DSC-50 manufactured by Shimadzu Corporation, the measurement sample was heated and measured at a heating rate of 10 ° C./min in a nitrogen atmosphere.

[Hydrogenation rate measurement]
The polymer sample was dissolved in deuterated acetone and measured by the integral value of the peak attributable to hydrogen of the double bond carbon in the range of chemical shift δ = 5.0 ^{to 7.0 ppm in the 1 H-NMR spectrum at 270 MHz.}

[Measurement of metal content]
A solution having a known sample amount was precisely weighed in a container, pyrolyzed with nitric acid on a microwave, and the residual metal component was quantified by an ICP-MS apparatus of Agilent Technologies HP-4500. Alternatively, the polymer sample of the solution was precisely weighed in a container, heated to evaporate the solvent, and then pyrolyzed with nitric acid in a microwave, and the residual metal component was quantified by the ICP-MS method.

[UV curing]
The coating film was cured by irradiating LED light having a wavelength of 365 nm using SE650UV manufactured by Climb Products Co., Ltd. as a light source.

[Blood sampling for hematological toxicity test and anticoagulant treatment]
Blood was collected from the auricular arteries of three rabbits by 5 mL each using a syringe and a needle supplemented with sodium heparin as an anticoagulant. The absorbance of the collected anticoagulant-added blood (also referred to as anticoagulant-treated blood) at a wavelength of 576 nm was measured, and blood in which no hemolysis was observed was used in the test.

[Sample adjustment of absorbance measurement for hemolysis rate calculation]
From a film with a film thickness of 70 to 72 μm (thickness of 10 μm in the case of a coated film) and a size of 21 cm × 10 cm, 70 sheets of size 2.0 cm × 1.5 cm are shredded, immersed in 70% ethanol for sterilization, and phosphorus. The mixture was mixed with acid buffered saline (35 mL), placed in an autoclave, and heated at 37 ° C. for 72 hours to obtain an extract of the subject. Next, 5 mL of the extract and 0.1 mL of anticoagulant-treated blood are added to a sterile tube, mixed, incubated at 37 ° C. for 1, 2 and 4 hours, and the extract is separated using a centrifuge and the supernatant Was collected to prepare a sample for absorbance measurement. Negative controls were similarly incubated and positive controls were used as is without incubation.

[Measurement of absorbance and calculation of hemolysis rate]
Using a UV-3310 spectrophotometer manufactured by Hitachi, Ltd., the absorbance at a wavelength of 500 to 600 nm was measured, and the hemolysis rate of each sample with an incubation time of 1, 2 and 4 hours after the addition of anticoagulant-treated blood was measured. Was calculated from the absorbance at a wavelength of 576 nm by the above-mentioned equation (2), and the average value was taken as the hemolysis rate.

[About cell type and culture medium]
Using mouse fibroblasts (hereinafter abbreviated as BALB / 3T3 cells), 10% fetal bovine serum (Calf Bovine Serum, CBS), high glucose, and D-MEM medium (L-glutamine, phenol red, sodium pyruvate) All subcultures and cell proliferation tests were performed in a solution containing (containing) and (hereinafter referred to as BALB / 3T3 cell solution).

[Sterilization method for cell culture equipment]
A circular culture film cut out to a diameter of 15 mm is placed on the bottom surface of a hole in a TCPS multi-well plate (manufactured by Corning), a 70% ethanol aqueous solution is added, and the film is immersed for 40 minutes to 1 hour. Soaked in PBS (−) for 15-40 minutes. Next, remove PBS (-), turn over the culture film placed on the bottom of the hole of the culture instrument (TCPS multi-well plate with the culture film placed on the bottom of the hole), perform the same operation, and culture. The front and back surfaces of the instrument were sterilized and dried overnight in a clean bench under a germicidal lamp.

[Evaluation of cell proliferation]
After 1, 3, and 7 days after the start of culture, the culture medium was removed from the humidified incubator, the medium was removed, and a mixed solution of 10% WST-8 (Cell Counting Kit-8) / 10% calf serum D-MEM medium was used. Was added and incubated in a humidified incubator for 3 hours. Then, 200 μl of the medium was transferred to a 96-well plate, and the absorbance at a wavelength of 450 nm was measured with a plate reader (SPECTRA max PLUS384, manufactured by Molecular Devices). The cell proliferation of each culture vessel was confirmed by the change in absorbance over time.

