【作者】 罗巍伟；

【导师】 贺英菊；

【作者基本信息】 四川大学 ， 药剂学， 2005， 硕士

【摘要】 穿琥宁在临床上广泛应用于治疗各类感染。目前,由于穿琥宁的稳定性以及质量问题,病人使用后偶然有不同程度的不良反应。引起不良反应的物质可能是高分子植物蛋白或穿琥宁水解氧化的降解产物及色素等。 本项研究建立了穿琥宁注射液含量测定的高效液相方法;测定了穿琥宁的主要理化性质;研究穿琥宁的降解产物及其降解过程;确定穿琥宁水溶液的水解动力学参数。经高效液相测定,穿琥宁水解符合一级降解反应,该药物的稳定性受溶液pH值,缓冲溶液的浓度,缓冲液种类以及温度的影响。 分别考察穿琥宁溶液在不同的pH值,不同的HP-β-CD浓度,不同温度下的降解动力学。使用曲线拟合的方法计算包合物的表观降解速率常数以及表观稳定常数。通过考察表面活性剂,非水溶剂对穿琥宁稳定性的影响,为制备合理处方提供依据。 在处方筛选和工艺优化的研究中,以注射剂的基本药剂学要求为指标,初步考察并确定了穿琥宁注射液的基本处方和制备工艺。 在穿琥宁注射液的质量评价研究中。完成了穿琥宁的化学、光谱、色谱鉴别和相关检查,增加了有关物质检查改进了含量测定的测定方法。 对穿琥宁注射液进行了初步稳定性研究,稳定性影响因素实验结果表明,高热、强光对注射液的质量有一定影响,提示本品应避光置于冷处保存。更多还原

【Abstract】 Potassium Dehydroandrographolidi Succinas (DAS-K) have extensive use in treat various infection in clinic. Up to date, the patients occasionally suffered from the side effects due to the stability and quality problems. The substances which cause the side effects are probably the vegetable proteins with high molecule or the degradation products and the pigments caused by the oxidative and hydrolytic degradation of the DAS-K.We developed a method to determine the content of DAS-K by HPLC; determine the primary physico-chemical property of DAS-K; study the degradation products from the DAS-K; the HPLC method was used to determine the degradation kinetic parameters of DAS-K aqueous solution. The hydrolytic degradation followed first-order kinetics as measured by HPLC. The stability of the drug was found to be dependent on pH, buffer concentration, buffer species and temperature.The degradation kinetics of DAS-K in aqueous solution was investigated at different pH, different HP- β -CD concentration and various temperatures. The apparent fate constant(kc) for degradation of DAS-K in inclusion complex and apparent stability constant(Ka) were calculated by the curve-fitting method.The basic prescription and preparation technology was initially defined by the study about formulation screening and technology optimizing , based on the pharmacy rule as indicator.In the quality study of the injection of DAS-K. The main components included that the chemical, spectrographic and chromatographic identification methods were set up, the HPLC method was developed for the content determination. Further more, the injection of DAS-K testing method of the correlated material was founded.The initial stability study showed that light, high temperature had some effects on the injection. The results suggest the injection of DAS-K should be preserved under cold enviroment way from light.更多还原