CN102497894A - 用于医疗器械的抗感染润滑剂及其制备方法 - Google Patents

用于医疗器械的抗感染润滑剂及其制备方法 Download PDF

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CN102497894A
CN102497894A CN201080041331XA CN201080041331A CN102497894A CN 102497894 A CN102497894 A CN 102497894A CN 201080041331X A CN201080041331X A CN 201080041331XA CN 201080041331 A CN201080041331 A CN 201080041331A CN 102497894 A CN102497894 A CN 102497894A
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solvent
coating material
antipathogen
lubricant
silicone oil
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M·Q·霍安格
M·A·卡恩
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Becton Dickinson and Co
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Abstract

包含多种溶剂的润滑抗菌涂层材料，其实现了相互混溶并提供大体上均匀的产品。提供了具有抗病原剂和用于溶解该抗病原剂的溶剂的涂层材料。涂层进一步包括润滑剂和用于溶解该润滑剂的溶剂。因此，涂层材料包含适于施加到期望表面的抗菌和润滑性质，以杀死已知引起导管相关血流感染的病原体或抑制其生长。

Description

用于医疗器械的抗感染润滑剂及其制备方法
发明背景
本公开一般地涉及润滑抗菌涂层材料。特别地，本公开讨论包含多种溶剂以实现材料成分的相互混溶性的硅油基抗菌涂层材料。
在医药和卫生保健领域中，患者的皮肤可能以多种方式和由于多种原因被刺穿。在一个例子中，由于手术原因，用尖锐的物体例如外科手术刀切割患者的皮肤。在另一个例子中，迫使套管或静脉内(“IV”)导管通过患者的皮肤进入内部空间，例如患者的脉管系统。在该例子中，套管或IV导管可用于将流体（例如，盐溶液、药物和/或全部肠外营养)灌注到患者体内、从患者处抽取流体（例如，血液)、和/或监测患者脉管系统的多种参数。
然而，当患者的皮肤被刺穿时，患者体内感染的可能性增加。的确，据估计每年仅在美国就有几十万患者患上由通过或由于IV导管或其他IV进入器械例如皮下注射针传染给患者的病原体引起的某种形式的血流感染。引起这些导管相关的血流感染的很多细菌病原体是常见的皮肤定居者(colonizer)，或是存在于患者的皮肤上的菌群，并且通常被认为是通过导管插入部位进入患者的身体。
通常，这些导管相关的血流感染引起患者生病，并且在某些情况下引起死亡。此外，因为某些感染是由耐抗生素的细菌菌株（例如耐二甲氧基苯青霉素金黄色葡萄球菌（Staphylococcus aureus)(“MRSA”)和耐万古霉素肠球菌(Enterococci)(“VRE”))引起的，所以这样的感染可能难以治疗并且流行程度可能增加。另外，因为患有血流感染的患者可能要求额外的医疗，所以导管相关的血流感染也可与增加的医疗成本相关。
