JPH032446B2 - - Google Patents
Info
- Publication number
- JPH032446B2 JPH032446B2 JP60160301A JP16030185A JPH032446B2 JP H032446 B2 JPH032446 B2 JP H032446B2 JP 60160301 A JP60160301 A JP 60160301A JP 16030185 A JP16030185 A JP 16030185A JP H032446 B2 JPH032446 B2 JP H032446B2
- Authority
- JP
- Japan
- Prior art keywords
- weight
- parts
- solution
- block
- formula
- 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.)
- Expired - Lifetime
Links
- 230000002785 anti-thrombosis Effects 0.000 claims description 27
- -1 polyoxyethylene Polymers 0.000 claims description 23
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 10
- 150000002009 diols Chemical class 0.000 claims description 10
- 229920002803 thermoplastic polyurethane Polymers 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000005442 diisocyanate group Chemical group 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 14
- 229920005989 resin Polymers 0.000 description 13
- 239000011347 resin Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 239000008280 blood Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- 239000011521 glass Substances 0.000 description 7
- 229920001451 polypropylene glycol Polymers 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 6
- 239000003146 anticoagulant agent Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- UPMLOUAZCHDJJD-UHFFFAOYSA-N 4,4'-Diphenylmethane Diisocyanate Chemical compound C1=CC(N=C=O)=CC=C1CC1=CC=C(N=C=O)C=C1 UPMLOUAZCHDJJD-UHFFFAOYSA-N 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- 229960002897 heparin Drugs 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- CWEFIMQKSZFZNY-UHFFFAOYSA-N pentyl 2-[4-[[4-[4-[[4-[[4-(pentoxycarbonylamino)phenyl]methyl]phenyl]carbamoyloxy]butoxycarbonylamino]phenyl]methyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCCCCC)=CC=C1CC(C=C1)=CC=C1NC(=O)OCCCCOC(=O)NC(C=C1)=CC=C1CC1=CC=C(NC(=O)OCCCCC)C=C1 CWEFIMQKSZFZNY-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- DSUFPYCILZXJFF-UHFFFAOYSA-N 4-[[4-[[4-(pentoxycarbonylamino)cyclohexyl]methyl]cyclohexyl]carbamoyloxy]butyl n-[4-[[4-(butoxycarbonylamino)cyclohexyl]methyl]cyclohexyl]carbamate Chemical compound C1CC(NC(=O)OCCCCC)CCC1CC1CCC(NC(=O)OCCCCOC(=O)NC2CCC(CC3CCC(CC3)NC(=O)OCCCC)CC2)CC1 DSUFPYCILZXJFF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229920002050 silicone resin Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical group NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical group OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical group CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Chemical group 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010037437 Pulmonary thrombosis Diseases 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Chemical group 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920003226 polyurethane urea Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
- Polyurethanes Or Polyureas (AREA)
Description
〔産業上の利用分野〕
本発明は、高強度と優れた抗血栓性を有するウ
レタン樹脂の製造方法に関する。
〔従来の技術〕
近年、人工心臓、人工心肺、人工血管、血管カ
テーテル、バイパスチユーブやバルーンポンプ
等、医療技術の高度化に伴い多くの医療機器が提
案され使用されている。これらの医療機器には、
多くの高分子化合物が使用されており、例えば、
ポリエチレン、ポリプロピレン、ポリ塩化ビニ
ル、ポリフツ化エチレン、ポリアミド、ポリエス
テル、ポリウレタン、ポリカーボネート、シリコ
