CN102176928A - 具有可控释放的抗菌剂的医学装置 - Google Patents
具有可控释放的抗菌剂的医学装置 Download PDFInfo
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- CN102176928A CN102176928A CN2009801398653A CN200980139865A CN102176928A CN 102176928 A CN102176928 A CN 102176928A CN 2009801398653 A CN2009801398653 A CN 2009801398653A CN 200980139865 A CN200980139865 A CN 200980139865A CN 102176928 A CN102176928 A CN 102176928A
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- surface coating
- hydrophilic surface
- hydrophilic
- medical apparatus
- coating
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Abstract
公开了一种医学装置,诸如尿管,包括衬底材料,配置在所述衬底材料的至少一部分表面上的亲水性表面涂层,例如聚乙烯吡咯烷酮(PVP),和配置在所述衬底材料和所述亲水性表面涂层之间的包含微动金属的抗菌层。此外,所述亲水性表面涂层具有足够大的厚度,从而足以提供微动金属离子经过亲水性表面涂层的可控释放,诸如在干燥时超过3μm的厚度。因此,微动金属离子释放时的变化被显著减小,从而能够改进对释放的控制。还公开了相应的方法。
Description
发明领域
本发明涉及一种医学装置,其包括衬底材料和亲水性表面涂层,所述涂层配置在所述衬底材料的至少一部分表面上。该医学装置还包含抗菌剂,并提供所述抗菌剂的预定和可控的释放。
此外,本发明涉及用于制造所述医学装置的方法。
发明背景
已知在导入医学装置过程中,使用亲水性涂层涂覆医学装置,例如,用于导入人的体腔,诸如血管、消化器官和泌尿系统的导管,至少涂覆在被导入或与粘膜等接触的可插入部分的表面上。关于所述亲水性涂层的优点是它在用水膨胀时,优选在即将导入人体前变得非常光滑并由此确保在最小组织损伤的条件下基本无痛导入。
已知大量用于制备亲水性表面涂层的方法。一种已知的亲水性涂层方法例如公开在EP 0 093 093中,其中使用异氰酸酯形成聚脲网络,以连接亲水性PVP和衬底。此外,EP 0 217 771描述一种将增加重量克分子渗透浓度的化合物加入至所述亲水性涂层的方法,以改进涂层的保水性和低摩擦力。此外,WO 98/58989描述通过照射交联并将水溶性增加重量克分子渗透浓度的化合物结合在其中的亲水性涂层。
然而,尽管遵守无菌的指导方针等,但是医学装置的使用,特别是将医学装置导入天然的和人工的身体开口,意味着细菌污染的风险。例如,插入和保持尿管引起与导管相关的感染的问题。当医学装置诸如导管导入至人的体腔内时,正常人防御屏障可以被穿透,这可以导致引入细菌、真菌、病毒、或组织样或多个有组织的细胞(multiple organized cell)。尿道感染(UTI),例如,是与使用尿管,包括间歇使用具有亲水性涂层的亲水性导管,相关的问题。估计大约1/4就医的脊髓受伤患者在它们就医过程中发生有症状的UTI。革兰士阴性杆菌(bacilli)占UTI病例的约60-70%,肠球菌(enterococci)占约25%且念珠菌属占约10%。众所周知,作为日常常规实施间歇性尿管插入的患者经常遭受有症状的UTI的问题。