在尝试限制医院、门诊患者、家庭护理和其他卫生保健情形中的血流感染(即，导管相关的感染)中，很多已经尝试向医疗器械和设备施加多种抗菌涂层。该抗菌涂层提供作为屏障，以防止通常与血流感染有关的病原体的生长或定居。然而，这样的抗菌涂层不是没有它们的缺点。例如，很多在涂层材料内的抗病原剂是水溶性的，并因此在与和患者有关的流体接触期间容易从医疗器械洗掉。此外，当被干燥时，某些最有效的抗病原剂留下粘性或有些粘的残留物，由此使其难以与医疗器械一起工作用于在医疗器械和患者之间要求润滑界面的过程。
因此，虽然目前存在用于涂布或以其他方式处理医疗器械表面以防止感染的技术，但挑战仍然存在。因此，提高目前的技术或甚至用其他技术代替目前的技术将是本领域中的改进。
发明内容
本申请涉及能够施加到血管内器械上以杀死多种病原体或防止多种病原体生长的润滑、抗菌涂层材料。在一些实施方式中，抗菌涂层材料包括选择来杀死多种病原体或抑制多种病原体生长的一种或多种抗病原剂。抗病原剂通常溶于水和具有不超过两个碳原子的低级醇中的至少一种。因此，涂层材料进一步包括用于将抗病原剂溶解在涂层材料内的溶剂。
抗菌涂层材料的进一步成分包括润滑剂，以确保经涂布的医疗器械和患者之间的润滑界面。在一些实施方式中，润滑剂选自一种或多种硅油。硅油通常溶于烃、酮、卤代烃和具有至少3个碳原子的高级醇中的至少一种。因此，该涂层材料进一步包括用于将润滑剂溶解在涂层材料内的溶剂。
本发明的重要特征是抗菌涂层材料的多种成分的相互混溶性。因此，在本发明的一些实施方式中，提供相互混溶的抗病原剂、抗病原溶剂、润滑剂和润滑剂溶剂的多种组合，以确保均匀的涂层材料。在一些实施方式中，涂层材料进一步包括聚乙氧基化表面活性剂，以进一步确保涂层的多种成分的混溶性。在其他实施方式中，结合多种溶剂，以获得相互混溶和均匀的涂层材料。
在一些实施方式中，改变抗菌涂层材料，以具有能够实现将材料施加在期望表面上的期望的任何合适特性。例如，在一些实施方式中，以液体形式提供涂层材料，其通过浸渍或刷抹被施加在医疗器械表面上。在其他实施方式中，以凝胶、乳膏、泡沫、气溶胶或具有期望稠度和粘度的另一种流体中的至少一种，提供涂层材料。
本发明的涂层材料可被施加到任何期望的表面上。例如，在一些实施方式中，涂层材料被直接施加到血管内医疗器械的外表面和内表面的至少一个上。在其他实施方式中，在刺穿或以其他方式损害皮肤以进行医疗过程之前，涂层材料被直接施加到患者皮肤上。
发明详述
为了提供本发明的完整理解，以下描述讨论具体细节。然而，本领域技术人员将理解，不使用这些具体细节，能实施本发明。的确，本发明可以任何合适的方式修改，并且可与工业中传统使用的任何合适的化学品、装置和技术结合使用。因此，本发明实施方式的以下更详细的描述不意欲限制范围，而仅代表一些目前优选的实施方式。另外，虽然以下讨论集中在卫生保健情形中使用本发明，但该抗菌材料可用于任何合适的情形中。
