目的 针对热毒宁注射液雾化吸入给药后可能的安全性风险开展研究，为热毒宁注射液雾化吸入临床应用提供基础和依据，探讨中药雾化吸入制剂临床前安全性评价的技术方法。方法 在GLP条件下开展热毒宁注射液大鼠雾化吸入单次给药和重复给药30 d毒性实验，大鼠黏膜刺激（伴随反复给药观察）和豚鼠全身主动过敏实验。在连续给药7 d后，分别在停药1、7、14 d时对热毒宁注射液在肺中检测到的31种成分进行分析。结果 大鼠单次口鼻暴露120 min/次、2次/d，动物未见明显异常；热毒宁低、中、高剂量（30、60、120 min/d）组大鼠口鼻吸入重复给药30 d、恢复期14 d毒性实验对血液学、血液生化、肺系数、尿液、组织病理学未见药物相关的病理改变，对呼吸道黏膜未见刺激性。豚鼠全身主动过敏实验为阴性。所分析到的热毒宁注射液的31种成分在停药14 d后所有成分均检测不到或者在检测限下。结论 热毒宁注射液雾化吸入给药对呼吸道黏膜无刺激和过敏，大鼠口鼻暴露1个月未见明显毒性反应，所测定的31种成分均能够在肺部代谢，无明显沉积。

Objective To carry out a study on the possible safety risks after the administration of Reduning Injection (热毒宁注射液) by atomization inhalation, to provide a basis for the clinical application of Reduning Injection by atomization inhalation, and to explore the methods of preclinical safety evaluation of traditional Chinese medicine nebulized inhalation preparations. Methods Toxicity tests for single-dose administration and repeated-dose administration for 30 d of Reduning Injection by nebulized inhalation in rats, and mucosal irritation in rats (observed with repeated administration) and active systemic anaphylaxis in guinea pigs were carried out under GLP conditions. The 31 components detected by the compositional analysis of Reduning Injection were examined in the lungs by stopping the drug for 1, 7, 14 d after seven consecutive days of administration. Results Rats were exposed orally and nasally 120 min/time, 2 times/d, and animals did not show obvious abnormalities; Reduning Injection low-, medium-, high-dose (30, 60, 120 min/d) groups of rats orally and nasally inhalation repeated administration of 30 d and recovery period of 14 d of toxicity test on the hematology, blood biochemistry, lung coefficients, urine, histopathology did not in the drug-related pathology, the mucous membranes of the respiratory tract did not see the irritation. The active systemic anaphylaxis in guinea pigs was negative. All 31 components analyzed for Reduning Injection were either undetectable or below the detection line after 14 d of withdrawal. Conclusion The nebulized inhalation administration of Reduning Injection did not cause irritation and sensitization to the respiratory mucosa, and no obvious toxic reaction was observed in rats exposed orally and nasally for one month, and all the 31 components determined were able to be metabolized in the lungs without any deposition.

R285.53

中国中医科学院科技创新工程重大攻关项目（CI2021A04615）；国家自然科学基金青年项目（82204740）；中国中医科学院中药研究所中药药理创新团队项目（CI2021B015）；中央级公益性科研院所基本科研业务费专项（ZXKT22045）；中国中医科学院科技创新工程课题（CI2023E001TS12）