ISSN 1674-3865  CN 21-1569/R
主管:国家卫生健康委员会
主办:中国医师协会
   辽宁省基础医学研究所
   辽宁中医药大学附属医院

中国中西医结合儿科学 ›› 2025, Vol. 17 ›› Issue (1): 33-38.doi: 10.20274/j.cnki.issn.1674-3865.2025.01.007

• 实验论著 • 上一篇    下一篇

黄英咳喘糖浆的成瘾性及急性毒性实验

武瑞莉,王雪峰,张秀英,史俊祖   

  1. 110847 沈阳,辽宁中医药大学第一临床学院2022级中医儿科学专业研究生(武瑞莉,史俊祖);110032 沈阳,辽宁中医药大学附属医院中医儿科(王雪峰,张秀英)
  • 收稿日期:2024-08-07 修回日期:2024-10-30 出版日期:2025-02-25 上线日期:2025-02-25
  • 通讯作者: 王雪峰,E-mail:lnzywxf@163.com
  • 基金资助:
    王雪峰全国名老中医药专家传承工作室建设项目(国中医药人教发〔2022〕75号)

Experiment on addiction and acute toxicity of Huangying Kechuan syrup

WU Ruili1,WANG Xuefeng2,ZHANG Xiuying2,SHI Junzu1   

  1. 1The First Clinical College of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China; 2Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China
  • Received:2024-08-07 Revised:2024-10-30 Published:2025-02-25 Online:2025-02-25
  • Contact: WANG Xuefeng,E-mail:lnzywxf@163.com
  • Supported by:
    Wang Xuefeng National Famous Traditional Chinese Medicine Experts Inheritance Studio Construction Project

摘要: 目的 观察黄英咳喘糖浆最大给药量产生的毒性反应以及是否具有成瘾性,为其临床安全应用提供实验依据。方法 (1)急性毒性实验:Balb/c幼鼠40只,雌雄各半,按性别随机分为雄性空白组、雌性空白组、雄性给药组和雌性给药组,每组各10只。给药组以黄英咳喘糖浆最大浓度33.25 g/kg(相当于临床剂量的100倍),按40 mL/kg灌胃给药,一日2次,间隔6 h。空白组给予相同体积,相同次数的蒸馏水。观察并记录给药14 d内的毒性反应、死亡情况、体质量和摄食量。对死亡动物及观察期结束后仍存活动物进行大体解剖,观察主要脏器变化,计算脏器质量和幼鼠体质量的比值,得到肺指数和脾指数。(2)成瘾性实验:将50只Balb/c幼鼠随机分为空白对照组、黄英低、中、高剂量组(分别相当于临床等效剂量的0.5、1、2倍)、复方甘草片组。按10 mL/kg灌胃给药,每日1次,连续7 d。最后一次给药2 h后予幼鼠腹部注射盐酸纳洛酮溶液(0.013 mg/kg)催促戒断,观察30 min内的相应戒断症状(跳跃反应、直立行为、理毛阵数,是否有咬牙、咀嚼、流泪、流涎、呼吸急促、扭体、死亡等),并称量戒断前和戒断后30 min幼鼠体质量。同时检查幼鼠外观、有无分泌物、粪便颜色、性状。检测指标包括:病理组织学检查、肝功能和肾功能相关血液生化指标(谷丙转氨酶、谷草转氨酶、碱性磷酸酶、尿素氮、总蛋白酶、肌酐)。结果 (1)急性毒性实验:黄英咳喘糖浆灌胃后未见明显毒性;动物外观体征、行为活动未见异常,眼、口鼻、肛门未见异常分泌物,粪便形状等未见异常。给药后第1、5、10、14天两组幼鼠体质量和摄食量,差异无统计学意义(P>0.05)。给药组肺脾指数与空白组相比,差异无统计学意义(P>0.05)。(2)成瘾性实验:注射纳洛酮后30 min内各组均未出现咬牙、咀嚼、流泪、流涎、呼吸急促、扭体、死亡等症状,黄英高、中、低剂量组和复方甘草片组幼鼠理毛阵数和直立行为与空白对照组相比差异无统计学意义(P>0.05)。黄英高、中、低剂量组幼鼠30 min内均未发生跳跃反应。复方甘草片组幼鼠共发生8次跳跃现象。各组幼鼠组织经解剖检测均未见明显的病理组织学异常。黄英各剂量组和复方甘草片组幼鼠血液生化指标变化与空白对照组相比,差异均无统计学意义(P>0.05)。结论 黄英咳喘糖浆在临床剂量100倍情况下,幼鼠并未出现中毒症状,且在临床用量和用药周期的前提下不具有成瘾性。

