CN105963339B - 猴耳环提取物在制备抗多重耐药铜绿假单胞菌药物中的应用 - Google Patents
猴耳环提取物在制备抗多重耐药铜绿假单胞菌药物中的应用 Download PDFInfo
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Abstract
本发明公开了猴耳环提取物在制备抗多重耐药铜绿假单胞菌及该类抗生素增敏药物中的应用。所述的猴耳环提取物由以下方法制备:猴耳环粗粉用水或乙醇水溶液提取,所得的提取液再用乙酸乙酯萃取,所得的萃取物即为目标产品。本发明首次公开猴耳环提取物在制备抗多重耐药铜绿假单胞菌及该类抗生素增敏药物中的应用。可作为天然的抗菌药物或抗生素增敏剂,应用于由铜绿假单胞菌引起的疾病治疗。作为中药提取物还具有低成本、副作用低等优点。
Description
技术领域
本发明涉及猴耳环提取物在制备抗耐药菌药物中的新用途。
背景技术
21世纪是多重耐药菌的时代,抗生素临床应用60年后,越来越多的院内感染和多重耐药菌感染成为目前临床抗菌治疗的一大难题,1961年Jerons报告第1例临床耐甲氧西林金黄色葡萄球菌(MRSA)感染患者,目前MRSA感染已逐渐遍及全球;2011年中国细菌耐药性监测临床中主要耐药菌的分布,大肠杆菌、肺炎克雷伯菌产超广谱β-内酰胺酶(ESBL)株分别平均为50.7%、38.5%,其耐药性的变迁和现状备受关注。另外据我国卫生部耐药监测协作组2010年度报告,鲍曼不动杆菌和铜绿假单胞菌在医院ICU分离的病原菌中居首位,鲍曼不动杆菌对亚胺培南和美罗培南的耐药率分别高达60.4%和61.4%。综上所述,在MRSA、产ESBL的各类细菌、多重耐药的鲍曼不动杆菌和铜绿假单胞菌的临床占有率逐年攀升,耐药率不断攀高的压力下,抗生素治疗面临着巨大的挑战。为避免细菌耐药现象的进一步恶化,专家学者力图发现新的抑制细菌生长以及治疗细菌引起疾病的新方法。已有研究报道证明中国传统中药如黄连、黄芩和连翘等对不同耐药细菌有一定的抑制效果,进一步研究中药抑制耐药菌生长的重点在于发现新的抑菌能力更强、耐药抑菌谱更广的中药。
猴耳环(Pithecellobium clypearia Benth),学名围涎树,是含羞草科猴耳环属植物猴耳环的干燥幼枝和叶,其性味苦涩寒,功效清热解毒、收湿敛疮,是治疗多种热毒症候独特的南方药材
目前有文献公开猴耳环以及其提取物具有抗病毒作用。中国专利CN103385912A公开了猴耳环的提取物具有抗MRSA作用及抗生素增敏作用,但该专利未提及该猴耳环提取物对多重耐药铜绿假单胞菌的抗菌作用及与抗生素联用的增敏作用。
发明内容
本发明公开了猴耳环提取物在制备抗多重耐药铜绿假单胞菌及该类抗生素增敏药物中的应用。
猴耳环提取物对左氧氟沙星或亚胺培南或阿米卡星或头孢他啶或头孢哌酮五类抗生素抗多重耐药铜绿假单胞菌具有明显的增敏作用。
所述的猴耳环提取物可以是猴耳环水提取物或猴耳环乙醇提取物。可由以下方法制备:猴耳环粗粉用水或乙醇水溶液提取,所得的提取液再用乙酸乙酯萃取,所得的萃取物即为目标产品。
本发明优选按体积比计浓度为60%的乙醇水溶液作为提取溶剂所制得的猴耳环提取物。
本发明的有益效果:本发明首次公开猴耳环提取物在制备抗多重耐药铜绿假单胞菌及该类抗生素增敏药物中的应用。尤其可作为天然的抗菌药物或抗生素增敏剂,应用于由铜绿假单胞菌引起的疾病治疗,本发明包括药物包括人用药物和其他动物用药物。作为中药提取物还具有低成本、副作用低等优点。
具体实施方式
本发明通过下述实施方案对猴耳环水或乙醇提取物的抗多重耐药铜绿假单胞菌的药理作用进行筛选。
以微量肉汤稀释法测定猴耳环提取物对多重耐药铜绿假单胞菌的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。
菌株:多重耐药铜绿假单胞菌(MDRPA,编号P1-P20)20株;铜绿假单胞菌质控菌株(PAE,ATCC27853)均由中山大学附属第一医院检验医学部临床微生物检验室提供,经中山大学附属第一医院临床微生物检验室检测确认其耐药性。
MH肉汤培养基:MH肉汤干粉(英国OXOID LTD.)2.1g,定容至100ml,NAOH调节pH至7.0,高压灭菌,置4℃冰箱备用。
方法:参照美国国立临床试验标准化委员会(NCCLS)推荐的微量肉汤稀释法操作。
本发明通过下述方法对猴耳环提取物对左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮抗多重耐药铜绿假单胞菌的增敏作用进行考察。
