JPS6287163A - Production of antithrombotic material - Google Patents
Production of antithrombotic materialInfo
- Publication number
- JPS6287163A JPS6287163A JP60228474A JP22847485A JPS6287163A JP S6287163 A JPS6287163 A JP S6287163A JP 60228474 A JP60228474 A JP 60228474A JP 22847485 A JP22847485 A JP 22847485A JP S6287163 A JPS6287163 A JP S6287163A
- Authority
- JP
- Japan
- Prior art keywords
- antithrombotic
- reducing agent
- polymerization
- salt
- tube
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- Treatments Of Macromolecular Shaped Articles (AREA)
- Materials For Medical Uses (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、抗血栓性材料の製造法に関する。[Detailed description of the invention] [Industrial application field] The present invention relates to a method for manufacturing antithrombotic materials.
さらに詳しくは、グラフト重合法による抗血栓性材料の
製造法に関する。More specifically, the present invention relates to a method for producing an antithrombotic material using a graft polymerization method.
人工血管は抗血栓性の要求される代表的な医用材料の１
つであるが、現状では十分な抗血栓性を有するのちは得
られておらず、ごく一部の領域で実用化されているにす
ぎない。すなわち、従来より大口径動脈用の人工血管と
してポリエステル編物あるいはポリテトラフルオロエチ
レンからなる多孔性材料などが使用されているが、これ
らの材料の抗血栓性は十分ではないので、小口径の動脈
や血液の流速の小さい静脈では短時間のうちに血栓を生
成し閉塞してしまい、使用することができなかった。Artificial blood vessels are one of the typical medical materials that require antithrombotic properties.
However, at present, sufficient antithrombotic properties have not been obtained, and they have only been put into practical use in a small number of areas. In other words, polyester knit fabrics or porous materials made of polytetrafluoroethylene have been used as artificial blood vessels for large-diameter arteries, but these materials do not have sufficient antithrombotic properties, so they cannot be used for small-diameter arteries or artificial blood vessels. In veins where the blood flow rate is low, blood clots form within a short period of time, resulting in occlusion, making it unusable.
また、特開昭４６−４２７５９号公報、特開昭５０−１
５０７９３号公報および特開昭５１−２４６５１号公報
等においては、ポリ （２−ヒドロキシエチル）メタク
リレートやポリビニルアルコールなどの親水性重合体を
架橋処理して得られるヒドロゲルからなる抗血栓性材料
が開示されているが、抗血栓性が不十分であるだけでな
く強度も小さいので、人工血管として使用するには問題
があった。また、特開昭４９−１２５４９３号公報およ
び特開昭５１−１２５９７８号公報においては、上記の
親水性重合体を形成する単量体を基材表面にグラフト重
合する方法が開示されているが、この方法では基材を適
当に選択することにより材料強度の改良はできても抗血
栓性については親水性重合体と同等の効果しか得られて
いないので、やはり小口径の動脈や静脈への適用は困難
であった。Also, JP-A-46-42759, JP-A-50-1
No. 50793 and Japanese Unexamined Patent Publication No. 51-24651 disclose antithrombotic materials comprising hydrogels obtained by crosslinking hydrophilic polymers such as poly(2-hydroxyethyl) methacrylate and polyvinyl alcohol. However, it has problems in its use as an artificial blood vessel because it not only has insufficient antithrombotic properties but also low strength. Further, JP-A-49-125493 and JP-A-51-125978 disclose a method of graft polymerizing a monomer forming the above-mentioned hydrophilic polymer onto the surface of a base material. Although this method can improve the material strength by appropriately selecting the base material, it is only as effective as a hydrophilic polymer in terms of antithrombotic properties, so it cannot be applied to small-diameter arteries or veins. was difficult.
さらに、特開昭４８−６６１８７号公報および特開昭５
３−１０６７７８号公報等にはヘパリンやウロキナーゼ
などの血液凝固抑制物質を材料の表面に固定して抗血栓
性を付与する方法が開示されている。この方法では初期
には優れた抗血栓性が得られるもののしだいに血液凝固
抑制効果が低下するので、長期間にわたって安定した抗
血栓性を得ることはできなかった。そして、このような
方法により製造される抗血栓性材料は、血液凝固抑制物
質が高価であることと滅菌が難しいために無菌的に製造
する必要があることからきわめて高価なものになるとい
う欠点があった。Furthermore, JP-A No. 48-66187 and JP-A No. 5
Publication No. 3-106778 and the like discloses a method of immobilizing a blood coagulation inhibitor such as heparin or urokinase on the surface of a material to impart antithrombotic properties. In this method, excellent antithrombotic properties can be obtained initially, but the blood coagulation inhibitory effect gradually decreases, so that stable antithrombotic properties cannot be obtained over a long period of time. Antithrombotic materials produced by this method have the disadvantage that they are extremely expensive because the blood coagulation inhibitor is expensive and sterilization is difficult, so they must be produced aseptically. there were.
