注射用酒石酸长春瑞滨胶束对中枢神经、消化、心血管和呼吸系统的安全药理学研究

Safety pharmacology study of vinorelbine tartrate micelle for injection

目的研究注射用酒石酸长春瑞滨胶束(NVB-m)对实验动物中枢神经系统、消化系统、心血管和呼吸系统的影响,从而观察药物潜在的对生理功能的不良影响,为临床实验提供依据及参考。方法①ICR小鼠随机分为对照组、空白胶束组、地西泮(阳性对照,3 mg/kg)组及NVB-m 4、8、16 mg/m2组和注射用酒石酸长春瑞滨(NVB)16 mg/m^2组,单次静脉推注给药,通过小鼠自主活动次数试验、转棒试验、协同睡眠试验分别对动物的运动功能、协调功能、翻正反射进行定量评价,观察药物对动物中枢神经系统的影响,②ICR小鼠随机分为对照组、空白胶束组、硫酸阿托品(阳性对照,20mg/kg)组及NVB-m 4、8、16 mg/m2组和NVB 16 mg/m2组,单次静脉推注给药,通过观察墨汁推进率的变化研究药物对胃肠消化系统的影响,③比格犬随机分为对照组、空白胶束组及NVB-m 4、8和16 mg/m^2组和NVB 16 mg/m^2组,单次静脉推注给药,多导生理信号记录仪分别在给药前、给药后0.25、0.50、1.00、2.00、4.00、6.00 h各记录1次心电、血压和呼吸波形,观察药物对动物心血管和呼吸系统的影响。结果与对照组比较,NVB-m和NVB组小鼠自主活动未见明显变化、平衡运动能力未见明显影响、未见与阈下剂量戊巴比妥钠协同睡眠作用,NVB-m组和NVB组小鼠未见墨汁推进率的明显变化,NVB-m组和NVB组比格犬未见药物相关的心电、血压和呼吸指标的明显变化。结论单次静脉给予16 mg/m^2的NVB-m和NVB,未见药物对实验动物中枢神经系统、消化系统、心血管和呼吸系统产生明显影响,NVB-m与NVB在相同剂量条件下比较,未见明显差异。

Objective To research the drug effects on laboratory animals' central nervous system,digestive system,cardiovascular system and respiratory system under the certain dosages thereby observing the potential adverse effects of the drug on physiological functions and providing basis and reference for clinical experiment.Methods ① ICR mice were randomly divided into control group,blank micelle group,diazepam(positive control,3 mg/kg) group,NVB-m 4,8 and 16 mg/m^2 group and NVB 16 mg/m^2 group.Single intravenous injection was administered.The motor function,coordination function and righting reflex of animals were quantitatively evaluated by the number of spontaneous activities test,rod rotation test and synergistic sleep test,and the influence of central nervous system was observed.② ICR mice were randomly divided into control group,blank micelle group,atropine sulfate(positive control,20 mg/kg),NVB-m 4,8 and 16 mg/m^2 groups and NVB 16 mg/m^2 groups.The effects of drugs on gastrointestinal digestive system were studied by observing the change of ink propulsion rate.③ Beagle dogs were randomly divided into control group,blank micelle group,NVB-m 4,8 and 16 mg/m^2 group and NVB 16 mg/m^2 group.Single intravenous injection was given.The ECG,blood pressure and respiratory waveforms were recorded by multi-channel physiological signal recorder before and after administration 0.25,0.50,1.00,2.00,4.00 and 6.00 hours respectively.The effects of drugs on cardiovascular and respiratory system were observed.Results No significant changes in spontaneous activities of mice after a single dose of NVB-m and NVB by intravenous injection were found.The balance and exercise abilities of mice showed no impacts.No function together with subthreshold dose of sodium pentobarbital to cause mice sleep were found.No significant changes in gastrointestinal propulsive effect of mice after a single dose of NVB-m and NVB by intravenous injection were found.No significant changes in cardiovascular and respiratory system of beagle dog after a single dose of NVB-m and NVB by intravenous injection were found.Conclusions A single dose of 16 mg/m^2 of NVB-m and NVB showed no significant influences on laboratory animals' central nervous system,digestive system,cardiovascular system and respiratory system.No significant difference were showed in the same dose of NVB-m and NVB.