【作者】 武博达；

【导师】 胡功政；

【作者基本信息】 河南农业大学 ， 基础兽医学， 2008， 硕士

【摘要】 本试验旨在通过研究复方头孢噻呋长效注射液的研制方法及其药动学特征,为长效注射液的研制和临床合理用药提供理论依据。首先通过体外抗菌试验测定不同配比头孢噻呋与舒巴坦的最小抑菌浓度和最小杀菌浓度筛选出复方药物的最佳配比。采用分散法制作复方头孢噻呋长效注射液,处方设计采用正交试验法;固定处方中其他敷料的含量,改变辅料A、磷脂、司盘的含量,以混悬液的沉降容积比、再分散性考察处方辅料对混悬液稳定性的影响。结果表明,只有当三者维持在一定量的比例时,混悬液在沉降容积比、再分散性方面才能表现最好效果。本试验采用高效液相色谱法,建立了在血浆中测定头孢噻呋及其去呋喃甲酰头孢噻呋相关的代谢物、舒巴坦的方法;该法灵敏度高,操作简单;浓度在0.25—40μg/ml时线性较好。动物体内药动学结果表明,自制复方头孢噻呋长效注射液的生物利用度是89.43%,达峰时间是1.47h,药物半衰期为15.53h;市售注射液的生物利用度是56.2%,达峰时间是0.69h,药物半衰期为9.32h;复方头孢噻呋长效注射液的生物利用度高于市售普通制剂68.06%。药动学数据结果表明,自制复方头孢噻呋长效注射液达到了缓释和提高生物利用度的目的。复方头孢噻呋长效注射液的研制在国内尚属首例,药物质量评定、药物体内药动学研究及生物利用度的测定结果表明长效注射液具有稳定性较好、长效缓释等优点,有着良好的开发应用前景。更多还原

【Abstract】 The experiment is for the purpose of studying the development method of the profound ceftiofur long-acting injection and its pharmacokinetics ,to provide theory basis for the development method of long-acting and clinical reasonale medication.The best ratio of ceftiofur and sulbactam was screened by minimal inhibitory concentration(MIC) and minimal bactericidal concentration(MBC) examined by in vitro antibacterial experiment.The profound ceftiofur long-acting injection is prepared by dispersion method,and the prescription is studied according to the orthogonal design of experiments.the ratio of suspending agent , phosphatide and span-80 is being adjusted to make the nature of suspension more stable in accordance with the ratio of sedimentation volume and redispersibility when the content of other adjuvant is determined.the result showed that the suspension could have stablest nature in the ratio of sedimentation volume and redispersibility just as the ratio of the three factors is most reasonable.In the research of the pharmacokinetics,the plasma concentration of sulbactam,ceftiofur and all desfuroylceftiofur-related metabolities were measured by high-performance liquid chromatography.Recovery and precision of the method was all excellent.The standard curve was linear in the range of 0.25~40μg/ml of sulbactam and ceftiofur and its metabolities.Pharmacokinetics and bioavailability were carried out in rabbits after a single intramuscular administration of the ceftiofur long-acting injection,the profound ceftiofur long-acting injection made by ourselves ,and market ceftiofur injection.the results of pharmacokinetics showed that the bioavailability, the peak time and the half-life time of the prolonged action injection of profound ceftiofur and market ceftiofur is 89.43%, 56.2%,1.47h,0.69h, 15.53h,9.32h respectively.the profound ceftiofur long-acting injection sustanined-release preparations,and it could make its bioavailability advanced.The preparation of the profound ceftiofur long-acting injection is the first case in domestic,the grade estimation,the pharmacokinetics study and the bioavailability suggest that the prolonged injection has good stability ,prolonged action ,slow–release and other merits,and possess satisfactory exploitation and application prospect.更多还原