克感利咽口服液对幼龄动物的药效学和急性毒性研究

Research on Pharmacodynamics and Acute Toxicity of Rheum and Pharyngitis Oral Solution on Juvenile Animals

目的研究克感利咽口服液(Rheum and Pharyngitis Oral Solution,RAPOS)对幼龄动物的药效学活性和急性毒性,为其在儿童风热感冒的临床应用提供科学的实验依据。方法选取80只21 d SD大鼠(相当于人龄3岁)随机分为8组,即空白对照组、模型组、阳性(双黄连口服液,ShuanghuanglianOral Solution,SHLOS)组及RAPOS 1、2、3、4、5组,每组10只,雌雄各半,分别建立内毒素所致的发热模型、角叉菜胶所致的足跖肿胀模型和环磷酰胺所致的免疫功能低下模型,考察RAPOS对幼龄大鼠的解热、抗炎和免疫功能增强作用;选取40只幼龄大鼠随机分为阴性对照组和RAPOS组,每组20只,雌雄各半,采用最大给药量法分别对21 d和40 d SD大鼠(相当于人龄6岁)给予RAPOS浸膏,给药后连续观察14 d,记录大鼠的毒副反应情况。结果药效学研究显示,RAPOS(3.4~6.8 g生药·kg^(-1))能明显降低大鼠体温(P<0.05);RAPOS(5.7、6.8 g生药·kg^(-1))能明显升高大鼠碳粒廓清指数K(P<0.05);6.8 g生药·kg^(-1)RAPOS能明显抑制大鼠足跖肿胀度、肿胀率和增加足跖肿胀抑制率、吞噬指数α、脾和胸腺脏器系数。急性毒性试验表明,对21 d和40 d大鼠的RAPOS浸膏最大给药量分别为70.8 g生药·kg^(-1)(相当于相应年龄临床拟用量的55.3倍)和141.5 g生药·kg^(-1)(相当于相应年龄临床日拟用量的124.1倍),除雄性大鼠体重降低、雌性大鼠一过性的体重降低、部分大鼠短时的软便稀便外,动物均未出现死亡和明显的急性毒性反应。结论RAPOS对幼龄动物具有显著地解热、抗炎和免疫功能增强作用,同时毒性较小。

OBJECTIVE To investigate the pharmacodynamic activities and acute toxicity of Rheum and Pharyngitis oral solution(RAPOS)in juvenile animals,so as to provide scientifically experimental support for its clinical application in children suffering from wind-heat cool.METHODS 80 of 21-days(21 d)SD rats(equal to 3-years-old people)were randomly divided into 8 groups,namely,blank control group,model group,positive(ShuangHuangLian oral solution,SHLOS)group and RAPOS 1,2,3,4,5 groups,10 rats(half male and half female)in each group,and the antipyretic,anti-inflammatory and immune-regulatory effects of RAPOS were explored on the basis of model of fever caused by bacterial endotoxin,paw edema caused by carrageen,as well as of low immune function caused by cyclophosphamide,respectively;40 of juvenile rats were randomly divided into the negative control group and the RAPOS group,20 rats(half male and half female)in each group,and the toxic as well as side effects of RAPOS extracts(14-days observation period after administration)in using 21 d and 40-days(40 d)rats(equal to 6-years-old people)were recorded,respectively,with the method of maximum administration dosage.RESULTS In pharmacodynamics study,it showed that RAPOS at the dose of from 3.4 to 6.8 g·kg^(-1) crude drug could significantly lower the body temperature(P<0.05);RAPOS at the dose of 5.7 and 6.8 g·kg^(-1) crude drugs could apparently improve the values of carbon clearance index K(P<0.05);while 6.8 g·kg^(-1) crude drug of RAPOS could remarkably inhibit the degree of swelling(P<0.05)as well as the rate of swelling,and simultaneously increase the phagocytic indexα(P<0.05),and spleen and thymus index(P<0.05 in both)in young 21 d rats.The acute toxicity tests displayed that,apart from weight loss in the male rats,rapid recovery of weight loss in the female rats,and temporal soft and loose stool in some rats,there was no death or obvious acute toxicity reactions in the 21 d and 40 d rats which was respectively treated with RAPOS extracts at the maximum administration dosage of 70.8 g·kg^(-1) crude drug(equivalent to 55.3 times of total daily dosage of 3-years-old people in clinic)and 141.5 g·kg^(-1) crude drug(equivalent to 124.1 times of total daily dosage of 6-years-old people in clinic).CONCLUSION RAPOS was demonstrated to have evidently anti-pyretic,anti-inflammatory and immune-enhancing effects on juvenile animals,and its toxicity is small.