为此,并为了维持医学装置的无菌性和清洁,医学装置,诸如尿管,可以用抗微生物化合物涂覆,从而预防细菌感染。例如US 2006/0240069公开了至少一种有机酸的盐,优选苯甲酸盐或山梨酸盐作为抗微生物剂的应用。此外,WO 00/09173公开了具有抗细菌活性、抗病毒活性和/或抗真菌活性的稳定组合物,其特征在于包含银化合物。光稳定的银化合物可以导入至导管或类似的医学装置中。
在很多年中,银和银盐已经用作抗微生物剂。银盐、银胶体和银络合物也已经被用于预防和控制感染。例如,胶态金属银已经局部用于结膜炎(conjunctivitis)、尿道炎(urethritis)和阴道炎(vaginitis)。其他金属,诸如金、锌、铜、和铈,在单独的或与银组合的条件下,也已经被发现具有抗微生物特性。这些和其他金属已经显示即使处于极小量也提供抗微生物行为,即称为“微动作用”的特性。
具有亲水性涂层和作为单独的层配置或导入至亲水层中的抗微生物组合物诸如银的医学装置的其他实例公开在US 7 378 156和EP 1 688 470中。
然而,关于在医学装置中使用微动金属作为抗微生物剂和抗菌剂的已知方法的问题是难以控制微动金属离子的释放。如果释放速率太低,则抗细菌特性将不充足,且同时太高的释放速率可能不舒服并甚至对患者有害,并且还导致更昂贵的产品。因此,存在对改良的所述类型的医学装置的需要,其中微动金属离子的释放速率可以得到更精确的控制。
发明概述
因此,本发明的目的是提供一种医学装置和制造所述医学装置的方法,从而容许对抗微生物剂或抗菌剂的释放速率的改良控制,并由此减轻先前已知的方案的上述问题。
该目的通过使用根据所附权利要求的医学装置和方法来实现。
根据本发明的第一方面,提供一种医学装置,其包括衬底材料,配置在所述衬底材料的至少一部分表面上的亲水性表面涂层,和配置在所述衬底材料和所述亲水性表面涂层之间的包含微动金属的抗菌层,其中所述亲水性表面涂层具有足够大的厚度,从而足以提供微动金属离子经过亲水性表面涂层的可控释放。
根据本发明的另一方面,提供一种医学装置,其包括衬底材料,配置在所述衬底材料的至少一部分表面上的亲水性表面涂层,和配置在所述衬底材料和所述亲水性表面涂层之间的包含微动金属的抗菌层,其中所述亲水性表面涂层具有在干燥时超过3μm的厚度。
本发明人已经意外地发现,通过将抗菌层配置在亲水性表面涂层下,微动金属离子的释放变得更加可预测和可控制。因此,使得为了预期的应用有效定制(tailor)抗菌特性,和最优化抗菌效果,和同时有效防止抗菌离子的任何过量释放(其可能对患者有害)变得可能。
优选地,亲水性表面涂层具有在干燥时超过5μm,和最优选超过10μm的厚度。还已经发现特别有利的是亲水性表面涂层具有在干燥时在5-30μm范围内,和优选在10-20μm范围内的厚度。
“微动金属”,在本申请中意指即使处于极小量也具有抗微生物或抗菌行为的任何金属。所述微动金属的实例是银,例如,采用银盐、银胶体和银络合物的形式,和其他金属,诸如金、锌、铜、和铈。
抗菌层的微动金属优选包括银。银离子具有被充分证明的和有效的抗菌效果,并已经被发现还可通过合适厚度的亲水性上层来充分地控制。
还优选地,抗菌层还包括稳定剂,诸如金和/或铂金属。
亲水性涂层和抗菌层有利地适合于提供0.01-1.0微克/cm2范围内,和优选0.05-0.5微克/cm2范围内,和最优选0.10-0.30微克/cm2范围内的微动金属的自由离子的可控释放。
亲水性表面涂层的亲水性聚合物优选是以下的至少一种:聚乙烯化合物,聚内酰胺,特别地诸如聚乙烯吡咯烷酮,多糖,特别地肝素,葡聚糖,黄原胶,衍生的多糖,羟丙基纤维素,甲基纤维素,聚氨酯,聚丙烯酸酯,聚羟基丙烯酸酯,聚甲基丙烯酸酯,聚丙烯酰胺,聚环氧烷,特别地聚环氧乙烷,聚乙烯醇,聚酰胺,聚丙烯酸,前述聚合物的共聚物,乙烯基化合物和丙烯酸酯或酐的共聚物,乙烯吡咯烷酮和丙烯酸羟基乙基甲基酯的共聚物,聚乙烯吡咯烷酮的阳离子共聚物和聚甲基乙烯醚和马来酸酐(maleinic acid anyhydride)的共聚物。更优选地,亲和性聚合物是聚乙烯吡咯烷酮。
