CN111670020A - 用于眼科植入物的抗微生物聚合物 - Google Patents
用于眼科植入物的抗微生物聚合物 Download PDFInfo
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- CN111670020A CN111670020A CN201880088235.7A CN201880088235A CN111670020A CN 111670020 A CN111670020 A CN 111670020A CN 201880088235 A CN201880088235 A CN 201880088235A CN 111670020 A CN111670020 A CN 111670020A
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- Prior art keywords
- methacrylate
- monomers
- phenylethyl
- antimicrobial
- monomer
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Abstract
一种用于眼科植入物的抗微生物聚合物,包括至少一种抗微生物单体,和至少一种选自丙烯酸、有机硅、乙烯基和胶原单体的其它单体。
Description
技术领域
本发明一般涉及眼科植入物装置及其制备和使用方法,更具体地,涉及用于眼科植入物装置的抗微生物聚合物,其通过将至少一种抗微生物单体与至少一种其他单体共聚而获得。
背景技术
感染是眼科植入手术的严重并发症。眼科植入物的实例包括眼内透镜、青光眼瓣膜和人造角膜,其也称为角膜假体。眼科植入手术后任何这些装置的不受控制的感染可导致视力丧失或甚至失去眼睛。
将眼科植入物与接触镜区分开很重要。虽然两者都被认为是医疗装置,但它们的正常功能的目的和要求却截然不同。
接触镜是“漂浮”在人泪膜上的透明镜片。它们不以任何方式物理附着在眼睛上,并且已知接触镜和组织之间的直接接触会引起并发症,包括角膜擦伤、感染和角膜瘢痕形成。接触镜的目的是折射光以使光线适当聚焦到视网膜上。
相比之下,眼科植入物是可嵌入眼组织内的透明、半透明或不透明的任意装置。眼科植入物必须与眼组织生物相容才能起作用。
用于降低眼科植入手术后感染风险的最常见策略是使用局部抗生素滴剂。然而,该方案具有明显的缺点,即需要依赖患者的依从性以确保适当地给药。在人造角膜植入物的情况下,感染问题尤其麻烦,其目前需要患者终生每日施用局部抗生素滴剂。使用这种抗生素是必要的,因为目前的人造角膜暴露于眼睛的非无菌表面。因此,存在持续的感染风险。
其他发明人已经认识到抗生素药物作为减少眼科植入手术后感染的方法的不足。Noolandi等人的美国专利6,976,997中公开提出了一种替代策略是将抗菌化学物质涂覆或共价键合到眼科植入物的表面。该方法的局限性在于涂层和共价键合的化学物质会随着时间的推移而从植入物表面被侵蚀掉。因此,可以预测这类植入物的抗菌性能会随着时间的推移而降低,从而增加感染的风险。
过去提出的另一种策略是向眼科植入物的聚合物注入抗菌金属离子。特别是,已提出银和铜金属作为注入用于眼科植入物的聚合物中的试剂。尽管在聚合物中使用游离金属离子作为抗菌剂已广泛用于商业塑料制品和一些短期一次性医疗装置(如导管)中,但已知金属离子会危害眼睛。
银质沉着(Argyrosis)是眼睛的银毒性的医学术语。据报道,银质沉着会导致结膜和虹膜的灰色变色。研究还发现银质沉着可导致白内障和视网膜黄斑病变,这两者都会威胁视力。
