CN101568257A - 抗菌剂及杀菌剂 - Google Patents

抗菌剂及杀菌剂 Download PDF

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CN101568257A
CN101568257A CNA2007800479796A CN200780047979A CN101568257A CN 101568257 A CN101568257 A CN 101568257A CN A2007800479796 A CNA2007800479796 A CN A2007800479796A CN 200780047979 A CN200780047979 A CN 200780047979A CN 101568257 A CN101568257 A CN 101568257A
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antibacterial agent
formula
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重原淳孝
尾藤昌巳
片山义博
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J Chemical Inc
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Toyoda Automatic Loom Works Ltd
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Abstract

本发明提供安全性非常高、对环境几乎无负担的抗菌剂及杀菌剂,所述抗菌剂以式[I][式中,R1和R2各自独立表示H或碱金属原子。]所表示的化合物为有效成分,所述杀菌剂以式[I][式中,R1和R2各自独立表示H或碱金属原子。]所表示的化合物为有效成分。

Description

抗菌剂及杀菌剂
技术领域
本发明涉及抗菌剂及杀菌剂,所述抗菌剂及杀菌剂具有优异的抗菌作用、杀菌作用,且安全性非常高,对环境几乎无负担。
背景技术
迄今为止开发了非常多的抗菌剂,并被用于各个领域。若将这些抗菌剂大致分类,则可分为银、陶瓷等无机类抗菌剂和山梨酸、苯甲酸及其盐等有机类抗菌剂。有机类抗菌剂以石油的挥发油为原料制备,在化妆品领域和食品领域,对羟基苯甲酸酯、苯甲酸、水杨酸、三氯生等广为人知。但现状是,上述抗菌剂或防腐剂多数在安全性方面存在问题,限制了添加的对象或添加量。
以抑制细菌(例如沙门氏菌)、酵母、霉菌等有害微生物为目的,用于动物饲料制造的被称为BIO-Add的抗菌剂含68%甲酸,但甲酸本身毒性非常高,在安全性方面存在问题。
源自安全性高的天然物质的抗菌剂也广为人知,但源自天然物质的抗菌剂不仅少,而且山萮菜硫醇(ワサビチオ一ル)等还存在成本高的问题。此外,近年来还必须考虑排放到自然界时对环境造成的负担。
作为源自天然物质的抗菌剂,源自柑橘类的抗菌剂广为人知(日本特开平8-317782号公报)。上述抗菌剂以将压榨柠檬果皮所得到的精油浓缩而得到的残渣纯化得到的化合物为有效成分,但为制成所需抗菌剂,必须调整浓度,所以制造方法复杂,不经济。
另外,报道过含有豆科植物紫穗槐提取物的抗菌剂(日本特开2004-256437号公报),但由于紫穗槐不属于栽培类植物,并且需要溶剂提取,所以不经济。日本特开2002-161075号公报记载的抗菌剂以与本发明相同的源自丹宁的没食子酸为原料,但合成需要有机溶剂。此外,必须使用冠醚等毒性高的物质。
此外,作为抗菌剂的有效成分,也报道过以天然物质类的阿魏酸为原料的阿魏酸酯化合物(日本特开2002-161004号公报),但从米糠中获得的阿魏酸本身价格昂贵,而且尚未确认酯化合物的安全性。
发明内容
本发明的目的在于:解决上述课题,提供安全性非常高、对环境几乎无负担的抗菌剂及杀菌剂。
本发明人为达成上述目的进行深入研究的结果发现,下式(I)所表示的2H-吡喃-2-酮-4,6-二羧酸(以下称“PDC”)或其碱金属盐对革兰氏阴性菌及革兰氏阳性菌具有抗菌作用及杀菌作用,从而完成本发明。
即,本发明提供以式(I)所表示的化合物为有效成分的抗菌剂:
