头孢托仑酯随机双盲对照治疗细菌性感染临床评价

为评价头孢托仑酯（ＭＥ１２０７）治疗细菌性感染的有效性和安全性，采用随机双盲对照试验和开放试验方法共治疗８０例患者，其中ＭＥ１２０７（Ａ药）与头孢克肟（Ｂ药）随机双盲各治疗２０例（呼吸系统和泌尿系统各１０对），ＭＥ１２０７开放试验治疗４０例（呼吸系统２０例、泌尿系统１０例、皮肤软组织感染１０例）。每日４００ｍｇ，疗程７～１４ｄ。ＭＥ１２０７痊愈率和有效率在对照试验中为８０％和９５％，在开放试验中为７５％和９２．５％，总痊愈率为７６．７％，总有效率为９３．３％，细菌培养阳性率为１００％，细菌清除率在对照试验和开放试验中分别为９５％和９２．５％。纸片法药敏试验中ＭＥ１２０７敏感株百分率为１００％，与头孢哌酮相同，而优于头孢克肟和头孢克洛，明显优于阿莫西林（４８．８％）。ＭＥ１２０７６０例中６例出现不良反应，表现为消化道反应３例，转氨酶升高２例，凝血酶原时间延长１例。与对照药头孢克肟相比在痊愈率、有效率、细菌清除率及不良反应发生方面均无显著性差异（Ｐ＞０．０５）。ＭＥ１２０７在每日４００ｍｇ剂量下治疗轻、中度细菌感染安全、有效。     

Identification and Characterization of Hydrolytic Degradation Products of Cefditoren Pivoxil using LC and LC-MS/TOF

The present research work was carried out to determine stability of cefditoren pivoxil, an orally absorbed prodrug that is rapidly hydrolysed by intestinal esterases to the active cephalosporin cefditoren. Cefditoren was subjected to stress conditions recommended by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline Q1A (R2). Cefditoren pivoxil was susceptible for degradation under acidic, alkaline and neutral hydrolytic conditions while it was stable under photolytic and thermal stress conditions. Separation of cefditoren and degradation products were carried out by using HPLC. The unknown degradation products were characterized by liquid chromatography-mass spectrometry/time of flight studies. Structures were proposed for each fragment based on best possible molecular formula and complete degradation pathways were reported for cefditoren and its degradants.     

高效液相色谱法测定头孢特仑酯胶囊的含量和有关物质

目的建立高效液相色谱法测定头孢特仑酯胶囊含量和有关物质的方法。方法色谱柱为依利特HypersilODS2柱,流动相为乙腈-0.01mol·L-1醋酸-醋酸钠缓冲液-水(380∶100∶520),检测波长为254nm,流速1.0mL·min-1。结果头孢特仑酯在0.1038-1.038mg·mL-1浓度范围内呈良好的线性关系,回归方程:Y=38831X 35.94,r=0.9999;平均回收率为100.3%(n=9)。结论该方法简便、快速、准确、灵敏度高,适用于头孢特仑酯胶囊的含量和有关物质测定。     

替比培南匹伏酯侧链的合成

目的:合成替比培南匹伏酯侧链1-(4,5-二氢-2-噻唑啉基)-3-巯基吖丁啶盐酸盐。方法:以2-甲硫基-2-噻唑啉为原料,经与3-羟基吖丁啶盐酸盐,甲烷磺酰氯,硫代乙酸钾以及水解4步反应合成1-(4,5-二氢-2-噻唑啉基)-3-巯基吖丁啶盐酸盐。结果:合成了1-(4,5-二氢-2-噻唑啉基)-3-巯基吖丁啶盐酸盐,总收率42%。结论:本方法可以方便地得到替比培南匹伏酯侧链1-(4,5-二氢-2-噻唑啉基)-3-巯基吖丁啶盐酸盐,提高了反应收率,简化了操作,降低了成本。     

头孢地尼与头孢特仑对照治疗急性泌尿系统细菌感染26例

目的:评价头孢地尼治疗急性泌尿系统细菌性感染的安全性和有效性.方法:采用随机、单盲及平行对照法,26例轻、中度急性肾盂肾炎和急性膀胱炎患者随机均分为试验组和对照组,试验组服用头孢地尼胶囊,对照组服用头孢特仑片,剂量均为100mg,tid,疗程7d.结果:试验组与对照组细菌清除率均为100.0%,痊愈率均为76.9%,总有效率分别为100.0%和92.3%,疗效差异无显著性.头孢地尼抗菌活性与头孢特仑相似(P＞0.05),而优于头孢克肟、阿莫西林 克拉维酸(P＜0.05).2组不良事件发生率均为7.7%,差异没有显著性(P＞0.05).结论:头孢地尼治疗敏感菌所致急性泌尿系统的轻、中度感染安全有效.     

