CN102271622A - 带有具备内部包被的套筒的眼内晶状体递送装置 - Google Patents

带有具备内部包被的套筒的眼内晶状体递送装置 Download PDF

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CN102271622A
CN102271622A CN2009801543549A CN200980154354A CN102271622A CN 102271622 A CN102271622 A CN 102271622A CN 2009801543549 A CN2009801543549 A CN 2009801543549A CN 200980154354 A CN200980154354 A CN 200980154354A CN 102271622 A CN102271622 A CN 102271622A
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穆特鲁·卡拉科勒
大卫·A·豆纳
苏珊特·穆查拉
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Abstract

公开了眼内晶状体递送装置(IOL)。所述装置包括具有内部包被的眼内晶状体套筒,其中所述包被包含聚合材料,该聚合材料与形成所述套筒的材料的聚合材料相容。优选地,所述包被、所述套筒或两者的聚合材料是聚氨酯材料。

Description

带有具备内部包被的套筒的眼内晶状体递送装置
相关申请的交叉引用
本申请根据35U.S.C.§119要求于2008年11月20日提交的美国临时专利申请第61/116,443号的优先权,通过引用将其全部内容并入本文。
发明领域
本发明涉及具有内部包被的眼内晶状体套筒,其中所述包被包含聚合材料,该聚合材料与形成所述套筒的材料的聚合材料相容。
发明背景
人类眼睛通过使光传递和折射通过称为眼角膜的透明外部,并进一步将图像经过晶状体聚焦在眼睛后部的视网膜来发挥提供视觉的功能。聚焦的图像质量取决于多种因素,包括眼睛的大小、形状和长度,以及眼角膜和晶状体的形状和透明度。
当外伤、年龄、疾病或其他因素导致个体的天然晶状体的透明度变差时,由于可被传递至视网膜的光减少而使视觉恶化。眼睛晶状体的这种缺陷通常被称为白内障。对该疾病状态的治疗是手术移除天然晶状体并植入眼内晶状体(IOL)。
尽管早期IOL由诸如聚甲基丙烯酸甲酯(PMMA)的硬塑料制成,但是由硅酮、软丙烯酸树脂和水凝胶制成的柔软的、可折叠的IOL变得越来越受欢迎,这是由于能够将这些柔软的晶状体折叠或卷曲并将它们通过较小的切口插入。卷曲或折叠晶状体的数种方法已被使用。一种受欢迎的方法是注射器套筒,其将晶状体折叠并提供相对小的直径腔,可将晶状体通过该腔推入眼睛,通常是利用柔软的尖端活塞。一种常用的注射器套筒设计在美国专利第4,681,102号(Bartell)中进行了说明,该注射器套筒设计包括分开的、纵向铰链式套筒。相似的设计在美国专利第5,494,484号和第5,499,987号(Feingold)以及美国专利第5,616,148号和第5,620,450号(Eagles,et al.)中有说明,通过引用将上述专利的全部内容并入本文。其他的套筒在美国专利第5,275,604号(Rheinish,et al.)、美国专利第5,653,715号(Reich,et al.)和美国专利第5,947,876号(Van Noy,et al.)中有描述,通过引用将上述专利的全部内容并入本文。
当利用活塞推动IOL通过套筒的小直径腔时,相对大的力量可以施加在活塞、套筒和/或IOL上。通常,需要使套筒能控制这些力来促进IOL的有效递送。这些力目前变得越来越受关注。具体而言,医疗界已经表示需要IOL套筒具有较小的喷嘴,而较小的喷嘴允许外科医生利用较小的切口将IOL递送至个体眼睛。这些较小的喷嘴产生较小的腔,在IOL递送过程中必须推动IOL通过所述较小的腔。因此,在IOL递送过程中,施加在IOL、套筒喷嘴和活塞上的力可以显著增加,并且对这些力的控制可以是富有挑战性的。
