CN1438873A - 可持续释放药物的输送装置及其使用方法和制造方法 - Google Patents
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Abstract
一种治疗哺乳动物有机体,以获得所需的局部或全身的生理或药理效果的方法和装置。该方法包括将一个持续释放药物的输送系统施用于需要这种治疗的哺乳动物有机体,使其处于需要释放该有效药剂的区域,且使该有效药剂以可控的方式通过该装置。该装置包括一个包含有效药剂的内芯或贮药装置、一个部分封闭贮药装置的不透管和一个处于管子端部的可透元件。
Description
发明的背景
技术领域
本发明涉及一种新颖的可持续释放药物的输送装置,而更具体地涉及一种多层的药物输送装置。
背景技术
多年来,人们已经开发出各种药品以帮助治疗各种各样的大小疾病。但是,在许多情况下这样的药物都不能在没有无毒副作用危险的前提下口服或静脉注射。
例如,静脉注射甘环核苷(GCV)对治疗艾滋病人的巨细胞病毒(CMV)视网膜炎是有效的,但是骨髓毒性则限制了它的使用。在静脉注射GCV治疗过程中,中性粒细胞的减少症(中性粒细胞绝对计数<1000)的发病率在30%至50%的范围。为了防止疾病的发展或复发,有必要连续维持GCV治疗,但尽管是维持治疗,仍有30%至50%的病人在治疗过程中出现旧病复发。与GCV全身给药相关联的问题还包括长期内置导尿管引起败血症的危险和不能同时接受已经证明可以延长艾滋病人的生命和提高其免疫功能的齐多夫定(AZT)治疗。
每周一次或二次玻璃体内注射200μg至400μg GCV给药可使艾滋病人的CMV视网膜炎得到暂时缓解。玻璃体内注射GCV较全身治疗能提供较高的眼内药物浓度,并且降低中性粒细胞减少症的发病率。目前对艾滋病人的CMV视网膜炎的治疗明显不是最理想的。甘环核苷是抑制病毒生长的,因此控制疾病需要持续给药。
由于某些药物所带来的危险,为了有助于治疗这些大小疾病,研究人员已经开发出使用这类药物的给药系统。许多这样的系统可提供减少不良副作用发生的释放速度。
以传统的给药方式(片剂、注射等),药物在身体的给定区域内的浓度是从无效浓度提高到有效浓度的。实际上该浓度经常会多少达到中毒阈值。然而,在较短的一段时间之后,随着药物在身体内或代谢变化或消失,药物浓度下降。药物浓度经常会降低到不再维持治疗的水平。然后进行第二次给药,并且重复这一过程。持续释放系统的目标是将药物浓度保持在治疗范围内,且最好是恒定的水平。
为了实现药物水平恒定,药物应该是以不随时间变化(所谓的零次幂释放)的速度从输送系统释放。但是,在许多系统中,释放速度是与时间(即“一次方”)或时间的平方根(或Fickian)成比例的。
利用某些类型的贮药系统,例如管子、纤维层压件或小球体,可以实现线性释放。在这些系统中,贮药装置被一层速度控制膜所覆盖。只要该膜的透过性不改变,并且只要贮药装置中的药物的浓度是恒定的(即只要贮药装置中的药物有剩余),则药物在整个膜上的扩散就是速度限制的和恒定的(零次幂)。
在基质系统中,药物通过整个基质扩散,并且随着其在基质内的溶解和扩散而释放出来。药物首先从基质的外表面扩散,此层耗尽,而后药物自该装置的内芯内的进一步释放则必须通过耗尽的基质扩散。最终的结果是释放速度减慢,而Fickian释放是通常的情形。采用基质系统,很难实现零次幂释放。同样的原理也适用于自胶体释放。
在某些易受生物侵蚀的系统中,通过基质的扩散设计为极其缓慢,且药物倾向于随着该系统的降解而释放。总体上人们已经发现,采用这种方法实现零次幂释放极其困难,因为大多数聚合物并不经历零次幂降解。“S”型动力是比较普通的情况。在Xue Shen Wu博士所著《Controlled Drug Delivery Systems》(第一部分)第32、33、44-46、63、66和67页(Technomic Publishing Co,Inc.,1996年)中提出了药物输送控制系统的总体讨论,其整体内容在此引用作为参考。
一种这类的输送装置是口服药丸或胶囊,其中含有药物,该药物包封在多层的在消化道内经过一段时间后溶解的成分中,因此能够使药物逐步或缓慢释放到系统内。
用于控制这类药物的给药的另一种类型的装置是这样生产的,给药物涂覆一层使药物能够通过的可渗透的聚合材料,以获得所需的效果。这类装置特别适合于在特定的局部区域对患者进行治疗,不必使患者的整个身体暴露于药物。由于能够使该药物的任何可能的副作用减至最小,所以是比较有利的。
这类系统特别适合于治疗眼病。将药物施放到眼睛的外表面的进展公开于授予Amold的美国专利No.4,014,335中,Amold专利描述了各种起到长时间将药物缓慢释放到泪膜的沉积物或贮药装置作用的眼内嵌入物。这些嵌入物用生物惰性的、不过敏的、在泪液中不溶解的柔性聚合材料制造。为了启动这些装置的治疗程序,该眼内嵌入物置于眼球的巩膜和眼睑之间的陷凹内,用于向眼睛给药。
用在泪液内不溶解的聚合材料制成的装置可以在所需的治疗过程中保持其形状和整体性,以起到以不受聚合材料的分解和腐蚀影响的速度向眼睛和周围的组织连续给药的贮药装置的作用。直到所需的治疗程序的终结,将该装置将自陷凹内取出。
在美国专利No.3,416,530中描述了用于将药物持续释放到眼睛的外表面的另一类型的装置,其通常用聚合物薄膜制成,带有多个在该装置的外部和内腔之间连通的毛细孔。尽管这种结构中的这些毛细孔对于将特定的药物释放到眼睛方面是有效的,但是它大大地增加了该装置制造的复杂性,因为在用各种聚合物大规模制造时难于控制这些孔的尺寸。
美国专利No.3,618,604所述的另一种装置不涉及这种毛细孔,但是代之以提供了通过聚合物薄膜的扩散来释放药物。如在该专利中所公开的,该装置的优选实施例包括一个在其内腔具有药物的密封的容器。然而,如美国专利No.4,014,335所述,这类装置有特殊的问题,如密封薄膜的边缘以形成该容器是一项困难的工作。另外,在这些装置的制造过程中由于变形而在薄膜壁内产生的应力和应变可能导致该贮药装置破裂和泄漏。
美国专利No.4,014,335所述的另一种这类装置包括一个三层层压件,其具有一对单独分离的用在泪液中不溶解的材料制成的第一和第三壁,其中一个壁用允许药物通过的药物释放材料制成,而另一壁用不允许药物通过的材料制成。
上述的系统和装置的目的在于,在用于获得特定的生理或药理效果的所需的局部或在全身位置,为治疗的患者提供有效的持续的药物释放。但是,有与其使用相关联的许多缺点,包括事实上经常难于获得所需的药物释放速度。需要一种更好的释放系统在治疗CMV视网膜炎方面具有特别重大的意义。
在开发本发明之前,已经开发了一种新颖的持续释放输送装置,其改进了上述的与药物输出相关联的许多问题。该装置公开于美国专利No.5,378,475(其整体内容在此引用作为参考),包括有效药剂基本不能透过的第一涂层和有效药剂能够可以透过的第二涂层。在该装置中,第一涂层覆盖至少一部分内芯;但是,至少一小部分内芯不用第一涂层覆盖。第二涂层基本上完全覆盖第一涂层和内芯的未覆盖部分。内芯未被第一涂层所覆盖的部分允许药剂通过而进入第二涂层,因此可以实现控制释放。
尽管美国专利No.5,378,475所述的装置解决了上述关于药物释放的许多问题,但该装置和制造该装置的方法不是没有问题的。特别是,适合于涂覆内芯的聚合物通常比较柔软,且在生产均匀薄膜方面会出现技术困难。当试图涂覆带有边缘的非球形物体时(例如圆柱形),这一点特别现实。在这种情况下,必须施加较厚的薄膜,以获得连续而均匀的涂层,这明显增大该装置的体积。因此,由于密封内芯的端部所需厚度的结果,该装置倾向于大于所需的尺寸。
上述美国专利No.5,902,598就制造其大小在装置体积对于该装置的设计起到限制作用的解剖位置能够有效给药的装置的问题提出了一些解决方案。尽管在原位输送药物有效,但是制造难度已经限制了这些装置的大规模制造。例如,上述应用中该装置直接包覆贮药装置的不透的内涂层一般用一层厚度不能支撑其自身重量的材料制成。
尽管从缩小该装置整个尺寸的观点看是有效的,且尽管仍然密封贮药装置,与上述专利的目标有很好的针对性,但是此内层的相对软弱使其难于承担带有药溶液、药浆或药物悬浮液的贮药装置的重量。因为此内层基本在结构上不能保持其形状而没有明显的塌陷,即,不具有尺寸稳定性或结构能力来接受插入其中的药物内芯而不改变形状,因此要制造该装置就必须使用相对固体的药物或含药混合物。在制造过程中将药浆装入不能保持其自身形状的内层导致药浆和内层的结合,因为该内层塌陷和含药混合物流出,所以在不损坏的情况下此结合极难处理。
装置尺寸的问题在设计用于植入有限的解剖位置,如眼睛的装置中极其重要。较大的装置对于植入和取出所要求的外科手术更为复杂。复杂性的增加导致并发症、更长的康复或恢复周期和潜在的副作用(例如增加散光的机会)。再者,要求实现均匀涂层的超大的聚合物减少植入物的潜在体积,且进一步限制了能够输送的药物量,潜在地限制了功效和持续时间。
作为上述全部的结果,在本领域仍需要改进制备为患者提供药物持续释放,以获得局部或全身生理或药理效果,特别是眼睛内使用的装置的设计和方法。
发明内容
因此,本发明的基本目的是提供一种适于控制和持续释放有效成分,以得到所需的局部或全身的生理或药理效果的装置。
本发明的另一目的是提供一种用于治疗哺乳动物有机体,例如人类的方法,以得到所需的局部或全身的生理或药理效果。该方法包括将持续释放药物的输送系统定位在需要释放药剂之处,并该药剂能够通过该装置到达所需治疗的区域。
本发明的又一目的是提供一个适于直接植入玻璃体内的眼内装置。人们惊奇地发现,本发明的这类装置能够对各种成分提供持续和控制的释放,对眼睛进行治疗,而且没有局部或全身的不良副作用。
本发明的又一目的是在减小眼内装置尺寸的同时,使其所含的药量最大,以延长植入时间。
本发明的又一目的是提供一个能够施加到一个眼内透镜的眼内输送系统,以防止炎症或后期的蒴状混浊。
本发明的又一目的是提供一种眼内输送系统,它能够直接插入玻璃体内,位于视网膜下,或在巩膜上,且其中插入可以通过注入该系统或用外科手术植入该系统实现。
根据第一实施例,一种持续释放药物的输送系统包括一个包含有在获得所需的局部或全身生理或药理效果方面有效的药剂有效剂量的内贮药装置,其包括一个上述药剂不能透过的内管,上述内管具有第一和第二端,且覆盖上述内贮药装置的至少一部分,上述内管的尺寸和构成材料是这样的,上述内管可以支撑其自身的重量;一个位于上述内管第一端的不透件,上述不透件防止上述药剂通过上述内管第一端流出上述贮药装置;和一个位于上述内管第二端的可透件,上述可透件允许上述药剂通过上述内管第二端扩散到上述贮药装置之外。
根据第二实施例,一种治疗哺乳动物有机体以获得局部或全身生理或药理效果的方法包括将持续释放药物的输送系统施用于需要这种治疗的有机体。
根据第三实施例,一种治疗哺乳动物有机体眼睛水肿和眼睛新血管化的方法包括,将一种持续释放药物的输送系统施用于需要这种治疗的哺乳动物有机体,该药物输送系统的贮药装置包括有效剂量的类固醇,能有效地获得所需的局部或全身的生理或药理效果。
根据第四实施例,一种提供控制的和持续的有效剂量给药的方法,以获得所需的局部或全身的生理或药理效果,包括在所需的位置外科植入一个持续释放药物的输送系统。
根据第五实施例,一种制造持续释放药物的输送系统的方法包括的步骤有,将端部部件连接一段管子上,构成一个导管状部件,该端部部件选自包括不透帽和可透塞的一组部件,将贮药装置放置在该导管状部件内,该贮药装置包含有有效药剂的有效剂量,和围绕该导管状部件的一部分形成外层,该外层的构成材料选自包括可透材料和不透材料的一组材料。
本发明的其他目的、特点和伴随优点对于本领域技术人员在结合附图阅读下面的根据本发明制成的实施例的详细说明之后将非常明显。
附图说明
现在将参照仅通过示例给出的装置和方法的优选实施例,并参照附图,对本申请的发明进行更详细的说明,其中:
图1是根据本发明的一持续释放药物的输送装置的一个实施例的放大截面图;
图2是根据本发明的持续释放药物的输送装置的第二实施例的放大截面图;
图3是根据本发明的持续释放药物的输送装置的第三实施例的放大截面图;
图4是图2所示实施例沿4-4线所取的横截面图;和
图5是根据本发明的制造药物输送装置的方法的实施例的示意图。
具体实施方式
参见附图,在全部几幅附图中,相同的参考标记表示相同的或对应的元件。
更具体地,本发明人发现了一种装置及其制备方法,用于控制和持续释放药剂或药物,有效获得所需的局部或全身的生理或药理效果。具体地讲,已经发现,通过用一不透元件密封该装置的贮药装置的至少一个表面,整个装置的制造变得更加简单,且该装置能够更好地输出药物,该不透元件能够支撑其自身重量,尺寸稳定,其能够接纳药物内芯而不改变形状和/或保持其自身的结构整体性,从而,用于扩散的表面积没有明显的改变。
即,在制造中使用管状材料支撑贮药装置,明显使得管子和贮药装置的处理更加容易,因为该管子完全支撑其自身重量和贮药装置的重量。因此,本发明肿所用的管子不是涂层的,因为涂层不能支撑其自身重量。另外,此刚性结构可以采用将药浆吸入管子的方法,能够制造较长的圆柱形装置。再进一步,因为根据本发明制造该装置相对容易,所以在一个装置中可以采用一个以上的贮药装置,可以有选择地包含一种以上的药物。
在该装置的使用过程中, 因为贮药装置的尺寸、形状或两者均随着药物从贮药装置中扩散出去而变化,所以保持该贮药装置的管子应具有足够的强度和刚性,以保持一个扩散区域,从而使得自贮药装置中的扩散速度基本上不会因为贮药装置内的变化而改变。作为例子而非限制,一种确认该管子的刚性是否足够的方法是,根据本发明制成一个装置,并测量药物在一段时间上自贮药装置的扩散速度。如果在特定的时间内药物扩散速度的变化超过基于横过装置的可能的化学梯度所预期的扩散速度的50%;则该管子的形状改变且刚性不足。另一个示例性试验是在一段时间内随药物的扩散来目测检测该装置,寻找管子局部或全部塌陷的迹象。
使用根据本发明的可透或不透管子,给回流,即流回到该装置内,制造了流动阻力。该管子或多根管子有助于防止大的蛋白质在贮药装置内溶解药物。另外,该管子或多根管子有助于防止氧化和蛋白质分解,以及防止其它生物制剂进入贮药装置和在其中浸蚀药物。
现在参见附图,图1给出了根据本发明的药物输送装置100的纵向截面图。装置100包括外层110,内管112,贮药装置、药物内芯、药物供给装置、药物仓库、药物基质、和/或药物悬浮液114,以及内帽116。外层110最好为可透层,即,该外层是允许包含在贮药装置114内的药物通过的。帽盖116位于管子112的一端。帽盖116最好用不透材料制成,即,该帽盖是贮药装置114内盛放的药物所不能透过的。帽盖116连接在内管112的端部118、120上,因此该帽盖和内管共同封闭了管内贮药装置114所处的空间,且内管112和帽盖116还共同构成一个帽盖或导管状部件。内管112和帽盖116可以单独制成并组装在一起,或者内管和帽盖也可以形成一个单一的、整体的、一体的元件。
外层110至少部分,最好全部包围管子112和帽盖116两者,如图1所示。尽管外层110仅部分覆盖管子112和帽盖116,特别是装置100的两端即可,但是所形成的外层最好将管子和帽盖两者完全包封住,从而为该装置提供结构的整体性,且便于后续制造和处理,因为该装置不易破碎和崩碎。尽管图1给出的帽盖116的外径与内管112的外径相同,但是帽盖的尺寸可以确定成多少小于或大于内管的外径,这也在本发明的实质和范围内。
如上所述,贮药装置114位于内管112的内侧。第一端122与帽盖116邻接,并被该帽盖有效的密封,该帽盖阻止药物从中通过扩散。在贮药装置114与帽盖116相反的另一端上,该贮药装置最好与外层110直接接触。正如将为本领域普通技术人员所容易理解的,随着药物自贮药装置114的释放,该贮药装置将收缩或改变形状,且因此可能在贮药装置与帽盖116相反的另一端不完全或不直接与外层110接触。由于外层110对贮药装置114内的药物是可透过的,所以该药物可自由地沿着第一流动路径124扩散到该贮药装置外,进入外层110与该贮药装置的开口端直接邻接的部分。自外层110,药物沿着流动路径126自由扩散到外层之外,并进入装置100插入或植入的组织或其它解剖结构中。或者,可以形成一些穿过内层112的孔,以在贮药装置114和可透外层110之间提供额外的流动路径126。
如以上所讨论的,通过为内管112提供相对刚性的材料,装置100的制造可更加容易。通过仅作为示例而非限制,参见图5,根据装置100的制作过程的第一实施例,截取一段管子毛坯材料作为初始材料。在与帽盖116相对的管子112的开口端,插入、注入、或者用其它方式放入贮药装置114,放入方式取决于在放入管子内时,贮药装置材料的粘度如何。如果贮药装置114比较强硬,即非常粘或者是固体的,贮药装置可以借助柱塞、推杆或类似物插入管子112内。如果贮药装置114相对稀松或是流体,即不是非常粘,贮药装置可以灌入、注入或抽入(例如借助真空)管内。这段管子,包括药物内芯,随后被切成多个部段,每部段构成一个管子112。将帽盖116连接到管子112的一端,因此构成一个封闭的帽盖或导管状结构。随后,得益于相对刚性的内管112,该内管和帽盖116可以较容易地处理,因为内管的尺寸和所构成的材料是能够支撑其自身重量、帽盖116的重量和贮药装置114的重量而不塌陷的。随后,管子可进行涂层。
根据本发明制造过程的另一个实施例,贮药装置114可以连同帽盖116插入一个模具,而内管112可以在该贮药装置和帽盖周围模铸而成。再一个替代方式,帽盖116可以与内管112整体制成。
与之相反,先有装置,包括那些包含仅围绕含药的贮药装置的一层涂层的装置,在制造过程的这一阶段必须进行特别处理,例如形成一个在处理过程中支撑涂层和贮药装置的支架并将贮药装置置于该支架上。正如本领域普通技术人员所容易理解的,通过本发明取消了这些额外的制造阶段和部件,简化了制造过程,随之可使生产率提高和成本降低。
图1仅给出了装置100几个部件相互间的位置,且为了便于图示,外层110和内管112具有大约相同的壁厚。尽管外层110和内管112的壁可以具有大约相同的厚度,但是内管的壁厚可以明显薄于或厚于外层的厚度,这也在本发明的实质和范围内。另外,装置100最好是圆柱形的,横截面(未示出)将表示该装置的圆形横截面。尽管最好将装置100制成带有圆形横截面的圆柱,但是为帽盖116、贮药装置114、内管112和/或外层110提供其它的横截面,例如椭圆、矩形、包括方形、三角形,以及其它规则的多边形或不规则的形状也在本发明的实质和范围内。再者,装置100可以有选择地在与帽盖116相反的一端再包括第二帽盖(未示出);此第二帽盖可以用于在制造过程中使装置的处理方便,且至少包括一个通孔,用于使药物能够自贮药装置114流向该装置。
图2给出了根据本发明第二实施例的装置200。装置200包括不透的内管212、贮药装置214和可透柱塞216。装置200可选择性地且最好包括一层不透外层210,该层增强该装置的机械整体性和尺寸稳定性,且有助于该装置的制造和处理。如图2所示,贮药装置214以类似于如上所述的贮药装置114和内管112的形式定位于内管212内。柱塞216位于内管212的一端,并于内管212的端部218、220连接到该内管上。尽管如图2所示,柱塞216可以在径向延伸超过内管212,但是该柱塞也可以与内管具有大体相同的径向大小,或较其略小的径向大小,这也在本发明的实质和范围内。由于柱塞216对贮药装置内所包含的药剂是可透过的,所以药剂可以通过该柱塞自贮药装置自由扩散。因此柱塞216必须具有一定的径向大小,至少要与贮药装置214的径向尺寸一样大,使得扩散到贮药装置之外的通道230只有通过柱塞。在内管212与柱塞216相对的一端,内管是封闭的或仅由外层210密封,如下所述。一个可取盘状形式的不透帽盖242可选择地定位在贮药装置的与柱塞216相对的一端。当设置时,帽盖242和内管212可以单独制成并组装在一起,或者内管和帽盖也可以形成一个单个整体的一体元件。
当设置时,外管或外层210至少部分且最好完全包围或包封内管212、贮药装置214、柱塞216和选用的帽盖242,直接与柱塞邻接的区域除外,该区域形成一孔口224。在优选实施例中,孔口224是一个自装置的外部通向柱塞216的孔或盲孔。由于外层210是用对贮药装置214内的药剂不透过的材料制成的,所以内管212和贮药装置214的与柱塞216相对的一端被有效密封,且不包括供药剂自贮药装置流出的扩散路径。根据优选实施例,孔口224在柱塞216的与贮药装置214的端部222相对的端部238上直接邻接该柱塞形成。因此柱塞216和孔口224分别包括通过柱塞和离开装置200的扩散路径230、232。
尽管图2所示实施例中的孔口224具有与内管212大体相同的径向尺寸,但是该孔口的尺寸可以确定成大些或小些,而这对在本领域普通技术人员是很明显的。例如,除在外层210的部分228、230之间径向构成孔口224外,可代之以去除部分228、230,直至线226,以增大孔口224的面积。如通过使外层210形成延伸覆盖并因此仅仅密封柱塞216的径向外表面240的一部分,或根本不覆盖柱塞的高径向外表面,从而可使孔口224进一步增大,由此可增大孔口224的总表面积,以包括柱塞的外表面积的一部分或全部,。
根据本发明再一个实施例,除了或代替直接邻接柱塞的端部238构成,装置200的孔口224可以直接邻接柱塞216的径向外表面240构成。如图4所示,孔口224可以包括自柱塞216径向向外延伸的部分234、236。这些部分可以包括柱塞216不被外层210所包封的,示于图4的下半部的,大的、连续的、周向的和/或纵向的部分236,和/或可以包括大量示于图4上部的,小的、周向间隔开的部分234。有利的是,直接邻接柱塞216的径向外表面240,以大量、小孔234的形式给柱塞216提供孔口224,以在孔口部分堵塞的情况下,能够有大量替代路径供药剂扩散出装置200。但是,大孔236的好处在于制造上比较容易,因为需要暴露以构成孔口224的只有柱塞216的一个单独区域。
根据本发明的另一个实施例,柱塞216用不透材料制成,而外层210用可透材料制成。通过钻孔形成通过透过一个或多个内层212、帽盖242和柱塞216的一个孔或多个孔,它使药物能够通过外层210自贮药装置214释放。根据另一个实施例,柱塞216作为单独的部件取消了,而可透外层210完全包封住内管212和帽盖242(如果提供)。这样,扩散路径230、232是通过外层210的,且不需要独立的孔口,如孔口224。通过以外层或管210完全包封其它结构,系统200提供有进一步的尺寸稳定性。另外可选择的是,可以保留柱塞216,而外层210也可以包封柱塞。
根据本发明的另一个实施例,内管212用可透材料制成,外层210用不透材料制成,且帽盖242或用可透材料或用不透材料制成。或者,可以取消帽盖242。如上所述,由于外层210对贮药装置214内的药剂是不透过的,所以柱塞216、孔口224和可选孔口234、236是药剂离开装置200通过的唯一通道。
以类似于上面参考图1所述的方式,使用相对刚性的内管212使装置200更容易制造。根据装置200制造过程的一个实施例,柱塞216和内管212的组合装载贮药装置214,类似于如上所述的贮药装置114是如何装载到内管112和帽盖116上。随后,如果提供,外层210围绕柱塞216、内管212、贮药装置214和当提供帽盖时的帽盖242形成,出于上述讨论的原因,构成不透外层。为了构成孔口224,材料随后自外层210去除,以暴露柱塞216的部分或全部外表面,如上所述。或者,通过将柱塞216的所需区域遮盖,孔口224可以在形成外层210的同时形成。