一般地，本发明涉及能够施加到血管内器械上以杀死多种病原体或防止多种病原体生长的润滑、抗菌涂层材料。如在此所用的，术语病原体和多种病原体可包括任何潜在有传染性的微生物，例如细菌(例如，波形细菌、革兰氏阴性细菌、革兰氏阳性细菌、需氧细菌、厌氧细菌、分枝杆菌、螺旋菌(spirochete)、表皮葡萄球菌(Staphylococcusepidermis)、金黄色葡萄球菌(Staphylococcus aureus)、大肠杆菌(Escerchiacoli)、普通变形杆菌(Proteus vulgaris)、粪链球菌(Staphylococcusfaecalis)、克雷白氏杆菌(Klebsiella)、产气肠杆菌(Enterobacteraerogenes)、奇异变形杆菌(Proteus mirabilis)和类似物)，真菌(例如，真菌孢子、黑曲霉(Aspergillus niger)、黄曲霉(Aspergillus flavus)、黑色根霉菌(Rhizopus nigricans)、植物标本分支孢子菌(Cladosporiumherbarium)、絮状麦皮癣菌(Epidermophyton Floccosum)、须毛癣菌(Trichophyton mentagrophytes)、荚膜组织胞浆菌(Histoplasmacapsulatum)和类似物)，酵母菌(例如，酿酒酵母(Saccharomycescerevisiae)、白色念珠菌(Candida albicans)和类似物)，病毒或其他潜在危险的微生物。
本发明的优选应用为将抗菌涂层材料直接施加到血管内器械例如静脉内导管的外表面上。在一些实施方式中，涂层材料仅被施加到那些直接接触患者的血管内器械的表面上。在其他实施方式中，涂层材料被施加到容易受到病原体定居的血管内器械的任何表面上。因此，当经涂布的血管内器械通过患者的皮肤进行放置时，涂层材料的抗菌性质杀死可潜在导致导管相关的血流感染(CRBSI)的病原体或防止其生长。
抗菌涂层材料包括选择来提供既抗感染又润滑的涂层材料的多种相互混溶的成分。通常，用多种粘度的硅油润滑用于患者护理的所有导管。硅油是基于碳的有机化合物的硅类似物，其基于硅而不是碳形成相对长和复杂的分子。硅油链由在四价硅原子处被多种其他种类取代的交替的硅氧烷原子形成。
本发明的实施方式包含用作抗菌材料内的润滑剂的硅油。根据本发明的实施方式，针对在抗菌涂层材料内它们的润滑性质和它们的混溶性，选择硅油。此外，选择硅油，以便它们通常缺少在水中和在其他与患者有关的流体如血液、汗水、水和尿中的溶解性。一旦施加到血管内器械的表面上，硅油成分防止涂层材料轻易从器械表面去除。因此，硅油通过确保涂层材料和血管外器械之间的粘合，保持涂层的抗菌性质。根据本发明使用的硅油的非限制性例子包括二甲基硅油、三氟丙基甲基硅氧烷和其组合。本领域技术人员将理解，其他硅油也可根据本发明的教导而被成功使用。
本发明的一个重要方面要求抗菌涂层材料的每种成分是相互混溶的，以便提供大体上均匀的涂层材料。因此，涂层材料包括多种易混溶地相容的成分，包括相容的溶剂，以将多种成分溶解到经混合以提供涂层材料的相互混溶的溶液中。因此，虽然某些成分在硅油中可溶，但其他成分可能不溶，因此需要额外的溶剂。另外，在一些实施方式中，需要溶剂以使硅油能够在涂层材料内溶解。
例如，在一些实施方式中，抗菌涂层材料进一步包括能够混溶地溶解硅油的溶剂。期望的硅油溶剂将通常是与涂层材料的其他成分相容或混溶的。合适的溶剂可包括多种烃、酮、卤代烃、和具有至少3个碳原子的醇。符合本发明和根据本发明的硅油溶剂的非限制性例子包括甲基九氟丁基醚、乙基九氟丁基醚和反式-1，2-二氯乙烯和聚乙氧基化表面活性剂。在一些实施方式中，涂层材料包括单一硅油溶剂。在其他实施方式中，涂层材料包括硅油溶剂的混合物。
