人凝血因子Ⅷ血管刺激性和溶血性试验研究

Experimental Study on Vascular Irritation and Hemolysis Test of Human Coagulation Factor Ⅷ

目的:评价公司自制人凝血因子Ⅷ产品的血管刺激性和溶血性。方法:依据《药品注册管理办法》和《药物刺激性、过敏性和溶血性研究技术指导原则》中有关规定,采用新西兰兔自身左右侧耳朵对照,每天给药1次,连续8 d,观察血管刺激性症状;末次给药后72 h、14 d分别取4只动物解剖,进行病理制片和组织病理学检查;以新西兰兔红细胞作为体外溶血试验对象,设阴性对照管(氯化钠注射液)、阳性对照管(注射用水)、不同药品稀释管,加样后置于37℃恒温箱中温育3 h,分别于15 min、30 min、45 min、1 h、2 h、3 h观察,判断红细胞溶解和凝集情况。结果:给药期间和停药期间,动物的一般观察未见明显异常。组织病理学检查及评分结果显示,末次给药后72 h和14 d,人凝血因子Ⅷ对新西兰兔耳缘静脉无刺激。阳性对照溶血反应为阳性,阴性对照和人凝血因子Ⅷ的各稀释度药液溶血反应均为阴性。结论:自制人凝血因子Ⅷ产品对新西兰兔未产生溶血性和血管刺激性。

Objective:To evaluate the vascular irritation and hemolysis of human coagulation factorⅧ.Methods:According to the Relevant Provisions of the Measures for the Administration of Drug Registration and the Technical Guidelines for the Study of Drug Irritation,Anaphylaxis And Hemolysis,the left and right sides of ear of New Zealand rabbits are used as controls.The drug is administered once a day for 8 consecutive days to observe the vascular irritation symptoms.Four animals are dissected 72 hours and 14 days after the last administration for pathological production and histopathological examination.New Zealand rabbit red blood cells are used as hemolysis test object in vitro.Negative control tube(sodium chloride injection),positive control tube(water for injection)and dilution tube of different drugs are set.After adding samples,they are incubated in 37℃incubator for 3 hours,and then observed in 15 minutes,30 minutes,45 minutes,1 hour,2 hours and 3 hours to determine the dissolution and agglutination of red blood cells.Results:There is no obvious abnormality in the general observation of animals during the administration period and the withdrawal period.Histopathological examination and scoring results show that at 72 hours and 14 days after the last administration,human coagulation factorⅧhad no stimulation on the auricular vein of New Zealand rabbits.The hemolysis reaction of the positive control is positive,while that of the negative control,human coagulation factorⅧand the listed control are all negative.Conclusions:No hemolysis and vascular irritation of the self-made human coagulation factorⅧproduct on New Zealand rabbits.