ストレプトキナーゼ 化学特性,用途語,生産方法
説明
Streptokinase is a protein produced by certain strains of hemolytic group
C streptococcus, and it was the first clinically useful fibrinolytic. Unlike other
plasminogen activators, streptokinase is not an enzyme and cannot break any bonds in a
plasminogen molecule by itself. It forms an equimolecular compound with plasminogen,
thus forming a streptokinase–plasminogen complex. In the plasminogenic region of the
resulting complex, certain conformational changes lead to a break in a few peptide bonds,
and transformation of this complex into a streptokinase–plasmin complex, or free plasmin,
which also decomposes fibrin.
使用
This drug has a half-life in the plasma of 15–30 min, and
is used intravenously to treat patients with severe, massive pulmonary embolism and
thrombus of the veins; it is also used during myocardial infarctions. Recently, a number of
streptokinase derivatives have been proposed, in particular acetylated derivatives, which
are developed for use as fibrinolytics.
一般的な説明
Streptokinase (Kabikinase, Streptase)is a catabolic 47,000-d protein secreted by group Cβ-hemolyticstreptococci. It is a protein with no intrinsic enzymaticactivity. Streptokinase activates plasminogen toplasmin, a proteolytic enzyme that hydrolyzes fibrin andpromotes the dissolution of thrombi. Plasminogen is activatedwhen streptokinase forms a 1:1 stoichiometric complexwith it. Allergic reactions to streptokinase occur commonlybecause of antibody formation in individuals treatedwith it. Furthermore, the antibodies inactivate streptokinaseand reduce its ability to prolong thrombin time.Streptokinase is indicated for acute myocardial infarction,for local perfusion of an occluded vessel, and before angiography,by intravenous, intra-arterial, and intracoronaryadministration, respectively.
作用機序
Streptokinase is a protein purified from culture broths of group C β-hemolytic streptococci bacteria.
Streptokinase contains a single polypeptide chain of 414-amino-acid residues with a molecular
weight of 47 kDa. Streptokinase by itself has no intrinsic enzymatic activity. To be active, it
must bind with plasminogen to form an activator complex (1:1 complex). This complex then acts to
convert uncomplexed plasminogen to the active fibrinolytic enzyme, plasmin. The
streptokinase/plasminogen complex not only degrades fibrin clots but also catalyzes the breakdown
of fibrinogen and factors V and VII. As a result, streptokinase is considered to be a fibrinnonspecific drug.
薬物動態学
Unfortunately, the half-life of the activator complex is less than 30 minutes, which frequently is too
short to completely lyse a thrombus. Anistreplase (APSAC; Eminase) is a 1:1 streptokinase/lysineplasminogen complex that has been acylated with an anisoyl group at the active-site serine within the lysine-plasminogen. Anistreplase is inactive as such, but following complexation with fibrin, the
anisoyl group is slowly cleaved, exposing the active site and, thus, leading to degradation of fibrin.
The pro-drug nature of anistreplase exhibits an improved pharmacokinetic profile, with anistreplase
acting as a semiselective lysis agent at the clot site. The inactivity of the circulating anistreplase
also allows this drug to be given as a very rapid intravenous infusion (typically, 30 U over 3–5
minutes). Tissue reperfusion following anistreplase therapy compares favorably to streptokinase
because of the extended half-life (90 minutes).
副作用
Because it is a foreign protein, streptokinase is associated with significant hypersensitivity
reactions. Most people have, at some point in their lives, had a streptococcal infection and,
therefore, have developed circulating antistreptococcal antibodies. These antibodies frequently are
active against streptokinase as well. The response of the streptokinase to these antibodies can vary
widely, from inactivation of the fibrinolytic properties of the protein to rash, fever, and rarely,
anaphylaxis. Significant allergic reactions to streptokinase occur in approximately 3% of patients.
ストレプトキナーゼ 上流と下流の製品情報
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