根据本发明制造过程的另一个实施例,贮药装置214可以连同柱塞216和帽盖242一起插入一个模具,而内管212可以围绕贮药装置、柱塞和帽盖模铸而成。
类似于上面参照装置100所讨论的方式,装置200的形状可以是多种形状和几何形状中的任一种。再者,装置100和装置200均可包括一个以上的贮药装置114、214,分别包括在一个以上的内管112、212内,多个贮药装置可以包括不同或同样的药剂或药物,用于扩散到贮药装置之外。在装置200中,多个贮药装置214可以定位成抵靠在单一的柱塞216上,或各贮药装置214可以有用于该贮药装置的特定柱塞。这种多贮药装置可以被单一外层110、210所包封,对于本领域的普通技术人员,这是容易理解的。
现在转到图3,图3给出一个根据本发明第三实施例的装置300。装置300包括可透外层310、不透内管312、贮药装置314、不透帽盖316和可透柱塞318。一个孔口320使柱塞318与装置的外部相连通,如上参照孔口224和柱塞216所述。内管312和帽盖316可以单独构成并组装在一起,或者内管和帽盖也可以制成单独整体的单体的元件。可透外层310的设置使得贮药装置或药芯314内的治疗药剂除了孔口320外,还能通过外层流动,且因此有助于提高整体输送速度。当然,正如本领域普通专业人士很容易理解的,柱塞318的透过性是药物输送速度的初级调节器,且是相应选择的。因此,形成外层310的材料可以特别选择,选择其粘附下层结构、帽盖316、管子312和柱塞,以及将整个结构保持在一起的能力。或者,通过内管312,可以提供一个或多个孔322,以提高药物自贮药装置314的流速。
本发明还涉及一种治疗哺乳动物有机体,以获得所需的局部或全身的生理或药理效果的方法。该方法包括将持续释放药物的输送系统施用到哺乳动物有机体,透过装置100的外层110、装置200的柱塞216、或装置300的柱塞318和外层310,接触哺乳动物有机体,使药剂发挥效用,获得所需的局部或全身的效果。本文所用的“给药”一词,指的是放置、插入、注入、植入或任何其它将装置暴露于哺乳动物有机体的手段。施用的方式取决于多项参数,包括响应或治疗的类型、药剂的类型和最佳的给药位置。
具体实施例中的装置在提供药剂控制和持续释放,有效获得所需的局部或全身生理或药理效果方面具有适用性,至少涉及以下领域:治疗初期癌性肿瘤(例如恶性胶质瘤);新血管化,包括眼睛新血管化;水肿,包括眼睛水肿;炎症,包括眼睛炎症;慢性疼痛,关节炎,风湿症;荷尔蒙缺乏,例如糖尿病和侏儒症;和例如在防止移植排异和在癌症治疗中,改善免疫反应。其它病症的广泛多样化也可以用本发明的药物输送装置防止或治疗。这些病症对于本领域普通技术人员是众所周知的。对于本领域普通技术人员,可以参考Goodman和Gilman的
The Pharmacological Basis of Therapeutics第8版,纽约Pergamon Press出版,1990年;和
Remington’s Pharmaceutical Sciences第18版,宾西法尼亚的Easton的Mack Pubblishing Co.出版,1990年;两者在此均引用作为参考。
另外,该装置适用于治疗感染HIV的哺乳动物有机体和涉及AIDS的机会性感染,例如巨细胞病毒感染、弓形体病、卡氏肺囊虫和鸟结核分支杆菌。
该装置特别适用于治疗眼睛病症,例如青光眼、增生性玻璃体视网膜病变、斑点水肿、包括糖尿病斑点水肿、老年性斑点退化、糖尿病视网膜病变、色素层炎、抑制血管再生和眼睛感染。该装置还特别适用于作为眼睛内装置治疗哺乳动物有机体,包括人类和用于兽医,涉及眼睛达林氏病,其中该装置用外科手术植入眼睛的玻璃体内。
如上所述,内芯或贮药装置含有药剂,有效获得所需局部或全身生理或药理效果。下列药剂分类可以与本发明装置结合使用:麻醉药和止痛剂,例如利多卡因和相关化合物,以及苯并安定(benzodiazepam)和相关化合物;抗癌药,例如5-氟尿嘧啶、阿得里亚霉素和相关化合物;抗炎药,例如6-甲强的松龙磷酸盐;抗真菌药,例如氟康唑和相关化合物;抗病毒药,例如磷甲酸三钠、三氟胸腺嘧啶核苷、阿昔洛韦、甘环核苷、DDI、DDC、和AZT;细胞传输/移动性逼近剂,例如秋水仙素、长春新碱、细胞松弛素B和相关化合物。抗青光眼药,例如β-阻断剂:噻吗洛尔〔β-受体阻滞药〕、倍他洛尔、阿替洛尔等;免疫反应调节剂,例如胞壁酰二肽和相关化合物;肽和蛋例如白质,例如环孢菌素、胰岛素、成长激素、胰岛素相关成长因子,热冲击蛋白质和相关化合物;类固醇化合物,例如地塞米松、泼尼松龙和相关化合物;皮质类固醇,例如氟轻松和相关化合物;和碳酸酐酶抑制剂。
除了上述药剂,其它药剂也适于治疗眼睛及其周围组织,产生有利的局部或全身生理或药理效果。这类药剂的例子包括神经保护剂,例如尼莫地平和相关化合物;抗生素,例如四环素、金霉素、地衣杆菌素、新霉素、多粘菌素、短杆菌肽、土霉素、氯霉素、庆大霉素和红霉素;抗菌制剂,例如磺胺类药物、磺胺醋酰、磺胺甲二唑和磺胺异恶唑;抗病毒药,包括碘苷;和其他抗生物制剂,例如呋喃西林、丙酸钠;抗过敏药,例如安他唑啉、美沙吡林、氯苯那敏(扑尔敏),美吡拉敏(吡拉明)和非尼拉敏(抗感明),抗炎症药,例如氢化可的松、氢化可的松醋酸盐、地塞米松21-磷酸盐,氟轻松、甲羟松、甲基强的松龙、泼尼松龙21-磷酸盐、泼尼松龙醋酸盐、氟米龙、倍他米松和曲米帕明;减充血剂,如苯福林、萘甲唑林和四氢唑林(tetrahydrazoline);缩瞳药和抗胆碱酯酶药,如匹鲁卡品、水杨酸毒扁豆碱、卡巴胆碱、二异丙基氟磷酸盐、二乙氧磷酰硫胆碱碘和癸二胺苯酯溴化盐;散瞳药,如硫酸阿托品、环喷托酯、后马托品、东莨菪碱、托吡卡胺、尤卡托品和羟基苯丙胺(羟苯丙胺);拟交感神经药,如肾上腺素;以及前体药物,如那些在Hans Bundgaard编辑,Elsevier Scientific Publishing Co.出版,Amsterdam,1985年出版的Design of Prodrugs中所述的。再次指出,鉴别其它药剂可以参考任何制药学教科书,如
Remington’s Pharmaceutical Sciences。
任何药学上可接受的形式,诸如化合物,即,自由基或药学上可接受的盐,或其酯,均可在本发明中实际应用。药学可接受的盐,例如,包括硫酸盐、乳酸盐、醋酸盐、硬脂酸盐、盐酸盐、酒石酸盐、马来酸盐和类似物。
大量的材料可以用来制造本发明的装置。唯一要求就是它们是惰性的/不产生免疫原和具有所需的透过能力的,如上所述。
适用于制造装置100、200和300的材料包括自然产生的或合成的材料,该材料与体液和/或眼睛组织生物相容的,且在该材料所接触的体液中基本不溶的。使用在眼液中快速溶解或高溶解度的材料是要避免的,因为外层110、210和310的溶解将影响药物释放的一致性,以及该系统在长时间内保持在位的能力。
与体液和/或眼睛组织生物相容的,且在该材料所接触的体液中基本不溶的,自然产生的或合成的材料包括,但不局限于,乙基醋酸乙烯酯、聚乙酸乙烯酯、交联聚乙烯醇、交联聚乙烯醇缩丁醛、乙烯乙基丙烯酸酯共聚物、聚乙基己基丙烯酸酯、聚氯乙烯、聚乙酸乙烯酯、增塑的乙烯乙烯基丙烯酸酯共聚物、聚乙烯醇、聚乙酸乙烯酯、乙烯氯乙烯共聚物、聚乙烯酯、聚乙烯丁酸酯、聚乙烯醇缩甲醛、聚酰胺、聚甲基丙烯酸甲酯、聚甲基丙烯酸丁酯、增塑的聚氯乙烯、增塑的尼龙、增塑的软尼龙、增塑的聚对苯二甲酸乙二醇酯、天然橡胶、聚异戊二烯、聚异丁烯、聚丁二烯、聚乙烯、聚四氟乙烯、聚偏氯乙烯、聚丙烯腈、交联聚乙烯基吡咯烷酮、聚三氟氯乙烯、氯化聚乙烯、聚(1、4’-异丙叉联苯羧酸酯)、偏二氯乙烯、丙烯腈共聚物、氯乙烯-二乙基fumerale共聚物、硅酮橡胶、特别是医用级的聚二甲基硅氧烷、乙烯-丙烯橡胶、硅酮-碳酸酯共聚物、偏二氯乙烯-氯乙烯共聚物、氯乙烯-丙烯腈共聚物、偏二氯乙烯-丙烯腈共聚物、金、铂和(外科用)不锈钢。
具体地,装置200的外层210可以用上面所列任意一种聚合物,或其他与体液和/或眼睛组织生物相容的,且在该材料所接触的体液中基本不溶的,且有效药剂基本不能透过的聚合物制成。此处所用“不透”一词指的是该层物质使有效药剂不能以所要求的速度通过以获得所需的局部或全身生理或药理疗效。
当内管112、212、312选择为不透的,即如上所述,使内芯或贮药装置的药剂不能通过而到达装置的邻接部分时,其目的是阻断药剂至装置的这些部分的通道,且由此控制药剂通过外层110、柱塞216和柱塞318自药物输送装置的释放。
外层的成分,例如聚合物必须进行选择,从而能够实现上述的控制释放。外层110和柱塞216的优选成分将取决于这些参数,如活性药剂、所需的控制速度和给药模式。实际药剂的一致性十分重要,因为例如,分子的尺寸在确定药剂进入外层110和柱塞216的释放速度时是决定性的。
帽盖116、242、316基本是有效药剂不能透过的,且可以覆盖内管未被外层覆盖的一部分。帽盖所用材料最好是聚合物,该材料的物理特性可以基于其承受后续加工步骤(例如热固化)而不使该装置变形的能力进行选择。用于不透外层210的材料,例如聚合物,可以基于容易涂覆到内管212上进行选择。帽盖116可以用以下材料之一制成,包括PTFE、聚碳酸酯、聚甲基丙烯、聚乙烯醇、高品质的乙烯-乙酸乙烯酯(9%乙烯,含量)和聚乙烯醇(PVA)。内管112、212、312可以用以下材料之一制成,包括PTFE、聚碳酸酯、聚甲基丙烯、聚乙烯醇、高品质的乙烯-乙酸乙烯酯(9%乙烯,含量)和聚乙烯醇。柱塞216、318可以用几种材料中的一种制成,包括交联的PVA,如上所述。
本发明装置的外层110、210、310和柱塞216、318必须是与体液和组织生物相容的,在该材料所接触的体液中是基本不溶的,且外层110和柱塞216、318对于获得所需疗效的药剂或有效成分是可透过的。
有效药剂向化学势能较低的方向扩散,即朝向装置的外表面。在装置的外表面,平衡再次建立。当外层110或柱塞216、318的两侧的条件保持恒定时,根据Fick扩散定律将建立有效药剂的稳定态流通量。药物借助扩散通过该材料的透过速度总体上取决于药物在其中的溶解度,以及取决于壁的厚度。这意味着制造外层110和柱塞216的合适材料的选择取决于所用的具体药物。
有效药剂透过本发明的聚合物层的扩散速度可以通过在下陷状态下进行的扩散单元研究确定。在下陷状态下进行的扩散单元研究中,当与供体代谢区的高浓度相比,药物在受体代谢区内的浓度基本为零。在这种条件下,药物的释放速度由下式给出:
Q/t=(D·K·A·DC)/h
其中Q是药物释放量,t是时间,D是扩散系数,K是分隔系数,A是表面积,DC是药物横跨薄膜的浓度差,h是膜的厚度。
在药剂是通过注满水的微孔透过材料层扩散的情况下,没有分隔现象。因此,K可以从方程中取消。在下陷条件下,如果供体侧的释放非常慢,则DC是基本恒定的,且等于供体代谢区的浓度。因此释放速度取决于表面积(A)、厚度(h)和薄膜的扩散率(D)。在本发明装置的结构中,尺寸(且由此,表面积)主要取决于有效药剂的规格。
因此,透过率值可以从Q相对时间曲线的斜率得出。透过率P可以通过下式同扩散系数D建立关系:
P=(K·D)/h
对于药剂可透过材料的透过率一旦建立,就可以确定必须用药剂不能透过的材料进行涂层的药剂表面积。这通过逐渐减少可得到的表面积直至获得所需的释放速度来完成。
适用于外层110和柱塞216、318的示例性微孔材料,例如记述于美国专利No.4,014,335中,在此整体引用作为参考。该材料包括交联的聚乙烯醇、聚烯烃或聚乙烯chmorides或交联的凝胶体;再生、不溶、不易受浸蚀的纤维素、酰化纤维素、酯化纤维素、醋酸丙酸纤维素、醋酸丁酸纤维素、醋酸钛酸盐纤维素、二乙基氨基醋酸纤维素、聚氨酯、聚碳酸酯,和由聚阳离子和聚阴离子改良的不溶胶原质的共沉淀物制成的微孔聚合物。对于外层110和柱塞216、318,交联聚乙烯醇是优选的。
本发明的装置可以用多种方式制成,这部分上面进行了比较详细的讨论。一旦贮药装置和内管连同帽盖116、242或柱塞216、318组装在一起,就可以施加外层。该外层可以通过将该装置一次或多次浸渍在含有所需聚合物的溶液内进行施加。或者,该外层可以通过滴、喷、刷或其他手段,将该装置的外表面涂上聚合物溶液。当采用聚乙烯酒精溶液得到外层时,所需的厚度可通过施加七次得到。每次涂层可在施加下一涂层之前干燥。最后,可以对该装置进行加热,以调节外层110或柱塞216、318的透过率。
在根据本发明装置的不透聚合物层应该足够厚,以防止药物通过未覆盖区以外的区释放,例如孔口224。出于对缩小植入装置的尺寸的期望,因此,不透层的厚度可以在约0.01至约2毫米之间,更好地是在约0.01至约0.5毫米之间,最好是在约0.01至约0.2毫米之间。
帽盖116、242也应该足够厚,以防治药物透过它释放。出于对缩小该植入物的尺寸的期望,不透帽盖116的厚度可以在约0.01至约2毫米之间,更好地是在约0.01至约0.5毫米之间,最好是在约0.01至约0.2毫米之间。
上述本发明如何制造该装置的说明仅仅是示例性的,不应被认为是以任何方式限制本发明的范围,多种化学成分对于本领域技术人员是众所周知的。具体地讲,制造该装置的方法取决于活性药剂和所选择的聚合物的同一性。给定活性药剂,给定外层、内管、柱塞和帽盖的化学成分,本领域技术人员应用传统的涂层技术可以很容易地制造本发明的装置。
治疗哺乳动物有机体以获得所需的局部或全身的生理或药理疗效的方法包括将本发明的持续释放药物的输送装置施用到哺乳动物有机体,并使该药剂持续通过该装置与哺乳动物有机体直接接触。
本发明的药物输送系统可以通过众所周知的施用方法,施用到哺乳动物有机体。这样的施用方式包括眼内、口、皮下、肌肉内、腹膜内、鼻内、真皮、大脑内,包括颅骨内和上皮内,关节内,包括踝关节、膝关节、臀、肩、肘、腕,直接进入肿瘤和类似物。另外,一个或多个装置可以同时施用,或一种以上药剂可以包括在内芯或贮药装置内,或在一个装置内可以提供一个以上的贮药装置。
本发明的药物输送系统特别适用于直接植入眼睛的玻璃体内,和适用于眼内透镜。
对于具有本领域普通技术人员,这些施用方法及其制备的技术是众所周知的。其制备技术在
Remingtong’s Pharmaceutical Sciences中提出。
该药物输送系统可以施用足够长的时间,并处于能够治疗所涉及疾病的状态。
对于局部药物输出,该装置可以用外科手术植入作用区或其附近。这是本发明用于治疗眼睛病症、初期肿瘤、风湿和关节炎症状,以及慢性疼痛的情况。
对于全身释放,该装置可以皮下、鼻内、动脉内、鞘膜内或腹膜内植入。这是装置要给出持续的全身水平时和避免过早新陈代谢时的情况。另外,这类装置可以口服施用。
在本发明的一个实施例中,可以制备一个含有有效治疗剂量的氟轻松作为有效药剂的眼内装置,用以减弱或防止眼睛新血管化形成。当用外科手术植入眼睛的玻璃体时,这类装置可以有效地用于治疗和抑制所不希望的眼睛新血管化形成、水肿或发炎。这类装置在治疗完成后可以长久存留在玻璃体内。这类装置中氟轻松的最佳用量在约0.01mg至约40mg的范围。更具体地,这类装置含有约0.01mg至约6mg的氟轻松。这些优选范围可以提供氟轻松从数小时至五年以上时间的持续释放。根据本发明的优选可透层用聚乙烯醇制成,其最好是交联的。装置100、200的优选不透部分,例如帽盖116和内管112、212最好用PTFE或乙基乙烯醇制成。
但这类装置准备植入眼睛的玻璃体时,该装置最好在各个方向均不超过7毫米,从而能够通过不超过7毫米的切口插入。这样,示于图1和2的该圆柱体装置高度最好不超过7毫米或直径不超过3毫米。内管112、212的壁厚最好在约0.01mm至约1.0mm的范围。外层110的壁厚最好在约0.01mm至约1.0mm的范围。外层210的最佳壁厚在约0.01mm至约1.0mm的范围。
尽管本发明的上述实施例是就有效药剂量的最佳范围和优选层的最佳厚度进行了说明的,但是这些优选形式没有对本发明进行限制的意思。正如对于本领域技术人员所容易理解的,这些优选量、材料和尺寸取决于施用的方法,所用的有效药剂,所用的聚合物,所需的释放速度和类似参数。同样,除上述以外,实际释放速度和释放持续时间还取决于多种参数,如所治疗的病状、患者的年龄和状态、给药方式、以及对于本领域技术人员是显而易见的其它参数。所有上述美国专利和其他出版物其全部内容在本文特此引用作为参考。
从上述说明,本领域普通技术人员可以容易地确知本发明的基本特点,且在不背离本发明实质和范围的前提下,能够进行多种改型和改进,以适合于多种用途和条件。同样,这些改型和/或改进旨在完全公正地处于下列权利要求的全部等效范围内。
Claims (40)
1.一种持续释放药物的输送系统,其包括:
一个药物内芯,其包括某种药剂的有效治疗剂量,能够获得所需的局部或全身的生理或药理效果;
一个所述药剂不能透过的内管,所述内管具有第一和第二端,且覆盖至少一部分所述药物内芯,所述内管的尺寸和制成内管的材料使得该内管尺寸稳定,以承纳所述药芯而不改变形状;
一个位于所述内管第一端的不透件,所述不透件防止所述药剂自所述药芯通过所述内管的第一端透过;和
一个位于所述内管第二端的可透件,所述可透件使所述药剂能自所述药芯通过所述内管第二端扩散。
2.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,所述内管是一种聚合物或金属。
3.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,所述不透件包括与所述内管第一端相接的不透帽盖。
4.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,其还包括包围所述内管的可透外层,且其中所述可透件包括一部分所述可透外层。
5.一种如权利要求4所述的持续释放药物的输送系统,其特征在于,其还包括通过所述不透内管使所述药芯与所述可透外层连通的孔。
6.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,其还包括包围所述内管的不透外层,且其中所述不透件包括一部分所述不透外层。
7.一种如权利要求6所述的持续释放药物的输送系统,其特征在于,所述可透件包括与所述内管第二端相接的可透柱塞。
8.一种如权利要求7所述的持续释放药物的输送系统,其特征在于,所述柱塞具有径向的外表面和与所述药芯相对的端表面,且所述不透外层覆盖至少一部分所述径向外表面和至少一部分所述柱塞端表面。
9.一种如权利要求7所述的持续释放药物的输送系统,其特征在于,在所述不透外层还包括一个孔口,其位置使所述药剂能够通过所述柱塞、通过所述孔口扩散出所述药芯,并扩散出所述装置。
10.一种如权利要求9所述的持续释放药物的输送系统,其特征在于,所述孔口在所述不透外层上形成,直接邻接所述柱塞的表面,包括所述柱塞端表面、柱塞径向表面,或两者。
11.一种如权利要求9所述的持续释放药物的输送系统,其特征在于,所述孔口在所述不透外层上形成,直接邻接所述柱塞径向表面,且其中所述孔口包括多个在所述不透外层上形成的直接邻接所述柱塞径向表面的孔。
12.一种如权利要求6所述的持续释放药物的输送系统,其特征在于,所述不透外层沿所述柱塞的径向表面延伸并覆盖该表面,且终止于所述柱塞端表面。
13.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,所述有效药剂是氟轻松。
14.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,所述有效药剂是尼莫地平。
15.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,所述有效药剂是类固醇。
16.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,所述有效药剂是神经保护剂(neuroprotectant)。
17.一种如权利要求1所述的持续释放药物的输送系统,其特征在于,所述不透内管用这样的材料制成,它能在所述系统暴露于浸蚀剂时阻止该浸蚀剂通过进入药物内芯。
18.一种治疗哺乳动物有机体以获得所需的局部或全身生理或药理效果的方法,其包括:
将根据权利要求1的持续释放药物的输送系统施用到需要这种治疗的哺乳动物有机体。
19.一种治疗哺乳动物有机体眼睛水肿、眼睛新血管化或眼睛炎症的方法,其包括:
将根据权利要求1的持续释放药物的输送系统施用到需要这种治疗的哺乳动物有机体,所述药物输送系统药物内芯包括有效治疗量的类固醇,以获得所需的局部或全身的生理或药理效果。
20.一种如权利要求19所述的方法,其特征在于,所述类固醇是皮质类固醇。
21.一种如权利要求20所述的方法,其特征在于,所述皮质类固醇是氟轻松。
22.一种用于提供控制和持续给药,有效获得所需的局部或全身生理或药理效果的方法,其包括:
将根据权利要求1所述的持续释放的药物输送系统插入所需位置。
23.一种如权利要求22所述的方法,其特征在于,所述插入步骤包括将所述系统注入到所需位置。
24.一种如权利要求22所述的方法,其特征在于,所述插入步骤包括将所述系统用外科手术植入所需位置。
25.一种如权利要求22所述的方法,其特征在于,所述插入步骤包括将所述系统插入从以下一组中选择的位置,包括眼睛的玻璃体、视网膜下和巩膜上。
26.一种如权利要求22所述的方法,其特征在于,所述有效药剂是皮质类固醇。
27.一种如权利要求26所述的方法,其特征在于,所述皮质类固醇是氟轻松。
28.一种如权利要求22所述的方法,其特征在于,所述有效药剂是一种神经保护剂。
29.一种如权利要求22所述的方法,其特征在于,所述神经保护剂是尼莫地平。
30.一种制造可持续给药的输送系统的方法,其包括的步骤:
将一个药芯放入管内,所述药芯含有活性药剂的有效治疗量;和
将一个端部部件置于所述管子上,构成一个端部封闭的管子,所述端部部件自以下一组中选择,包括不透帽盖和可透柱塞。
31.一种如权利要求30所述的方法,其特征在于,其还包括围绕一部分所述管子形成外层,所述外层用选自以下一组的材料制成,包括可透材料和不透材料。
32.一种如权利要求30所述的方法,其特征在于,所述放置端部部件的步骤包括将所述端部部件连接到一段所述管子上,以形成一个容器状部件。
33.一种如权利要求30所述的方法,其特征在于,所述放置药芯的步骤包括将所述药芯放入一段管子内,该段管子的尺寸和构成材料是这样的,在所述放置过程中使所述管子段尺寸上稳定。
34.一种如权利要求32所述的方法,其特征在于,所述连接步骤包括使所述端部部件与所述管子段的第一端对接,留下未覆盖的的所述管子段的第二端。
35.一种如权利要求32所述的方法,其特征在于,所述连接步骤包括将一个不透帽盖连接到所述管子段,且其中所述构成外层的步骤包括构成可透材料的外层。
36.一种如权利要求32所述的方法,其特征在于,所述连接步骤包括将一个可透柱塞连接到所述管子段,且其中所述构成外层的步骤包括构成不透材料的外层。
37.一种如权利要求36所述的方法,其特征在于,进一步包括的步骤有:
在所述不透外层上形成一个直接与所述可透柱塞邻接的孔口。
38.一种如权利要求37所述的方法,其特征在于,所述形成孔口的步骤进一步包括形成的孔口直接与所述柱塞的与所述药芯相对的端表面直接邻接。
39.一种如权利要求37所述的方法,其特征在于,所述形成孔口的步骤进一步包括形成的孔口直接与所述柱塞的径向表面相邻接。