抗菌涂层材料的重要成分为选择来杀死多种病原体或防止多种病原体生长的抗病原剂。通常基于其抑制病原体活性的能力和结合涂层材料的其他成分的混溶性选择期望的抗病原剂。相容、高效的抗病原剂的非限制性例子包括双醋酸洗必泰、葡萄糖酸洗必泰、三氯生、苯扎氯铵、对氯间二甲苯酚(PCMX)和其他已知抑制细菌生长的药剂。
最高效抗病原剂溶于水或低级醇，例如具有不超过两个碳原子的醇。然而，这些药剂通常不溶于硅油，由此使其难以在硅油中溶解某些抗病原剂，例如双醋酸洗必泰和三氯生。因此，在本发明的一些实施方式中，期望在涂层材料内包括能够混溶地溶解抗病原剂的溶剂。相容的抗病原剂溶剂的非限制性例子包括水和低级醇，例如甲醇和乙醇。
抗菌涂层材料可包括提供能够施加到血管内器械上的相互混溶的抗感染涂层所需的任何合适浓度的前述成分。现在参考表1，其显示了根据本发明代表性实施方式的多种抗菌涂层材料的九种制剂。
表1
Figure BDA0000144124600000051
在一些实施方式中，加到涂层材料中的硅油被高度浓缩，由此需要加入相对小的量。例如，制剂1、2和4-6，每个都包括高粘性和浓缩的12,500cSt硅酮，由此导致涂层材料总重量的仅3％归因于硅油。相反，制剂3、8和9每个都包含二甲基硅氧烷和三氟丙基甲基硅氧烷硅油的较低浓缩的混合物，由此导致制剂总重量的大约84％至90％归因于硅油。最后，制剂7同时包括高度浓缩的12,500cSt硅酮(3％)和硅油的混合物(89.8％)，大约93％的总百分比重量归因于硅油。
每种制剂都包括至少一种溶剂，以帮助增溶硅油。在一些实施方式中，多种硅油溶剂被加到制剂中。例如，制剂7包括单一卤代烃溶剂，而制剂1-3和5各包含两种卤代烃溶剂，提供每种溶剂或溶剂的组合以溶解它们各自的硅油。相似地，制剂4和6各包含三种卤代烃溶剂。相比之下，制剂8和9不包含任何卤代烃溶剂，而包含聚乙氧基化表面活性剂，Cremophor
Figure BDA0000144124600000061
对于包含非卤代溶剂的制剂，例如制剂8和9，发现加入少量聚乙氧基化表面活性剂提高涂层材料内硅油的混溶性。因此，在本发明的一些实施方式中，硅油溶剂必须包括卤代烃溶剂和聚乙氧基化表面活性剂中的至少一种。
每种制剂都包括至少一种抗病原剂。根据本发明的抗病原剂可包括能够杀死或以其他方式阻碍病原体生长的任何单一化合物、化学品、试剂、药物、基质(substrate)或溶液。此外，根据本发明的抗病原剂可包括能够杀死或以其他方式阻碍病原体生长的化合物、化学品、试剂、药物、基质或溶液的任何组合。根据本发明多种实施方式的常见的抗病原剂包括双醋酸洗必泰、葡萄糖酸洗必泰、三氯生、苯扎氯铵、对氯间二甲苯酚(PCMX)和其他已知抑制细菌生长的药剂。
在一些实施方式中，基于抗病原剂的抑制特定病原体或病原体种类的能力选择抗病原剂。例如，制剂1至8每一种包含涂层材料总重量的大约0.1％至7.5％的多种浓度的双醋酸洗必泰。双醋酸洗必泰为同时杀死革兰氏阳性和革兰氏阴性微生物的化学抗菌剂。也因为其抑菌性质经常使用双醋酸洗必泰。因此，制剂1至8通常被提供用于那些期望防止细菌生长的应用中。相比之下，制剂9同时包括双醋酸洗必泰和三氯生抗病原剂。三氯生是效力大的广谱抗细菌和抗真菌剂。因此，除了杀死细菌微生物外，制剂9也对真菌微生物有效，由此使制剂9成为更广泛的抗菌涂层材料。
如以上所提及的，本发明的一些实施方式进一步包括能够混溶地溶解抗病原剂的溶剂。通常，选择该抗病原体溶剂，以溶解抗病原剂，以便抗菌涂层材料内的所有成分相互混溶。该抗病原体溶剂选自水和包含不超过两个碳原子的低级醇中的至少一种。表1的制剂每一种包含涂层材料总重量的大约5.13％至30.0％的溶剂乙醇。如实现相互混溶性所需要的，基于其他成分的浓度选择多种浓度的乙醇溶剂。