このように従来から多くの提案がなされているにもかか
わらず現状では人工血管とし小口径の動脈や静脈などに
も適用し得るほど優れた抗血栓性を長期間にわたって維
持することのできる材料は得られていなかった。Despite the many proposals that have been made in the past, there are currently no materials that can maintain antithrombotic properties so excellent that they can be applied to small-diameter arteries and veins as artificial blood vessels. I wasn't getting it.
本発明者らは、抗血栓性を改良するために種々検討した
結果、高分子材料からなる基材表面上に、水溶性でかつ
実質的に非イオン性の重合体をきわめて少１（１〜１０
０μｇ／ｃｎｆ）結合することにより、多量に結合した
場合よりも飛躍的に抗血栓性が改良されることを見出し
、先に特願昭５９−８７４３２号として特許出願を行っ
た。As a result of various studies to improve antithrombotic properties, the present inventors have found that a water-soluble and substantially nonionic polymer is added to the surface of a base material made of a polymeric material in an extremely small amount (1 to 1). 10
It was discovered that the antithrombotic properties were dramatically improved by binding (0 μg/cnf) compared to when a large amount was bound, and a patent application was previously filed as Japanese Patent Application No. 87432/1983.
上記の特許出願にかかる発明は、優れた抗血栓性材料を
提供するものであるが、本発明者らの経験によれば、同
じ結合量であっても結合した重合体の鎖長によって抗血
栓性に差ができる可能性がある。しかしながら、従来よ
り行われているグラフト重合法によっては、重合体の鎖
長が常に一定の範囲になるように制御するのは難しかっ
た。The invention related to the above patent application provides an excellent antithrombotic material, but according to the experience of the present inventors, the antithrombotic effect varies depending on the chain length of the bound polymer even if the amount of binding is the same. There may be gender differences. However, with the conventional graft polymerization method, it is difficult to control the chain length of the polymer so that it always falls within a certain range.
本発明の目的は、重合体の鎖長を最適範囲に制御し、極
めて高い抗血栓性を有する製品を製造できる方法を提供
することにある。また本発明の他の目的は、高い抗血栓
性を有する製品を安定して製造することのできる方法を
提供することにある。An object of the present invention is to provide a method that can control the chain length of a polymer within an optimal range and produce a product with extremely high antithrombotic properties. Another object of the present invention is to provide a method for stably producing a product having high antithrombotic properties.
上述した目的は、グラフト重合の際にレドックス還元剤
及び／または重合調整剤を共存させることによって達成
される。すなわち本発明は高分子材料からなる基材表面
上に遊離ラジカルまたはペルオキシドを生成させ、次い
でレドックス還元剤及び／または重合調整剤の存在下に
水溶性単量体を作用させて基材表面上に該水溶性単量体
をグラフト重合することを特徴とする抗血栓性材料の製
造法である。The above-mentioned object is achieved by coexisting a redox reducing agent and/or a polymerization regulator during graft polymerization. That is, the present invention generates free radicals or peroxides on the surface of a substrate made of a polymeric material, and then applies a water-soluble monomer to the surface of the substrate in the presence of a redox reducing agent and/or a polymerization regulator. This is a method for producing an antithrombotic material, characterized by graft polymerizing the water-soluble monomer.
レドックス還元剤及び重合調整剤の使用量は使用する化
合物の種類によって最適範囲が異なるが、概ね１０−’
ｍｏｌ／ １２〜１０ｍｏｌ／ １の範囲の濃度で使用
するのが適当である。The optimum amount of the redox reducing agent and polymerization regulator varies depending on the type of compound used, but it is approximately 10-'
It is suitable to use it at a concentration in the range of mol/12 to 10 mol/1.
