目的 通過霧化微細(xì)粒子空氣動力學(xué)特性測定和小鼠經(jīng)口鼻霧化吸入毒性研究，評估喜炎平注射液霧化吸入可行性，為其臨床應(yīng)用提供參考。方法 采用新一代級聯(lián)撞擊器和霧化器系統(tǒng)（采用2種霧化器，壓縮空氣霧化器和超聲霧化器，測算藥物霧化吸入空氣動力學(xué)直徑（MMAD）、幾何標(biāo)準(zhǔn)偏差（GSD）、微細(xì)粒子分?jǐn)?shù)（FPF），并采用呼吸模擬器測定喜炎平注射液霧化吸入的遞送總量和遞送速率。采用inExpose吸入染毒暴露系統(tǒng)，小鼠經(jīng)口鼻吸入喜炎平注射液低、中、高劑量（25、50、125 mg/kg，是臨床等效劑量的3、6、15倍）連續(xù)4周，停藥恢復(fù)2周，吸入正常空氣為對照組。觀察小鼠一般狀態(tài)，每組動物在給藥期結(jié)束和恢復(fù)期結(jié)束各處死10只，雌雄各半。小鼠處死前取血，檢測血液學(xué)指標(biāo)、血清生化指標(biāo)；動物均乙醚吸入麻醉后進(jìn)行尸體剖檢，原位觀察組織外觀，重點(diǎn)觀察其口腔黏膜、鼻中隔黏膜、氣管及肺部；剖取主要臟器——腦、肝、脾、腎、心、肺，進(jìn)行臟器系數(shù)檢測；取左肺進(jìn)行HE染色，觀察組織病理學(xué)變化。結(jié)果 喜炎平注射液可以霧化吸入肺部（支氣管、細(xì)支氣管）并有一定比例在肺部沉降存留，兒童、成人模式下遞送總量、遞送速率依次增加。吸入刺激性結(jié)果顯示，試驗(yàn)期間未觀察到動物死亡和咳嗆等刺激性異常表現(xiàn)；與對照組比較，喜炎平注射液各劑量組動物血液學(xué)指標(biāo)、血清生化、臟器系數(shù)、主要組織檢查、肺部組織病理學(xué)均無顯著改變。結(jié)論 在體外霧化吸入模擬條件下，喜炎平注射液可吸入肺部（支氣管、細(xì)支氣管），并有一定比例在肺部沉降存留；連續(xù)吸入4周對小鼠呼吸道黏膜和肺部無顯著刺激性和病理學(xué)改變，初步認(rèn)為其霧化吸入給藥是安全可行的。

Objective To explore the feasibility inhaled atomized Xiyanping Injection through determination of aerodynamic characteristics of atomized fine particles and safety of atomized inhalation in mice provide reference for clinical application. Mehtods The new generation of cascade impactor and atomizer system (There were two kinds of atomizers, the compressed air atomizer:Germany Bray medical atomizer Turbo BOY N and the ultrasonic atomizer:Yuyue medical atomizer 503M) was used with COPLEY Scientific Limited CITDAS software to calculate mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD) and fine particle fraction (FPF). The total delivery amount and delivery rate of Xiyanping Injection were measured by respiratory simulator. Inexpose inhalation exposure system was used, mice were exposed to low, medium and high doses of Xiyanping injection (25, 50 and 125 mg/kg, which were 3, 6 and 15 times of the clinical equivalent dose) through oral and nasal inhalation for 4 consecutive weeks, withdrawal for two weeks of drug, mice in the control group inhaled normal air. To observe the general state of mice, 10 mice in each group were killed at the end of the administration period and the end of the recovery period, half male and half female. Blood samples were taken before the mice were killed to detect the changes of hematological indexes and serum biochemistry; autopsy was performed after the animals were anesthetized with ether inhalation, and the appearance of the tissues was observed in situ, focusing on the oral mucosa, nasal septum mucosa, trachea and lung; the main organs brain, liver, spleen, kidney, heart and lung were dissected to detect the organ coefficient; the left lung was stained with HE to observe the histopathology change. Results Xiyanping Injection can be atomized into the lungs (bronchi and bronchioles) and a certain proportion of it remains in the lungs. The total delivery amount and delivery rate of Xiyanping Injection increase in turn in children and adults. The results of inhalation irritation showed that no death and cough were observed during the experiment. Compared with control group, there were no significant changes in hematological indexes, serum biochemistry, organ coefficient, main histological examination and lung histopathology in all dose groups of Xiyanping Injection. Conclusion Under the condition of in vitro the existing nebulized inhalation, Xiyanping Injection can be inhaled into the lungs (bronchi, bronchioles) and a high proportion of drugs remain in the lungs, and there was no obvious irritation to the respiratory mucosa, indicating that the application of nebulized inhalation is relatively safe and feasible.

R965.3