JP6395252B2 - Medical device material, and medical device, antithrombotic material and cell culture substrate using the same - Google Patents
Medical device material, and medical device, antithrombotic material and cell culture substrate using the same Download PDFInfo
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- JP6395252B2 JP6395252B2 JP2014157657A JP2014157657A JP6395252B2 JP 6395252 B2 JP6395252 B2 JP 6395252B2 JP 2014157657 A JP2014157657 A JP 2014157657A JP 2014157657 A JP2014157657 A JP 2014157657A JP 6395252 B2 JP6395252 B2 JP 6395252B2
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- medical device
- polymer
- water
- meth
- acrylate
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Description
本発明は、医療用具用材料に関する。より詳しくは、生体成分又は生体組織と接触して使用される医療用具の材料として好適な医療用具用材料に関する。 The present invention relates to a medical device material. More specifically, the present invention relates to a medical device material suitable as a material for a medical device used in contact with a biological component or biological tissue.
高分子化合物は、原料となる単量体を選択することで様々な特性のものを設計することが可能であり、工業製品から日用品まで様々な用途に幅広く用いられている。このような高分子化合物の用途の1つに医療用具用途がある。医療用具は、血液等の生体成分や生体組織と接触する環境下で使用され、医療用具表面と生体成分や生体組織との親和性が低い場合、生体防御機構が活性化され、血液が凝固して血栓が形成される等の不具合が生じる。このため、医療用具は少なくとも生体成分や生体組織と接触する表面が生体適合性の高い材料で形成されていることが必要となる。 High molecular compounds can be designed with various characteristics by selecting monomers as raw materials, and are widely used in various applications from industrial products to daily necessities. One of the uses of such a polymer compound is a medical device. Medical devices are used in an environment where they come into contact with biological components or biological tissues such as blood, and when the surface of the medical devices is low in affinity with biological components or biological tissues, the biological defense mechanism is activated and blood coagulates. This causes problems such as the formation of blood clots. For this reason, at least the surface which contacts a biological component or a biological tissue needs to be formed from a highly biocompatible material for the medical device.
高分子化合物が医療分野等で使用可能な生体適合性の高い材料となるためには、高分子化合物を水和した場合の高分子化合物表面に存在する水の状態が重要であると考えられている。一般に高分子化合物に水が水和した場合、高分子化合物の表面には、高分子化合物と強い相互作用を有して凍結しない水(不凍水)と、不凍水よりも高分子化合物の表面から離れて存在し、高分子化合物との相互作用が弱い自由水とが存在するが、高分子化合物の中には、不凍水と自由水との間に、高分子化合物又は不凍水と中間的な相互作用をする水(中間水)を有するものがあることが明らかになってきている。生体成分や生体組織は、血液中や体液中で水和殻を形成して安定しており、この水和殻が異物表面や不凍水に接触して攪乱又は破壊されると生体成分や生体組織が高分子材料表面に吸着し、生体防御機構が活性化されると考えられるが、高分子材料の表面の不凍水層の上に中間水が安定に存在することで、生体成分や生体組織と接触してもタンパク質や細胞表面の水和構造が破壊されにくくなり、これにより高分子化合物が生体適合性の高いものとなることが明らかになってきている。(非特許文献1〜3参照)。即ち、生体適合性の発現に関して、中間水の有無が本質的に重要であるとことが、広く認識されるようになっている。 In order for a polymer compound to be a highly biocompatible material that can be used in the medical field, the state of water present on the polymer compound surface when the polymer compound is hydrated is considered important. Yes. In general, when water is hydrated to a polymer compound, the surface of the polymer compound has a strong interaction with the polymer compound and does not freeze (antifreeze water). There is free water that exists away from the surface and weakly interacts with the polymer compound, but in some polymer compounds, there is a polymer compound or antifreeze water between the antifreeze water and the free water. It has become clear that some have water (intermediate water) that interacts with them. Biological components and biological tissues are stable by forming hydration shells in blood and body fluids, and when these hydration shells are disturbed or destroyed by contact with the surface of foreign matter or antifreeze water, It is thought that the tissue is adsorbed on the surface of the polymer material and the biological defense mechanism is activated, but the intermediate water is stably present on the antifreeze layer on the surface of the polymer material, so It has become clear that protein and cell surface hydration structures are less likely to be destroyed even when they come into contact with tissue, and that this makes polymer compounds highly biocompatible. (Refer nonpatent literature 1-3.). That is, it is widely recognized that the presence or absence of intermediate water is essential for the expression of biocompatibility.
このような医療分野で使用される高分子材料として、含水時の平衡含水率が所定の値であり、示差走査熱量計測定における昇温過程において0℃以下で水の低温結晶化に基づく発熱ピークが観測される状態の水を有することができ、ガラス転移温度が0℃以下である水不溶性の血液適合性高分子(特許文献1参照)が開示され、また、同様の特性が要求される細胞培養基材として、中性水溶液に難溶性であるヒアルロン酸単独で形成されたゲルを含有する細胞培養用基材(特許文献2参照)が開示されている。更に、物質表面への細胞の吸着頻度が当該物質表面の水層の状態に応じて変化し、また、細胞の種類によっても吸着頻度が異なることを見出し、これを利用して特定の細胞を選択的に吸着させて溶液から分離する細胞分離方法(特許文献3参照)が開示されている。 As a polymer material used in such a medical field, the equilibrium moisture content at the time of moisture content is a predetermined value, and an exothermic peak based on low-temperature crystallization of water at 0 ° C. or less in a temperature rising process in differential scanning calorimetry measurement. A water-insoluble blood compatible polymer (see Patent Document 1) having a glass transition temperature of 0 ° C. or lower is disclosed, and cells having similar characteristics are required. As a culture substrate, a cell culture substrate (see Patent Document 2) containing a gel formed of hyaluronic acid alone that is hardly soluble in a neutral aqueous solution is disclosed. Furthermore, the frequency of cell adsorption on the surface of the substance changes depending on the state of the water layer on the surface of the substance, and the frequency of adsorption varies depending on the type of cell, and this is used to select specific cells. A cell separation method (see Patent Document 3) in which the sample is adsorbed and separated from the solution is disclosed.
上記のとおり、生体適合性の高い材料と中間水との関係について研究報告がされており、また、生体適合性材料等の開発も活発に行われている。
医療用用具等に用いることのできる生体適合性の高い材料の需要は高く、このような中間水を含む新たな材料を開発することができれば、医療用用具等に使用可能な高分子材料の選択の幅を広げることができ、今後の医療の発展に資する点からも好ましい。
As described above, research reports have been made on the relationship between highly biocompatible materials and intermediate water, and biocompatible materials and the like are being actively developed.
