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硫酸化乳糖酸酰胺的抗血栓形成和出血作用的药理学概况

Pharmacologic profile of the antithrombotic and bleeding actions of sulfated lactobionic acid amides.

作者信息

Raake W, Klauser R J, Meinetsberger E, Zeller P, Elling H

机构信息

Department of Pharmacology, Luitpold-Werk, München, Germany.

出版信息

Semin Thromb Hemost. 1991;17 Suppl 1:129-35.

PMID:2068566
Abstract
  1. The introduced bis-lactobionic acid amides represent a new group of synthetic polyanions with a molecular weight of 2387 to 2514d. The compounds are homogeneous and chemically defined. 2. The in vitro blood coagulation parameters (APTT, Heptest, anti-Xa, thrombin time, and anti-IIa) are only marginally altered by these compounds. 3. In a rat model of venous thrombosis using endothelial damage as the thrombogenic stimulus, the antithrombotic activity of the bis-lactobionic acid amides was shown in a dose- and time-dependent manner. 4. LW 10082 and LW 10121 prolong the bleeding time at dosages about 10 times less than that of heparin. The safety/efficacy index appears to be wider for these compounds than for heparin. 5. In subchronic toxicologic studies in rats, LW 10082 was well tolerated up to a dosage of 100 mg/kg body weight. 6. The anticoagulant and antithrombotic activities of the bis-lactobionic acid amides decrease gradually with the increasing number of methylene groups in the alkylene chain.
摘要
  1. 引入的双乳糖醛酸酰胺代表了一组新的合成聚阴离子,分子量为2387至2514d。这些化合物是均质的且化学性质明确。2. 这些化合物对体外凝血参数(活化部分凝血活酶时间、希普测试、抗Xa、凝血酶时间和抗IIa)仅有轻微影响。3. 在以内皮损伤作为血栓形成刺激因素的大鼠静脉血栓形成模型中,双乳糖醛酸酰胺的抗血栓活性呈剂量和时间依赖性表现。4. LW 10082和LW 10121在剂量约为肝素的十分之一时延长出血时间。这些化合物的安全/有效性指数似乎比肝素更宽。5. 在大鼠的亚慢性毒理学研究中,LW 10082在高达100mg/kg体重的剂量下耐受性良好。6. 双乳糖醛酸酰胺的抗凝和抗血栓活性随着亚烷基链中亚甲基基团数量的增加而逐渐降低。

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