菌株:多重耐药铜绿假单胞菌(MDRPA,编号P1-P20)20株;铜绿假单胞菌质控菌株(PAE,ATCC27853)均由中山大学附属第一医院检验医学部临床微生物检验室提供,经中山大学附属第一医院临床微生物检验室检测确认其耐药性。
MH肉汤培养基:MH肉汤干粉(英国OXOID LTD.)2.1g,定容至100ml,NAOH调节pH至7.0,高压灭菌,置4℃冰箱备用。
方法:参照美国国立临床试验标准化委员会(NCCLS)推荐的棋盘稀释法操作。以下通过具体的实施例进一步说明本发明的技术方案。
实施例1
猴耳环提取物的制备方法
猴耳环(Pithecellobium clypearia Benth)由广州市花城制药厂提供。取适量猴耳环药材打成粗粉,用水或乙醇回流2次,每次2小时,过滤;合并滤液,浓缩得浸膏(水或乙醇提取物)。取浸膏用水混悬后,用乙酸乙酯萃取,萃取三次,合并乙酸乙酯萃取液,浓缩得乙酸乙酯萃取物。
所述的乙醇提取物可由10-95%乙醇回流制得。
实施例2
猴耳环水提取物抗多重耐药铜绿假单胞菌的抑菌杀菌试验及分别与左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮联合的增敏药效考察。
1.实验方法
1)最低抑菌浓度(MIC)的测定:
猴耳环水提取物、左氧氟沙星(LVX)、亚胺培南(IMP)、阿米卡星(AMK)、头孢他啶(CAZ)、头孢哌酮(CFP)分别在MH肉汤培养基中进行一系列倍比稀释,每孔50μl,调节接种菌为1.0×106CFU/ml,每孔50μl菌液。35℃培养;24小时,无沉淀出现的最低抗菌药物的浓度为其最低抑菌浓度(MIC)。
2)最低杀菌浓度(MBC)的测定:
采用平板涂布计数法,从1)项无菌生长的孔中吸取50ul菌悬液至血平板上,均匀涂布,35℃培养24小时,菌落计数,使最初的实验活菌数减少99.9%或以上所需要的最低抗菌药物的浓度为其最低杀菌浓度(MBC)。
通过测定药物的最低抑菌浓度(MIC)和最低杀菌浓度(MBC),并对数据进行统计得出MIC50、MIC90、MBC50、MBC90,来评价药物抗多重耐药铜绿假单胞菌的作用。
3)棋盘稀释法:
棋盘稀释法在96孔无菌培养板中进行,将猴耳环水提取物及左氧氟沙星(LVX)、亚胺培南(IMP)、阿米卡星(AMK)、头孢他啶(CAZ)、头孢哌酮(CFP)分别在MH肉汤培养基中倍比稀释成系列浓度,以两药各自1/4MIC到4MIC分别进行联合,每孔A药B药各加25μL,调整菌悬液的浓度为1.0×106CFU/ml,每孔接种50μL菌液,35℃孵育24h后观察A药B药联合后对多重耐药铜绿假单胞菌的最低抑菌浓度(MIC)。
通过计算部分抑菌指数(FIC)来评价猴耳环水提取物与抗生素联合抗菌的相互作用,FIC≤0.5为协同作用,0.5﹤FIC≤1为相加作用,1﹤FIC≤2为无关作用,FIC﹥2为拮抗作用;并根据无菌生长孔找出猴耳环水提取物和抗生素的最佳浓度配比,最终评价猴耳环水提取物增强抗生素效力的作用。
2.实验结果
猴耳环水提取物及五种抗生素(左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮)对多重耐药铜绿假单胞菌的体外抑菌试验结果见表1。
猴耳环水提取物对多重耐药铜绿假单胞菌的体外杀菌试验结果见表2。
经过统计分析,猴耳环水提取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌和杀菌的MIC50、MIC90见表3。
经过统计分析,猴耳环提取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90见表4。
猴耳环水提取物与五种抗生素的联合药敏试验的FIC值及FIC值的分布统计结果见表5、表6。
猴耳环水提取物对五种抗生素的增敏作用及联用后其MIC50、MIC90见表7-表12。
表1猴耳环水提取物及五种抗生素对多重耐药铜绿假单胞菌体外抑菌试验结果
表2猴耳环水提取物对多重耐药铜绿假单胞菌的体外杀菌试验结果
表3猴耳环水提取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌的MIC50、MIC90统计结果
表4猴耳环水提取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90
表5猴耳环水提取物与五种抗生素的联合药敏试验的FIC值
表6猴耳环水提取物与五种抗生素的联合药敏试验FIC值的分布统计结果