40.一种如权利要求37所述的方法,其特征在于,所述形成孔口的步骤进一步包括形成多个孔口。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102552106A (zh) * | 2004-04-30 | 2012-07-11 | 阿勒根公司 | 延长缓释超过2个月的类固醇眼内植入物 |
CN1901850B (zh) * | 2003-11-13 | 2012-10-03 | 普西维达公司 | 具有可生物侵蚀基质芯和可生物侵蚀皮的注射用缓释植入剂 |
CN105025974A (zh) * | 2013-03-12 | 2015-11-04 | 普西维达公司 | 包含硅基载体粒子的药物递送装置 |
CN112752568A (zh) * | 2018-08-15 | 2021-05-04 | 微思有限公司 | 具有用于流动路径修饰的可生物降解材料的持续释出部件及相应的药物输送装置 |
Families Citing this family (276)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1154691A4 (en) * | 1999-01-05 | 2004-07-07 | Massachusetts Eye & Ear Infirm | TARGETED ADMINISTRATION OF REGULATED RELEASE MEDICINE TO RETINA AND CHOROID THROUGH SCLEROTIC |
US6217895B1 (en) * | 1999-03-22 | 2001-04-17 | Control Delivery Systems | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US20040121014A1 (en) * | 1999-03-22 | 2004-06-24 | Control Delivery Systems, Inc. | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US8556967B2 (en) * | 1999-04-09 | 2013-10-15 | Faezeh Mona Sarfarazi | Interior bag for a capsular bag and injector |
US7943162B2 (en) * | 1999-10-21 | 2011-05-17 | Alcon, Inc. | Drug delivery device |
US6416777B1 (en) * | 1999-10-21 | 2002-07-09 | Alcon Universal Ltd. | Ophthalmic drug delivery device |
US20040175410A1 (en) * | 2000-04-26 | 2004-09-09 | Control Delivery Systems, Inc. | Sustained release device and method for ocular delivery of carbonic anhydrase inhibitors |
US6375972B1 (en) | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
US20040208910A1 (en) * | 2000-04-26 | 2004-10-21 | Control Delivery Systems, Inc. | Sustained release device and method for ocular delivery of adrenergic agents |
ES2312456T3 (es) * | 2000-08-30 | 2009-03-01 | Johns Hopkins University | Dispositivos para suministro intraocular de farmacos. |
WO2002056863A2 (en) * | 2000-12-29 | 2002-07-25 | Bausch & Lomb Incorporated | Sustained release drug delivery devices |
JP4184082B2 (ja) * | 2001-01-03 | 2008-11-19 | ボシュ・アンド・ロム・インコーポレイテッド | 複数の薬剤を備えた徐放薬剤送達装置 |
JP2004521882A (ja) | 2001-01-03 | 2004-07-22 | ボシュ・アンド・ロム・インコーポレイテッド | 組立式透過性プラグを備えた徐放薬剤送達装置 |
US20020148138A1 (en) * | 2001-04-06 | 2002-10-17 | Egan Brian A. | Smart tread boot covers |
US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
CA2444894C (en) * | 2001-04-26 | 2013-06-25 | Control Delivery Systems, Inc. | Sustained release drug delivery system containing codrugs |
US20040022853A1 (en) * | 2001-04-26 | 2004-02-05 | Control Delivery Systems, Inc. | Polymer-based, sustained release drug delivery system |
WO2002089767A1 (en) * | 2001-05-03 | 2002-11-14 | Massachusetts Eye And Ear Infirmary | Implantable drug delivery device and use thereof |
EP2316394B1 (en) | 2001-06-12 | 2016-11-23 | The Johns Hopkins University | Reservoir device for intraocular drug delivery |
JP2004535431A (ja) * | 2001-06-22 | 2004-11-25 | サザン バイオシステムズ, インコーポレイテッド | ゼロ次長期放出同軸インプラント |
CA2448558A1 (en) * | 2001-07-10 | 2003-01-23 | Teva Pharmaceutical Industries, Ltd. | Drug delivery system for zero order, zero order-biphasic, ascending or descending drug delivery |
CN1203814C (zh) | 2001-07-23 | 2005-06-01 | 爱尔康公司 | 眼部药物输送装置 |
WO2003009784A1 (en) * | 2001-07-23 | 2003-02-06 | Alcon, Inc. | Ophthalmic drug delivery device |
IN2014DN10834A (zh) * | 2001-09-17 | 2015-09-04 | Psivida Inc | |
US20060034929A1 (en) * | 2001-12-27 | 2006-02-16 | Brubaker Michael J | Sustained release drug delivery devices with prefabricated permeable plugs |
WO2003071986A2 (en) * | 2002-02-22 | 2003-09-04 | Control Delivery Systems, Inc. | Method for treating otic disorders |
AU2003218127B2 (en) * | 2002-03-11 | 2007-07-12 | Alcon, Inc. | Implantable drug delivery system |
EP1495121A2 (en) * | 2002-04-18 | 2005-01-12 | Lynkeus Biotech GmbH | Means and methods for the specific inhibition of genes in cells and tissue of the cns and/or eye |
WO2003092665A2 (en) * | 2002-05-02 | 2003-11-13 | Massachusetts Eye And Ear Infirmary | Ocular drug delivery systems and use thereof |
US8871241B2 (en) * | 2002-05-07 | 2014-10-28 | Psivida Us, Inc. | Injectable sustained release delivery devices |
BR0309844A (pt) * | 2002-05-07 | 2005-02-15 | Control Delivery Sys Inc | Processos para formação de um dispositivo para a distribuição de droga |
KR20060013632A (ko) | 2002-05-17 | 2006-02-13 | 오쎄라 파마슈티걸즈, 인크. | 백내장 및 다른 안질환 발병의 개선 |
US6976584B2 (en) | 2002-06-26 | 2005-12-20 | Bausch & Lomb Incorporated | Package for surgical implant |
CN100435880C (zh) * | 2003-02-28 | 2008-11-26 | 微创医疗器械(上海)有限公司 | 一种药物洗脱介入医疗器械及其制备方法 |
US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
AU2003301347A1 (en) * | 2002-10-17 | 2004-05-04 | Control Delivery Systems, Inc. | Methods for monitoring treatment of disease |
WO2004058272A1 (en) * | 2002-12-20 | 2004-07-15 | Control Delivery Systems, Inc. | Steroid compositions for intraocular use |
ATE477337T1 (de) | 2003-01-16 | 2010-08-15 | Univ Pennsylvania | Zusammensetzungen und verfahren zur sirna-hemmung von icam-1 |
ES2338420T3 (es) * | 2003-01-24 | 2010-05-07 | Psivida Us Inc. | Dispositivo y procedimiento de liberacion sostenida para la administracion ocular de inhibidores de la anhidrasa carbonica. |
ATE440595T1 (de) * | 2003-01-24 | 2009-09-15 | Psivida Inc | Vorrichtung mit verlängerter freisetzung und verfahren zur okularen verabreichung von adrenergen wirkstoffen |
MXPA05007717A (es) * | 2003-01-24 | 2005-09-30 | Control Delivery Sys Inc | Liberacion controlada de agentes altamente solubles. |
US20050019400A1 (en) * | 2003-01-27 | 2005-01-27 | Deveney Thomas William | Controlled-release drug delivery system |
WO2004073551A2 (en) * | 2003-02-18 | 2004-09-02 | Massachusetts Eye And Ear Infirmary | Transscleral drug delivery device and related methods |
US9445901B2 (en) * | 2003-03-12 | 2016-09-20 | Deger C. Tunc | Prosthesis with sustained release analgesic |
US20050261668A1 (en) * | 2003-03-28 | 2005-11-24 | Bausch & Lomb Incorporated | Drug delivery device |
US7037521B2 (en) * | 2003-03-28 | 2006-05-02 | Bausch & Lomb Incorporated | Using a laser for cutting a hole in a capsule for controlled drug delivery |
US8246974B2 (en) * | 2003-05-02 | 2012-08-21 | Surmodics, Inc. | Medical devices and methods for producing the same |
DE602004028638D1 (de) * | 2003-05-02 | 2010-09-23 | Surmodics Inc | System zur kontrollierten Freisetzung eines bioaktiven Wirkstoffs im hinteren Bereich des Auges |
US7589107B2 (en) | 2003-05-19 | 2009-09-15 | Othera Holding, Inc. | Amelioration of vitrectomy-induced cataracts |
US7825134B2 (en) * | 2003-05-19 | 2010-11-02 | Othera Holding, Inc. | Amelioration of cataracts, macular degeneration and other ophthalmic diseases |
EP1635875B8 (en) * | 2003-06-26 | 2008-12-24 | pSivida Inc | In-situ gelling drug delivery system |
CN1842321B (zh) * | 2003-06-26 | 2012-07-04 | 控制递送系统有限公司 | 生物蚀解性缓释递药系统 |
ES2379466T3 (es) * | 2003-06-26 | 2012-04-26 | Psivida Us, Inc. | Sistema de suministro de fármacos de liberación sostenida bioerosionables |
DE602004007802T2 (de) * | 2003-06-26 | 2008-04-17 | Mediolanum Pharmaceuticals Ltd. | Subcutane implantate mit begrenzter initialer wirkstoff-freisetzung und deren anschliessende lineare veränderliche verlängerte freisetzung |
US8491883B2 (en) * | 2003-06-27 | 2013-07-23 | Advanced Technologies And Regenerative Medicine, Llc | Treatment of amyotrophic lateral sclerosis using umbilical derived cells |
US8790637B2 (en) | 2003-06-27 | 2014-07-29 | DePuy Synthes Products, LLC | Repair and regeneration of ocular tissue using postpartum-derived cells |
US9572840B2 (en) | 2003-06-27 | 2017-02-21 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue using postpartum-derived cells |
WO2005038012A2 (en) * | 2003-06-27 | 2005-04-28 | Ethicon Incorporated | Cartilage and bone repair and regeneration using postpartum-derived cells |
US8518390B2 (en) | 2003-06-27 | 2013-08-27 | Advanced Technologies And Regenerative Medicine, Llc | Treatment of stroke and other acute neural degenerative disorders via intranasal administration of umbilical cord-derived cells |
US7875272B2 (en) | 2003-06-27 | 2011-01-25 | Ethicon, Incorporated | Treatment of stroke and other acute neuraldegenerative disorders using postpartum derived cells |
US9592258B2 (en) | 2003-06-27 | 2017-03-14 | DePuy Synthes Products, Inc. | Treatment of neurological injury by administration of human umbilical cord tissue-derived cells |
US20040265356A1 (en) * | 2003-06-30 | 2004-12-30 | Bausch & Lomb Incorporated | Drug delivery device |
US20050054586A1 (en) * | 2003-06-30 | 2005-03-10 | Bartels Stephen P. | Treatment of ophthalmic disorders |
CA2522592A1 (en) * | 2003-07-10 | 2005-02-03 | Alcon, Inc. | Ophthalmic drug delivery device |
US7585517B2 (en) * | 2003-09-18 | 2009-09-08 | Macusight, Inc. | Transscleral delivery |
AU2004292957C1 (en) * | 2003-11-13 | 2011-04-28 | Eyepoint Pharmaceuticals Us, Inc. | Injectable sustained release implant having a bioerodible matrix core and a bioerodible skin |
JP4975440B2 (ja) * | 2003-11-20 | 2012-07-11 | オセラ・ホールディング・インコーポレイテッド | 黄斑変性およびその他の眼科疾患の改善 |
US20050148948A1 (en) * | 2003-12-19 | 2005-07-07 | Caputa Steven G. | Sutureless ophthalmic drug delivery system and method |
US7211272B2 (en) | 2003-12-22 | 2007-05-01 | Bausch & Lomb Incorporated | Drug delivery device |
US20050137538A1 (en) * | 2003-12-22 | 2005-06-23 | Bausch & Lomb Incorporated | Drug delivery device |
US20050136095A1 (en) * | 2003-12-22 | 2005-06-23 | Brian Levy | Drug delivery device with suture ring |
US20050158365A1 (en) * | 2003-12-22 | 2005-07-21 | David Watson | Drug delivery device with mechanical locking mechanism |
CA2554424A1 (en) * | 2004-01-26 | 2005-08-11 | Control Delivery Systems, Inc. | Controlled and sustained delivery of nucleic acid-based therapeutic agents |
US20060018949A1 (en) * | 2004-04-07 | 2006-01-26 | Bausch & Lomb Incorporated | Injectable biodegradable drug delivery system |
US20050232972A1 (en) * | 2004-04-15 | 2005-10-20 | Steven Odrich | Drug delivery via punctal plug |
