新方甘草片药物依赖性潜力实验研究

EXPERIMENAL STUDY ON THE DEPENDENCE-PRODUCING POTENTIAL OF GLYCYRRHIZA NOVEL COMPOUND TABLET

新方甘草片是在复方甘草片基础上改变其中阿片粉含量而试制的一种新型镇咳药。本研究对其致依赖性潜力进行了实验评价。实验分别采用三种不同动物——大鼠、小鼠、恒河猴和五种实验模型;其中包括注射及灌胃两种不同给药途径。根据药厂提供的成人镇咳日剂量计算出动物相应日剂量(corresponding dailydose,简称CDD)。小鼠自然戒断实验中恒量给药实验组剂量分别相当于新方甘草片1—36倍CDD中的吗啡量,实验为期30天,停药后未见明显戒断症状。另以剂量递增方式给药20天,结果显示10倍CDD以上剂量组小鼠停药后出现明显体重下降。催促实验采用大鼠和恒河猴为实验样本。大鼠分为腹腔注射和灌胃两组。腹腔注射给药组的结果显示20倍CDD以上剂量组大鼠出现体重降低和戒断行为表现;灌胃组大鼠给药10天后腹腔注射阿片受体拮抗剂,可见40倍CDD组大鼠表现出明确的戒断症状。对八只猴的实验结果表明:无论催促戒断或自然戒断实验,25倍CDD以上剂量组均表现程度不等的戒断症状。本项研究结果表明,新方甘草片在正常口服剂量下,其致依赖性潜力不大。考虑到某些慢性病人长期用药或增加剂量的情况,则应警惕可能出现的依赖性倾向。

Glycyrrhiza novel compound tablet is a new prescriptionwhich is as same as the one of the old glycyrrhiza compound tablet exceptthe content of opium powder is increased. For this reason, the assessmentof dependence-producing potential of the new prescription had to be checked up in animals before being used in the clinic. Three different animals(mice, rats and monkeys) and five different experimental models wereused in the present study. The basic dosage used in this study for theanimals is the Corresponding Daily Dose (CDD) which was calculatedaccording to the human daily dose. Withdrawal syndromes didn't be foundin nature withdrawal experiments in mice after administrating morphinewith 36 times of the CDD as the maximal dosage for 30 days. The withdra-wal syndromes have been found as the morphine to be given on 10 timesof CDD or more in such a way that within 20 days period, the dosagewere given intraperitoneally in a progressively increacing manner in mice.In the precipitation tests, the dosage is 20-40 times of CDD in rats byintraperitoneally and intragastric respectively. The results showed thatthe withdrawal syndromes could be produced by diprenorphine as the 20 or40 times of CDD of morphine to be used in a progressivelly increacingprogramme by intraperitoneally and intragastic respectively. The resultsfrom monkeys showed that the withdrawal syndromes can be precipitatedby naloxone after 25 or 50 times of CDD of morphine to be given subcu-taneously for 60 days, and the nature withdrawal syndromes can be foundafter administrating for 90 days. The withdrawal syndromes can be foundneither in the precipitation test nor the nature withdrawal test as the 5times of CDD to be given to the monkeys. All the results suggested thatas a new antitussive, the potential of physical dependence of glycyrrhizanovel compound tablet is quite weak.