复方恩诺沙星溶液剂的研制及药效学研究

发布时间：2018-03-19 20:21

本文选题：恩诺沙星　切入点：甲氧苄啶　出处：《西北农林科技大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:本研究将恩诺沙星(ENR)与乳酸甲氧苄啶(TMP)配伍,通过体外抗菌活性确定最佳配比,制备出复方恩诺沙星溶液,并考察其质量标准、稳定性、体外联合抗菌试验以及安全性,为该复方药物接下来的的临床应用积累资料,并提供科学依据。方法:(1)研制与质量控制:通过对多杀性巴氏杆菌、无乳链球菌、金黄色葡萄球菌、大肠埃希菌进行体外抑菌试验,确定两种药物最佳比例及配方;(2)质量评价:通过双波长系数倍率法计算得到该复方溶液剂中恩诺沙星和乳酸甲氧苄啶的含量,并对该溶液剂进行稳定性考察;(3)体外联合抑菌试验:通过试管肉汤稀释法测定两药联合时对四种细菌的FIC指数,对联合使用效果进行考察;(4)安全性评价:通过急性毒性试验测定小鼠经口毒性半数致死量。结果:(1)研制与质量控制:恩诺沙星与乳酸甲氧苄啶的最佳比例为2:1;以蒸馏水作为主要溶剂,加入适量的助溶剂和抗氧化剂,按照工艺流程制出成品,经过质量检查,该制剂的澄明度检查无可见异物,pH为5.0-5.2,符合溶液剂的要求;(2)质量评价:建立了药物含量测定方法,在286nm及329nm处测得吸光度,ENR与TMP分别在5-20μg/mL和2.5-10μg/mL范围内线性关系良好;对该溶液进行高温和低温试验、强光照射试验、加速试验进行考察,结果表明强光实验ENR和TMP含量分别减少7.59%和4.83%,高温实验ENR和TMP含量分别减少5.67%和1.40%,低温试验ENR和TMP含量基本无变化,加速试验后,ENR和TMP含量各减少5.41%和4.40%;(3)体外联合抑菌试验:恩诺沙星和乳酸甲氧苄啶联合使用,对多杀性巴氏杆菌、金黄色葡萄球菌表现为协同作用,对致病性大肠埃希菌、无乳链球菌表现为相加作用;(4)安全性评价:该制剂对小鼠经口毒性的LD50为1301.33 mg/kg。结论:研制出复方恩诺沙星溶液剂并建立了药物含量测定方法;质量评价符合规定要求;体外联合抑菌试验表明二者联合具有正向效应;半数致死量试验表明该溶液剂为低毒药物。
[Abstract]:Objective: to prepare compound enrofloxacin solution with enrofloxacin enrofloxacin (ENR) and trimethoprim lactate (TMPL) by in vitro antibacterial activity, and to investigate its quality standard, stability, in vitro combined antibacterial test and safety. Methods: preparation and quality control of Pasteurella multocida, Streptococcus lactococcus, Staphylococcus aureus, Streptococcus multocida, Staphylococcus aureus. In vitro bacteriostatic test of Escherichia coli was carried out to determine the optimum proportion of the two drugs and the quality evaluation of the formula: the contents of enrofloxacin and trimethoprim lactate in the compound solution were calculated by double wavelength coefficient multiplier method. The stability of the solution was investigated. The combined bacteriostatic test in vitro was carried out. The FIC index of four kinds of bacteria was determined by the broth dilution method. Safety evaluation of the combined use: the lethal dose of oral toxicity in mice was determined by acute toxicity test. Results: development and quality control: the optimum ratio of enrofloxacin and trimethoprim lactate was 2: 1; the optimal ratio of enrofloxacin to trimethoprim lactate was 2: 1; the optimal ratio of enrofloxacin to trimethoprim lactate was 2: 1; Distilled water as the main solvent, Adding appropriate amount of cosolvent and antioxidants, the finished product was produced according to the technological process. After quality inspection, the clarity of the preparation was not detected. The pH value of the preparation was 5.0-5.2, which met the requirements of the solution agent. The quality evaluation was established: a method was established for the determination of the content of the drug. At 286nm and 329nm, the linear relationship between TMP and absorbance was obtained in the range of 5-20 渭 g / mL and 2.5-10 渭 g / mL, respectively. The results showed that the contents of ENR and TMP were decreased by 7.59% and 4.83 respectively, the contents of ENR and TMP were decreased by 5.67% and 1.40 in high temperature experiment, and the contents of ENR and TMP in low temperature test were almost unchanged. In vitro combined bacteriostatic test: Enrofloxacin combined with trimethoprim lactate showed synergistic effect on Pasteurella multocida and Staphylococcus aureus, and on pathogenic Escherichia coli. Safety evaluation of streptococcus lactobacillus: the LD50 of oral toxicity of this preparation to mice was 1301.33 mg / kg. Conclusion: compound enrofloxacin solution was developed and a method for determination of its content was established. The combined bacteriostasis test in vitro showed that the combination had positive effect, and the 50% lethal dose test showed that the solution was a low toxic drug.
【学位授予单位】：西北农林科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S859.79

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