US20110028548A1 (en) * | 2004-04-19 | 2011-02-03 | Strategic Science & Technologies, Llc | Beneficial effects of increasing local blood flow |
WO2005105133A2 (en) * | 2004-04-23 | 2005-11-10 | Massachusetts Eye And Ear Infirmary | Methods and compositions for preserving the viability of photoreceptor cells |
US20050244465A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Drug delivery systems and methods for treatment of an eye |
CN1964711A (zh) * | 2004-05-25 | 2007-05-16 | 奥特拉药物公司 | 眼睛选择性药物及前体药物 |
US20060024350A1 (en) * | 2004-06-24 | 2006-02-02 | Varner Signe E | Biodegradable ocular devices, methods and systems |
EP2803357B1 (en) | 2004-06-25 | 2020-11-18 | The Johns-Hopkins University | Angiogenesis inhibitors |
WO2006014484A2 (en) * | 2004-07-02 | 2006-02-09 | Surmodics, Inc. | Methods and devices for the treatment of ocular conditions |
EP2377569A1 (en) * | 2004-07-02 | 2011-10-19 | QLT Plug Delivery, Inc. | Treatment medium delivery device and methods for delivery of such treatment mediums to the eye using such a delivery device |
US7117870B2 (en) * | 2004-07-26 | 2006-10-10 | Clarity Corporation | Lacrimal insert having reservoir with controlled release of medication and method of manufacturing the same |
EP1781264B1 (en) * | 2004-08-04 | 2013-07-24 | Evonik Corporation | Methods for manufacturing delivery devices and devices thereof |
US8246569B1 (en) | 2004-08-17 | 2012-08-21 | California Institute Of Technology | Implantable intraocular pressure drain |
US20160106717A1 (en) | 2004-09-24 | 2016-04-21 | Gen Pharma Holdings LLC | Cai-based systems and methods for the localized treatment of uveitis |
US20060068012A1 (en) * | 2004-09-29 | 2006-03-30 | Bausch & Lomb Incorporated | Process for preparing poly (vinyl alcohol) drug delivery devices with humidity control |
US20060067978A1 (en) * | 2004-09-29 | 2006-03-30 | Bausch & Lomb Incorporated | Process for preparing poly(vinyl alcohol) drug delivery devices |
US20060067980A1 (en) * | 2004-09-30 | 2006-03-30 | Bausch & Lomb Incorporated | Capsule for encasing tablets for surgical insertion into the human body |
WO2006039333A1 (en) * | 2004-09-30 | 2006-04-13 | Bausch & Lomb Incorporated | Ophthalmic drug release device for multiple drug release |
BRPI0518582A2 (pt) * | 2004-11-24 | 2008-11-25 | Therakine Corp | implante para liberaÇço de medicamento intra-ocular |
US20070276481A1 (en) * | 2004-12-08 | 2007-11-29 | Renner Steven B | Drug delivery device |
US20060134162A1 (en) * | 2004-12-16 | 2006-06-22 | Larson Christopher W | Methods for fabricating a drug delivery device |
US20060166361A1 (en) * | 2004-12-21 | 2006-07-27 | Agnieszka Seyda | Postpartum cells derived from placental tissue, and methods of making, culturing, and using the same |
US20060171930A1 (en) * | 2004-12-21 | 2006-08-03 | Agnieszka Seyda | Postpartum cells derived from umbilical cord tissue, and methods of making, culturing, and using the same |
US20060153815A1 (en) * | 2004-12-21 | 2006-07-13 | Agnieszka Seyda | Tissue engineering devices for the repair and regeneration of tissue |
US20060135918A1 (en) * | 2004-12-22 | 2006-06-22 | Bausch & Lomb Incorporated | Reusable drug delivery device |
US20060134175A1 (en) * | 2004-12-22 | 2006-06-22 | Stephen Bartels | Drug eluting pharmaceutical delivery system for treatment of ocular disease and method of use |
US20060134176A1 (en) * | 2004-12-22 | 2006-06-22 | Bausch & Lomb Incorporated | Pharmaceutical delivery system and method of use |
US20060134174A1 (en) * | 2004-12-22 | 2006-06-22 | Bausch & Lomb Incorporated | Pharmaceutical delivery system and method of use |
PL1831356T3 (pl) | 2004-12-23 | 2017-07-31 | DePuy Synthes Products, Inc. | Komórki poporodowe pochodzące z tkanki pępowinowej i sposoby ich wytwarzania i stosowania |
CA2589063C (en) | 2004-12-23 | 2016-08-09 | Ethicon Incorporated | Treatment of parkinson's disease and related disorders using postpartum derived cells |
DK1848431T3 (en) * | 2005-02-09 | 2016-04-18 | Santen Pharmaceutical Co Ltd | LIQUID FORMULATIONS FOR TREATMENT OF DISEASES OR CONDITIONS |
US8663639B2 (en) * | 2005-02-09 | 2014-03-04 | Santen Pharmaceutical Co., Ltd. | Formulations for treating ocular diseases and conditions |
JP2008535847A (ja) * | 2005-04-08 | 2008-09-04 | サーモディクス,インコーポレイティド | 網膜下に送達するための持続放出インプラント |
US20060258994A1 (en) * | 2005-05-12 | 2006-11-16 | Avery Robert L | Implantable delivery device for administering pharmacological agents to an internal portion of a body |
WO2006127592A2 (en) * | 2005-05-26 | 2006-11-30 | Othera Pharmaceuticals, Inc. | Use of hydroxylamine derivates for inhibiting vitrectomy-induced cataracts |
US20060292202A1 (en) * | 2005-06-27 | 2006-12-28 | Bausch & Lomb Incorporated | Drug delivery device |
BRPI0615962A2 (pt) | 2005-07-27 | 2011-05-31 | Univ Florida | uso de um composto selecionado do grupo que consiste em um inibidor proteassomal, um inibidor de autofagia, um inibidor lisossomal, um inibidor do trasporte de proteìna do er ao golgi, um inibidor de chaperonina hsp90, um ativador da resposta a choque térmico, um inibidor de glicosidade, e um inibidor de histona deacetilase, uso de 11-cis-retinal ou 9-cis-retinal e um composto selecionado do grupo que consiste em um inibidor proteassomal, um inibidor de autofagia, um inibidor lissosomal, um inibidor do transporte de proteìna do er ao golgi, um inibidor de chaperonina hsp90, um ativador de resposta a choque térmico, um inibidor de glicosidase, e um inibidor de histona deacetilase, método para aumentar a quantidade de um conformação bioquimicamente funcional de uma proteìna em uma célula, composição farmacêutica para o tratamento de um pcd ocular, composição farmacêutica para o tratamento de retinite pigmentosa, kit para o tratamento de um pcd ocular, kit para o tratamento de retinite pigmentosa, método para a identificação de um composto útil para o tratamento de um indivìduo que tem um pcd ocular, método para a identificação de um composto útil para o tratamento de um indivìduo que tem retinite pigmentosa, uso de um inibidor proteassomal ou um inibidor de autofagia e método para a produção de uma proteìna recombinante em uma conformação bioquimicamente funcional |
EP2182078B1 (en) * | 2005-09-01 | 2012-02-01 | Bristol-Myers Squibb Company | Biomarkers and methods for determining sensitivity to vascular endothelial growth factor receptor-2 modulators |
US20070212397A1 (en) * | 2005-09-15 | 2007-09-13 | Roth Daniel B | Pharmaceutical delivery device and method for providing ocular treatment |
WO2007067807A1 (en) * | 2005-12-07 | 2007-06-14 | Alacrity Biosciences, Inc. | Tetracyclines for treating ocular diseases and disorders |
WO2007070870A1 (en) * | 2005-12-16 | 2007-06-21 | Ethicon, Inc. | Compositions and methods for inhibiting adverse immune response in histocompatibility-mismatched transplantation |
EP1979050B1 (en) * | 2005-12-28 | 2017-04-19 | DePuy Synthes Products, Inc. | Treatment of peripheral vascular disease using postpartum-derived cells |
US9125906B2 (en) | 2005-12-28 | 2015-09-08 | DePuy Synthes Products, Inc. | Treatment of peripheral vascular disease using umbilical cord tissue-derived cells |
JP5528708B2 (ja) | 2006-02-09 | 2014-06-25 | 参天製薬株式会社 | 安定な製剤ならびにそれらを調製および使用する方法 |
US20070203190A1 (en) * | 2006-02-22 | 2007-08-30 | Ghanshyam Patil | Hydroxylamines and derivatives for the inhibition of complement activation |
MX2008011714A (es) * | 2006-03-14 | 2008-11-12 | Univ Southern California | Dispositivo de mems y metodo de administracion de agentes terapeuticos. |
CN101443004B (zh) | 2006-03-23 | 2013-03-06 | 参天制药株式会社 | 用于与血管通透性有关的疾病或病症的制剂 |
CN103393483B (zh) | 2006-03-31 | 2016-08-24 | 玛提治疗有限公司 | 用于鼻泪系统的药物释放方法、结构及组合物 |
WO2007133758A1 (en) * | 2006-05-15 | 2007-11-22 | Physical Pharmaceutica, Llc | Composition and improved method for preparation of small particles |
ES2390499T3 (es) | 2006-06-12 | 2012-11-13 | Opko Pharmaceuticals, Llc | Composiciones y métodos para la inhibición de la angiogénesis por sirna |
US20080045911A1 (en) * | 2006-06-21 | 2008-02-21 | Borgia Maureen J | Punctal plugs for the delivery of active agents |
US9474645B2 (en) * | 2006-06-21 | 2016-10-25 | Johnson & Johnson Vision Care, Inc. | Punctal plugs for the delivery of active agents |
US9173773B2 (en) * | 2006-06-21 | 2015-11-03 | Johnson & Johnson Vision Care, Inc. | Punctal plugs for the delivery of active agents |
US20080086101A1 (en) * | 2006-08-25 | 2008-04-10 | David Freilich | Ophthalmic insert |
US7872118B2 (en) * | 2006-09-08 | 2011-01-18 | Opko Ophthalmics, Llc | siRNA and methods of manufacture |
US20100034808A1 (en) * | 2006-11-21 | 2010-02-11 | Toru Nakazawa | Compositions and methods for preserving cells of the eye |
US20080145405A1 (en) * | 2006-12-15 | 2008-06-19 | Kunzler Jay F | Drug delivery devices |
CA2674076A1 (en) * | 2006-12-26 | 2008-07-10 | Qlt Plug Delivery, Inc. | Drug delivery implants for inhibition of optical defects |
WO2008103613A2 (en) | 2007-02-22 | 2008-08-28 | Othera Holding, Inc. | Hydroxylamine compounds and methods of their use |
US20080265343A1 (en) * | 2007-04-26 | 2008-10-30 | International Business Machines Corporation | Field effect transistor with inverted t shaped gate electrode and methods for fabrication thereof |
EP2205191B1 (en) | 2007-09-07 | 2014-11-12 | Mati Therapeutics Inc. | Lacrimal implant |
CN102670352A (zh) * | 2007-09-07 | 2012-09-19 | Qlt股份有限公司 | 用于泪腺植入物的插入和抽出工具 |
MX2010002616A (es) * | 2007-09-07 | 2010-08-04 | Qlt Plug Delivery Inc | Nucleos de farmaco para la liberacion sostenida de agentes terapeuticos. |
EP3372205A1 (en) | 2007-09-07 | 2018-09-12 | Mati Therapeutics Inc. | Lacrimal implant detection |
US9775882B2 (en) * | 2007-09-20 | 2017-10-03 | Medtronic, Inc. | Medical devices and methods including polymers having biologically active agents therein |
UA99152C2 (ru) * | 2007-10-05 | 2012-07-25 | Этикон, Инкорпорейтед | Восстановление и регенерация почечной ткани с использованием клеток, полученных с человеческой ткани пупочного канатика |
WO2009061988A1 (en) | 2007-11-08 | 2009-05-14 | Alimera Sciences, Inc. | Ocular implantation device |
EP2666510B1 (en) | 2007-12-20 | 2017-10-18 | University Of Southern California | Apparatus for controlled delivery of therapeutic agents |
EP2222281B1 (en) | 2007-12-20 | 2018-12-05 | Evonik Corporation | Process for preparing microparticles having a low residual solvent volume |
EP2266643B1 (en) * | 2008-01-03 | 2015-06-17 | University Of Southern California | Implantable drug-delivery devices, and apparatus and methods for refilling the devices |
MX2010008998A (es) * | 2008-02-18 | 2010-11-26 | Qlt Plug Delivery Inc | Implantes lagrimales y metodos relacionados. |
FR2927798B1 (fr) * | 2008-02-25 | 2011-03-04 | C L Investissements | Procede de fabrication d'un dispositif contraceptif intra-uterin et installation pour la mise en oeuvre de ce procede |
CN104623741A (zh) | 2008-04-30 | 2015-05-20 | 马缇医疗股份有限公司 | 复合泪管植入物及相关方法 |
US9199035B2 (en) * | 2008-05-08 | 2015-12-01 | Minipumps, Llc. | Drug-delivery pumps with dynamic, adaptive control |
CN102202706A (zh) | 2008-05-08 | 2011-09-28 | 迷你泵有限责任公司 | 可植入药物传送装置与用于填充该装置的设备和方法 |
EP2323716B1 (en) | 2008-05-08 | 2015-03-04 | MiniPumps, LLC | Drug-delivery pumps |
WO2009137780A2 (en) * | 2008-05-08 | 2009-11-12 | Replenish Pumps, Llc | Implantable pumps and cannulas therefor |
US9333297B2 (en) | 2008-05-08 | 2016-05-10 | Minipumps, Llc | Drug-delivery pump with intelligent control |
CA2722971C (en) * | 2008-05-09 | 2019-05-07 | Qlt Plug Delivery, Inc. | Sustained release delivery of active agents to treat glaucoma and ocular hypertension |
NZ593743A (en) | 2008-12-04 | 2012-07-27 | Opko Ophthalmics Llc | Compositions and methods for selective inhibition of pro-angiogenic vegf isoforms |
US10179900B2 (en) * | 2008-12-19 | 2019-01-15 | DePuy Synthes Products, Inc. | Conditioned media and methods of making a conditioned media |
PL2379088T3 (pl) | 2008-12-19 | 2018-07-31 | DePuy Synthes Products, Inc. | Leczenie płuca oraz chorób i zaburzeń płucnych |
BRPI0923070A2 (pt) * | 2008-12-19 | 2016-06-14 | Atrm Llc | "usos de composições para regeneração e reparo de tecido neural após lesão, as referidas composições, e kit" |
SI2379087T1 (sl) * | 2008-12-19 | 2015-01-30 | DePuy Synthes Products, LLC | Celice, izpeljane iz popkovniäśnega tkiva, za zdravljenje nevropatske boleäśine in spastiäśnosti |
WO2010071844A1 (en) * | 2008-12-19 | 2010-06-24 | Qlt Plug Delivery, Inc | Substance delivering punctum implants and methods |
WO2010088548A1 (en) | 2009-01-29 | 2010-08-05 | Forsight Labs, Llc | Posterior segment drug delivery |
US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
US9636255B2 (en) | 2009-02-13 | 2017-05-02 | Dose Medical Corporation | Uveoscleral drug delivery implant and methods for implanting the same |
JP5576405B2 (ja) * | 2009-02-23 | 2014-08-20 | キュー エル ティー インク. | 涙管インプラント及び関連する方法 |
EP2405967B1 (en) * | 2009-03-12 | 2020-09-23 | Delpor, Inc. | Implantable device for long-term delivery of drugs |
AU2010229651B2 (en) * | 2009-03-26 | 2014-05-08 | Advanced Technologies And Regenerative Medicine, Llc | Human umbilical cord tissue cells as therapy for Alzheimer' s disease |
WO2010111627A1 (en) * | 2009-03-26 | 2010-09-30 | Psivida Us, Inc. | Implantable formulations of bisphosphonic acids |
CN105726201B (zh) * | 2009-05-18 | 2020-08-25 | 多斯医学公司 | 给药眼植入物 |
WO2012071476A2 (en) | 2010-11-24 | 2012-05-31 | David Haffner | Drug eluting ocular implant |
US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
WO2010141729A1 (en) | 2009-06-03 | 2010-12-09 | Forsight Labs, Llc | Anterior segment drug delivery |
IN2012DN00352A (zh) | 2009-06-16 | 2015-08-21 | Bikam Pharmaceuticals Inc | |
WO2011008897A2 (en) | 2009-07-14 | 2011-01-20 | Board Of Regents, The University Of Texas System | Methods for making controlled delivery devices having zero order kinetics |
US8808257B2 (en) * | 2009-08-31 | 2014-08-19 | Johnson & Johnson Vision Care, Inc. | Methods and apparatus for pulsatile release of medicaments from a punctal plug |
RU2012127772A (ru) * | 2009-12-04 | 2014-01-10 | ОПКО ОФТЭЛМИКС, ЭлЭлСи | Композиции и способы для ингибирования vegf |
CA2785468A1 (en) * | 2009-12-23 | 2011-06-30 | Psivida Us, Inc. | Sustained release delivery devices |
WO2013022801A1 (en) | 2011-08-05 | 2013-02-14 | Forsight Vision4, Inc. | Small molecule delivery with implantable therapeutic device |
EP2555749B1 (en) * | 2010-04-06 | 2016-10-26 | Allergan, Inc. | Sustained-release reservoir implants for intracameral drug delivery |
AU2011242465B2 (en) | 2010-04-23 | 2017-01-19 | Massachusetts Eye And Ear Infirmary | Methods and compositions for preserving photoreceptor and retinal pigment epithelial cells |
WO2011139594A2 (en) * | 2010-04-27 | 2011-11-10 | Medtronic, Inc. | Artificial bursa for intra-articular drug delivery |
WO2011161666A2 (en) * | 2010-06-21 | 2011-12-29 | White Innovation Ltd. | Enclosed liquid capsules |
EP2585057B1 (en) | 2010-06-25 | 2017-08-23 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Methods of treatment using sterculic acid |
JP2012025708A (ja) * | 2010-07-27 | 2012-02-09 | Sepa Sigma Inc | 膜透過機構を異にする複数の徐放機構を利用した徐放化局所投与剤 |
PL2600812T3 (pl) | 2010-08-05 | 2022-01-24 | Forsight Vision4, Inc. | Urządzenie do leczenia oczu |
WO2012019139A1 (en) | 2010-08-05 | 2012-02-09 | Forsight Vision4, Inc. | Combined drug delivery methods and apparatus |
CN105435338B (zh) | 2010-08-05 | 2019-03-26 | 弗赛特影像4股份有限公司 | 用于药物输送的注入器装置和方法 |
WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
US20120237975A1 (en) | 2010-10-01 | 2012-09-20 | Jason Schrum | Engineered nucleic acids and methods of use thereof |
US20140024598A1 (en) | 2010-11-01 | 2014-01-23 | Demetrios Vavvas | Methods and compositions for preserving retinal ganglion cells |
US20140031769A1 (en) | 2010-11-19 | 2014-01-30 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
US8679093B2 (en) | 2010-11-23 | 2014-03-25 | Microchips, Inc. | Multi-dose drug delivery device and method |
WO2012088306A2 (en) * | 2010-12-22 | 2012-06-28 | Psivida Us, Inc. | Two-piece injectable drug delivery device with heat-cured seal |
EP2673049A4 (en) * | 2011-02-11 | 2015-04-08 | Psivida Inc | METHOD FOR THE TREATMENT OF MOLECULAR SOILS WITH ANTIOTE THERAPEUTICS |
US10286146B2 (en) | 2011-03-14 | 2019-05-14 | Minipumps, Llc | Implantable drug pumps and refill devices therefor |
US9919099B2 (en) | 2011-03-14 | 2018-03-20 | Minipumps, Llc | Implantable drug pumps and refill devices therefor |
US9603997B2 (en) | 2011-03-14 | 2017-03-28 | Minipumps, Llc | Implantable drug pumps and refill devices therefor |
AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
US9133082B2 (en) | 2011-06-14 | 2015-09-15 | Bikam Pharmaceuticals, Inc. | Opsin-binding ligands, compositions and methods of use |
WO2013003467A2 (en) | 2011-06-27 | 2013-01-03 | Massachusetts Eye And Ear Infirmary | Methods for treating ocular inflammatory disorders |
EP4249059A3 (en) | 2011-06-28 | 2023-11-29 | ForSight Vision4, Inc. | An apparatus for collecting a sample of fluid from a reservoir chamber of a therapeutic device for the eye |
WO2013025840A1 (en) | 2011-08-15 | 2013-02-21 | Massachusetts Eye And Ear Infirmary | Methods for preserving photoreceptor cell viability following retinal detachment |
DK3290024T3 (da) | 2011-08-29 | 2019-06-03 | Mati Therapeutics Inc | Vedvarende indgivelse af aktive midler til behandling af glaukom og okulær hypertension |
US9974685B2 (en) | 2011-08-29 | 2018-05-22 | Mati Therapeutics | Drug delivery system and methods of treating open angle glaucoma and ocular hypertension |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
CN106073986B (zh) | 2011-09-14 | 2019-01-11 | 弗赛特影像5股份有限公司 | 治疗患者的眼睛的装置 |
SI2755600T1 (sl) | 2011-09-16 | 2021-08-31 | Forsight Vision4, Inc. | Naprava za izmenjavo tekočine |
EP3682905B1 (en) | 2011-10-03 | 2021-12-01 | ModernaTX, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
CA2888805C (en) | 2011-10-21 | 2020-07-14 | Massachusetts Eye And Ear Infirmary | Methods and compositions for promoting axon regeneration and nerve function |
CN104023760A (zh) | 2011-10-28 | 2014-09-03 | 普莱萨格生命科学公司 | 药物递送方法 |
US8685106B2 (en) * | 2011-11-15 | 2014-04-01 | Abraham Lin | Method of a pharmaceutical delivery system for use within a joint replacement |
EP2785346A4 (en) | 2011-11-30 | 2015-04-29 | Bikam Pharmaceuticals Inc | OPSINBINDING LIGANDS, COMPOSITIONS THEREOF, AND METHOD OF USE THEREOF |
AU2012346537A1 (en) | 2011-12-01 | 2014-07-17 | Bikam Pharmaceuticals, Inc. | Opsin-binding ligands, compositions and methods of use |
RS63244B1 (sr) | 2011-12-16 | 2022-06-30 | Modernatx Inc | Kompozicije modifikovane mrna |
KR101981450B1 (ko) | 2011-12-23 | 2019-08-28 | 디퍼이 신테스 프로덕츠, 인코포레이티드 | 인간 제대 조직-유래된 세포의 검출 |
US10010448B2 (en) | 2012-02-03 | 2018-07-03 | Forsight Vision4, Inc. | Insertion and removal methods and apparatus for therapeutic devices |
US10182932B2 (en) | 2012-02-21 | 2019-01-22 | Allurion Technologies, Inc. | Methods and devices for deploying and releasing a temporary implant within the body |
WO2014074625A1 (en) | 2012-02-21 | 2014-05-15 | Allurion Technologies, Inc. | Anatomically adapted ingestible delivery systems and methods |
US8974483B2 (en) | 2012-02-21 | 2015-03-10 | Allurion Technologies, Inc. | Methods and devices for deploying and releasing a temporary implant within the body |
JP6311936B2 (ja) * | 2012-02-21 | 2018-04-18 | アルリオン テクノロジーズ, インク. | 体内で一時的なインプラントを展開および排出する方法および装置 |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
EP2833892A4 (en) | 2012-04-02 | 2016-07-20 | Moderna Therapeutics Inc | MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF PROTEINS AND PEPTIDES ASSOCIATED WITH ONCOLOGY |
US10501512B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides |
US9827401B2 (en) | 2012-06-01 | 2017-11-28 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US9308355B2 (en) | 2012-06-01 | 2016-04-12 | Surmodies, Inc. | Apparatus and methods for coating medical devices |
WO2014031676A1 (en) * | 2012-08-20 | 2014-02-27 | O-Ray Pharma, Inc. | Process for manufacturing drug delivery formulations |
WO2014066775A1 (en) | 2012-10-26 | 2014-05-01 | Forsight Vision5, Inc. | Ophthalmic system for sustained release of drug to eye |
ES2921623T3 (es) | 2012-11-26 | 2022-08-30 | Modernatx Inc | ARN modificado terminalmente |
US10981961B2 (en) | 2013-03-11 | 2021-04-20 | University Of Florida Research Foundation, Incorporated | Delivery of card protein as therapy for occular inflammation |
EP2968113B8 (en) | 2013-03-14 | 2020-10-28 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
US10517759B2 (en) | 2013-03-15 | 2019-12-31 | Glaukos Corporation | Glaucoma stent and methods thereof for glaucoma treatment |
SG11201507294WA (en) | 2013-03-15 | 2015-10-29 | Taris Biomedical Llc | Drug delivery devices with drug-permeable component and methods |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
CN105246438B (zh) | 2013-03-28 | 2018-01-26 | 弗赛特影像4股份有限公司 | 用于输送治疗物质的眼科植入物 |
AU2014329452B2 (en) | 2013-10-03 | 2019-06-20 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
EP3089748A4 (en) | 2014-01-02 | 2017-09-27 | Massachusetts Eye & Ear Infirmary | Treating ocular neovascularization |
EP3148491B1 (en) | 2014-05-29 | 2020-07-01 | Glaukos Corporation | Implants with controlled drug delivery features and manufacturing method for said implants |
MY182497A (en) | 2014-07-15 | 2021-01-25 | Forsight Vision4 Inc | Ocular implant delivery device and method |
WO2016020901A1 (en) | 2014-08-07 | 2016-02-11 | Acerta Pharma B.V. | Methods of treating cancers, immune and autoimmune diseases, and inflammatory diseases based on btk occupancy and btk resynthesis rate |
BR112017002466A2 (pt) | 2014-08-08 | 2017-12-05 | Forsight Vision4 Inc | formulações estáveis e solúveis de inibidores da tirosina cinase do receptor, e métodos para a sua preparação |
US10363163B2 (en) * | 2014-09-11 | 2019-07-30 | EyePoint Pharmaceuticals, Inc. | Injector apparatus |
US10507101B2 (en) | 2014-10-13 | 2019-12-17 | W. L. Gore & Associates, Inc. | Valved conduit |
SG11201703726XA (en) | 2014-11-10 | 2017-06-29 | Forsight Vision4 Inc | Expandable drug delivery devices and method of use |
WO2016168141A1 (en) | 2015-04-13 | 2016-10-20 | Forsight Vision5, Inc. | Ocular insert composition of semi-crystalline or crystalline pharmaceutically active agent |
WO2016172704A1 (en) | 2015-04-23 | 2016-10-27 | Taris Biomedical Llc | Drug delivery devices with drug-permeable component and methods |
US10669321B2 (en) | 2015-06-08 | 2020-06-02 | Retinal Solutions Llc | Retinal capillary regeneration with synthetic norrin protein |
US10206978B2 (en) | 2015-06-08 | 2019-02-19 | Retinal Solutions Llc | Norrin regulation of junction proteins and the use thereof to treat epithelial or endothelial membrane leakage induced edema |
US10202429B2 (en) | 2015-06-08 | 2019-02-12 | Retinal Solutions Llc | Norrin regulation of cellular production of junction proteins and use to treat retinal vasculature edema |
WO2017040853A1 (en) | 2015-09-02 | 2017-03-09 | Glaukos Corporation | Drug delivery implants with bi-directional delivery capacity |
US11564833B2 (en) | 2015-09-25 | 2023-01-31 | Glaukos Corporation | Punctal implants with controlled drug delivery features and methods of using same |
US10172740B2 (en) | 2015-11-06 | 2019-01-08 | David E Freilich | Lacrimal stent |
CN108367079B (zh) | 2015-11-12 | 2022-11-22 | 灰色视觉公司 | 用于治疗的聚集性微粒 |
KR20180084104A (ko) | 2015-11-20 | 2018-07-24 | 포사이트 비젼4, 인크. | 연장 방출 약물 전달 장치를 위한 다공성 구조물 |
JP7009384B2 (ja) | 2016-04-05 | 2022-01-25 | フォーサイト・ビジョン フォー・インコーポレーテッド | 移植可能な眼薬送達デバイス |
CA3022830A1 (en) * | 2016-04-20 | 2017-10-26 | Harold Alexander Heitzmann | Bioresorbable ocular drug delivery device |
RU2019102933A (ru) | 2016-07-05 | 2020-08-05 | Янссен Байотек, Инк. | Лечение сосудистого заболевания сетчатки с использованием клеток-предшественников |
JP2020514407A (ja) | 2017-01-24 | 2020-05-21 | マクリーゲン, インク.Macregen, Inc. | アポリポプロテイン模倣物を用いる加齢黄斑変性と他の眼疾患の治療 |
CA3054497A1 (en) | 2017-03-03 | 2018-09-07 | Macregen, Inc. | Treatment of age-related macular degeneration and other eye diseases with one or more therapeutic agents |
US11523940B2 (en) | 2017-03-17 | 2022-12-13 | W. L. Gore & Associates, Inc. | Delivery aids for glaucoma shunts |
CN110662543A (zh) | 2017-03-23 | 2020-01-07 | 灰色视觉公司 | 用于治疗眼部疾病的药物和组合物 |
CA3057875A1 (en) | 2017-05-10 | 2018-11-15 | Graybug Vision, Inc. | Extended release microparticles and suspensions thereof for medical therapy |
EP3654941A1 (en) | 2017-07-17 | 2020-05-27 | Keith Roizman | Topical delivery of therapeutic agents comprising cell-penetrating peptides for use for the treatment of age-related macular degeneration and other eye diseases |
WO2019023617A1 (en) * | 2017-07-27 | 2019-01-31 | University Of Utah Research Foundation | DEVICE FOR DELIVERY OF THERAPEUTIC PRODUCT |
WO2019103906A1 (en) | 2017-11-21 | 2019-05-31 | Forsight Vision4, Inc. | Fluid exchange apparatus for expandable port delivery system and methods of use |
EP4344724A2 (en) | 2018-02-26 | 2024-04-03 | Allurion Technologies, Inc. | Automatic-sealing balloon-filling catheter system |
WO2019226516A1 (en) | 2018-05-24 | 2019-11-28 | Celanese EVA Performance Polymers Corporation | Implantable device for sustained release of a macromolecular drug compound |
CN111989068A (zh) | 2018-05-24 | 2020-11-24 | 塞拉尼斯伊娃高性能聚合物公司 | 用于持续释放大分子药物化合物的可植入器件 |
CN112638464B (zh) | 2018-07-06 | 2021-12-14 | 阿勒里恩科技公司 | 二元流体控制阀系统 |
CN109172963B (zh) * | 2018-10-19 | 2021-05-14 | 青岛大学附属医院 | 具有连续给药功能的雾化理疗器 |
WO2020112816A1 (en) | 2018-11-29 | 2020-06-04 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US11678983B2 (en) | 2018-12-12 | 2023-06-20 | W. L. Gore & Associates, Inc. | Implantable component with socket |
US11497900B2 (en) | 2018-12-13 | 2022-11-15 | Allurion Technologies, Inc. | Enhanced fluid delivery system |
US11039954B2 (en) | 2019-03-21 | 2021-06-22 | Microoptx Inc. | Implantable ocular drug delivery devices and methods |
CN110046067B (zh) * | 2019-04-22 | 2023-10-31 | 无线生活(杭州)信息科技有限公司 | 接口测试方法及装置 |
US11819590B2 (en) | 2019-05-13 | 2023-11-21 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
JP2022553408A (ja) | 2019-10-24 | 2022-12-22 | デニス・イー・ラボンバード | 眼用デバイスおよび薬物送達システムならびにそのケース |
WO2023031277A1 (en) | 2021-08-31 | 2023-03-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the treatment of ocular rosacea |
Family Cites Families (195)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3416350A (en) | 1966-02-23 | 1968-12-17 | Martin Marietta Corp | Gripping structure |
US3416530A (en) | 1966-03-02 | 1968-12-17 | Richard A. Ness | Eyeball medication dispensing tablet |
US3896819A (en) | 1969-04-01 | 1975-07-29 | Alejandro Zaffaroni | IUD having a replenishing drug reservoir |
US3854480A (en) * | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
US3630200A (en) | 1969-06-09 | 1971-12-28 | Alza Corp | Ocular insert |
US3618604A (en) | 1969-06-09 | 1971-11-09 | Alza Corp | Ocular insert |
US3632739A (en) | 1969-12-29 | 1972-01-04 | Sandoz Ag | Solid sustained release pharmaceutical preparation |
US3980463A (en) | 1970-11-16 | 1976-09-14 | Sumitomo Chemical Company, Limited | Process for producing granular composition for use in agriculture and horticulture |
US3829570A (en) * | 1971-01-26 | 1974-08-13 | Boehringer Sohn Ingelheim | Therapeutic compositions and method |
US3993071A (en) | 1971-09-09 | 1976-11-23 | Alza Corporation | Bioerodible ocular device |
US3948254A (en) * | 1971-11-08 | 1976-04-06 | Alza Corporation | Novel drug delivery device |
US3828777A (en) | 1971-11-08 | 1974-08-13 | Alza Corp | Microporous ocular device |
US3892570A (en) * | 1972-04-18 | 1975-07-01 | Xerox Corp | Light activating imaging process |
US4177256A (en) | 1973-04-25 | 1979-12-04 | Alza Corporation | Osmotic bursting drug delivery device |
US4036227A (en) | 1973-04-25 | 1977-07-19 | Alza Corporation | Osmotic releasing device having a plurality of release rate patterns |
US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
US4351337A (en) | 1973-05-17 | 1982-09-28 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery device, and process for preparing and using the same |
US3914402A (en) | 1973-06-14 | 1975-10-21 | Alza Corp | Ophthalmic dosage form, for releasing medication over time |
US3961628A (en) | 1974-04-10 | 1976-06-08 | Alza Corporation | Ocular drug dispensing system |
US4142526A (en) | 1974-12-23 | 1979-03-06 | Alza Corporation | Osmotic releasing system with means for changing release therefrom |
US4014335A (en) | 1975-04-21 | 1977-03-29 | Alza Corporation | Ocular drug delivery device |
US4014355A (en) * | 1975-08-11 | 1977-03-29 | Dynell Electronics Corporation | Bidet and hygienic cleansing arrangement |
US4034758A (en) | 1975-09-08 | 1977-07-12 | Alza Corporation | Osmotic therapeutic system for administering medicament |
US3977404A (en) | 1975-09-08 | 1976-08-31 | Alza Corporation | Osmotic device having microporous reservoir |
US4077407A (en) | 1975-11-24 | 1978-03-07 | Alza Corporation | Osmotic devices having composite walls |
US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
US4014334A (en) | 1976-02-02 | 1977-03-29 | Alza Corporation | Laminated osmotic system for dispensing beneficial agent |
US4247498A (en) | 1976-08-30 | 1981-01-27 | Akzona Incorporated | Methods for making microporous products |
US4111203A (en) | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system with means for improving delivery kinetics of system |
US4111201A (en) | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system for delivering selected beneficial agents having varying degrees of solubility |
US4256108A (en) | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
US4519909A (en) | 1977-07-11 | 1985-05-28 | Akzona Incorporated | Microporous products |
US4186184A (en) | 1977-12-27 | 1980-01-29 | Alza Corporation | Selective administration of drug with ocular therapeutic system |
JPS54119021A (en) | 1978-03-06 | 1979-09-14 | Nippon Kayaku Co Ltd | Carcinostatic agent |
