中国药业2025，Vol.34Issue(20)：32-35,4.DOI:10.3969/j.issn.1006-4931.2025.20.008
吸入用异丙托溴铵溶液自研药安全性评价
Safety Evaluation of Self-Developed Ipratropium Bromide Solution for Inhalation
摘要
Abstract
Objective To evaluate the safety of self-developed ipratropium bromide solution for inhalation.Methods The aerodynamics particle diameter of self-developed and innovator ipratropium bromide solution for inhalation in first administration of respiratory system irritation test and active systemic anaphylaxis was measured by the aerodynamic particle spectrum.The mass median aerodynamic diameter(MMAD)and geometric standard deviation(GSD)were calculated by TSI software.A total of 18 Japanese white rabbits were randomly divided into the negative control group(0.9%Sodium Chloride Injection),the reference control group(innovator drug)and the test group(self-developed drug),with six rabbits in each group.They were given 2 mL each time by atomization method,4 times a day,for 7 d.24 h after the last administration and after 14 d(the recovery period),the respiratory system reaction was observed,and the histopathological changes of nose,pharynx,larynx,trachea,bronchus and lung were analyzed.A total of 30 Hartley guinea pigs were randomly divided into the negative control group(0.5 mL 0.9%Sodium Chloride Injection),model group(0.6 mL 10%Ovalbumin Solution),reference control group(0.5 mL innovator drug),low-and high-dose groups(0.25 mL and 0.5 mL self-developed drug),with 6 ones in each group.According to the corresponding medication dose of each group,sensitization was induced by atomization,once every other day,a total of 3 times.Excitation by atomization(the excitation amount was twice the sensitization amount)on the 14th and 21st days after the last administration,the allergic reactions were observed.Results The proportions of the aerodynamics particle diameter of self-developed drug and innovator drug in the first administration of respiratory system irritation test were(90.98±1.02)%and(89.14±0.76)%,respectively.The proportions of the aerodynamics particle diameter lower than 5 µm in the first administration of active systemic anaphylaxis self-developed drug and innovator drug were(96.39±0.81)%and(91.59±1.72)%,respectively.The MMAD and GSD were generally consistent,both met the requirements of the Chinese Pharmacopoeia(2020 Edition,Volume Ⅳ).There were no symptoms such as asthma,cough,vomiting,asphyxia and other symptoms,and no obvious respiratory stimulation,there were no significant differences in pathological morphology of nose,pharynx,larynx,trachea,bronchus and lung,and common inflammatory secretions and inflammatory cell infiltration were mainly distributed in nasal cavity,respiratory tract and lung.There was no allergic reaction in guinea pigs in negative control group,reference control group,low-and high-dose groups.Conclusion The particle diameter of self-developed ipratropium bromide solution for inhalation meets the requirements of liquid preparation for atomization,and shows good safety in animal experiments.关键词
吸入用异丙托溴铵溶液/自研药/呼吸系统刺激试验/全身主动过敏试验/雾化吸入/安全性Key words
ipratropium bromide solution for inhalation/self developed drug/respiratory system irritation test/active systemic anaphylaxis/atomization inhalation/safety分类
医药卫生引用本文复制引用
胡皓,杨娴,侯海婷,赵方红,左亚茹,陈伟..吸入用异丙托溴铵溶液自研药安全性评价[J].中国药业,2025,34(20):32-35,4.基金项目
河北省重大科技支撑计划项目[242W2601Z]. （）