为了缓和IOL递送过程中产生的力,通常在套筒的内表面施加低摩擦的包被,以允许IOL更容易地通过由该内表面所界定的腔。然而,IOL套筒的常规包被应用起来复杂,且可涉及多个层和多种不同的材料。相应地,这种包被难于以一致的方式施加,并且会占据IOL正常通过的腔的空间。
除了包被之外,还可以通过利用能处理这些力的材料来实现IOL递送力的控制,尤其是递送套筒的材料。然而,发现适于插入任何眼睛内并表现出所需的处理IOL递送力的物理特性,而且同时与应用在IOL递送套筒内表面的包被相容的材料是相当富有挑战性的。
鉴于上述,需要提供IOL套筒和包被组合,其中所述包被相对于常规包被有所改善,并且形成套筒的材料与改善的包被相容,并同时仍能表现出所需的物理特性。
发明概述
因此,本发明涉及IOL递送装置。所述装置包括具有主体部分和喷嘴的递送套筒,所述主体部分和喷嘴包括界定了沿着所述主体部分和喷嘴延伸的腔的内表面。所述内表面由聚合材料形成,所述聚合材料是聚氨酯材料或具有异质骨架的非烯族聚合材料。包被被置于内表面上,且所述包被由聚氨酯材料和亲水性材料形成。
包被的聚氨酯材料形成交联的或线性的基质,且亲水性材料分散在整个基质中。优选地,所述包被是直接设置在套筒的内表面上的单层,而且在所述单层上没有任何包被层,但是其它配置也是可以的。
还优选的是所述套筒和内表面由单一的聚合材料形成,但这不是必须的,除非另外说明。所述内表面的材料的弯曲模量通常为至少200MPa,更通常为至少1200MPa,且更通常为至少2000MPa。此外,所述内表面的材料的硬度通常为至少50D,更通常为至少75D,且更可能为至少90D。
附图简要说明
图1是按照本发明一个方面的示例性IOL递送装置的图。
图2是图1的IOL递送装置的一部分的截面图。
发明的详细描述
本发明提供IOL递送装置,所述装置包括由材料形成的递送套筒和与该材料相容的包被。所述递送套筒的材料优选表现出能适应将IOL递送通过所述套筒的过程中产生的力的物理特性。而且,所述套筒材料与所述包被之间的相容性可允许便于施加包被。通常,所述套筒的材料是聚合材料,该聚合材料与包被的聚合材料来自相同家族或表现出对所述聚合材料的材料的亲和力。在优选的实施方案中,所述套筒和包被(例如,形成包被材料的基质)都由聚氨酯材料形成。
参照图1,显示了示例性IOL递送装置10,其包括具有主体部分14和喷嘴16的套筒12。套筒12,尤其是主体部分14和喷嘴16,界定了内表面18,内表面18界定了沿着套筒12、主体部分14和喷嘴16的长(L)延伸的腔20。内表面18由本发明的包被22覆盖。喷嘴16通常被设置为能插入眼睛的切口,以助于将IOL通过喷嘴16递送进眼睛中。如图所示,喷嘴16具有与轴24垂直的内径(ID)和外径(OD),轴24沿着喷嘴的长度方向延伸,该轴与图1-3中所示的长(L)相同。优选地,喷嘴16的内径、外径或两者小于6毫米(mm),更通常为小于3mm,仍然更通常为小于2.5mm且甚至有可能小于1.9mm,但这不是必须的,除非另外表明。
所述套筒通常可以由多种聚合材料形成,并可以由单一聚合材料或多种聚合材料形成。当利用多种聚合材料时,它们可以是分层的或混合的。可能的聚合材料的实例包括但不限于,聚氨酯、聚碳酸酯、聚砜、聚醚酰亚胺、聚醚嵌段酰胺、聚丙烯、聚丙烯酸酯和聚甲基丙烯酸酯、聚乙烯或聚丙烯共聚物、聚氯乙烯、环氧化物、聚酰胺、聚酯或与橡胶、硅氧烷或其它聚合物的共聚物、以上的组合等。
通常优选地,形成所述套筒和/或所述腔的内表面的材料是相对亲水性的,且表现出所需的水接触角,用于使该材料与包被的匹配聚合材料更相容,所述匹配聚合材料优选为聚氨酯材料。该接触角通常至少50°,更通常为至少70°,且甚至更通常为至少75°。该接触角还通常小于85°且更通常为小于80°。对于本发明,可以利用卧滴接触角测量技术测量接触角。
