复方苦参灌肠剂急性毒性及直肠黏膜刺激实验研究

[目的]通过对复方苦参灌肠剂的急性毒性及直肠黏膜刺激性进行实验研究,为临床安全用药提供参考。[方法]应用可供灌肠最大浓度(0.7 g/mL)和最大容积(0.04 mL/g)复方苦参灌肠剂,24 h内重复给药两次,连续观察并记录给药后14 d内小鼠的中毒症状和死亡数,观察小鼠精神、活动状态、毛发色泽、饮食、排泄物、体质量变化及毒性反应,14 d后解剖观察心、肝、脾、肺、肾、结肠并进行病理学检查。对SD大鼠多次直肠给药进行直肠黏膜刺激实验,大鼠给药量为临床灌肠用药剂量,连续给药并观察7 d,第1次给药24 h后解剖1只大鼠,观察直肠黏膜充血水肿情况,以积分评价方法判断药物对直肠黏膜是否有刺激性,并进行病理检查,末次给药24 h后解剖5只大鼠,处理同前,其余大鼠停药观察1周,如果此病理检查结果有异常,则停药观察的动物需行组织病理学检查,否则只需解剖肉眼观察。[结果]急性毒性实验:实验组大鼠体质量增长趋势与对照组比较无统计学意义(P0.05)。实验组与正常对照组给药后30 min内出现倦怠懒动,2 h后恢复正常活动、饮食,随后14 d内各观察指标如外观、行为、饮食、排泄物均正常,无死亡小鼠,14 d后解剖所有小鼠,各内脏无肉眼可观察到的异常变化。直肠黏膜刺激实验:实验组与正常对照组体质量均有不同程度增长趋势,两组比较无统计学差异(P0.05)。动物解剖未见药物引起的直肠黏膜充血水肿等现象,积分评价法判断药物对直肠黏膜无刺激性,两次组织病理学检查未见明显病理改变,停药后的大鼠解剖无肉眼可见病理改变,无死亡大鼠。[结论]该实验条件下,小鼠灌肠最大给药量为56 g生药/kg,相当于人每日用量的14.6倍。实验表明临床拟用灌肠剂量是安全的。复方苦参灌肠剂多次大鼠直肠给药,对直肠黏膜无刺激性作用。

Experimental study on acute toxicity and rectal mucosal stimulation of compound sophorae enema

[Objective] To provide a reference for clinically safe medication through experimental research on the acute toxicity and rectal mucosal irritation of compound Sophorae enema.[Methods] Apply the compound sophorae enema with maximum concentration (0.7 g/mL) and volume (0.4 mL/10 g) available for enema,repeated administration twice within 24 h. Observing and recording the spirit,activity status,hair color,diet,excrement,weight change,toxic reactions and deaths of mice within 14 days after administration. The heart,liver,spleen,lung,kidney and colon were dissected and pathologically examined 14 days later. Rectal mucosal stimulation experiments were performed on SD rats for multiple rectal administrations. The dose of the rats was the clinical enema dose,which was continuously administered and observed for 7 days. One rat was dissected 24 h after the first administration,and the rectal mucosal congestion and edema were observed with the naked eyes. The point evaluation method is used to determine whether the drug is irritating to the rectal mucosa,and pathological examination is performed. Five rats were dissected 24 hours after the last administration,and the treatment was the same as before. The remaining rats were discontinued for one week. If there were abnormal results in this pathological examination,the discontinued animals should be subjected to histopathological examination;otherwise,only the anatomy and visual observation were needed.[Results] Acute toxicity test:there was no statistically significant difference in the weight gain trend between the experimental group and the control group (P>0.05). Burnout and laziness appeared within 30 minutes after administration in the experimental group and the normal control group,and normal activities and diet resumed after 2 h. All observation indicators such as appearance,behavior,diet,and excreta were normal within 14 days. No dead mice. No visceral abnormal changes were observed in all viscera of all mice at necropsy. Rectal mucosal stimulation experiment:The body weight of the experimental group and the control group increased in different degrees without significant differences (P>0.05). The rectal mucosal congestion and edema caused by the drug were not seen in the animal anatomy. The integral evaluation method judged that the drug was not irritating to the rectal mucosa. The two histopathological examinations did not show obvious pathological changes. There were no macroscopic pathological changes in the anatomy of the rats after drug withdrawal,and no dead rats.[Conclusion] Under the experimental conditions,the maximum dose of mice enema is 56 g crude drug/kg,which is equivalent to 14.6 times the daily dosage of humans. Experiments show that the clinical enema dose is safe. Compound sophorae enema was administered rectally to rats several times without irritating effect on rectal mucosa.