CN102802413A - 包括萌芽物和抗菌剂的组合物 - Google Patents
包括萌芽物和抗菌剂的组合物 Download PDFInfo
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- CN102802413A CN102802413A CN201180009870XA CN201180009870A CN102802413A CN 102802413 A CN102802413 A CN 102802413A CN 201180009870X A CN201180009870X A CN 201180009870XA CN 201180009870 A CN201180009870 A CN 201180009870A CN 102802413 A CN102802413 A CN 102802413A
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Abstract
本申请涉及一种抗菌组合物，该抗菌组合物包括萌芽物和抗菌剂，其中的萌芽物增加了病原体对来自抗菌剂的攻击的易感性，而其中的抗菌剂并不抑制萌芽物。本申请同样提供了一种包含这种抗菌组合物的抗菌抹布、洗手液和涂料，以及使用这种组合物对表面进行消毒的方法。
Description
技术领域
本申请涉及一种具有抗菌性质的组合物，以及使用这种组合物消毒表面的方法。本申请尤其涉及一种对形成病原体的孢子具有有效抗菌活性的组合物。
背景技术
形成病原体的孢子，例如：梭状芽孢杆菌，为重要的致病原。在英国，梭状芽孢杆菌是院内腹泻的主要原因，并是英国医院内的相当数量的死亡的致死原因。最近数据显示梭状芽孢杆菌感染的案例数量有所下降。然而，虽然有所下降，梭状芽孢杆菌的案例仍然几乎是抗甲氧西林金黄色葡萄球菌(MRSA)案例的10倍。当前，聚合酶链式反应（PCR）核糖核酸型027是最普遍的从梭状芽孢杆菌处分离的核糖核酸型，接下来是核糖核酸型106和101。
感染患者在环境中分泌出大量的作为感染储主的梭状芽孢杆菌孢子和细胞。因此，患者通常通过吸入来自污染环境的孢子而获得这种有机体。一旦吸入，这种孢子可以在胃部的酸性环境下存活，并可以进入肠胃道，在肠胃道中它们可以萌芽生成营养细胞以产生毒素A和B，这些毒素便在易感染病人中引起疾病。
孢子萌芽是不可逆过程，其中高度稳定，静止的孢子转变成新陈代谢的活性细胞。萌芽在几个阶段进行，首先通过在细胞质膜上与萌芽受体结合而被活化。随后失去耐热性和不同的阳离子，包括：钾，氢和钠，以及钙和吡啶二羧酸(DPA)的络合物。这样导致核心的部分重新水合，然而，在皮层没有分解之前该有机体不容易成为完全的水合物。随着皮层的水解，小的酸性可溶性蛋白分解，细胞的代谢活性便启动。
众所周知，梭状芽孢杆菌可以通过暴露于萌芽溶液而模拟生成孢子，该萌芽溶液包含甘氨酸和牛磺胆酸盐的结合。这种从孢子状态的转变引起病原体容易受到抗菌剂的攻击，该抗菌剂例如：双氯苯双胍己烷。背景技术的目的为设计萌芽/根除利用病原体萌芽后易感性的实验方案。这种实验方案如图1所示。特别地，背景技术尝试设计抗菌溶液，该抗菌溶液刺激萌芽，并具有抗菌剂来攻击萌芽病原体。然而，以这种方式的抗菌剂对萌芽溶液具有抑制效果，使得萌芽/根除方式在临床条件上的成就的受限。
本发明的目的在于提供一种替代性的抗菌组合物，该组合物克服以上问题并在临床重要的病原体上具有效果。
发明内容
