JP2010280636A - Proliferation inhibiting material of smooth muscle cell - Google Patents
Proliferation inhibiting material of smooth muscle cell Download PDFInfo
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本発明は、平滑筋細胞の増殖抑制材料に関し、特に平滑筋細胞の増殖が問題となる医療器具等に用いることができる平滑筋細胞の増殖抑制材料に関する。 The present invention relates to a smooth muscle cell growth inhibitory material, and more particularly to a smooth muscle cell proliferation inhibitory material that can be used in a medical device or the like in which smooth muscle cell proliferation is a problem.
医療の発達と共に、血管内に留置するステントや、埋め込み式の人工心臓等の生体内で使用する医療器具の使用が増加している。しかし、医療器具を生体内に埋め込むと、生体が異物として認識するため、血栓形成をはじめとする種々の生体反応が惹起されるという問題がある。 With the development of medical treatment, the use of medical instruments used in vivo such as stents placed in blood vessels and implantable artificial hearts is increasing. However, when a medical instrument is embedded in a living body, the living body recognizes it as a foreign substance, which causes a problem that various biological reactions such as thrombus formation are induced.
例えば、医療器具に生じる血栓形成を低減する方法を考えた場合、ヘパリン又はウロキナーゼ等の抗血栓性薬剤により医療器具をコーティングする方法が知られている。しかし、薬剤のコーティングは剥がれやすく効果が持続しないという問題がある。また、薬剤による副作用の問題も知られている。 For example, when considering a method of reducing thrombus formation in a medical device, a method of coating a medical device with an antithrombotic drug such as heparin or urokinase is known. However, there is a problem that the drug coating is easily peeled off and the effect is not sustained. In addition, the problem of side effects caused by drugs is also known.
そこで、薬剤にたよるのではなく、医療器具自体を抗血栓性の材料により形成したり、医療器具の表面に抗血栓性に優れた強固な皮膜を形成したりする方法が検討されている。中でも、ダイヤモンド様炭素（ＤＬＣ）膜により医療器具を覆う方法は、耐久性に優れているため特に注目されている。 In view of this, a method of forming the medical device itself with an antithrombotic material or forming a strong film with excellent antithrombogenicity on the surface of the medical device is being studied instead of depending on a drug. Among them, a method of covering a medical device with a diamond-like carbon (DLC) film is particularly attracting attention because of its excellent durability.
さらに、ＤＣＬ膜の抗血栓性を向上させるために、ＤＬＣ膜の表面に親水性の官能基を導入したり、抗血栓性の薬剤を固定したりすることも検討されている（例えば、特許文献１を参照。）。 Furthermore, in order to improve the antithrombogenicity of the DCL membrane, introduction of a hydrophilic functional group or immobilization of an antithrombotic drug on the surface of the DLC membrane has been studied (for example, Patent Documents). 1).
しかしながら、短時間の使用が前提である透析器及び人工心肺等においては血栓形成の防止の観点から材料の設計をすれば十分であるが、ステント及び人工血管等の埋め込み医療器具を目指す場合には、血液適合性だけでなく組織適合性をも考慮する必要がある。例えば、血管内留置ステントを考えた場合、血管を構成する平滑筋細胞とＤＬＣ膜等の材料との相互作用を調べることは重要である。ＤＬＣ膜を医療器具の材料として考えた場合、抗血栓性についてはこれまで検討されているが、平滑筋細胞等の組織細胞との相互作用についてはほとんど検討されていない。 However, in dialyzers and heart-lung machines that are premised on short-term use, it is sufficient to design materials from the viewpoint of preventing thrombus formation, but when aiming for implantable medical devices such as stents and artificial blood vessels It is necessary to consider not only blood compatibility but also tissue compatibility. For example, when considering an indwelling stent, it is important to examine the interaction between the smooth muscle cells constituting the blood vessel and a material such as a DLC film. When a DLC film is considered as a material for a medical device, antithrombotic properties have been studied so far, but little interaction with tissue cells such as smooth muscle cells has been studied.