The demand for materials with high biocompatibility that can be used for medical devices is high, and if new materials containing such intermediate water can be developed, selection of polymer materials that can be used for medical devices, etc. This is also preferable from the viewpoint that it can expand the range of medical treatment and contribute to the future development of medical care.
本発明は、上記現状に鑑みてなされたものであり、水和時に中間水を有する新たな高分子化合物を含む医療用具用材料を提供することを目的とする。 This invention is made | formed in view of the said present condition, and aims at providing the material for medical devices containing the new high molecular compound which has intermediate water at the time of hydration.
本発明者は、水和時に中間水を有する新たな高分子化合物について種々検討したところ、構造中にカルボキシル基又はその塩を2つ有する所定の構造のアクリル酸誘導体由来の構造を有する重合体が、水和時に中間水を有し、生体適合性を有する医療用具用材料として使用できることを見いだし、本発明に到達したものである。
ここで、本発明における生体適合性とは、生体に強い悪影響や強い刺激を与えないことから、生体成分、生体組織及び生体由来の物質のいずれか1以上と共存することが可能である属性を意味する。例えば、生体適合性を有する材料は、典型的には、血栓の生成を抑制する性質である抗血栓性、血液の凝固を抑制する性質である抗血液凝固性、補体を活性化させ難い性質、白血球を減少させ難い性質、生体組織に炎症を引き起こし難い性質、腫瘍を形成し難い性質等のいずれか1以上の性質を有する。
As a result of various studies on new polymer compounds having intermediate water during hydration, the present inventors have found that a polymer having a structure derived from an acrylic acid derivative having a predetermined structure having two carboxyl groups or salts thereof in the structure. It has been found that the present invention can be used as a medical device material having intermediate water at the time of hydration and having biocompatibility.
Here, the biocompatibility in the present invention does not give a strong adverse effect or a strong stimulus to a living body, and therefore has an attribute that can coexist with any one or more of a biological component, a biological tissue and a biological substance. means. For example, biocompatible materials typically have anti-thrombogenic properties that inhibit thrombus formation, anti-blood coagulation properties that inhibit blood coagulation, and properties that make complements difficult to activate. It has one or more properties such as a property that it is difficult to reduce leukocytes, a property that it is difficult to cause inflammation in living tissue, and a property that it is difficult to form a tumor.
すなわち本発明は、下記式(1); That is, the present invention provides the following formula (1);
(式中、nは、0〜2の数を表す。X、Yは、それぞれ独立に水素原子、アルカリ金属原子、又は、アンモニウム基を表す。)で表される単量体由来の構造単位を有する重合体を含むことを特徴とする医療用具用材料である。
以下に本発明を詳述する。
なお、以下において記載する本発明の個々の好ましい形態を2つ以上組み合わせたものもまた、本発明の好ましい形態である。
(Wherein n represents a number from 0 to 2. X and Y each independently represent a hydrogen atom, an alkali metal atom, or an ammonium group). It is the material for medical devices characterized by including the polymer which has.
The present invention is described in detail below.
A combination of two or more preferred embodiments of the present invention described below is also a preferred embodiment of the present invention.
上記式(1)で表される単量体由来の構造単位を有する重合体は、構造中に2つのカルボキシル基又はその塩を有するが、このような構造中に複数のカルボキシル基又はその塩を有する重合体で中間水を多く保持することができるものはこれまでには知られていない。
本発明の構造の重合体が中間水を保持するメカニズムについては明らかではないが、2つのカルボキシル基が、適度な空間的配置をとることにより、カルボニル酸素への強い水和が弱められることに起因すると考えられる。
また、この重合体は、不凍水量に対して中間水量を比較的、多く吸着し得ることも特徴の1つである。
本発明の医療用具用材料は、上記式(1)で表される単量体由来の構造単位を有する重合体を含む限り、その他の材料を含んでいてもよい。
また、上記式(1)で表される単量体由来の構造単位を有する重合体を1種含んでいてもよく、2種以上含んでいてもよい。
なお、上記式(1)で表される単量体由来の構造単位とは、上記式(1)で表される単量体の炭素−炭素二重結合が単結合になった構造単位であり、具体的には、下記式(2)で表すことができる。なお、上記式(1)で表される単量体由来の構造単位は、下記式(2)で表される構造であれば、式(1)で表される単量体を重合する以外の方法で形成された構造単位であっても良い。
The polymer having a structural unit derived from the monomer represented by the formula (1) has two carboxyl groups or salts thereof in the structure, and a plurality of carboxyl groups or salts thereof are contained in such a structure. A polymer having a large amount of intermediate water has not been known so far.
Although it is not clear about the mechanism by which the polymer having the structure of the present invention retains intermediate water, it is caused by the fact that the two carboxyl groups have an appropriate spatial arrangement, so that strong hydration to carbonyl oxygen is weakened. I think that.
Further, this polymer is also characterized by being able to adsorb a relatively large amount of intermediate water relative to the amount of antifreeze water.
The medical device material of the present invention may contain other materials as long as it contains a polymer having a structural unit derived from the monomer represented by the above formula (1).
Moreover, 1 type of the polymer which has a structural unit derived from the monomer represented by the said Formula (1) may be included, and 2 or more types may be included.
The structural unit derived from the monomer represented by the formula (1) is a structural unit in which the carbon-carbon double bond of the monomer represented by the formula (1) is a single bond. Specifically, it can be represented by the following formula (2). In addition, if the structural unit derived from the monomer represented by the above formula (1) is a structure represented by the following formula (2), other than polymerizing the monomer represented by the formula (1) It may be a structural unit formed by a method.
(式(2)中、n、X及びYは、式(1)と同じである。) (In Formula (2), n, X, and Y are the same as Formula (1).)
上記式(1)において、X、Yは、それぞれ独立に水素原子、アルカリ金属原子、又は、アンモニウム基を表すが、アルカリ金属原子としては、ナトリウム又はカリウムが好ましい。より好ましくは、ナトリウムである。
上記式(1)において、nは、0〜2の数を表すが、好ましくは、1又は2である。より好ましくは2である。
In the formula (1), X and Y each independently represent a hydrogen atom, an alkali metal atom, or an ammonium group, and the alkali metal atom is preferably sodium or potassium. More preferably, it is sodium.