表7猴耳环水提取物对头孢他啶的增敏作用及联用后的MIC
表8猴耳环水提取物对头孢哌酮的增敏作用及联用后的MIC
表9猴耳环水提取物对阿米卡星的增敏作用及联用后的MIC
表10猴耳环水提取物对亚胺培南的增敏作用及联用后的MIC
表11猴耳环水提取物对左氧氟沙星的增敏作用及联用后的MIC
表12联用后五种抗生素的MIC50、MIC90
猴耳环水提取物单用对多重耐药铜绿假单胞菌的MIC50为800μg/ml,MIC90为1600μg/ml,MBC50为1600μg/ml,MBC90为1600μg/ml;
对20株多重耐药铜绿假单胞菌,猴耳环水提取物与头孢他啶联用的FIC均≤2表明两药无拮抗作用,其中有45%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环水提取物在浓度≤单用MIC时,使头孢他啶MIC50从单用的32μg/ml降至8μg/ml,降低了75%;MIC90从256μg/ml降至64μg/ml,降低75%;
猴耳环水提取物与头孢哌酮联用对20株多重耐药铜绿假单胞菌FIC均≤2表明两药两药无拮抗作用,其中35%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环水提取物在浓度≤单用MIC时,使头孢哌酮MIC50从单用的64μg/ml降至0.5μg/ml,降低了99.2%;MIC90从512μg/ml降至256μg/ml,降低50%;
猴耳环水提取物与阿米卡星联用FIC均≤2表明两药没有拮抗作用,其中35%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环水提取物在浓度≤单用MIC时,使阿米卡星MIC50从单用的1μg/ml降至0.0625μg/ml,降低了93.75%;MIC90从32μg/ml降至2μg/ml,降低93.75%;
猴耳环水提取物与亚胺培南联用后FIC均≤2表明两药没有拮抗作用,其中40%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环水提取物在浓度≤单用MIC时,使亚胺培南MIC50从单用的32μg/ml降至2μg/ml,降低了93.75%;MIC90从64μg/ml降至16μg/ml,降低75%;
猴耳环水提取物与左氧氟沙星联用抗20株多重耐药铜绿假单胞菌,FIC均≤2表明两药无拮抗作用,其中15%FIC值≤0.5表明两药有一定程度的协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环水提取物在浓度≤单用MIC时,使左氧氟沙星MIC50从单用的4μg/ml降至1μg/ml,降低了75%;MIC90从32μg/ml降至8μg/ml,降低75%。
实施例3
猴耳环10%乙醇提取物抗多重耐药铜绿假单胞菌的抑菌杀菌试验及分别与左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮联合的增敏药效考察。
1.实验方法:按本发明实施例2项下方法测定并评价。
2.实验结果:
猴耳环10%乙醇提取物及五种抗生素(左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮)对多重耐药铜绿假单胞菌的体外抑菌试验结果见表13。
猴耳环10%乙醇提取物对多重耐药铜绿假单胞菌的体外杀菌试验结果见表14。
经过统计分析,猴耳环10%乙醇提取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌和杀菌的MIC50、MIC90见表15。
经过统计分析,猴耳环提取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90见表16。
猴耳环10%乙醇提取物与五种抗生素的联合药敏试验的FIC值及FIC值的分布统计结果见表17、表18。
猴耳环10%乙醇提取物对五种抗生素的增敏作用及联用后其MIC50、MIC90见表19-表24。
表13猴耳环10%乙醇提取物及五抗生素对多重耐药铜绿假单胞菌体外抑菌试验结果
表14猴耳环10%乙醇提取物对多重耐药铜绿假单胞菌的体外杀菌试验结果
表15猴耳环10%乙醇提取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌的MIC50、MIC90统计结果
表16猴耳环10%乙醇提取物的乙酸乙酯萃取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90
