【作者】 黄伟；

【导师】 孙非；

【作者基本信息】 吉林大学 ， 生物化学与分子生物学， 2006， 硕士

【摘要】 建立绿脓杆菌(Pseudomonas aeruginosa)ATCC27853、金黄色葡萄球菌(Staphylococcus aureus)ATCC25925、大肠杆菌(Escherichia coli)ACTT25922致小鼠腹腔感染模型,通过药物治疗试验和腹腔液细菌学检查,在药效学方面比较氨苄西林钠/丙磺舒钠复方注射液(质量比3:1)和氨苄西林钠单方注射液抗感染方面的治疗效果,结果表明:(1)受试药物氨苄西林钠/丙磺舒钠复方注射液治疗组比对照药物氨苄西林钠单方注射液治疗组小鼠总保护率分别高出7.50%、8.34%和8.33%,平均生存日分别延长0.525d、0.634d和0.583d,ED50值分别高出14.41mg/kg、9.64mg/kg和6.23mg/kg,去除丙磺舒钠在复方制剂比重中占25%的影响,氨苄西林钠在复方制剂中的ED50值比在单方制剂中分别减少18.57%、20.48%和21.57%;(2)在ICR小鼠体内,受试药物氨苄西林钠/丙磺舒钠复方注射液针对绿脓杆菌、金黄色葡萄球菌、大肠杆菌腹腔感染的治疗指数TI分别为9.51、10.23、12.20;(3)腹腔液细菌学检查方面,除绿脓杆菌AMP/PRO266.67mg/kg组与AMP450mg/kg组腹腔液细菌计数在统计学上无差别外,其余受试药物所选三个剂量组的腹腔液细菌计数结果在统计学上显著低于对照药物450mg/kg剂量组。分析上述试验结果可知:(1)受试药物氨苄西林钠/丙磺舒钠复方注射液在小鼠体内抗绿脓杆菌、金黄色葡萄球菌和大肠杆菌感染的治疗效果优于对照药物氨苄西林钠单方注射液;(2)丙磺舒钠能够增强氨苄西林钠在小鼠体内的抗菌疗效;(3)氨苄西林钠/丙磺舒钠复方注射液在抗感染治疗中具有较高的安全性;(4)丙磺舒钠可以作为一种注射型抗菌增效剂与抗生素联合应用于抗感染治疗。更多还原

【Abstract】 Initially antibiotics are product of metabolism of microorganisms which are able to inhibit or kill other microorganisms. Since 1940 penicillin was applied to clinic, many important antibiotics, such as streptomycin, chloromycetin, tetracycline and so on, emergence one after the other. In 1960’s antibiotics walked into an age of semisynthesis after artificial semisynthetic penicillin was successfully synthetized. Ampicillin is a kind of semisynthetic penicillin, hydrogen of benzyl group in side chain R1 of penicillin replaced by amino group, which made it easy for ampicillin to permeate the coat of lipopolysaccharide and phospholipid of bacterial cell wall and destroy the synthesis of peptidoglycan. Therefore, ampicillin is a broad-spectrum antibiotic which has a strong antibacterial action against Gram-negative bacteria. When the carboxyl group of ampicillin was combined with sodium, ampicillin became ampicillin sodium, a dissolvable substance proper for intramuscular or intravenous injection. The antibacterial activity of ampicillin is similar to that of Penicillin G against Gram-positive bacteria, superior to it against Streptococcus riridans and enterococci, but inferior to it against other bacteria, and ineffective against penicillin G-resistant Staphylococcus aureus. Some Gram-negative bacteria, such as gonococci, meningococcus, Hemophilus influenzae, Bacillus pertussis, Escherichia coli, Bacillus paratyphosus, Bacillus typhi, Bacillus dysenteriae, Proteus mirabilis, Bacterium burgeri and so on, are sensitive to ampicillin but easily develop drug resistance. Ampicillin mainly cures various organ infections caused by sensitive bacteria, including urinary system, respiratory apparatus, biliary tract, intestinal tract, meningitis, encarditis and et al. Animal experiments and human body researches have established that the most important parameter determining in vivo antibacterial activity of beta-lactams is duration of serum free drug concentration above MIC of the specific pathogen. We called this phenomenon time-dependence killing mechanism. A T>MIC of 40-50% of the更多还原