本発明によればレドックス還元剤及び／または重合調整
剤を使用しない場合にくらべてより優れた抗血栓性材料
が得られるが、その理由は、基材に結合するグラフト重
合体の結合数が増すとともにその鎖長は一定の範囲に制
限されるためではないかと推定される。すなわち、レド
ックス還元剤あるいは重合調整剤は基材表面上のペルオ
キシドを効率よくラジカルに変換し、基材表面にグラフ
ト重合の開始点を多数形成させるので、グラフト重合体
の結合数が増加する。そしてこれらの化合物は連鎖移動
剤としても作用するので、重合体鎖の伸長が抑制され重
合度は比較的低い範囲に制限されるものと考えられる。According to the present invention, a material with better antithrombotic properties can be obtained than when no redox reducing agent and/or polymerization regulator is used, because the number of bonds of the graft polymer bonded to the base material increases. It is also presumed that this is because the chain length is limited to a certain range. That is, the redox reducing agent or polymerization regulator efficiently converts peroxide on the surface of the substrate into radicals and forms many starting points for graft polymerization on the surface of the substrate, thereby increasing the number of bonds in the graft polymer. Since these compounds also act as chain transfer agents, it is thought that elongation of the polymer chain is suppressed and the degree of polymerization is limited to a relatively low range.
このように、比較的鎖長の短い重合体が多数結合した場
合の方が、同じ結合重量でも鎖長の長い重合体が少量結
合した場合よりも優れた抗血栓性を示すものと考えられ
る。In this way, it is thought that when a large number of polymers with relatively short chain lengths are bound together, the antithrombotic property is superior to when a small amount of polymers with long chain lengths are bound together even at the same binding weight.
本発明を実施するには、まず高分子材料からなる基材表
面上に遊離ラジカルまたはペルオキシドを生成させる。To carry out the present invention, free radicals or peroxides are first generated on the surface of a substrate made of a polymeric material.
遊離ラジカルまたはペルオキシドを生成させる方法とし
ては、（１）電子線やガンマ線などの高エネルギー放射
線を照射する方法、（２）紫外線を照射する方法、（３
）低温プラズマ放電処理、（４）グロー放電処理、（５
）オゾン処理および（６）過酸化ベンゾイルのようなラ
ジカル重合開始剤を添加する方法などがある。また、基
材としは公知の高分子材料のほとんどが使用可能であり
、ポリエチレン、ポリプロピレン、エチレン−プロピレ
ン共重合体、エチレン−酢酸ビニル共重合体、ポリ塩化
ビニル、ポリ塩化ビニリデン、ポリスチレン、ポリアク
リロニトリル、ポリ少チルメタクリレート、スチレン−
ブタジェン系ブロック共重合体、アクリロニトリル−ブ
タジェン−スチレン系ブロック共重合体、ポリブタジェ
ン、ポリイソプレン、ポリテトラフルオロエチレン、ポ
リエチレンテレフタレート、ポリエチレンイソフタレー
ト、ポリブチレンテレタレート、ポリ゛エーテルーエス
テル系ブロック共重合体、ポリカーボネート、ポリアミ
ド、ポリウレタン、ポリスルホン、ポリエーテルスルホ
ン、シリコーン、セルロースおよび酢酸セルロースなど
を例示することができる。基材の形態については、非多
孔質、多孔質、織物、編物などいずれの形態でもよく、
形状についてもチューブ状、円筒状、シート状、板状、
ブロック状、繊維状など使用目的に応じていかなる形状
のものでも使用できる。また、′これらは単一の材料か
ら構成されていてもよいし、複数の材料からなる複合構
造物であってもよい。Methods for generating free radicals or peroxides include (1) irradiation with high-energy radiation such as electron beams and gamma rays, (2) irradiation with ultraviolet rays, and (3) irradiation with ultraviolet rays.
) low temperature plasma discharge treatment, (4) glow discharge treatment, (5
) Ozone treatment and (6) a method of adding a radical polymerization initiator such as benzoyl peroxide. In addition, most of the known polymeric materials can be used as the base material, including polyethylene, polypropylene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, polyvinyl chloride, polyvinylidene chloride, polystyrene, and polyacrylonitrile. , polylessyl methacrylate, styrene-
Butadiene block copolymer, acrylonitrile-butadiene-styrene block copolymer, polybutadiene, polyisoprene, polytetrafluoroethylene, polyethylene terephthalate, polyethylene isophthalate, polybutylene terethalate, polyether ester block copolymer , polycarbonate, polyamide, polyurethane, polysulfone, polyethersulfone, silicone, cellulose, and cellulose acetate. The form of the base material may be non-porous, porous, woven, knitted, etc.
Regarding the shape, there are tube-like, cylindrical, sheet-like, plate-like,
It can be used in any shape, such as block or fiber, depending on the purpose of use. Furthermore, these may be made of a single material, or may be a composite structure made of a plurality of materials.