关键词: 黄英咳喘糖浆, 成瘾性, 宣肺止咳, 化痰平喘, 小鼠

Abstract: Objective To observe the toxic reactions of the maximum dose of Huangying Kechuan syrup and whether it is addictive,in order to provide experimental evidence for its safe clinical application.Methods (1) Acute toxicity experiment:40 Balb/c young mice,half male and half female,were randomly divided into male blank group,female blank group,male drug administration group and female drug administration group,with 10 mice in each group.The drug administration groups were given Huangying Kechuan syrup at the maximum concentration of 33.25 g/kg (equivalent to 100 times of the clinical dose) by gavage at 40 mL/kg,twice a day,at a 6-hour interval.The blank groups were given the same volume of distilled water at the same frequency.Toxic reactions,death,body weight and food intake within 14 days of administration were observed and recorded.Gross dissection was performed on the dead animals and those still alive at the end of the observation period to observe the changes in major organs,and the ratios of organ weight to body weight of the young mice were calculated to obtain the lung index and spleen index.(2) Addiction experiment:50 Balb/c young mice were randomly divided into blank control group,low,medium and high-dose Huangying groups (comparable to 0.5,1 and 2 times of the clinical equivalent dose),and compound glycyrrhiza tablet group.The drugs were administered by gavage at 10 mL/kg once a day for 7 consecutive days.Two hours after the last administration,naloxone hydrochloride solution (0.013 mg/kg) was injected intraperitoneally to induce withdrawal in the young mice.The corresponding withdrawal symptoms (jumping response,upright behavior,grooming frequency,whether there was tooth grinding,chewing,tearing,salivation,rapid breathing,writhing,death,etc.) within 30 minutes were observed,and the body weight of the young mice before and 30 minutes after withdrawal was measured.At the same time,the appearance of the young mice,whether there was secretion,fecal color and traits were examined.The detection indicators included:histopathological examination and blood biochemical indicators related to liver and kidney function (alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea nitrogen,total proteinase,creatinine).Results (1)In the acute toxicity experiment,no obvious toxicity was observed after administration of Huangying Kechuan syrup by gavage.There were no abnormal signs of the appearance of the animals or behaviors,and no abnormal secretions were found in the eyes,nose,mouth or anus; no abnormalities were observed in the shape of the feces.There was no statistically significant difference in body weight or food intake between the two groups of young mice on the 1st,5th,10th and 14th day of administration (P>0.05).The lung and spleen indices of the drug administration groups showed no statistically significant difference compared with those of the blank groups (P>0.05).(2)In the addiction experiment,within 30 minutes after injection of naloxone,there were no symptoms such as tooth grinding,chewing,tearing,salivation,rapid breathing,writhing and death.The grooming frequency and upright behavior in the high,medium and low-dose Huangying groups and the compound glycyrrhiza tablet group compared with the blank control group,the difference was not statistically significant(P>0.05).No jumping response occurred in the 30 minutes after administration in the high,medium and low-dose Huangying groups.In the compound glycyrrhiza tablet group,8 times of jumping phenomena occurred.No obvious histopathological abnormalities were found in the tissues of the young mice after dissection.There was no statistically significant difference in the blood biochemical indicators of the young mice in the Huangying groups and compound glycyrrhiza tablet group compared with the blank control group (P>0.05).Conclusion At 100 times of the clinical dose,no toxic symptoms are observed in the young mice after administration of Huangying Kechuan syrup,which is not addictive under the premise of clinical dosage and administration period.

Key words: Huangying Kechuan syrup, Addiction, Ventilating the lung to relieve cough, Resolving phlegm and relieving asthma, Mice