JP2743480B2 - Antithrombotic polymer material - Google Patents
Antithrombotic polymer materialInfo
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- JP2743480B2 JP2743480B2 JP1149099A JP14909989A JP2743480B2 JP 2743480 B2 JP2743480 B2 JP 2743480B2 JP 1149099 A JP1149099 A JP 1149099A JP 14909989 A JP14909989 A JP 14909989A JP 2743480 B2 JP2743480 B2 JP 2743480B2
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- polymer material
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- antithrombotic
- graft
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Description
【発明の詳細な説明】 (産業上の利用分野) 本発明は、抗血栓性高分子材料に関するものである。Description: TECHNICAL FIELD The present invention relates to an antithrombotic polymer material.
(従来の技術及び発明が解決しようとする問題点) 従来、高分子材料を使用した人工血管や人工心臓等、
或いは、カテーテルや輸血用チューブ等の血液処理用器
具等の利用が盛んに行われている。周知のように、血液
は異物と接触すると凝固するので、上記各種医療用器具
に使用される高分子材料には抗血栓性を付与しなければ
ならない。(Problems to be solved by conventional technology and invention) Conventionally, artificial blood vessels and artificial hearts using polymer materials,
Alternatively, blood processing instruments such as catheters and blood transfusion tubes have been actively used. As is well known, blood coagulates when it comes in contact with foreign matter, and therefore, the polymeric material used in the above various medical devices must be provided with antithrombotic properties.
従来、高分子材料の表面にヘパリン等の抗血液固性物
質を付着又は塗布する方法等が提案されているが、それ
ら抗血液凝固性物質と高分子材料との結合力は一般的に
弱く、その効果の持続時間は必ずしも十分ではなかっ
た。Conventionally, a method of attaching or coating an anti-blood solid substance such as heparin to the surface of a polymer material has been proposed, but the binding force between the anti-coagulant substance and the polymer material is generally weak, The duration of the effect was not always sufficient.
(問題点を解決するための手段) そこで、本発明者らは、抗血液凝固性物質と高分子材
料との結合力が改善された抗血栓性高分子材料を提供す
べく鋭意検討した結果、抗トロンビン活性を有するアル
ギニン誘導体がそのカルボン酸基を介して結合している
付加重合可能なエチレン性化合物を、グロー放電等でプ
ラズマ処理された高分子材料の表面にグラフト重合させ
ることにより、所期の目的が達成されることを知得し、
本発明に到達した。(Means for Solving the Problems) Accordingly, the present inventors have conducted intensive studies to provide an antithrombotic polymer material having an improved binding force between the anticoagulant substance and the polymer material. By graft-polymerizing an addition-polymerizable ethylenic compound, to which an arginine derivative having antithrombin activity is bonded via its carboxylic acid group, on the surface of a polymer material plasma-treated by glow discharge or the like, Know that the purpose of is achieved,
The present invention has been reached.
即ち、本発明の要旨は、プラズマ処理された高分子材
料に、抗トロンビン活性を有するアルギニン誘導体が該
誘導体のカルボン酸基を介して結合している付加重合可
能なエチレン性化合物を、グラフト重合させて得られる
ことを特徴とする抗血栓性高分子材料に存する。That is, the gist of the present invention is to graft polymerize an addition-polymerizable ethylenic compound in which an arginine derivative having antithrombin activity is bonded via a carboxylic acid group of the derivative to a plasma-treated polymer material. An antithrombotic polymer material characterized by being obtained by:
以下本発明を説明するに、本発明の抗血栓性高分子材
料における抗血栓性成分は、少なくとも1個のカルボン
酸基を有し、抗トロンビン活性を有するアルギニン誘導
体であって、例えば、特開昭52−97934号公報、特開昭5
5−33499号公報、ヨーロッパ公開特許第8746号公報、ジ
ャーナル オブ メデイカル ケミストリー(J.Med.Ch
em.)23,1293〜1299(1980)、或いは、バイオケミスト
リー(Biochemistry)23,85〜90(1984)に記載されて
いるような化合物が挙げられる。中でも下記一般式
(I)で表されるアルギニン誘導体が好適である。Hereinafter, the present invention will be described. The antithrombotic component in the antithrombotic polymer material of the present invention is an arginine derivative having at least one carboxylic acid group and having antithrombin activity. JP-A-52-97934, JP-A-5-97934
No. 5-33499, European Patent No. 8746, Journal of Medical Chemistry (J. Med. Ch.)
