Experimental Study on the Safety and Pharmacology of Aerosol Inhalation of Qingyan Lihou Atomization Liquid (清咽利喉雾化液雾)

Author：SONG Ling, GAO Yunhang, LI Han, CHEN Tengfei, HOU Hongping, PENG Bo, CHEN Weiya, YE Zuguang, ZHANG Guangping

Unit：Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

Quote：引用：宋玲，高云航，李晗，陈腾飞，侯红平，彭博，陈韡亚，叶祖光，张广平.清咽利喉雾化液雾化吸入给药的安全性和药效研究[J].中医药导报,2025,31(3):10-17.

DOI：10.13862/j.cn43-1446/r.2025.03.003

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Abstract：

Objective: To explore the feasibility of aerosol inhalation of Qingyan Lihou atomization liquid through safety of inhalation and pharmacology study in vivo and vitro, provide reference for clinical application. Methods: According to The Technical Guidelines for The Study of Irritability, Hhypersensitivity and Hemolysis of Drugs, the irritative reaction of Qingyan Lihou atomization liquid inhalation on rat respiratory mucosa were investigated by pathological examination and leukocyte count in bronchoalveolar lavage fluid (BALF). The anaphylaxis of guinea pigs was studied by observing the symptoms of anaphylaxis. In vivo, Qingyan Lihou atomization liquid was divided into three doses, low dose (atomization for 5 min), medium dose (atomization for 10 min) and high dose (atomization for 20 min). The antitussive effects of Qingyan Lihou atomization liquid were observed using the concentrated ammonia water cough method. The expectorant effects of Qingyan Lihou atomization liquid were established by phenol red expectorant test on mice. In vitro, Qingyan Lihou atomization liquid were divided into three doses, low dose (0.10%), medium dose (0.25%) and high dose (0.50%). Protection of Qingyan Lihou atomization liquid on damage of cell membrane and mitochondria in BEAS-2B cell induced by CSE and MH-S cell induced by LPS were detected by cell triple staining method through BioTekCytaion5 high content imaging. It was used to verify whether Qingyan Llihou atomization liquid can suppress inflammation in BEAS-2B cell induced by CSE and MH-S cell induced by LPS. Influence on oxidative stress of MH-S cell was discussed by MH-S cell induced by H2O2. Results: Aerosol inhalation of Qingyan Lihou atomization liquid didn't show obvious irritation on oral and nasal mucosa of rats, and active whole body allergy test was negative. In ammonia cough method, the positive control group showed longer cough latency than model group (P<0.01), and the positive control group and high dose group showed less coughing frequency than model group (P<0.01 or P<0.05). In the method of phenol red excretion experiment, the positive control group, high dose group and medium dose showed more tracheal phenol red excretion than model group (P<0.01). In vitro, low dose, medium dose and high dose groups showed protective effect on damage of BEAS-2B cells induced by CSE and MH-S cells induced by LPS. The content of IL-1β and TNF-αwere significantly decreased in BEAS-2B cells induced by CSE and MH-S cells induced by LPS, in the high dose group. Low dose, medium dose and high dose groups improved the oxidative stress of MH-S cells induced by H2O2, and the high dose group significantly increased the SOD level of MH-S cells induced by H2O2. Conclusion: There was no obvious irritation of oral mucosa, throat tissue and respiratory system in rats, and no systemic allergic reaction was observed in guinea pigs. Inhalation of Qingyan Lihou atomization liquid showed antitussive and expectorant effect. Qingyan Lihou atomization liquid had protective effects on BESA-2B cell injury induced by CSE, MH-S cell injury induced by LPS and oxidative stress induced by H2O2.

Key words：Qingyan lihou atomization liquid; inhalation; safety; antitussive and expectorant; cell injury protection; mice; guinea pig

摘要：目的：通过对清咽利喉雾化液进行安全性评价和药效学研究，评估清咽利喉雾化液吸入给药的可行性。方法：参照《药物刺激性、过敏性和溶血性研究技术指导原则》，通过病理检查及肺泡灌洗液白细胞计数来观察清咽利喉雾化液吸入给药对大鼠呼吸道黏膜的刺激性反应。通过对过敏反应症状的观察来探究其对豚鼠的过敏反应。体内实验方面，将清咽利喉雾化液分为低（雾化5 min）、中（雾化10 min）、高（雾化20 min）3个剂量，采用浓氨水引咳法研究清咽利喉雾化液吸入对咳嗽小鼠的止咳作用，应用酚红排泌法研究其对酚红排泌模型小鼠的祛痰作用。体外实验方面，将清咽利喉雾化液分为低（0.10%）、中（0.25%）、高（0.50%）3个剂量，采用BioTekCytaion5高内涵成像仪，通过三染法观察不同浓度的清咽利喉雾化液对香烟烟雾提取液（CSE）诱导的BEAS-2B细胞和细菌内毒素（LPS）诱导的MH-S细胞的细胞膜和线粒体损伤的保护作用。采用CSE诱导BEAS-2B细胞损伤，采用LPS诱导MH-S细胞损伤，观察清咽利喉雾化液对BEAS-2B细胞损伤及MH-S细胞损伤的保护作用。采用H2O2诱导MH-S细胞氧化应激，探讨清咽利喉雾化液对MH-S细胞氧化应激的影响。结果：清咽利喉雾化液吸入给药对大鼠鼻黏膜和口腔黏膜均无明显的刺激性，亦未出现豚鼠全身过敏反应。小鼠咳嗽实验中，阳性对照组小鼠咳嗽潜伏期长于模型对照组（P<0.01或P<0.05），阳性对照组和清咽利喉雾化液高剂量组小鼠咳嗽次数少于模型对照组（P<0.05）；酚红排泌实验中，阳性对照组、清咽利喉雾化液高剂量组、清咽利喉雾化液中剂量组小鼠酚红排泌均高于模型对照组（P<0.01）。体外实验中，清咽利喉雾化液低、中、高剂量组对CSE诱导的BEAS-2B细胞和LPS诱导的MH-S细胞的损伤都有保护作用；清咽利喉雾化液高剂量组能降低CSE诱导的BEAS-2B细胞和LPS诱导的MH-S细胞的IL-1β和TNF-α的含量；清咽利喉雾化液低、中、高剂量组对H2O2诱导的MH-S细胞氧化应激有改善作用，其中清咽利喉雾化液高剂量组能升高H2O2诱导的MH-S细胞的SOD水平。结论：清咽利喉雾化液吸入给药未对大鼠口腔黏膜、咽喉部组织及呼吸系统造成明显的刺激作用，豚鼠未产生全身过敏反应。清咽利喉雾化液吸入给药具有一定止咳祛痰功效。清咽利喉雾化液对CSE导致的BESA-2B细胞损伤、LPS诱导的MH-S细胞损伤以及H2O2诱导的MH-S细胞氧化应激均有一定的改善作用。

关键词：清咽利喉雾化液；雾化吸入；安全性；镇咳祛痰；细胞损伤保护；小鼠；豚鼠

Release time：2025-12-14

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