眼睛中的铜毒性会导致角膜周围出现被称为Kayser-Fleischer环的特征性绿环。此外,研究表明铜毒性可诱发眼部并发症,如眼内炎症(葡萄膜炎)、出血、玻璃体液化、低眼压、虹膜缺血和视网膜损伤。
此外,游离金属离子也可能会随着时间的推移从聚合物中浸出,因此,聚合物可能会随着时间的推移丧失其抗微生物性质。
由于上述原因,本领域仍需要一种降低眼科植入手术后微生物感染风险的改进的组合物和方法。
发明内容
本发明提供用于眼科植入物的抗微生物聚合物,其通过将至少一种抗微生物单体与至少一种选自丙烯酸、有机硅、乙烯基和胶原单体的其他单体共聚而获得。本发明还提供了制备用于眼科植入物的抗微生物聚合物的方法,通过使至少一种抗微生物单体与至少一种选自丙烯酸、有机硅、乙烯基和胶原单体的其它单体反应,得到所述抗微生物聚合物;和在所述眼科植入物中使用所述抗微生物聚合物。
本发明的共聚物是抗微生物的、生物相容的、并且可逆变形,同时也是透明的、半透明的或不透明的。这些特征是被设计用于通过小切口植入眼组织内的眼科植入物所期望的最佳功能。此外,由于不仅仅是共聚物的表面,而是整个共聚物具有抗微生物特性,因此由这类共聚物制成的眼科植入物即使植入物的表面随时间被侵蚀也不会失去其抗微生物特性。这对于暴露于眼睛表面的眼科植入物尤其重要,因为眨眼会导致聚合物材料的侵蚀。当本发明聚合物的表面被侵蚀时,表面下的抗微生物聚合物仍可杀死微生物,从而降低患者的感染风险。
附图说明
图1示出了一种抗微生物的、透明的、生物相容的、可逆变形的聚合物的聚合的实施方案。
具体实施方式
本公开提供了用于眼科植入物的抗微生物聚合物,其通过将至少一种抗微生物单体与至少一种选自丙烯酸、有机硅、乙烯基或胶原单体的其他单体共聚而获得。所得抗微生物聚合物提供抗微生物的、生物相容的且可逆变形的植入物,其也是透明的、半透明的或不透明的。这些特征是被设计用于通过小切口植入眼组织内的眼科植入物所期望的最佳功能。此外,由于不仅仅是共聚物的表面,而是整个共聚物具有抗微生物特性,因此由这类共聚物制成的眼科植入物即使植入物的表面随时间被侵蚀也不会失去其抗微生物特性。这对于暴露于眼睛表面的眼科植入物尤其重要,因为眨眼会导致聚合物材料的侵蚀。
有许多类型的眼科植入物,其中一种是人造角膜。在人造角膜中,共聚物被认为是抗微生物的、透明的、生物相容的和可逆可变形的。在一些情况下,眼科植入物不需要是透明的以执行其预期功能。例如,视轴外的青光眼瓣膜、视网膜假体和角膜内植入物不需要折射光作为其功能的一部分,因此它们可以是半透明的或不透明的。在这些情况下,本发明的聚合物可以是半透明的或不透明的。各种眼科植入物及其方法已在美国专利8,029,515、7,901,421和7,223,275中有充分描述,出于所有目的,其通过引用整体并入本文。
抗微生物聚合物是一类具有抗微生物活性或抑制微生物(如细菌、真菌和/或原生动物)生长能力的聚合物。这些聚合物模拟活体动物的免疫系统中用于杀死各种微生物的抗微生物肽。抗微生物聚合物通常是非挥发性的和化学稳定的,并且在医学领域中用作对抗感染的手段,在食品工业中用于防止细菌污染,并且在水卫生中用于抑制饮用水中微生物的生长。
抗微生物聚合物通过使微生物细胞破裂而杀死接触的微生物。例如,抗微生物聚合物通常带有正电荷,可以容易地吸附在细菌细胞壁的带负电荷的表面上。一旦被吸附,抗微生物聚合物会穿过细胞壁进行扩散,与细胞膜结合并破坏细胞膜。虽然通过阳离子抗微生物聚合物可以最好地实现吸附,但小分子抗微生物剂由于其低分子量而在扩散方面表现优异。细胞膜的破坏和随后细胞质成分的泄漏可使细菌死亡。