优选地,所述亲水性表面涂层包括这样的亲水性聚合物,所述亲水性聚合物在使用润湿液润湿时获得显著降低的表面摩擦力。更优选地,所述亲水性表面涂层包括聚乙烯吡咯烷酮(PVP)。
所述亲水性涂层优选形成聚脲网络,由此所述聚脲网络与衬底中的所述活性氢基团形成共价键。备选地,亲水性涂层可以与衬底中的活性氢基团形成酯键或环氧键。
根据一个实施方案,衬底材料的涂层可以通过包括以下步骤的方法来制备:对衬底的表面顺序地首先涂覆包含0.05-40%(重量/体积)异氰酸酯化合物的第一溶液和随后涂覆包含0.5-50%(重量/体积)聚乙烯吡咯烷酮的溶液,并在升高的温度下固化。
然而,其他亲水性涂层也是可行的,诸如包含与衬底直接交联的亲水性聚合物的涂层。交联可以通过照射,例如通过电子束或UV光来实现。
根据本发明的制造方法特别适合于制造导管,和特别地尿管。然而,该制造方法也有效用于许多其他类型的具有亲水性涂层的医学装置。因此,根据本发明的方法不限于尿管。本发明有效使用的所述其他医学装置的实例是血管导管和其他类型的导管,内窥镜和喉镜,饲管,或排出或气管内应用的管,避孕套,创伤敷料,隐形眼镜,植入物,体外血液导管,膜例如用于透析的膜,血液滤器和用于循环辅助的装置。
本发明可用于大量多样的不同衬底材料。然而,优选地,衬底由聚合物材料制成。衬底可以例如包括以下中的至少一种:聚氨酯,胶乳橡胶,硅橡胶,其他橡胶,聚氯乙烯(PVC),其他乙烯基聚合物,聚酯,聚丙烯酸酯,聚酰胺,聚烯烃,热塑弹性体,苯乙烯嵌段共聚物(SBS),或聚醚嵌段酰胺(PEBA)。
所述涂层溶液还可以包括溶解的增加重量克分子渗透浓度的化合物,诸如氯化钠。其他增加重量克分子渗透浓度的化合物,诸如尿素和EP 0 217 771中讨论的增加重量克分子渗透浓度的化合物也是可行的,所述文件通过引用并入本文。
根据本发明的另一方面,提供了一种从包含微动金属的抗菌层获得微动金属的可控释放的方法,其包括以下步骤:提供衬底材料;将抗菌层配置在所述衬底材料的至少一部分表面上;和将亲水性表面涂层配置在所述抗菌层的顶层上,其中所述亲水性表面涂层具有足够大的厚度,从而足以提供微动金属离子经由亲水性表面涂层的可控释放。
根据本发明的再一方面,提供了一种从包含微动金属的抗菌层获得微动金属的可控释放的方法,其包括以下步骤:提供衬底材料;将抗菌层配置在所述衬底材料的至少一部分表面上;和将亲水性表面涂层配置在所述抗菌层的顶层上,其中所述亲水性表面涂层具有在干燥时超过3μm的厚度。
通过在后的本发明的两方面,与关于首先讨论的实施方案中所讨论的类似的优势和特定实施方案是可获得的。
本发明的这些和其他方面参考以下所述的实施方案清楚并得出。
优选实施方案说明
在以下具体说明中,将描述本发明的优选实施方案。然而,应该理解不同实施方案的特征在实施方案之间是可交换的,并可以以不同的方式组合,除非特别指明其他情形。亲水性医学装置可以用于许多不同的目的,和用于插入不同类型的体腔。然而,以下讨论特别关注优选的应用领域,尿管,尽管本发明不限于这种具体的导管类型或甚至这种具体的医学装置类型。本领域中技术人员应该理解,本发明的概念不限于任何某种类型的装置,而是可以用于不同类型的医学装置。
在导管的情形中,长管的至少一部分形成将被经由使用者身体开口,诸如在尿管情形中的尿道,插入的可插入长度。可插入长度通常,在亲水性导管的上下文中,意指用亲水性材料,例如PVP涂覆并可插入患者尿道的长管长度。典型地,其对于女性患者是80-140mm且对于男性患者是200-350mm。