em.) 23, from 1,293 to 1,299 (1980), or, Biochemistry (Biochemistry) 23, include compounds such as those described in 85-90 (1984). Among them, an arginine derivative represented by the following general formula (I) is preferable.
〔上記式中、R1は (式中、R3はC1〜C6のアルキル基、C2〜C7のアルコキシ
アルキル基またはテトラヒドロフルフリル基を表し、R4
はC1〜C3のアルキレン基を表す。)または (式中、R5は水素原子またはC1〜C4のアルキル基を表
す。)を表し、R2は (式中、R6及びR7は水素原子、C1〜C4のアルコキシ基ま
たはC1〜C4のアルキルアミノ基を表す。)または (式中、R8は水素原子またはC1〜C4のアルキル基を表
す。)を表し、mは3〜4の整数を表す。〕 上記式中、R1は または で表される基を表す。又、R3はメチル基、エチル基、プ
ロピル基、ブチル基、ペンチル基、ヘキシル基等のC1〜
C6のアルキル基、メトキシメチル基、メトキシエチル
基、エトキシメチル基、エトキシエチル基、ブトキシメ
チル基、ブトキシエチル基等のC2〜C7のアルコキシアル
キル基またはテトラヒドロフルフリル基を表し、R4はメ
チレン基、エチレン基、プロピレン基等のC1〜C3のアル
キレン基を表し、R5は水素原子またはメチル基、エチル
基、プロピル基、ブチル基等のC1〜C4のアルキル基を表
す。 [In the above formula, R 1 is (Wherein, R 3 represents an alkyl group, an alkoxyalkyl group or a tetrahydrofurfuryl group of C 2 -C 7 of C 1 ~C 6, R 4
Represents an alkylene group of C 1 -C 3. ) Or (Wherein, R 5 represents a hydrogen atom or a C 1 -C 4 alkyl group), and R 2 represents (Wherein, R 6 and R 7 represent a hydrogen atom, a C 1 -C 4 alkoxy group or a C 1 -C 4 alkylamino group) or (In the formula, R 8 represents a hydrogen atom or a C 1 to C 4 alkyl group.), And m represents an integer of 3 to 4. In the above formula, R 1 is Or Represents a group represented by R 3 is a C 1 to C 3 group such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group.
Alkyl C 6, represents a methoxymethyl group, methoxyethyl group, ethoxymethyl group, ethoxyethyl group, a butoxymethyl group, alkoxyalkyl group or a tetrahydrofurfuryl group of C 2 -C 7 such as butoxyethyl, R 4 methylene group, ethylene group, an alkylene group of C 1 -C 3 such as a propylene group, R 5 is a hydrogen atom or a methyl group, an ethyl group, a propyl group, an alkyl group of C 1 -C 4, such as butyl Represent.
で表される基を表す。又、R6及びR7は水素原子、メトキ
シ基、エトキシ基、プロポキシ基、ブトキシ基等のC1〜
C4のアルコキシ基またはメチルアミノ基、エチルアミノ
基、プロピルアミノ基、ブチルアミノ基、ジメチルアミ
ノ基、ジエチルアミノ基、メチルエチルアミノ基、メチ
ルプロピルアミノ基等のC1〜C4のアルキルアミノ基を表
し、R8は水素原子またはメチル基、エチル基、プロピル
基、ブチル基等のC1〜C4のアルキル基を表す。mは3〜
4の整数を表す。〕 上記アルギニン誘導体の具体例としては、例えば、下
記表1に示すような化合物が挙げられる。 Represents a group represented by R 6 and R 7 each represent a hydrogen atom, a methoxy group, an ethoxy group, a propoxy group, a C 1 to
Alkoxy or methylamino group of C 4, ethylamino group, propylamino group, butylamino group, dimethylamino group, diethylamino group, methylethylamino group, an alkylamino group of C 1 -C 4, such as methyl propylamino group R 8 represents a hydrogen atom or a C 1 -C 4 alkyl group such as a methyl group, an ethyl group, a propyl group, and a butyl group. m is 3 ~
Represents an integer of 4. Specific examples of the arginine derivative include, for example, compounds shown in Table 1 below.
