Source: https://patents.google.com/patent/CN100341470C/en
Timestamp: 2019-07-20 11:39:32
Document Index: 749221093

Matched Legal Cases: ['art 15', 'art 62', 'art 62', 'art 62', 'art 87', 'art 62', 'art 62', 'art 62', 'art 62', 'art 15', 'art 17', 'art 15']

CN100341470C - Ophthalmic drug delivery device - Google Patents
Ophthalmic drug delivery device Download PDF
CN100341470C
CN100341470C CN 00813192 CN00813192A CN100341470C CN 100341470 C CN100341470 C CN 100341470C CN 00813192 CN00813192 CN 00813192 CN 00813192 A CN00813192 A CN 00813192A CN 100341470 C CN100341470 C CN 100341470C
CN 00813192
CN1376042A (en
约瑟夫·雅各比
爱尔康公司
2000-10-12 Application filed by 爱尔康公司 filed Critical 爱尔康公司
2002-10-23 Publication of CN1376042A publication Critical patent/CN1376042A/en
2007-10-10 Application granted granted Critical
2007-10-10 Publication of CN100341470C publication Critical patent/CN100341470C/en
本发明涉及一种用于人眼的药物释放装置。 The present invention relates to a human eye means for releasing medicament. 人眼有一个巩膜、多块眼外肌，其中包括一块下斜肌和一个黄斑。 The human eye has a sclera, a plurality of extraocular muscles, including an inferior oblique muscle, and a macula. 本发明的该装置包括一种药物活性药剂，和一个具有一种几何形状的基体，该几何形状便于将该装置植入到巩膜的一个外表面上，在该下斜肌以下，并且将药物活性药剂配置到黄斑之上，并且不需要断开或切开所述多块眼外肌中的任何一块。 The device of the invention comprises a pharmaceutically active agent, and a base body having a geometric shape, the geometry of the device to facilitate implantation of one outer surface of the sclera, the inferior oblique muscle in the following, and the pharmaceutically active agent disposed above the macula, and does not require any opening or cutting a plurality of the outer muscles of the eye.
眼药释放装置 Ophthalmic release device
本申请要求系列号为60/160,673、申请日为1999年十月二十一日、名称为“药物释放装置”的美国临时申请的权益，该临时申请已包括在本说明书中。 This application claims the series No. 60 / 160,673, filed October 21, 1999, the benefit of US Provisional Application name of "drug delivery device", the provisional application has been included in this description.
本发明一般涉及用于局部释放药物活性药剂到机体组织中有生物适应性的植入物。 The present invention relates generally to topical release pharmaceutical active agents to body tissue in the biocompatible implant. 更具体但不构成限制的是，本发明涉及用于局部释放药物活性药剂到眼后部有生物适应性的植入物。 More particularly, but not limit, the present invention relates to a pharmaceutically active agent for local delivery to the back of the eye with a biocompatible implant.
眼后部的几种疾病威胁着视力。 Several diseases back of the eye threaten vision. 与年龄相关的黄斑变性(ARMD)、脉络膜新血管形成(CNV)、视网膜病变(如糖尿病性视网膜病变、玻璃体视网膜病变)、视网膜炎(如巨细胞病毒性视网膜炎(CMV))、眼色素层炎、黄斑水肿、青光眼和神经病变是这些疾病的几个例子。 Age-related macular degeneration (of ARMD), choroidal neovascularization (the CNV), retinopathies (e.g., diabetic retinopathy, vitreoretinopathy), retinitis (e.g., cytomegalovirus retinitis (the CMV)), uveitis inflammation, macular edema, glaucoma, and neuropathies are several examples of these diseases.
与年龄相关的黄斑变性(ARMD)是导致老年性视觉缺失的首要原因。 Age-related macular degeneration (ARMD) is the leading cause of visual loss in the elderly. ARMD攻击视觉中心并使其模糊，使得阅读、驾驶和其它细致的工作变得困难或不可能完成。 ARMD attacks the center of vision and make it vague, making reading, driving, and other detailed work difficult or impossible. 单就美国来说每年就有约200,000新的ARMD病例发生。 On the United States alone each year about 200,000 new cases of ARMD occur. 最近的估计显示超过75岁的人群中大约有百分之四十、超过60岁的人群中大约有百分之二十在某些程度上患了黄斑变性。 Recent estimates show that more than 75-year-old crowd of about 40 percent over 60 years of a crowd of about twenty percent suffering from macular degeneration to some extent. “湿”的ARMD是最常见的产生视觉缺失的ARMD类型。 "Wet" ARMD ARMD is the most common type of produce visual missing. 在湿ARMD中，新形成的脉络膜血管(脉络膜新血管形成(CNV))渗出液体并且导致视网膜的损害逐渐加重。 In wet ARMD, newly formed choroidal blood vessels (choroidal neovascularization (the CNV)) leak fluid and cause damage to the retina gradually increased.
对于ARMD中的特殊病例CNV，目前有三种治疗方法，(a)光焊接(b)使用血管生成抑制剂(c)光动力治疗。 For the special cases of ARMD CNV, there are three methods of treatment, (a) photo solder (b) the use of angiogenesis inhibitors (c) photodynamic therapy. 光焊接是治疗CNV的最普通的方法。 Light welding is the most common method of treating CNV. 然而，当CNV靠近中央凹时，光焊接会损伤视网膜，因而是不可行的。 However, when close to the central recess CNV, retinal light damage will be welded, and therefore is not feasible. 另外，在超过一定时间后，光焊接常常导致CNV复发。 Further, after a certain amount of time, often leading to CNV recurrence of light welding. 将抗血管形成的化合物以口服或胃肠外(非眼部)的给药作为一种对ARMD的系统治疗也在进行试验。 Anti-angiogenic compounds to be administered orally or parenterally (non-ocular) as a system for the treatment of ARMD is also tested. 然而，由于药物特有的代谢限制，系统给药常常给眼睛提供的是达不到治疗效果的药物浓度。 However, since the drug-specific metabolic restrictions, systemic administration usually provides the eye to reach the therapeutic effect of drug concentration. 因此，为了使眼内达到有效的药物浓度，需要或者采用不可接受的高剂量或采用重复的传统剂量。 Therefore, to achieve effective intraocular drug concentrations, employed as needed or unacceptably high dose or repetitive conventional doses employed. 在眼周注射这些化合物通常导致药物迅速冲出，并且经眼周脉管系统和软组织滴流到总循环系统中。 These compounds generally lead to drug periocular injection out quickly, ocular and peripheral vasculature and soft tissue trickle overall circulation system. 重复进行眼周注射可能会导致严重的、通常是致盲的并发症，比如视网膜脱落和眼内炎。 Repeated periocular injections may result in severe, often blinding complications, such as retinal detachment and endophthalmitis. 光动力治疗是一种新技术，其长期效果仍然在很大程度上不为人所知。 Photodynamic therapy is a new technology, its long-term effects are still largely unknown.
为了防止与上述治疗相关的并发症，并且提供更好的眼科治疗，研究人员已经建议采用各种植入物，旨在对眼睛局部地释放抗血管生成化合物。 In order to prevent complications related to the above treatments and to provide better eye treatment, researchers have suggested various implants aimed at eyes release anti-angiogenic compounds locally. 授予Wong的美国专利第5,824,072号提示了一个不可生物降解的聚合物植入物，在该植入物中配置了药物活性药剂。 U.S. Patent No. 5,824,072 to Wong suggesting a non-biodegradable polymeric implant, the pharmaceutically active agent disposed in the implant. 该药物活性药剂通过植入物的聚合物基体扩散到目标组织。 The diffusion of the pharmaceutically active agent to the target tissue through the polymeric matrix implant. 该药物活性药剂包括治疗黄斑变性和糖尿病性视网膜病变的药物。 The pharmaceutically active agent comprises a pharmaceutical treatment of macular degeneration and diabetic retinopathy. 该植入物基本上被放置在泪液中，在眼睛外表面的无血管区域，并且可以固定在结膜或巩膜中；在巩膜外层或巩膜内层一个无血管的区域之上；基本上在脉络膜空间上一个无血管的区域内，例如在睫状环或一个外科诱导的无血管区域；或者可直接与玻璃体连通。 The implant is placed substantially in the tear fluid, the outer surface of the eye avascular region, and may be secured in the conjunctiva or sclera; sclera on the outer or inner layer of a sclera avascular region; substantially choroid a spatially avascular region, such as in avascular area or a pars plana surgical induced; or in direct communication with the vitreous.
授予Gwon等人的美国专利第5,476,511号揭示了一个放置在眼睛结膜之下的聚合物植入物。 U.S. Patent No. 5,476,511 granted to Gwon et al., Discloses an eye placed under the conjunctiva polymer implant. 该植入物可以用来释放用于治疗ARMD的新血管抑制剂和用于治疗视网膜病变、视网膜炎的药物。 It can be used to release the implant, retinitis medicament for the treatment of ARMD and neovascular inhibitors for the treatment of retinopathy. 药物活性药剂通过植入物的聚合物基体进行扩散。 Pharmaceutically active agent diffuses through the polymeric matrix implant.
授予Ashton等人的美国专利第5,773,019号揭示了不可生物腐蚀的聚合物植入物，该植入物用来释放的某些药物，其中包括血管抑制类固醇和例如用于治疗眼色素层炎的环孢菌素。 Ashton et al., U.S. Patent No. 5,773,019 discloses a non-bioerodable polymer implant, certain drugs used to release the implant, including angiostatic steroids for the treatment such as a ring, and uveitis in cyclosporin. 药物活性药剂也是通过植入物的聚合物基体进行扩散的。 Pharmaceutically active agent is diffused through the polymeric matrix implant.
以上所述的所有植入物都需要进行仔细的设计和加工，以便通过聚合物基体(即基体装置)或聚合物膜片(即储存装置)将药物活性药剂有控制地扩散到需要进行治疗的位置。 All of the above implants require careful design and processing in order by a polymer matrix (i.e., matrix devices) or polymer membrane (i.e., reservoir devices) to the pharmaceutically active agent in a controlled manner the diffusion of the need for treatment position. 药物从这些装置的释放分别依赖于基体或膜片的孔隙率和扩散特性。 Drug release from these devices depends on the porosity and are diffusion characteristics of the matrix or membrane. 必须为每一种用于该装置的药物定制这些参数。 These parameters must be customized for each of the drugs of the apparatus. 结果，这些需求通常增加了这种植入物的复杂性和成本。 Consequently, these requirements generally increase the complexity and cost of such implants.
授予Peyman的美国专利第5,824,073号揭示了在眼内定位的压头。 U.S. Patent No. 5,824,073 granted to Peyman discloses a positioning head in intraocular pressure. 该压头有一个凸出的部分，用来压凹眼睛黄斑区之上的巩膜或对眼睛黄斑区之上的巩膜施加压力。 The ram has a projecting portion for pressing the concave top of the sclera macular area of ​​the eye or applying pressure to the sclera over the macular area of ​​the eye. 该专利申请揭示了，这种压力增加了脉络膜充血和通过视网膜下新血管形成膜的血液流量，这又反过来增加了出血和视网膜下液体的累积。 This patent application discloses, this pressure increase choroidal congestion and blood flow through the film formed subretinal neovascularization, which in turn increases the cumulative bleeding and subretinal fluid.
因此，在有生物适应性的植入物领域需要一种可外科植入的眼药释放装置，该装置可以安全、有效、可控制速率地局部释放各种药物活性药剂。 Thus, in the field of biocompatible implant has a need for a surgically implantable ophthalmic release device, the device is safe, effective, rate may be locally controlled release of various pharmacologically active agents. 植入该装置的外科操作将是安全、简单、迅速的并且可以对门诊病人实施。 Implanting the surgical operating apparatus will be safe, simple, fast and can be implemented for outpatients. 理想地，该装置应该在制造上是方便和经济的。 Ideally, the device should be manufactured in a convenient and economical. 另外，由于它的多功能性，并且可以释放各种药物活性药剂，这种植入物也应该可以用于眼科门诊研究，以便释放为患者产生一种特殊身体状态的药物。 Further, due to its versatility, and can release a variety of pharmaceutically active agents, such an implant should also be used in ophthalmology clinic studies, in order to release the body to produce a special state of the drug for patients. 在需要局部释放药物活性药剂到眼睛后部以抵抗ARMD、CNV、视网膜病变、视网膜炎、眼色素层炎、黄斑水肿、青光眼和神经病变的情况下，尤其需要这种眼药释放装置。 In the case of active agents desired for local release of the drug to the back of the eye to resist ARMD, CNV, retinopathies, retinitis, uveitis, macular edema, glaucoma, and neuropathies, particularly in need of such ophthalmic release means.
本发明的目的在于提供一种用于人眼的药物释放装置，所述眼有一个巩膜、多块眼外肌，其中包含一块下斜肌和一个黄斑，所述装置包括：一种药物活性药剂；和一个具有一个几何形状的基体，该几何形状有利于将所述装置植入到所述巩膜的一个外表面上，在所述下斜肌的下面，并且所述药物活性药剂配置在所述黄斑之上，并且不需要断开或切开所述多块眼外肌中的任何一块。 Object of the present invention is to provide a drug release device of the human eye, said eye having a sclera, a plurality of extraocular muscles, which comprises a lower oblique and a macula, said device comprising: a pharmaceutically active agent ; and the pharmaceutically active agent having a geometric configuration a matrix shape, the geometry facilitates implanting the device into an outer surface of the sclera, below the lower oblique muscle, and in the above the macula, and does not require any opening or cutting a plurality of the outer muscles of the eye.
本发明是关于用于人眼的药物释放装置。 The present invention relates to a drug release device of the human eye. 人眼有一个巩膜、一块下斜肌和一个黄斑。 The human eye has a sclera, an inferior oblique muscle, and a macula. 本发明的装置包括一种药物活性药剂，该装置的几何形状便于将该装置植入到巩膜的外表面上、下斜肌之下，并且将药物活性药剂配置在黄斑之上。 Apparatus of the present invention comprises a pharmaceutically active agent, the geometry of the device to facilitate implantation of the device into the outer surface of the sclera, beneath the inferior oblique muscle, and the pharmaceutically active agent disposed above the macula. 所述装置还包括：一个具有巩膜表面和一条槽的基体，所述巩膜表面用来直接放置到所述巩膜的所述外表面上，所述槽具有一个在所述巩膜上的开口；和一个内核，该内核配置在所述槽中，并且包括所述药物活性药剂。 Said apparatus further comprising: a scleral surface and a substrate having a groove, said scleral surface for placement directly onto the outer surface of the sclera, said groove having a sclera of said opening; and a kernel, which is arranged in the groove, and comprising the pharmaceutically active agent. 由于其独特的几何形状，对于需要局部释放药物活性药剂到眼后部，以便抵抗ARMD、CNV、视网膜病变、视网膜炎、眼色素层炎、黄斑水肿、青光眼和神经病变的情况，这种装置是特别有用的。 Because of its unique geometry, the need for local release of pharmaceutically active agents to the back of the eye, so as to resist ARMD, CNV, retinopathies, retinitis, uveitis, macular edema cases, glaucoma and neuropathy, such a device is particularly useful.
为了更彻底地理解本发明及其更多的目的和优点，在以下参考附图所作的描述中进行了说明，其中：图1显示了人眼的侧剖面图，和一个根据本发明植入到眼后部的眼药释放装置；图2是图1中眼睛沿2-2线的横剖面详图；图3是表示人眼在其位置上的三维示意图；图4显示了部分地移去侧直肌后图3中的眼睛；图5是一个表示人眼的前视图；图6是一个表示人眼的后视图；图7是根据本发明的第一优选实施例的人体右眼眼药释放装置的透视的、从眼眶处看的视图；图8是在图7和图9中所示的、包括一块下斜肌匹配斜面的眼药释放装置的透视、从眼眶处看的视图；图9是图7所示的眼药释放装置的透视、从巩膜处看的视图；图10是用于本发明的眼药释放装置的椭圆形的药核或药片的透视图；图11是用于本发明的眼药释放装置的两个匹配的、半椭圆形药核或药片的透视图 For a more complete understanding of the present invention and further objects and advantages, it is described in the following description with reference to the accompanying drawings, in which: Figure 1 shows a side cross-sectional view of the human eye's view and in accordance with the present invention implanted into a ophthalmic releasing means back of the eye; Fig. 2 is a cross-sectional detail view of one of the eyes along line 2-2; FIG. 3 is a three dimensional schematic view of a human eye in its position representation; FIG. 4 shows a partially removed side FIG rectus eye 3; FIG. 5 is a front view of a human eye; FIG. 6 is a rear view illustrating the human eye; FIG. 7 is a human eye ophthalmic released according to a first preferred embodiment of the present invention perspective, a view from the eyes of the apparatus; FIG. 8 is, comprising a delivery means under fluoroscopy ophthalmic matching oblique ramp, a view from the eyes shown in FIG. 7 and FIG. 9; FIG. 9 is a perspective view of the ophthalmic release means shown in Figure 7, a view from the sclera; FIG. 10 is a perspective view of the drug core or tablet for ophthalmic apparatus of the present invention the release of the oval; FIG. 11 is used in the present ophthalmic invention release the two matching means, a perspective view of a semi-ellipse of the drug core or tablet 图12是图7和图9所示的人体左眼眼药释放装置的透视、从眼眶处看的视图；图13是在图12和图14中所示的、包括一块下斜肌匹配斜面的眼药释放装置的透视、从眼眶处看的视图；图14是图7和图9中所示的人体左眼眼药释放装置的透视、从巩膜处看的视图；图15是在图7和图9中所示的、包括该装置锥形纵向部分的眼药释放装置的透视、从眼眶处看的视图；图16是图7和图9中所示眼药释放装置的缩短型式的透视、从眼眶处看的视图；图17是图16所示的包括一块下斜肌匹配斜面的眼药释放装置的透视、从眼眶处看的视图；图18是根据本发明的第二优选实施例的人体右眼眼药释放装置的透视、从眼眶处看的视图；图19是图18所示的包括一块下斜肌匹配斜面的眼药释放装置的透视、从眼眶处看的视图；图20是本发明的第三优选实施例的人体右眼眼药释放装置的透视、从 12 is a perspective human eye ophthalmic release device shown in FIG. 7 and FIG. 9, a view from the eyes; FIG. 13 is comprising an at FIG. 12 and FIG. 14 matching oblique ramp ophthalmic release device perspective, a view from the eyes; FIG. 14 is a perspective human eye ophthalmic release device shown in FIG. 7 and FIG. 9, a view from the sclera; FIG. 7 and FIG. 15 is a As shown in FIG. 9, the tapered portion of the device includes a longitudinal ophthalmic apparatus releasing perspective view, a view from the eyes; FIG. 16 is a shortened version of the ophthalmic releasing device shown in perspective view in FIGS. 7 and 9, a view from the orbital; FIG. 17 is a one matching the oblique ramp ophthalmic apparatus releasing a perspective view shown in FIG. 16, a view from the eyes; FIG. 18 is a preferred embodiment according to the second embodiment of the present invention. human eye ophthalmic apparatus releasing a perspective, a view from the eyes; FIG. 19 is shown in FIG. 18 comprises a delivery means under fluoroscopy ophthalmic matching oblique ramp, a view from the eyes; FIG. 20 is human eye ophthalmic third preferred embodiment of the present invention the release device is a perspective view, from 眶处看的视图；和图21是图20中所示的包括一块下斜肌匹配斜面的眼药释放装置的透视、从眼眶处看的视图。 A view of the orbital; and FIG. 21 is shown in FIG. 20 comprises a lower inclined surface matching oblique perspective ophthalmic apparatus releasing, at a view from the eyes.
本发明的优选实施例及其优点可以通过参考附图1到图21得到最好的理解，其中相同的标记符号将用在各图中相同的或相对应的部件上。 Preferred embodiments of the present invention and its advantages by reference to Figures 1 to 21 is best understood in which the same reference numerals will be used in the various figures the same or corresponding parts.
图1到图6说明了对于理解本发明很重要的人眼的各部分。 Figures 1 to 6 illustrate various portions of the present invention is very important for an understanding of the human eye. 参见图1，其中示意地显示了人眼90。 Referring to Figure 1, schematically shows the human eye 90. 眼90有一个角膜92、一个晶状体93、玻璃体95、一个巩膜100、一个脉络膜99、一个视网膜97和一个视觉神经96。 Eye 90 has a cornea 92, a lens 93, vitreous 95, a sclera 100, a choroid 99, a retina 97, and an optic nerve 96. 眼90通常被分为前部89和后部88。 Eye 90 is generally divided into a front portion 89 and rear portion 88. 眼90的前部89包括眼90的在锯齿缘11前面的部分。 Eye 90 includes a front portion 89 eye portion 90 of the serrated edge 11 on the front. 眼90的后部88通常包括眼90在锯齿缘11后面的部分。 Back of the eye 90 of the eye 88 generally includes a rear portion 90 of the serrated edge 11. 视网膜97在靠近睫状环13的地方、在视神经乳头盘19的后面、以环绕的方式与脉络膜99实际相连。 97 in close proximity to the retina ciliary ring 13, the back 19 of the optic disc, choroid manner to surround 99 actually connected. 视网膜97有一个位于视神经乳头盘19侧面附近的黄斑98。 A retina 97 positioned near the optic disc 19 side surface 98 of the macula. 在眼科中众所周知，黄斑98主要包括视网膜锥体，并且是视网膜97中视敏度最高的区域。 It is well known in ophthalmology, 98 including macular retinal cones and is the region with the highest visual acuity in the retina 97. 一个眼球筋膜或眼球囊101配置在巩膜100上。 A Tenon's capsule 101 or eye 100 disposed on the sclera. 结膜94盖住了边缘115(球状结膜)后面的眼球90的一个短区域，并且上折(上陷凹)或下折(下陷凹)来分别盖住上眼睑78和下眼睑79的内部区域。 Conjunctiva 94 covers a short area of ​​the edge 115 (spherical conjunctiva) behind the eyeball 90 and upper flap (upper pouch) or folded (lower pouch) respectively cover the upper eyelid 78 and lower eyelid 79 of the interior region. 结膜94配置在眼球筋膜101的顶部。 Conjunctiva 94 disposed at the top of Tenon 101.
如图1和2所示，并且如下面所要详细描述的那样，装置50最好直接配置在巩膜100的外表面上，在眼球筋膜101以下，以便治疗大多数的眼后部疾病。 As shown in FIG. 1 and 2, and as will be described in detail below, device 50 is preferably disposed directly on the outer surface of sclera 100, below Tenon's 101, most of the back of the eye in order to treat the disease. 此外，为了治疗人类的ARMD和CNV，装置50最好直接配置在巩膜100的外表面上，在眼球筋膜101以下，并且使装置50的内核靠近黄斑98。 Further, in order to treat humans and the CNV in ARMD, apparatus 50 is preferably disposed directly on the outer surface of the sclera 100 in the Tenon's 101, and the core 50 proximate macula 98.
图3显示了在其眼眶112中的人体左眼90。 Figure 3 shows in its left eyes 112 of the body 90. 如图3所见，下斜肌107在侧直肌105之下延伸。 Seen in Figure 3, inferior oblique muscle 107 extending beneath the rectus muscle 105 side. 下斜肌107插入巩膜100的插入线107a位于侧直肌105的上边界之上。 The oblique line 107 is inserted into sclera 100 is inserted 107a positioned above the upper boundary side of the rectus muscle 105. 当然，人体右眼90中下斜肌的位置是图3中的人体左眼90的该位置的镜像。 Of course, the inferior oblique muscle in the human eye 90 is a mirror image position of the location in the human eye 90 of FIG. 3. 角膜92、结膜94、上直肌103、下直肌104、上斜肌106和边缘115都显示在图3中。 Cornea 92, the conjunctiva 94, superior rectus muscle 103, inferior rectus muscle 104, superior oblique edges 106 and 115 are shown in FIG.
图4类似地显示了在其眼眶112中的人体左眼90。 FIG. 4 similarly shows in its left eyes 112 of the body 90. 然而，侧直肌105的一部分在图4中没有显示，以便使通常被肌肉隐藏起来的巩膜100和视觉神经96成为可见的。 However, the side portion of the rectus muscle 105 is not shown in FIG. 4, so that the muscles are usually hidden up sclera 100 and optic nerve 96 become visible. 在图4中，下斜肌107插入巩膜100的一条插入线107b比图3中所示的插入线107a低，这显示了在人眼中下斜肌的插入线的典型的生理变化。 In FIG. 4, an inferior oblique muscle 107 is inserted into sclera 100 is lower than insertion line 107b 107a inserted line shown in FIG. 3, which shows a typical oblique physiological changes in the eyes of the interpolated line.
图5示意性地显示了一个人眼90带着其四块直肌的前视图，即上直肌103、中间直肌108、下直肌104和侧直肌105。 FIG 5 schematically shows a human eye 90 with its four rectus front view, i.e., the superior rectus muscle 103, the intermediate 108 rectus, inferior rectus muscle, and lateral rectus 104 105. 图5还显示了在图5中由边界线115表示的边缘，和由图5中的边界线113表示的直肌的插入线。 Figure 5 also shows the edge, and the interpolated line rectus boundary line 113 in FIG. 5 shown in FIG. 5, represented by the boundary line 115.
在图6中示意性地显示了人眼90的后视图。 In FIG. 6 schematically shows a rear view of human eye 90. 图6显示了上直肌103、侧直肌105、下直肌104、中间直肌108、上斜肌106、下斜肌107和其插入线107a、视觉神经96、睫状管109、巩膜100、在黄斑98上面的巩膜区域110、长睫状动脉111和涡状静脉114的位置。 Figure 6 shows the superior rectus muscle 103, the lateral rectus muscle 105, inferior rectus muscle 104, the intermediate rectus muscle 108, the superior oblique muscle 106, the inferior oblique muscle 107 and its insertion line 107a, the optic nerve 96, ciliary tube 109, sclera 100 , in the area of ​​sclera 110 above macula 98, the position of the vortex veins 111 and 114 of the long ciliary artery.
图7和图9示意性地显示了根据本发明第一优选实施例的人体右眼眼药释放装置50。 7 and FIG. 9 schematically shows a human eye ophthalmic a first preferred embodiment of the present invention, the release means 50. 装置50可以用于任何需要将药物活性药剂局部释放到眼中的情况。 Means 50 may be used in any pharmaceutically active agent is released into the local situation in the eyes. 装置50特别适用于需要将药物活性药剂局部释放到眼睛后部的情况。 Device 50 particularly useful for local delivery of pharmaceutically active agents to the case back of the eye. 装置50的一个优选的应用是为了治疗ARMD、视网膜新血管形成(CNV)、视网膜病变、视网膜炎、眼色素层炎、黄斑水肿、青光眼和神经病变而将药物活性药剂释放到视网膜上靠近黄斑的区域中。 One preferred application device 50 is for treatment of ARMD, retinal neovascularization (the CNV), retinopathies, retinitis, uveitis, macular edema, glaucoma and neuropathy pharmaceutically active agent is released into the retina near the macula area.
装置50通常包括基体21，该基体21有一个凸的、圆顶形的眼眶表面12和一个凹的、圆顶形的巩膜表面14。 Apparatus 50 generally includes a base 21, the base 21 has a convex dome shaped orbital surface 12 and a concave, dome-shaped scleral surface 14. 所设计的巩膜表面14的曲率半径便于它与巩膜100直接接触。 The radius of curvature of the scleral surface 14 is designed to facilitate it in direct contact with sclera 100. 更好是使巩膜表面14的曲率半径等于平常人眼90的曲率半径91。 More preferably scleral surface 14 of radius of curvature equal to the radius of curvature of 90 normal human eye 91. (见图1)眼眶表面12最好被设计成具有便于植入眼球筋膜101以下的曲率半径。 (See FIG. 1) Orbital surface 12 is preferably designed with a radius of curvature to facilitate implantation below the Tenon 101. 当从上面看时，基体21最好有一个大概为“F-形”的几何形状，其中有纵向部分15、横向部分18和其间的弯曲部分32。 When viewed from above, the substrate 21 preferably has an approximately "F- shaped" geometry with a longitudinal part 15 in which the curved portion 18 and lateral portions 32 therebetween. 纵向部分15和横向部分18最好在弯曲部分32处相连，以形成一个约为九十度的角度。 Longitudinal portion 15 and transverse portion 18 is preferably connected to the curved portion 32, to form an angle of approximately ninety degrees. 纵向部分15有一个近端25、一个圆形边缘24、一个止动部分36和一个缺口42。 Longitudinal portion 15 has a proximal end 25, a rounded edge 24, a stopper portion 36 and a notch 42. 正如以下将要详细描述的那样，缺口42被设计用来容纳下斜肌107的起始端部。 As will be described in detail above, the notch 42 is designed to receive the lower portion of the starting end 107 of oblique. 止动部分36确定了缺口42的下部并且最好比通常是凸起的眼眶表面12的其余部分稍微升高一些。 Stopper portion 36 determines the lower apertures 42 and the remainder portion 12 is preferably slightly higher than that of the generally convex orbital surface number. 如下面将要详细所述的那样，止动部分36通过与下斜肌107的前边界相接触，防止装置50向视觉神经96过分前移。 As will be described in detail above, the stopper portion 36 by contacting with the front oblique lower boundary 107, over-preventing means 5096 is advanced to the optic nerve. 横向部分18有一个远端58、一个圆形边缘28和一个在巩膜表面14上有开口64的槽或空腔20。 Transverse portion 18 has a distal end 58, a rounded edge 28 and a scleral surface 14 on the opening 64 of the groove or cavity 20. 槽20和开口64最好为椭圆形。 Groove 20 and the opening 64 is preferably elliptical. 如下将要详细说明的那样，横向部分18可以使空腔20直接放置在巩膜100上的与黄斑98重叠的区域。 As will be described in detail above, the transverse portion 18 of the cavity 20 can be placed directly on the sclera 100 macular region 98 overlap.