本発明においては、遊離ラジカルまたはペルオキシドを
生成させた基材に水溶性単量体を作用させてグラフト重
合を行うが、使用する水溶性単量体としては、アクリル
アミド、ジメチルアクリルアミド、メタクリルアミド、
ビニルピロリドンおよび、アクリル酸またはメタクリル
酸のポリアルキレングリコールエステルなどを例示する
ことができる。これらは単独で使用してもよいし、２種
類以上を同時に使用することもできる。また、水溶性単
量体はそのまま使用することもできるが、水溶液の形で
使用するのが好ましい。In the present invention, graft polymerization is performed by allowing a water-soluble monomer to act on a base material in which free radicals or peroxides have been generated. Examples of the water-soluble monomers used include acrylamide, dimethylacrylamide, methacrylamide,
Examples include vinylpyrrolidone and polyalkylene glycol esters of acrylic acid or methacrylic acid. These may be used alone or in combination of two or more. Moreover, although the water-soluble monomer can be used as it is, it is preferable to use it in the form of an aqueous solution.
本発明において使用するレドックス還元剤とは過酸化物
などの酸化性物質とレドックス反応を起こす還元性物質
であり、塩化第１鉄、硫酸第１鉄、モール塩などの２価
の鉄塩、酸性亜硫酸ソーダ、ロンガリット、アスコルビ
ン酸またはその塩及び酒石酸などを例示することができ
る。また、重合調整剤とは、重合速度あるいは重合度を
抑制する作用を有する化合物でありチオグリコール酸、
アリルアルコール、イソプロピルアルコール及びメタノ
ールなどの各種アルコール類ならびにエチルメルカプタ
ン、プロピルメルカプタン及びブチルメルカプタンなど
のメルカプタン類を例示することができる。The redox reducing agent used in the present invention is a reducing substance that causes a redox reaction with an oxidizing substance such as peroxide, and includes divalent iron salts such as ferrous chloride, ferrous sulfate, Mohr's salt, acidic Examples include sodium sulfite, Rongalite, ascorbic acid or a salt thereof, and tartaric acid. In addition, a polymerization regulator is a compound that has the effect of suppressing the polymerization rate or degree of polymerization, such as thioglycolic acid,
Examples include various alcohols such as allyl alcohol, isopropyl alcohol and methanol, and mercaptans such as ethyl mercaptan, propyl mercaptan and butyl mercaptan.
グラフト重合は、基材表面上に生成した遊離ラジカルま
たはペルオキシドが開始剤となって、水溶性単量体と接
触させると直ちに反応が開始される。反応は常温でも進
行するが、場合によっては加熱あるいは冷却してもよい
。In graft polymerization, free radicals or peroxides generated on the surface of a substrate act as an initiator, and the reaction is initiated immediately upon contact with a water-soluble monomer. The reaction proceeds at room temperature, but may be heated or cooled depending on the case.
以下、実施具体例により本発明をさらに具体的に説明す
る。なお、以下の例においては、抗血栓性の指標として
タンパク質の吸着特性を利用した。Hereinafter, the present invention will be explained in more detail with reference to specific examples. In the following examples, protein adsorption properties were used as an index of antithrombotic properties.
すなわち、抗血栓性の優れたものほどＩｇＧのような糖
タンパク質の吸着が少ないと言われているので、ＩｇＧ
の吸着量を測定して抗血栓性を評価した。In other words, it is said that the better the antithrombotic properties, the less adsorption of glycoproteins such as IgG.
The antithrombotic properties were evaluated by measuring the amount of adsorption.
実施例１
針状電極をボリウ・レタンチューブの両端にセットし、
印加電圧５０Ｖ、５０ｍ Ｉｌ ／ｍｉｎ空気流下で５
秒間グロ、−放電を行い、チューブ表面を処理した。次
いでこのチューブを種々の濃度のモール塩を含むジメチ
ルアクリルアミドの１．５ ｍｏｌ／Ｉｌ水溶液に浸清
し、窒素雰囲気下３０℃で２０時間グラフト重合を行っ
た。 次いで牛ガンマグロブリン（ＩｇＧ）をフルオレ
セインイソチオシアネート（ＦＩＴＣ）で螢光ラベルし
、これに非螢光ラベルＩｇＧを混合して全タンパク質濃
度が２■／ ｍ １の水溶液を調整し、この液にグラフ
ト重合処理したチューブを浸漬して３７℃で３時間タン
パク質を吸着させた。Example 1 Needle-shaped electrodes were set at both ends of a polyurethane tube,
5 under applied voltage 50V, 50m Il/min air flow
The tube surface was treated by flashing and discharging for seconds. Next, this tube was immersed in a 1.5 mol/Il aqueous solution of dimethylacrylamide containing various concentrations of Mohr's salt, and graft polymerization was performed at 30° C. for 20 hours in a nitrogen atmosphere. Next, bovine gamma globulin (IgG) was fluorescently labeled with fluorescein isothiocyanate (FITC), and non-fluorescently labeled IgG was mixed with this to prepare an aqueous solution with a total protein concentration of 2 μ/m 1, and the grafts were added to this solution. The polymerized tube was immersed to adsorb proteins at 37°C for 3 hours.
