CN102368975A - 用于治疗角膜水肿的疏水性假内皮植入物 - Google Patents

用于治疗角膜水肿的疏水性假内皮植入物 Download PDF

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CN102368975A
CN102368975A CN2010800098160A CN201080009816A CN102368975A CN 102368975 A CN102368975 A CN 102368975A CN 2010800098160 A CN2010800098160 A CN 2010800098160A CN 201080009816 A CN201080009816 A CN 201080009816A CN 102368975 A CN102368975 A CN 102368975A
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奥弗尔·达夫纳
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Abstract

一种眼科植入物(10),其包括疏水性假内皮植入物(10)以及应用于其的粘合剂(14),所述粘合剂(14)能够将所述植入物(10)粘合到角膜(12)的后部,使得该植入物(10)作为能使角膜(12)脱水的防水层。

Description

用于治疗角膜水肿的疏水性假内皮植入物
本发明大体上涉及用于治疗过度充水的、水肿角膜的内皮植入物。
发明背景
眼睛感觉功能的质量极大地取决于光通过角膜和晶状体传导的质量,以及这些器官的光学质量以及角膜和眼睛晶状体的透明度,以及其他因素。
眼科领域的专家知道角膜透明度通常取决于角膜保持在脱水状态的能力。角膜脱水状态由数种相互依赖的因素所影响,其中最重要的是在角膜、内皮的最深细胞层中存在的活动泵。手术、外伤、感染或先天性易染病体质引起的超过一定水平的任何内皮功能的破坏使得水流入角膜的所有层从而扭曲其透明度。这种状况的病态不仅仅在于视力的明显下降,还在于在晚期阶段可能导致明显的疼痛及疤痕,被称为大疱性角膜炎的情况。
另一个关于使角膜脱水的重要生理机制为在觉醒期间当眼睛张开时将水从泪液膜中蒸发。通过将水从泪液膜中蒸发进行脱水,其在眼睛表面留下更浓缩的溶液,使得泪液膜更高渗。该高渗的泪液膜通过渗透作用从角膜本身吸引了更多水分;在夜晚的情况相反。市场上可获得一些高渗溶液眼滴液增强了这种机制,但不幸地是由于眼皮的眨眼它们的作用是短暂的。
当前,对不健康的水肿状态没有保守治疗。一些外科手术已逐步发展以解决这种问题:从经典的全厚度角膜移植到最近发展的称之为深板层剥离角膜成形术(DLEK)以及后弹力层角膜成形术(DSEK)的外科手术。在后者中,从患病眼睛的角膜中移除基质组织的薄后部或微透镜(lenticule)(连同连接的后弹力层膜及内皮细胞)。在供体眼睛上进行类似的手术以获得供体组织。当供体组织放置在受体眼中时,不需要缝合以将移植物保持在宿主的角膜上。所有这些手术具有供体依赖性的缺点。
发明内容
如下面详细所述,本发明涉及用于治疗水肿性眼睛将人造疏水性假内皮植入物植入到角膜的后表面。
根据本发明的一个实施方案提供了一种眼部植入物,其包括疏水性假内皮植入物以及应用于其上的粘合剂,所述粘合剂能够将植入物粘合到角膜的后部,从而该植入物作为使角膜脱水的防水层。
根据本发明的一个实施方案提供了一种治疗角膜水肿的方法,包括用粘合剂将疏水性假内皮植入物粘合到角膜的后部,使得该植入物作为使角膜脱水的防水层。
植入物由清澈、透明、生物可相容的材料构成,并且可以是刚性的、半刚性的或可折叠的。
所述粘合剂可放置在植入物和角膜后表面之间,仅仅位于植入物角膜界面的外围或整个界面表面或其他任何组合。
可在将植入物粘合到角膜后部之前移除角膜后部的一部分(尽管并非必须移除),例如举例来说,基质组织的薄后部连同后弹力层膜及连接于其上的内皮细胞,或仅仅是后弹力层膜的薄的后部及连接于其上的内皮细胞。
在设计植入物时可考虑患者的屈光状态,使得能够屈光矫正,包括散光矫正以及减轻水肿状态。
植入物可设计为多种尺寸,例如从1-2mm上至6mm或更大的覆盖后部角膜整个表面的半径或之间的任何尺寸。
植入物的厚度可从几微米高至大于100微米。该厚度可等于整个植入物直径或可在其不同部分不同使得具有屈光度,例如,在外围相对于中央较薄或相反。
尤其在刚性植入物的情况下可考虑角膜后表面的曲率以提供更好的粘附。
附图说明
从下面结合附图的详细描述将更全面的理解且领会本发明,其中:
图1和2为根据本发明的一个实施方案构造并且操作的疏水性假内皮植入物的前面和侧面的简化视图;以及
图3为根据本发明的一个实施方案用于将图1和2的植入物粘合到角膜后部的方法的简化流程图。