ーン樹脂等が挙げられる。しかし、これらの高分
子化合物を血液が直接接触する部分の材料として
使用するためには、抗血栓性が不十分である。す
なわち、これらの高分子材料を血液に接触させる
と血小板やフイブリンの付着が開始され、これを
そのまま放置すると血栓が形成される。そして、
この血栓が血流を停止させたり、血管内を移動
し、脳血栓症や肺血栓症等の合併症を引起こし、
生命をおびやかす可能性もある。
したがつて、これらの使用は比較的短時間に限
られ、また、ヘパリン等の抗凝固剤が使用され
る。しかし、ヘパリン等の抗凝固剤を使用した場
合、出血時に止血が困難といつた弊害もあり、特
に血管外科手術等においては使用しないことが好
ましい。このため、抗凝固剤を使用しないでも血
液凝固を阻止できる高分子材料が望まれており、
種々の方法が提案されている。１つの有効な方法
は、高分子材料表面上に適当な官能基を有する分
子鎖を導入し、抗凝固剤であるヘパリン線溶系物
質であるウロキナーゼをイオン結合、あるいは共
有結合により化学的に固定する方法である。しか
し、この方法は、生理活性物質を使用するがため
に、製造工程も複雑となり、コストが高くなり勝
ちである。また、高分子材料表面上にヒドロキシ
エチルメタクリレート、ビニルピロリドン、アク
リルアミド、ビニルアルコールやポリエチレング
リコール鎖を有するモノマーをプラズマや放射線
を用いてグラフト重合し、ヒドロゲル層を形成す
る方法があるが、この方法は製品形態において細
部にわたる均一な処理が難しい。
一方、セグメント化ポリウレタンのような、ミ
クロ相分離構造を有するウレタン樹脂が優れた抗
血栓性を有していることは良く知られている。こ
のようなウレタン樹脂としては、米国エチコン社
のバイオマー、サーメデツクス社のテコフレツク
ス、コントロン社のカルデイオサンがよく知られ
ている。しかし、これら公知のウレタン樹脂化合
物は、なお多くの欠点を有する。カルデイオサン
は、現存するウレタン樹脂化合物において抗血栓
性に優れるものの１つであるが、機械的強度が不
十分であり、ポリエーテルウレタンと数個のアセ
テート末端を有するシリコーン樹脂を適当な溶媒
中で混合し、成形時に脱酢酸反応により架橋体と
するという製法であるため、成形時の反応条件に
より優れた抗血栓性を再現性よく得られないとい
う欠点がある。他方、バイオマーやテコフレツク
スは機械的強度において優れているが、抗血栓性
は十分でない。
〔発明が解決しようとする問題点〕
本発明者らは、これらのウレタン樹脂が有して
いる抗血栓性に着目し、これを更に強化すると共
に機械的性能に優れた材料を開発するべく研究を
重ねた結果、特公昭58−8700号公報に示したごと
く、特定のポリオキシエチレン−ポリオキシプロ
ピレンブロツクコポリエーテルジオールとジイソ
シアネートとの反応物であるプレポリマーにジア
ミン化合物を作用させて得られるウレタン樹脂化
合物において抗血栓性を向上できるとの知見を得
た。
しかし、このものは、機械的特性がやや劣つて
いた。
本発明の目的は、十分な機械的特性と良好な抗
血栓性の２つの性質を両立し、生体内で安全に使
用できるウレタン樹脂の製造方法を提供すること
にある。
〔問題点を解決するための手段〕
本発明を概説すれば、本発明は、優れた力学的
特性を有し、高度の抗血栓性を有するウレタン樹
脂の製造方法に関する発明であつて、下記一般式
：
（式中ｌ、ｍ及びｎは各々１〜100の整数を示す）
で表され、かつ数平均分子量500〜5000、ポリオ
キシエチレン含量10〜50重量％であるブロツクコ
ポリエーテルジオールに、下記一般式：
HO〔（――Ｒ）−xＯ〕−yＨ ……〔〕
（式中Ｒは
[Industrial Field of Application] The present invention relates to a method for producing a urethane resin having high strength and excellent antithrombotic properties. [Prior Art] In recent years, as medical technology has become more sophisticated, many medical devices have been proposed and used, such as artificial hearts, heart-lung machines, artificial blood vessels, vascular catheters, bypass tubes, and balloon pumps. These medical devices include
Many polymeric compounds are used, for example,
Examples include polyethylene, polypropylene, polyvinyl chloride, polyethylene fluoride, polyamide, polyester, polyurethane, polycarbonate, silicone resin, and the like. However, these polymer compounds do not have sufficient antithrombotic properties to be used as materials for parts that come into direct contact with blood. That is, when these polymeric materials come into contact with blood, platelets and fibrin begin to adhere, and if this is left as is, a thrombus is formed. and,
This thrombus may stop blood flow or move within blood vessels, causing complications such as cerebral thrombosis and pulmonary thrombosis.
It can also be life-threatening. Therefore, their use is limited to relatively short periods of time, and anticoagulants such as heparin are used. However, when an anticoagulant such as heparin is used, there are disadvantages such as difficulty in stopping bleeding, and therefore, it is preferable not to use it particularly in vascular surgery. For this reason, there is a need for polymeric materials that can prevent blood coagulation without the use of anticoagulants.