その後チユーブ面をゆるやかに緩衝液で洗浄して非吸着
タンパク質を除去し、さらにオートクレーブを用いて３
気圧１時間の条件下で吸着タンパク質を加水分解して、
ＦＩＴＣの螢光強度を励起波長４９０ｎｍ、螢光波長５
２０ｒａ＋で測定した。測定結果と別に作成しておいた
検量線とから吸着したＩｇＧ量を算出した。結果を表１
に示す。After that, the surface of the tube was gently washed with a buffer solution to remove unadsorbed proteins, and then the tube was placed in an autoclave for 3
Hydrolyze the adsorbed protein under atmospheric pressure for 1 hour,
The fluorescence intensity of FITC was set to an excitation wavelength of 490 nm and a fluorescence wavelength of 5.
Measured at 20ra+. The amount of IgG adsorbed was calculated from the measurement results and a separately prepared calibration curve. Table 1 shows the results.
Shown below.
表１ モール塩濃度とＩｇＧ吸着量との関係表１から明
らかなように、モール塩を使用するとＩｇＧの吸着が極
めて少なくなり、抗血栓性が優れていることがわかる。Table 1 Relationship between Mohr's salt concentration and IgG adsorption amount As is clear from Table 1, when Mohr's salt is used, IgG adsorption is extremely small, indicating that it has excellent antithrombotic properties.
また、モール塩の濃度は１０−’ ｍｏｌ／ １以上で
あれば抗血栓性にほとんど変化はない。Further, if the concentration of Mohr's salt is 10-' mol/1 or more, there is almost no change in antithrombotic properties.
実施例２
実施例１と同様にしてポルウレタンチューブをグロー放
電処理し、このチューブをジメチルアクリルアミドを１
．５ｍｏｌ／１．モール塩を１０−” ｍａｔ／ｉ含有
する水溶液に浸漬して３０℃で１〜２０時間グラフト重
合を実施した。次いで実施例１と同様にしてＩｇＧの吸
着量を測定した。結果を表２に示す。Example 2 A polyurethane tube was treated with glow discharge in the same manner as in Example 1, and this tube was treated with dimethylacrylamide for 1 hour.
．． 5mol/1. Mohr's salt was immersed in an aqueous solution containing 10-'' mat/i and graft polymerization was carried out at 30°C for 1 to 20 hours.Then, the amount of IgG adsorption was measured in the same manner as in Example 1.The results are shown in Table 2. show.
表２ 重合時間とＩｇＧ吸着量との関係表２から明らか
なように、重合時間が３時間以上であれば、抗血栓性は
ほぼ一定になることがわかる。Table 2 Relationship between polymerization time and IgG adsorption amount As is clear from Table 2, if the polymerization time is 3 hours or more, the antithrombotic properties become almost constant.
実施例３
実施例１と同様にしてポリウレタンチューブをグロー放
電処理し、このチューブをジメチルアクリルアミドを１
．５ｍｏｌ ／ ＩＩ 、 アリルアルコールを２〜
ｌＯ重量％含有する３種類の水溶液に浸漬して６０℃で
５時間グラフト重合を実施した。次いで実施例１と同様
にしてＩｇＧの吸着量を測定した。Example 3 A polyurethane tube was treated with glow discharge in the same manner as in Example 1, and this tube was treated with dimethylacrylamide for 1 hour.
．． 5 mol/II, allyl alcohol 2~
Graft polymerization was carried out at 60° C. for 5 hours by immersion in three types of aqueous solutions containing 10% by weight. Next, the amount of IgG adsorption was measured in the same manner as in Example 1.
結果を表３に示す。The results are shown in Table 3.
実施例４
実施例１と同様にしてポリウレタンチューブをグロー放
電処理し、このチューブをジメチルアクリルアミドを１
．５＋ｗｏｌ ／ ｉｔ 、 アリルアルコールを５重
量％含有する水溶液に浸漬して６０℃で０．２５〜２４
時間グラフト重合を実施した。次いで実施例１と同様に
してＩｇＧの吸着量を測定した。結果を表４に示す。Example 4 A polyurethane tube was treated with glow discharge in the same manner as in Example 1, and this tube was treated with dimethylacrylamide for 1 hour.