US4290426A (en) | 1978-05-04 | 1981-09-22 | Alza Corporation | Dispenser for dispensing beneficial agent |
US4260736A (en) * | 1978-08-14 | 1981-04-07 | Kureha Kagaku Kogyo Kabushiki Kaisha | Steroid hormone-antitumor derivatives |
US4200098A (en) | 1978-10-23 | 1980-04-29 | Alza Corporation | Osmotic system with distribution zone for dispensing beneficial agent |
US4304232A (en) | 1979-03-14 | 1981-12-08 | Alza Corporation | Unit system having multiplicity of means for dispensing useful agent |
US4283394A (en) * | 1979-08-06 | 1981-08-11 | Research Corporation | Cytotoxic nucleoside-corticosteroid phosphodiesters |
US4326525A (en) | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
US4304765A (en) | 1980-10-14 | 1981-12-08 | Alza Corporation | Ocular insert housing steroid in two different therapeutic forms |
US4322323A (en) | 1980-12-01 | 1982-03-30 | Alza Corporation | Erodible device comprising surfactant for modifying the rate of erosion of the device |
US4327725A (en) | 1980-11-25 | 1982-05-04 | Alza Corporation | Osmotic device with hydrogel driving member |
US4484922A (en) | 1981-06-25 | 1984-11-27 | Rosenwald Peter L | Occular device |
JPS5835110A (ja) | 1981-08-28 | 1983-03-01 | Tetsuo Kato | 徐放性マイクロカプセル |
US4730013A (en) | 1981-10-08 | 1988-03-08 | Merck & Co., Inc. | Biosoluble ocular insert |
US4475916A (en) | 1982-03-18 | 1984-10-09 | Merck & Co., Inc. | Osmotic drug delivery system |
DK90883A (da) | 1982-03-18 | 1983-09-19 | Merck & Co Inc | Beholder til osmotisk afgivelse af et stof eller en stofblanding |
US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
US4432965A (en) | 1982-07-09 | 1984-02-21 | Key Pharmaceuticals, Inc. | Quinidine sustained release dosage formulation |
US4519801A (en) | 1982-07-12 | 1985-05-28 | Alza Corporation | Osmotic device with wall comprising cellulose ether and permeability enhancer |
US4522625A (en) | 1982-09-29 | 1985-06-11 | Alza Corporation | Drug dispenser comprising wall formed of semipermeable member and enteric member |
US4478818A (en) | 1982-12-27 | 1984-10-23 | Alza Corporation | Ocular preparation housing steroid in two different therapeutic forms |
US4673405A (en) | 1983-03-04 | 1987-06-16 | Alza Corporation | Osmotic system with instant drug availability |
US4627850A (en) | 1983-11-02 | 1986-12-09 | Alza Corporation | Osmotic capsule |
JPS60100516A (ja) | 1983-11-04 | 1985-06-04 | Takeda Chem Ind Ltd | 徐放型マイクロカプセルの製造法 |
US4777049A (en) | 1983-12-01 | 1988-10-11 | Alza Corporation | Constant release system with pulsed release |
EP0147780A3 (en) | 1984-01-03 | 1987-03-11 | Merck & Co. Inc. | Drug delivery device |
IT1206166B (it) | 1984-07-26 | 1989-04-14 | Sigma Tau Ind Farmaceuti | Dispositivo per rilasciare una sostanza in un fluido di dissoluzione con cinetica di ordine zero e procedimento per la sua preparazione |
US4692336A (en) | 1984-03-19 | 1987-09-08 | Alza Corporation | Self controlled release device for administering beneficial agent to recipient |
US4716031A (en) | 1984-03-21 | 1987-12-29 | Alza Corporation | Drug dispenser comprising a multiplicity of members acting together for successfully dispensing drug |
US4615698A (en) | 1984-03-23 | 1986-10-07 | Alza Corporation | Total agent osmotic delivery system |
DE3580384D1 (de) | 1984-04-09 | 1990-12-13 | Toyo Boseki | Praeparat mit verzoegerter freigabe zum aufbringen auf die schleimhaeute der mundhoehle. |
US4657543A (en) | 1984-07-23 | 1987-04-14 | Massachusetts Institute Of Technology | Ultrasonically modulated polymeric devices for delivering compositions |
US4743247A (en) | 1984-08-13 | 1988-05-10 | Alza Corporation | Process for manufacturing dosage form |
US4927687A (en) | 1984-10-01 | 1990-05-22 | Biotek, Inc. | Sustained release transdermal drug delivery composition |
IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
US4863735A (en) | 1985-02-19 | 1989-09-05 | Massachusetts Institute Of Technology | Biodegradable polymeric drug delivery system with adjuvant activity |
US4913906B1 (en) | 1985-02-28 | 2000-06-06 | Yissum Res Dev Co | Controlled release dosage form of valproic acid |
US4609374A (en) | 1985-04-22 | 1986-09-02 | Alza Corporation | Osmotic device comprising means for governing initial time of agent release therefrom |
US4624847A (en) | 1985-04-22 | 1986-11-25 | Alza Corporation | Drug delivery device for programmed delivery of beneficial drug |
US4693886A (en) | 1985-04-22 | 1987-09-15 | Alza Corporation | Osmotic device with inert core |
US4720384A (en) | 1985-05-03 | 1988-01-19 | E. I. Du Pont De Nemours And Company | Manufacture of hollow fine tubular drug delivery systems |
JPS6210381A (ja) | 1985-07-08 | 1987-01-19 | 大成建設株式会社 | 空気膜構造物における膜面接合装置 |
US4898733A (en) | 1985-11-04 | 1990-02-06 | International Minerals & Chemical Corp. | Layered, compression molded device for the sustained release of a beneficial agent |
US4717567A (en) | 1985-11-25 | 1988-01-05 | Eastman Kodak Company | Rumen-stable pellets |
IT1188212B (it) | 1985-12-20 | 1988-01-07 | Paolo Colombo | Sistema per il rilascio a velocita' controllata di sostanze attive |
US4764364A (en) * | 1986-02-25 | 1988-08-16 | S R I International | Method of preparing bioerodible polymers having pH sensitivity in the acid range and resulting product |
US4814323A (en) | 1986-03-25 | 1989-03-21 | Andrieu J M | Process for the treatment and the prevention of AIDS and other disorders induced by the LAV/HTLV III virus |
EP0243111A3 (en) * | 1986-04-17 | 1989-06-07 | Castex Products Limited | Pellet for administration to ruminants |
US5141752A (en) | 1986-05-09 | 1992-08-25 | Alza Corporation | Delayed drug delivery device |
US5342622A (en) | 1986-05-16 | 1994-08-30 | The State Of Victoria | Subdermal biocompatible implants |
US4959217A (en) | 1986-05-22 | 1990-09-25 | Syntex (U.S.A.) Inc. | Delayed/sustained release of macromolecules |
US4832957A (en) | 1987-12-11 | 1989-05-23 | Merck & Co., Inc. | Controlled release combination of carbidopa/levodopa |
US4786500A (en) | 1986-06-26 | 1988-11-22 | Alza Corporation | Programmable agent delivery system |
US4927632A (en) | 1986-06-26 | 1990-05-22 | Alza Corporation | Selective pulsed drug delivery system |
JPH0794384B2 (ja) | 1986-09-01 | 1995-10-11 | 帝国製薬株式会社 | 徐放性口腔内用製剤 |
US5147647A (en) | 1986-10-02 | 1992-09-15 | Sohrab Darougar | Ocular insert for the fornix |
US4830860A (en) | 1986-10-30 | 1989-05-16 | Pfizer Inc. | Stressed polymeric device for controlled release of a substance to an ambient environment |
HU205861B (en) | 1986-12-19 | 1992-07-28 | Sandoz Ag | Process for producing hydrosole of pharmaceutically effective material |
US4806382A (en) | 1987-04-10 | 1989-02-21 | University Of Florida | Ocular implants and methods for their manufacture |
US4861627A (en) | 1987-05-01 | 1989-08-29 | Massachusetts Institute Of Technology | Preparation of multiwall polymeric microcapsules |
US4789513A (en) | 1987-06-05 | 1988-12-06 | P.C.E. Corp. | Coextrusion apparatus and process |
EP0303306B1 (en) * | 1987-08-08 | 1993-03-10 | Akzo N.V. | Contraceptive implant |
US4891223A (en) | 1987-09-03 | 1990-01-02 | Air Products And Chemicals, Inc. | Controlled release delivery coating formulation for bioactive substances |
KR920003601B1 (ko) | 1987-09-03 | 1992-05-04 | 유니버시티 어브 죠지아 리서취 화운데이션 인코포레이티드 | 점안 싸이클로스포린(cyclosporin)의 조성물 |
US4839342A (en) | 1987-09-03 | 1989-06-13 | University Of Georgia Research Foundation, Inc. | Method of increasing tear production by topical administration of cyclosporin |
US5035891A (en) * | 1987-10-05 | 1991-07-30 | Syntex (U.S.A.) Inc. | Controlled release subcutaneous implant |
SE8703881D0 (sv) | 1987-10-08 | 1987-10-08 | Haessle Ab | New pharmaceutical preparation |
US4994273A (en) | 1987-11-02 | 1991-02-19 | Merck & Co., Inc. | Solubility modulated drug delivery device |
IT1223150B (it) | 1987-11-18 | 1990-09-12 | Ubaldo Conte | Compressa per uso oftalmico e rilascio controllato della sostanza attiva |
US4945089A (en) * | 1987-12-29 | 1990-07-31 | Alcon Laboratories, Inc. | Use of tetrahydrocortexolone to prevent elevations in intraocular pressure caused by corticosteroids |
US4877618A (en) | 1988-03-18 | 1989-10-31 | Reed Jr Fred D | Transdermal drug delivery device |
WO1989009066A1 (en) * | 1988-03-24 | 1989-10-05 | Bukh Meditec A/S | Controlled release composition |
US4865846A (en) | 1988-06-03 | 1989-09-12 | Kaufman Herbert E | Drug delivery system |
US4882150A (en) | 1988-06-03 | 1989-11-21 | Kaufman Herbert E | Drug delivery system |
US4946456A (en) * | 1988-08-26 | 1990-08-07 | Alza Corp. | Fluid imbibing pump activated by capillary action of a fabric or polymeric sleeve |
US5124392A (en) | 1988-10-03 | 1992-06-23 | Alcon Laboratories, Inc. | Pharmaceutical compositions and methods of treatment to prevent and treat corneal scar formation produced by laser irradiation |
US5360611A (en) | 1988-10-03 | 1994-11-01 | Alcon Laboratories, Inc. | Pharmaceutical compositions and methods of treatment of the cornea following ultraviolet laser irradiation |
US5306500A (en) | 1988-11-21 | 1994-04-26 | Collagen Corporation | Method of augmenting tissue with collagen-polymer conjugates |
US5174999A (en) | 1988-12-13 | 1992-12-29 | Alza Corporation | Delivery system comprising fluid ingress and drug egress |
DD295760A5 (de) | 1989-01-31 | 1991-11-14 | Martin-Luther-Universitaet Halle Wittenberg,De | Arzneistoffreigabesystem mit kotrollierter wirkstoffreisetzung |
US5098443A (en) | 1989-03-23 | 1992-03-24 | University Of Miami | Method of implanting intraocular and intraorbital implantable devices for the controlled release of pharmacological agents |
FR2645029B1 (fr) | 1989-03-28 | 1997-09-12 | Cordis Sa | Membrane de reservoir implantable sous la peau d'un patient |
US5028435A (en) | 1989-05-22 | 1991-07-02 | Advanced Polymer Systems, Inc. | System and method for transdermal drug delivery |
DK469989D0 (da) * | 1989-09-22 | 1989-09-22 | Bukh Meditec | Farmaceutisk praeparat |
US5120548A (en) | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