大多数细菌细胞壁是带负电的,因此,大多数抗微生物聚合物带正电荷以促进吸附过程。抗衡离子的结构或与聚合物相关的平衡电荷的离子也影响抗微生物活性。与聚合物形成强离子对的抗衡阴离子阻碍了抗微生物活性,因为抗衡离子阻止聚合物与细菌相互作用。然而,形成松散离子对或易于与聚合物分离的离子对活性表现出积极影响,因为它允许聚合物与细菌自由相互作用。
图1示出了一种抗微生物的、透明的、生物相容的、可逆变形的聚合物的聚合的实施方案。在该图中,抗微生物聚合物通过将至少一种抗微生物单体与至少一种选自丙烯酸、有机硅、乙烯基或胶原单体的其他单体共聚而获得。聚合后,所得聚合物网络包括在整个网络中间隔开的固定化抗微生物聚合物。
在一个实施方案中,抗菌单体选自季铵盐类单体。季铵盐类单体的一非限制性实例是1-[12-(甲基丙烯酰氧基)十二烷基]吡啶溴化物(MDPB)。
CH2=C(CH3)C(O)O(CH2)12N+(C5H5)Br-
MDPB
当与牙科粘接剂和牙科树脂共聚时,MDPB已被用作抗微生物单体以降低龋齿的风险。
在其他实施方案中,至少一种抗微生物单体是季铵盐类单体,例如甲基丙烯酰氧乙基十六烷基二甲基氯化铵(DMAE-CB)。
CH2=C(CH3)C(O)O(CH2)2N+(CH3)2(CH2)15CH3 Cl-
DMAE-CB
还可以增加可掺入聚合物材料中的抗微生物单体的量,并随后通过改变季铵盐类单体以具有两个可聚合的甲基丙烯酸部分来增强抗菌活性。
因此,在其他实施方案中,至少一种抗微生物单体是季铵盐类单体,例如2-甲基丙烯酰氧乙基十二烷基甲基溴化铵(MAE-DB)。
CH2=C(CH3)C(O)O(CH2)2N+(CH3)(CH2)2O(O)CC(CH3)=CH2(CH2)12CH3 Br-
MAE-DB
在其他实施方案中,至少一种抗微生物单体是季铵盐类单体,例如2-甲基丙烯酰氧乙基十六烷基甲基溴化铵(MAE-HB)。
CH2=C(CH3)C(O)O(CH2)2N+(CH3)(CH2)2O(O)CC(CH3)=CH2(CH2)16CH3 Br-
MAE-HB
在其他实施方案中,至少一种抗微生物单体是季铵盐类单体,例如双(2-甲基丙烯酰氧乙基)二甲基溴化铵(IDMA-1)。
CH2=C(CH3)C(O)O(CH2)2N+(CH3)2(CH2)2O(O)CC(CH3)=CH2 Br-
IDMA-1
在其他实施方案中,至少一种抗微生物单体可以基于烷基链长度而不同。这些的实例包括但不限于甲基丙烯酸二甲基氨基丙酯(DMAPM)、甲基丙烯酸二甲基氨基己酯(DMAHM)、甲基丙烯酸二甲基氨基庚酯(DMAHPM)、甲基丙烯酸二甲基氨基辛酯(DMAOM)、甲基丙烯酸二甲基氨基壬酯(DMANM)、甲基丙烯酸二甲基氨基癸酯(DMADM)、甲基丙烯酸二甲基氨基十一烷基酯(DMAUDM)、甲基丙烯酸二甲基氨基十二烷基酯(DMADDM)、甲基丙烯酸二甲基氨基十三烷基酯(DMATDM)、甲基丙烯酸二甲基氨基十四烷基酯(DMATTDM)、甲基丙烯酸二甲基氨基十五烷基酯(DMAPDM)、甲基丙烯酸二甲基氨基十六烷基酯(DMAHDM)、甲基丙烯酸二甲基氨基十七烷基酯(DMAHPDM)、甲基丙烯酸二甲基氨基十八烷基酯(DMAODM)、甲基丙烯酸二甲基氨基十九烷基酯(DMANDM)、甲基丙烯酸二甲基氨基二十烷基酯(DMAIOM)、甲基丙烯酸二甲基氨基二十一烷基酯(DMAHOM)、甲基丙烯酸二甲基氨基二十二烷基酯(DMADOM)和/或其组合。
在其他实施方案中,抗微生物单体可具有伯氨基、仲氨基或叔氨基。这些类型的抗菌单体的实例包括但不限于邻-、间-和/或对-二甲基氨基甲基苯乙烯、N-(2-二甲氨基乙基)丙烯酰胺、N-(2-氨基乙基)丙烯酰胺、正丁基丙烯酰胺和二烯丙基二甲基铵盐。