本発明においては、上記アルギニン誘導体が、そのカ
ルボン酸基を介して結合している付加重合可能なエチレ
ン性化合物を、高分子材料にグラフト重合させる。 In the present invention, the arginine derivative is graft-polymerized to a polymer material with an addition-polymerizable ethylenic compound bonded via its carboxylic acid group.
該エチレン性化合物としては、グラフト重合し得るエ
チレン性不飽和基と、上記アルギニン誘導体のカルボン
酸基と結合し得る基、例えばアミノ基を有するものであ
ればいずれも使用し得る。As the ethylenic compound, any compound having an ethylenically unsaturated group capable of undergoing graft polymerization and a group capable of binding to the carboxylic acid group of the arginine derivative, for example, an amino group, may be used.
例えば、アクリル酸、メタクリル酸等の不飽和カルボ
ン酸ハライドとH2N−(CH2)n−NH2(n=1〜10)等
のジアミン類とを反応させて得られるような化合物が挙
げられる。For example, compounds obtained by reacting unsaturated carboxylic acid halides such as acrylic acid and methacrylic acid with diamines such as H 2 N— (CH 2 ) n —NH 2 (n = 1 to 10) are exemplified. Can be
高分子材料としては特に制限はないが、例えば、ポリ
ウレタン、ポリアミド、ポリプロピレン、ポリ塩化ビニ
ル、ポリエチレン、ポリ塩化ビニリデン、ポリスチレ
ン、ポリカーボネート、ポリウレア、ポリエステル等が
使用できる。Although there is no particular limitation on the polymer material, for example, polyurethane, polyamide, polypropylene, polyvinyl chloride, polyethylene, polyvinylidene chloride, polystyrene, polycarbonate, polyurea, polyester and the like can be used.
高分子材料への前記アルギニン誘導体を有する付加重
合可能なエチレン性化合物のグラフト重合には、まず、
高分子材料の表面をグロー放電或いはコロナ放電等でプ
ラズマ処理する。グロー放電の場合は、0.1〜0.3Torr、
0.1〜10mA、5秒〜3分程度の条件で処理し、また、コ
ロナ放電の場合は、大気中、最大印加電圧10〜20kV、5
秒〜3分程度の条件で処理する。In the graft polymerization of an addition-polymerizable ethylenic compound having the arginine derivative onto a polymer material, first,
Plasma treatment is performed on the surface of the polymer material by glow discharge or corona discharge. 0.1-0.3 Torr for glow discharge,
The treatment is performed under the conditions of 0.1 to 10 mA for about 5 seconds to 3 minutes. In the case of corona discharge, the maximum applied voltage is 10 to 20 kV in the atmosphere.
The processing is performed under the condition of about 2 to 3 minutes.
次いで、プラズマ処理した高分子材料を、前記アルギ
ニン誘導体を有する付加重合可能なエチレン性化合物の
5〜80%水溶液に浸し、UV照射または加熱処理すること
によって高分子材料の表面にグラフト重合させる。Next, the polymer material subjected to the plasma treatment is immersed in a 5-80% aqueous solution of an addition-polymerizable ethylenic compound having the arginine derivative, and is subjected to UV irradiation or heat treatment to be graft-polymerized on the surface of the polymer material.