Various methods have been proposed. One effective method is to introduce molecular chains with appropriate functional groups onto the surface of a polymeric material, and chemically immobilize urokinase, an anticoagulant heparin fibrinolytic substance, through ionic or covalent bonds. It's a method. However, since this method uses a physiologically active substance, the manufacturing process is complicated and the cost tends to be high. There is also a method in which a hydrogel layer is formed by graft polymerizing monomers having hydroxyethyl methacrylate, vinyl pyrrolidone, acrylamide, vinyl alcohol, or polyethylene glycol chains on the surface of a polymer material using plasma or radiation. It is difficult to uniformly process every detail in the product form. On the other hand, it is well known that urethane resins having a microphase-separated structure, such as segmented polyurethane, have excellent antithrombotic properties. As such urethane resins, Biomer manufactured by Ethicon, USA, Tecoflex manufactured by Thermedex, and Cardiosan manufactured by Kontron are well known. However, these known urethane resin compounds still have many drawbacks. Cardiosan is one of the existing urethane resin compounds with excellent antithrombotic properties, but its mechanical strength is insufficient, so it is difficult to mix polyether urethane and a silicone resin with several acetate ends in an appropriate solvent. However, since the manufacturing method involves forming a crosslinked product by deacetic acid reaction during molding, there is a drawback that excellent antithrombotic properties cannot be obtained with good reproducibility depending on the reaction conditions during molding. On the other hand, Biomer and Tecoflex have excellent mechanical strength, but do not have sufficient antithrombotic properties. [Problems to be Solved by the Invention] The present inventors focused on the antithrombotic properties of these urethane resins, and conducted research to further strengthen these properties and develop materials with excellent mechanical performance. As a result, as shown in Japanese Patent Publication No. 58-8700, a urethane obtained by reacting a diamine compound with a prepolymer which is a reaction product of a specific polyoxyethylene-polyoxypropylene block copolyether diol and a diisocyanate was obtained. We have found that antithrombotic properties can be improved in resin compounds. However, this material had somewhat inferior mechanical properties. An object of the present invention is to provide a method for producing a urethane resin that has both sufficient mechanical properties and good antithrombotic properties and can be used safely in vivo. [Means for Solving the Problems] To summarize the present invention, the present invention relates to a method for producing a urethane resin having excellent mechanical properties and high antithrombotic properties. formula: (In the formula, l, m and n each represent an integer from 1 to 100)
A blocked copolyether diol having a number average molecular weight of 500 to 5000 and a polyoxyethylene content of 10 to 50% by weight has the following general formula: HO[(--R) -xO ] -yH ...[ ] (In the formula, R is
以下、本発明を実施例によつて更に具体的に説
明するが、本発明はこれに限定されない。
実施例 １
ポリオキシエチレン(A)ブロツク及びポリオキシ
プロピレン(B)ブロツクより成るＡブロツク含量40
重量％、数平均分子量1600のＡ−Ｂ−Ａ型ブロツ
クコポリエーテルジオール25.6重量部と数平均分
子量1300のポリテトラメチレングリコール31.2重
量部を均一に混合したものをＮ，Ｎ−ジメチルア
セトアミド1000重量部中に溶解した後、４，4′−
ジフエニルメタンジイソシアネート21.5重量部を
加え、窒素気流下110℃で２時間かくはんしなが
ら反応させプレポリマーを得た。そしてこの溶液
を室温まで冷却し、エチレンジアミン2.90重量部
をＮ，Ｎ−ジメチルアセトアミド500重量部中に
溶解した溶液を約１時間で滴下、更に１時間反応
を続けた。次いで１，４−ブタンジオール５重量
部を加えてイソシアネート基末端を封止した後、
無水酢酸5.1重量部を添加し、ポリマーのアミノ
基末端を処理し反応を終了した。
得られた反応溶液を水中に注ぎ析出させた後、
十分に洗浄を行い90℃で減圧乾燥を行つた。この
時の収率は95％であつた。そして更にソツクスレ
ー抽出器を用いてアセトンで低分子量物質を除去
し、室温で減圧乾燥し目的の樹脂を得た。
次に、得られた樹脂の12.5％Ｎ，Ｎ−ジメチル
アセトアミド溶液を作成し、細孔径5μmのフイル
ターを用いて加圧過を行つた。そして得られた
溶液を水平なガラス板上に流延し、減圧下60℃に
て徐々にＮ，Ｎ−ジメチルアセトアミドを除去し
100μm厚のフイルムを得た。このフイルムの機械
的特性を測定するために引張試験機により、引張
破断強度、引張伸び率、引張初期弾性率を求め
た。その結果を他の例と一緒に後記第１表に示
す。
続いて抗血栓性の評価を行つた。抗血栓性はイ
ンビトロでの抗血栓性テストを２種類行つた。１
つはリー・ホワイト（Lee−White）法である。
すなわち、直径12mm、長さ100mmのすり合せ栓付
きガラス試験管の内壁に樹脂を均一にコーテイン
グし、これに採血直後のヒト血液１mlを入れ、37
℃に保ちながら５分経過後から１分間ごとにこの
試験管を45゜傾けて血液の凝固状態を観察し、血
液が流動しなくなる時間を測定した。同様の操作
をガラス試験管のみで行い凝固に要した時間を１
として、これに対する相対値をもつて抗血栓性の
尺度とした。したがつて相対値の大なるものほど
抗血栓性に優れる。この結果を他の例と一緒に第
２表に示す。
次に抗血栓性の評価を今井らの開発した動力学
的方法〔ジヤーナル・オブ・バイオメデイカル・
マテリアルズ・リサーチ（J.Biomed.Mater.