在一些实施方式中，抗菌涂层材料包括多于一种类型的醇。在这样的实施方式中，涂层材料可包括任何合适数量的醇，包括2、3、4或更多种醇。另外，抗病原溶剂可包括醇的任何合适的组合。在一个实施例中，溶剂包括甲醇和乙醇。
本领域技术人员将理解，可通过使用多种溶剂和溶剂的组合实现抗菌涂层材料成分的相互混溶性。本领域技术人员也将理解，可包括某些溶剂，以有意地增加或降低涂层材料的有效性。例如，在一些实施方式中，可包括较高浓度的所选择的溶剂，例如醇，以进一步抑制病原体的生长。在其他实施方式中，所选择的溶剂，例如醇，可与软化剂或增湿剂结合，以消除与溶剂有关的皮肤刺激和干燥。
如以上所提及的，在一些实施方式中，抗病原剂溶剂包括水。在这样的实施方式中，可以以任何合适的水溶液向抗菌涂层材料提供水，包括稀释醇或其他包含水的溶液。然而，在一些实施方式中，水包括纯化水，例如美国药典(“USP”)水或去离子水。例如，在抗病原溶剂包括水的情况下，涂层材料可包括任何合适量的水。的确，在一些实施方式中，除了硅油、硅油溶剂、抗病原剂、醇和/或任何其他合适的成分外，涂层材料的剩余部分包括水。在一些实施方式中，涂层材料包括大约1％至大约99％的水。
在一些实施方式中，抗菌涂层进一步包括至少一种额外的杀生物剂。在这样的实施方式中，额外的杀生物剂可包括任何合适的杀死、减少或以其他方式阻止病原体增殖，同时允许抗菌涂层材料消毒和润滑血管内器械的表面并适于在人皮肤上使用的化学品或多种化学品。合适的杀生药剂的一些例子包括银和/或铜离子和纳米颗粒(例如，tinosan二氢柠檬酸银)、磺胺嘧啶银(silver sulphadiazine)、咪唑、三唑、烯丙胺、苯酚、六氯酚、抗生素和磺酰胺。
在抗菌涂层材料包括额外的杀生物剂的情况下，涂层材料可包括任何合适部分的杀生物剂。在一个实例中，额外的杀生物剂占涂层材料总重量的大约0.01％至大约10％。在另一个实例中，以重量计，杀生物剂占涂层材料的大约0.1％至大约5％。仍然在另一个实例中，以重量计，额外的杀生物剂占抗菌涂层材料的大约0.5％至大约2％。
除了上述成分，抗菌涂层材料可包括任何合适浓度的任何合适成分，其允许涂层材料润滑地消毒表面，适于皮肤使用，并防止病原体的定居。这类任选成分的一些例子可包括增稠剂、中和剂、pH调节剂、金属盐、染料、香料和/或其他合适的化学品。
抗菌涂层材料也可被改变以具有期望能够使材料施加到期望的表面上的任何合适的特性。例如，在一些实施方式中，涂层材料包括通过浸渍或刷抹施加到静脉内器械表面上的液体。在其他实施方式中，涂层材料包括凝胶、乳膏、泡沫、气溶胶或具有期望稠度/粘度的另一种流体中的至少一种。
可以任何合适的方式使用抗菌涂层材料。例如，涂层材料可被放置在容器上和/或容器中，从其中可分配或以其他方式使用材料，以清洁物体。在这样的情况，涂层材料可被放置在具有允许与涂层材料一起使用同时允许涂层材料如期望那样起作用的任何部件、装置或特性的任何合适的容器上和/或容器中。合适容器的一些例子可包括吸收材料（例如，小毛巾、纱网、拭子、拭子条、海绵、带有供应流体储槽施加器的海绵、织物、一块纤维等)、喷雾瓶、气溶胶分配器，或任何其他合适的容器。
在抗菌涂层材料被放置在吸收材料上和/或吸收材料中的情况下，该材料可包括当吸收材料接触（例如，擦拭)表面时能够吸收涂层材料、释放一些材料并且适于在人皮肤上使用的任何合适物质。合适物质的一些例子可包括棉花、纸、纤维素、毛制品、聚酯、聚丙烯、织物，或能够形成能够将涂层施加在表面上的吸收物体的另一种材料。