[Calculation of cell viability]
The number of cells confirmed by observing the cells grown by culturing with a light-dark microscope and the number of autofluorescent dead cells observed using an all-in-one fluorescence microscope BZ-X700 (manufactured by Keyence) were counted, and the cells were counted. The survival rate was calculated from the formula of survival rate (%) = [(number of dead cells) / (number of cells confirmed by observation with a light-dark microscope)] × 100.

[Autofluorescence observation of members]
Using the FP-6600 spectrophotometer manufactured by JASCO Corporation, the scan speed is 2000 nm / min, the excitation side bandwidth is 5 nm, and the fluorescence side band is in each wavelength range of the excitation light measurement range of 200 to 1000 nm and the fluorescence measurement range of 200 to 1000 nm. The measurement was performed under the condition of a width of 6 nm.

[High-pressure steam sterilization method]
A test piece cut out to a size of 30 mm × 30 mm is sandwiched from above and below with a tubular SUS tube having an inner diameter of 15 mm × a height of 20 mm to prepare a container having a shape fixed with a SUS clip, and using an autoclave, 2 atm. It was sterilized by high pressure steam at 121 ° C. for 15 minutes under the steam atmosphere of the above, and dried overnight in a clean bench under a sterilization lamp.

[Solid viscoelasticity measurement]
Using RSA-III (manufactured by TA Instruments), using a test piece cut out to a width of 10 mm and a length of 30 mm, in tension mode, the temperature range is 0 to 160 ° C, and the heating rate is 3 ° C / The storage elastic modulus (Pa) at 120 ° C. was confirmed by measurement under the conditions of min and a frequency of 1 Hz.

[Production Example 1] Polymer 1
In a tetrahydrofuran solution of 5,5,6-trifluoro-6- (trifluoromethyl) bicyclo [2.2.1] hept-2-ene (100 g) and 1-hexene (0.268 g), Mo (N-N- ^{_{2,6-Pr i 2 C 6 H}} 3) (CHCMe 2 Ph) ( tetrahydrofuran was added a solution of OBu ^t) ₂ (50mg), a ring-opening metathesis polymerization monomer was performed to consume completely at 70 ° C. .. The olefin portion of the obtained polymer was hydrogenated at 160 ° C. in the presence of a 5% palladium-supported carbon catalyst (5 g) to carry out a poly (1,1,2-trifluoro-2-trifluoromethyl-3,5-) poly (1,1,2-trifluoro-2-trifluoromethyl-3,5-). A solution of cyclopentylene ethylene) in tetrahydrofuran was obtained.
The obtained solution was pressure-filtered with a filter having a pore size of 0.1 μm, the solution from which the palladium-supported carbon catalyst had been removed was added to methanol, the white polymer was filtered off, the solvent was completely removed, and the mixture was dried to obtain 99 g of polymer 1. It was.
The obtained polymer 1 contained a structural unit represented by the above general formula (1). The hydrogenation rate was 100%, the Mo and Pd metal contents were 10 ppb or less as analyzed by ICP-MS, the weight average molecular weight (Mw) was 78,000, the molecular weight distribution (Mw / Mn) was 1.70, and the glass transition. The temperature was 110 ° C. and the storage elastic modulus at 120 ° C. was 3 × 10 ⁶ Pa.

[Example 1] Member 1
The polymer 1 synthesized in Production Example 1 is dissolved in methyl isobutyl ketone at a concentration of 30% by mass, the solution is pressure-filtered with a filter having a pore size of 1 μm, and then filtered through a filter with a pore size of 0.1 μm to filter the methyl isobutyl ketone of the polymer 1. The solution was prepared. Next, a methyl isobutyl ketone solution of polymer 1 was applied to a glass substrate, coated uniformly using an applicator, dried at 140 ° C. for 60 minutes and peeled off to prepare a single-layer film member 1 having a thickness of 70 μm. ..

Next, the obtained film was shredded, sterilized, placed in an autoclave together with phosphate buffered saline (35 mL), and heated at 37 ° C. for 72 hours to prepare an extract for measuring absorbance. Three samples were prepared by mixing the extract (5 mL) and anticoagulant-treated blood (0.1 mL) in a sterile tube, and each was incubated at 37 ° C. for 1, 2 or 4 hours. After the lapse of a predetermined time, the sample was placed in a centrifuge (780 G) and allowed to stand for 5 minutes, and the supernatant was collected to prepare a sample for absorbance measurement.