Res.）第６巻第165頁（1972）〕に準じて行つた。
すなわち、得られたフイルムを３cm平方に切取
り、すり合め栓付きガラス時計皿の凹面に付着さ
せ、37℃の恒温条件下、犬より採血したACD血
250μをこの上に滴下、続いて、0.1M塩化カル
シウム水溶液25μを添加し凝固反応を開始させ
た。15分経過後、水を添加して反応を停止させ、
生じた血餅をホルマリンで固定、常温で減圧乾燥
後、化学天秤にて重量を測定した。同様の操作を
ガラス時計皿のみで行い生じた血餅重量を100と
し、これに対する相対重量をもつて抗血栓性の尺
度とした。したがつて相対重量が低いものほど抗
血栓性に優れる。この結果を他の例と一緒に後記
第２表に示す。
比較例 １
ポリオキシエチレン(A)ブロツク及びポリオキシ
プロピレン(B)ブロツクより成るＡブロツク含量40
重量％、数平均分子量1600のＡ−Ｂ−Ａ型ブロツ
クコポリエーテル型ジオール64重量部と４，4′−
ジフエニルメタンジイソシアネート21.5重量部を
Ｎ，Ｎ−ジメチルアセトアミド1000重量部中に溶
解し、窒素気流下、110℃で２時間かくはんしな
がら反応させプレポリマーを得た。この溶液を室
温まで冷却し、エチレンジアミン4.32重量部を
Ｎ，Ｎ−ジメチルアセトアミド中に溶解した溶液
を約２時間で滴下し、１時間反応を続けた。そし
て実施例１と同様にしてポリマー末端を処理して
反応を終了した。得られた反応溶液を実施例１と
同様にして水洗、精製を行い、次いで機械的特性
及び抗血栓性について調べた。この結果を併せて
第１表及び第２表に示す。
比較例 ２
市販のセグメント化ポリウレタンウレアである
バイオマー（米国エチコン社）に関しフイルム及
び内壁をコートした試験管を作成し、実施例１と
同様にして機械的特性及び抗血栓性について調べ
た。この結果を併せて第１表及び第２表に示す。
実施例 ２
ポリオキシエチレン(A)ブロツク及びポリオキシ
プロピレン(B)ブロツクより成るＡブロツク含量10
重量％、数平均分子量2000のＡ−Ｂ−Ａ型ブロツ
クコポリエーテルジオールを56重量部と数平均分
子量1600のポリプロピレングリコール19.2重量部
を均一に混合した後、Ｎ，Ｎ−ジメチルアセトア
ミド1000重量部中に均一に溶解し、次いで４，
4′−ジフエニルメタンジイソシアネート25重量部
を加え、窒素気流下80℃で４時間かくはんしなが
ら反応させてプレポリマーを得た。この溶液を室
温まで冷却し、エチレンジアミン4.32重量部を
Ｎ，Ｎ−ジメチルアセトアミド500重量部中に溶
解した溶液を約２時間で滴下し、更に１時間かく
はんを続けた。そして実施例１と同様にして停止
反応を行つた。反応溶液を実施例１と同様の方法
により水洗、精製を行い、目的の樹脂を得た。次
いで樹脂の機械的特性及び抗血栓性について、実
施例１と同様の方法により調べた。この結果を第
１表及び第２表に示す。
比較例 ３
ポリオキシエチレン(A)ブロツク及びポリオキシ
プロピレン(B)ブロツクより成るＡブロツク含量10
重量％、数平均分子量2000のＡ−Ｂ−Ａ型ブロツ
クコポリエーテルジオール80重量部と４，4′−ジ
フエニルメタンジイソシアネート25重量部をＮ，
Ｎ−ジメチルアセトアミドを反応溶媒とし、窒素
気流下80℃で４時間かくはんを続けて、プレポリ
マーを得た。この溶液を室温まで冷却し、エチレ
ンジアミン4.32重量部をＮ，Ｎ−ジメチルアセト
アミド500重量部中に溶解した溶液を２時間かけ
て滴下し、１時間反応させた後、実施例１と同様
の方法により停止反応を行つた。反応溶液を実施
例１と同様の方法により水洗、精製を行い目的の
樹脂を得た。次に、得られた樹脂の機械的特性及
び抗血栓性について、実施例１と同様の方法によ
り調べた。この結果を第１表及び第２表に示す。
実施例 ３
ポリオキシエチレン(A)ブロツク及びポリオキシ
プロピレン(B)ブロツクより成るＡブロツク含量40
重量％、数平均分子量1000のＡ−Ｂ−Ａ型ブロツ
クコポリエーテルジオール80重量部と数平均分子
量2000のポリテトラメチレングリコールを均一に
混合した後、Ｎ，Ｎ−ジメチルアセトアミド1000
重量部中に溶解し、４，4′−ジフエニルメタンジ
イソシアネート20.5重量部を加え、窒素気流下80
℃で４時間かくはんしながら反応させてプレポリ
マーを得た。この溶液を室温まで冷却し、エチレ
ンジアミン2.52重量部をＮ，Ｎ−ジメチルアセト
アミド500重量部中に溶解した溶液を約２時間で
滴下、更に１時間反応を続けた。そして実施例１
と同様にして停止反応を行つた後、実施例１と同
様にして水洗、精製を行い目的の樹脂を得た。次
いで、樹脂の機械的特性及び抗血栓性を実施例１
と同様の方法により調べた。この結果を第１表及
び第２表に示す。
比較例 ４
ポリオキシエチレン(A)ブロツク及びポリオキシ
プロピレン(B)ブロツクより成るＡブロツク含量40