．． 5+wol/it, 0.25-24 at 60℃ by immersion in an aqueous solution containing 5% by weight of allyl alcohol.
Time graft polymerization was carried out. Next, the amount of IgG adsorption was measured in the same manner as in Example 1. The results are shown in Table 4.
表４ 重合時間とＩｇＧ吸着量との関係実施例５
実施例１と同様にしてポリウレタンチューブをグロー放
電処理し、このチューブをアクリルアミドを１０重量％
、モール塩を１０−” ｍｏｌ／ ｌ含有する水溶液に
浸漬して、３０℃で３時間グラフト重合を実施した。次
いで実施例１と同様にしてＩｇＧの吸着量を測定したと
ころ、０．２６μｇ／−であったり
これに対し、モール塩を使用しない場合のＩｇＧ吸着量
は０．４１μｇ／ｃＡであった。Table 4 Relationship between polymerization time and IgG adsorption amount Example 5 A polyurethane tube was treated with glow discharge in the same manner as in Example 1, and this tube was treated with 10% by weight of acrylamide.
, Mohr's salt was immersed in an aqueous solution containing 10-'' mol/l, and graft polymerization was carried out at 30°C for 3 hours.Then, the adsorption amount of IgG was measured in the same manner as in Example 1, and it was found to be 0.26 μg/l. In contrast, the amount of IgG adsorption when Mohr's salt was not used was 0.41 μg/cA.
実施例６
実施例１と同様にしてポリウレタンチューブをグロー放
電処理し、このチューブをジメチルアクリルアミドを１
’、 ５ ｍｏｌ／ ｌ 、 アスコルビン酸を０．２
〜１．０重量％含有する３種類の水溶液に浸漬して、４
０℃で２０時間グラフト重合を実施した。次いで実施例
１と同様にしてＩｇＧの吸着量を測定した。結果を表５
に示す。Example 6 A polyurethane tube was treated with glow discharge in the same manner as in Example 1, and this tube was treated with dimethylacrylamide for 1 hour.
', 5 mol/l, ascorbic acid 0.2
4 by immersing it in three types of aqueous solutions containing ~1.0% by weight.
Graft polymerization was carried out at 0°C for 20 hours. Next, the amount of IgG adsorption was measured in the same manner as in Example 1. Table 5 shows the results.
Shown below.
実施例７
実施例１と同様にしてポリウレタンチューブをグロー放
電処理し、このチューブをジメチルアクリルアミドを１
．５ｍｏｌ／ ｌ 、チオグリコール酸を０．２〜１．
０重量％含有する３種類の水溶液に浸漬して４０℃で２
０時間グラフト重合を実施した。次いで実施例１と同様
にしてＩｇＧの吸着量を測定した。結果を表６に示す。Example 7 A polyurethane tube was treated with glow discharge in the same manner as in Example 1, and this tube was treated with dimethylacrylamide for 1 hour.
．． 5 mol/l, thioglycolic acid 0.2-1.
It was immersed in three types of aqueous solutions containing 0% by weight at 40℃ for 2 hours.
Graft polymerization was carried out for 0 hours. Next, the amount of IgG adsorption was measured in the same manner as in Example 1. The results are shown in Table 6.
実施例８
実施例１と同様にしてポリエチレンチューブをグロー放
電処理し、このチューブをジメチルアクリルアミドを１
．５ｍｏｌ／ ｌ 、 アリルアルコールを５重量％含
有する水溶液に浸漬して６０℃で０．２５〜２４時間グ
ラフト重合を実施した。次いで実施例１と同様にしてＩ
ｇＧの吸着量を測定した。結果を表７に示す。Example 8 A polyethylene tube was treated with glow discharge in the same manner as in Example 1, and this tube was treated with dimethylacrylamide for 1 hour.
．． Graft polymerization was carried out at 60° C. for 0.25 to 24 hours by immersing the sample in an aqueous solution containing 5 mol/l and 5% by weight of allyl alcohol. Then, in the same manner as in Example 1, I
The adsorption amount of gG was measured. The results are shown in Table 7.
表７ 重合時間とｒｇＧ吸着量との関係〔発明の効果〕
以上の結果から明らかなように、本発明の方法によれば
極めて優れた抗血栓性を有する材料を容易に製造するこ
とができる。しかも、レドックス還元剤及び重合調整剤
の効果は広い範囲で安定しているので、常に一定した品
質のものを製造することができる。Table 7 Relationship between polymerization time and rgG adsorption amount [Effects of the invention] As is clear from the above results, according to the method of the present invention, a material having extremely excellent antithrombotic properties can be easily produced. Moreover, since the effects of the redox reducing agent and the polymerization regulator are stable over a wide range, products of constant quality can always be produced.
また、レドックス還元剤あるいは重合調整剤を使用する
ことによって、グラフト重合時のホモ重合体の生成が抑
制され、得られた抗血栓性材料の表面に付着するホモ重
合体は量も少なく重合度も低いので、それを除去する操
作も容易になる。In addition, by using a redox reducing agent or a polymerization regulator, the formation of homopolymers during graft polymerization is suppressed, and the amount of homopolymers that adhere to the surface of the obtained antithrombotic material is small and the degree of polymerization is low. Since it is low, the operation to remove it is also easy.
Claims (5)
たはペルオキシドを生成させ、次いでレドックス還元剤
及び／または重合調整剤の存在下に水溶性単重体を作用
させて上記基材表面上に該水溶性単量体をグラフト重合
することを特徴とする抗血栓性材料の製造法。(1) Free radicals or peroxides are generated on the surface of a base material made of a polymeric material, and then a water-soluble monomer is applied to the surface of the base material in the presence of a redox reducing agent and/or a polymerization regulator. A method for producing an antithrombotic material, which comprises graft polymerizing a water-soluble monomer.
範囲第１項記載の製造法。(2) The production method according to claim 1, wherein the redox reducing agent is a divalent iron salt.
項記載の製造法。(3) Claim 2 in which the divalent iron salt is Mohr's salt
Manufacturing method described in section.
ット、アスコルビン酸またはその塩及び酒石酸からなる
群より選ばれた１種または２種以上の化合物である特許
請求の範囲第１項記載の製造法。(4) The production method according to claim 1, wherein the redox reducing agent is one or more compounds selected from the group consisting of acidic sodium sulfite, Rongalite, ascorbic acid or its salt, and tartaric acid.
ール、イソプロピルアルコール、メタノール、エチルメ
ルカプタン、プロピルメルカプタン及びブチルメルカプ
タンからなる群より選ばれた１種または２種以上の化合
物である特許請求の範囲第１項記載の製造法。(5) The polymerization regulator is one or more compounds selected from the group consisting of thioglycolic acid, allyl alcohol, isopropyl alcohol, methanol, ethyl mercaptan, propyl mercaptan, and butyl mercaptan. The manufacturing method described in item 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60228474A JPH084618B2 (en) | 1985-10-14 | 1985-10-14 | Manufacturing method of antithrombogenic material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60228474A JPH084618B2 (en) | 1985-10-14 | 1985-10-14 | Manufacturing method of antithrombogenic material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6287163A true JPS6287163A (en) | 1987-04-21 |
| JPH084618B2 JPH084618B2 (en) | 1996-01-24 |
Family
ID=16877044
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60228474A Expired - Lifetime JPH084618B2 (en) | 1985-10-14 | 1985-10-14 | Manufacturing method of antithrombogenic material |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH084618B2 (en) |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63305876A (en) * | 1987-06-09 | 1988-12-13 | Japan Atom Energy Res Inst | Preparation of antitherombogenic material |
| JPS6479211A (en) * | 1987-09-21 | 1989-03-24 | Nippon Medical Supply | Graft-copolymerization onto surface of plastic tube |
| JPH09173462A (en) * | 1995-09-29 | 1997-07-08 | Target Therapeutics Inc | Multi-cover stainless steel guide wire |
| JP2003064226A (en) * | 2001-08-29 | 2003-03-05 | Tosoh Corp | Polyethylene-based resin composition for lamination extrusion, laminate using the same and method of manufacturing laminate |
| JP2013155307A (en) * | 2012-01-30 | 2013-08-15 | Sumitomo Rubber Ind Ltd | Surface-modifying method and surface modification elastomer |
| JP2013159667A (en) * | 2012-02-02 | 2013-08-19 | Sumitomo Rubber Ind Ltd | Surface modification method and surface-modified elastic body |
| JP2013159629A (en) * | 2012-02-01 | 2013-08-19 | Sumitomo Rubber Ind Ltd | Surface modification method and surface-modified elastic body |
| JP2014132059A (en) * | 2013-01-07 | 2014-07-17 | Sumitomo Rubber Ind Ltd | Surface modification method and surface modified elastic material |
| US9339845B2 (en) | 2012-05-16 | 2016-05-17 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US9469736B2 (en) | 2011-06-03 | 2016-10-18 | Sumitomo Rubber Industries, Ltd. | Surface-modifying method and elastic body with modified surface |
| US9738744B2 (en) | 2013-06-11 | 2017-08-22 | Sumitomo Rubber Industries, Ltd. | Surface modification method for three-dimensional object and syringe gasket |
| US9752003B2 (en) | 2012-11-30 | 2017-09-05 | Sumitomo Rubber Industries, Ltd. | Surface-modified elastic body |