From the UV absorbance spectrum, the absorbance at a wavelength of 576 nm was 0.06 (heating 1 hour), 0.08 (heating 2 hours), 0.07 (heating 4 hours), and the hemolytic rate was 0.13% (heating 1 hour). ), 0.14% (heating for 2 hours), 0.13% (heating for 4 hours), and the average value of the hemolytic rate was 0.13%. (As an example of the measurement result, the UV absorbance spectrum when the sample heated for 4 hours is measured is shown in FIG. 1).

[Example 2] Member 2
Same as Production Example 1 except that the type of fluorine-containing cyclic olefin monomer was changed to 5,6-difluoro-5-pentafluoroethyl-6-trifluoromethylbicyclo [2.2.1] hept-2-ene. 97 g of polymer 2 was obtained by the above method. The obtained polymer 2 contained a structural unit represented by the general formula (1). The hydrogenation rate was 100%, the Mo and Pd metal contents were 10 ppb or less as analyzed by ICP-MS, the weight average molecular weight (Mw) was 91000, the molecular weight distribution (Mw / Mn) was 1.93, and the glass transition. The temperature was 104 ° C. and the storage elastic modulus at 120 ° C. was 2 × 10 ⁶ Pa. Next, a single-layer film member 2 having a thickness of 70 μm was produced by the same method as in Example 1.

The absorbance of the member 2 adjusted and measured by the same method as in Example 1 was 0.01 (heating 1 hour), 0.01 (heating 2 hours), 0.02 (heating 4 hours), and the hemolytic rate was It was 0.03% (heating 1 hour), 0.03% (heating 2 hours), 0.04% (heating 4 hours), and the average value of the hemolytic rate was 0.03%.

[Example 3] Member 3
Production Example except that the type of fluorine-containing cyclic olefin monomer was changed to 5,6-difluoro-5-heptafluoro-iso-propyl-6-trifluoromethylbicyclo [2.2.1] hept-2-ene. 98 g of polymer 3 was obtained by the same method as in 1. The obtained polymer 3 contained a structural unit represented by the general formula (1). The hydrogenation rate was 100%, the Mo and Pd metal contents were 10 ppb or less as analyzed by ICP-MS, the weight average molecular weight (Mw) was 142000, the molecular weight distribution (Mw / Mn) was 1.40, and the glass transition. temperature was 137 ° C., the storage modulus of 120 ° C. was 7 × ¹⁰ 8 Pa. Next, a single-layer film member 3 having a thickness of 72 μm was produced by the same method as in Example 1.

The absorbance of the member 3 adjusted and measured by the same method as in Example 1 was 0.05 (heating 1 hour), 0.07 (heating 2 hours), 0.06 (heating 4 hours), and the hemolytic rate was It was 0.13% (heating 1 hour), 0.14% (heating 2 hours), 0.14% (heating 4 hours), and the average value of the hemolytic rate was 0.14%.

[Example 4] Member 4
3-Ethyl-3 {[(3-ethyloxetane) as the photocurable compound (B) in 100 g of a methylisobutylketone solution prepared by dissolving the fluorine-containing cyclic olefin polymer 1 (A) prepared in Example 1 at a concentration of 30% by mass. 20 g of a mixture of -3-yl) methoxy] methyl} oxetane and 1,7-octadiene epoxide in a mass ratio of 9/1, and 0. A solution containing 8 g was prepared, pressure-filtered with a filter having a pore size of 1 μm, and then filtered with a filter having a pore size of 0.1 μm to prepare a photocurable composition 1 (ratio of component (A) to component (B): [(A) / (B) = 60/40]). Next, a photocurable composition 1 was applied to a PET film manufactured by Toray Industries, Inc. having a thickness of 50 μm using a bar coater, dried at 120 ° C. for 10 minutes, allowed to cool to room temperature, and then irradiated with UV light having a wavelength of 365 nm. did. A composite sheet in which the photocurable composition 1 is coated again on the surface opposite to the coated surface in the same manner, dried and irradiated with UV, and the photocurable composition 1 is coated on both sides of the PET film with a thickness of 10 μm. Member 4 was produced.

The absorbance of the member 4 adjusted and measured by the same method as in Example 1 was 0.08 (heating 1 hour), 0.05 (heating 2 hours), 0.06 (heating 4 hours), and the hemolytic rate was It was 0.15% (heating 1 hour), 0.13% (heating 2 hours), 0.14% (heating 4 hours), and the average value of the hemolytic rate was 0.14%.