UV照射は、水銀ランプにより4〜30℃、6〜24時間の
条件で行ない、また、加熱処理は、60〜130℃で3〜12
時間の条件で行う。その際、前記アルギニン誘導体を有
する付加重合可能なエチレン性化合物のグラフト量は0.
1〜10mg/cm2の範囲となるように選ぶのがよい。UV irradiation is performed by a mercury lamp at 4 to 30 ° C. for 6 to 24 hours, and heat treatment is performed at 60 to 130 ° C. for 3 to 12 hours.
Perform under time conditions. At this time, the graft amount of the addition-polymerizable ethylenic compound having the arginine derivative is 0.
It is good to choose so as to be in the range of 1 to 10 mg / cm 2 .
かくして本発明の抗血栓性高分子材料を得ることがで
きる。Thus, the antithrombotic polymer material of the present invention can be obtained.
(実施例) 以下に実施例を挙げて更に本発明を具体的に説明す
る。(Example) Hereinafter, the present invention will be described more specifically with reference to examples.
実施例1 (1) −78℃に冷却した1.0mmol塩化アクリルの酢酸
エチル溶液15mlを、−4℃の2.0mmolエチレンジアミン
の酢酸エチル溶液に、激しく撹拌下、徐々に滴下して、
−4℃で1時間反応させた後、室温で更に4時間反応さ
せた。反応終了後、溶媒を除去し、68℃の酢酸エチル10
0mlを加え、生成物を抽出した。55〜65℃の温度で沈澱
を過した後、酢酸エチルを30〜40℃で減圧下留去し、
室温下、12時間真空乾燥して白色粉末状のN−アミノエ
チレンアクリルアミド0.8gを得た。Example 1 (1) 15 ml of a 1.0 mmol solution of acrylic chloride in ethyl acetate cooled to −78 ° C. was gradually added dropwise to a solution of 2.0 mmol of ethylenediamine in ethyl acetate at −4 ° C. with vigorous stirring.
After reacting at -4 ° C for 1 hour, the reaction was further performed at room temperature for 4 hours. After completion of the reaction, the solvent was removed, and ethyl acetate 10
0 ml was added and the product was extracted. After passing the precipitate at a temperature of 55 to 65 ° C, ethyl acetate was distilled off under reduced pressure at 30 to 40 ° C,
Vacuum drying was performed at room temperature for 12 hours to obtain 0.8 g of N-aminoethylene acrylamide as a white powder.
次いで、0℃下、0.10mmolの(2R,4R)−4−メチル
−1−〔N2−((RS)−3−メチル−1,2,3,4−テトラ
ヒドロ−8−キノリンスルホニル)−L−アルギニル〕
−2−ピペリジンカルボン酸(以下、MD−805と称す
る)、0.11mmolのジシクロヘキシルカルボジイミド及び
0.15mmolのヒドロキシベンゾトリアゾールを含有するDM
F溶液20mlに、上記で得た0.1mmolのN−アミノエチレン
アクリルアミド20mlを加えて、撹拌しながら室温で72時
間反応させた。反応終了時に、60mlの酢酸エチルを加
え、次いで、4%炭酸水素ナトリウム、10%クエン酸及
び飽和食塩水で順次3回ずつ洗浄した後、酢酸エチルを
留去し、得られる残留物をシリカゲルクロマトグラフィ
ー〔展開溶媒:酢酸エチル/クロロホルム=3/1〕で分
離精製し、酢酸エチル/エチルエーテル=10/1で再結晶
し、真空乾燥してN−アミノエチレンアクリルアミドと
MD−805の反応生成物(以下、CM−MD−805と称する)を
得た。収率は63.5%であった。図1にCM−MD−805とMD
−805のIRスペクトルを示した。また、元素分析の結果
は下記の通りであった。Then, at 0 ° C., 0.10 mmol of (2R, 4R) -4-methyl-1- [N 2 -((RS) -3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)- L-arginyl]
-2-piperidinecarboxylic acid (hereinafter referred to as MD-805), 0.11 mmol of dicyclohexylcarbodiimide and
DM containing 0.15 mmol of hydroxybenzotriazole
To 20 ml of the F solution, 20 ml of 0.1 mmol of N-aminoethyleneacrylamide obtained above was added, and the mixture was reacted at room temperature for 72 hours with stirring. At the end of the reaction, 60 ml of ethyl acetate was added, followed by washing three times with 4% sodium bicarbonate, 10% citric acid and saturated saline sequentially, and then ethyl acetate was distilled off. The resulting residue was subjected to silica gel chromatography. It was separated and purified by chromatography [developing solvent: ethyl acetate / chloroform = 3/1], recrystallized from ethyl acetate / ethyl ether = 10/1, dried in vacuo, and dried with N-aminoethylene acrylamide.