Figure A20078004797900041
[式中,R1及R2各自独立表示H或碱金属原子。]。
本发明也提供以式(I)所表示的化合物为有效成分的杀菌剂:
Figure A20078004797900042
[式中,R1及R2各自独立表示H或碱金属原子。]。
根据本发明,PDC或其碱金属盐具有优异的抗菌作用及杀菌作用。
因此,PDC或其碱金属盐源自天然物质,作为安全性非常高、对环境几乎无负担的抗菌剂及杀菌剂的成分,在工业上实用。
实施发明的最佳方式
本发明的抗菌剂及杀菌剂分别以PDC或其碱金属盐为有效成分。作为碱金属原子,可列举出锂、钠、钾等。
PDC的制备方法无特别限制,例如可列举出以下方法:以香草醛、丁香醛、香草酸、丁香酸或原儿茶酸为原料,培养在假单胞菌属细菌(恶臭假单胞菌Pseudomonas putida PpY1100)中导入PDC的发酵生产质粒pKTVLABC的转化细胞(日本特开2005-278549号公报)。就PDC的碱金属盐而言,在日本特开2005-278549号公报记载的制备方法中,通过使氯化钠等盐存在于含有PDC的微生物发酵液中,可高纯度且高收率地获得PDC的碱金属盐。
本发明的抗菌剂及杀菌剂中,式(I)所表示的PDC或其碱金属盐的含量通常为0.1-20%质量,优选0.1-10%质量,更优选0.1-5%质量。
本发明的抗菌剂及杀菌剂表现出对各种细菌优异的抗菌作用及杀菌作用,作为所述细菌,例如可列举出金黄色葡萄球菌、枯草杆菌、凝固酶阴性葡萄球菌、链球菌、肠球菌等革兰氏阳性菌,大肠杆菌、痢疾杆菌、沙门氏菌、鼠疫耶氏菌等革兰氏阴性菌等。
本发明的抗菌剂及杀菌剂在下列目的下可加入饮食品、香妆品、口腔用品、药品、准标准药物(医薬部外品quasi drug)等,上述目的为例如:以涂布在生物体表面除菌消毒为特征的皮肤杀菌,以抑制牙齿表面及口腔内不希望的菌丛的增殖为特征的抗菌。当添加本发明的抗菌剂及杀菌剂以制备口腔用品、药品等时,在不损害本发明效果的范围内,可掺混通常用于口腔用品、药品等的成分。
实施例
以下列举实施例对本发明进行详细说明,但本发明不受下列实施例的任何限制。
实施例1
[材料]
(1)受试物质
PDC(式(I)中R=H)(纯度:99%,性状:粉末,保存条件:室温)
PDC根据日本特开2005-278549号公报中记载的方法制备。
(2)10%、1.0%、0.1%受试物质的各水溶液的制备
(2-1)10%水溶液
称量1g受试物质,用灭菌纯化水(日本药典纯化水:日本新药株式会社制,高压蒸气灭菌处理)配成10mL。
(2-2)1.0%水溶液
将10%水溶液用灭菌纯化水稀释10倍。
(2-3)0.1%水溶液
将10%水溶液用灭菌纯化水稀释100倍。
(3)菌株
金黄色葡萄球菌金黄亚种(Staphylococcus aureus subsp.aureus)(NBRC 13276)
大肠杆菌(Escherichia coli)(NBRC 3972)
肠炎沙门氏菌(Salmonella Enteritidis)(NBRC 3313)
括号内表示标准菌株编号。
(4)培养基
胰酶大豆琼脂培养基(トリプケ-スソイ寒天培地)(SCD培养基,日本Biomerieux公司制)
(5)灭菌培养皿
灭菌NE培养皿(荣研器材株式会社制)
[抗菌性试验]
在35±2℃下将上述菌株用SCD琼脂培养基培养18-24小时,然后混悬于灭菌纯化水中,将符合MacFarland No.1浊度的混悬液作为接种菌液。用琼脂培养基根据琼脂平板倾注法测定接种菌液浓度(表1)。
表1
  接种菌   浓度(cfu/mL)
  金黄色葡萄球菌金黄亚种   14×107
  大肠杆菌   37×107
  肠炎沙门氏菌   22×107
分别准备10%、1.0%、0.1%受试物质的各水溶液及灭菌纯化水(对照)各3mL(n=1)。室温下将0.03mL上述接种菌液接种到各试验溶液中。在刚接种后、接种15分钟后及接种180分钟后,在0.5mL试验溶液中加入49.5mL的灭菌磷酸缓冲液(Pro-media MV2-1000,(株)Elmex),混合。制备上述各混合液的10倍系列稀释溶液,测定活菌数,换算成1mL供试品或对照品中的菌数。活菌数的测定根据《第14版日本药典活菌数测定琼脂倾注培养法》进行。结果如表2所示。
表2