在另一实施方案中,抗微生物单体可以与抗微生物肽共价连接。抗微生物肽的实例包括但不限于:通过2-4个二硫键稳定的β-折叠肽(例如人α-和β-防御素、真菌防御素(plectasin)或猪源抗微生物肽(protegrin));α-螺旋肽(例如LL-37、天蚕素(cecropins)或爪蟾素(magainins));富含甘氨酸、脯氨酸、色氨酸、精氨酸或组氨酸的延伸结构(例如indolicidin);具有一或二硫键的环肽(例如细菌素)。
在一个实施方案中,所述至少一种其他单体选自丙烯酸、有机硅、乙烯基或胶原单体。这些单体可与上述至少一种抗微生物单体进行聚合,以提供用于眼科植入物的抗微生物聚合物。例如,眼科植入物可以由单个坯料或材料块形成,通常是通常用于形成眼内透镜(IOL)的聚合物水凝胶,例如甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物,或疏水丙烯酸材料。聚合物水凝胶材料还可具有疏水和亲水性质,例如经过等离子体表面处理的甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物。或者,眼科植入物可以由基于胶原的水凝胶进行成型、机械加工或激光切割。
在一个实施方案中,至少一种其他单体选自疏水性丙烯酸单体。疏水性丙烯酸单体的实例包括但不限于:
丙烯酸苯乙酯、甲基丙烯酸苯乙酯和丁二醇二丙烯酸酯的单体,它们形成丙烯酸苯乙酯和甲基丙烯酸苯乙酯的共聚物,与丁二醇二丙烯酸酯交联(AcryIOL),购自爱尔康(Alcon),沃思堡市6201南高速公路诺华公司分部,TX 76134-2001;
丙烯酸乙酯、甲基丙烯酸乙酯、2,2,2-三氟乙基甲基丙烯酸酯的单体,与乙二醇二甲基丙烯酸酯交联,它们形成丙烯酸乙酯、甲基丙烯酸乙酯和2,2,2-三氟乙基甲基丙烯酸酯的共聚物,与乙二醇二甲基丙烯酸酯交联((AMO)),购自强生视力康公司,圣安娜市圣安德鲁P1街1700号,CA 92705;
甲基丙烯酸苯乙酯、丙烯酸正丁酯和氟烷基甲基丙烯酸酯的单体,它们形成甲基丙烯酸苯乙酯、丙烯酸正丁酯和氟烷基甲基丙烯酸酯的交联共聚物(AF-(HOYA)),购自豪雅公司,日本东京都新宿区中落合2丁目7番5号;
丙烯酸苯乙酯、甲基丙烯酸苯乙酯和丁二醇二丙烯酸酯的单体,它们形成丙烯酸苯乙酯、甲基丙烯酸苯乙酯的共聚物,与丁二醇二丙烯酸酯交联(HI56),购自公司,艾塞克斯郡萨弗伦沃尔登希尔山卡尔顿大厦,CB11 3AU;
2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的单体,它们形成2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的共聚物(BENZ HF-1.2),购自奔驰研发公司,萨拉索塔市帕克兰大道6447号,FL 34243;和
2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的单体,它们形成2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的共聚物(Benz HF-2),购自奔驰研发公司,萨拉索塔市帕克兰大道6447号,FL 34243。
在一个实施方案中,至少一种其他单体选自亲水性丙烯酸单体。亲水性丙烯酸单体的实例包括但不限于:
