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利福平复合新药的研制

Development and Study on New Drug of Rifampin Combined Medicament

【作者】 薛莲

【导师】 赵宏坤; 万仁忠;

【作者基本信息】 山东农业大学 , 预防兽医学, 2004, 硕士

【摘要】 采用药敏片法测试临床常见的细菌性传染病病原菌对利福平的敏感性,找出该药的抗菌谱。通过液体两倍稀释法和液体棋盘稀释法,测定14种单药、8种组合药物对主要病原菌的最低抑菌浓度(MIC),以确定利福平复合新药的体外抗菌活性。结果显示,单一用药时,庆大霉素、新霉素、环丙沙星、蒽诺沙星、丁胺卡那霉素对这些病原菌的抑菌效果较好;与单一用药相比较,上述药物分别与利福平联合使用后,MIC值都明显降低。添加中药有效成分提取物制成复合药物后,比不加时的抑菌效果显著提高。采用添加协同杀菌因子的方法,对利福平的耐药性进行试验检测和增强其对病灶的穿透作用试验。通过合理配方,研制出中西药组合的复合新药物,主要成分为利福平和黄芩、甘草等中药有效成分提取物。同时,研制出药物的粉针剂剂型,观察了在各种常规条件下的稳定性,明确了其最佳保存条件。为了给该药的临床使用提供更加充分的科学依据,本研究以奶山羊为实验动物模型,观察分析利福平复合新药在奶山羊血液和乳汁内的代谢情况,测试该药的使用剂量、毒性和治疗效果,找出其最佳治疗剂量,并达到高效低毒的技术指标。将利福平复合新药用于治疗临床型乳房炎,观察分析了药物在患牛体内的代谢情况。研究发现使用乳池内注入法乳汁内药物的有效浓度可维持较长时间,可使乳区炎症在一个疗程后(3-5天)消失。穴位注射法有相似的效果,但临床上不易操作;乳房基部注射也有良好的局部治疗效果;肌肉注射药物代谢快,炎症部位集聚效果较差。通过试验得知,利福平复合新药具有良好的体内外抗菌效果,对一些<WP=6>因药物难以到达病灶而不能彻底治愈的疾病,如乳房炎等产生非常理想的治疗效果,并且该复合药物可减少利福平耐药菌株的产生,并增强其疗效。

【Abstract】 RFP was dissolved by proper solvent, then select bacteroidal disease’s bacteria which were famillar in clinic, at the same time, we tested sesentive activity of bacteria for RFP through drug-sensitivity test,according as this results we educed the antimicrobial activity chart of RFP. To study and compare the antimicrobial activity of Rifampin Combined Medicament in vitro.The MIC determinations of single drug, six combined drugs and Rifampin Combined Medicament, against 5 isolates of veterinary origin were performed using the method of both two-fold dilutions and liquid-chessboard diluted method.The results showed that , Ciprofloxacin, Gentamycin, Neomycin,Enoxacin,Amikacin were more active than other drugs in this examination. Furthermore, if they were combined with RFP ,the MICs were all decreased. After appended adjuvant to Rifampin+Amikacin, the anti-microbial activity was improved remarkably. Conclusion: Rifampin Combined Medicament has good anti-microbial activity in vitro models. After cooperated sterilize drugs were added to Rifampin Combined Medicament,we carried on the anti-Rafimpin bacteria control test and through logical combination, we developed new combined medicament which was composed by Chinese traditional medicine and Weston medicine and its primary ingredient were Rifampin,effective distilled substance of Chinese traditional medicine, bacterial’s DNA enzyme inhibit factor, target inducing factor, metabolized inducing factor, etc. At the same time, we develop the <WP=8>drug’s powdery shape and tested the stability under some kinds of ordinary conditions to find the optimal preserve condition.In order to offer sufficient scientific basis for the usage of Rifampin Combined Medicament, this study through animal test analysed the metabolism of Rifampin Combined Medicament in goat’s blood and milk, then detected bovine mastitis in a cattle farm. At the same time, the therapeutic study with Rifampin Combined Medicament was carried out in bovine clinical mastitis, abserved the metabolizing in its body ,the results showed that medicine in the breast can keep a long time with effective concentration and make the inflammation disappeared in a period of treatment(three-five days).Point injection has the similar effect, but difficult to handle in clinic; basal injection also has well effect in local circle; if we use muscle injection, medicine only can keep a short time .Through the experiment, we can deduce that Rifampin Combined Medicament has good anti-microbial activity in vitro models, also, it can produce very good treated effect for some diseases which was difficult to cure for medicine not easy to arrive the focus such as mastitis. Besides above merit, Rifampin Combined Medicament can reduce the anti-Rafimpin bacteria come into being and enhance the treated effect.

  • 【分类号】S859.79
  • 【被引频次】1
  • 【下载频次】317
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