涂层材料可被施加到基本上任何表面上。在一个实例中，涂层材料被直接施加到皮肤上（例如，以消毒手，在皮肤被刺穿前清洁患者的一部分皮肤，在其被刺穿后清洁和护理患者的皮肤等)。在另一个实例中，涂层材料被施加到非生命物体上，例如医疗器械、地面、椅子、门把手、桌子、电脑键盘、电脑鼠标等。
涂层材料可以任何合适的方式用于涂布表面。例如，物体例如医疗器械（例如，导管、注射器、外科手术刀，或用于卫生保健情形中的另一物体)可用抗菌材料进行涂布。在该实例中，涂层材料以任何合适的方式被施加到物体上，包括通过擦拭（例如，经由吸收材料)、喷洒、浸泡、喷雾、浸没，或以其他方式将涂层材料施加到物体上。另外，在该实例中，当用抗菌材料涂布物体时，涂层材料提供了不会通过接触患者而轻易被去除的抗病原剂润滑层。因此，抗病原体材料层可保留在物体上一段时间，并且由此起到防止病原体的生长和降低将定居在物体涂布表面上的病原体量。
实施例
如下，通过抑制实验区测试制剂3(见上面表1)的抗菌剂效力。通过混溶地混合双醋酸洗必泰(0.49％)、三氯生(0.49％)、USP乙醇(13.85％)、二甲基硅氧烷和三氟丙基甲基硅氧烷(84.09％)和聚乙氧基化表面活性剂Cremophor
Figure BDA0000144124600000091
1.09％)，提供抗菌涂层材料。抗菌涂层材料随后被施加到Becton
Figure BDA0000144124600000092
Q-SyteTM导管部件的外表面上。随后在USP水中冲洗第一组涂布的导管部件，以去除任何未结合的涂层材料，并且不冲洗第二组涂布的导管部件。最后，单独在USP水中冲洗第三组未涂布的导管部件(对照组)。
一式三份的铜绿假单胞菌（P.aerugmosa)、金黄色葡萄球菌(S.aureus)、大肠杆菌(E.coli)和白色念珠菌(C.albicans)病原体样品被放置在琼脂糖生长培养基上。每一样品中的一个接受经冲洗的涂布导管部件，每一样品中的一个接受未经冲洗的涂布导管部件，和每一样品中的一个接受未涂布的对照导管部件。这十二个样品随后在37℃下温育七天。每天从温育器取出样品和测量抑制区。实验结果在以下的表2至4中示出。
表2
用制剂9完全涂布的导管部件
Figure BDA0000144124600000101
表3
冲洗的用制剂9涂布的导管部件
Figure BDA0000144124600000102
表4
冲洗的未涂布导管部件(对照)
Figure BDA0000144124600000103
表2显示了来自包含完全涂布和未冲洗的导管部件的病原体样品的结果。如显示的，制剂9的抗菌涂层材料显示在七天时间期间显著抑制金黄色葡萄球菌和大肠杆菌病原体。此外，尽管与金黄色葡萄球菌和大肠杆菌相比，白色念珠菌显示了稍小的抑制，但铜绿假单胞菌显示了对制剂9的显著耐受性。
表3显示了来自包含经冲洗的涂布导管部件的病原体样品的结果。如显示的，制剂9的抗菌涂层材料显示在七天时间期间显著抑制金黄色葡萄球菌和大肠杆菌病原体，尽管预洗了导管部件。同样，铜绿假单胞菌和白色念珠菌病原体显示预洗后对涂层材料的很小抑制或无抑制。这些结果证实了由于硅油成分引起的涂层材料的粘合性质，和抗病原剂与涂层材料其余成分的相互混溶性。