A reaction product of MD-805 (hereinafter referred to as CM-MD-805) was obtained. The yield was 63.5%. Figure 1 shows CM-MD-805 and MD
The IR spectrum of -805 was shown. The results of elemental analysis were as follows.
計算値 C:55.1%,H:7.28%,N:18.54% 分析値 C:55.76%,H:7.02%,N:18.72% MD−805の代わりに、対照として、t−ブトキシカル
ボニルアルギニンを使用する外は同様にしてN′−t−
ブトキシカルボニルアミド−N−アミノエチレンアクリ
ルアミド(以下、CM−Argと称する)を得た。Calculated C: 55.1%, H: 7.28%, N: 18.54% Analytical C: 55.76%, H: 7.02%, N: 18.72% Instead of MD-805, t-butoxycarbonylarginine is used as a control. N'-t-
Butoxycarbonylamide-N-aminoethyleneacrylamide (hereinafter referred to as CM-Arg) was obtained.
元素分析の結果は下記の通りであった。 The results of the elemental analysis were as follows.
計算値 C:51.89%,H:8.11%,N:22.70% 分析値 C:51.74%,H:8.32%,N:22.54% (2) ジャーナル オブ バイオメディカル マチリ
アル リサーチ(J.Biomed.Mater.Res.),20,1157(198
6)の記載に従って合成したポリウレタン〔ポリテトラ
メチレングリコール:4,4′−ジフェニルメタンジイソシ
アナート:ブタンジオール=1:2:1(仕込比)〕のフィ
ルム(1.5cm×1.5cm)をグロー放電処理(条件:0.2Tor
r,5mA,1分間)し、上記(1)で得たCM−MD−805の
(a)5%、(b)10%、(c)15%及び(d)20%の
水溶液に入れて、窒素雰囲気下、20℃で24時間UV照射し
てポリウレタンフィルムの表面にCM−MD−805をグラフ
ト重合させた。反応終了後、蒸留水で3回洗浄し、室温
で乾燥させた。得られた生成物を以下、GR−PEU−MD
(a,b,c,d)とする。Calculated value C: 51.89%, H: 8.11%, N: 22.70% Analysis value C: 51.74%, H: 8.32%, N: 22.54% (2) Journal of Biomedical Materials Research (J. Biomed. Mater. Res. ), 20,1157 (198
Glow discharge treatment of a polyurethane (polytetramethylene glycol: 4,4'-diphenylmethane diisocyanate: butanediol = 1: 2: 1 (charge ratio)) film (1.5 cm × 1.5 cm) synthesized as described in 6). (Condition: 0.2Tor
r, 5 mA, 1 minute), and put it in an aqueous solution of (a) 5%, (b) 10%, (c) 15% and (d) 20% of CM-MD-805 obtained in (1) above. UV irradiation was performed at 20 ° C. for 24 hours in a nitrogen atmosphere to graft-polymerize CM-MD-805 on the surface of the polyurethane film. After the completion of the reaction, the resultant was washed three times with distilled water and dried at room temperature. The obtained product is hereinafter referred to as GR-PEU-MD
(A, b, c, d).
CM−MD−805の代わりにCM−Argを使用する外は同様に
して、GR−PEU−AR(a,b,c,d)を合成した。GR-PEU-AR (a, b, c, d) was synthesized in the same manner except that CM-Arg was used instead of CM-MD-805.
