猪源纤维蛋白封闭剂的急性毒性研究

摘要

Objective:The study was designed to investigate the acute toxicity in animals of Porcine Fibrin Sealant Kit,to understand the potential toxic target organs and reversible degree of damage,and to provide reference for the main observation indexes in clinical trials.Methods:In this study,acute toxicity test of single intraperitoneal injection administration was studied in ICR mice,SD rats,and Beagles,and acute toxicity was investigated in SD rats with topical administration on hepar.Twenty-one days had needed to observe for searching the potential toxic reaction.After the gross anatomy,there were no abnormal toxic reactions were observed with the naked eye.Results:In these conditions,the LD50 of this kit was greater than 2280 mg/kg in mice through intraperitoneal injection;The maximum tolerance dose in rats by intraperitoneal injection of fibrin sealant was 684 mg/kg;The maximum tolerance dose of fibrin sealant by topical administration on rat hepar was 342 mg/kg;Concentration of 68 mg/kg and 228 mg/kg were intraperitoneal injection in Beagles,and no observable adverse effect level(NOAEL)concentration was 68 mg/kg and the minimum toxic reaction dose was 228 mg/kg of the kit.Conclusion:There was no obvious toxicity in animals of Porcine Fibrin Sealant Kit within clinical dosage.%目的:研究猪源纤维蛋白封闭剂对机体的急性毒性反应,了解毒性靶器官和损害的可逆程度,为临床试验主要观察指标提供参考.方法:本研究通过对ICR小鼠、SD大鼠和Beagle犬进行腹腔单次给药急性毒性研究,并对SD大鼠肝脏局部给药急性毒性研究,观察期为21天,经大体解剖后肉眼观察有无异常.结果:在本试验条件下,腹腔注射纤维蛋白封闭剂对小鼠的半数致死量LD50大于2280 mg/kg;腹腔注射纤维蛋白封闭剂对大鼠的最大耐受量为684 mg/kg;剖腹肝脏局部给予纤维蛋白封闭剂对大鼠的最大耐受量为342 mg/kg;Beagle犬腹腔注射纤维蛋白封闭剂68mg/kg和228mg/kg,最大无毒性反应剂量为68 mg/kg,最小毒性反应剂量为228 mg/kg.结论:猪源纤维蛋白封闭剂在临床剂量使用时无明显毒性反应.