本文選題：恩諾沙星　切入點：甲氧芐啶　出處：《西北農林科技大學》2015年碩士論文　論文類型：學位論文

【摘要】：目的:本研究將恩諾沙星(ENR)與乳酸甲氧芐啶(TMP)配伍,通過體外抗菌活性確定最佳配比,制備出復方恩諾沙星溶液,并考察其質量標準、穩(wěn)定性、體外聯(lián)合抗菌試驗以及安全性,為該復方藥物接下來的的臨床應用積累資料,并提供科學依據。方法:(1)研制與質量控制:通過對多殺性巴氏桿菌、無乳鏈球菌、金黃色葡萄球菌、大腸埃希菌進行體外抑菌試驗,確定兩種藥物最佳比例及配方;(2)質量評價:通過雙波長系數(shù)倍率法計算得到該復方溶液劑中恩諾沙星和乳酸甲氧芐啶的含量,并對該溶液劑進行穩(wěn)定性考察;(3)體外聯(lián)合抑菌試驗:通過試管肉湯稀釋法測定兩藥聯(lián)合時對四種細菌的FIC指數(shù),對聯(lián)合使用效果進行考察;(4)安全性評價:通過急性毒性試驗測定小鼠經口毒性半數(shù)致死量。結果:(1)研制與質量控制:恩諾沙星與乳酸甲氧芐啶的最佳比例為2:1;以蒸餾水作為主要溶劑,加入適量的助溶劑和抗氧化劑,按照工藝流程制出成品,經過質量檢查,該制劑的澄明度檢查無可見異物,pH為5.0-5.2,符合溶液劑的要求;(2)質量評價:建立了藥物含量測定方法,在286nm及329nm處測得吸光度,ENR與TMP分別在5-20μg/mL和2.5-10μg/mL范圍內線性關系良好;對該溶液進行高溫和低溫試驗、強光照射試驗、加速試驗進行考察,結果表明強光實驗ENR和TMP含量分別減少7.59%和4.83%,高溫實驗ENR和TMP含量分別減少5.67%和1.40%,低溫試驗ENR和TMP含量基本無變化,加速試驗后,ENR和TMP含量各減少5.41%和4.40%;(3)體外聯(lián)合抑菌試驗:恩諾沙星和乳酸甲氧芐啶聯(lián)合使用,對多殺性巴氏桿菌、金黃色葡萄球菌表現(xiàn)為協(xié)同作用,對致病性大腸埃希菌、無乳鏈球菌表現(xiàn)為相加作用;(4)安全性評價:該制劑對小鼠經口毒性的LD50為1301.33 mg/kg。結論:研制出復方恩諾沙星溶液劑并建立了藥物含量測定方法;質量評價符合規(guī)定要求;體外聯(lián)合抑菌試驗表明二者聯(lián)合具有正向效應;半數(shù)致死量試驗表明該溶液劑為低毒藥物。
[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.
【學位授予單位】：西北農林科技大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：S859.79

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