各ポリウレタンフィルムへのCM−MD−805及びCM−Arg
のグラフト量の測定は、次のようにして行った。即ち、
各ポリウレタンフィルムを6N塩酸2mlに入れて110℃12時
間加水分解反応し、反応後、6N塩酸及び水酸化ナトリウ
ムで中和して、ホウ酸緩衝液(pH8.5)を加えて全量10m
lとする。これにフルラム(25mgフルラム/100mlアセト
ン)を加え、直ちに混合し、390mmで励起して、480nmの
螢光発射強度により含有量を定量した。その結果を図2
に示した。尚、グラフト重合していないポリウレタンフ
ィルム(以下PEUと称する)を対照として測定した。CM-MD-805 and CM-Arg for each polyurethane film
The amount of the graft was measured as follows. That is,
Each polyurethane film was placed in 2 ml of 6N hydrochloric acid and subjected to a hydrolysis reaction at 110 ° C. for 12 hours. After the reaction, the reaction was neutralized with 6N hydrochloric acid and sodium hydroxide, and a borate buffer (pH 8.5) was added to a total volume of 10 m.
l. Fluram (25 mg fluram / 100 ml acetone) was added thereto, mixed immediately, excited at 390 mm, and the content was quantified by the fluorescence emission intensity at 480 nm. Figure 2 shows the result.
It was shown to. In addition, it measured using the polyurethane film (henceforth PEU) without a graft polymerization as a control.
試験例1 (a) GR−PEU−MD膜表面での血栓の生成率 イヌのクエン酸加全血をポリマー膜上に200μ滴下
し0.1M塩化カルシウム溶液を20μ加えた後、37℃に20
分間放置し、生成した血栓をホルマリンで固定し乾燥
後、秤量することにより測定した。Test Example 1 (a) Production rate of thrombus on GR-PEU-MD membrane surface 200 μl of canine citrated whole blood was dropped on the polymer membrane, and 20 μl of 0.1 M calcium chloride solution was added.
The mixture was allowed to stand for 1 minute, the formed thrombus was fixed with formalin, dried, and weighed to measure.
ガラス板上で上述の実験を行った時に生成した血栓量
を100%とし、実施例1で得られたGR−PEU−MD(a,b,c,
d)の血栓生成率を求めた。その結果を表2に示した。
比較として、PEU及び実施例1で得られたGR−PEU−AR
(a,b,c,d)を使用した場合の結果を併記した。The amount of thrombus generated when the above experiment was performed on a glass plate was set to 100%, and the GR-PEU-MD (a, b, c,
The thrombus formation rate of d) was determined. The results are shown in Table 2.
For comparison, PEU and GR-PEU-AR obtained in Example 1 were used.
The results when (a, b, c, d) were used are also shown.
(b) GR−PEU−MD膜表面の血小板の粘着量 クエン酸加成犬の多血小板血しょう(PRP)200μを
GR−PEU−MD(d)の表面に滴下した。37℃、20分間浸
漬させた後、生理的食塩水溶液(PBS)で2回洗浄し、
2.5%グルタルアルデヒドを含むPBS中で20時間固定化処
理した。次いで、エタノールで脱水処理し、乾燥させた
後、膜の表面をSEMで観察して、膜表面への血小板の粘
着量を測定した。その結果を表3に示した。比較とし
て、PEU及びGR−PEU−AR(d)を使用した場合の結果を
併記した。 (B) Adhesion of platelets on GR-PEU-MD membrane surface Platelet-rich plasma (PRP) of citrated dogs
It was dropped on the surface of GR-PEU-MD (d). After immersion at 37 ° C for 20 minutes, it was washed twice with physiological saline solution (PBS),
The cells were fixed in PBS containing 2.5% glutaraldehyde for 20 hours. Next, after dehydration treatment with ethanol and drying, the surface of the membrane was observed with an SEM to measure the amount of platelet adhesion to the membrane surface. Table 3 shows the results. For comparison, the results when PEU and GR-PEU-AR (d) were used are also shown.
