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目的评价1种以新鲜冰冻血浆为原料制备的人凝血因子Ⅷ(FⅧ)产品的药物安全性。方法按照《中国药典》方法对小鼠和豚鼠腹腔注射FⅧ做异常毒性试验;采用体外试管法进行兔红细胞体外溶血试验;采用同体自身对照法进行兔血管刺激性试验;对FⅧ制备过程的添加剂残留量进行毒理分析。结果小鼠和豚鼠经腹腔注射本品<30min均无异常反应,观察期结束时,小鼠平均增加体重>50%,豚鼠平均增加体重>20%;体外溶血试验在15、30、45min,60、120和180 min均未观察到兔红细胞溶血,也未见红细胞聚集;多次和单次静脉注射新西兰兔,除部分对照组和试验组动物出现由于给药时机械操作或反复给药引起的与本品无关的红斑和轻微血管扩张外,均未见明显异常;本品的铝残留量<30μg/L,抗-A抗-B血凝素均<1∶64,Tween-80残留量<100μg/m L、磷酸三丁酯残留量<10μg/m L、聚乙二醇残留量<0.5 g/L。结论该FⅧ产品经动物及体外的药理毒理试验和病毒安全性试验证明是安全的,可用于临床。
Objective To evaluate the drug safety of a human factor VIII product prepared from fresh frozen plasma. Methods According to “Chinese Pharmacopoeia” method, intraperitoneal injection of FⅧ was performed to mice and guinea pigs for abnormal toxicity test. In vitro rabbit hemolysis of rabbit erythrocytes was performed by in vitro test. Rabbit vascular irritation test was performed by self-control method. Additive residues Amount of toxicological analysis. Results The mice and guinea pigs were injected intraperitoneally with no abnormal reaction for <30 min. At the end of the observation period, the mice gained an average weight of> 50% and the guinea pigs gained an average weight of> 20%. The in vitro hemolysis tests were performed at 15, 30, 45, No rabbit erythrocyte hemolysis or erythrocyte aggregation was observed at 120 and 180 min. New Zealand rabbits were intravenously injected in multiple and single doses except for some of the control and experimental animals, which were caused by mechanical manipulation or repeated administration And the product has nothing to do with erythema and slight vasodilatation, no obvious abnormalities; the product of aluminum residues <30μg / L, anti-A anti-B hemagglutinin <1:64, Tween-80 residues < 100μg / m L, tributyl phosphate residues <10μg / m L, polyethylene glycol residues <0.5 g / L. Conclusion The FⅧ product has been proved safe by animal and in vitro pharmacological and toxicological tests and virus safety tests and can be used clinically.