[Example 5] Member 5
The ratio of the fluorine-containing cyclic olefin polymer 1 (A) adjusted in Example 1 to the photocurable compound (B) was changed to (A) / (B) = 95/5, and the photocuring initiator was changed to CPI-100P. A composite in which the photocurable composition 2 is coated on both sides of the PET film with a thickness of 10 μm by the same method as in Example 4 except that the photocurable composition 2 is prepared by changing to (manufactured by Sun Appro). The sheet member 5 was produced.

The absorbance of the member 5 adjusted and measured by the same method as in Example 1 was 0.02 (heating 1 hour), 0.01 (heating 2 hours), 0.01 (heating 4 hours), and the hemolytic rate was It was 0.04% (heating 1 hour), 0.03% (heating 2 hours), 0.03% (heating 4 hours), and the average value of the hemolytic rate was 0.03%.

[Example 6]
The autofluorescence of the single-layer film member produced in Examples 1, 2 and 3 was measured in each wavelength range of the excitation light measurement range of 200 to 1000 nm and the fluorescence measurement range of 200 to 1000 nm, and the fluorescence intensity distribution was confirmed. No fluorescence was observed, which showed autofluorescence from the members of.

[Example 7]
The bottom surface of the recess of the 6-hole TCPS multi-well plate manufactured by Corning Inc. was cut out, and the single-layer film member 1 described in Example 1 was attached to the bottom surface to prepare a medical device as a cell culture container in which the bottom of the container was composed of the member 1. After sterilization with ethanol, a suspension of BALB / 3T3 cells (10 mL) adjusted to 7500 cells / mL in 10% calf serum D-MEM medium was seeded in the recesses of the culture vessel, covered, and transferred to the incubator. Then, the culture was started under sterile air at 37 ° C. and a carbon dioxide gas concentration of 5%.

In the evaluation of cell proliferation by the WST-8 method, the absorbance after 1 day was 0.52 ± 0.03, 1.70 ± 0.03 after 3 days, and 4.45 ± after 7 days. It was 0.09. The absorbance increased linearly with the elapsed days, and no attenuation of cell proliferation was observed even after 7 days. Moreover, when the autofluorescence of the cells cultured for 7 days was observed, the green fluorescence indicating dead cells was not observed, and it was confirmed that 100% of the cells were living cells. Furthermore, when the drug-metabolizing enzyme activity was evaluated with NADPH dehydrogenase of this cultured cell, it was found that the drug-metabolizing enzyme activity was similar to that of the ecosystem with a cell survival rate of almost 100%.

[Example 8]
A medical device as a cell culture container in which the bottom of the container is made of the composite sheet member 4 was produced by the same method as in Example 7 except that the member to be bonded was changed to the member 4 produced in Example 4. Next, BALB / 3T3 cells were cultured in the same manner as in Example 7.

In the evaluation of cell proliferation by the WST-8 method, the absorbance after 1 day was 0.41 ± 0.01, 1.34 ± 0.02 after 3 days, and 3.35 ± after 7 days. It was 0.08. The absorbance increased linearly with the elapsed days, and no attenuation of cell proliferation was observed even after 7 days. Moreover, when the autofluorescence of the cells cultured for 7 days was observed, the green fluorescence indicating dead cells was not observed, and it was confirmed that 100% of the cells were living cells. Furthermore, when the drug-metabolizing enzyme activity was evaluated with NADPH dehydrogenase of this cultured cell, it was found that the drug-metabolizing enzyme activity was similar to that of the ecosystem with a cell survival rate of almost 100%.

