摘要
目的对国产药用气雾剂辅料1,1,1,2-四氟乙烷(hydrofluoroalkane-134a,HFA-134a)进行吸入毒理安全性评价。方法对国内2个主要生产厂家的药用吸入气雾剂HFA-134a样品进行大鼠21 d重复吸入亚慢性毒性试验和Hartley豚鼠主动全身过敏试验。结果2个厂家的HFA-134a剂量分别为(2140±58)g·m^(-3)和(2129±59)g·m^(-3)时,21 d重复吸入(每天2 h),出现统计学差异的指标有:血液学部分指标(中性粒细胞数、嗜碱性粒细胞、嗜碱性粒细胞比率、单核细胞比率、红细胞容积、血小板计数)、血液生化学部分指标(白蛋白、总胆红素、氯离子、钾离子)、尿液检测部分指标(亚硝酸盐、白细胞、尿胆原、蛋白和胆红素)、部分脏器器官的脏器湿重值和脏器系数值(肾脏、胸腺、心脏、垂体、肺脏)。未见豚鼠全身致敏反应。结论国产药用气雾剂辅料HFA-134a在相当于临床最大用量的250倍下连续染毒21 d,对大鼠部分脏器和血尿生化指标有一定的毒性作用,但在临床正常应用中是否吸入安全还需进一步进行安全性评价研究。
OBJECTIVE To evaluate the inhalation safety of domestic pharmaceutical metered-dose inhalers accessories hydrofluoroalkane(HFA)-134a.METHODS The 21 d repeat dose inhalation toxicity study and Hartley guinea pig active systemic anaphylaxis for samples from two major domestic manufacturers were tested.RESULTS SD rats were exposed nose-only separately to the samples from two major domestic manufacturers at the concentration of(2140±58)g·m^(-3) and(2129±59)g·m^(-3) respectively for 21 consecutive days(2 h each day),there were statistically significant differences in the following indicators:some indicators of hematology such as neutrophil count,basophil,basophil ratio,monocyte ratio,hematocrit and platelet count,some indicators of blood biochemistry such as albumin content,total bilirubin content,chloride ion and potassium ion,some indicators of urine such as nitrite,leukocytes,urobilinogen,protein and bilirubin,organ weight and coefficients of kidney,thymus,heart,pituitary and lung.No systemic sensitization reaction were observed in guinea pigs.CONCLUSION The domestic pharmaceutical HFA-134a have certain toxic effects on some organs,blood and urine biochemical indicators of SD rats exposed to 250 times of the clinical maximum dose for continuously 21 d,however,further research is need to access whether inhalation is safe in normal clinical dose.
作者
赵燕君
林飞
仪忠勋
孙会敏
杨会英
ZHAO Yanjun;LIN Fei;YI Zhongxun;SUN Huimin;YANG Huiying(NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,National Institutes for Food and Drug Control,Beijing 100050,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2024年第3期341-346,共6页
Chinese Journal of Modern Applied Pharmacy
基金
中国食品药品检定研究院中青年发展研究基金课题(2020C2)。
关键词
药用吸入气雾剂
抛射剂
1
1
1
2-四氟乙烷
吸入毒理
安全性评价
pharmaceutical metered-dose inhalers
propellant
hydrofluoroalkane-134a
inhalation toxicology
safety evaluation
作者简介
赵燕君,女,硕士,助理研究员,E-mail:zhaoyanjun24@163.com;通信作者:孙会敏,男,博士,研究员,E-mail:sunhm@126.com;通信作者:杨会英,女,主任技师,E-mail:yanghuiying@nicpbp.org.cn。