                                                                  (cfu/mL)
Figure A20078004797900071
由表2可知,本发明的抗菌剂及杀菌剂即使在0.1%质量的低浓度下也可有效抑制细菌的增殖。
实施例2
(1)受试物质
PDC(式(I)中R=H)(纯度:99%,性状:粉末,保存条件:室温)
所述PDC根据日本特开2005-278549号公报中记载的方法制备。
(2)20%受试物质水溶液的制备
称量2g受试物质,用10mL的灭菌纯化水(日本药典纯化水:日本新药株式会社制,高压蒸气灭菌处理)溶解。
(3)对照物质
BIO-Add(组成:68%甲酸、20%丙酸、12%水分,性状:水溶液,保存条件:室温,Trouw Nutrition International公司制)
(4)菌株
金黄色葡萄球菌金黄亚种(Staphylococcus aureus subsp.aureus)(NBRC 13276)
大肠杆菌(Escherichia coli)(NBRC 3972)
肠炎沙门氏菌(Salmonella Enteritidis)(NBRC 3313)
括号内表示标准菌株编号。
(5)培养基
胰酶大豆琼脂培养基(SCD培养基,日本Biomerieux公司制)
SCDLP肉汤培养基(荣研化学株式会社制)
(6)灭菌NE培养皿(荣研器材株式会社制)
[抗菌性试验]
在35±2℃下将上述菌株用SCD琼脂培养基培养18-24小时,然后混悬于灭菌纯化水中,将符合MacFarland No.1浊度的混悬液作为接种菌液。用琼脂培养基根据琼脂平板倾注法测定接种菌液浓度(表3)。
表3
  接种菌   浓度(cfu/mL)
  金黄色葡萄球菌金黄亚种   20×107
  大肠杆菌   26×107
  肠炎沙门氏菌   46×107
分别准备20%受试物质水溶液、对照物质原液及灭菌纯化水(对照)各3mL(n=1)。室温下将0.03mL上述接种菌液接种到各试验溶液中。在刚接种后、接种15分钟后及接种180分钟后,按下列条件进行中和:
受试物质:
将0.5mL试验溶液加入4.5mL 0.25mol/L灭菌氢氧化钠水溶液(氢氧化钠:和光纯药工业株式会社制)中,混合后立即加入45mL灭菌磷酸缓冲液(Pro-media MV2-1000,(株)Elmex),混合。
对照物质:
将0.5mL试验溶液加入4.5mL 2.0mol/L灭菌氢氧化钠水溶液中,混合后立即加入45mL灭菌磷酸缓冲液,混合。
灭菌纯化水(对照):
在0.5mL试验溶液中加入49.5mL灭菌磷酸缓冲液,混合。制备上述各中和液的10倍系列稀释溶液,测定活菌数,换算成1mL供试品或对照品中的菌数。活菌数的测定根据《第14版日本药典活菌数测定琼脂倾注培养法》进行。结果如表4所示。
表4
                                                                     (cfu/mL)
Figure A20078004797900091
如表4所示,本发明的抗菌剂及杀菌剂表现出与对照物质BIO-Add相同程度的抗菌作用及杀菌作用。
产业上的利用可能性
PDC或其碱金属盐可用于安全性非常高、对环境几乎无负担的抗菌剂及杀菌剂的制备。

Claims (2)

1.抗菌剂,所述抗菌剂以式[I]所表示的化合物为有效成分,式(I):
Figure A2007800479790002C1
式中,R1和R2各自独立表示H或碱金属原子。
2.杀菌剂,所述杀菌剂以式[I]所表示的化合物为有效成分,式(I):
Figure A2007800479790002C2
式中,R1和R2各自独立表示H或碱金属原子。
CNA2007800479796A 2006-12-22 2007-12-18 抗菌剂及杀菌剂 Pending CN101568257A (zh)

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WO2009151146A1 (ja) * 2008-06-12 2009-12-17 株式会社豊田自動織機 抗菌剤及び殺菌剤
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