导管的长柄/管由衬底材料制成。衬底可以由任何聚合物材料制成,所述聚合物材料是本技术领域中公知的并所述亲水性聚合物与其粘附,诸如聚氨酯,胶乳橡胶,其他橡胶,聚氯乙烯,其他乙烯基聚合物,聚酯和聚丙烯酸酯。然而,优选地,衬底由包含聚烯烃和含有具有活性氢基团的分子的组合物的聚合物共混物,和优选包含具有活性氢基团的分子的组合物制成。聚烯烃可以包括选自以下组的至少一种聚合物:聚乙烯,聚丙烯,和苯乙烯嵌段共聚物(SBS)。含有具有活性氢基团的分子的组合物可以是具有经由氮与聚合物结合的活性氢基团的聚合物,诸如聚酰胺或聚氨酯。
在至少一部分衬底上,提供抗菌涂层。该抗菌层包含微动金属。所述抗菌层的许多不同类型是本身已知的,并可以用于实现本发明。
例如,一种用于获得抗微生物医学装置的常规方法是使金属银直接沉积在衬底表面上,例如,通过蒸汽涂覆、溅射涂覆、或离子束涂覆。
另一种将银涂覆在衬底上的方法包括由溶液中沉积或电沉积银。为了改进粘附性,可以使用包含沉积剂和稳定剂,诸如金和铂金属,或备选地,可能在银化合物和衬底表面之间形成化学络合物。例如,可能使用如Sodervall等的US 5 395 651,US 5 747 178和5 320 908中所述的具有银的抗菌涂层,这些文件的公开内容通过引用并入本文。
将亲水性涂层配置在形成导管柄的至少一部分衬底上,和在上述抗菌涂层的顶层上。亲水性聚合物涂层可以包括选自以下各项的材料:聚乙烯化合物,多糖,聚氨酯,聚丙烯酸酯或乙烯基化合物和丙烯酸酯或酐的共聚物,特别地聚环氧乙烷,聚乙烯吡咯烷酮,肝素,葡聚糖,黄原胶,聚乙烯醇,羟丙基纤维素,甲基纤维素,乙烯吡咯烷酮和丙烯酸羟基乙基甲基酯的共聚物,或聚甲基乙烯醚和马来酸酐的共聚物。优选的亲水性聚合物是聚乙烯吡咯烷酮。
提供亲水性表面涂层具有足够大的厚度,从而足以提供微动金属离子经由亲水性表面涂层的可控释放。特别优选地,亲水性表面涂层具有在干燥时超过3μm,并且其甚至更优选超过5μm,和最优选超过10μm的厚度。还已经发现特别有利的是亲水性表面涂层具有在干燥时在5-30μm范围内,和优选在10-20μm范围内的厚度。
该涂层还可以包含增加重量克分子渗透浓度的化合物,如例如在EP 0 217 771教导地。
现更详细地公开用于涂覆衬底的优选方法。长柄的外表面优选使用稳定的亲水性涂料来涂覆,其通过对衬底的表面顺序地首先涂覆包含0.05-40%(重量/体积)异氰酸酯化合物的溶液和随后涂覆包含0.5-50%(重量/体积)聚乙烯吡咯烷酮的溶液,并在升高的温度下固化来实现。异氰酸酯溶液可以有利地含有0.5-10%(重量/体积)异氰酸酯化合物,和可以优选地包含1-6%(重量/体积)异氰酸酯化合物。通常,异氰酸酯溶液仅需要与所述表面短暂接触,例如5-60秒。
将异氰酸酯溶液涂覆于衬底表面导致在衬底表面上形成的具有未反应的异氰酸酯基团的涂层。将聚乙烯吡咯烷酮溶液涂覆于衬底表面则导致形成亲水性聚乙烯吡咯烷酮-聚脲互聚物涂层。该亲水性涂层的固化将异氰酸酯化合物结合在一起,从而形成结合亲水性聚乙烯吡咯烷酮的稳定的非反应性网络。为了突出优点,固化发生在存在含水气体,例如环境空气的条件下,以容许异氰酸酯基团与水反应产生胺,所述胺迅速与其他异氰酸酯基团反应,以形成尿素交联。此外,所述方法可以包括在涂覆聚乙烯吡咯烷酮溶液之前蒸发异氰酸酯溶液的溶剂的步骤和在固化亲水性涂层之前蒸发聚乙烯吡咯烷酮溶液的溶剂的步骤。这可以例如通过空气干燥来进行。
异氰酸酯化合物优选每分子包括至少两个未反应的异氰酸酯基团。异氰酸酯可以选自2,4-二异氰酸甲苯酯和4,4′-二苯基甲烷二异氰酸酯,或六亚甲基二异氰酸酯的五聚物和氰尿酸酯型二异氰酸甲苯酯,或三聚的六亚甲基二异氰酸酯缩二脲或其混合物。
用于异氰酸酯化合物的溶剂优选是不与异氰酸酯基团反应的溶剂。优选的溶剂是二氯甲烷,但也可能使用例如乙酸乙酯,丙酮,氯仿,甲乙酮和二氯化乙烯。