(発明の効果) 本発明の抗血栓性高分子材料は、抗血栓性成分が比較
的低分子量であるので高分子材料により多く導入でき、
しかも、グラフト重合しているので高分子材料との結合
も従来に比し良好で、長時間の効果の持続が期待でき、
各種血液処理用器具に有利に使用し得る。 (Effect of the Invention) The antithrombotic polymer material of the present invention can be introduced into the polymer material more since the antithrombotic component has a relatively low molecular weight,
In addition, since it is graft-polymerized, the bond with the polymer material is better than before, and the effect can be maintained for a long time.
It can be advantageously used for various blood processing instruments.
図1はMD−805及びCM−MD−805のIRスペクトルを示す図
で、(A)はMD−805のIRスペクトル、(B)はCM−MD
−805のIRスペクトル、はアリルを示す吸収、は第
二アミドを示す吸収、はスルホンアミドを示す吸収を
表す。また、縦軸は吸収、横軸は波長(cm-1)を示す。 図2は実施例1で得たGR−PEU−MD(a,b,c,d)(図中、
△で示される)及びGR−PEU−AR(a,b,c,d)(図中、○
で示される)におけるグラフト重合されたCM−MD−805
及びCM−Arg量を表す図である。また、縦軸はグラフト
重合されたCM−MD−805又はCM−Argの含有量(×10-6mo
l/cm2)、横軸はCM−MD−805又はCM−Argの含有量
(%)を示す。FIG. 1 is a diagram showing the IR spectra of MD-805 and CM-MD-805, wherein (A) is the IR spectrum of MD-805 and (B) is the CM-MD.
The IR spectrum of -805 indicates absorption indicating allyl, absorption indicating secondary amide, and absorption indicating sulfonamide. The vertical axis indicates absorption, and the horizontal axis indicates wavelength (cm -1 ). FIG. 2 shows GR-PEU-MD (a, b, c, d) obtained in Example 1 (in the figure,
(Shown by △) and GR-PEU-AR (a, b, c, d) (in the figure, ○
CM-MD-805)
FIG. 6 is a diagram showing the amount of CM-Arg. The vertical axis indicates the content of the graft-polymerized CM-MD-805 or CM-Arg (× 10 −6 mo
l / cm 2 ), and the horizontal axis indicates the content (%) of CM-MD-805 or CM-Arg.
Claims (1)
ンビン活性を有するアルギニン誘導体が該誘導体のカル
ボン酸基を介して結合している付加重合可能なエチレン
性化合物を、グラフト重合させて得られることを特徴と
する抗血栓性高分子材料。1. An addition-polymerizable ethylenic compound in which an arginine derivative having antithrombin activity is bonded via a carboxylic acid group of the derivative to a plasma-treated polymer material, which is obtained by graft polymerization. An antithrombotic polymer material, characterized in that:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1149099A JP2743480B2 (en) | 1989-06-12 | 1989-06-12 | Antithrombotic polymer material |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1149099A JP2743480B2 (en) | 1989-06-12 | 1989-06-12 | Antithrombotic polymer material |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH0315479A JPH0315479A (en) | 1991-01-23 |
JP2743480B2 true JP2743480B2 (en) | 1998-04-22 |
Family
ID=15467677
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP1149099A Expired - Fee Related JP2743480B2 (en) | 1989-06-12 | 1989-06-12 | Antithrombotic polymer material |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP2743480B2 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5344455A (en) * | 1992-10-30 | 1994-09-06 | Medtronic, Inc. | Graft polymer articles having bioactive surfaces |
WO2000015271A1 (en) * | 1998-09-14 | 2000-03-23 | Kawasumi Laboratories, Inc. | Intravascular stent |
-
1989
- 1989-06-12 JP JP1149099A patent/JP2743480B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
JPH0315479A (en) | 1991-01-23 |
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