最后，表4显示了来自包含未涂布导管部件的病原体样品或对照样品的结果。如显示的，没有制剂9的涂层材料，所有样品都显示无抑制。因此，已经证明本发明的抗菌涂层材料在杀死或防止通常引起血流感染的几种病原体的增殖上是高效的。
在不脱离其结构、方法或其他必不可少的特性下，本发明可以以其他具体形式体现，如在此广义描述的和要求保护的。所描述的实施方式和实施例在每个方面都被认为仅是说明性的，而不是限制性的。因此，本发明的范围通过所附权利要求说明，而不是通过前面的描述。进入权利要求等价物的含义和范围内的所有变化都被包括在它们的范围内。

Claims (20)

1.一种抗菌组合物，包括：
抗病原剂；
能够溶解所述抗病原剂的第一溶剂，所述溶剂选自水、C1醇和C2醇；
润滑剂；和
能够溶解所述润滑剂的第二溶剂，其中所述第一溶剂和所述第二溶剂是相互混溶的。
2.根据权利要求1所述的组合物，其中所述润滑剂为硅油。
3.根据权利要求1所述的组合物，其中所述第二溶剂为烃、酮、卤代烃和具有至少3个碳原子的醇中的至少一种。
4.根据权利要求1所述的组合物，其中所述第二溶剂为聚乙氧基化表面活性剂。
5.根据权利要求1所述的组合物，其中所述抗病原剂为双醋酸洗必泰、葡萄糖酸洗必泰、三氯生、苯扎氯铵和对氯间二甲苯酚(PCMX)中的至少一种。
6.根据权利要求2所述的组合物，其中所述硅油为二甲基硅氧烷和三氟丙基甲基硅氧烷中的至少一种。
7.根据权利要求3所述的组合物，其中所述第二溶剂包括两种或更多种烃、酮、卤代烃、具有至少三个碳原子的醇，和其组合。
8.一种制造抗菌组合物的方法，所述方法包括：
选择抗病原剂；
选择能够溶解所述抗病原剂的第一溶剂，所述溶剂选自水、C1醇和C2醇；
将所述抗病原剂溶解在所述第一溶剂中，以提供第一混溶的溶液；
选择润滑剂；
选择能够溶解所述润滑剂的第二溶剂；
将所述润滑剂溶解在所述第二溶剂中，以提供第二混溶的溶液；和
均匀混合所述第一和第二混溶的溶液。
9.根据权利要求8所述的方法，其中所述润滑剂为硅油。
10.根据权利要求8所述的方法，其中所述第二溶剂为烃、酮、卤代烃和具有至少3个碳原子的醇中的至少一种。
11.根据权利要求8所述的方法，其中所述第二溶剂为聚乙氧基化表面活性剂。
12.根据权利要求8所述的方法，其中所述抗病原剂为双醋酸洗必泰、葡萄糖酸洗必泰、三氯生、苯扎氯铵和对氯间二甲苯酚(PCMX)中的至少一种。
13.根据权利要求9所述的方法，其中所述硅油为二甲基硅氧烷和三氟丙基甲基硅氧烷中的至少一种。
14.根据权利要求10所述的方法，其中所述第二溶剂包括两种或更多种烃、酮、卤代烃、具有至少三个碳原子的醇，和其组合。
15.一种用于防止导管相关血流感染的血管内系统，所述系统包括：
具有外表面的血管进入器械；和
施加至所述外表面的抗菌涂层，所述抗菌涂层包括：
抗病原剂；
能够溶解所述抗病原剂的第一溶剂，所述溶剂选自水、C1醇和C2醇；
润滑剂；和
能够溶解所述润滑剂的第二溶剂，其中所述第一溶剂和所述第二溶剂是相互混溶的。
16.根据权利要求15所述的系统，其中所述润滑剂为硅油。
17.根据权利要求15所述的系统，其中所述血管进入器械进一步包括注射器。
18.根据权利要求15所述的系统，其中所述第二溶剂为烃、酮、卤代烃和具有至少3个碳原子的醇中的至少一种。
19.根据权利要求15所述的系统，其中所述第二溶剂为聚乙氧基化表面活性剂。
20.根据权利要求16所述的系统，其中所述硅油为二甲基硅氧烷和三氟丙基甲基硅氧烷中的至少一种。
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