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目的根据新药申报要求,研究聚乙二醇修饰重组人血管内皮抑制素(M2ES)对小鼠自主活动和协同睡眠的影响,以确定其可能关系到人安全性的非期望药理作用。方法 120只BALB/c小鼠,随机分为4组:对照组和M2ES低、中、高剂量组,分别单次尾iv氯化钠注射液和6、12、24 mg/kg的M2ES注射液。测定给药前和给药后15、60、120、240、360 min小鼠5 min内的自发活动次数,以及对阈下剂量戊巴比妥钠致小鼠睡眠的影响。结果与对照组比较,M2ES低、中、高剂量组在给药前后各时间点小鼠的自主活动次数以及睡眠发生率均差异不显著。结论 M2ES在24 mg/kg及其以下剂量下对小鼠自主活动无显著性影响,与阈下催眠剂量的戊巴比妥钠无明显协同催眠作用。
OBJECTIVE: To investigate the effect of polyethylene glycol-modified recombinant human endostatin (M2ES) on spontaneous activity and synergetic sleep in mice based on the requirements of new drug application to determine the unintended pharmacological effects that might be related to human safety. Methods 120 BALB / c mice were randomly divided into 4 groups: control group and M2ES low, medium and high dose groups, single tail iv sodium chloride injection and 6,12,24 mg / kg M2ES injection . The number of spontaneous motions in mice at 15, 60, 120, 240 and 360 minutes before and after administration of pentobarbital sodium and the effect of subthreshold doses of sodium pentobarbital on the mice’s sleep were measured. Results Compared with the control group, there was no significant difference in the frequency of spontaneous activity and the incidence of sleep between the mice in low, middle, and high dose of M2ES before and after administration. Conclusions M2ES has no significant effect on autonomic activity in mice at doses below 24 mg / kg and no significant synergistic hypnosis with subliminal hypnotic dose of sodium pentobarbital.