实施方案的详细描述
应当注意Dohlman C.H.,Brown S.I.,Martola E.L.的“ReplacementOf The Endothelium With Alloplatic Material:A New Technique InConeal Surgery”,Trans Am Acad Ophthalmol Otolaryngol.,1967 71(5),851-864,在此称之为Dohlman-Brown-Martola,描述了在患有大疱性角膜炎(角膜水肿)的患者眼中进行流体屏障手术。在Dohlman-Brown-Martola中,将透明的有机硅膜缝合在患者角膜后表面或角膜移植物上。在一些患者中,在粘附所述有机硅膜前将后弹力层膜及内皮移除。Dohlman C.H.,Freeman H.M.的“Recent Advances In TheUse Of Alloplastic Materials In Ocular Surgery”,Journal DocumentaOphthalmologica,1968,25(1),1-20,也论述了在眼睛中使用异质材料,尤其是PMMA(聚甲基丙烯酸甲酯)以及有机硅作为角膜植入物。该文章提到一种由透明有机硅橡胶制成的人工内皮,其直接缝在角膜的后表面,与Dohlman-Brown-Martola相同。
不受任何理论的限制,应当相信缝合线的使用不利于疏水性植入物的成功。因而,如现在所解释的,与现有技术相反,本发明不使用缝合线;而使用不同的粘合材料将植入物粘合至角膜的后部。
现在参考图1和图2,其图示了根据本发明的一个实施方案所构造并操作的疏水假内皮植入物10。该疏水假内皮植入物10可用于取代在DSEK手术中来自供体的植入物。植入物10作为能使角膜脱水的防水层。
植入物10可由清澈的、透明的、生物相容的材料构造,所述材料例如但不局限于,聚甲基丙烯酸甲酯(PMMA),有机硅,有机硅橡胶,胶原,透明质酸(包含钠、钾和它们的其他盐),水凝胶,例如丙烯酸或甲基丙烯酸水凝胶,例如甲基丙烯酸羟乙基酯或甲基丙烯酸酸共聚物/部分水解的聚(2-羟乙基甲基丙烯酸酯)(已知为PolyHEMA),聚砜,热不稳定材料和其他相对硬的或相对软的以及柔韧的生物惰性光学材料,或这种材料的任意组合,例如囊封在聚合物中的凝胶。因此植入物10可例如为刚性的、半刚性的或可折叠的。
在将植入物10粘合至角膜的后部之前,如在PLK中或DSEK中,从患病眼睛的角膜中移除基质组织薄的后部或微透镜(lenticule)(连同连接的后弹力层膜及内皮细胞)。或者,如在后弹力层剥离内层角膜成形术(Descemets strip endokeratoplasty)中,只移除后弹力层膜和内皮细胞。或者,可将植入物粘附在角膜内皮上而不剥离任何后表面。
使用粘合剂14将植入物10粘合至角膜12的后部(图1显示了角膜12的后侧)。粘合剂14可放置在植入物10和角膜12的后部表面之间,仅仅处于植入角膜界面的外围或在整个界面表面上或任意其他的组合(图3)。依照本发明合适使用的粘合剂包括,例如,但不局限于,聚L-赖氨酸(Poly-L-lysine)和聚D-赖氨酸(poly-D-lysine)。基于简要的目的,每个聚L-赖氨酸和聚D-赖氨酸在下文中无差别地称之为“聚赖氨酸”。其他合适的粘合剂包括,但不局限于:纤连蛋白、层粘连蛋白、I,II,III和IV型胶原、血小板反应蛋白、聚苯乙烯、玻连蛋白、聚精氨酸和血小板因子IV。粘合剂可包含上述其中之一或它们的任何组合。根据本发明的一个实施方案,一种或者多种粘合剂可与一种或者多种细胞毒性剂相结合,其中细胞毒性剂可施加在植入物的内表面上或其外表面上的中心处或二者皆是或二者皆不,以便防止通过在植入物上生长新组织而产生不透明体。合适的细胞毒性剂包含,但不局限于,核糖体抑制蛋白,例如但不局限于皂草素和蓖麻毒素。其他的据信与本发明联合使用时有效的细胞毒性剂包含,但不局限于,抗有丝分裂药,例如,甲氨蝶呤、5-氟尿嘧啶、柔红霉素、阿霉素、米托蒽醌、长春花生物碱、长春碱、秋水仙碱以及细胞松弛素,和例如莫能菌素和乌本苷的离子载体。
为了防止角膜由于完全阻断了诸如葡萄糖等的营养材料而萎缩,植入物10可形成有一个或多个通孔16以控制流至或来自于角膜的一小股流体,这将对营养支持是足够的但不会导致角膜水肿。
在本发明的另一个实施方案中,植入物10的外表面(朝向角膜)可具有亲水特性从而进一步加强至角膜的粘合力,因此产生疏水-亲水植入物。可在植入物设计中考虑病人的屈光状态因此使得屈光矫正的同时减轻水肿的状态。
本领域技术人员可以理解的是本发明并不局限于已经具体示出的和在此描述的。本发明的范围包含在此描述特征的组合和亚组合以及本领域技术人员基于阅读前面的描述对它们进行的且不存在于现有技术中的修改和改变。

Claims (16)

1.一种治疗角膜水肿的方法,其包括
用粘合剂(14)将疏水性假内皮植入物(10)粘合到角膜(12)的后部,使得该植入物(10)作为使角膜(12)脱水的防水层。
2.根据权利要求1的方法,其中所述植入物(10)由清澈、透明、生物相容的材料构造。
3.根据权利要求1的方法,其中所述植入物(10)是刚性的。
4.根据权利要求1的方法,其中所述植入物(10)是可折叠的。
5.根据权利要求2的方法,其中所述材料包括下列的至少一种:聚甲基丙烯酸甲酯(PMMA)、有机硅、有机硅橡胶、胶原、透明质酸、丙烯酸水凝胶、甲基丙烯酸水凝胶、甲基丙烯酸羟乙酯、甲基丙烯酸共聚物/部分水解的聚(甲基丙烯酸2-羟乙基酯、聚砜以及热不稳定材料。
6.根据权利要求1的方法,其中在将所述植入物(10)粘合到角膜(12)的后部之前移除角膜(12)后部的一部分。
7.根据权利要求6的方法,其中在将所述植入物(10)粘合到角膜(12)的后部之前,从角膜(12)移除基质组织薄的后部连同后弹力层膜及连接于其上的内皮细胞。
8.根据权利要求6的方法,其中在将所述植入物(10)粘合到角膜(12)的后部之前,从角膜(12)移除后弹力层膜薄的后部及连接于其上的内皮细胞。
9.根据权利要求1的方法,其中所述粘合剂(14)包含以下至少一种:聚赖氨酸、纤连蛋白、层粘连蛋白、I,II,III和IV型胶原、血小板反应蛋白、玻连蛋白、聚精氨酸和血小板因子IV。
10.根据权利要求1的方法,其中所述粘合剂(14)与至少一种细胞毒性剂相结合。
11.一种眼科植入物(10),其包含:
疏水性假内皮植入物(10)以及应用于其上的粘合剂(14),所述粘合剂(14)能够将所述植入物(10)粘合到角膜(12)的后部,使得该植入物(10)作为能使角膜(12)脱水的防水层。
12.根据权利要求11的植入物(10),其中所述植入物(10)由清澈、透明、生物相容的材料构造。
13.根据权利要求11的植入物(10),其中所述植入物(10)是刚性的。
14.根据权利要求11的植入物(10),其中所述植入物(10)是可折叠的。
15.根据权利要求12的植入物(10),其中所述材料包括下列的至少一种:聚甲基丙烯酸甲酯(PMMA)、有机硅、有机硅橡胶、胶原、透明质酸、丙烯酸水凝胶、甲基丙烯酸水凝胶、甲基丙烯酸羟乙酯、甲基丙烯酸共聚物/部分水解的聚(甲基丙烯酸2-羟乙基酯、聚砜以及热不稳定材料。
16.根据权利要求11的植入物(10),其中所述植入物(10)形成有至少一个通孔(16)。
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