新方甘草片药物依赖性潜力实验研究

来源 :中国临床药理学杂志 | 被引量 : 0次 | 上传用户:ni00ni
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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。 Xinfangcao tablets is a new type of antitussive that is made on the basis of compound licorice tablets to change the opiate content. This study conducted an experimental evaluation of its dependence potential. Three different animal experiments - rats, mice, rhesus monkeys and five experimental models were used in the experiment. Two different routes of administration including injection and gavage were included. The corresponding dailydose (corresponding dailydose, CDD for short) was calculated based on the daily cough dose provided by the pharmaceutical factory. The dose of constant dose administration in mice natural withdrawal experiment was equivalent to the amount of morphine in 1-40 folds of CDD of Xinfangcao, the experimental period was 30 days. No obvious withdrawal symptoms were observed after withdrawal. Another dose-increasing manner for 20 days, the results showed that 10 times the CDD above dose group mice with significant weight loss after withdrawal. Urging rats and rhesus monkeys as experimental samples. Rats were divided into intraperitoneal injection and gavage two groups. The results of intraperitoneal injection administration group showed that the body weight loss and withdrawal behavior of rats in the above 20 times of CDD dose groups were observed. Oral receptor antagonist was injected intraperitoneally 10 days after administration in the intragastric administration group, showing 40-fold CDD group A clear withdrawal symptoms. The experimental results on eight monkeys showed that withdrawal symptoms or spontaneous abstinence experiments showed that withdrawal symptoms of 25-fold CDD and above showed varying degrees of withdrawal symptoms. The results of this study show that the new square licorice tablets in the normal oral dose, its dependence-dependent potential is not large. Taking into account the long-term medication for some chronic patients or to increase the dose of the situation, should be alert to the possible dependence trends.
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