表17猴耳环10%乙醇提取物的乙酸乙酯萃取物与五种抗生素的联合药敏试验的FIC值
表18猴耳环10%乙醇提取物的与五种抗生素的联合药敏试验FIC值的分布统计结果
表19猴耳环10%乙醇提取物的乙酸乙酯萃取物对头孢他啶的增敏作用及联用后的MIC
表20猴耳环10%乙醇提取物对头孢哌酮的增敏作用及联用后的MIC
表21猴耳环10%乙醇提取物对阿米卡星的增敏作用及联用后的MIC
表22猴耳环10%乙醇提取物对亚胺培南的增敏作用及联用后的MIC
表23猴耳环10%乙醇提取物对左氧氟沙星的增敏作用及联用后的MIC
表24联用后五种抗生素的MIC50、MIC90
猴耳环10%乙醇提取物单用对多重耐药铜绿假单胞菌的MIC50为800μg/ml,MIC90为1600μg/ml,MBC50为1600μg/ml,MBC90为1600μg/ml;
对20株多重耐药铜绿假单胞菌,猴耳环10%乙醇提取物与头孢他啶联用的FIC均≤2表明两药无拮抗作用,其中有35%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环10%乙醇提取物的在浓度≤单用MIC时,使头孢他啶MIC50从单用的32μg/ml降至16μg/ml,降低了50%;MIC90从256μg/ml降至64μg/ml,降低75%;
猴耳环10%乙醇提取物与头孢哌酮联用对20株多重耐药铜绿假单胞菌FIC均≤2表明两药两药无拮抗作用,其中35%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环10%乙醇提取物在浓度≤单用MIC时,使头孢哌酮MIC50从单用的64μg/ml降至4μg/ml,降低了93.75%;MIC90从512μg/ml降至256μg/ml,降低50%;
猴耳环10%乙醇提取物与阿米卡星联用FIC均≤2表明两药没有拮抗作用,其中30%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环10%乙醇提取物在浓度≤单用MIC时,使阿米卡星MIC50从单用的1μg/ml降至0.0625μg/ml,降低了93.75%;MIC90从32μg/ml降至4μg/ml,降低87.5%;
猴耳环10%乙醇提取物与亚胺培南联用后FIC均≤2表明两药没有拮抗作用,其中50%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环10%乙醇提取物的乙酸乙酯萃取物在浓度≤单用MIC时,使亚胺培南MIC50从单用的32μg/ml降至2μg/ml,降低了93.75%;MIC90从64μg/ml降至16μg/ml,降低75%;
猴耳环10%乙醇提取物与左氧氟沙星联用抗20株多重耐药铜绿假单胞菌,FIC均≤2表明两药无拮抗作用,其中15%FIC值≤0.5表明两药有一定程度的协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环15%乙醇提取物在浓度≤单用MIC时,使左氧氟沙星MIC50从单用的4μg/ml降至1μg/ml,降低了75%;MIC90从32μg/ml降至4μg/ml,降低87.5%。
实施例4
猴耳环60%乙醇提取物抗多重耐药铜绿假单胞菌的抑菌杀菌试验及分别与左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮联合的增敏药效考察。
1.实验方法:按本发明实施例2项下方法测定并评价。
2.实验结果:
猴耳环60%乙醇提取物及五种抗生素(左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮)对多重耐药铜绿假单胞菌的体外抑菌试验结果见表25。
猴耳环60%乙醇提取物对多重耐药铜绿假单胞菌的体外杀菌试验结果见表26。
经过统计分析,猴耳环60%乙醇提取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌和杀菌的MIC50、MIC90见表27。
经过统计分析,猴耳环提取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90见表28。
猴耳环60%乙醇提取物与五种抗生素的联合药敏试验的FIC值及FIC值的分布统计结果见表29、表30。
猴耳环60%乙醇提取物对五种抗生素的增敏作用及联用后其MIC50、MIC90见表31-表36。
表25猴耳环60%乙醇提取物及五种抗生素对多重耐药铜绿假单胞菌体外抑菌试验结果