[Example 9]
5,5,6-trifluoro-6-trifluoromethyl-bicyclo [2.2.1] hept-2-ene (13.2 g) and 8,8,9-trifluoro-9-trifluoromethyl-tetracyclo [4.4.0.1 ^2,5 . 1 ^7,10] -3-two monomers of dodecene (17.3 g), and tetrahydrofuran 1,5-hexadiene (0.27g), Mo (N- 2,6-Pr i 2 C 6 H _{3) (CHCMe} 2 Ph) _{(tetrahydrofuran} was added a solution of OBu ^t) ₂ (17mg), was carried out ring-opening metathesis polymerization completely reacted consumed monomers at 70 ° C.. The olefin portion of the obtained polymer was hydrogenated at 160 ° C. under hydrogen pressurization using a 5% palladium / alumina-supported hydrogenation catalyst (2.3 g) to carry out a poly (1,1,2-trifluoro-). 2-trifluoromethyl-3,5-cyclopentylene ethylene) / (3,3,4-trifluoro-4-trifluoromethyl-7,9-tricyclo [4.3.0.1 ^{2, 5]} deca A tetrahydrofuran solution of a copolymer of nilenethylene) was obtained. The solution was added to methanol, the white polymer was filtered off and dried to give 47 g of polymer 4. The hydrogenation rate is 100%, the composition ratio [A] / [B] = 50/50, the weight average molecular weight (Mw) is 75,000, the molecular weight distribution (Mw / Mn) is 3.06, and the glass transition temperature is 149 ° C. The storage elastic modulus at 120 ° C. was 2 × 10 ⁹ Pa. Next, a single-layer film member 6 having a thickness of 70 μm was produced by the same method as in Example 1.
The absorbance of the member 6 adjusted and measured by the same method as in Example 1 was 0.02 (heating 1 hour), 0.01 (heating 2 hours), 0.02 (heating 4 hours), and the hemolytic rate was It was 0.02% (heating 1 hour), 0.02% (heating 2 hours), 0.03% (heating 4 hours), and the average value of the hemolytic rate was 0.02%.

[Example 10]
Poly (1,1,2-trifluoro-2-trifluoromethyl-3, in the same manner as in Example 9 except that the monomer ratio was changed to [A] / [B] = 80/20, 5-cyclopentylene ethylene) / (3,3,4-trifluoro-4-trifluoromethyl-7,9-tricyclo [4.3.0.1 ^{2, 5]} de crab Ren ethylene) copolymer A tetrahydrofuran solution was obtained. The solution was added to methanol, the white polymer was filtered off and dried to give 50 g of polymer 5. The hydrogenation rate is 100%, the composition ratio [A] / [B] = 80/20, the weight average molecular weight (Mw) is 71000, the molecular weight distribution (Mw / Mn) is 3.01, and the glass transition temperature is 179 ° C. The storage elastic modulus at 120 ° C. was 3 × 10 ⁹ Pa. Next, a single-layer film member 7 having a thickness of 65 μm was produced by the same method as in Example 1.
The absorbance of the member 7 adjusted and measured by the same method as in Example 1 was 0.01 (heating 1 hour), 0.01 (heating 2 hours), 0.01 (heating 4 hours), and the hemolytic rate was It was 0.01% (heating 1 hour), 0.02% (heating 2 hours), 0.01% (heating 4 hours), and the average value of the hemolytic rate was 0.01%.

[Example 11]
The monomer species of the structural unit [A] is 5,6-difluoro-5-pentafluoroethyl-6-trifluoromethylbicyclo [2.2.1] hept-2-ene, and the monomer ratio is [A] / [ Poly (1,1,2-trifluoro-2-trifluoromethyl-3,5-cyclopentyleneethylene) / (in the same manner as in Example 9 except that it was changed to B] = 20/80. 3,3,4-trifluoro-4-trifluoromethyl-7,9-tricyclo [4.3.0.1 ^{2, 5]} to obtain a tetrahydrofuran solution of a copolymer of de crab Ren ethylene). The solution was added to methanol, the white polymer was filtered off and dried to give 52 g of polymer 6. The hydrogenation rate is 100%, the composition ratio [A] / [B] = 80/20, the weight average molecular weight (Mw) is 69000, the molecular weight distribution (Mw / Mn) is 2.91, and the glass transition temperature is 116 ° C. The storage elastic modulus at 120 ° C. was 2 × 10 ⁶ Pa. Next, a single-layer film member 8 having a thickness of 70 μm was produced by the same method as in Example 1.
The absorbance of the member 8 adjusted and measured by the same method as in Example 1 was 0.03 (heating 1 hour), 0.03 (heating 2 hours), 0.03 (heating 4 hours), and the hemolytic rate was It was 0.02% (heating 1 hour), 0.02% (heating 2 hours), 0.02% (heating 4 hours), and the average value of the hemolytic rate was 0.02%.

