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与羧基葡聚糖结合的人血红蛋白作为一种潜在的红细胞替代物。II——药物毒理学评价。

Human hemoglobin conjugated to carboxylate dextran as a potential red blood cell substitute. II--Pharmacotoxicological evaluation.

作者信息

Menu P, Faivre B, Labrude P, Riffard P, Grandgeorge M, Vigneron C

机构信息

Faculté de Pharmacie, Nancy, France.

出版信息

Artif Cells Blood Substit Immobil Biotechnol. 1994;22(3):543-9. doi: 10.3109/10731199409117882.

DOI:10.3109/10731199409117882
PMID:7527720
Abstract

A solution of human hemoglobin bound to benzene tetracarboxylate substituted dextran, whose physicochemical characteristics are defined in part I, was evaluated in vivo as a potential red blood cell substitute. Further experiments show: - the confirmation of a lack of acute toxicity in mice and guinea pigs after injection of 12.5%, 25% and 50% of the blood mass and the absence of death in rabbits having undergone three successive 25% hemorrhagic shocks in three week intervals. A plasma half-life of 9.5 +/- 0.5 hours in 70-75% hemorrhagic shocks on guinea pigs and the absence of dex-BTC-Hb in thoracic and abdominal cavities. No tissue oedema was noticed. Total hemoglobinuria did not exceed 10% of the injected hemoglobin quantity and only involved free hemoglobin. A lack of death in 70-75% hemorrhagic shocks and survival times ranging from 10 hours to 3 days in total exchange transfusions in guinea pig experiments.

摘要

一种结合了苯四羧酸盐取代葡聚糖的人血红蛋白溶液,其物理化学特性在第一部分中已有定义,该溶液在体内被评估为一种潜在的红细胞替代物。进一步的实验表明:在给小鼠和豚鼠注射相当于12.5%、25%和50%血容量的该溶液后,证实其无急性毒性,并且在每隔三周经历三次连续25%失血性休克的兔子中未出现死亡。在豚鼠70 - 75%失血性休克模型中,该溶液的血浆半衰期为9.5±0.5小时,且胸腔和腹腔中未检测到葡聚糖 - 苯四羧酸盐 - 血红蛋白。未观察到组织水肿。总血红蛋白尿不超过注射血红蛋白量的10%,且仅涉及游离血红蛋白。在豚鼠实验的全血交换输血中,70 - 75%失血性休克模型中未出现死亡,存活时间为10小时至3天。

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