In said formula (1), although n represents the number of 0-2, Preferably it is 1 or 2. More preferably 2.
上記式(1)で表される単量体由来の構造単位を有する重合体は、式(1)で表される単量体のみを原料として得られる重合体であってもよく、式(1)で表される単量体とその他の単量体とを含む単量体成分を原料として得られる共重合体であってもよい。
式(1)で表される単量体由来の構造単位を有する重合体が共重合体である場合、ランダム重合、ブロック重合、交互重合のいずれの形態のものであってもよい。
The polymer having a structural unit derived from the monomer represented by the formula (1) may be a polymer obtained using only the monomer represented by the formula (1) as a raw material. ) And a copolymer obtained by using a monomer component containing another monomer as a raw material.
When the polymer having a structural unit derived from the monomer represented by the formula (1) is a copolymer, it may be in any form of random polymerization, block polymerization, and alternating polymerization.
上記式(1)で表される単量体由来の構造単位を有する重合体は、全単量体単位100質量%に対して、上記式(1)で表される単量体由来の構造単位を10〜100質量%有することが好ましい。このような割合で含むことで、得られる重合体が医療用具用材料としてより好適なものとなる。より好ましくは、上記式(1)で表される単量体由来の構造単位を20〜100質量%有することであり、更に好ましくは、30〜100質量%有することである。 The polymer having the structural unit derived from the monomer represented by the formula (1) is a structural unit derived from the monomer represented by the formula (1) with respect to 100% by mass of all the monomer units. It is preferable to have 10-100 mass%. By containing in such a ratio, the obtained polymer becomes more suitable as a medical device material. More preferably, it is having 20-100 mass% of structural units derived from the monomer represented by the above formula (1), and more preferably 30-100 mass%.
上記式(1)で表される単量体由来の構造単位を有する重合体が、上記式(1)で表される単量体由来の構造単位以外のその他の構造単位を有する場合、当該その他の構造単位を形成する単量体としては、(メタ)アクリル酸メチル、(メタ)アクリル酸エチル、(メタ)アクリル酸n−プロピル、(メタ)アクリル酸i−プロピル、(メタ)アクリル酸n−ブチル、(メタ)アクリル酸s−ブチル、(メタ)アクリル酸t−ブチル、(メタ)アクリル酸n−アミル、(メタ)アクリル酸s−アミル、(メタ)アクリル酸t−アミル、(メタ)アクリル酸n−ヘキシル、(メタ)アクリル酸2−エチルヘキシル、(メタ)アクリル酸イソデシル、(メタ)アクリル酸トリデシル、(メタ)アクリル酸シクロヘキシル、(メタ)アクリル酸シクロヘキシルメチル、(メタ)アクリル酸オクチル、(メタ)アクリル酸ラウリル、(メタ)アクリル酸ステアリル、(メタ)アクリル酸ベンジル、(メタ)アクリル酸フェニル、(メタ)アクリル酸イソボルニル、(メタ)アクリル酸アダマンチル、(メタ)アクリル酸トリシクロデカニル、(メタ)アクリル酸2−ヒドロキシエチル、(メタ)アクリル酸2−ヒドロキシプロピル、(メタ)アクリル酸3−ヒドロキシプロピル、(メタ)アクリル酸2−ヒドロキシブチル、(メタ)アクリル酸3−ヒドロキシブチル、(メタ)アクリル酸4−ヒドロキシブチル、(メタ)アクリル酸2−メトキシエチル、(メタ)アクリル酸2−エトキシエチル、(メタ)アクリル酸フェノキシエチル、(メタ)アクリル酸テトラヒドロフルフリル、(メタ)アクリル酸グリシジル、(メタ)アクリル酸β−メチルグリシジル、(メタ)アクリル酸β−エチルグリシジル、(メタ)アクリル酸(3,4−エポキシシクロヘキシル)メチル、(メタ)アクリル酸N,N−ジメチルアミノエチル、α−ヒドロキシメチルアクリル酸メチル、α−ヒドロキシメチルアクリル酸エチル等の(メタ)アクリル酸エステル類;スチレン、α−メチルスチレン、α−クロロスチレン、p−t−ブチルスチレン、p−メチルスチレン、p−クロロスチレン、o−クロロスチレン、2,5−ジクロロスチレン、3,4−ジクロロスチレン、ビニルトルエン、メトキシスチレン等の芳香族ビニル類;メチルマレイミド、エチルマレイミド、イソプロピルマレイミド、シクロヘキシルマレイミド、フェニルマレイミド、ベンジルマレイミド、ナフチルマレイミドなどのN置換マレイミド類が挙げられる。これらの共重合可能な他の単量体は、単独でまたは2種以上を組み合わせて使用できる。これらの中でも、(メタ)アクリル酸エステル類が好ましい。より好ましくは、(メタ)アクリル酸アルキルエステルであり、更に好ましくは、アルキルエステルのアルキル基の炭素数が1〜8の(メタ)アクリル酸アルキルエステルであり、特に好ましくは、(メタ)アクリル酸n−ブチルである。 When the polymer having the structural unit derived from the monomer represented by the formula (1) has other structural units other than the structural unit derived from the monomer represented by the formula (1), the other As the monomer for forming the structural unit, methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, i-propyl (meth) acrylate, (meth) acrylate n -Butyl, s-butyl (meth) acrylate, t-butyl (meth) acrylate, n-amyl (meth) acrylate, s-amyl (meth) acrylate, t-amyl (meth) acrylate, (meta ) N-hexyl acrylate, 2-ethylhexyl (meth) acrylate, isodecyl (meth) acrylate, tridecyl (meth) acrylate, cyclohexyl (meth) acrylate, (meth) acrylic acid Hexylmethyl, octyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, benzyl (meth) acrylate, phenyl (meth) acrylate, isobornyl (meth) acrylate, (meth) acrylic acid Adamantyl, tricyclodecanyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 3-hydroxypropyl (meth) acrylate, 2-hydroxy (meth) acrylate Butyl, 3-hydroxybutyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate, 2-methoxyethyl (meth) acrylate, 2-ethoxyethyl (meth) acrylate, phenoxyethyl (meth) acrylate, (Meth) acrylic acid tetrahydrofurfuryl, (meta Glycidyl acrylate, β-methylglycidyl (meth) acrylate, β-ethylglycidyl (meth) acrylate, methyl (meth) acrylate (3,4-epoxycyclohexyl), N, N-dimethylamino (meth) acrylate (Meth) acrylic acid esters such as ethyl, methyl α-hydroxymethyl acrylate, ethyl α-hydroxymethyl acrylate; styrene, α-methyl styrene, α-chlorostyrene, pt-butyl styrene, p-methyl styrene , P-chlorostyrene, o-chlorostyrene, 2,5-dichlorostyrene, 3,4-dichlorostyrene, vinyltoluene, methoxystyrene, and other aromatic vinyls; methylmaleimide, ethylmaleimide, isopropylmaleimide, cyclohexylmaleimide, phenyl Maleimide, benzyl N-substituted maleimides such as maleimide and naphthylmaleimide are exemplified. These other copolymerizable monomers can be used alone or in combination of two or more. Among these, (meth) acrylic acid esters are preferable. (Meth) acrylic acid alkyl ester is more preferred, (meth) acrylic acid alkyl ester having 1 to 8 carbon atoms in the alkyl ester alkyl group is more preferred, and (meth) acrylic acid is particularly preferred. n-Butyl.