2-羟乙基甲基丙烯酸酯和2-乙氧基乙基甲基丙烯酸酯的单体,它们形成2-羟乙基甲基丙烯酸酯和2-乙氧基乙基甲基丙烯酸酯的共聚物(Benz IOL 125),购自奔驰研发公司,萨拉索塔市帕克兰大道6447号,FL 34243;和
2-羟乙基甲基丙烯酸酯和甲基丙烯酸甲酯的单体,它们形成2-羟乙基甲基丙烯酸酯和甲基丙烯酸甲酯的共聚物(BenzFlex 26),购自奔驰研发公司,萨拉索塔市帕克兰大道6447号,FL 34243。
在实施方案中,所述至少一种其他单体与角膜、眼睛和身体是生物相容的。合适的单体包括但不限于一种或多种选自胶原、氨基甲酸酯、甲基丙烯酸-2-羟乙酯、乙烯基吡咯烷酮、甲基丙烯酸甘油酯、乙烯醇、乙二醇、甲基丙烯酸、有机硅、丙烯酸、碳氟化合物单体和具有磷酸胆碱的单体。
在一个实施方案中,至少一种其他单体包含水凝胶。在其他实施方案中,该材料包含甲基丙烯酸和甲基丙烯酸羟乙酯(PHBMA/MAA)。
在其他实施方案中,所述至少一种其他单体是包含可逆变形的丙烯酸单体的材料,例如用于眼内透镜的材料。合适的单体的实例包括但不限于甲基丙烯酸羟乙酯和甲基丙烯酸甲酯。在另外的方面,单体提供本质上是亲水的可变形的聚合物,以允许植入物的光学表面平滑润湿。可润湿性是眼科植入物可以使泪膜充当良好的光学界面的重要特征。
在其他实施方案中,眼科植入物可以由促进植入物表面上皮形成的单体制造。这种材料的实例包括胶原和N-异丙基丙烯酰胺、胶原和1-乙基-3,3'(二甲基-氨基丙基)-碳二亚胺以及胶原和N-羟基琥珀酰亚胺(EDC/NHS)。在其他方面,聚合物可另外含有细胞外基质蛋白,例如纤连蛋白、层粘连蛋白、P物质、胰岛素样生长因子-1,或肽序列,例如纤连蛋白粘附促进肽或肽(FAP)。
在一个实施方案中,至少一种其他单体是丙烯酸单体。丙烯酸类单体的非限制性实例包括但不限于丙烯酸甲酯(MA)和甲基丙烯酸甲酯(MMA)。MA和MMA是分别具有下式的有机化合物:CH2=CHCO2CH3和
CH2=C(CH3)CO2CH3。这些无色液体大规模生产,分别用于生产聚甲基丙烯酸酯(PMA)和聚甲基丙烯酸甲酯(PMMA)。虽然MA和MMA是刺激物并且可能致癌,但MA和MMA的聚合物是生物相容的、可抵抗长期暴露于温度,以及人体组织的化学和细胞作用。丙烯酸单体可与上述至少一种抗微生物单体进行聚合,以提供用于眼科植入物的抗微生物聚合物。
在一个实施方案中,所述至少一种其他单体是有机硅。有机硅具有下式:R2SiO,其中R为有机基团,例如甲基、乙基或苯基。有机硅可以进行聚合以形成聚硅氧烷,其包括重复的无机硅-氧主链(---Si-O-Si-O-Si-O---),其中有机侧基R连接到四价硅原子上。通过改变-Si-O-链长度、侧基和交联,可以合成具有多种性质和组成的聚硅氧烷。它们的稠度可以从液体到凝胶,到橡胶到硬塑料变化。最常见的硅氧烷是线性聚二甲基硅氧烷(PDMS),一种硅油。有机硅单体还可以与上述至少一种抗微生物单体进行聚合,以提供用于眼科植入物的抗微生物聚合物。
在一个实施方案中,至少一种其他单体是乙烯基单体。乙烯基单体的非限制性实例包括但不限于乙烯基酯(丙烯酸酯)、乙烯基碳酸酯(ROC(O)OCH=CH2)和乙烯基氨基甲酸酯(R’R”NC(O)OCH=CH2)。这些单体已显示出通常适用于许多生物医学应用。特别地,如乙烯基碳酸酯和乙烯基氨基甲酸酯的单体通常具有较低的细胞毒性,但与丙烯酸酯的反应性相似。例如,可以容易地调节乙烯基碳酸酯和乙烯基氨基甲酸酯的降解以提供无毒的低分子量聚乙烯醇作为降解产物和各种其它无毒的醇,例如甘油或聚乙二醇。该概念还用于在组织工程用水凝胶领域中提供透明质酸和明胶的乙烯基酯衍生物。乙烯基单体还可以与上述至少一种抗微生物单体进行聚合,以提供用于眼科植入物的抗微生物聚合物。