为了缩短必需的反应时间和固化时间,可以添加用于异氰酸酯固化的合适催化剂。这些催化剂可以溶解在异氰酸酯溶液或聚乙烯吡咯烷酮溶液中,但是优选溶解在后者中。不同类型的胺是特别有效的,例如二胺,还例如三亚乙基二胺。优选地,使用脂族胺,所述脂族胺在用于所述涂层的干燥和固化温度下是可挥发的,并且还是无毒的。合适的胺的实例是N,N′二乙基乙二胺,六亚甲基二胺,乙二胺,对二氨基苯,1,3-丙二醇-对氨基苯甲酸二酯和二氨基二环辛烷。
优选使用的聚乙烯吡咯烷酮具有104-107的平均分子量,其最优选的平均分子量是约105。具有这样的分子量的聚乙烯吡咯烷酮可商购,例如,以商标Kollidon(BASF)。可以使用的用于聚乙烯吡咯烷酮的合适溶剂的实例是二氯甲烷(优选),乙酸乙酯,丙酮,氯仿,甲乙酮和二氯化乙烯。聚乙烯吡咯烷酮在溶液中的比例优选是0.5-10%(重量/体积),且最优选2-8%(重量/体积)。处于溶剂中的聚乙烯吡咯烷酮通过通过浸渍、喷雾等短期地,例如在5-50秒期间内涂覆。
涂层的固化优选在50-130℃下,例如在烤箱中进行5-300min的持续时间。
然而,使用其他类型的亲水性涂层,诸如通过UV或e-束照射交联的涂层也是可行的。
在优选的实施方案中,亲水性涂层含有增加重量克分子渗透浓度的化合物,例如选自氯化钠和氯化钾、碘化物、柠檬酸盐和苯甲酸盐。增加重量克分子渗透浓度的化合物可以以属于同一申请人的EP 0 217 771中详述的方式应用。
实验结果
关于该实验,利用材料聚丙烯,聚乙烯聚酰胺(Polyethen Polyamide)和苯乙烯-乙烯/丁烯-苯乙烯共聚物(Styren-ethen/buten-styren co-polymer)的组合的衬底材料来制备导管,所述材料通常以商品名Meliflex来销售。
所有的导管衬底均用抗菌涂料来涂覆。该涂料基本如US 5 395 651和US 5 747 178中所述涂覆,这两份文件均通过引用并入本文。因此,衬底首先用铬酸预处理,并然后通过将衬底浸渍在包含溶解在酸化的软化水中的0.01-0.2克/升的含有锡离子的盐的稀释活化溶液来活化。在该处理后,使衬底在软化水中漂洗。随后,使衬底浸渍在包含不超过0.10克/升的有效量的含银盐,更具体地硝酸银,还原剂和沉积控制剂的沉积溶液中。沉积后,从沉积溶液中取出被涂覆的衬底并在软化水在漂洗。最后,使该衬底浸渍在包含处于稀酸中的0.001-0.1克/升的铂盐和金盐的稳定溶液中。在稳定化处理后,再次将衬底在软化水中漂洗,并随后干燥。
不同量的银用于不同类型的导管的涂层中(见下)。
在抗菌涂层的顶层上,将亲水性涂料涂覆于衬底上,形成本发明的实例,而使一些参照导管不含亲水性涂层,作为比较例。
根据本发明制备的衬底根据已知的涂覆方法来涂覆,其中使用异氰酸酯来形成聚脲网络以结合PVP。更特别地,根据比较例的涂层通过使衬底浸渍在包含二异氰酸酯(称为Desmodur IL)的底层涂料溶液(primer solution)中15秒来制备,所述二异氰酸酯溶解在二氯甲烷中达到浓度2%(重量/体积)。导管随后在环境温度下干燥60秒,并然后浸渍在含有溶解在二氯甲烷中的7%(重量/体积)的聚乙烯吡咯烷酮(PVP K90)的溶液中3秒。然后容许导管在35℃冲洗30分钟,随后在80℃固化60分钟,并最后容许冷却至室温并在水中漂洗。
亲水性涂层具有在干燥时10-20μm,和在润湿时100-200μm的厚度。
基于以上,测试以下导管组:
A)具有抗菌银涂层但无亲水性涂层的导管。
B)具有比A)中更高的银浓度的抗菌银涂层和亲水性涂层的导管。
C)具有与A)中几乎相同浓度的抗菌银涂层和亲水性涂层的导管。需注意,根据A)和C)的导管基本相同,区别在于导管A不具有任何亲水性涂层。
关于这些导管,测量表面的总银浓度,和还有当在人造尿中分别溶浸15秒、30秒和5分钟时释放的银量。每次测试每组中的至少三个不同的导管。