上記式(1)で表される単量体由来の構造単位を有する重合体は、重量平均分子量が1,000〜1,000,000であることが好ましい。重量平均分子量がこのような範囲であると、耐久性や機械強度に優れた材料となり好ましい。重量平均分子量は、より好ましくは、5,000〜500,000であり、更に好ましくは、10,000〜300,000である。
重合体の重量平均分子量は、ゲルパーミエーションクロマトグラフィー(GPC)により、実施例に記載の測定条件で測定することができる。
The polymer having a structural unit derived from the monomer represented by the above formula (1) preferably has a weight average molecular weight of 1,000 to 1,000,000. When the weight average molecular weight is in such a range, a material excellent in durability and mechanical strength is preferable. The weight average molecular weight is more preferably 5,000 to 500,000, and still more preferably 10,000 to 300,000.
The weight average molecular weight of the polymer can be measured by gel permeation chromatography (GPC) under the measurement conditions described in the examples.
上記式(1)で表される単量体由来の構造単位を有する重合体は、ガラス転移温度が40〜200℃であることが好ましい。重合体がこのようなガラス転移温度を有することで、表面のベタツキを抑えることができる。ガラス転移温度は、より好ましくは、50〜170℃であり、更に好ましくは、60〜150℃である。
ガラス転移温度は、示差走査熱量測定(DSC)により測定することができる。
The polymer having a monomer-derived structural unit represented by the above formula (1) preferably has a glass transition temperature of 40 to 200 ° C. When the polymer has such a glass transition temperature, surface stickiness can be suppressed. The glass transition temperature is more preferably 50 to 170 ° C, and still more preferably 60 to 150 ° C.
The glass transition temperature can be measured by differential scanning calorimetry (DSC).
上記式(1)で表される単量体由来の構造単位を有する重合体は、中間水量が重合体100質量%に対して、1質量%以上とできることが好ましい。中間水量は、より好ましくは、2質量%以上であり、更に好ましくは、3質量%以上である。中間水量を上記範囲とすることで、血小板のような小さな浮遊系の細胞や、血漿タンパク質の吸着を有効に回避することができる。中間水量の上限は、医療用具用材料をどのような目的で使用するかによって異なるため、一概に述べることはできないが、例えば、がん細胞や肝細胞を変質することなく選択的に吸着する目的で使用する場合は30質量%以下とすることが好ましい。 The polymer having a structural unit derived from the monomer represented by the above formula (1) preferably has an intermediate water amount of 1% by mass or more with respect to 100% by mass of the polymer. The amount of intermediate water is more preferably 2% by mass or more, and further preferably 3% by mass or more. By setting the amount of intermediate water in the above range, adsorption of small floating cells such as platelets and plasma proteins can be effectively avoided. The upper limit of the amount of intermediate water varies depending on the purpose for which the medical device material is used, so it cannot be described in general. For example, the purpose of selectively adsorbing cancer cells and hepatocytes without alteration When it is used in the above, it is preferably 30% by mass or less.
また、一般に、医療用具用材料としては、不凍水量に対する中間水量の割合(中間水量/不凍水量)が大きな値で水を保持しうる材料が好ましく、上記式(1)で表される単量体由来の構造単位を有する重合体においても不凍水量に対する中間水量(中間水量/不凍水量)を0.1以上とできることが好ましい。また、0.2以上とできることがより好ましい。
所定量の水を含水した重合体を一旦充分に冷却した後、ゆっくりした速度で昇温させながら吸熱、発熱量を観察してゆくと、0℃以下の特定の温度域で発熱が観察され、0℃付近の温度で吸熱が観察される。0℃以下の特定の温度域で発熱は、過冷却により準安定な状態で凝固していた中間水が加熱により規則化(コールドクリスタリゼーション)を生じたことによるものと考えられる。また、0℃付近の温度での吸熱のうち、0℃以下の温度域での吸熱は中間水の低温融解によるものであり、0℃での吸熱は自由水の融解によるものである。したがって、0℃以下の特定の温度域で発熱量、0℃付近の温度で吸熱量、及び、全含水量から中間水、自由水、不凍水の量を求めることができる。
中間水の存在、並びに、中間水や不凍水の量は、示差走査熱量計(DSC)測定を用いて実施例に記載の方法で確認することができる。
In general, the material for medical devices is preferably a material that can hold water with a large ratio of the intermediate water amount to the antifreeze water amount (intermediate water amount / antifreeze water amount), and is simply expressed by the above formula (1). Even in a polymer having a structural unit derived from a monomer, it is preferable that the intermediate water amount (intermediate water amount / antifreeze water amount) with respect to the antifreeze water amount can be 0.1 or more. Moreover, it is more preferable that it can be 0.2 or more.
Once the polymer containing a predetermined amount of water has been sufficiently cooled, heat absorption and heat generation are observed while raising the temperature at a slow rate, and heat generation is observed in a specific temperature range of 0 ° C. or less. An endotherm is observed at a temperature around 0 ° C. Heat generation in a specific temperature range of 0 ° C. or lower is considered to be due to the fact that the intermediate water solidified in a metastable state due to supercooling causes ordering (cold crystallization) by heating. Of the endotherm at temperatures near 0 ° C., the endotherm in the temperature range below 0 ° C. is due to low-temperature melting of the intermediate water, and the endotherm at 0 ° C. is due to melting of free water. Accordingly, the amount of heat generated at a specific temperature range of 0 ° C. or lower, the amount of heat absorbed at a temperature near 0 ° C., and the amount of intermediate water, free water, and antifreeze water can be determined from the total water content.
