一种人凝血因子Ⅷ产品的临床前药物安全性评价

Safety evaluation on human coagulation factor Ⅷ

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 safety of a plasma derived human coagulation factor Ⅷ（ FⅧ）. Methods Abnormal toxicity test were performed on rat guinea pig according to Chinese Pharmacopoeia. Hemolysis test of rabbit erythrocyte was performed by tube method in vitro. Rabbit vascular irritation test was performed by self-control method. The toxicity of the reagent residues was analyzed. Results No abnormal toxicity,no hemolysis reaction,no irritant reaction were found in the above tests. All the reagent residues were in safe ranges. Conclusion According to the results of pharmacological,toxicological test and the virus safety test,this FⅧ product is safety for clinical use.