中国药物警戒 ›› 2026, Vol. 23 ›› Issue (6): 656-662.
DOI: 10.19803/j.1672-8629.20260238

• 基础与临床研究 • 上一篇    下一篇

蒿芩滴鼻剂安全性评价研究

何韬1, 王新堂1Δ, 颜玉文2, 刘燕1, 程江南1, 顾政一1, 毛艳1,*   

  1. 1新疆维吾尔自治区药物研究院,新疆维吾尔药重点实验室,新疆 乌鲁木齐 830010;
    2苏州华测生物技术有限公司,江苏 苏州 215300
  • 收稿日期:2026-03-25 出版日期:2026-06-15 发布日期:2026-06-18
  • 通讯作者: *毛艳,女,硕士,研究员·硕导,中药新药研发与质量控制。E-mail: maoyan7529@163.com
  • 作者简介:何韬,男,硕士,助理研究员,中药新药研究与开发。Δ为并列第一作者。
  • 基金资助:
    新疆维吾尔自治区重大科技专项项目（2021A03002-1）; 新疆维吾尔自治区自然科学基金资助项目（2021D01E25）; “天山英才”医药卫生高层次人才培养计划项目（TSYC202401B034）

Safety Assessment of Haoqin Nasal Drops

HE Tao1, WANG Xintang1Δ, YAN Yuwen2, LIU Yan1, CHENG Jiangnan1, GU Zhengyi1, MAO Yan1,*   

  1. 1Xinjiang Institute of Materia Medica, Key Laboratory of Xinijang Uygur Medicine, Urumqi Xinjiang 830010, China;
    2CTI Biotechnology (Suzhou) Co., Ltd, Suzhou Jiangsu 215300, China
  • Received:2026-03-25 Online:2026-06-15 Published:2026-06-18

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摘要： 目的 观察蒿芩滴鼻剂大鼠单次给药和13周重复给药可能出现的毒性反应,为其临床试验及临床安全用药提供参考。方法 单次给药毒性试验中,大鼠给予最大给药体积（0.4 mL·kg-1）、最大给药剂量（1 440 mg生药·kg-1）的蒿芩滴鼻剂,观察14 d内的一般状态、体重及摄食量、毒性症状及死亡情况,并对主要组织脏器进行组织病理学检查;重复给药毒性试验中,蒿芩滴鼻剂低、中、高剂量组大鼠分别给予67.5、135.0、270.0 mg生药·kg-1 13周,每天观察大鼠一般状态,每周称量体重,分别于给药13周及停药后4周,检测指标包括血液学指标、凝血指标、血液生化指标、尿液指标、脏器系数及组织病理学检查。结果 单次给药毒性试验中,大鼠的一般状态、体重及摄食量等指标均无异常;13周重复给药毒性试验中,与溶媒对照组比,给药期结束,部分给药组的个别指标如红细胞和平均红细胞血红蛋白浓度、网织红细胞、血红蛋白、红细胞比积和尿素等具有统计学差异,但属正常范围波动。高剂量组1例雄性肝脏肝细胞空泡变、1例雌性动物骨髓造血干细胞轻微减少,结合血液生化等指标的检测结果,考虑为大鼠的自发性病变。结论 蒿芩滴鼻剂单次给药的最大耐受量（MTD）为1 440 mg生药·kg-1（约为400倍临床拟用剂量）,13周重复给药的无毒反应剂量（NOAEL）为270 mg生药·kg-1（约为75倍临床拟用剂量）,表明该药在拟临床使用剂量范围及疗程内未见明显的毒性反应,在治疗剂量范围内安全性较高,可为该药进一步开展临床试验提供参考。

关键词: 蒿芩滴鼻剂, 单次给药, 重复给药, 最大耐受量, 无毒反应剂量, 安全性评价, 大鼠

Abstract: Objective To assess the safety of Haoqin nasal drops and provide a reference for safe clinical medications for allergic rhinitis (AR). Methods In single-dose toxicity test, SD rats were administered with the maximum tolerated dose (0.4 mL·kg-1) of Haoqin nasal drops, which was equivalent to 1440 mg crude drug/kg. The overall state, body weight, food intake, toxic symptoms, and mortality of these rats were observed over a period of 14 days, followed by histopathological examination of major tissues and organs. In the repeated dose toxicity test, SD rats were divided into high-dose(270.0 mg·kg-1), medium-dose (135.0 mg·kg-1), low-dose(67.5 mg·kg-1) groups and a control group, with 30 rats in each. The rats were administered with this drug for 13 weeks, followed by 4 weeks of recovery. The overall state of these rats was observed daily while their body weight was measured weekly. Such indexes were recorded as parameters of hematology, coagulation and blood biochemistry, urine indexes, organ coefficients and results of histopathological examination. Results In the single-dose toxicity test, the overall state, body weight, food intake and other indicators of rats were normal. In the repeated-dose toxicity test, some of the indicators of the medication group, such as red blood cell count and the average hemoglobin concentration of red blood cells, reticulocytes, hemoglobin, hematocrit and urea at the end of the dosing period, were statistically different from those of the control group, but within the normal range of fluctuation. In the high-dose group, there was one case of male hepatocyte vacuolation and one case of a slight decrease in female bone marrow hematopoietic stem cells. The two cases were considered a spontaneous disease in rats based on blood biochemical indicators. Conclusion The MTD of Haoqin nasal drops is 1440 mg crude drug/kg (equivalent to 400 times the intended clinical dose) for a single administration, and the NOAEL for the 13-week repeated doses is 270 mg crude drug/kg (equivalent to 75 times the intended clinical dose). Haoqin nasal drops show no significant toxicity and prove quite safe at therapeutic dosages.

Key words: Haoqin Nasal Drops, Single Administration, Repeated Administration, MTD, NOAEL, Safety Assessment, Rats

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