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