优选地,接受包被的套筒的材料基本上或完全是非聚烯烃的。这表示形成套筒和/或形成套筒腔内表面的材料所含有的任何聚烯烃、尤其是聚丙烯和聚乙烯在重量上小于50%,更通常为小于30%,更通常为小于20%且甚至可能小于5%,并且在一个优选的实施方案中,完全没有任何聚烯烃。通常优选地,形成套筒和/或形成套筒腔内表面的材料是聚氨酯材料(即,包含大部分聚氨酯的材料)。如本文所用,包含大部分聚氨酯表示包含的聚氨酯在重量上为至少20%,更通常为至少40%且可能为至少70%。
套筒和/或腔内表面的聚氨酯材料可以完全或基本上完全由聚氨酯形成,而没有与其混合或与其共聚的任何其它类型聚合物。可选择地,所述聚氨酯材料可以是聚氨酯和一种或多种其它聚合物的混合物或聚氨酯和一种或多种其它聚合物的共聚物。通常优选地,热塑性材料完全或基本上完全是热塑性的,但这不是必须的,除非另外表明。示例性的共聚物可以包括但不限于聚氨酯/聚醚共聚物、聚酯/聚氨酯共聚物、其组合等。
示例性的合适的聚氨酯材料包括可从密歇根州米德兰Dow ChemicalCompany购得的商品名为ISOPLAST
Figure BPA00001403370600041
2531和ISOPLAST
Figure BPA00001403370600042
2530的刚性热塑性氨酯。另一个示例性的合适的聚氨酯材料是热塑性聚氨酯弹性体,其可以为共聚物。这类聚氨酯材料的实例是基于聚氨酯材料的聚醚,其通常是脂肪族的且以商品名PELLETHANE
Figure BPA00001403370600051
2362 75D和PELLETHANE
Figure BPA00001403370600052
2363 65D出售,它们也可以从密歇根州米德兰Dow Chemical Company购得。其它合适的热塑性聚氨酯共聚物包括但不限于芳香族聚醚/聚氨酯共聚物、聚己内酰胺共聚多酯/聚氨酯共聚物等。还应当考虑到前面提到的任何聚合材料的组合都可以用作套筒的材料。
尽管套筒和界定腔的表面的材料优选是聚氨酯材料,但是应当考虑到可以使用其它材料,其中所述材料的性质与聚氨酯相似并因此表现出对包被相似的亲和力。这类材料通常具有本文所描述的水接触角。而且,这类材料通常是与异质骨架的聚合物,且那些骨架在它们的单体、寡聚物或两者中通常包含碳原子和氧原子。聚碳酸酯是这些备选材料的良好实例。另一个合适的实例包括聚醚酰胺共聚物,例如以商品名PEBAX
Figure BPA00001403370600053
出售的那些,它们可从地址为420,rue d′Estienne d′Orves,F-92705Colombes Cedex France的Arkema购得。
为了用作IOL递送套筒,套筒的材料具有所需的弯曲模量和所需的硬度是理想的。通常地,所述弯曲模量为至少200MPa,更通常为至少1200MPa且甚至更通常为至少2000MPa。所述弯曲模量通常小于5000MPa,更通常小于3000MPa且甚至更通常小于2600MPa。可以按照ASTM D790测量弯曲模量。通常,所述硬度为至少50D,更通常为至少75D且甚至可能至少90D。所述硬度通常小于120D,更通常小于100D且甚至可能小于95D。可以按照橡胶性质硬度计硬度的ASTM D2240标准测试方法测量硬度。
优选地,包被22的材料包含大部分的聚合材料,该聚合材料与形成套筒12的内表面18的聚合材料相匹配(即,来自同一家族)。具体而言,优选地,所述匹配材料(即,包被的聚合材料和形成套筒12的内表面18的聚合材料)具有至少70%、更优选至少90%的相同的单体重复单元、寡聚重复单元或两者。可选择地或额外地,所述匹配材料可以由至少70%、更优选至少90%的氨酯结构组成。
当包被材料被施加并干燥后,与套筒内表面的聚合材料相匹配的包被的聚合材料在重量上优选为所述包被材料的至少30%,更通常为至少40%且甚至更通常为至少45%。当包被材料被施加并干燥后,所述聚合材料在重量上还通常不超过所述包被材料的约90%,更通常不超过约80%且甚至更通常不超过约60%。该匹配的聚合材料可以来自任何在套筒材料方面所论述的家族。优选地,所述匹配聚合物材料是聚氨酯材料。
当使用时,聚氨酯在被合并入包被之前通常具有特定的性质。聚氨酯在23℃下具有的黏性通常为至少约50厘泊(cps),更特别为至少100cps。聚氨酯在23℃下的黏性通常不超过约390cps且更通常不超过约250cps。聚氨酯还通常具有约30-50且更特别为约35-41的固体含量。聚氨酯还通常具有约6.0-约10且更优选约7.5-约9.0的pH。
