西林瓶和预灌封注射剂吸附破伤风疫苗的非临床制剂安全性研究  

Safety study of non-clinical preparations of adsorbed tetanus vaccine in vial and pre-filled syringe

作　　者：朱楠 马伟 陈雪 邵丽娟 黄元元 胡利平 胡文龙 葛海兵 王坚 沈微微 Zhu Nan;Ma Wei;Chen Xue;Shao LiJuan;Huang Yuanyuan;Hu Liping;Hu Wenlong;Ge Haibing;Wang Jian;Shen Weiwei(R&D Department,Aimei Weixin Biopharmaceutical(Zhejiang)Co.,Ltd,NingBo 315600,China;Toxicology Department,WestChina-Frontier PharmaTech Co.,Ltd.,Chengdu 610041,China;Department of Quality Control,AIM Explorer Life Sciences Co.,Ltd.,Shanghai 201100,China)

机构地区：[1]艾美卫信生物药业(浙江)有限公司研发部,宁波315600 [2]成都华西海圻医药科技有限公司毒理研究部,成都610041 [3]艾美探索者生命科学研发有限公司质量控制部,上海201100

出　　处：《国际生物制品学杂志》2024年第2期79-84,共6页International Journal of Biologicals

基　　金：宁波市科技创新2025重大专项(重大科技任务攻关项目)(2022Z122)。

摘　　要：目的研究西林瓶和预灌封注射剂吸附破伤风疫苗在非临床阶段的安全性差异,为预灌封注射剂型临床使用的安全性提供参考。方法对西林瓶和预灌封注射剂吸附破伤风疫苗分别进行体外溶血试验、主动全身过敏试验和肌肉刺激试验以评价其制剂安全性。取兔1只进行体外溶血试验,观察样品的溶血情况;取豚鼠36只进行主动全身过敏试验,观察豚鼠出现的全身反应及死亡情况;取兔16只进行肌肉刺激试验,观察注射局部的刺激反应,并进行组织病理学检查。结果2种吸附破伤风疫苗在体外溶血试验中,对兔红细胞皆有凝聚作用,未见溶血;主动全身过敏试验中,在0.1 ml和0.5 ml致敏剂量下均未见过敏反应;肌肉刺激试验中,单次注射0.5 ml后注射部位肌肉可见轻度刺激性,停药后可恢复,与疫苗中含有铝佐剂相关。结论西林瓶和预灌封注射剂吸附破伤风疫苗安全性均良好。Objective To investigate the difference in safety of vial and prefilled syringe of adsorbed tetanus vaccine in the non-clinical phase and to provide reference for the safety of clinical use of prefilled syringe.Methods The safety of adsorbed tetanus vaccine in vial or prefilled syringe was evaluated by in vitro hemolysis test,active systemic allergy test and muscle stimulation test.One rabbit was taken for in vitro hemolysis test to observe the hemolysis of the sample.Thirty-six guinea pigs were taken for active systemic allergy test to observe the systemic reaction and death.Sixteen rabbits were taken for muscle stimulation test,and the stimulation reaction of injection area was observed visually,and pathological examination was carried out on tissues.Results Both adsorbed tetanus vaccines had a coagulation effect on rabbit red blood cells with no hemolysis after in vitro hemolysis test.After active systemic allergy test,there was no allergic reaction at the sensitization doseges of 0.1 ml and 0.5 ml.Through the muscle stimulation test,a single injection of 0.5 ml showed mild irritation on the muscles at the injection site which recovered after the treatment stopped,which was related to the aluminum adjuvant contained in the vaccine.Conclusion The adsorbed tetanus vaccines in vial and prefilled syringe both show good safety.

关 键 词：预灌封注射器 破伤风 体外溶血试验 主动全身过敏试验 肌肉刺激试验 

分 类 号：R378.8[医药卫生—病原生物学] Q939.93[医药卫生—基础医学]