重量％、数平均分子量1000のＡ−Ｂ−Ａ型ブロツ
クコポリエーテルジオール40重量部を、1000重量
部のＮ，Ｎ−ジメチルアセトアミド中に溶解した
後、４，4′−ジフエニルメタンジイソシアネート
20.5重量部を加え窒素気流下80℃で４時間かくは
んしながら反応させてプレポリマーを得た。この
溶液を室温まで冷却し、エチレンジアミン2.52重
量部をＮ，Ｎ−ジメチルアセトアミド500重量部
中に溶解した溶液を約２時間で滴下、更に１時間
反応を続けた。そして実施例１と同様にして停止
反応を行つた後、実施例１と同様にして水洗、精
製を行い樹脂を得た。
次にこの樹脂の機械的特性及び抗血栓性につい
て、実施例１と同様の方法により調べた。この結
果を第１表及び第２表に示す。
EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto. Example 1 A block content 40 consisting of polyoxyethylene (A) block and polyoxypropylene (B) block
% by weight, a uniform mixture of 25.6 parts by weight of A-B-A type blocked copolyether diol with a number average molecular weight of 1600 and 31.2 parts by weight of polytetramethylene glycol with a number average molecular weight of 1300 was mixed with 1000 parts by weight of N,N-dimethylacetamide. After dissolving in 4,4′-
21.5 parts by weight of diphenylmethane diisocyanate was added and reacted with stirring at 110° C. for 2 hours under a nitrogen stream to obtain a prepolymer. This solution was then cooled to room temperature, and a solution of 2.90 parts by weight of ethylenediamine dissolved in 500 parts by weight of N,N-dimethylacetamide was added dropwise over about 1 hour, and the reaction was continued for another 1 hour. Next, 5 parts by weight of 1,4-butanediol was added to seal the isocyanate group terminals, and then
5.1 parts by weight of acetic anhydride was added to treat the amino group terminals of the polymer and terminate the reaction. After pouring the obtained reaction solution into water and precipitating it,
It was thoroughly washed and dried under reduced pressure at 90°C. The yield at this time was 95%. Further, low molecular weight substances were removed with acetone using a Soxhlet extractor, and the resin was dried under reduced pressure at room temperature to obtain the desired resin. Next, a 12.5% solution of the obtained resin in N,N-dimethylacetamide was prepared and subjected to pressure filtration using a filter with a pore diameter of 5 μm. The resulting solution was then cast onto a horizontal glass plate, and N,N-dimethylacetamide was gradually removed at 60°C under reduced pressure.