与背景技术中的仅与牛磺胆酸盐结合的甘氨酸组合物相比，本申请的发明人发现包含氨基酸和牛磺胆酸钠结合的特定组合物能提高孢子生殖活性。此外，发明人还发现特定的抗菌剂在作为组合物中防腐剂的同时可以有有效地杀灭萌芽的孢子。这些试剂并没有背景技术中所观察到的用于萌芽/根除的抗菌剂对病原体的萌芽的抑制效果。
此外，本申请的发明人发现，同样刺激营养细胞从梭状芽孢杆菌孢子处生成的同时，本发明的组合物能预防梭状芽孢杆菌营养细胞的孢子生殖。这在临床条件上非常有利。在医院治疗的患者排泄出许多营养细胞（还有孢子）。该营养细胞会最终形成孢子，而孢子随后作为疾病传输的载体。保持细胞处于营养形式则比较优选，因为它们会自然地被空气消灭，它们完全厌氧，或在医院中用作普遍的硬表层消毒剂。本发明的组合物因此具有两种方式进攻，首先，将孢子转化成营养细胞，其次，保持营养细胞处于营养形式。
本发明的一个方面提供了一种抗菌组合物，该抗菌组合物包括萌芽物和抗菌剂，其中所述萌芽物增加病原体对抗菌剂进攻的易感性，且其中的抗菌剂并没有抑制萌芽。
本发明的第二个方面提供了一种抗菌抹布，所述抗菌抹布包括经过本发明组合物浸渍的织物，网或纱布类材料。本发明的第三个方面提供了一种抗菌洗手液或用于对非生物表面涂层的涂料，该洗手液或涂料包括本发明的组合物。
本发明的第四个方面提供了一种消毒表面的方法，使得该表面摆脱病原体，该方法包括用本发明的组合物或含有本发明组合物的抗菌抹布或涂料以使病原体萌芽和被消灭的足够长的时间来接触表面。
本发明的抗菌组合物包括与抗菌剂结合的萌芽物。所述萌芽物选自至少两种氨基酸。所述氨基酸优选为组氨酸，精氨酸，天冬氨酸，甘氨酸的结合。更优选为组氨酸，精氨酸，天冬氨酸，甘氨酸和缬氨酸的结合。发明人所展示的这种氨基酸的特定结合尤其利于增加了细菌萌芽效果。
孢子所提供的量为适用于刺激有效的孢子繁殖。优选地，孢子的量为最终组合物的1至10nM。萌芽溶液中的氨基酸成分的量为50mM (组氨酸), 50mM (甘氨酸), 50mM (精氨酸), 50mM 1:50 (缬氨酸) 和50mM (天冬氨酸)。
抗菌剂为一种一旦接触病原体微生物所在的表面，能有效杀灭病原体微生物的试剂。优选地，抗菌剂在孢子繁殖后的萌芽阶段为有效的或可以消灭病原体。该抗菌剂同样有效杀灭没有形成孢子的病原体。
优选地，抗菌剂为苯扎氯铵和苯甲醇的结合。抗菌组合物中，苯扎氯铵与苯甲醇的比例为1:50。抗菌剂所提供的量（相对于抗菌组合物中抗菌剂的总量而言）为0.01%至2%。
抗菌组合物以临床环境下用于消毒表面的形式来提供。优选地，该表面为非生物的表面。可替代地，该表面可以为患者，医生或护工的皮肤。优选地，该组合物的形式为液体，凝胶，泡沫或喷雾，这些形式可以便利地用于所需要处理的表面。在另一个实施例中，抗菌抹布包括经过抗菌组合物浸渍的织物，网或纱布类材料。该组合物同样可以以药片形式提供。这种药片形式例如在清洁较大表面面积时，可溶于适量的水，然后医院清洁人员再将所得溶液当做消毒剂使用。在一个实施例中，该表面为人的皮肤，然后，该抗菌组合物的形式可以为洗手液或抹布。
优选地，该抗菌组合物的形式为涂料，该涂料涂在待处理的表面上。与背景技术的抗菌剂相比，这种涂料特别有利，一旦干燥后，便有效地在长时间周期内消灭病原体，背景技术的抗菌剂一旦干燥便有效，但在特定时间长度内，抗菌剂导致对萌芽剂的抑制。该抗菌剂更优选地以涂漆的形式存在，该涂漆在应用的表面上形成不会轻易擦掉的硬膜。
本发明的抗菌组合物一般可以消毒广谱病原体的表面。该组合物对形成细菌的孢子特别有效。这种孢子形成细菌的的一个实施例为梭状芽孢杆菌。然而，该组合物可以对其它例如：MRSA，绿脓杆菌，白念珠菌和黑曲霉菌株的病原体同样有效。以下结合附图和表格，通过实施例来对本发明的实施进行详细说明：其中，
图1简要地展示了背景技术中使用的萌芽/根除实验方案。
图2展示了梭状芽孢杆菌NCTC 1 1204孢子的CFU（菌落数）/mL对数值减少所述梭状芽孢杆菌NCTC 1 1204孢子暴露在不同的萌芽溶液1小时，接着进行10分钟的热冲击。
图3展示了暴露于每种氨基酸萌芽溶液1小时后，梭状芽孢杆菌NCTC 1 1204孢子的CFU/mL的对数值减少，接着在70℃下，进行10分钟的热冲击。
图4展示了用核糖核酸型027, 001 , 106和菌株 NCTC 1 1204的梭状芽孢杆菌孢子培养一小时后，在同样包含6.9mM牛磺胆酸钠的萌芽溶液中的氨基酸组合（精氨酸，天冬氨酸，甘氨酸和组氨酸）浓缩物的效果。
图5展示了暴露于不同萌芽溶液，并随后进行10分钟的热冲击后，不同的梭状芽孢杆菌菌株孢子的CFU/mL的对数值减少。
图6展示了pH值对Tris缓冲液中梭状芽孢杆菌NCTC 1 1204孢子萌芽的效果，所述Tris缓冲液包括10mM的精氨酸，天冬氨酸，组氨酸和甘氨酸，以及6.9mlV1的牛磺胆酸钠。
图7展示了在1小时暴露于不同萌芽溶液，接着进行热冲击或用冰冷却的处理后，梭状芽孢杆菌孢子的CFU/mL的对数值减少。(AA=氨基酸, ST=牛磺胆酸钠, BZC=苯扎氯铵, BZA= 苯甲醇)。
图8展示了在1小时暴露于不同萌芽溶液，接着进行热冲击或用冰冷却的处理后，梭状芽孢杆菌孢子的CFU/mL的对数值减少(CHG=氯己定二葡糖酸盐)。
图9展示了在PBS（对照）中培养的梭状芽孢杆菌营养细胞的计数，24小时后的孢子计数为100%。
图10展示了在本发明萌芽溶液中梭状芽孢杆菌营养细胞的计数，72小时后100%的计数仍然为营养细胞。
表1展示了在1小时暴露于不同萌芽溶液，接着进行热冲击或用冰冷却的处理后，梭状芽孢杆菌孢子的CFU/mL的对数值减少。
实施例1：用于萌芽溶液氨基酸的组合
梭状芽孢杆菌菌株
将核糖核酸型106菌株（18587），核糖核酸型001菌株（8565） （Health Protection Agency，英国东北）以及家典型菌种保藏中心（NCTC）11204参照菌株，连同三种核糖核酸型027菌株，R20291 (Anaerobic Reference Laboratory 加的夫), 18040和15900 (HPA, 英国东北)一起使用。
梭状芽孢杆菌孢子悬浮液的制备
梭状芽孢杆菌孢子如之前所述来制备（Shetty 等 , 1999）。用梭状芽孢杆菌的相关菌株来接种血琼脂平板，并在37℃下厌氧地培养(iniMACS anaerobic work station, Don Whitley, Shipley, 英国)72小时，随后在收集所有的菌落并置于10mL50%生理盐水（0.9% w/v）和50%甲基化酒精之前，移开所述平板并在常温下放置24小时。所述悬浮液在用玻璃棉过滤之前进行完全地涡旋混合，并在4℃下保存直到使用。在每次实验之前，孢子悬浮液以13000rpm速度离心5分钟，并在消毒的蒸馏水中重新悬浮。
氨基酸
在实验中使用了以下氨基酸：甘氨酸，L-异亮氨酸， L-脯氨酸，D-丙氨酸，L-谷氨酸，L-丝氨酸 ，L-苏氨酸，L-天冬氨酸，L-精氨酸， L-缬氨酸， L-亮氨酸，L-谷氨酰胺，L-色氨酸和L -天冬酰胺（都来自英国Sigma-Aldrich公司），L-赖氨酸，L-组氨酸和L-蛋氨酸（BDH）, L-β-苯基丙氨酸（Fisons公司）L-半胱氨酸（Fluka公司）。酪氨酸由于不溶于蒸馏水，所以没有进行测试。
作为共同萌芽物的不同氨基酸对梭状芽孢杆菌孢子的效果
所有的萌芽溶液包含0.4% (w/v)的氨基酸（之前研究使用的甘氨酸浓度（Wheeldon 等., 2008））和13.8mM(w/v)的牛磺胆酸钠(Sigma-Aldrich公司, 英国)，（在十二指肠中加倍生理浓度(Leverrier 等., 2003)），将该牛磺胆酸钠溶于蒸馏水中，并在121℃下高压灭菌15分钟来消毒。同样测试包含13.8mM牛磺胆酸钠(ST)的加倍强度的硫乙醇酸盐培养基(Oxid, 英国)，用于与其它萌芽溶液作对比。如果梭状芽孢杆菌长孢子(包含 106 CFU/mL)，便随后将一百微升的每种萌芽溶液加多100μL,并完全涡旋混合。1小时后，将整个200μL的体积加入9.8mL 的威尔金查而根培养基（Wilkins Chalgren broth） (Oxoid, 英国)，使其在70℃下平衡10分钟，或用冰使其冷却。经过合适的稀释，在加入15mL的，包含0.1 % (w/v) ST 和5% (v/v) 脱纤维马血的 molton 苛养厌氧菌琼脂(FAA) (Lab M, 英国)之前，将1mL的样品置于消毒的皮氏（Petri）培养皿中。平板在37℃下厌氧培养48小时之前，进行完全混合。上述方法是来自Levinson和Hyatt (1966)的改进。
梭状芽孢杆菌孢子萌芽所需要的氨基酸的最佳浓度的确定
精氨酸，天冬氨酸，甘氨酸和组氨酸以200，20，2，0.2和0.02mM的量制备，连同13.8mM的ST（在实验中以1:2稀释时为双倍效果），一起溶于蒸馏水中。加热所有溶液直到溶解，并用高压灭菌来消毒。用与以上相同的方法来测试不同浓度的萌芽溶液对梭状芽孢杆菌NCTC 1 1204，核糖核酸型027 (R20291 )，001和106的效果。
针对六种不同的梭状芽孢杆菌菌株的孢子，氨基酸和牛磺胆酸盐的功效。
分别单独或混合加入精氨酸、天冬氨酸、甘氨酸和组氨酸 (20mM w/v) 至13.8mM (w/v) ST，并加热溶解于蒸馏水中，然后高压灭菌消毒。用以上的相同方法来确定这些氨基酸溶液对梭状芽孢杆菌核糖核酸型001、106、027 (R20291 , 15900和18040)和NCTC 1 1204的孢子的功效。
缓冲萌芽溶液的pH值对梭状芽孢杆菌孢子的萌芽效果
将精氨酸，天冬氨酸，甘氨酸和组氨酸（20mM w/v），13.8mM (w/v)ST和200mM (w/v) Tris溶于蒸馏水中，在用过滤或高压灭菌消毒之前用盐酸调节pH值至5，6，7，8和9。用与以上相同的方法来测试对梭状芽孢杆菌NCTC 1 1204孢子的每份缓冲溶液。
实施例2-具有抗菌和防腐的萌芽溶液对梭状芽孢杆菌的功效
萌芽溶液
一种溶液包含100mM (w/v)甘氨酸，组氨酸，缬氨酸，天冬氨酸和精氨酸，13.8mM (w/v)牛磺胆酸钠, 100mM (w/v) Tris缓冲液, 0.04% (w/v)苯扎氯铵以及2% (v/v)的苯甲醇，将该溶液用蒸馏水调整至所需体积，并用盐酸调节pH值至7。加热该溶液，并在过滤通过0.2pm的孔尺寸之前，加热并完全混合该溶液，以溶解所有的成分（该溶液在实验中以1：2来稀释时，为加倍功效）。
梭状芽孢杆菌孢子悬浮液的制备
梭状芽孢杆菌孢子的制备如上所述
缓冲液
缓冲液的改进来自Espigares 等, (2003)，并包含以下成分：120mL (v/v)吐温（Tween）-80，25mL (v/v) 的40%偏亚硫酸钠，15.69g (w/v)五水硫代硫酸钠，10g (w/v)L-半胱氨酸，4g (w/v) 卵磷脂，用蒸馏水制成1000mL溶液，并将pH值调节至7，用高压灭菌消毒。
萌芽效果测试
将100微升的萌芽溶液加入100μL的梭状芽孢杆菌孢子中（包含106 CFU/mL），并完全涡旋混合。对于对照样，将100μL的消毒蒸馏水与100μL的梭状芽孢杆菌孢子悬浮液混合。孢子悬浮液同样用包含氯苄烷铵和Tris缓冲液（没有氨基酸或牛磺胆酸盐），具有Tris缓冲液的苯甲醇（没有氨基酸或牛磺胆酸盐），以及包含五种氨基酸和牛磺胆酸盐的溶液（无抗菌剂）来培养。一小时后，将整个200μL体积的溶液加入9.8mL缓冲液中（如上所述），在70℃下平衡10分钟（热冲击来杀灭萌芽细胞），或用冰块冷却（对照）。经过合适的稀释后，在加入包含0.1 % (w/v) 的ST 和5% (v/v) 脱纤维马血的molten苛养厌氧菌琼脂(molten Fastidious Anaerobe Agar FAA) (Lab M, 英国)之前，将1mL的样品置于消毒的皮氏（Petri）培养皿中。该平板在37℃下厌氧培养48小时（mini ACS Anaerobic Workstation，Don Whitley Scientific 公司）前，进行完全混合。上述方法从之前Levinson和 Hyatt (1966)的研究中改进。
结果和讨论
作为与甘氨酸共同萌芽物的其它氨基酸对梭状芽孢杆菌NCTC 11204孢子的功效
用精氨酸，天冬氨酸或组氨酸，甘氨酸和ST来培养梭状芽孢杆菌NCTC 1 1204， 并在热冲击后，产生CFU/mL的较大对数值减少，分别为2.78 (99.8%), 3.06 (9.99%)和3.12 (99.9%)。缬氨酸（具有甘氨酸和ST）和亮氨酸（具有甘氨酸和ST）分别产生CFU/mL的对数值减少分别为：1 .72 (98.1 %)和1 .62 (97.6%)，这和只有甘氨酸和ST (1 .85对数值减少 (98.6%))较为相似。所有的其它氨基酸测试所产生的对数值减少小于只有甘氨酸和牛磺胆酸盐所产生的对数值减少。
单独的共同萌芽物和与甘氨酸以及牛磺胆酸钠的结合对梭状芽孢杆菌NCTC 11204孢子的功效
与用精氨酸和天冬氨酸或具有ST的组氨酸来培养孢子相比，当最初筛选的四种最有效氨基酸(精氨酸, 天冬氨酸,组氨酸和甘氨酸)一起置于具有ST的溶液，并用梭状芽孢杆菌孢子培养时，在热冲击之后产生了CFU/mL为3.71 (99.9%)的更大对数值减少，但没有甘氨酸时，每个溶液产生少于一个对数值的减少。
梭状芽孢杆菌孢子萌芽所需的氨基酸最佳浓度的确定
当氨基酸的浓度处于10到100mM之间时，在所有的菌株测试中，梭状芽孢杆菌孢子的萌芽为最理想。低于这个浓度时，在0.1mM及以下浓度处观察，梭状芽孢杆菌孢子的萌芽就会小于一个对数值减少而显著下降。在所有的梭状芽孢杆菌菌株中，当孢子暴露于100mM的氨基酸，而没有热冲击时，可以观察到CFU/mL的显著下降。
氨基酸和牛磺胆酸盐钠对于梭状芽孢杆菌PCR核糖核酸型027的不同菌株孢子的功效。
暴露于与ST结合的四种氨基酸的梭状芽孢杆菌PCR核糖核酸型027的所有菌株产生的对数值减少与当孢子暴露于硫乙醇酸盐流体培养基和ST所产生的对数值减少相似。当与甘氨酸和牛磺胆酸钠结合时，在每个核糖核酸型027菌株处观察，天冬氨酸与组氨酸都增加了CFU/mL的对数值减少。然而，当加入甘氨酸和ST时，精氨酸并没有引起CFU/mL对数值下降的更进一步提高。更有趣的是，与R20291菌株相比，对于硫乙醇酸盐流体培养基或四种氨基酸与ST结合，两种临床菌株（18040 和15900）产生显著的更大的对数值下降。
对于六种不同的梭状芽孢杆菌菌株的孢子，氨基酸和牛磺胆酸钠的功效
在暴露于氨基酸和硫乙醇酸盐溶液之后，观察到梭状芽孢杆菌的NCTC 1 1204参照菌株产生了CFU/mL的最大对数值减少。在每个不同的测试的萌芽溶液中，PGR核糖核酸型001所产生的对数值减少与PCR核糖核酸型207所产生的对数值减相似。例如，梭状芽孢杆菌核糖核酸型001和027 R20291在用四种氨基酸和ST培养，并且进行热冲击后所产生的CFU.Ml的对数值减少分别为：2.12 (99.2%) 和1 .98 (99%)。
缓冲萌芽溶液的pH值对梭状芽孢杆菌NCTC 11204孢子萌芽的效果
缓冲萌芽溶液的pH值大大地影响着用氨基溶液（和ST）培养后，接着进行热冲击所产生的CFU/mL的对数值减少。在酸性的pH为5时，萌芽溶液没有产生任何CFU/mL的对数值减少。在中性的pH6.98时，所观察到CFU/mL (99.9%)中3.32的对数值下降，该pH值为理想的pH值。更大碱性的pH8.81没有增加所观察到的CFU/mL的对数值减少，但程度比酸性pH程度要更小。
具有抗菌剂和防腐剂的萌芽溶液对梭状芽孢杆菌的效果
将梭状芽孢杆菌孢子用氨基酸和Tris缓冲液中的牛磺胆酸盐混合物培养一小时，并进行热冲击后产生CFU/mL (99.9% 减少)的3个对数值减少。然而，如果没有热冲击，在用氨基酸溶液培养后，剩余孢子的数量中只有很少的减少（0.13对数值减少）。用包含Tris中的苯扎氯铵或Tris中的苯甲醇来培养梭状芽孢杆菌孢子时，无论进行或没有进行热冲击都产生CFU/mL小于0.3的非常低的对数值减少。然而，当梭状芽孢杆菌孢子用包含氨基酸，牛磺胆酸盐，苯扎氯铵和Tris的苯甲醇培养时，如果用冰处理孢子则有2.77的CFU/mL对数值减少(99.8% 减少)，如果用热冲击处理孢子则有2.99的CFU/mL对数值减少(99.9% 减少)。
发明人同样发现EDTA和双氯苯双胍己烷抑制萌芽溶液，其中苯扎氯铵和苯甲醇并没有影响萌芽。苯扎氯铵和苯甲醇并不能杀灭孢子，且不能引发萌芽。用苯扎氯铵，苯甲醇，氨基酸和牛磺胆酸钠培养1小时之后，没有经过热处理的孢子被杀灭，而孢子似乎与包含苯扎氯铵和苯甲醇的萌芽溶液中发生萌芽时才能被杀灭。
缓冲液被发现对梭状芽孢杆菌细胞和其它细菌没有毒性，并有效地使抗菌剂失去活性。因此，用苯扎氯铵，本甲醇，氨基酸和牛磺胆酸钠培养1小时后，所产生的CFU/mL的下降不可能是琼脂板“延续”效果的结果。
本发明还发现苯扎氯铵和苯甲醇不会影响萌芽溶液的效果。苯扎氯铵和苯甲醇因此展示了防腐功效，并似乎可以杀灭梭状芽孢杆菌的萌芽孢子。
萌芽溶液对孢子形成的抑制效果
结果展示在图9和10中，在萌芽溶液的存在下培养72小时后，计数为100%的仍为营养细胞，同时在对照物中（PBS中培养细胞），24小时后计数100%的孢子。这样的结果表明本发明的萌芽溶液阻止了梭状芽孢杆菌营养细胞的孢子繁殖。
Claims (10)
1.一种抗菌组合物，其特征在于，所述抗菌组合物包括萌芽物和抗菌剂，其中所述萌芽物增加病原体对来自抗菌剂的攻击的易感性，其中所述抗菌剂并不抑制所述萌芽物。
2.一种根据权利要求1所述的组合物，其特征自傲与在于，所述萌芽物包括牛磺胆酸盐和至少两种氨基酸。
3.根据权利要求2所述的组合物，其特征在于，所述牛磺胆酸盐为牛磺胆酸钠，所述至少两种氨基酸为组氨酸、精氨酸、天冬氨酸、甘氨酸和缬氨酸。
4.根据前面任一项权利要求所述的组合物，其特征在于，细菌病原体选自：梭状芽孢杆菌、抗甲氧西林金黄色葡萄球菌(MRSA)、绿脓杆菌、白色念珠菌和黑曲菌。
5.根据前面任一项权利要求所述的组合物，其特征在于，所述抗菌剂包括苯扎氯铵和苯甲醇。
6.根据前述任一项权利要求所述的组合物，其特征在于，相对于最终组合物，所述萌芽物的量为1至10mM，而抗菌剂的量为0.01 %至2%。
7.根据前述任一项权利要求所述的组合物，其特征在于，所述组合物的形式为液体、凝胶、泡沫、喷雾或药片。