表26猴耳环60%乙醇提取物对多重耐药铜绿假单胞菌的体外杀菌试验结果
表27猴耳环60%乙醇提取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌的MIC50、MIC90统计结果
表28猴耳环60%乙醇提取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90
表29猴耳环60%乙醇提取物与五种抗生素的联合药敏试验的FIC值
表30猴耳环60%乙醇提取物与五种抗生素的联合药敏试验FIC值的分布统计结果
表31猴耳环60%乙醇提取物对头孢他啶的增敏作用及联用后的MIC
表32猴耳环60%乙醇提取物对头孢哌酮的增敏作用及联用后的MIC
表33猴耳环60%乙醇提取物对阿米卡星的增敏作用及联用后的MIC
表34猴耳环60%乙醇提取物对亚胺培南的增敏作用及联用后的MIC
表35猴耳环60%乙醇提取物对左氧氟沙星的增敏作用及联用后的MIC
表36联用后五种抗生素的MIC50、MIC90
猴耳环60%乙醇提取物单用对多重耐药铜绿假单胞菌的MIC50为400μg/ml,MIC90为800μg/ml,MBC50为1600μg/ml,MBC90为1600μg/ml;
对20株多重耐药铜绿假单胞菌,猴耳环60%乙醇提取物与头孢他啶联用的FIC均≤2表明两药无拮抗作用,其中有40%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环60%乙醇提取物在浓度≤单用MIC时,使头孢他啶MIC50从单用的32μg/ml降至8μg/ml,降低了75%;MIC90从256μg/ml降至64μg/ml,降低75%;
猴耳环60%乙醇提取物与头孢哌酮联用对20株多重耐药铜绿假单胞菌FIC均≤2表明两药两药无拮抗作用,其中20%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环60%乙醇提取物在浓度≤单用MIC时,使头孢哌酮MIC50从单用的64μg/ml降至4μg/ml,降低了93.75%;MIC90从512μg/ml降至256μg/ml,降低50%;
猴耳环60%乙醇提取物与阿米卡星联用FIC均≤2表明两药没有拮抗作用,其中20%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环60%乙醇提取物在浓度≤单用MIC时,使阿米卡星MIC50从单用的1μg/ml降至0.0625μg/ml,降低了93.75%;MIC90从32μg/ml降至2μg/ml,降低93.75%;
猴耳环60%乙醇提取物与亚胺培南联用后FIC均≤2表明两药没有拮抗作用,其中15%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环60%乙醇提取物在浓度≤单用MIC时,使亚胺培南MIC50从单用的32μg/ml降至2μg/ml,降低了93.75%;MIC90从64μg/ml降至16μg/ml,降低75%;
猴耳环60%乙醇提取物与左氧氟沙星联用抗20株多重耐药铜绿假单胞菌,有4株FIC大于2呈拮抗作用,其中10%FIC值≤0.5表明两药有一定程度的协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环60%乙醇提取物在浓度≤单用MIC时,使左氧氟沙星MIC50从单用的4μg/ml降至1μg/ml,降低了75%;MIC90从32μg/ml降至8μg/ml,降低75%。
实施例5
猴耳环95%乙醇提取物抗多重耐药铜绿假单胞菌的抑菌杀菌试验及分别与左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮联合的增敏药效考察。
1.实验方法:按本发明实施例2项下测定并评价。
2.实验结果:
猴耳环95%乙醇提取物的乙酸乙酯萃取物及五种抗生素(左氧氟沙星、亚胺培南、阿米卡星、头孢他啶、头孢哌酮)对多重耐药铜绿假单胞菌的体外抑菌试验结果见表13。
猴耳环95%乙醇提取物的乙酸乙酯萃取物对多重耐药铜绿假单胞菌的体外杀菌试验结果见表14。
经过统计分析,猴耳环95%乙醇提取物的乙酸乙酯萃取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌和杀菌的MIC50、MIC90见表15。
经过统计分析,猴耳环提取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90见表16。