在一个实施方案中,至少一种其他单体是胶原单体。单个胶原蛋白分子(原胶原,tropocollagen)用于组成较大的胶原聚集体,例如原纤维。原纤维由三条多肽链组成,每条链都被确认具有左旋螺旋。这三个左旋螺旋被扭曲成右旋三螺旋或微纤维,一种由氢键稳定的配合四元结构。然后每个微纤维与其相邻的微纤维相互交叉。此外,胶原单体可以使用各种连接物与一种或多种丙烯酸酯或乙烯基单体连接。胶原单体还可以与上述至少一种抗微生物单体进行聚合,以提供用于眼科植入物的抗微生物聚合物。在一个实施方案中,眼科植入物可包括胶原和N-异丙基丙烯酰胺、胶原和1-乙基-3,3'(二甲基-氨基丙基)-碳二亚胺以及胶原和N-羟基琥珀酰亚胺(EDC/NHS)。
在上文中,参考具体的示例性实施例对本公开进行了描述。然而,显而易见的是,在不脱离如权利要求中所阐述的本公开的更广泛的精神和范围的情况下,可以对其进行各种修改和改变。因此,说明书和附图应被视为说明性的而非限制性的。应当理解,本公开能够使用各种其他组合和实施例,并且能够在如本文所表达的发明构思的范围内进行任何改变或修改。
Claims (22)
1.一种用于眼科植入物的抗微生物聚合物,包括
至少一种抗微生物单体;和
至少一种其他单体,所述其他单体选自:丙烯酸单体、疏水性丙烯酸单体、亲水性丙烯酸单体、有机硅单体、乙烯基单体和胶原单体。
2.根据权利要求1所述的抗微生物聚合物,其中所述疏水性丙烯酸聚合物选自:丙烯酸苯乙酯、甲基丙烯酸苯乙酯和丁二醇二丙烯酸酯的单体,它们形成丙烯酸苯乙酯和甲基丙烯酸苯乙酯的共聚物,与丁二醇二丙烯酸酯交联(IOL);丙烯酸乙酯、甲基丙烯酸乙酯、2,2,2-三氟乙基甲基丙烯酸酯的单体,与乙二醇二甲基丙烯酸酯交联,它们形成丙烯酸乙酯、甲基丙烯酸乙酯和2,2,2-三氟乙基甲基丙烯酸酯的共聚物,与乙二醇二甲基丙烯酸酯交联((AMO));甲基丙烯酸苯乙酯、丙烯酸正丁酯和氟烷基甲基丙烯酸酯的单体,它们形成甲基丙烯酸苯乙酯、丙烯酸正丁酯和氟烷基甲基丙烯酸酯的交联共聚物((HOYA));丙烯酸苯乙酯、甲基丙烯酸苯乙酯和丁二醇二丙烯酸酯的单体,它们形成丙烯酸苯乙酯、甲基丙烯酸苯乙酯的共聚物,与丁二醇二丙烯酸酯交联(HI56);2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的单体,它们形成2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的共聚物(BENZ HF-1.2);2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的单体,它们形成2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的共聚物(Benz HF-2),且
所述亲水性丙烯酸聚合物选自:甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的单体,它们形成甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物(CI26);甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的单体,它们形成甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物(MICS22);甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的单体,它们形成甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物(CI18);2-羟乙基甲基丙烯酸酯和2-乙氧基乙基甲基丙烯酸酯的单体,它们形成2-羟乙基甲基丙烯酸酯和2-乙氧基乙基甲基丙烯酸酯的共聚物(Benz IOL 125);2-羟乙基甲基丙烯酸酯和甲基丙烯酸甲酯的单体,它们形成2-羟乙基甲基丙烯酸酯和甲基丙烯酸甲酯的共聚物(BenzFlex 26)。
