浓缩型兽用双黄连口服液的急性毒性及亚慢性毒性试验

目的]评价浓缩型兽用双黄连口服液的用药安全性,为其临床用药提供参考依据.方法]以昆明系小鼠为试验对象,通过开展浓缩型兽用双黄连口服液的急性毒性及亚慢性毒性试验,确定其临床应用的主要毒性作用及毒性作用靶器官.其中,急性毒性试验设20.00、10.00、5.00、2.50和1.25 g/kg 5个剂量组,试验开始当天在24 h内分2~3次对小鼠进行灌胃给药;最大耐受量试验用药剂量为240.00 g/kg,试验开始当天在24 h内分2次对小鼠进行灌胃给药,每次0.80 mL/只;亚慢性毒性试验设每天灌服0.16、0.08和0.04 mL/只3个剂量组,连续灌胃给药28 d.结果]急性毒性试验小鼠灌胃给药后30 min内精神萎靡,安静,呼吸变慢,但30 min后恢复正常,未出现中毒症状和死亡现象,未能测出半数致死量(LD50).小鼠对浓缩型兽用双黄连口服液的最大耐受量大于240.00 g/kg.亚慢性毒性试验期间,各用药组小鼠的体重、脏器(肝脏、脾脏和肾脏)指数和血清学指标(谷丙转氨酶、谷草转氨酶、尿素氮和肌酐含量)与空白对照组相比均无显著差异(P>0.05);病理组织切片观察发现,仅高剂量组小鼠的肝脏有损伤,肝细胞有点状坏死灶,肝细胞索凌乱,细胞界限模糊不清,细胞核着色减弱,其他脏器组织切片均无异常变化.结论]浓缩型兽用双黄连口服液对小鼠无急性毒性作用,长期连续用药也无亚慢性毒性作用,安全性较高.

Acute toxicity and subchronic toxicity tests for veterinary concentrated Shuanghuanglian oral liquid

Objective]Evaluation on the safety of veterinary concentracted Shuanghuanglian oral liquid was conduct-ed to provide reference for its clinical application.Method]Taking Kunming mice as experimental subjects,the main toxicity and toxicological target organs of clinical application were determined by carrying out the acute toxicity and sub-chronic toxicity tests for concentrated Shuanghuanglian oral liquid. Acute toxicity test set five dose groups(20.00,10.00, 5.00,2.50 and 1.25 g/kg). Mice were intragastrically administered for 2-3 times within 24 h on test day. The maximum tolerated dose was 240.00 g/kg,and mice were intragastrically administered twice a day for 24 h with 0.80 mL each at the start of the experiment. The mice in the subchronic toxicity test were treated with the drug at dose of 0.16,0.08 or 0.04 mL each mice a day for 28 d by continuous intragastric administration.Result]For mice in acute toxicity test,within 30 min after intragastric administration,mice were apathetic,quiet and their slowed down breath,but returned to normal state after 30 min. No symptoms of poisoning and death were presented,and median lethal dose(LD50)was failed to detect. The maximum tolerated dose of veterinary concentrated Shuanghuanglian oral liquid to mice is more than 240.00 g/kg. During the subchronic toxicity test,body weight,organs(liver,spleen and kidney)indexes,serology indexes(glu-tamic pyruvic transaminase,glutamic oxalacetic transaminase,urea nitrogen and creatinine content) in mice of each group were not significantly different when compared with those in the blank control group(P>0.05). Histopathological examination showed that only the high dose group had liver injury,a little necrosis in liver cells,messy liver cell lines, unclear cell boundaries,weakened nuclear staining,but no abnormal changes in other organs were detected.Conclusion]The veterinary concentracted Shuanghuanglian oral liquid has no acute toxicity to mice,and long-term medication does not pose subchronic toxicity to mice. Therefore it is safe.