A film with a thickness of 100 μm was obtained. In order to measure the mechanical properties of this film, tensile strength at break, tensile elongation, and initial tensile modulus were determined using a tensile tester. The results are shown in Table 1 below along with other examples. Subsequently, antithrombotic properties were evaluated. Two types of in vitro antithrombotic tests were conducted to determine antithrombotic properties. 1
One is the Lee-White method.
That is, the inner wall of a glass test tube with a stopper of 12 mm in diameter and 100 mm in length was uniformly coated with resin, and 1 ml of freshly drawn human blood was poured into it.
The test tube was tilted at 45 degrees every minute after 5 minutes had elapsed while maintaining the temperature at 0.degree. C. to observe the coagulation state of the blood, and the time until the blood stopped flowing was measured. The same operation was performed using only a glass test tube, and the time required for solidification was 1
The relative value to this was used as a measure of antithrombotic activity. Therefore, the larger the relative value, the better the antithrombotic property. The results are shown in Table 2 along with other examples. Next, the antithrombotic property was evaluated using the kinetic method developed by Imai et al.
Materials Research (J.Biomed.Mater.
Res.) Vol. 6, p. 165 (1972)].
That is, the obtained film was cut into 3 cm square pieces, attached to the concave surface of a glass watch glass with a stopper, and ACD blood collected from a dog was placed at a constant temperature of 37°C.
250μ of the solution was dropped thereon, followed by the addition of 25μ of a 0.1M aqueous calcium chloride solution to initiate a coagulation reaction. After 15 minutes, water was added to stop the reaction.
The resulting blood clot was fixed with formalin, dried under reduced pressure at room temperature, and then weighed using an analytical balance. A similar operation was carried out using only the glass watch glass, and the weight of the resulting blood clot was set as 100, and the relative weight to this was used as a measure of antithrombotic activity. Therefore, the lower the relative weight, the better the antithrombotic property. The results are shown in Table 2 below along with other examples. Comparative Example 1 A block content consisting of polyoxyethylene (A) block and polyoxypropylene (B) block: 40
64 parts by weight of A-B-A block copolyether type diol with a number average molecular weight of 1600 and 4,4'-
21.5 parts by weight of diphenylmethane diisocyanate was dissolved in 1000 parts by weight of N,N-dimethylacetamide, and reacted with stirring at 110° C. for 2 hours under a nitrogen stream to obtain a prepolymer. This solution was cooled to room temperature, and a solution of 4.32 parts by weight of ethylenediamine dissolved in N,N-dimethylacetamide was added dropwise over about 2 hours, and the reaction was continued for 1 hour. The end of the polymer was treated in the same manner as in Example 1 to complete the reaction. The obtained reaction solution was washed with water and purified in the same manner as in Example 1, and then examined for mechanical properties and antithrombotic properties. The results are also shown in Tables 1 and 2. Comparative Example 2 A test tube coated with a film and an inner wall was prepared using Biomer (Ethicon, USA), which is a commercially available segmented polyurethane urea, and its mechanical properties and antithrombotic properties were examined in the same manner as in Example 1. The results are also shown in Tables 1 and 2. Example 2 A block content 10 consisting of polyoxyethylene (A) block and polyoxypropylene (B) block
After uniformly mixing 56 parts by weight of A-B-A block copolyether diol with a number average molecular weight of 2000 and 19.2 parts by weight of polypropylene glycol with a number average molecular weight of 1600, the mixture was mixed in 1000 parts by weight of N,N-dimethylacetamide. Dissolve uniformly in 4,
25 parts by weight of 4'-diphenylmethane diisocyanate was added and reacted with stirring at 80° C. for 4 hours under a nitrogen stream to obtain a prepolymer. This solution was cooled to room temperature, and a solution of 4.32 parts by weight of ethylenediamine dissolved in 500 parts by weight of N,N-dimethylacetamide was added dropwise over about 2 hours, and stirring was continued for an additional hour. Then, a termination reaction was carried out in the same manner as in Example 1. The reaction solution was washed with water and purified in the same manner as in Example 1 to obtain the desired resin. Next, the mechanical properties and antithrombotic properties of the resin were examined in the same manner as in Example 1. The results are shown in Tables 1 and 2. Comparative Example 3 A block content consisting of polyoxyethylene (A) block and polyoxypropylene (B) block: 10
80 parts by weight of A-B-A block copolyether diol with a number average molecular weight of 2000 and 25 parts by weight of 4,4'-diphenylmethane diisocyanate were mixed with N,
Using N-dimethylacetamide as a reaction solvent, stirring was continued for 4 hours at 80° C. under a nitrogen stream to obtain a prepolymer. This solution was cooled to room temperature, and a solution of 4.32 parts by weight of ethylenediamine dissolved in 500 parts by weight of N,N-dimethylacetamide was added dropwise over 2 hours. After reacting for 1 hour, the same method as in Example 1 was carried out. A termination reaction was performed. The reaction solution was washed with water and purified in the same manner as in Example 1 to obtain the desired resin. Next, the mechanical properties and antithrombotic properties of the obtained resin were examined in the same manner as in Example 1. The results are shown in Tables 1 and 2. Example 3 A block content consisting of polyoxyethylene (A) block and polyoxypropylene (B) block: 40
After uniformly mixing 80 parts by weight of A-B-A block copolyether diol with a number average molecular weight of 1000 and polytetramethylene glycol with a number average molecular weight of 2000, 1000 parts by weight of N,N-dimethylacetamide was added.