[Example 12]
A medical device as a cell culture container in which the bottom of the container is made of the composite sheet member 6 was produced by the same method as in Example 7 except that the member to be bonded was changed to the member 6 produced in Example 9. Next, BALB / 3T3 cells were cultured in the same manner as in Example 7.
In the evaluation of cell proliferation by the WST-8 method, the absorbance after 1 day was 0.40 ± 0.01, 1.31 ± 0.02 after 3 days, and 3.15 ± after 7 days. It was 0.08. The absorbance increased linearly with the elapsed days, and no attenuation of cell proliferation was observed even after 7 days. Moreover, when the autofluorescence of the cells cultured for 7 days was observed, the green fluorescence indicating dead cells was not observed, and it was confirmed that 100% of the cells were living cells. Furthermore, when the drug-metabolizing enzyme activity was evaluated with NADPH dehydrogenase of this cultured cell, it was found that the drug-metabolizing enzyme activity was similar to that of the ecosystem with a cell survival rate of almost 100%.

[Example 13]
The composite sheet member 9 was produced in the same manner as in Example 4 except that the fluorine-containing cyclic olefin polymer was changed to the polymer 4 synthesized in Example 9.
The absorbance of the member 9 adjusted and measured by the same method as in Example 1 was 0.02 (heating 1 hour), 0.01 (heating 2 hours), 0.01 (heating 4 hours), and the hemolytic rate was It was 0.01% (heating 1 hour), 0.02% (heating 2 hours), 0.01% (heating 4 hours), and the average value of the hemolytic rate was 0.01%.
Next, a medical device as a cell culture container in which the bottom of the container was made of the composite sheet member 9 was produced by the same method as in Example 7 except that the member to be bonded was changed to the composite sheet member 9. Next, BALB / 3T3 cells were cultured in the same manner as in Example 7.
In the evaluation of cell proliferation by the WST-8 method, the absorbance after 1 day was 0.38 ± 0.01, 1.29 ± 0.02 after 3 days, and 3.09 ± after 7 days. It was 0.08. The absorbance increased linearly with the elapsed days, and no attenuation of cell proliferation was observed even after 7 days. Moreover, when the autofluorescence of the cells cultured for 7 days was observed, the green fluorescence indicating dead cells was not observed, and it was confirmed that 100% of the cells were living cells. Furthermore, when the drug-metabolizing enzyme activity was evaluated with NADPH dehydrogenase of this cultured cell, it was found that the drug-metabolizing enzyme activity was similar to that of the ecosystem with a cell survival rate of almost 100%.

[Example 14]
Using a NGF-0404-T vacuum forming machine manufactured by Fuse Vacuum Co., Ltd., a single-layer film member 1 (size: 200 mm × 200 mm) having a thickness of 70 μm produced by the same method as in Example 1 was used, and a diameter of 15 mm was placed on the stage. , A heat vacuum forming was performed using a mold in which cylindrical SUS rods having a height of 18 mm were arranged in 3 rows and 3 columns. By pressing the mold against the single-layer film member 1 and releasing it to the atmosphere under the conditions of a heating temperature of 105 ° C. and a vacuum degree of 1 kPa, nine concave shapes having a diameter of 15 mm and a depth of 18 mm are formed in a plane of 200 mm × 200 mm. A medical device (container 7) as a cell culture container was prepared. Next, BALB / 3T3 cells were cultured in the same manner as in Example 7.
In the evaluation of cell proliferation by the WST-8 method, the absorbance after 1 day was 0.32 ± 0.01, 1.23 ± 0.01 after 3 days, and 3.03 ± after 7 days. It was 0.06. The absorbance increased linearly with the elapsed days, and no attenuation of cell proliferation was observed even after 7 days. Moreover, when the autofluorescence of the cells cultured for 7 days was observed, the green fluorescence indicating dead cells was not observed, and it was confirmed that 100% of the cells were living cells. Furthermore, when the drug-metabolizing enzyme activity was evaluated with NADPH dehydrogenase of this cultured cell, it was found that the drug-metabolizing enzyme activity was similar to that of the ecosystem with a cell survival rate of almost 100%.

[Example 15]
The autofluorescence of the single-layer film members 6, 7, and 8 produced in Examples 9, 10, and 11 was measured in each wavelength range of the excitation light measurement range of 200 to 1000 nm and the fluorescence measurement range of 200 to 1000 nm, and the fluorescence intensity was measured. When the distribution was confirmed, no fluorescence was observed, which showed autofluorescence from any of the members.

[Example 16]
Members 1, 2, 3, 4, 5, 6, 7, 8 and 9 produced in Examples 1, 2, 3, 4, 5, 9, 10, 11 and 13 have a size of 30 mm × 30 mm, respectively. The film cut out in 1 was sandwiched from above and below with a SUS tube having an inner diameter of 15 mm and a height of 20 mm, and a container having a shape fixed with a SUS clip was produced. Then, under a steam atmosphere of 2 atm, high-pressure steam sterilization was performed at 121 ° C. for 15 minutes. After that, the shape of the container taken out from the autoclave was observed, but no container had defects due to thermal deformation during high-pressure steam sterilization, and all the containers had the same normal shape as at the time of manufacture. It was then dried overnight in a clean bench under germicidal lamps.