猴耳环95%乙醇提取物的乙酸乙酯萃取物与五种抗生素的联合药敏试验的FIC值及FIC值的分布统计结果见表17、表18。
猴耳环95%乙醇提取物的乙酸乙酯萃取物对五种抗生素的增敏作用及联用后其MIC50、MIC90见表19-表24。
表37猴耳环95%乙醇提取物及五种抗生素对多重耐药铜绿假单胞菌体外抑菌试验结果
表38猴耳环95%乙醇提取物对多重耐药铜绿假单胞菌的体外杀菌试验结果
表39猴耳环95%乙醇提取物及五种抗生素对多重耐药铜绿假单胞菌的体外抑菌的MIC50、MIC90统计结果
表40猴耳环95%乙醇提取物对多重耐药铜绿假单胞菌的杀菌的MBC50、MBC90
表41猴耳环95%乙醇提取物与五种抗生素的联合药敏试验的FIC值
表42猴耳环95%乙醇提取物与五种抗生素的联合药敏试验FIC值的分布统计结果
表43猴耳环10%乙醇提取物对头孢他啶的增敏作用及联用后的MIC
表44猴耳环95%乙醇提取物对头孢哌酮的增敏作用及联用后的MIC
表45猴耳环95%乙醇提取物对阿米卡星的增敏作用及联用后的MIC
表46猴耳环95%乙醇提取物对亚胺培南的增敏作用及联用后的MIC
表47猴耳环95%乙醇提取物对左氧氟沙星的增敏作用及联用后的MIC
表48联用后五种抗生素的MIC50、MIC90
猴耳环95%乙醇提取物单用对多重耐药铜绿假单胞菌的MIC50为800μg/ml,MIC90为800μg/ml,MBC50为1600μg/ml,MBC90为1600μg/ml;
对20株多重耐药铜绿假单胞菌,猴耳环95%乙醇提取物与头孢他啶联用的FIC均≤2表明两药无拮抗作用,其中有25%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环95%乙醇提取在浓度≤单用MIC时,使头孢他啶MIC50从单用的32μg/ml降至16μg/ml,降低了50%;MIC90从256μg/ml降至128μg/ml,降低50%;
猴耳环95%乙醇提取物与头孢哌酮联用对20株多重耐药铜绿假单胞菌FIC均≤2表明两药两药无拮抗作用,其中40%FIC值≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环95%乙醇提取物在浓度≤单用MIC时,使头孢哌酮MIC50从单用的64μg/ml降至4μg/ml,降低了93.75%;MIC90从512μg/ml降至128μg/ml,降低75%;
猴耳环95%乙醇提取物与阿米卡星联用FIC均≤2表明两药没有拮抗作用,其中40%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环95%乙醇提取物在浓度≤单用MIC时,使阿米卡星MIC50从单用的1μg/ml降至0.12μg/ml,降低了87.5%;MIC90从32μg/ml降至4μg/ml,降低87.5%;
猴耳环95%乙醇提取物与亚胺培南联用后FIC均≤2表明两药没有拮抗作用,其中40%FIC≤0.5呈协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环95%乙醇提取物在浓度≤单用MIC时,使亚胺培南MIC50从单用的32μg/ml降至4μg/ml,降低了75%;MIC90从64μg/ml降至16μg/ml,降低75%;
猴耳环95%乙醇提取物与左氧氟沙星联用抗20株多重耐药铜绿假单胞菌,FIC均≤2表明两药无拮抗作用,其中10%FIC值≤0.5表明两药有一定程度的协同作用;对20株多重耐药多重耐药铜绿假单胞菌,猴耳环15%乙醇提取物在浓度≤单用MIC时,使左氧氟沙星MIC50从单用的4μg/ml降至1μg/ml,降低了75%;MIC90从32μg/ml降至4μg/ml,降低87.5%。
Claims (4)
1.猴耳环提取物在制备抗生素抗多重耐药铜绿假单胞菌增敏药物中的应用,所述的抗生素是左氧氟沙星或亚胺培南或阿米卡星或头孢他啶或头孢哌酮。
2.如权利要求1所述的应用,其特征在于,所述的猴耳环提取物由以下方法制备:猴耳环粗粉用水或乙醇水溶液提取,所得的提取液再用乙酸乙酯萃取,所得的萃取物即为目标产品。
3.如权利要求2所述的应用,其特征在于,所述的乙醇水溶液是按体积比计,浓度为10%-95%的乙醇水溶液。
4.如权利要求3所述的应用,其特征在于,所述的乙醇水溶液是按体积比计,浓度为60%的乙醇水溶液。
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