20.5 parts by weight of 4,4'-diphenylmethane diisocyanate was added to the solution, and the solution was heated to 80% by weight under a nitrogen stream.
A prepolymer was obtained by reacting at ℃ for 4 hours with stirring. This solution was cooled to room temperature, and a solution of 2.52 parts by weight of ethylenediamine dissolved in 500 parts by weight of N,N-dimethylacetamide was added dropwise over about 2 hours, and the reaction was continued for an additional hour. And Example 1
After carrying out the termination reaction in the same manner as in Example 1, water washing and purification were carried out in the same manner as in Example 1 to obtain the desired resin. Next, the mechanical properties and antithrombotic properties of the resin were evaluated in Example 1.
It was investigated using the same method. The results are shown in Tables 1 and 2. Comparative Example 4 A block content consisting of polyoxyethylene (A) block and polyoxypropylene (B) block: 40
After dissolving 40 parts by weight of A-B-A block copolyether diol having a number average molecular weight of 1000 in 1000 parts by weight of N,N-dimethylacetamide, 4,4'-diphenylmethane diisocyanate was dissolved.
20.5 parts by weight was added and reacted with stirring at 80° C. for 4 hours under a nitrogen stream to obtain a prepolymer. This solution was cooled to room temperature, and a solution of 2.52 parts by weight of ethylenediamine dissolved in 500 parts by weight of N,N-dimethylacetamide was added dropwise over about 2 hours, and the reaction was continued for an additional hour. After carrying out the termination reaction in the same manner as in Example 1, water washing and purification were carried out in the same manner as in Example 1 to obtain a resin. Next, the mechanical properties and antithrombotic properties of this resin were examined in the same manner as in Example 1. The results are shown in Tables 1 and 2.
【表】【table】
【表】【table】
以上説明したように、本発明方法による抗血栓
性ウレタン樹脂は、抗血栓性及び機械的特性に優
れており、医療機器の血液接触部位においても、
安全に使用することのできる医用材料として好適
である。
具体的な応用例としては、血管内留置カテーテ
ル、血液回路、血液バイパスチユーブ、バルーン
ポンプ、また、血液浄化用吸着剤の被膜材料や膜
型人工臓器材料として使用することができる。
As explained above, the antithrombotic urethane resin produced by the method of the present invention has excellent antithrombotic properties and mechanical properties, and can be used in blood contact areas of medical devices.
It is suitable as a medical material that can be used safely. As specific application examples, it can be used for intravascular indwelling catheters, blood circuits, blood bypass tubes, balloon pumps, and as coating materials for blood purification adsorbents and membrane-type artificial organ materials.
Claims (1)
す）で表され、かつ数平均分子量500〜5000、ポ
リオキシエチレン含量10〜50重量％であるブロツ
クコポリエーテルジオールに、下記一般式： HO〔（――Ｒ）−xＯ〕−yＨ ……〔〕 （式中Ｒは【式】又は− CH2CH2CH2CH2−で示される基、ｘ及びｙは
各々１〜100の整数を示す）で表され、かつ数平
均分子量500〜5000のポリエーテルジオールを、
10〜90モル％の範囲内で、かつ全ジオール中に占
めるポリオキシエチレン含量が５〜45重量％にな
るように混合し、次いでジオール１モル当り2.01
〜3.50モルの割合で有機ジイソシアネートを反応
させ、次いで1.01〜2.50モルの割合のジアミン化
合物で鎖延長することを特徴とする優れた力学的
特性を有し、高度の抗血栓性を有するウレタン樹
脂の製造方法。[Claims] 1. The following general formula: (In the formula, l, m and n each represent an integer of 1 to 100), and has a number average molecular weight of 500 to 5000 and a polyoxyethylene content of 10 to 50% by weight. Formula: HO [(--R)- x O]- y H...[] (In the formula, R is a group represented by [formula] or - CH 2 CH 2 CH 2 CH 2 -, x and y are each 1 - represents an integer of 100) and has a number average molecular weight of 500 to 5000,
The polyoxyethylene content is mixed within the range of 10 to 90 mol% and the polyoxyethylene content in the total diol is 5 to 45% by weight, and then 2.01% by weight per mol of diol.