3.根据权利要求1所述的抗微生物聚合物,其中所述抗微生物聚合物是透明的、不透明的或半透明的。
4.根据权利要求1所述的抗微生物聚合物,其中所述抗微生物聚合物是可逆变形的。
5.根据权利要求1所述的抗微生物聚合物,其中所述眼科植入物是人造角膜、青光眼瓣膜、视网膜假体或角膜内植入物。
6.根据权利要求1所述的抗微生物聚合物,其中所述抗微生物单体是季铵盐类单体。
7.根据权利要求6所述的抗微生物聚合物,其中所述季铵盐类单体是:1-[12-(甲基丙烯酰氧基)十二烷基]吡啶溴化物(MDPB)、甲基丙烯酰氧乙基十六烷基二甲基氯化铵(DMAE-CB)、2-甲基丙烯酰氧乙基十二烷基甲基溴化铵(MAE-DB)、2-甲基丙烯酰氧乙基十六烷基甲基溴化铵(MAE-HB)、双(2-甲基丙烯酰氧乙基)二甲基溴化铵(IDMA-1)。
8.根据权利要求1所述的抗微生物聚合物,其中所述抗微生物单体包括具有伯氨基、仲氨基或叔氨基的单体。
9.根据权利要求8所述的抗微生物聚合物,其中所述抗微生物单体是对二甲基氨基甲基苯乙烯、N-(2-二甲氨基乙基)丙烯酰胺、N-(2-氨基乙基)丙烯酰胺、正丁基丙烯酰胺或二烯丙基二甲基铵盐。
10.根据权利要求1所述的抗微生物聚合物,其中所述抗微生物单体与抗微生物肽共价连接。
11.根据权利要求1所述的抗微生物聚合物,其中所述至少一种其他单体是:选自丙烯酸甲酯(MA)和甲基丙烯酸甲酯(MMA)的丙烯酸单体;具有下式的有机硅单体:R2SiO,其中R为甲基、乙基或苯基;或选自乙烯基碳酸酯和乙烯基氨基甲酸酯的乙烯基单体。
12.一种制备用于眼科植入物的抗微生物聚合物的方法,包括:
使至少一种抗微生物单体与选自丙烯酸单体、疏水性丙烯酸单体、亲水性丙烯酸单体、有机硅单体、乙烯基单体和胶原单体中的至少一种其他单体反应,得到抗微生物聚合物;和
在眼科植入物中使用所述抗微生物聚合物。
13.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述疏水性丙烯酸聚合物选自:丙烯酸苯乙酯、甲基丙烯酸苯乙酯和丁二醇二丙烯酸酯的单体,它们形成丙烯酸苯乙酯和甲基丙烯酸苯乙酯的共聚物,与丁二醇二丙烯酸酯交联(IOL);丙烯酸乙酯、甲基丙烯酸乙酯、2,2,2-三氟乙基甲基丙烯酸酯的单体,与乙二醇二甲基丙烯酸酯交联,它们形成丙烯酸乙酯、甲基丙烯酸乙酯和2,2,2-三氟乙基甲基丙烯酸酯的共聚物,与乙二醇二甲基丙烯酸酯交联((AMO));甲基丙烯酸苯乙酯、丙烯酸正丁酯和氟烷基甲基丙烯酸酯的单体,它们形成甲基丙烯酸苯乙酯、丙烯酸正丁酯和氟烷基甲基丙烯酸酯的交联共聚物((HOYA));丙烯酸苯乙酯、甲基丙烯酸苯乙酯和丁二醇二丙烯酸酯的单体,它们形成丙烯酸苯乙酯、甲基丙烯酸苯乙酯的共聚物,与丁二醇二丙烯酸酯交联(HI56);2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的单体,它们形成2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的共聚物(BENZ HF-1.2);2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的单体,它们形成2-苯乙基丙烯酸酯和2-苯乙基甲基丙烯酸酯的共聚物(Benz HF-2),且