| US9758605B2 (en) | 2012-11-20 | 2017-09-12 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US9963565B2 (en) | 2014-10-02 | 2018-05-08 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US10189944B2 (en) | 2013-04-25 | 2019-01-29 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US10214608B2 (en) | 2015-08-03 | 2019-02-26 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified body |
| US10280274B2 (en) | 2014-01-06 | 2019-05-07 | Sumitomo Rubber Industries, Ltd. | Method for modifying surface and surface modified elastic body |
| US10344109B2 (en) | 2012-09-10 | 2019-07-09 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US10647829B2 (en) | 2013-06-20 | 2020-05-12 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface modification body |
| US10759918B2 (en) | 2015-08-03 | 2020-09-01 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS49125493A (en) * | 1973-04-02 | 1974-11-30 | ||
| JPS60147447A (en) * | 1984-01-10 | 1985-08-03 | Toyo Soda Mfg Co Ltd | Agricultural and horticultural film with outstanding sustainability in antifogging potential |
-
1985
- 1985-10-14 JP JP60228474A patent/JPH084618B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS49125493A (en) * | 1973-04-02 | 1974-11-30 | ||
| JPS60147447A (en) * | 1984-01-10 | 1985-08-03 | Toyo Soda Mfg Co Ltd | Agricultural and horticultural film with outstanding sustainability in antifogging potential |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63305876A (en) * | 1987-06-09 | 1988-12-13 | Japan Atom Energy Res Inst | Preparation of antitherombogenic material |
| JPS6479211A (en) * | 1987-09-21 | 1989-03-24 | Nippon Medical Supply | Graft-copolymerization onto surface of plastic tube |
| JPH09173462A (en) * | 1995-09-29 | 1997-07-08 | Target Therapeutics Inc | Multi-cover stainless steel guide wire |
| JP2003064226A (en) * | 2001-08-29 | 2003-03-05 | Tosoh Corp | Polyethylene-based resin composition for lamination extrusion, laminate using the same and method of manufacturing laminate |
| US9469736B2 (en) | 2011-06-03 | 2016-10-18 | Sumitomo Rubber Industries, Ltd. | Surface-modifying method and elastic body with modified surface |
| JP2013155307A (en) * | 2012-01-30 | 2013-08-15 | Sumitomo Rubber Ind Ltd | Surface-modifying method and surface modification elastomer |
| JP2013159629A (en) * | 2012-02-01 | 2013-08-19 | Sumitomo Rubber Ind Ltd | Surface modification method and surface-modified elastic body |
| JP2013159667A (en) * | 2012-02-02 | 2013-08-19 | Sumitomo Rubber Ind Ltd | Surface modification method and surface-modified elastic body |
| US9321872B2 (en) | 2012-02-02 | 2016-04-26 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US9339845B2 (en) | 2012-05-16 | 2016-05-17 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US10344109B2 (en) | 2012-09-10 | 2019-07-09 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US9758605B2 (en) | 2012-11-20 | 2017-09-12 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US9752003B2 (en) | 2012-11-30 | 2017-09-05 | Sumitomo Rubber Industries, Ltd. | Surface-modified elastic body |
| US9540493B2 (en) | 2013-01-07 | 2017-01-10 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| JP2014132059A (en) * | 2013-01-07 | 2014-07-17 | Sumitomo Rubber Ind Ltd | Surface modification method and surface modified elastic material |
| US10189944B2 (en) | 2013-04-25 | 2019-01-29 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US9738744B2 (en) | 2013-06-11 | 2017-08-22 | Sumitomo Rubber Industries, Ltd. | Surface modification method for three-dimensional object and syringe gasket |
| US10647829B2 (en) | 2013-06-20 | 2020-05-12 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface modification body |
| US10280274B2 (en) | 2014-01-06 | 2019-05-07 | Sumitomo Rubber Industries, Ltd. | Method for modifying surface and surface modified elastic body |
| US9963565B2 (en) | 2014-10-02 | 2018-05-08 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
| US10214608B2 (en) | 2015-08-03 | 2019-02-26 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified body |
| US10759918B2 (en) | 2015-08-03 | 2020-09-01 | Sumitomo Rubber Industries, Ltd. | Surface modification method and surface-modified elastic body |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH084618B2 (en) | 1996-01-24 |
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