平滑筋細胞は血管の収縮及び弛緩を制御する細胞である。平滑筋細胞は何らかの刺激を受けると増殖する性質を有していることが知られている。血管内にステント等を留置した場合に、平滑筋細胞が刺激を受けると平滑筋細胞が異常に増殖し、血管が狭窄してしまう。このため、血管内に留置する医療器具は平滑筋細胞に刺激を与えにくく、平滑筋細胞の増殖を抑制する機能を有している必要がある。また、内皮細胞に速やかに覆われる特性を有していれば、血栓形成のリスクを大幅に低減することができる。 Smooth muscle cells are cells that control vasoconstriction and relaxation. It is known that smooth muscle cells have the property of proliferating when subjected to some kind of stimulation. When a stent or the like is placed in a blood vessel, if the smooth muscle cell is stimulated, the smooth muscle cell proliferates abnormally and the blood vessel is narrowed. For this reason, a medical instrument placed in a blood vessel is unlikely to stimulate smooth muscle cells and needs to have a function of suppressing the growth of smooth muscle cells. Moreover, if it has the characteristic of being covered quickly by endothelial cells, the risk of thrombus formation can be greatly reduced.
本発明は、本願発明者らによって得られた平滑筋細胞の増殖とＤＬＣ膜の表面状態との相間に基づいてなされたものであり、医療器具等に適した平滑筋細胞の増殖を抑制する材料を実現できるようにすることを目的とする。 The present invention was made on the basis of the phase between the smooth muscle cell proliferation obtained by the inventors of the present application and the surface state of the DLC film, and is a material that suppresses the proliferation of smooth muscle cells suitable for medical instruments and the like. It aims to be able to realize.
前記の目的を達成するため、本発明は平滑筋細胞の増殖抑制材料を、カルボキシル基導入量が少ないダイヤモンド様炭素膜とする。 In order to achieve the above-mentioned object, the present invention uses a diamond-like carbon film with a small amount of carboxyl group introduction as a material for inhibiting smooth muscle cell proliferation.
具体的に、本発明に係る平滑筋細胞の増殖抑制材料は、基材の表面に形成されたダイヤモンド様炭素膜と、ダイヤモンド様炭素膜の表面に導入されたカルボキシル基とを備え、カルボキシル基の導入率は、３．５％以下であることを特徴とする。 Specifically, the smooth muscle cell proliferation-suppressing material according to the present invention comprises a diamond-like carbon film formed on the surface of a substrate and a carboxyl group introduced on the surface of the diamond-like carbon film, The introduction rate is characterized by being 3.5% or less.
本発明の平滑筋細胞の増殖抑制材料は、カルボキシル基の導入率（ＣＯＯ／Ｃ）が３．５％以下のダイヤモンド様炭素（ＤＬＣ）膜を備えている。平滑筋細胞の増殖率は、ＤＬＣ膜表面のカルボキシル基の量が少ないほど低くなる。ＣＯＯ／Ｃが３．５％以下の場合には、通常の細胞培養プレートよりも増殖率が低くなる。従って、平滑筋細胞の増殖率が抑制された生体適合性に優れた材料となる。 The smooth muscle cell growth inhibitory material of the present invention includes a diamond-like carbon (DLC) film having a carboxyl group introduction rate (COO / C) of 3.5% or less. The proliferation rate of smooth muscle cells decreases as the amount of carboxyl groups on the surface of the DLC film decreases. When COO / C is 3.5% or less, the growth rate is lower than that of a normal cell culture plate. Therefore, it becomes a material excellent in biocompatibility in which the proliferation rate of smooth muscle cells is suppressed.
本発明の平滑筋細胞の増殖抑制材料は、ダイヤモンド様炭素膜の表面に導入されたアミノ基をさらに備えていてもよい。アミノ基の導入率は平滑筋細胞の増殖率には影響しないが、内皮細胞の増殖率を向上させることができる。 The smooth muscle cell growth inhibitory material of the present invention may further comprise an amino group introduced on the surface of the diamond-like carbon film. The introduction rate of amino groups does not affect the proliferation rate of smooth muscle cells, but can improve the proliferation rate of endothelial cells.
本発明に係るステントは、本発明の平滑筋細胞の増殖抑制材料を備えていることを特徴とする。 The stent according to the present invention comprises the smooth muscle cell growth inhibitory material of the present invention.