所述亲水性丙烯酸聚合物选自:甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的单体,它们形成甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物(CI26);甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的单体,它们形成甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物(MICS22);甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的单体,它们形成甲基丙烯酸羟乙酯和甲基丙烯酸甲酯的共聚物(CI18);2-羟乙基甲基丙烯酸酯和2-乙氧基乙基甲基丙烯酸酯的单体,它们形成2-羟乙基甲基丙烯酸酯和2-乙氧基乙基甲基丙烯酸酯的共聚物(Benz IOL 125);2-羟乙基甲基丙烯酸酯和甲基丙烯酸甲酯的单体,它们形成2-羟乙基甲基丙烯酸酯和甲基丙烯酸甲酯的共聚物(BenzFlex 26)。
14.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述抗微生物聚合物是透明的、不透明的或半透明的。
15.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述抗微生物聚合物是可逆变形的。
16.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述眼科植入物是人造角膜、青光眼瓣膜、视网膜假体或角膜内植入物。
17.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述抗微生物单体是季铵盐类单体。
18.根据权利要求17所述的制备抗微生物聚合物的方法,其中所述季铵盐类单体是:1-[12-(甲基丙烯酰氧基)十二烷基]吡啶溴化物(MDPB)、甲基丙烯酰氧乙基十六烷基二甲基氯化铵(DMAE-CB)、2-甲基丙烯酰氧乙基十二烷基甲基溴化铵(MAE-DB)、2-甲基丙烯酰氧乙基十六烷基甲基溴化铵(MAE-HB)、双(2-甲基丙烯酰氧乙基)二甲基溴化铵(IDMA-1)。
19.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述抗微生物单体包括具有伯氨基、仲氨基或叔氨基的单体。
20.根据权利要求19所述的制备抗微生物聚合物的方法,其中所述抗微生物单体是对二甲基氨基甲基苯乙烯、N-(2-二甲氨基乙基)丙烯酰胺、N-(2-氨基乙基)丙烯酰胺、正丁基丙烯酰胺或二烯丙基二甲基铵盐。
21.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述抗微生物单体与抗微生物肽共价连接。
22.根据权利要求12所述的制备抗微生物聚合物的方法,其中所述至少一种其他单体是:选自丙烯酸甲酯(MA)和甲基丙烯酸甲酯(MMA)的丙烯酸单体;具有下式的有机硅单体:R2SiO,其中R为甲基、乙基或苯基;或选自乙烯基碳酸酯和乙烯基氨基甲酸酯的乙烯基单体。
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