US5294604A (en) | 1989-12-20 | 1994-03-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating ocular diseases by periocular administration of cyclosporine A or G |
EP0514406B1 (en) | 1990-01-30 | 1994-03-02 | Akzo Nobel N.V. | Article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances |
US5201764A (en) | 1990-02-28 | 1993-04-13 | Autogenesis Technologies, Inc. | Biologically compatible collagenous reaction product and articles useful as medical implants produced therefrom |
US5178866A (en) | 1990-03-23 | 1993-01-12 | Alza Corporation | Dosage form for delivering drug to the intestine |
US5324280A (en) | 1990-04-02 | 1994-06-28 | Alza Corporation | Osmotic dosage system for delivering a formulation comprising liquid carrier and drug |
US5156623A (en) | 1990-04-16 | 1992-10-20 | Olympus Optical Co., Ltd. | Sustained release material and method of manufacturing the same |
US5091185A (en) | 1990-06-20 | 1992-02-25 | Monsanto Company | Coated veterinary implants |
GR1001529B (el) | 1990-09-07 | 1994-03-31 | Elmuquimica Farm Sl | Μέ?οδος για την λήψη νέων 21-εστέρων της 16-17-ακετάλης της πρ να-1,4-διενο-3,20-διόνης. |
DE69102140T2 (de) | 1990-09-28 | 1994-09-08 | Pfizer | Wirkstoffabgabevorrichtung die ein hydrophobisches mittel enthält. |
IS3778A7 (is) | 1990-10-31 | 1992-05-02 | Amgen Inc. | Aðferð til að gefa dýrum vaxtarhormón, þar sem gefnu magni er stýrt |
US5378475A (en) | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
NZ286242A (en) | 1991-03-26 | 1997-11-24 | Csl Ltd | Use of veterinary implant as a single dose vaccination system: rupturable polymer film coating around core of active agent and water soluble excipient |
US5226902A (en) | 1991-07-30 | 1993-07-13 | University Of Utah | Pulsatile drug delivery device using stimuli sensitive hydrogel |
EP0600004B1 (en) | 1991-08-23 | 1998-12-02 | The Gillette Company | Sustained-release martrices for dental application |
FR2682090B1 (fr) | 1991-10-03 | 1993-12-31 | Holzstoff Holding Sa | Systeme-reservoir pour diffusion prolongee d'un principe actif. |
US5178635A (en) | 1992-05-04 | 1993-01-12 | Allergan, Inc. | Method for determining amount of medication in an implantable device |
US5512293A (en) * | 1992-07-23 | 1996-04-30 | Alza Corporation | Oral sustained release drug delivery device |
US5314419A (en) * | 1992-10-30 | 1994-05-24 | Pelling George E | Method for dispensing ophthalmic drugs to the eye |
US5840881A (en) * | 1992-11-27 | 1998-11-24 | Takeda Chemical Industries, Ltd. | Composition containing a water-insoluble or slightly water-soluble compound with enhanced water-solubility |
US5538735A (en) | 1993-02-19 | 1996-07-23 | Ahn; Sam S. | Method of making a drug delivery system using hollow fibers |
US5393536A (en) * | 1993-04-05 | 1995-02-28 | Crane Plastics Company | Coextrusion apparatus |
US5770589A (en) | 1993-07-27 | 1998-06-23 | The University Of Sydney | Treatment of macular degeneration |
JPH0748246A (ja) | 1993-08-06 | 1995-02-21 | Fujisawa Pharmaceut Co Ltd | 徐放性注入剤 |
CA2169292C (en) | 1993-08-12 | 2010-11-23 | E. Edward Baetge | Improved compositions and methods for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules |
US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
JP3720386B2 (ja) | 1993-12-27 | 2005-11-24 | 住友製薬株式会社 | 薬物放出制御製剤 |
DK0740650T3 (da) | 1994-01-28 | 2004-09-27 | Univ Kentucky Res Found | Codrugs som metode til styret transport af lægemiddel |
US6051576A (en) * | 1994-01-28 | 2000-04-18 | University Of Kentucky Research Foundation | Means to achieve sustained release of synergistic drugs by conjugation |
US5474979A (en) | 1994-05-17 | 1995-12-12 | Allergan, Inc. | Nonirritating emulsions for sensitive tissue |
CA2193806A1 (en) | 1994-06-22 | 1995-12-28 | Michael Cardamone | Controlled release device and method |
US5435998A (en) | 1994-08-03 | 1995-07-25 | Abelson; Mark B. | Treatment of low-tension glaucoma by topical administration of calcium channel blocking agents |
KR100201352B1 (ko) * | 1995-03-16 | 1999-06-15 | 성재갑 | 단일주사 백신 제형 |
US5569429A (en) | 1995-05-05 | 1996-10-29 | Randcastle Extrusion Systems, Inc. | Dynamic seal and sealing method |
US5554187A (en) | 1995-08-18 | 1996-09-10 | Rizzo, Iii; Joseph | Medication dispensing intra-ocular lens system |
US5773019A (en) | 1995-09-27 | 1998-06-30 | The University Of Kentucky Research Foundation | Implantable controlled release device to deliver drugs directly to an internal portion of the body |
US6283951B1 (en) | 1996-10-11 | 2001-09-04 | Transvascular, Inc. | Systems and methods for delivering drugs to selected locations within the body |
US6039975A (en) * | 1995-10-17 | 2000-03-21 | Hoffman-La Roche Inc. | Colon targeted delivery system |
DE19539361A1 (de) | 1995-10-23 | 1997-04-24 | Basf Ag | Verfahren zur Herstellung von mehrschichtigen, festen Arzneiformen zur oralen oder rektalen Verabreichung |
US6441047B2 (en) | 1995-11-17 | 2002-08-27 | Alcon Manufacturing Ltd.. | Combination therapy for treating glaucoma |
US5797898A (en) * | 1996-07-02 | 1998-08-25 | Massachusetts Institute Of Technology | Microchip drug delivery devices |
ZA981610B (en) * | 1997-03-24 | 1999-08-26 | Alza Corp | Self adjustable exit port. |
AU729870B2 (en) * | 1997-03-31 | 2001-02-15 | Alza Corporation | Diffusional implantable delivery system |
TW358031B (en) * | 1997-04-11 | 1999-05-11 | Akze Nobel N V | Drug delivery system for 2 or more active substances |
FR2766088B1 (fr) | 1997-07-17 | 2001-01-05 | Dow Corning Sa | Dispositifs a liberation controlee d'un agent pharmaceutique, leur fabrication par co-extrusion et article intermediaire |
US6055453A (en) | 1997-08-01 | 2000-04-25 | Genetronics, Inc. | Apparatus for addressing needle array electrodes for electroporation therapy |
US5902598A (en) | 1997-08-28 | 1999-05-11 | Control Delivery Systems, Inc. | Sustained release drug delivery devices |
JP3240593B2 (ja) | 1998-02-16 | 2001-12-17 | 株式会社高研 | 可溶性コラーゲンパウダーを担体とする医薬徐放剤 |
US6267154B1 (en) * | 1998-06-05 | 2001-07-31 | Abbott Laboratories | System for storing mixing and administering a drug |
US6217895B1 (en) * | 1999-03-22 | 2001-04-17 | Control Delivery Systems | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US6368658B1 (en) * | 1999-04-19 | 2002-04-09 | Scimed Life Systems, Inc. | Coating medical devices using air suspension |
US6606992B1 (en) | 1999-06-30 | 2003-08-19 | Nektar Therapeutics | Systems and methods for aerosolizing pharmaceutical formulations |
US20030105121A1 (en) * | 1999-07-27 | 2003-06-05 | Bernard Bihari | Method of preventing lipodystrophy syndrome or reversing a pre-existing syndrome in HIV-infected patients being treated with antiretroviral agents |
US6491683B1 (en) | 1999-09-07 | 2002-12-10 | Alza Corporation | Osmotic dosage form composed of an extruded polymer tube form |
US6267058B1 (en) * | 1999-10-01 | 2001-07-31 | Flight Rail Corporation | Coupling mechanism for magnetically coupled transportation module |
US6331313B1 (en) * | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
CA2544460C (en) | 1999-10-22 | 2009-04-07 | Allergan, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
KR100416242B1 (ko) * | 1999-12-22 | 2004-01-31 | 주식회사 삼양사 | 약물전달체용 생분해성 블록 공중합체의 액체 조성물 및이의 제조방법 |
US6375972B1 (en) * | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
US20040115268A1 (en) * | 2000-04-26 | 2004-06-17 | Control Delivery Systems, Inc. | Systemic delivery of antiviral agents |
US6242058B1 (en) * | 2000-05-12 | 2001-06-05 | Dow Corning Corporation | Method for forming coatings from radiation curable compositions containing alkenyl ether functional polyisobutylenes |
AU2001289653A1 (en) | 2000-07-14 | 2002-01-30 | Universiteit Gent | Composite solid shaped articles for the controlled delivery of biologically active ingredients |
EP1213014B1 (en) | 2000-12-07 | 2005-04-20 | Warner-Lambert Company LLC | Process and system for uniform release drug delivery |
CA2444894C (en) | 2001-04-26 | 2013-06-25 | Control Delivery Systems, Inc. | Sustained release drug delivery system containing codrugs |
WO2002089767A1 (en) * | 2001-05-03 | 2002-11-14 | Massachusetts Eye And Ear Infirmary | Implantable drug delivery device and use thereof |
JP2004535431A (ja) | 2001-06-22 | 2004-11-25 | サザン バイオシステムズ, インコーポレイテッド | ゼロ次長期放出同軸インプラント |
AUPR602401A0 (en) | 2001-06-29 | 2001-07-26 | Smart Drug Systems Inc | Sustained release delivery system |
AU2002351739A1 (en) | 2001-12-18 | 2003-06-30 | Novo Nordisk A/S | Solid dose micro implant |
AU2003234443A1 (en) | 2002-05-01 | 2003-11-17 | Beth Israel Deaconess Medical Center | Use of anti-cd1 antibodies for the modulation of immune responses |
BR0309844A (pt) | 2002-05-07 | 2005-02-15 | Control Delivery Sys Inc | Processos para formação de um dispositivo para a distribuição de droga |
US8871241B2 (en) | 2002-05-07 | 2014-10-28 | Psivida Us, Inc. | Injectable sustained release delivery devices |
AU2003287666A1 (en) | 2002-11-13 | 2004-06-03 | Control Delivery Systems, Inc. | Systemic delivery of antiviral agents |
AU2004292957C1 (en) | 2003-11-13 | 2011-04-28 | Eyepoint Pharmaceuticals Us, Inc. | Injectable sustained release implant having a bioerodible matrix core and a bioerodible skin |
CA2554424A1 (en) | 2004-01-26 | 2005-08-11 | Control Delivery Systems, Inc. | Controlled and sustained delivery of nucleic acid-based therapeutic agents |
US8147865B2 (en) | 2004-04-30 | 2012-04-03 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
US8119154B2 (en) | 2004-04-30 | 2012-02-21 | Allergan, Inc. | Sustained release intraocular implants and related methods |
EP1937210B1 (en) | 2005-10-18 | 2017-05-31 | Allergan, Inc. | Ocular therapy using glucocorticoid derivatives selectively penetrating posterior segment tissues |
CA2670990A1 (en) | 2006-12-01 | 2008-06-12 | Allergan, Inc. | Method for determining optimum intraocular locations for drug delivery systems |
JP2013515735A (ja) | 2009-12-23 | 2013-05-09 | アリメラ・サイエンシーズ,インコーポレーテッド | 眼内でのコルチコステロイド使用に伴う眼圧の発生を減少させる方法 |
-
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