[Example 17]
When the container 7 having nine concave shapes formed in the plane of 200 mm × 200 mm described in Example 14 was sterilized by high pressure steam in the same manner as in Example 16 and the shape was observed, the container 7 had a normal shape as in the case of manufacture. I had it. It was then dried overnight in a clean bench under germicidal lamps.

[Example 18]
BALB / 3T3 cells were cultured in the same manner as in Example 7, except that containers 1, 6 and 7 sterilized by the high-pressure steam described in Example 16 were used.
In the evaluation of cell proliferation by the WST-8 method, the absorbance in container 1 after 1 day was 0.39 ± 0.02, 1.29 ± 0.01 after 3 days, and 3 after 7 days. It is .11 ± 0.08, the absorbance in container 6 after 1 day is 0.42 ± 0.02, 1.32 ± 0.01 after 3 days, and 3.14 ± after 7 days. It is 0.04, the absorbance in the container 7 after 1 day is 0.36 ± 0.01, 1.26 ± 0.01 after 3 days, and 3.08 ± 0.03 after 7 days. Met. In all of the containers 1, the container 6 and the container 7, the absorbance increased linearly with the elapsed days, and no decrease in cell proliferation was observed even after 7 days. Moreover, when the autofluorescence of the cells cultured for 7 days was observed, green fluorescence indicating dead cells was not observed in any of the containers 1, the container 6, and the container 7, and it was confirmed that 100% of the cells were live cells. Furthermore, when the drug-metabolizing enzyme activity was evaluated with NADPH dehydrogenase of this cultured cell, it was found that the drug-metabolizing enzyme activity was similar to that of the ecosystem with a cell survival rate of almost 100%.

[Comparative Example 1]
Activated alumina was added to a cyclohexanone solution in which styrene (25 g) was dissolved at 30% by mass under a nitrogen stream, and after stirring, filtration was performed to remove t-butylcatechol, which is a polymerization inhibitor. Next, a cyclohexanone solution in which n-butyllithium was dissolved was prepared, a cyclohexanone solution of styrene was charged in an autoclave under nitrogen, and then cyclohexanone of n-butyllithium was charged, and the reaction was started by heating to 80 ° C. After 1 hour, the mixture was allowed to cool to room temperature, the lid of the autoclave was opened, the contents were taken out, dropped into methanol to precipitate a white powder, separated by filtration, and dried by heating to obtain a white polystyrene solid (24 g). It was. Next, the white powder was dissolved in methyl isobutyl ketone at a concentration of 30% by mass to prepare a film-like member 10 having a thickness of 70 μm made of polystyrene by the same method as in Example 1.

The hemolysis rate calculated from the absorbance measured by preparing the subject in the same manner as in Example 1 was 3% (heating 1 hour), 5% (heating 2 hours), and 9% (heating 4 hours). The hemolysis rate increased with the passage of time heated in.

[Comparative Example 2]
Autofluorescence was observed in the same manner as in Example 6 using a test piece obtained by cutting out the bottom of a γ-ray sterilized 6-hole TCPS multi-well plate (manufactured by Corning), which is a medical device as a cell culture container. did. Strong autofluorescent signals were observed in the excitation light measurement range of 250 to 400 nm, the fluorescence measurement range of 280 to 500 nm, and the excitation light measurement range of 580 to 900 nm and the fluorescence measurement range of 260 to 400 nm. In the culture test of BALB / 3T3 cells described later (Comparative Example 3), an attempt was made to directly observe the autofluorescence, but the autofluorescence of the cells could not be observed due to the strong green fluorescence emitted from the container.

[Comparative Example 3]
Using a γ-ray sterilized 6-well TCPS multi-well plate (manufactured by Corning), seed BALB / 3T3 cell solution in the same manner as in Example 7, cover and move to an incubator, 37 ° C., carbon dioxide concentration 5 Culturing was started under% sterile air.

