摘要
目的:评价以健康人血浆为原料制备的人纤溶酶原制剂的临床前安全性。方法:采用体外试管法观察制剂对兔红细胞溶血及凝集的影响,并采用分光光度法测定溶血率;采用同体自身对照法进行兔血管刺激性试验;采用小鼠和豚鼠腹腔注射的方法进行异常毒性试验;采用食蟹猴静脉注射进行急性毒性试验。结果:制剂在体外对兔红细胞无溶血作用,不引起兔红细胞凝聚,各供试品管的溶血率均小于5%;在浓度为60 U/mL、剂量为200 U/kg的条件下静脉输注给予新西兰兔,每天给药1次,连续给药7 d,注射局部未见与制剂相关的刺激性反应;小鼠和豚鼠分别经腹腔注射制剂,观察期内无异常反应,观察期结束时每只动物体质量均增加;单日多次经静脉给予食蟹猴人纤溶酶原的最大耐受剂量大于600 U/kg。结论:本制剂安全,可用于临床研究。
Objective:To evaluate the preclinical safety of human plasminogen prepared from healthy human plasma.Methods:The effects of the product on hemolysis and agglutination of rabbit red blood cells(RBCs)are observed using an in vitro test tube method,with hemolysis rates determined by spectrophotometry.The vascular irritation test in rabbits is conducted using a self-controlled method on the same animal.Abnormal toxicity tests are performed by intraperitoneal injection of the product in mice and guinea pigs.Acute toxicity is assessed via intravenous injection in cynomolgus monkeys.Results:The product shows no hemolytic activity or erythrocyte agglutination in vitro,with hemolysis rates in all test tubes lower than 5%.Intravenous infusion in New Zealand rabbits at a concentration of 60 U/mL and dose of 200 U/kg(once daily for 7 consecutive days)induces no irritation at the injection site.Intraperitoneal administration in mice and guinea pigs causes no adverse reactions during the observation period,with all animals exhibiting weight gain by the end of the study.The maximum tolerated dose of human plasminogen in cynomolgus monkeys after singleday multiple intravenous injections exceeded 600 U/kg.Conclusion:This human plasminogen is safe and can be used in clinical studies.
作者
张战
李季男
张运佳
吴燕
侯明霞
甄细娥
王雪云
郭采平
朱路平
ZHANG Zhan;LI Jinan;ZHANG Yunjia;WU Yan;HOU Mingxia;ZHEN Xi’e;WANG Xueyun;GUO Caiping;ZHU Luping(Shenzhen Weiguang Biological Products Co.,Ltd.,Shenzhen 518107,China;Talengen Institute of Life Sciences Co.,Ltd.,Shenzhen 518026,China)
出处
《生物化工》
2025年第4期6-12,共7页
Biological Chemical Engineering
关键词
人纤溶酶原
溶血性
血管刺激性
异常毒性
急性毒性
human plasminogen
hemolysis
vascular irritation
abnormal toxicity
acute toxicity
