[发明专利]包含莫匹罗星及新霉素的抗微生物组合物

说明书

本发明的特征在于包含莫匹罗星及新霉素的组合物、其调配物及使用该组合物治疗微生物感染的方法。

技术领域

本发明提供一种包含莫匹罗星(mupirocin)及新霉素(neomycin)的组合物，用于预防及治疗微生物感染。

相关申请案的交叉引用

本申请案主张2015年8月5日申请的美国临时专利申请案第62/201,380号的优先权，该临时专利申请案的内容以全文引用的方式并入本文中。

背景技术

莫匹罗星为抑制细菌异白胺酰-tRNA合成酶介导的Ile-tRNA胺酰化且因此抑制蛋白质转译的抗微生物剂。参见Hughes J,Mellows G.,「On the mode of action ofpseudomonic acid:inhibition of protein synthesis in Staphylococcus aureus,」The Journal of Antibiotics,31:330-335(1978)；Hughes J,Mellows G.,「Inhibitionof isoleucyl-transfer ribonucleic acid synthetase in Escherichia coli bypseudomonic acid,」The Biochemical Journal 176:305-318(1978)；Hughes J,MellowsG.,「Interaction of pseudomonic acid A with Escherichia coli B isoleucyl-tRNAsynthetase,」The Biochemical Journal 191:209-219(1980)。该药剂对大多数革兰氏阳性菌种表现出优异的抗菌活性，无对现有抗生素的交叉抗性，在人体内吸收良好，但在活体内亦迅速降解，因此不适合全身使用。参见Sutherland R,Boon RJ,Griffin KE,MastersPJ,Slocombe B,White AR.,「Antibacterial activity of mupirocin(pseudomonicacid),a new antibiotic for topical use,」Antimicrob Agents Chemother 27:495-498(1985)。然而，基于莫匹罗星的软膏已经验证对于金黄色葡萄球菌(S.aureus)皮肤及伤口感染的治疗为有效的，且近来亦已成为手术前鼻腔去定殖的护理标准。参见Beale AS,Gisby J,Sutherland R.,「Efficacy of mupirocin calcium ointment in thetreatment of experimental wound infections caused by methicillin-resistantstrains of Staphylococcus aureus,」Journal of Chemotherapy(Florence,Italy)1:397-398(1989)；Moy JA,Caldwell-Brown D,Lin AN,Pappa KA,Carter DM.,「Mupirocin-resistant Staphylococcus aureus after long-term treatment of patients withepidermolysis bullosa,Journal of the American Academy of Dermatology 22:893-895(1990)；Rode H,de Wet PM,Millar AJ,Cywes S.,「Bactericidal efficacy ofmupirocin in multi-antibiotic resistant Staphylococcus aureus burn woundinfection,The Journal of Antimicrobial Chemotherapy 21:589-595(1988)；Rode H,Hanslo D,de Wet PM,Millar AJ,Cywes S.,「Efficacy of mupirocin in methicillin-resistant Staphylococcus aureus burn wound infection,」Antimicrob AgentsChemother33:1358-1361(1989)；Coates T,Bax R,Coates A.,「Nasal decolonization ofStaphylococcus aureus with mupirocin:strengths,weaknesses and futureprospects,」The Journal of Antimicrobial Chemotherapy 64:9-15(2009)。实际上，莫匹罗星介导的鼻腔去定殖已显示有效减少烧伤感染、肺部感染、透析患者感染、手术部位感染、骨科感染及医疗工作者与重症监护病房患者间的金黄色葡萄球菌传播。参见MupirocinStudy Group,「Nasal mupirocin prevents Staphylococcus aureus exit-siteinfection during peritoneal dialysis,」Journal of the American Society ofNephrology:JASN 7:2403-2408(1996)；Gaspar MC,Uribe P,Sanchez P,Coello R,CruzetF.,「Hospital personnel who are nasal carriers of methicillin-resistantStaphylococcus aureus,Usefulness of treatment with mupirocin,」EnfermedadesInfecciosasy Microbiologia Clinica 10:107-110(1992)；Gernaat-van der Sluis AJ,Hoogenboom-Verdegaal AM,Edixhoven PJ,Spies-van Rooijen NH.,「Prophylacticmupirocin could reduce orthopedic wound infections.1,044patients treated withmupirocin compared with 1,260historical controls,」Acta OrthopaedicaScandinavica 69:412-414(1998)；Kluytmans JA,Mouton JW,VandenBergh MF,MandersMJ,Maat AP,Wagenvoort JH,Michel MF,Verbrugh HA.,「Reduction of surgical-siteinfections in cardiothoracic surgery by elimination of nasal carriage ofStaphylococcus aureus,」Infection Control and Hospital Epidemiology:theofficial journal of the Society of Hospital Epidemiologists of America 17:780-785(1996)；Mackie DP,van Hertum WA,Schumburg TH,Kuijper EC,Knape P,MassaroF.,「Reduction in Staphylococcus aureus wound colonization using nasalmupirocin and selective decontamination of the digestive tract in extensiveburns,」Burns:Journal of the International Society for Burn Injuries 20增刊1:S14-17；discussion S17-18(1994)；Talon D,Rouget C,Cailleaux V,Bailly P,Thouverez M,Barale F,Michel-Briand Y.,「Nasal carriage of Staphylococcusaureus and cross-contamination in a surgical intensive care unit:efficacy ofmupirocin ointment,」The Journal of Hospital Infection30:39-49(1995)；WenischC,Laferl H,Szell M,Smolle KH,Grisold A,Bertha G,Krause R.,「A holisticapproach to MRSA eradication in critically ill patients with MRSA pneumonia,」Infection 34:148-154(2006)。然而，金黄色葡萄球菌莫匹罗星抗性的出现已降低该药剂作为鼻腔去定殖药剂以及作为皮肤及伤口感染的治疗选择的功效。