在优选的实施方案中,所述包被包含聚合匹配材料、亲水性材料,且任选地包含交联剂或交联物。在该实施方案中,所述聚合匹配材料通常可交联形成基质,该基质适于促进保留亲水性材料。美国专利第6,238,799中提供了这类包被的实例,通过引用将其并入本文用于所有目的。合适的包被的另一实例以商品名LUBRILAST
Figure BPA00001403370600061
出售且可从AdvancedSurface Technologies,9 Linnell Circle,Billerica,MA 01821购得。
所述亲水性材料通常是的这样聚合物:所述聚合物在水的存在下膨胀以提供“光滑(slippery)”或光滑(lubricous)的表面。示例性的亲水性聚合物包括但不限于,诸如聚(乙烯吡咯烷酮)(PVP)等的聚(N-乙烯基内酰胺)、聚(环氧乙烷)(PEO)、聚(环氧丙烷)(PPO)、聚丙烯酰胺、诸如甲基纤维素等的纤维素制品、诸如丙烯酸和甲基丙烯酸等的聚丙烯酸、聚乙烯醇,以及聚乙烯醚等。
包被中聚合匹配材料(例如聚氨酯)与亲水性聚合物在重量上的比值通常为约10∶1-约1∶10,更通常为约5∶1-约1∶5,仍然更通常为约2∶1-约1∶2且甚至仍更通常为约1.3∶1-约1∶1.3。
在特别优选的实施方案中,所述亲水性材料是PVP或包含PVP。PVP可以具有一种K值或K值的混合,所述K值从K15或可能更低至K90或可能更高。优选的PVP具有的K值为约80-110。PVP的平均分子量通常为至少约500,000道尔顿,更通常为至少800,000道尔顿且甚至更通常为至少1.0M道尔顿。PVP的分子量还通常小于约3.0M道尔顿,更通常小于约1.8M道尔顿且甚至更通常小于约1.4M道尔顿。
所述包被的匹配聚合材料的交联反应可以是自发的,使得聚合物自身的官能团形成交联。合适的能自交联的官能团包括但不限于,氧化干燥的醇酸树脂、甲醛缩合物、羟甲基丙烯酰胺和烯丙基。例如,这种交联可以通过加热或施加UV能量而启动。可以加热至150℃或更高温度。
在其它实施方案中,可以通过将交联剂添加至包被组合物中来启动交联反应。可以在即将进行包被操作之前将该交联剂添加至包被组合物。可选择地,可以在包被之后将被包被的物质暴露于交联剂,例如使干燥的包被在含有交联剂的水性溶液中膨胀。合适的交联剂包括但不限于,多官能氮丙啶、多官能碳二亚胺和多官能环氧化物。通常,所述交联剂是双官能化合物或三官能化合物;然而,使用具有任何数量的官能团的多官能交联剂被考虑在本发明的范围内。交联剂可以与支持聚合物形成一种或多种交联和/或可以与邻近交联剂形成交联。交联剂还可以与IOL套筒表面上的活性底物部分发生反应,尤其当对表面进行预处理使其暴露于官能团而在表面上产生官能团时。这导致亲水性聚合物的较高的交联密度,这在某些情况下是可取的,例如当亲水性聚合物分子量较低、与支持聚合物的亲和力不足时,或当支持聚合物具有低水平的官能部分时。
可以用多种聚合物模塑或成形技术来形成IOL套筒。实例包括但不限于,压缩模塑或注射模塑(例如,热塑性注射模塑或反应注射模塑)。可以对待用包被进行包被的套筒表面进行处理(例如,等离子体处理),从而将反应性基团提供给表面,这在上文讨论过了。在优选的实施方案中,包括界定腔的内表面的套筒是用单一连续材料进行注射模塑。
通常,通过将匹配聚合材料与亲水性材料以及任选的交联剂在水性介质或其它介质中混合来形成包被。在优选的实施方案中,将匹配聚合材料和亲水性材料分别提供在水性介质中,并用搅拌棒将它们在容器(例如,烧瓶或烧杯)中混合以形成混合物。然后,在将包被施加于IOL套筒之前的一小段时间,将交联剂混入该混合物中。
可以利用多种技术将包被施加于套筒腔的内表面。例如,所述包被可以是浸涂的、擦涂的、刷涂的或以其它方式施加。在一个优选的实施方案中,使用诸如针的注射装置将包被材料在诸如喷嘴区域和临近喷嘴的区域填充套筒内腔,在递送过程中IOL沿着喷嘴区域和临近喷嘴的区域移动。以这种方式,允许包被与腔的内表面相联(即,附着和/或与其反应)。然后将额外的包被从套筒清除(即,引流)。此后,通过加热和/或水分蒸发使包被干燥。
包被通常提供能容纳和保留水的表面,并进而提供光滑表面。然后在IOL的递送过程中,IOL可以相对容易地沿着被包被的表面滑动。这对于被递送通过相对狭窄的腔的较软的IOL的递送尤其有利。因此,所述递送系统非常适用于将疏水性丙烯酸可折叠的IOL递送进个体眼睛中。
有利的是,当聚氨酯且尤其是聚氨酯共聚物材料或聚碳酸酯被用作套筒材料时,那些材料能提供非常适用于IOL套筒、尤其是适用于套筒喷嘴的特性。而且,那些材料还非常适于与包被的聚氨酯匹配聚合物材料一起使用,因为这种包被能直接附着IOL套筒表面和/或与IOL套筒表面结合。这允许以单层的形式施加包被,并且能避免常规IOL包被的一层或多层和/或一个或多个施加步骤。例如,至少一种常规IOL包被需要套筒内表面被进行等离子体处理,且需要在施加所需的包被之前对内表面施加基底层。使用优选的单层包被时,不需要基底层、甚至可能不需要等离子体处理。
申请人特别合并了本公开所引用的所有参考文献的全部内容。此外,当以范围、优选范围或列出上限优选值或下限优选值的形式给出量、浓度或其他值或参数时,应当理解为具体公开了任何范围上限或优选值和任何范围下限或优选值的任何配对所形成的所有范围,不管是否单独公开了此范围。当本文列举了数值范围时,除非另外表明,所述范围意图包括其端点和所述范围内的所有整数和分数。当限定范围时,并未意图将本发明的范围限制于列举的具体值。
参照本发明说明书和本文所公开的本发明的实践,本发明的其他实施方案对于本领域技术人员是显而易见的。本说明书和实例应仅理解为举例说明,权利要求书及其等同物表明本发明的真正范围和实质。

Claims (17)

1.IOL递送装置,所述装置包括:
具有主体部分和喷嘴的递送套筒,所述主体部分和喷嘴包括内表面,该内表面界定了沿着所述主体部分和喷嘴延伸的腔,其中至少所述内表面由聚合材料形成,所述聚合材料是聚氨酯材料或具有异质骨架的非烯烃聚合材料;以及
设置在所述内表面上的包被,其中所述包被由聚氨酯材料和亲水性材料形成。
2.如权利要求1所述的装置,其中所述包被基本上仅由聚氨酯材料和亲水性材料组成。
3.如权利要求1或2所述的装置,其中所述亲水性材料包含聚乙烯吡咯烷酮。
4.如前述权利要求中任一项所述的装置,其中所述包被的聚氨酯材料形成交联的或线性的基质,并且所述亲水性材料分散在所述整个基质中。
5.如前述权利要求中任一项所述的装置,其中所述包被是直接设置在所述套筒内表面上的单层,在所述单层上没有任何包被层。
6.如前述权利要求中任一项所述的装置,其中所述包被被直接设置在所述内表面上,在所述包被和所述内表面之间没有任何基底包被。
7.如前述权利要求中任一项所述的装置,其中所述套筒和所述内表面由单一聚合材料形成。
8.如权利要求7所述的装置,其中所述单一聚合物材料是聚合物的混合物或共聚物。
9.如前述权利要求中任一项所述的装置,其中所述包被还包含交联物。
10.如前述权利要求中任一项所述的装置,其中所述内表面的材料的弯曲模量为至少1200MPa。
11.如权利要求10所述的装置,其中所述弯曲模量小于3000MPa。
12.如前述权利要求中任一项所述的装置,其中所述内表面的材料的硬度为至少75D。
13.如权利要求12所述的装置,其中所述硬度小于100D。
14.如前述权利要求中任一项所述的装置,其中所述包被中聚氨酯材料与亲水性聚合物在重量上的比值为约10∶1-约1∶10。
15.如前述权利要求中任一项所述的装置,其中所述亲水性材料是PVP或包含PVP,且所述PVP的K值为约80-110,且所述PVP的平均分子量为至少800,000道尔顿且小于约1.8M。
16.如前述权利要求中任一项所述的装置,其中所述套筒包括喷嘴,且所述喷嘴的内径、外径或两者小于2.5mm。
17.如前述权利要求中任一项所述的装置,其中所述内表面的聚合材料是聚氨酯。
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