这些测量的结果显示在下表1中:
表1:从不同导管中浸出的银量的测量值
银离子释放的平均程度计算为浸出的银量和平均总银量的平均商。
从这些测量结果,以下内容特别值得注意:
-浸出的银量对于不具有亲水性涂层的组A与对于组B和组C相比变化更显著。该作用对于更长的溶浸时间还更加显著。
-因此,可以得出这样的结论,即亲水性涂层具有稳定化作用,使得银离子从抗菌涂层的释放更加可预测和可控制。
-平均浸出银量对于在涂层中具有大致相同的总银量的组A和C几乎相同。
-因此,可以推断亲水性涂层对银离子从抗菌涂层的释放的总水平不具有明显影响。
-在降低银离子释放水平所经历的变化方面的巨大改进对于组B和C几乎相同。同时,组B中总银量与组C相比是大约双倍。
因此,该阳性作用明显不取决于抗菌涂层中银离子总量。
结论和总结
本发明现在已经关于不同的实施方案进行了讨论。然而,本领域中技术人员应该理解若干其他的备选方案是可能的。例如,可以使用许多其他类型的包含微动金属的抗菌涂层,以及其他类型的亲水性涂层。还可能将本发明用于除尿管以外的其他类型的导管,诸如血管导管等,或用于其他类型的具有亲水性涂层的医学装置。
本领域熟练技术人员应该理解与上述那些类似的若干这样的备选方案可以在不偏离本发明精神的前提下使用,并且全部这些改变应该被认为是本发明的一部分,如所述权利要求中所限定的那样。
Claims (15)
1.一种医学装置,包括衬底材料,配置在所述衬底材料的至少一部分表面上的亲水性表面涂层,和配置在所述衬底材料和所述亲水性表面涂层之间的包含微动金属的抗菌层,其中所述亲水性表面涂层具有足够大的厚度,从而足以提供微动金属离子经过亲水性表面涂层的可控释放。
2.一种医学装置,包括衬底材料,配置在所述衬底材料的至少一部分表面上的亲水性表面涂层,和配置在所述衬底材料和所述亲水性表面涂层之间的包含微动金属的抗菌层,其中所述亲水性表面涂层具有在干燥时超过3μm的厚度。
3.前述权利要求中任一项的医学装置,其中所述亲水性表面涂层具有在干燥时超过5μm,且优选超过10μm的厚度。
4.前述权利要求中任一项的医学装置,其中所述亲水性表面涂层具有在干燥时在5-30μm范围内,且优选在10-20μm范围内的厚度。
5.前述权利要求中任一项的医学装置,其中所述抗菌层的微动金属包括银,和优选地还包括稳定剂,诸如金和/或铂金属。
6.前述权利要求中任一项的医学装置,其中所述亲水性表面涂层和所述抗菌层适合于提供0.01-1.0微克/cm2范围内,和优选0.05-0.5微克/cm2范围内,和最优选0.10-0.30微克/cm2范围内的微动金属的自由离子的可控释放。
7.前述权利要求中任一项的医学装置,其中所述亲水性表面涂层包括亲水性聚合物,诸如聚乙烯吡咯烷酮(PVP),所述亲水性聚合物在使用润湿液润湿时获得显著降低的表面摩擦力。
8.前述权利要求中任一项的医学装置,其中所述亲水性聚合物是以下的至少一种:聚乙烯化合物,聚内酰胺,特别地诸如聚乙烯吡咯烷酮,多糖,特别地肝素,葡聚糖,黄原胶,衍生的多糖,羟丙基纤维素,甲基纤维素,聚氨酯,聚丙烯酸酯,聚羟基丙烯酸酯,聚甲基丙烯酸酯,聚丙烯酰胺,聚环氧烷,特别地聚环氧乙烷,聚乙烯醇,聚酰胺,聚丙烯酸,前述聚合物的共聚物,乙烯基化合物和丙烯酸酯或酐的共聚物,乙烯吡咯烷酮和丙烯酸羟基乙基甲基酯的共聚物,聚乙烯吡咯烷酮的阳离子共聚物和聚甲基乙烯醚和马来酸酐的共聚物。
9.前述权利要求中任一项的医学装置,其中所述医学装置是导管,且优选尿管。
10.前述权利要求中任一项的医学装置,其中所述亲水性表面涂层还包含增加重量克分子渗透浓度的化合物。
11.一种从包含微动金属的抗菌层获得微动金属离子的可控释放的方法,包括以下步骤:
提供衬底材料;
将抗菌层配置在所述衬底材料的至少一部分表面上;和