of urethane resins with excellent mechanical properties and high antithrombotic properties, characterized by reacting with organic diisocyanates in a proportion of ~3.50 mol and then chain-extending with diamine compounds in a proportion of 1.01-2.50 mol. Production method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60160301A JPS6222818A (en) | 1985-07-22 | 1985-07-22 | Production of antithrombotic urethane resin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60160301A JPS6222818A (en) | 1985-07-22 | 1985-07-22 | Production of antithrombotic urethane resin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6222818A JPS6222818A (en) | 1987-01-31 |
| JPH032446B2 true JPH032446B2 (en) | 1991-01-16 |
Family
ID=15712002
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60160301A Granted JPS6222818A (en) | 1985-07-22 | 1985-07-22 | Production of antithrombotic urethane resin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6222818A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4621113A (en) * | 1985-10-07 | 1986-11-04 | The Dow Chemical Company | Repeating block, oligomer-free, polyphase, thermoformable polyurethanes and method of preparation thereof |
| US5795633A (en) * | 1994-08-22 | 1998-08-18 | Nippon Zeon Co., Ltd. | Material composition and shaped article |
| JP2006130064A (en) * | 2004-11-05 | 2006-05-25 | National Cardiovascular Center | Stent delivery system |
| JP2006141555A (en) * | 2004-11-17 | 2006-06-08 | National Cardiovascular Center | Stent and its production method |
-
1985
- 1985-07-22 JP JP60160301A patent/JPS6222818A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6222818A (en) | 1987-01-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4880883A (en) | Biocompatible polyurethanes modified with lower alkyl sulfonate and lower alkyl carboxylate | |
| US5017664A (en) | Biocompatible polyurethane devices wherein polyurethane is modified with lower alkyl sulfonate and lower alkyl carboxylate | |
| Park et al. | Heparin immobilization onto segmented polyurethaneurea surfaces—effect of hydrophilic spacers | |
| EP0699103B1 (en) | Surface modified biocompatible membranes | |
| JP5702857B1 (en) | Antithrombogenic hollow fiber membrane and filter | |
| JPS588700B2 (en) | Method for producing antithrombotic high modulus polyurethane compound | |
| WO1997013575A1 (en) | Polysulfone membrane for purifying blood | |
| JPS61200114A (en) | Antithrombotic polyurethane compound and production thereof | |
| US5116361A (en) | Sulfonated polyethyleneoxide-substituted polymers with improved blood compatibility | |
| JP4060888B2 (en) | Thermoplastic polyurethane with active substance | |
| CN107216435B (en) | poly (urethane-urea) with side chain of phosphatide polyethylene glycol and preparation method thereof | |
| JPS62215621A (en) | Synthetic substance ready to adsorb large quantity of heparin firmly and manufacture | |
| Kruft et al. | Studies on two new radiopaque polymeric biomaterials | |
| JPH032446B2 (en) | ||
| JPH0311787B2 (en) | ||
| US5216087A (en) | Process for the preparation of sulfonated polyethyleneoxide-substituted polymers with improved blood compatibility | |
| JPS6015335B2 (en) | blood handling equipment | |
| Feng | Some advances in synthetic biomedical polymers | |
| Piao et al. | Synthesis and characterization of poly (dimethylsiloxane)-poly (ethylene oxide)-heparin CBABC type block copolymers | |
| Park et al. | PEO-Modified Surface-In Vitro, Ex Vivo, and In Vivo Blood Compatibility | |
| JPH0536065B2 (en) | ||
| JPH06184266A (en) | Antithrombogenic polyurethane elastomer and medical tool | |
| JPH04248826A (en) | Gas-diffusible material excellent in blood compatibility | |
| JP4338351B2 (en) | Blood compatible material | |
| JPH0343424A (en) | High-molecular material compatible with blood |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |