口服三苯双脒3种不同溶液抗小鼠旋毛虫成囊期幼虫效果观察

Efficacy of three different liquid oral preparations of tribendimidine against encapsulated Trichinella spiralis larvae in mice

目的观察口服三苯双脒3种不同溶剂溶液抗小鼠旋毛虫成囊期幼虫的效果。方法 BALB/c小鼠40只,随机均分为4组,每鼠口饲感染旋毛虫成囊期幼虫50条。感染后第29d,分别用不同溶剂配制的三苯双脒治疗,其中吐温溶剂组三苯双脒用7%吐温-80和3%乙醇溶解,羧纤溶剂组三苯双脒用1%羧甲基纤维素和3%乙醇溶解,羟环溶剂组三苯双脒用7%羟丙基-β-环糊精和3%乙醇溶解,三苯双脒剂量均为200mg/(kg.d),连续给药6d,对照组不治疗。治疗后14d,取小鼠膈肌和腓肠肌,压片法检查成囊期幼虫,观察其存活情况,计数活虫数、死虫数及总虫数,计算克肌肉减虫率、死亡率及相对药效率,以评价药物疗效。结果实验期间所有小鼠未见药物不良反应。与对照组相比,3个治疗组膈肌和腓肠肌中成囊期幼虫总虫数和存活虫数均显著减少(P<0.05或P<0.01),死亡虫数显著增加(P<0.05或P<0.01),以羟环溶剂组的疗效最好。以减虫率计算,羧纤溶剂组对膈肌和腓肠肌中成囊期幼虫相对药效率分别为吐温溶剂组的1.61和2.46倍,羟环溶剂组相应为2.13和2.49倍;以死虫率计算,羧纤溶剂组分别为1.55和1.79倍,羟环溶剂组分别为2.51和2.16倍。结论用1%羧甲基纤维素和3%乙醇或7%羟丙基-β-环糊精和3%乙醇配制三苯双脒的生物药效率和抗旋毛虫成囊期幼虫效果显著提高,以三苯双脒羟环溶液的效果更佳。

Objective To observe the efficacy of three different liquid oral preparations of tribendimidine（TBD） against encapsulated Trichinella spiralis larvae in mice.Methods Forty BALB/c mice were divided equally into 4 groups in which each mouse was orally infected with 50 encapsulated T.spiralis larvae.On day 29 post-infection,TBD 200 mg/（kg·d） in three different liquid oral preparations was orally administered via a gastric tube to three treatment groups for 6 d.The control group was not treated.For the Tween group,TBD was dissolved in 7% Tween-80 and 3% ethanol.For the CMC group,TBD was dissolved in 1% carboxymethyl cellulose（CMC） and 3% ethanol.For the HP-β-CD group,TBD was dissolved in 7% hydroxypropyl-β-cyclodextrin（HP-β-CD） and 3% ethanol.Mice were sacrificed on day 14 post-treatment,encapsulated larvae in the diaphragm and gastrocnemius muscle were observed by compressing the muscle,and the number of total worms,living worms,and dead worms were counted.The therapeutic efficacy was estimated on the basis of the average quantity of encapsulated larvae per gram of muscle.Results During the treatment period,none of the mice had an adverse reaction.Compared to the control group,the three treatment groups had significantly fewer（P〈0.05 or P〈0.01） total worms and living worms in the diaphragm and gastrocnemius muscle and significantly more（P〈0.01） dead worms.Efficacy was greatest in the HP-β-CD group among the three treatment groups.The total worm reduction was evaluated.The relative bioavailability of TBD in the CMC and HP-β-CD groups increased significantly in comparison to that in the Tween group（diaphragm： 1.61 and 2.13-fold;gastrocnemius muscle： 2.46 and 2.49-fold）.Dead worms were counted and tallies were greater in the CMC and HP-β-CD groups（1.55 and 2.51-fold in the diaphragm;2.51 and 2.16-fold in the gastrocnemius muscle）.Conclusion Results indicated that TBD dissolved in 7% HP-β-CD and 3% ethanol or 1% CMC and 3% ethanol had significantly greater bioavailability of TBD and greater efficacy against encapsulated Trichinella spiralis larvae in mice.TBD dissolved in 7% HP-β-CD and 3% ethanol had the highest efficacy.