将亲水性表面涂层配置在所述抗菌层的顶层上,其中所述亲水性表面涂层具有足够大的厚度,从而足以提供微动金属离子经由亲水性表面涂层的可控释放。
12.一种从包含微动金属的抗菌层获得微动金属离子的可控释放的方法,包括以下步骤:
提供衬底材料;
将抗菌层配置在所述衬底材料的至少一部分表面上;和
将亲水性表面涂层配置在所述抗菌层的顶层上,其中所述亲水性表面涂层具有在干燥时超过3μm的厚度。
13.权利要求11或12的方法,其中所述亲水性涂层形成聚脲网络,其中所述聚脲网络与所述衬底中的所述活性氢基团形成共价键。
14.权利要求13的方法,其中涂覆衬底材料的步骤包括以下子步骤:对衬底的表面顺序地首先涂覆包含0.05-40%(重量/体积)异氰酸酯化合物的溶液和随后涂覆包含0.5-50%(重量/体积)聚乙烯吡咯烷酮的溶液,和在升高的温度下固化。
15.权利要求11或12的方法,其中所述亲水性涂层与所述衬底通过照射交联。
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- 2009-10-09 CA CA2736932A patent/CA2736932C/en not_active Expired - Fee Related
- 2009-10-09 AU AU2009305471A patent/AU2009305471B2/en not_active Ceased
- 2009-10-09 CN CN2009801398653A patent/CN102176928A/zh active Pending
- 2009-10-09 JP JP2011530496A patent/JP5685539B2/ja not_active Expired - Fee Related
- 2009-10-09 US US12/576,358 patent/US20100086580A1/en not_active Abandoned
- 2009-10-09 WO PCT/EP2009/063188 patent/WO2010043565A1/en active Application Filing
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CN113382756A (zh) * | 2018-11-30 | 2021-09-10 | 斯特拉塔卡系统有限公司 | 涂覆和/或浸渍输尿管导管或支架及其制造方法 |
CN116570768A (zh) * | 2023-03-10 | 2023-08-11 | 浙江大学 | 一种多层力学仿生缓释抗菌气管补片及其制备方法 |
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AU2009305471B2 (en) | 2013-11-14 |
BRPI0920314B1 (pt) | 2018-07-17 |
EP2177238B1 (en) | 2016-11-09 |
US20100086580A1 (en) | 2010-04-08 |
BRPI0920314A2 (pt) | 2016-02-23 |
CA2736932A1 (en) | 2010-04-22 |
EP2177238A1 (en) | 2010-04-21 |
JP5685539B2 (ja) | 2015-03-18 |
JP2012504995A (ja) | 2012-03-01 |
AU2009305471A1 (en) | 2010-04-22 |
WO2010043565A1 (en) | 2010-04-22 |
CA2736932C (en) | 2017-03-07 |
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