摘要
目的通过研究重组人干扰素α2b注射液(假单胞菌)及羟乙基淀粉雾化吸入对SD大鼠生理指标以及肺、气管、支气管等组织器官的影响,以探讨该药物和辅料用于雾化吸入的安全性。方法将大鼠随机分为羟乙基淀粉40组和重组人干扰素α2b组,分别给予500万IU/ml重组人干扰素α2b注射液(假单胞菌)和6%羟乙基淀粉40注射液,均按照1∶2比例用0.9%生理盐水进行稀释,每天1次、每次30 min雾化吸入给药,连续给药14 d,停药恢复14 d。给药期及恢复期每天观察各组大鼠一般状况,每周测定1次体重及摄食量。给药结束及恢复期结束进行血液学、血液生化检测及大体解剖观察、脏器重量测定、组织病理学检查。结果试验药物的质量中位数气动粒径为3.56 μm,几何标准偏差为1.84 μm,符合经雾化吸入抵达和在下呼吸道沉积的粒径要求;羟乙基淀粉40组和重组人干扰素α2b组大鼠一般状况、体重及摄食量、血液学及血液生化指标均未见异常;两组大鼠口腔黏膜、舌、鼻腔(鼻旁窦)、喉、气管、主支气管、肺未见异常组织病理学改变,心脏、肝脏、脾脏、肾脏、生殖系统等所检查的脏器或组织亦均未见异常组织病理学改变。结论重组人干扰素α2b注射液(假单胞菌)的药雾粒径能够抵达并在下呼吸道沉淀,连续雾化吸入给药14 d具有良好的安全性,所用辅料羟乙基淀粉40雾化吸入亦具有较高的安全性。
Objective To investigate the effects of recombinant human interferon alpha 2b injection(P.putida)and hydroxyethyl starch inhalation on physiological indexes and tissues and organs of SD rats, such as lungs, trachea and bronchus, and thus to explore the safety of the drug and excipients for inhalation. Methods Rats were randomly divided into two groups(hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group).5 million IU/ml recombinant human interferon alpha 2b injection or 6% hydroxyethyl starch 40 injection were given respectively, which were diluted with 0.9% sodium chloride injection in a radio of 1: 2.Both groups were given aerosol inhalation for 30 minutes once a day for 14 days.Within 14 days after administration, the behavior of rats and the degree of toxicity were continuously observed.During the drug administration and recovery period, the clinical signs of the rats in each group were observed daily, and the body weight and food consumption were measured once a week.At the end of drug administration and the end of recovery period, hematology test, blood biochemical test, gross anatomical observation, organ weight determination, and histopathological examination were performed. Results The mass median aerodynamic diameter(MMAD)of the drug mist was 3.56 μm, and the geometric standard deviation(GSD)was 1.84 μm, which met the particle size requirements of arrival and deposition in the lower respiratory tract via atomization inhalation.No abnormality in clinical signs, body weight and food consumption, hematology and blood biochemical indexes were found in hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group.No abnormal histopathological changes were observed in oral mucosa, tongue, nasal cavity(paranasal sinus), larynx, trachea, main bronchial tube, lung, heart, liver, spleen, kidney, reproductive system and other organs or tissues examined. Conclusion Results suggest the drug particle size of recombinant human interferon alpha 2b injection(pseudomonas)can reach
作者
刘斌
尚云晓
卢叶丹
Liu Bin;Shang Yunxiao;Lu Yedan(National Chengdu Center for Safety Evaluation of Drugs, Chengdu 610041, China;Department of Pediatric Respiratory, Shengjing Hospital of China Medical University, Shenyang 110004, China;Toxicology Department, National Chengdu Center for Safety Evaluation of Drugs, Chengdu 610041, China)
出处
《国际儿科学杂志》
2019年第9期692-697,共6页
International Journal of Pediatrics
关键词
重组人干扰素Α2B
注射液
雾化吸入
羟乙基淀粉40
安全性
Recombinant human interferon alpha 2b
Injection
Aerosol inhalation
Hydroxyethyl starch 40
Safety
