ウロキナーゼ

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Danger

• 危険有害性情報

  H334：吸入するとアレルギー、喘息または、呼吸困難 を起こすおそれ

• 注意書き

  P261：粉じん/煙/ガス/ミスト/蒸気/スプレーの吸入を避ける こと。

  P284：呼吸用保護具を着用すること。

  P501：内容物/容器を．．．に廃棄すること。

ウロキナーゼ 価格

ウロキナーゼ 化学特性,用途語,生産方法

• 解説

  ウロキナーゼ，EC 3.4.21.31．血液中のプラスミノーゲンをプラスミンに変換させる機能を有する酵素で，プラスミノーゲン活性化剤である．ヒトの尿中より単離され，分子量5.5×104 のものと3.1×104 のものとがある．また最近，腎細胞培養液からも得られるようになった．血栓溶解剤として大量生産され，各種血栓症の治療に用いられている．

  1947年にヒトの尿中から発見されたタンパク分解酵素で、血漿(けっしょう)中に存在するプラスミノーゲンを活性化してプラスミンの形成を促すところから、各種血栓症、塞栓症(そくせんしょう)の治療のほか、マイトマイシンCなどの制癌(せいがん)剤との併用効果を適応としている。これはプラスミンが血液凝固の際に生じるフィブリンを溶解したり、細胞膜の透過性を亢進(こうしん)する作用を有するので、血栓や塞栓を溶解したり、癌細胞を取り囲むフィブリンを溶解し制癌剤の癌細胞への滲達(しんたつ)性を強めるためである。

• 説明

  Urokinase is an enzyme that is extracted from human urine or kidney cells, which directly cleaves specific peptide bonds, in particular the Arg-560–Val-561 bond in the plasminogen molecule, thus transforming it into plasmin.

• 化学的特性

  White or almost white, amorphous powder.

• 使用

  The effect of systemic administration of urokinase is unclear. One study reported the effectiveness of superselective ophthalmic artery fibrinolytic therapy of urokinase for CRVO. Urokinase was infused through a microcatheter into the ostium of the ophthalmic artery via the femoral artery. Six eyes of 26 patients had a significant improvement in VA 24 hours after the fibrinolysis; eyes with combined central retinal artery occlusion and CRVO with recent visual impairment appeared to be the most responsive.

• 一般的な説明

  Urokinase (Abbokinase) is a glycosylatedserine protease consisting of 411 amino acid residues,which exists as two polypeptide chains connected by a singledisulfide bond. It is isolated from human urine or tissueculture of human kidneys. The only known substrate ofurokinase is plasminogen, which is activated to plasmin, afibrinolytic enzyme. Unlike streptokinase, urokinase is adirect activator of plasminogen. Urokinase is nonantigenicbecause it is an endogenous enzyme and, therefore, may beused when streptokinase use is impossible because of antibodyformation. It is administered intravenously or by theintracoronary route. Its indications are similar to those ofstreptokinase.

• 作用機序

  Urokinase is an enzyme with the ability to directly degrade fibrin and fibrinogen. It is now isolated from cultures of human fetal kidney cells and is composed of two polypeptide chains with molecular weights of 32 and 54 kDa.

• 薬物動態学

  This method of isolation is much more efficient than the original isolation of urokinase from human urine. Because of its source, the human body does not see urokinase as a foreign protein. Therefore, it lacks the antigenicity associated with streptokinase and frequently is used for patients with a known hypersensitivity to streptokinase. Plasmin cannot be used directly because of the presence of naturally occurring plasmin antagonists in plasma. No such inhibitors of urokinase exist in the plasma, however, allowing this enzyme to have clinical utility. Even so, urokinase is much more expensive (threefold the price of streptokinase) and has an even shorter half-life (15 minutes). Urokinase also has other fibrin-nonspecific actions similar to streptokinase.

• 安全性プロファイル

  An experimental teratogen. Experimental reproductive effects. Used in the treatment of diseases caused by blood clots.

• 純化方法

  Crystallisation of this enzyme is induced at pH 5.0 to 5.3 (4o) by careful addition of NaCl with gentle stirring until the solution becomes turbid (silky sheen). The NaCl concentration is increased gradually (over several days) until 98% of saturation is achieved whereby urokinase crystallises out as colourless thin brittle plates. It can be similarly recrystallised to maximum specific activity [104K CTA units/mg of protein (Sherry et al. J Lab Clin Med 64 145 1964)]. [Lesuk et al. Science 147 880 1965, NMR: Bogusky et al. Biochemistry 28 6728 1989.] Itisa plasminogen activator [Gold et al. Biochem J 262 1989, de Bock & Wang Med Res Rev 24(1) 13 2004].

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