本発明に係る平滑筋細胞の増殖抑制材料によれば、医療器具等に適した平滑筋細胞の増殖を抑制する材料を実現できる。 According to the smooth muscle cell proliferation-suppressing material according to the present invention, a material that suppresses the proliferation of smooth muscle cells suitable for a medical instrument or the like can be realized.
（一実施例）
本発明の一実施例に係る平滑筋細胞の増殖抑制材料は、ダイヤモンド様炭素（ＤＬＣ）膜等の炭素質膜であり、カルボキシル基を有している。以下に、その構成及び製造方法について詳細に説明する。
(Example)
The smooth muscle cell growth inhibitory material according to one embodiment of the present invention is a carbonaceous film such as a diamond-like carbon (DLC) film and has a carboxyl group. Below, the structure and manufacturing method are demonstrated in detail.
−炭素質膜の形成−
基材の表面にダイヤモンド様炭素（ＤＬＣ）膜を形成した。細胞培養の際には基材として直径１５ｍｍのカバーガラスを用いた。ＤＬＣ膜は化学気相堆積（ＣＶＤ）法を用いて形成した。具体的には、基材を載置したチャンバ内にＣ2Ｈ2を流量が１５０ｓｃｃｍ（ｃｍ3／分、但し１気圧、０℃）で、圧力が３Ｐａ（２２ｍＴｏｒｒ）となるように導入し、ＲＦ電極に１００Ｗの高周波電力を印加した。これにより、カルボキシル基導入率が０％で膜厚が０．１３μｍのＤＬＣ膜を得た。なお、ＤＬＣ膜とは、ｓｐ2炭素−炭素結合（グラファイト結合）及びｓｐ3炭素−炭素結合（ダイヤモンド結合）を含むアモルファス膜である。
-Formation of carbonaceous film-
A diamond-like carbon (DLC) film was formed on the surface of the substrate. In the cell culture, a cover glass having a diameter of 15 mm was used as a substrate. The DLC film was formed using a chemical vapor deposition (CVD) method. Specifically, C 2 H 2 was introduced into the chamber on which the substrate was placed so that the flow rate was 150 sccm (cm 3 / min, where 1 atm, 0 ° C.) and the pressure was 3 Pa (22 mTorr), A high frequency power of 100 W was applied to the RF electrode. As a result, a DLC film having a carboxyl group introduction rate of 0% and a film thickness of 0.13 μm was obtained. The DLC film is an amorphous film containing sp 2 carbon-carbon bonds (graphite bonds) and sp 3 carbon-carbon bonds (diamond bonds).
ＤＬＣ膜の形成には他の方法を用いてもよい。例えば、スパッタ法、ＤＣマグネトロンスパッタ法、ＲＦマグネトロンスパッタ法、プラズマイオン注入法、重畳型ＲＦプラズマイオン注入法、イオンプレーティング法、アークイオンプレーティング法、イオンビーム蒸着法又はレーザーアブレーション法等を用いることができる。 Other methods may be used for forming the DLC film. For example, sputtering method, DC magnetron sputtering method, RF magnetron sputtering method, plasma ion implantation method, superposition type RF plasma ion implantation method, ion plating method, arc ion plating method, ion beam evaporation method, laser ablation method or the like is used. be able to.
また、基材とＤＬＣ膜との間にアモルファスシリコン等からなる中間層を形成してもよい。また、ＤＬＣ膜の膜厚は、特に限定されるものではないが、０．００５μｍ〜３μｍの範囲が好ましく、より好ましくは０．０１μｍ〜１μｍの範囲である。 An intermediate layer made of amorphous silicon or the like may be formed between the base material and the DLC film. The thickness of the DLC film is not particularly limited, but is preferably in the range of 0.005 μm to 3 μm, more preferably in the range of 0.01 μm to 1 μm.
−カルボキシル基導入率の調整−
得られたＤＬＣ膜にプラズマを照射することにより、官能基導入率が異なるＤＬＣ膜を形成した。プラズマ照射は平行平板型のプラズマ照射装置により行った。ターボ分子ポンプを使用し、高真空条件下でプラズマ処理を行える装置と、ロータリーポンプのみを使用し、低真空条件下でプラズマ処理を行える装置とを用いた。プラズマ照射装置のチャンバ内にＤＬＣ膜を形成した基材をセットした後、チャンバ内の圧力を１×１０-3Ｐａ以下又は２Ｐａ以下まで排気する。次に、チャンバ内にガスを所定の流量で導入し、平行平板電極の間に高周波電力を印加することによりプラズマを発生させた。高周波電力は、高真空条件の場合には１００Ｗとし、低真空条件の場合には３０Ｗとした。ガス流量の調整はマスフローコントローラにより行い、プラズマ照射時のチャンバ内圧力は高真空条件の場合には１Ｐａとし、低真空条件の場合には１３０Ｐａとした。高周波電力は、マッチングボックスを介して接続された高周波電源を用いて印加した。プラズマの生成に用いたガスは、アルゴン（Ａｒ）、アセチレン（Ｃ2Ｈ2）、アンモニア（ＮＨ3）及び酸素（Ｏ2）である。これにより、カルボキシル基導入率が１．５％〜３．９％までの９種類のサンプルを形成した。
-Adjustment of carboxyl group introduction rate-
The obtained DLC film was irradiated with plasma to form DLC films with different functional group introduction rates. Plasma irradiation was performed by a parallel plate type plasma irradiation apparatus. An apparatus capable of performing plasma processing under high vacuum conditions using a turbo molecular pump and an apparatus capable of performing plasma processing under low vacuum conditions using only a rotary pump were used. After setting the base material on which the DLC film is formed in the chamber of the plasma irradiation apparatus, the pressure in the chamber is exhausted to 1 × 10 −3 Pa or less or 2 Pa or less. Next, gas was introduced into the chamber at a predetermined flow rate, and plasma was generated by applying high-frequency power between the parallel plate electrodes. The high frequency power was 100 W for high vacuum conditions and 30 W for low vacuum conditions. The gas flow rate was adjusted by a mass flow controller, and the pressure in the chamber at the time of plasma irradiation was 1 Pa in a high vacuum condition and 130 Pa in a low vacuum condition. The high frequency power was applied using a high frequency power source connected via a matching box. The gases used for generating the plasma are argon (Ar), acetylene (C 2 H 2 ), ammonia (NH 3 ), and oxygen (O 2 ). Thus, nine types of samples having a carboxyl group introduction rate of 1.5% to 3.9% were formed.
−官能基導入率の測定−
ＤＬＣ膜の表面におけるカルボキシル基の導入率及び窒素の導入率はＸ線光電子分光（ＸＰＳ）測定により評価した。ＸＰＳ測定には、日本電子株式会社製の光電子分光装置ＪＰＳ−９０１０ＭＣを用いた。Ｘ線源にはアルミニウムＫα線を用い、加速電圧が１２．５ｋＶで、エミッション電流が１０ｍＡの条件でＸ線を発生させた。試料中から任意に選択した直径５ｍｍのエリアについて測定を行った。また、Ｘ線を試料に対して４５度の角度で入射させ、検出角度を試料面に対して９０度とすることにより、５ｎｍ程度の深さまでの組成を測定した。
-Measurement of functional group introduction rate-
The introduction rate of carboxyl groups and the introduction rate of nitrogen on the surface of the DLC film were evaluated by X-ray photoelectron spectroscopy (XPS) measurement. For the XPS measurement, a photoelectron spectrometer JPS-9010MC manufactured by JEOL Ltd. was used. Aluminum X-ray was used as the X-ray source, and X-rays were generated under the conditions of an acceleration voltage of 12.5 kV and an emission current of 10 mA. Measurement was performed on an area of 5 mm in diameter arbitrarily selected from the sample. Further, the composition up to a depth of about 5 nm was measured by making X-rays incident on the sample at an angle of 45 degrees and setting the detection angle to 90 degrees with respect to the sample surface.
結合エネルギーの測定領域は、２７４ｅＶ〜２９４ｅＶ、３８９ｅＶ〜４０９ｅＶ及び５２２ｅＶ〜５４２ｅＶとし、それぞれ炭素１ｓ（Ｃ１ｓ）、窒素１ｓ（Ｎ１ｓ）及び酸素１ｓ（Ｏ１ｓ）のピークを得た。Ｃ１ｓのナローピークをピークフィッティングすることにより全炭素に対するカルボキシル基量（ＣＯＯ／Ｃ）を求めた。また、Ｎ１ｓピークの面積とＮ１ｓピーク、Ｃ１ｓピーク及びＯ１ｓピークの面積の和との比率から窒素の導入量（Ｎ／Ｃ＋Ｎ＋Ｏ）を求めた。 The binding energy measurement regions were 274 eV to 294 eV, 389 eV to 409 eV, and 522 eV to 542 eV, and peaks of carbon 1s (C1s), nitrogen 1s (N1s), and oxygen 1s (O1s) were obtained, respectively. The amount of carboxyl groups (COO / C) relative to the total carbon was determined by peak fitting the narrow peak of C1s. The amount of nitrogen introduced (N / C + N + O) was determined from the ratio of the area of the N1s peak and the sum of the areas of the N1s peak, the C1s peak, and the O1s peak.
−平滑筋細胞の増殖性の測定−
細胞の増殖率は次の様にして求めた。ＣＯＯ／Ｃの値が異なる種々のＤＬＣ膜がコートされた直径１５ｍｍのカバーグラスを７０％エタノールにより滅菌した後、２４穴の細胞培養用マルチプレート（Costar 3516、コーニング社）の底に置き、超純水により３回洗浄した。カバーグラスの表面に人冠動脈由来の平滑筋細胞（Cell Applications社：ＨＣＡＳＭＣ）を１×１０4cell/well（５００μＬ）の密度で播種した。播種の後、温度を３７℃とし、５％炭酸ガス雰囲気で４日間継続して培養を行った。培地には、Cell Applications社より販売されている各細胞専用の培地を使用し、培地交換は毎日行った。４日間培養した後の細胞増殖率をCell-Counting-Kit8（同仁化学製）を用いて求めた。測定法はキットに添付のマニュアルに従い行った。各ＤＬＣ膜における増殖率の比較は、増殖した細胞数に対応する細胞内のミトコンドリアの活性により生じるWST-8 frmazanの濃度（吸光度）をマイクロプレートリーダーを用いて求め、市販の細胞培養プレート（ＴＣＰ）上で培養を行った場合の吸光度を１００％とし、これに対する各サンプルの％増殖率を算出すことにより増殖性を比較検討した。
-Measurement of smooth muscle cell proliferation-
The cell growth rate was determined as follows. A 15 mm diameter cover glass coated with various DLC films with different COO / C values was sterilized with 70% ethanol, and then placed on the bottom of a 24-well cell culture multiplate (Costar 3516, Corning). Washed 3 times with pure water. Human coronary artery-derived smooth muscle cells (Cell Applications: HCASMC) were seeded on the surface of the cover glass at a density of 1 × 10 4 cell / well (500 μL). After sowing, the temperature was 37 ° C., and the culture was continued for 4 days in a 5% carbon dioxide atmosphere. As the medium, a medium dedicated to each cell sold by Cell Applications was used, and the medium was changed every day. The cell growth rate after culturing for 4 days was determined using Cell-Counting-Kit8 (Dojindo). The measurement method was performed according to the manual attached to the kit. For comparison of the growth rate in each DLC membrane, the concentration (absorbance) of WST-8 frmazan produced by intracellular mitochondrial activity corresponding to the number of cells grown was obtained using a microplate reader, and a commercially available cell culture plate (TCP ) When the above culture was performed, the absorbance was set to 100%, and the proliferation rate was compared by calculating the% growth rate of each sample.
−平滑筋細胞の増殖性の評価−
図１は、ＣＯＯ／Ｃの値と平滑筋細胞の増殖率との関係を示している。図１に示すようにＣＯＯ／Ｃの値が大きくなると増殖率の値が大きくなった。ＣＯＯ／Ｃの値が３．５％以下の場合には、平滑筋細胞の増殖率が１００％未満となったが、ＣＯＯ／Ｃの値が３．５％を越えると平滑筋細胞の増殖率が１００％を越え、ＴＣＰよりも平滑筋細胞が増殖しやすくなった。ＴＣＰは優れた細胞増殖性を示すように処理がなされているが、カルボキシル基導入率が低いＤＬＣ膜は、ＴＣＰよりも優れた平滑筋細胞の増殖抑制材料となることが示された。
-Evaluation of smooth muscle cell proliferation-
FIG. 1 shows the relationship between the value of COO / C and the proliferation rate of smooth muscle cells. As shown in FIG. 1, the growth rate increased as the value of COO / C increased. When the value of COO / C was 3.5% or less, the proliferation rate of smooth muscle cells was less than 100%, but when the value of COO / C exceeded 3.5%, the proliferation rate of smooth muscle cells. Exceeded 100%, and smooth muscle cells proliferated more easily than TCP. Although TCP has been treated to exhibit excellent cell growth properties, a DLC film having a low carboxyl group introduction rate has been shown to be a superior smooth muscle cell growth inhibitory material than TCP.
平滑筋細胞の増殖性は、カルボキシル基を含まない場合に最も小さくなると推測される。しかし、カルボキシル基を含まない未処理のＤＬＣ膜の場合、内皮細胞の増殖性も低くなってしまう。このため、平滑筋細胞の増殖性を抑え且つ内皮細胞の増殖性を高く保つためには、カルボキシル基が導入されたＤＬＣ膜であることが必要である。 It is estimated that smooth muscle cell proliferation is minimized when a carboxyl group is not included. However, in the case of an untreated DLC film that does not contain a carboxyl group, the proliferation of endothelial cells is also lowered. For this reason, in order to suppress the proliferation of smooth muscle cells and keep the proliferation of endothelial cells high, it is necessary to be a DLC film into which a carboxyl group has been introduced.
図２は、窒素含有率（Ｎ／Ｃ＋Ｎ＋Ｏ）に対して平滑筋細胞の増殖率をプロットしている。窒素含有率の値と平滑筋細胞の増殖率との間にはほとんど相間が認められなかった。窒素含有量の値と平滑筋細胞の増殖率との間には相関が認められなかったが、内皮細胞の増殖率はＤＬＣ膜の表面に導入されたアミノ基の量によって変化することが知られている。従って、アンモニアプラズマを照射してカルボキシル基とアミノ基を含むＤＬＣ膜を形成すれば、平滑筋細胞の増殖抑制できると共に、内皮細胞の増殖を促進できる材料とすることが可能となる。 FIG. 2 plots the proliferation rate of smooth muscle cells against the nitrogen content (N / C + N + O). Almost no interphase was observed between the nitrogen content value and the smooth muscle cell proliferation rate. There was no correlation between the value of nitrogen content and the proliferation rate of smooth muscle cells, but the proliferation rate of endothelial cells was known to change depending on the amount of amino groups introduced on the surface of the DLC membrane. ing. Therefore, if a DLC film containing a carboxyl group and an amino group is formed by irradiating ammonia plasma, a material capable of suppressing the proliferation of smooth muscle cells and promoting the proliferation of endothelial cells can be obtained.
また、アミノ基を導入する場合にはアンモニアに代えて他の塩基性窒素含有化合物を用いることも可能である。塩基性窒素含有化合物としては、一般式がＮＲ1Ｒ2Ｒ3により示される有機アミン類（但し、Ｒ1、Ｒ2及びＲ3は水素、−ＣＨ3、−Ｃ2Ｈ5、−Ｃ3Ｈ7又は−Ｃ4Ｈ8であり、Ｒ1、Ｒ2及びＲ3は互いに同一であっても、異なっていてもよい。）又はベンジルアミン及びその２級、３級アミン等が挙げられる。但し、アンモニアがコスト、取り扱いの容易さから好ましい。 When introducing an amino group, other basic nitrogen-containing compounds can be used instead of ammonia. Examples of basic nitrogen-containing compounds include organic amines represented by the general formula NR 1 R 2 R 3 (wherein R 1 , R 2 and R 3 are hydrogen, —CH 3 , —C 2 H 5 , —C 3 H 7 or —C 4 H 8 , and R 1 , R 2 and R 3 may be the same or different from each other.) Or benzylamine and its secondary and tertiary amines. However, ammonia is preferable because of cost and ease of handling.
基材は、どのような材質であってもよい。具体的には、特に限定されるものではないが例えば、鉄、ニッケル、クロム、銅、チタン、白金、タングステン又はタンタル等の金属を基材として用いることができる。また、これらの合金である、ＳＵＳ３１６Ｌ等のステンレス鋼、Ｔｉ−Ｎｉ合金若しくはＣｕ−Ａｌ−Ｍｎ合金等の形状記憶合金、Ｃｕ−Ｚｎ合金、Ｎｉ−Ａｌ合金、チタン合金、タンタル合金、プラチナ合金又はタングステン合金等の合金を用いることもできる。また、アルミニウム、シリコン若しくはジルコン等の酸化物、窒化物若しくは炭化物等の生体不活性なセラミックス又はアパタイト若しくは生体ガラス等の生体活性を有するセラミックスでもよい。さらに、ポリメタクリル酸メチル（ＰＭＭＡ）、高密度ポリエチレン、ポリアセタール、ポリエチレンテレフタレート（ＰＥＴ）等のポリエステル、ポリカーボネート樹脂若しくはポリスルホン等の高分子樹脂又はポリジメチルシロキサン等のシリコンポリマー若しくはポリテトラフルオロエチレン等のフッ素系ポリマー等であってもよい。 The base material may be any material. Specifically, although not particularly limited, for example, a metal such as iron, nickel, chromium, copper, titanium, platinum, tungsten, or tantalum can be used as the base material. Further, these alloys are stainless steel such as SUS316L, shape memory alloy such as Ti—Ni alloy or Cu—Al—Mn alloy, Cu—Zn alloy, Ni—Al alloy, titanium alloy, tantalum alloy, platinum alloy or An alloy such as a tungsten alloy can also be used. Moreover, bioactive ceramics, such as oxides, such as aluminum, a silicon | silicone, or a zircon, nitride, or carbide | carbonized_material, or ceramics which have bioactivity, such as apatite or a biological glass, may be sufficient. Further, polyester such as polymethyl methacrylate (PMMA), high density polyethylene, polyacetal, polyethylene terephthalate (PET), polymer resin such as polycarbonate resin or polysulfone, silicon polymer such as polydimethylsiloxane, or fluorine such as polytetrafluoroethylene A polymer may be used.
また、形状もどのような形状であってもよく、医療器具等の状態に成形されたものであっても、板材、棒材又は線材等の成形前の材料の状態であってもよい。特に、平滑筋細胞の増殖抑制材料によりステント等の血管内に留置する医療器具の表面を被覆すれば、再狭窄が生じにくい医療器具を実現することが可能となる。 Further, the shape may be any shape, and it may be formed in a state of a medical instrument or the like, or may be in a state of a material before forming, such as a plate material, a rod material, or a wire material. In particular, if the surface of a medical device to be placed in a blood vessel such as a stent is covered with a smooth muscle cell growth inhibitory material, a medical device in which restenosis is unlikely to occur can be realized.
本発明に係る平滑筋細胞の増殖抑制材料は、平滑筋細胞の増殖を抑制する材料を実現でき、平滑筋細胞の増殖が問題となる医療器具等に用いることができる平滑筋細胞の増殖抑制材料等として有用である。 The smooth muscle cell proliferation-suppressing material according to the present invention can realize a material that inhibits smooth muscle cell proliferation, and can be used for a medical instrument or the like in which smooth muscle cell proliferation is a problem. Useful as such.
Claims (3)
前記ダイヤモンド様炭素膜の表面に導入されたカルボキシル基とを備え、
前記カルボキシル基の導入率は、３．５％以下であることを特徴とする平滑筋細胞の増殖抑制材料。 A diamond-like carbon film formed on the surface of the substrate;
A carboxyl group introduced on the surface of the diamond-like carbon film,
The material for inhibiting the proliferation of smooth muscle cells, wherein the introduction rate of the carboxyl group is 3.5% or less.
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| JP2002516721A (en) * | 1998-06-03 | 2002-06-11 | ナムローゼ・フェンノートシャップ・ベーカート・ソシエテ・アノニム | Stent with diamond-like coating |
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