两性霉素B脂质体局部毒性研究  

Local Toxicity Evaluation of Amphotericin B Liposome

作　　者：方云涛 蔡正清 邵卿 FANG Yuntao;CAI Zhengqing;SHAO Qing(Jiangsu Pharmaceutical Research Institute Co.,Ltd,Nanjing Jiangsu 210000,China)

机构地区：[1]江苏省药物研究所有限公司,江苏南京210000

出　　处：《药品评价》2023年第7期821-824,共4页Drug Evaluation

摘　　要：目的评价两性霉素B脂质体(Lipo-AB)的安全性。方法(1)血管刺激性试验:成年健康实验兔耳缘静脉滴注Lipo-AB,每天一次,连续3 d。给药容积为5 mL/kg。观察血管组织是否有变性或坏死等刺激性反应。(2)体外溶血:将不同量的供试品、兔红细胞悬液、葡萄糖注射液及蒸馏水加入试管,观察3 h内是否出现溶血或红细胞聚集现象。(3)主动全身过敏试验:健康豚鼠致敏给药3次,隔日腹腔注射,末次致敏后14 d静脉激发。观察动物注射后有无过敏反应症状。(4)被动皮肤过敏试验:在SD大鼠背部皮内注射抗体血清,24 h后激发,测量皮肤内侧蓝斑的直径。结果2 mg/mL Lipo-AB并未对家兔血管产生刺激性反应;亦未发现溶血/红细胞凝集现象;豚鼠全身主动过敏试验及被动皮肤过敏反应结果均为阴性。结论在此次实验条件下,Lipo-AB并未显示出局部毒性。Objective To evaluate the safety of amphotericin B liposome(Lipo-AB).Methods 1.Blood vascular irritation test:the adult healthy experimental rabbits were intravenously injected with Lipo-AB at the ear margin,once a day for 3 days at the dose of 5 mL/kg,then examined the the irritating reactions such as degeneration or necrosis at the injection place.2.In vitro hemolysin test:after adding different amounts of test substance,rabbit red blood cell suspension,glucose injection and distilled water in the tube,then observed whether hemolysis or red blood cell aggregation occurs within 3 hours.3.Systemic active anaphylaxis test:guinea pigs were injected with Lipo-AB,once every other day,continuously for three times.After 14 d from the end time of sensitization,to stimulation and to observe whether allergic reactions occurred within 30 mins.4.Passive cutaneous anaphylaxis test:SD rats were injected antiserum for inducing passive sensitization,stimulated after 24 hours,we examine the diameter of blue spots inside of the skin.Results Under the dosage of 2 mg/mL,no hemolysis,agglutination,and irritation of vascular was observed,the reaction of systemic active anaphylaxis test and passive cutaneous anaphylaxis test were negative.Conclusion under the present experimental condition,Lipo-AB did not showed any local toxicity.

关 键 词：两性霉素B脂质体 毒性试验 过敏反应 刺激性 溶血试验 

分 类 号：R965[医药卫生—药理学]