In the evaluation of cell proliferation by the WST-8 method, the absorbance after 1 day was 0.27 ± 0.03, 1.88 ± 0.11 after 3 days, and 3.15 ± after 7 days. It was 0.23. The slope of absorbance diminished with respect to the number of days elapsed. In addition, when cells cultured for 7 days were collected from a container and transferred to a glass well plate and autofluorescence was observed, green fluorescence indicating dead cells was observed, and the number of cells based on the number of cells confirmed with a light-dark field microscope was observed. The survival rate was calculated to be 85%. Furthermore, when the drug-metabolizing enzyme activity was evaluated with NADPH dehydrogenaase of cells cultured for 7 days, the drug-metabolizing function of the cells was not expressed.

[Comparative Example 4]
6-well TCPS multiwell plate glass transition temperature measured by cutting out a part of the (Corning) is 100 ° C., the storage modulus of 120 ° C. in the solid viscoelasticity measurement was 8 × 10 5 ^Pa. Then, high-pressure steam sterilization at 121 ° C. for 15 minutes was carried out in a steam atmosphere of 2 atm. The 6-hole TCPS multi-well plate taken out from the autoclave was deformed by heat due to heating, and the whole was distorted and the seeding surface of the cells became rough, so that it could not be adapted to cell culture.

A fluorine-containing cyclic olefin polymer containing a structural unit represented by the general formula (1) of the present invention, or a repeating structure represented by the structural unit [A] represented by the general formula (1) and the general formula (2). High-pressure steam sterilization is performed by using a medical device in which a member composed of a fluorine-containing cyclic olefin polymer containing the unit [B] or a composition containing the fluorine-containing cyclic olefin polymer is arranged on a surface in contact with blood or cells. Medical products made of biocompatible materials that are adaptable and do not generate biotoxic components that induce blood coagulation, cell proliferation attenuation, cell mutation, death, etc. in fields such as medical care, drug discovery development using cells, and regenerative medicine. Equipment can be provided.

Claims (6)

A medical device component that constitutes an extracorporeal circulation circuit for a catheter, blood bag, stent, or heart-lung machine that comes into direct contact with blood.
The member is composed of a fluorine-containing cyclic olefin polymer containing a structural unit represented by the following general formula (1), and is calculated from the absorbance at a wavelength of 576 nm, which is the maximum UV absorption of oxygenated hemoglobin in a hemolytic toxicity test. A member for a medical device, which is made of a biocompatible material having a hemolysis rate of 0% or more and 2% or less.

(In the formula (1), R ^{1 to} R ⁴ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{1 to} R ⁴ may be the same or different from ^{each other, and R 1 to} R ⁴ may be bonded to each other to form a ring structure.) In the medical device member according to claim 1,
The fluorine-containing cyclic olefin polymer contains a structural unit [A] represented by the general formula (1) and a repeating structural unit [B] represented by the following general formula (2), and the molar ratio [A] thereof. / [B] is a member for medical devices in which 90/10 to 10/90.

In the formula (2), R ^{5 to} R ⁸ are fluorine, an alkyl group having 1 to 10 carbon atoms containing fluorine, an alkoxy group having 1 to 10 carbon atoms containing fluorine, or 2 carbon atoms containing fluorine. It is an alkoxyalkyl group of 10 to 10. R ^{5 to} R ⁸ may be the same or different from ^{each other, and R 5 to} R ⁸ may be bonded to each other to form a ring structure.) The medical device member according to claim 1 or 2, wherein the member does not emit fluorescence in the entire region having a fluorescence wavelength of 200 nm or more and 1000 nm or less, and an excitation wavelength of 200 nm or more and 1000 nm or less. The member is characterized by being composed of a fluorine-containing cyclic olefin polymer composition containing the fluorine-containing cyclic olefin polymer, a photocurable compound, and a photocuring initiator, and the fluorine-containing cyclic olefin polymer. The claim that the mass ratio of the fluorine-containing cyclic olefin polymer to the photocurable compound in the composition (the fluorine-containing cyclic olefin polymer / the photocurable compound) is 99.9 / 0.1 to 30/70. The member for a medical device according to any one of 1 to 3. The medical device member according to any one of claims 1 to 4.
A member for a medical device, wherein the storage elastic modulus (E') at 120 ° C. in the solid viscoelasticity measurement of the fluorine-containing cyclic olefin polymer is 1 × 10 ⁶ to 1 × 10 ^{10 Pa.} A medical device including the medical device member according to any one of claims 1 to 5 .
The medical device is a catheter, blood bag, stent, or extracorporeal circulation circuit for heart-lung machine that is in direct contact with blood .

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