吸入用乙酰半胱氨酸溶液自研药非临床安全性评价  

Non-Clinical Safety Evaluation of Self-Made Acetylcysteine Solution for Inhalation

作　　者：刘静欢 孙立杰[1,3] 杨娴 LIU Jinghuan;SUN Lijie;YANG Xian(Shijiazhuang No.4 Pharmaceutical Co.,Ltd.,Shijiazhuang,Hebei,China 050000;College of Pharmacy,Hebei Medical University,Shijiazhuang,Hebei,China 050000;Hebei Large Capacity Injection Engineering Technology Research Center,Shijiazhuang,Hebei,China 050000)

机构地区：[1]石家庄四药有限公司,河北石家庄050000 [2]河北医科大学药学院,河北石家庄050000 [3]河北省大容量注射剂工程技术研究中心,河北石家庄050000

出　　处：《中国药业》2024年第6期61-64,共4页China Pharmaceuticals

基　　金：河北省创新能力提升计划项目[225A2704D];河北省高层次人才资助项目[B2022003038]。

摘　　要：目的为吸入用乙酰半胱氨酸溶液自研药的临床安全使用提供依据。方法取18只雄性日本大耳白兔,按体质量分层随机化分组法分为阴性对照组(等体积0.9%氯化钠注射液)、上市品对照组(原研药0.1 mg/mL)和给药组(自研药0.1 mg/mL),各6只。雾化吸入给药35 mg/kg,给药体积均为0.35 mL/kg,各组均给予相应药物,每日上午、下午各1次,连续14 d。记录呼吸道刺激性症状发生及恢复时间。分别于末次给药24 h及14 d后,各组取3只兔处死并解剖,肉眼观察刺激反应,采用苏木素-伊红染色,观察病理形态。取30只Hartley豚鼠,按体质量分层随机化分组法分为阴性对照组(0.9%氯化钠注射液0.8 mL/d)、阳性对照组(0.9%氯化钠注射液0.8 mL/d)、上市品对照组[原研药80 mg/d(0.8 mL/d)]及低剂量组[自研药40 mg/d(0.4 mL/d)]和高剂量组[自研药80 mg/d(0.8 mL/d)],各6只,各组动物隔日致敏(10%卵白蛋白溶液0.6 mL/d)1次,共3次。分别于末次致敏14 d及21 d后,各组取3只豚鼠,按2倍致敏剂量进行激发。根据过敏反应发生率和发生程度综合评价主动全身过敏反应发生情况。结果各组兔的外观、行为、粪便等均正常,给药后无咳嗽等症状;大体解剖均未见明显异常;与阴性对照组和上市品对照组比较,给药组未见药物延迟或蓄积作用。各组豚鼠未出现与给药相关的异常症状,过敏反应均为阴性。结论吸入用乙酰半胱氨酸溶液自研药对日本大耳白兔无明显呼吸道刺激作用,对豚鼠无明显的全身致敏作用。Objective To provide a basis for the clinical safe use of self-made Acetylcysteine Solution for Inhalation.Methods Eighteen Japanese male white rabbits were selected and divided into the negative control group(equal volume of 0.9%Sodium Chloride Injection),the marketed drug control group(original-patented drug,0.1 mg/mL),the treatment group(self-made drug,0.1 mg/mL)by the stratified randomization method based on body mass,with six rabbits in each group.The drugs were given by atomizing inhalation at a dosage of 35 mg/kg and a volume of 0.35 mL/kg.Each group was given the corresponding drug once a day in the morning and afternoon for 14 d.The occurrence and recovery time of respiratory irritation symptoms was recorded.After 24 h and 14 d of the last administration,three rabbits in each group were selected for dissection respectively,and the irritation reaction was observed by naked eyes.The hematoxylin-eosin staining was used to observe pathological morphology.Thirty Hartley guinea pigs were selected and divided into the negative control group(0.9%Sodium Chloride Injection,0.8 mL/d),the positive control group(0.9%Sodium Chloride Injection,0.8 mL/d),the marketed drug control group[original-patented drug,80 mg/d(0.8 mL/d)],the low-dose group[self-made drug,40 mg/d(0.4 mL/d)],and the high-dose group[self-made drug,80 mg/d(0.8 mL/d)]by the stratified randomization method based on body mass,with six guinea pigs in each group.Guinea pigs in each group were given drugs(10%ovalbumin solution,0.6 mL/d)once every other day for three times.After 14 d and 21 d of the last administration,three guinea pigs in each group were selected and stimulated at the twice dose of the above administration.The active systemic allergic reaction was comprehensively evaluated based on the incidence and severity of the allergic reactions.Results The appearance,behavior and feces in each group of rabbits were normal,and there was no relevant symptoms such as cough;after gross anatomy,no obvious abnormality was observed;and there was no drug dela

关 键 词：吸入用乙酰半胱氨酸溶液 自研药 安全性评价 呼吸道刺激性试验 主动全身过敏性试验 

分 类 号：R965[医药卫生—药理学]