The presence of intermediate water, and the amount of intermediate water and antifreeze water can be confirmed by the method described in Examples using differential scanning calorimetry (DSC) measurement.
本発明の医療用具用材料に含まれる重合体は、上記式(1)で表される単量体と、必要に応じてその他の単量体とを含む単量体成分を原料とした重合反応により製造することができる。
重合反応は、重合開始剤の存在下で重合反応を行うことが好ましい。重合開始剤としては、例えば、過酸化水素;過硫酸ナトリウム、過硫酸カリウム、過硫酸アンモニウム等の過硫酸塩;ジメチル2,2’−アゾビス(2−メチルプロピオネート)、2,2’−アゾビス(イソブチロニトリル)等のアゾ系化合物;過酸化ベンゾイル、過酢酸、ジ−t−ブチルパーオキサイド等の有機過酸化物等が好適である。これらの重合開始剤は、単独で使用されてもよく、2種以上の混合物の形態で使用されてもよい。
重合開始剤の使用量としては、単量体の使用量1モルに対して、0.1g以上、25g以下であることが好ましく、0.1g以上、10g以下であることがより好ましい。
The polymer contained in the medical device material of the present invention is a polymerization reaction using a monomer component containing the monomer represented by the above formula (1) and, if necessary, another monomer as a raw material. Can be manufactured.
The polymerization reaction is preferably performed in the presence of a polymerization initiator. Examples of the polymerization initiator include hydrogen peroxide; persulfates such as sodium persulfate, potassium persulfate, and ammonium persulfate;
The amount of the polymerization initiator used is preferably 0.1 g or more and 25 g or less, more preferably 0.1 g or more and 10 g or less with respect to 1 mol of the monomer used.
上記重合反応は、溶媒を使用せずに行っても良いが、溶媒を使用することが好ましい。溶媒としては、水;メタノール、エタノール、イソプロピルアルコール等の低級アルコール類;アセトン、メチルエチルケトン、ジエチルケトン等の低級ケトン類;ジメチルエーテル、ジオキサン等のエーテル類;ジメチルホルムアルデヒド等のアミド類;酢酸エチル、酢酸ブチル等の低級エステル類;トルエン、キシレン等の芳香族類などが挙げられる。これらの溶媒は、単独で使用されてもあるいは2種以上の混合物の形態で使用されてもよい。
溶媒の使用量としては、単量体100質量%に対して40〜250質量%が好ましい。
The polymerization reaction may be performed without using a solvent, but it is preferable to use a solvent. Solvents include water; lower alcohols such as methanol, ethanol and isopropyl alcohol; lower ketones such as acetone, methyl ethyl ketone and diethyl ketone; ethers such as dimethyl ether and dioxane; amides such as dimethylformaldehyde; ethyl acetate and butyl acetate Lower esters such as toluene; aromatics such as toluene and xylene. These solvents may be used alone or in the form of a mixture of two or more.
As a usage-amount of a solvent, 40-250 mass% is preferable with respect to 100 mass% of monomers.
上記重合反応は、通常、0℃以上で行われることが好ましく、また、150℃以下で行われることが好ましい。より好ましくは、40℃以上であり、更に好ましくは、60℃以上であり、特に好ましくは、80℃以上である。また、より好ましくは、120℃以下であり、更に好ましくは、110℃以下である。上記重合温度は、重合反応において、常にほぼ一定に保持する必要はなく、一度または二度以上変動(加温または冷却)しても良い。 The polymerization reaction is usually preferably carried out at 0 ° C. or higher, and is preferably carried out at 150 ° C. or lower. More preferably, it is 40 degreeC or more, More preferably, it is 60 degreeC or more, Most preferably, it is 80 degreeC or more. Moreover, More preferably, it is 120 degrees C or less, More preferably, it is 110 degrees C or less. The polymerization temperature does not always need to be kept substantially constant in the polymerization reaction, and may vary (warming or cooling) once or twice or more.
本発明の医療用具用材料に含まれる重合体の製造方法は、上記重合反応工程以外の他の工程を含んでいてもよい。例えば、熟成工程、中和工程、重合開始剤や連鎖移動剤の失活工程、希釈工程、乾燥工程、濃縮工程、精製工程等が挙げられる。
また、上記重合反応工程の代わりに、例えば上記式(1)で表される単量体のエステルと、必要に応じてその他の単量体を重合する工程の後に、得られた重合体を加水分解することにより、本発明の医療用具用材料に含まれる重合体を製造しても良い。
The method for producing a polymer contained in the medical device material of the present invention may include a step other than the polymerization reaction step. For example, an aging step, a neutralization step, a deactivation step of a polymerization initiator or a chain transfer agent, a dilution step, a drying step, a concentration step, a purification step, and the like can be mentioned.
Further, instead of the polymerization reaction step, for example, after the step of polymerizing an ester of the monomer represented by the above formula (1) and other monomers as necessary, the obtained polymer is hydrolyzed. The polymer contained in the medical device material of the present invention may be produced by decomposing.
本発明の医療用具用材料は、上記のような中間水を含む重合体を含むものであって、生体成分や生体組織との親和性が高いことから、血液と接触しても血栓を生じにくい抗血栓性材料として好適に使用することができ、各種医療用具の生体成分又は生体組織と接触する部分を構成する材料としても好適に使用することができる。更に、本発明の医療用具用材料は、細胞培養基材としても好適に使用することができる。
このような、本発明の医療用具用材料を用いてなる医療用具であって、該医療用具は、生体成分又は生体組織と接触する部分が前記医療用具用材料を用いて構成される医療用具もまた、本発明の1つであり、本発明の医療用具用材料を用いてなる抗血栓性材料や細胞培養基材もまた、本発明の1つである。
本発明の医療用具用材料を用いてなる医療用具は、医療用具の生体成分又は生体組織と接触する部分を本発明の医療用具用材料で表面処理し、本発明の医療用具用材料を保持させる方法を用いて製造することができる。このように、本発明の医療用具用材料は、医療用具の表面処理剤として用いることができる。
The medical device material of the present invention contains a polymer containing intermediate water as described above, and has high affinity with biological components and tissues, so that it does not easily cause thrombus even when it comes into contact with blood. It can be suitably used as an antithrombotic material, and can also be suitably used as a material constituting a part that comes into contact with a biological component or biological tissue of various medical devices. Furthermore, the medical device material of the present invention can be suitably used as a cell culture substrate.
Such a medical device using the medical device material of the present invention, the medical device also includes a medical device in which a portion in contact with a biological component or a biological tissue is configured using the medical device material. In addition, an antithrombotic material and a cell culture substrate that are one of the present invention and use the material for a medical device of the present invention are also one of the present invention.
The medical device using the medical device material of the present invention has a surface treatment of the portion of the medical device that comes into contact with a biological component or biological tissue with the medical device material of the present invention, and holds the medical device material of the present invention. It can be manufactured using a method. Thus, the medical device material of the present invention can be used as a surface treatment agent for medical devices.
各種医療用具の生体成分又は生体組織と接触する部分に本発明の医療用具用材料を保持させる方法としては、医療用具の表面を医療用具用材料でコーティングする方法、放射線、電子線、紫外線等の活性エネルギー線によるグラフト重合を利用して医療用具の表面と医療用具用材料とを結合させる方法、医療用具の表面の官能基と医療用具用材料とを反応させて結合させる方法等、種々の方法を用いることができる。コーティング法を用いる場合、医療用具用材料をコーティングする方法として、塗布法、スプレー法、ディップ法等のいずれの方法を用いてもよい。 Examples of a method for holding the medical device material of the present invention in a portion that comes into contact with a biological component or biological tissue of various medical devices include a method of coating the surface of the medical device with the medical device material, radiation, electron beam, ultraviolet light, etc. Various methods such as a method of bonding the surface of a medical device and a material for a medical device using graft polymerization by active energy rays, a method of bonding a functional group on the surface of a medical device and a material for a medical device, etc. Can be used. When the coating method is used, any method such as an application method, a spray method, or a dip method may be used as a method for coating a medical device material.
本発明の医療用具用材料を保持させる医療用具の材質は特に制限されず、ポリエチレン、ポリプロピレン、ポリ塩化ビニル、ポリ塩化ビニリデン、ポリフッ化ビニリデン、ポリテトラフルオロエチレン、ハロゲン化ポリオレフィン、ポリエチレンテレフタレート、ポリカーボネート、ポリアミド、アクリル樹脂、スチロール樹脂等のいずれの材質のものであってもよい。 The material of the medical device for holding the medical device material of the present invention is not particularly limited, and polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride, polytetrafluoroethylene, halogenated polyolefin, polyethylene terephthalate, polycarbonate, Any material such as polyamide, acrylic resin, and styrene resin may be used.
本発明の医療用具用材料を細胞培養基材として使用する場合、医療用具用材料をそのまま用いてもよく、所定の基材上にコーティングして用いてもよい。
基材の材質は特に制限されず、木綿、麻等の天然高分子、ポリエステル、ナイロン、オレフィン、ポリアミド、ポリウレタン、ポリアクリロニトリル、ポリ(メタ)アクリレート等の合成高分子等を用いることができる。
基材の形態も特に制限されず、成形体、繊維、不織布、多孔質体、粒子、フィルム、シート、チューブ、中空糸や粉末等のいずれの形態でもよい。
When the medical device material of the present invention is used as a cell culture substrate, the medical device material may be used as it is, or may be coated on a predetermined substrate.
The material of the substrate is not particularly limited, and natural polymers such as cotton and hemp, synthetic polymers such as polyester, nylon, olefin, polyamide, polyurethane, polyacrylonitrile, and poly (meth) acrylate can be used.
The form of the substrate is not particularly limited, and may be any form such as a molded body, fiber, nonwoven fabric, porous body, particle, film, sheet, tube, hollow fiber, and powder.
本発明の医療用具用材料は、人工血管や人工臓器等の人工生体組織用や、血液フィルター、各種カテーテル、若しくは各種ステント等;生体組織と接触する用具用の部材として、また、細胞培養基材、血液透析装置用の部材、血液若しくは組織検査用器具の部材等;生体由来成分(細胞や血液等)と接触する用具用の部材として適用することができる。
すなわち、本発明における医療用具には、生体組織と接触する用具、生体由来成分(細胞や血液等)と接触する用具等が含まれる。
すなわち、本発明における医療用具用材料は、生体組織や生体由来成分(細胞や血液等)と接触する医療用具、細胞培養基材、抗血栓性材料に用いられる物を言う。
The medical device material of the present invention is used for artificial biological tissues such as artificial blood vessels and artificial organs, blood filters, various catheters, various stents, etc .; as a member for tools that come into contact with biological tissues, and as a cell culture substrate It can be applied as a member for tools that come into contact with components derived from living organisms (cells, blood, etc.);
That is, the medical tool in the present invention includes a tool that comes into contact with a living tissue, a tool that comes into contact with a biological component (cell, blood, etc.), and the like.
That is, the material for a medical device in the present invention refers to a material used for a medical device, a cell culture substrate, or an antithrombotic material that comes into contact with a biological tissue or a biological component (cell, blood, etc.).
本発明の医療用具用材料は、上述の構成よりなり、水和時に中間水を含む重合体を含むものであり、医療用具、抗血栓性材料や細胞培養基材等に好適に用いることができる。 The medical device material of the present invention has the above-described configuration and includes a polymer containing intermediate water at the time of hydration, and can be suitably used for a medical device, an antithrombotic material, a cell culture substrate, and the like. .
以下に実施例を掲げて本発明を更に詳細に説明するが、本発明はこれらの実施例のみに限定されるものではない。なお、特に断りのない限り、「部」は「重量部」を、「%」は「質量%」を意味するものとする。 The present invention will be described in more detail with reference to the following examples. However, the present invention is not limited to these examples. Unless otherwise specified, “part” means “part by weight” and “%” means “mass%”.
合成例2で製造された重合体の重量平均分子量、ガラス転移温度は、以下の装置、条件で測定した。
<重量平均分子量>
重量平均分子量は、ゲル浸透クロマトグラフ(GPCシステム、東ソー社製)を用いて、ポリアクリル酸換算により求めた。
<ガラス転移温度>
ガラス転移温度(Tg)は、JIS K7121の規定に準拠して求めた。具体的には、示差走査熱量計(リガク製、Thermo plus EVO DSC−8230)を用い、窒素ガス雰囲気下、約10mgのサンプルを常温から200℃まで昇温(昇温速度20℃/分)して得られたDSC曲線から、始点法により評価した。リファレンスにはα−アルミナを用いた。
The weight average molecular weight and glass transition temperature of the polymer produced in Synthesis Example 2 were measured using the following apparatus and conditions.
<Weight average molecular weight>
The weight average molecular weight was determined in terms of polyacrylic acid using a gel permeation chromatograph (GPC system, manufactured by Tosoh Corporation).
<Glass transition temperature>
The glass transition temperature (Tg) was determined in accordance with JIS K7121 regulations. Specifically, using a differential scanning calorimeter (Rigaku, Thermo plus EVO DSC-8230), a sample of about 10 mg was heated from room temperature to 200 ° C. (
(合成例1)
温度計、滴下装置、冷却管、撹拌装置を備えた反応容器にアクリル酸メチル1500重量部(メトキノンを300ppm含む)、トルエン1480重量部を加え、撹拌しながら内温が85℃になるまで加熱する。これにトルエン20重量部に溶解させたトリス(ジエチルアミノ)ホスフィン1.5重量部を滴下後、撹拌しながら4時間反応させた。続いて、得られた反応液を200Torrで蒸留し、始めに未反応のアクリル酸メチルと溶媒のトルエンを留去し、その後、15Torrまで圧力を下げ、2−メチレングルタル酸ジメチルを得た。
次に、得られた2−メチレングルタル酸ジメチル100重量部、硫酸7.7重量部、水100重量部を温度計、メタノール留出管、撹拌装置を備えた反応容器に仕込んで攪拌した。上記反応液の内温を110℃に保ち、メタノールを留出させながら6時間反応させた。反応後、撹拌しながら冷却し、白色結晶を析出させ、ろ過、乾燥を行い、2−メチレングルタル酸の白色結晶を得た。
(Synthesis Example 1)
Add 1500 parts by weight of methyl acrylate (containing 300 ppm of methoquinone) and 1480 parts by weight of toluene to a reaction vessel equipped with a thermometer, a dropping device, a condenser, and a stirrer, and heat until the internal temperature reaches 85 ° C. while stirring. . To this was added dropwise 1.5 parts by weight of tris (diethylamino) phosphine dissolved in 20 parts by weight of toluene, and the mixture was reacted for 4 hours with stirring. Subsequently, the obtained reaction liquid was distilled at 200 Torr. First, unreacted methyl acrylate and the solvent toluene were distilled off, and then the pressure was reduced to 15 Torr to obtain dimethyl 2-methyleneglutarate.
Next, 100 parts by weight of the obtained dimethyl 2-methyleneglutarate, 7.7 parts by weight of sulfuric acid, and 100 parts by weight of water were charged into a reaction vessel equipped with a thermometer, a methanol distillation tube, and a stirring device and stirred. The internal temperature of the reaction solution was kept at 110 ° C. and reacted for 6 hours while distilling methanol. After the reaction, the mixture was cooled with stirring to precipitate white crystals, which were filtered and dried to obtain 2-methyleneglutaric acid white crystals.
(合成例2)
攪拌装置、温度センサー、冷却管および窒素導入管を備えた反応装置に、合成例1で得られたメチレングルタル酸(MGA)50重量部と、イオン交換水50重量部とを仕込み、これに窒素を通じつつ、80℃まで昇温させた後、重合開始剤として 過硫酸カリウム0.18重量部を加えた。更に3時間毎に過硫酸カリウム0.18重量部を3回加え、12時間にわたり重合を行なった。得られた重合体溶液をアセトンにより再沈及び洗浄し、減圧で乾燥することにより、淡黄色の固体の重合体(p−MGA)を得た。得られた重合体の1H−NMRチャート(溶媒;重水)を図1に示す。得られた重合体の重量平均分子量は26,000であり、ガラス転移温度は、125℃であった。
(Synthesis Example 2)
A reactor equipped with a stirrer, a temperature sensor, a cooling pipe, and a nitrogen introduction pipe was charged with 50 parts by weight of methylene glutaric acid (MGA) obtained in Synthesis Example 1 and 50 parts by weight of ion-exchanged water. Then, the temperature was raised to 80 ° C., and 0.18 part by weight of potassium persulfate was added as a polymerization initiator. Further, 0.18 part by weight of potassium persulfate was added three times every 3 hours, and polymerization was carried out for 12 hours. The obtained polymer solution was reprecipitated and washed with acetone, and dried under reduced pressure to obtain a light yellow solid polymer (p-MGA). FIG. 1 shows a 1 H-NMR chart (solvent: heavy water) of the obtained polymer. The weight average molecular weight of the obtained polymer was 26,000, and the glass transition temperature was 125 ° C.
(合成例3)
攪拌装置、温度センサー、冷却管および窒素導入管を備えた反応装置に、市販の試薬特級イタコン酸(ItA)50重量部と、イオン交換水50重量部とを仕込み、これに窒素を通じつつ、80℃まで昇温させた後、重合開始剤として 過硫酸カリウム0.18重量部を加えた。更に3時間毎に過硫酸カリウム0.18重量部を3回加え、12時間にわたり重合を行なった。得られた重合体溶液をアセトンにより再沈及び洗浄し、減圧で乾燥することにより、淡黄色の固体の重合体(p−ItA)を得た。得られた重合体の重量平均分子量は20,000であった。
(Synthesis Example 3)
A reactor equipped with a stirrer, a temperature sensor, a cooling tube and a nitrogen introduction tube was charged with 50 parts by weight of a commercially available reagent-grade itaconic acid (ItA) and 50 parts by weight of ion-exchanged water. After raising the temperature to 0 ° C., 0.18 parts by weight of potassium persulfate was added as a polymerization initiator. Further, 0.18 part by weight of potassium persulfate was added three times every 3 hours, and polymerization was carried out for 12 hours. The obtained polymer solution was reprecipitated and washed with acetone, and dried under reduced pressure to obtain a light yellow solid polymer (p-ItA). The weight average molecular weight of the obtained polymer was 20,000.