8.一种抗菌抹布，其特征在于，所述抗菌抹布包括用前述任一项权利要求所述的组合物浸渍的织物、网或纱布类材料。
9.抗菌洗手液、或者用于涂抹在非生物表面上的涂料或漆，其特征在于，包含根据权利要求1-7中任一项所述的组合物。
10.一种消毒表面、从而使得表面基本无病原体的方法，其特征在于，所述方法包括：使所述表面与权利要求1-7中任一项所述的组合物、或者权利要求8所述的抗菌抹布、或者权利要求8所述的涂料接触足够长的时间，以使病原体萌芽并被杀灭。
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| US20110135702A1 (en) | 2009-12-09 | 2011-06-09 | Hoffman Douglas R | Sporicidal composition for clostridium difficile spores |
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| US6656919B1 (en) * | 2002-01-11 | 2003-12-02 | Clarence L. Baugh | Method and a product for the rapid decontamination and sterilization of bacterial endospores |
| WO2003061610A1 (en) * | 2002-01-18 | 2003-07-31 | Walker Edward B | Antimicrobial and sporicidal composition |
| US20080254010A1 (en) * | 2007-03-12 | 2008-10-16 | Joseph Myron Sasser | Controlling Clostridium difficile-Associated Disease in the Gastrointestinal Tract |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107466207A (zh) * | 2015-04-02 | 2017-12-12 | 拜奥特罗尔有限公司 | 抗微生物组合物 |
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| US20130142856A1 (en) | 2013-06-06 |
| DK2536278T3 (en) | 2015-01-12 |
| US20160157490A1 (en) | 2016-06-09 |
| US10244758B2 (en) | 2019-04-02 |
| WO2011101661A1 (en) | 2011-08-25 |
| JP2013519720A (ja) | 2013-05-30 |
| US9314028B2 (en) | 2016-04-19 |
| EP2536278B1 (en) | 2014-11-05 |
| CN102802413B (zh) | 2014-08-06 |
| EP2536278A1 (en) | 2012-12-26 |
| ES2527242T3 (es) | 2015-01-21 |
| JP5735990B2 (ja) | 2015-06-17 |
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