盐酸头孢他美酯健康人体药动学研究

 目的　研究头孢他美酯在健康人体内的药动学。方法 18名健康志愿者单剂量po盐酸头孢他美酯片500mg ,采用高效液相色谱法测定血浆和尿中活性代谢物头孢他美药物浓度。结果　药动学参数末端相消除半衰期(t_1/2)、峰浓度(c_max)、AUC_0～12分别为:(2.52±0.47)h,(3.67±0.98)μg·mL^-1,(21.10±5.19)μg·h·mL^-1。结论　头孢他美的体内过程符合二室开放模型,主要经肾脏排出体外,12h累积尿排百分率为(36.00±8.62)%。     

舒巴坦匹酯原料残留溶剂的评价

目的:建立测定舒巴坦匹酯中残留溶剂的方法。方法:对挥发性较强的二氯甲烷、乙酸乙酯、乙醇采用气相色谱顶空进样法测定;对不宜挥发的N,N-二甲基甲酰胺(DMF)采用气相色谱直接进样法测定含量,限度与欧洲药典1999年增补版的标准一致。结果:二氯甲烷、乙酸乙酯和乙醇在2～400μg·ml~(-1),N,N-二甲基甲酰胺在7～680μg·ml~(-1)范围内呈良好的线性关系。结论:本方法简便、快速、准确。     

头孢他美酯与头孢克肟随机对照治疗细菌性感染疗效分析

对４０例下呼吸道及泌尿道感染患者分别使用头孢他美酯和头孢克肟进行了胡机对照临床观察。     

Effects of sugar ester and hydroxypropyl methylcellulose on the physicochemical stability of amorphous cefditoren pivoxil in aqueous suspension

The improvement in physicochemical stability of amorphous cefditoren pivoxil (CDTR-PI) in aqueous suspensions by addition of sugar ester (SE) and hydroxypropyl methylcellulose (HPMC) was explained by prolonging the induction period prior to crystallization and the reduction in crystal peak intensity. Furthermore, the stabilizing effect of these additives in a multiple additive system was greater than in a single additive system. To determine the mechanism, by which these additives stabilized the amorphous CDTR-PI, we evaluated the surface states of CDTR-PI in suspension by measuring Raman spectra and zeta potential. The change in Raman spectra demonstrated that SE and HPMC interacted with CDTR-PI at the same interaction sites on CDTR-PI. The zeta potential reflected the adsorption phenomena of the additives and indicated that both SE and HPMC adsorbed onto particles of CDTR-PI with no apparent competitive interaction and the response was complementary. It was considered, based on this study, that HPMC and SE would stabilize amorphous CDTR-PI by different mechanisms; HPMC would mainly inhibit crystal growth by small amount of adsorption and SE would inhibit both crystal growth and nucleation by large amount of adsorption. This was considered to result in the hybrid effect in the multiple additive system.     

头孢妥仑匹酯治疗下呼吸道感染性疾病疗效观察

目的：评价头孢妥仑匹酯片治疗下呼吸道感染性疾病的临床疗效及安全性。方法：120例下呼吸道感染的患者随机分为治疗组60例、对照纽60例,分别给予头孢妥仑匹酯和头孢克肟口服,1次200mg,bid治疗,疗程7～14d。结果：头孢妥仑匹酯和头孢克肟组的总有效率分别为95％和83％,细菌清除率为94．2％和66．7％,不良反应发生率分别为3．3％和6．0％,2组差别有统计学意义（P〈0．05）。结论：头孢妥仑匹酯片治疗下呼吸道感染疗效好。安全性高。