(実施例1及び比較例1)
上記合成例2で合成した重合体の中間水量を以下の方法により測定した。比較例1として、生体適合性に優れた重合体として広く認められているポリビニルピロリドン(和光純薬工業社製試薬 K−30)についても同様の測定を行った。結果を表1に示す。
合成例2で合成した重合体の各含水率での示差走査熱量測定チャートを図2に示し、表1に示した、合成例2で合成した重合体及びポリビニルピロリドンの中間水量と中間水量/不凍水量比との関係を図にしたものを図3に示す。
<中間水量の測定>
試料となる重合体をメタノールに溶解した0.2重量%溶液をPET製の円板上にキャストし、スピンコーターを用いて2回コーティングを行った。含湿雰囲気への暴露により飽和含水を与える方法により適量の水を含水させた。含水後の各試料の所定量を取り、あらかじめ重量を測定した酸化アルミパンの底に薄く広げた。示差走査熱量計(DSC−8230、リガク社製)を用いて、室温から−100℃まで冷却し、ついで10分間保持した後、昇温速度2.5℃/min.で−100℃から50℃まで加熱を行う過程での吸発熱量の測定を行った。なお、予め各試料の基材に用いたPET基板は有意な量の含水を生じないことを確認した。
各試料について、DSC測定後にアルミパンにピンホールをあけて真空乾燥後、その重量減少分を含水量として求めた。含水量(WC)は、基材に用いたPET基板の質量を除外した上で、以下の式(I)で求めた。
含水量(WC)=(W1−W0)/W0 (I)
(W0:試料の乾燥重量(g)、W1:試料の含水重量(g))
次に、各含水量におけるコールドクリスタリゼーションに伴う発熱量と0℃付近の吸熱量の関係から、不凍水と中間水の最大量を求めてW0で除することにより、それぞれの試料における不凍水量と中間水量とした。
(Example 1 and Comparative Example 1)
The intermediate water content of the polymer synthesized in Synthesis Example 2 was measured by the following method. As Comparative Example 1, the same measurement was performed for polyvinylpyrrolidone (reagent K-30 manufactured by Wako Pure Chemical Industries, Ltd.), which is widely recognized as a polymer excellent in biocompatibility. The results are shown in Table 1.
The differential scanning calorimetry chart at each moisture content of the polymer synthesized in Synthesis Example 2 is shown in FIG. 2, and the intermediate water amount and the intermediate water amount / invalid water amount / absence of the polymer synthesized in Synthesis Example 2 and polyvinylpyrrolidone shown in Table 1 are shown in Table 1. Fig. 3 shows the relationship with the frozen water ratio.
<Measurement of intermediate water volume>
A 0.2 wt% solution in which a sample polymer was dissolved in methanol was cast on a PET disc, and coating was performed twice using a spin coater. An appropriate amount of water was hydrated by a method of providing a saturated water content by exposure to a humid atmosphere. A predetermined amount of each water-containing sample was taken and spread thinly on the bottom of an aluminum oxide pan whose weight was measured in advance. Using a differential scanning calorimeter (DSC-8230, manufactured by Rigaku Corporation), the temperature was cooled from room temperature to −100 ° C. and then held for 10 minutes, and then the rate of temperature increase was 2.5 ° C./min. In the process of heating from −100 ° C. to 50 ° C., the endothermic heat generation amount was measured. It was confirmed that the PET substrate used as the base material for each sample did not produce a significant amount of water.
About each sample, after DSC measurement, the pinhole was made to the aluminum pan, and it vacuum-dried, and calculated | required the weight loss as water content. The water content (WC) was determined by the following formula (I) after excluding the mass of the PET substrate used for the base material.
Water content (WC) = (W1-W0) / W0 (I)
(W0: dry weight of sample (g), W1: wet weight of sample (g))
Next, the maximum amount of antifreeze water and intermediate water is obtained from the relationship between the calorific value associated with cold crystallization at each water content and the endothermic amount near 0 ° C., and divided by W0 to obtain the non-freeze in each sample. The amount of frozen water and the amount of intermediate water were used.
(実施例2)
合成例3で合成したp−ItAのDSC測定を行い、p−ItAが中間水を保持することを確認した。図4にDSCの測定結果を示す。0℃以下に融解ピークがあり、中間水の存在が確認された。
(Example 2)
DSC measurement of p-ItA synthesized in Synthesis Example 3 was performed, and it was confirmed that p-ItA retained intermediate water. FIG. 4 shows the DSC measurement results. There was a melting peak below 0 ° C., and the presence of intermediate water was confirmed.
実施例1、2の結果から、ポリメチレングルタル酸(p−MGA)及びポリイタコン酸(p−ItA)は、含水時に中間水を有する重合体であり、医療用具用材料として使用できる重合体であることが確認された。また、ポリメチレングルタル酸は、同じ中間水量で比較すると、ポリビニルピロリドンよりも不凍水に対する中間水の割合が大きいことも確認された。
From the results of Examples 1 and 2, polymethylene glutaric acid (p-MGA) and polyitaconic acid (p-ItA) are polymers having intermediate water when containing water, and can be used as materials for medical devices. It was confirmed. It was also confirmed that polymethylene glutaric acid had a higher ratio of intermediate water to antifreeze water than polyvinylpyrrolidone when compared with the same amount of intermediate water.
Claims (5)
PVG−CONR 1 R 2
[式中、PVGはビニル(CH=CR 1 −)、アクリラド(CH 2 =CR 1 COO−R 4 −)、アクリルアミド(CH 2 =CR 1 CONR 5 −R 6 −)からなる群から選択される共重合しうるビニル基であり;R 1 はH、−CH 2 COOR 7 及びC 1 〜C 5 アルキルの群から選択され;R 2 、R 3 、R 4 、R 5 、R 6 及びR 7 は同一でも異なってもよく且つ置換されていてもいなくてもよく、H、C 1 〜C 6 アルキル、フェニル及びシクロヘキシルからなる群から選択される]で表されるアミドアクリル由来の繰り返し単位を有するものを除く)を含むことを特徴とする医療用具用材料(歯科用修復材料の封鎖材を除く)。 The material used for the part which contacts a biological component or a biological tissue of the medical device used in contact with a biological component or a biological tissue, Comprising: This material is following formula (1);
PVG-CONR 1 R 2
Wherein, PVG is vinyl (CH = CR 1 -), Akurirado (CH 2 = CR 1 COO- R 4 -) - is selected from the group consisting of acrylamide (CH 2 = CR 1 CONR 5 -R 6) R 1 is selected from the group of H, —CH 2 COOR 7 and C 1 -C 5 alkyl; R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are copolymerizable vinyl groups; Having a repeating unit derived from an amide acrylic represented by the following formula: selected from the group consisting of H, C 1 -C 6 alkyl, phenyl and cyclohexyl, which may be the same or different and may be unsubstituted characterized in that it comprises a excluding) medical device materials (excluding sealants of dental restorative materials).
該医療用具は、生体成分又は生体組織と接触する部分が前記医療用具用材料を用いて構成されていることを特徴とする医療用具。 A medical device using the medical device material according to claim 1 or 2,
The medical device is characterized in that a portion in contact with a biological component or a biological tissue is configured using the medical device material.
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