新型水包油佐剂SP01的安全性评价  

Safety of a novel oil-in-water adjuvant SP01

作　　者：姜佳琪 于姝[2] 邢丽[2] 段跃强[2] 孟和宝力高 牛燕[1] 王希良[2] 额尔敦[1,3] 

机构地区：[1]内蒙古医科大学基础医学院免疫学教研室,内蒙古呼和浩特010021 [2]中国人民解放军军事医学科学院微生物流行病研究所病原微生物生物安全国家重点实验室,北京100071 [3]中国人民解放军第253医院免疫中心,内蒙古呼和浩特010021

出　　处：《中国生物制品学杂志》2014年第7期885-889,共5页Chinese Journal of Biologicals

摘　　要：目的通过动物实验评价新型水包油佐剂SP01的安全性。方法通过昆明小鼠安全药理试验、昆明小鼠急性毒性试验、Hartley豚鼠过敏反应试验、溶血性试验、日本大白兔局部刺激性试验、SD大鼠长期毒性试验及BALB/c小鼠致突变、致畸、致瘤试验,对水包油佐剂SP01的安全性进行全面评价。结果水包油佐剂SP01对昆明小鼠的自主活动无明显影响;急性毒性试验中可观察到水包油佐剂SP01组昆明小鼠给药后无死亡,体重明显增加,且各组织器官无病理变化;水包油佐剂SP01注射豚鼠未见任何过敏反应及症状;溶血性试验结果显示,水包油佐剂SP01在体外对兔红细胞无溶血作用,不引起红细胞凝聚;将水包油佐剂SP01经日本大白兔耳缘静脉注射连续刺激5 d后,佐剂组与氯化钠注射液组家兔耳缘静脉给药部位肉眼观察均无明显变化,病理切片显微镜观察均未见炎性浸润、血管周围组织出血及坏死等刺激现象;将水包油佐剂SP01经肌肉连续注射大鼠1个月,佐剂组大鼠体重明显增加,精神状态、食欲、睡眠情况与氯化钠注射液组无明显差异,停药后连续观察3个月,大鼠精神状态、食欲、睡眠情况均良好;将水包油佐剂SP01连续经BALB/c小鼠腿部肌肉注射14 d后,其肌肉组织病理切片显示,与氯化钠注射液组小鼠的肌肉组织无明显差异。结论水包油佐剂SP01对实验动物无急性毒性、过敏反应、局部性刺激、长期毒性及致突变、致畸、致瘤作用,是安全、可应用的油类佐剂,本研究为该系列水包油佐剂的临床应用提供了实验依据。Objective To evaluate the safety of a novel oil-in-water adjuvant by animal experiment. Methods The safety of oil-in-water adjuvant SP01 was evaluated comprehensively by pharmacological test and acute toxicity test in Kunming mice,allergy test in Hartley guinea pigs,hemolytic test,local irritation test in Japanese white rabbits,longterm toxicity test in SD rats,as well as mutagenicity,teratogenicity and carcinogenicity tests in BALB / c mice. Results Oil-in-water adjuvant SP01 showed no significant effect on the autonomous activity of Kunming mice. All the mice in acute toxicity test survived after treatment with the adjuvant,with bodyweights gained significantly but no pathological change in various tissues or organs. No any allergic reactions or symptoms were observed in the guinea pigs treated with the adjuvant. The adjuvant showed no hemolytic effect in vitro and caused no red cell agglutination. No obvious changes were observed visually in the injection sites of rabbits injected i.v. with the adjuvant and sodium chloride solution at ear edges for 5 d,while no inflammatory infiltration,bleeding or necrosis in peripheral tissues of blood vessels by microscopy of pathological sections. The bodyweights of rats injected i.m. with the adjuvant for one month increased significantly,while the spiritual status,appetite and sleeping showed no significant difference with those injected with sodium chloride solution as control and were normal during an observation period of 3 months after withdrawing of injection. Pathological examination showed no significant difference between the muscle tissues of mice injected i.m. with the adjuvant and with sodium chloride solution for 14 d. Conclusion Oil-in-water adjuvant SP01 showed no acute toxicity,allergic reaction,local irritation,long-term toxicity or mutagenicity,teratogenicity and carcinogenicity in animal experiment,which was safe and applicable. The study provided an experimental basis for clinical application of this series of oil-in-water adjuvant.

关 键 词：水包油佐剂 动物实验 安全性评价 

分 类 号：R392-33[医药卫生—免疫学]