甲型乙型肝炎联合疫苗的制剂安全性试验研究

目的 评价甲型乙型肝炎联合疫苗是否具有肌肉刺激性、急性毒性和过敏性反应。方法 家兔后肢股四头肌im 0.5 mL甲型乙型肝炎联合疫苗，每天给药1次，连续给药2 d，停药2和21 d后对注射部位进行肉眼和病理组织学检查；小鼠后肢im 0.2 mL甲型乙型肝炎联合疫苗，给药1次后观察小鼠的不良反应情况；豚鼠后肢隔日im 0.5 mL甲型乙型肝炎联合疫苗，连续注射3次，分别于末次致敏后第14和21 d iv给予1.0 mL甲型乙型肝炎联合疫苗进行激发，观察豚鼠30 min内是否出现过敏反应。结果 甲型乙型肝炎联合疫苗可导致注射部位肌肉局灶性炎细胞浸润，停药21 d后肌肉组织无异常；在本实验条件中，未见对小鼠有明显的毒性反应；豚鼠全身主动过敏反应阴性。结论 甲型乙型肝炎联合疫苗无全身主动过敏性反应且毒性较低，对肌肉有轻度的刺激反应，但其刺激作用可恢复。

Safety evaluation of hepatitis A and hepatitis B combined vaccine

Objective To evaluate whether hepatitis A and hepatitis B combined vaccine (HABV) has muscular stimulation, acute toxicity, and anaphylaxis. Methods Rabbits were im administrated with HABV (0.5 mL, once daily continuously for 2 d), and macrography and pathological examination of injection site were conducted on the days 2 and 21 d after the last administration. Mice were im administrated once with HABV (0.2 mL) and observed continuously for 14 d for acute toxical symptoms. Guinea pigs were im administrated with HABV (0.5 mL) every other day for three times successively, and on the Days 14 and 21 after the last sensitization, HABV (1.0 mL) was iv administrated to observe whether the allergic reaction appeared within 30 min. Results It showed that HABV could induce the focal inflammatory cell infiltration and histopathologic changes disappear at day 21 after stopping administration. No evidence of acute toxicity in mice and allergic reaction on guinea pig in vivo was observed. Conclusion There is gentle stimulation on quadriceps femoris in rabbits, no sensitization on guinea pig in vivo, the low toxicity treated with HABV. There is muscular stimulation, which is reversible.