利用正交试验设计,筛选、优化处方和工艺,制备阿维菌素纳米脂质体,并考察其稳定性.采用改良薄膜分散法制备阿维菌素纳米脂质体(AVMNL),用透射电镜、激光粒度分布仪等对其理化性质进行研究.用紫外可见分光光度法测定AVMNL中AVM(阿维菌素)的质量浓度,并通过热稳定试验和光照试验考察其稳定性.结果显示,制备方法的最佳处方工艺组合为卵磷脂与胆固醇,其质量比为9∶1,AVM与磷脂质量比为1∶10,缓冲液PBS的pH为7.0,超声裂解时间为5 min,蒸发温度为40℃,冻融3次.AVMNL是乳白色均一稳定的牛奶状液体,其平均粒径为198.2 nm.AVMNL在不同温度下放置0、5、10d后,无分层、沉淀现象发生,色泽均呈乳白色,包封率和药物质量浓度均未发生明显变化.3批AVMNL在光照度为(4 500±500)lx、2.0～5.0℃放置0、5、10d后,其外观未发生明显变化,为乳状均一的液体,无絮凝、药物析出现象,但药物的包封率和质量浓度有所降低.制备的纳米脂质体符合要求,粒径分布范围窄,且比较均匀,对热稳定,对光的稳定性较差,应避光保存.

In order to prepare compound metronidazole dispersible tablets,metronidazole and oxytetracy-cline hydrochloride were used as the main drugs,and appropriate auxiliary materials were selected to make dispersible tablets in this experiment.Orthogonal experiment was used to screen prescription of the drug and conduct the selection of the granulation size.The quality inspection of dispersible tablets of the com-pound metronidazole included the check of character,the weight difference,the hardness,pH,disintegra-tion time and uniform dispersion.The dispersible tablets of compound metronidazole were prepared and the contents of metronidazole and oxytetracycline hydrochloride were determined by UV spectrophotome-try.The results showed that metronidazole accounted for 200 g/kg,oxytetracycline hydrochloride accoun-ted for 100 g/kg,CMS-Na accounted for 150 g/kg,starch is accounted for 250 g/kg MCC is accounted for 250 g/kg and sucrose accounted for 50 g/kg.The contents of metronidazole and oxytetracycline hydrochlo-ride were determined by UV spectrophotometry,and the recovery rate was high and the precision was good.The result of the quality inspection of dispersible tablets was accord with the request of the tablet in China Drug Standard.Compound metronidazole dispersible tablets had fast disintegration speed,convenient use,simple preparation process,high stability and good compliance and then can be used for veterinary clinic.

【Objective】 The study was conducted to prepare compound oxytetracycline hydrochloride injection and determine its mass concentration.【Method】 The formula components and approximate dosage of the compound oxytetracycline hydrochloride injection were determined through pre-test.We used sodium metabisulfite,magnesium chloride,ethanolamine and complex organic solvent as effecting factors,and took changes of the mass concentration of metronidazole and oxytetracycline hydrochloride as the selection standard.Finally the optimal formula of compound oxytetracycline hydrochloride injection was determined using orthogonal experiment L9(34).We also determined the mass concentrations of metronidazole and oxytetracycline hydrochloride in the compound injection by UV spectrophotometry,and calculated the recovery percent and the precision.【Result】 The optimized formula of compound oxytetracycline hydrochloride injection(in 100 mL Volume) was composed of metronidazole 2.5 g,oxytetracycline hydrochloride 5.0 g,magnesium chloride 3 g,sodium Pyrosulfite 0.2 g,complex organic solvent(composed of N,N-dimethyl formamide and polyethy leneglycol 400 with a volume ratio of 2∶1) 40 mL,ethanolamine 4 mL,and water for injection.There was fine linear relationship between the mass concentration and absorbance when metronidazole and oxytetracycline hydrochloride was 1-30 μg/mL.The average recovery of metronidazole was(99.22±1.48)%,and its coefficient of variation was 1.49%.The average recovery of oxytetracycline hy-drochloride was(98.22±1.24)%,and its coefficient of variation was 1.26%.By measuring the daily precision and the day to day precision,the average concentration of metronidazole and oxytetracycline hydrochloride was high,and the relative standard deviation was low and no greater than 2.00%.【Conclusion】 The production of injection formula was reasonable and practical for stable potency with high recovery percent of metronidazole and oxytetracycline hydrochloride.

The pharmacokinetics of maquindox in control and pathological groups of rabbits were analyzed and given references for clinical treatment.12 rabbits were randomly divided into 2 groups.Group A was the control group,and group B was tested group with experimental renal injury.24 h before the experiment,rabbits in group B were treated with a hypodermic injection of HgCl2(1.5 mL/kg).Both group of rabbits were treated with a rapid single-dosage intravenous injection of Maquindox(20 mg/kg).The blood samples were collected from heart 8 times within 6 hours after injection.The mass concentrations of Maquindox in serum were detected by HPLC.The results showed that the disposition of Maquindox in rabbits matched with non-absorption one-compartment open model.The optimal concentration-time equations of the three groups were:ρcontrol group=25.564 2e-0.371 6t,ρrenal injury=20.026 6e-0.099 8t.Compared with the control group,t1/2 renal injury prolonged by 276.16%;kel renal injury decreased by 73.14%;CLB renal injury decreased by 69.91%;AUC renal injury increased by 187.57%.It can be concluded that the pharmacokinetics parameters of Maquindox in rabbit pathological model have changed apparently,so it is necessary to lengthen the dosing interval or lessen the dosage of Maquindox on the pathological occasions.