在图10中所示的内核81最好布置在槽20中。 81 shown in FIG. 10 in the core is preferably disposed in the groove 20. 如图10所示，内核81最好是一个包括一种或多种药物活性药剂的药片。 As shown, the core 81 preferably comprises one or more pharmaceutically active agents in the tablet 10. 药片81最好具有椭圆形的基体46，该基体46具有凹的、圆顶形的巩膜表面85和凸的、圆顶形的眼眶表面86。 Yl tablet 81 preferably has an oval body 46, 46 has a concave, dome-shaped scleral surface 85 of the base and a convex, dome-shaped orbital surface 86. 基体46上还最好配置一个周边的斜角87。 46 is also preferably arranged on a peripheral bevel 87 of the base body. 另外，如图11所示，内核也可以包括匹配的、半椭圆形的药片82a和82b。 Further, as shown, the core 11 may include a mating, semi-oval tablets 82a and 82b. 药片82a最好有与药片81的基体46的一半相同的基体47。 Tablet 82a preferably has the same half of the base 46 of the base 81 of the tablet 47. 药片82b最好有与药片81的基体46的另一半相同的基体48。 Another tablet 82b preferably has a base 81 of the tablet 46 of the base 48 of the same half. 另外，内核81或内核82a和82b也可以包括一种传统的水凝胶、胶、膏或其它半固体帛剂，在该制剂中有一种或多种药物活性药剂。 Further, the core 81 or the core 82a and 82b may also comprise a conventional hydrogel, gel, paste, or other semi-solid agent silk, with one or more pharmaceutically active agents in the formulation.
回到图9，保持零件62最好配置在开口64的附近。 Referring back to FIG. 9, the holding part 62 is preferably arranged in the vicinity of the opening 64. 保持零件62防止内核81掉出槽20。 Holding part 62 to prevent the core 81 from falling out of the groove 20. 当内核81是一个药片时，保持零件62最好是一个配置在开口64周边的连续的框或凸缘，该零件设计用来容纳药片81的斜边87。 When the core 81 is a tablet, a holding part 62 is preferably arranged in the periphery of the opening 64 or a continuous flange block, the oblique part 87 designed to accommodate the tablets 81. 另外，保持零件62还可以包括一个或多个从基体21延伸到开口64中的零件。 The holding part 62 may further comprise one or more from the base body 21 extends into an opening 64 in the part.
虽然在图9和11中没有显示出，但内核81也可以包括一种悬浊液、溶液、粉末或其组合，其中包含了药物活性药剂。 Although not shown in FIGS. 9 and 11, but the core 81 may also include one suspension, solution, powder, or combination thereof, which comprises a pharmaceutically active agent. 在本实施例中，巩膜表面14上没有开口64，而悬浊液、溶液、粉末或其组合通过在内核81以下的相对薄的巩膜表面14或其它膜扩散。 In this embodiment, no openings 14 on the surface of the sclera 64, and the suspension, solution, powder, or a combination of the core 81 in the relatively thin scleral surface 14 or other membrane diffusion. 另外，装置50还可以不带槽20或内核81，而以悬浊液、溶液、粉末或其组合形式存在的药物活性药剂散布在装置50的整个基体21中。 Further, apparatus 50 also may not be slotted core 20 or 81, and to the suspension, the pharmaceutically active agent present solution, a powder or a combination of dispersed throughout the base body 21 of apparatus 50. 在此实施例中，药物活性药剂通过基体21扩散到目标组织中。 Embodiment, the pharmaceutically active agent diffuses into the target tissue through the matrix 21 in this embodiment.
装置50的几何形状和尺寸最大限度地连通了内核81中的药物活性药剂和在巩膜表面14以下的目标组织。 Geometry and dimensions of device 50 maximize communication with the pharmaceutically active agent in the core 81 and the target tissue 14 of the sclera surface. 巩膜表面14最好实际上接触到巩膜100的外表面。 Scleral surface 14 is preferably actually in contact with the outer surface of sclera 100. 另外，巩膜表面14也可以靠近巩膜100的外表面。 Further, scleral surface 14 may be close to the outer surface of the sclera 100. 例如，装置50可以配置在正好在巩膜100外表面之上的眼周组织中，或者在巩膜100中的薄层内。 For example, device 50 may be disposed at the eye tissue just above the outer surface of sclera 100, a thin layer or in the sclera 100.
基体21包括一种有生物适应性的、不可生物腐蚀的材料。 21 comprises a kind of matrix biocompatible, non-bioerodible material. 基体21最好包括一种有生物适应性的、不可生物腐蚀聚合物组合物。 Preferably comprises a base 21 with a biocompatible, non-bioerodable polymeric composition. 所述聚合物组合物可以是一种均聚物、一种直链、支链、交连的共聚物或一种混合物。 The polymer composition may be a homopolymer of a linear, branched, cross-linked copolymer or a mixture. 适合用于所述聚合物组合物的聚合物例子包括硅氧烷、聚乙烯醇、乙烯醋酸乙烯酯、聚乳酸、尼龙、聚丙烯、聚碳酸酯、纤维素、醋酸纤维素、聚乙二醇酸、聚乳-乙二醇酸、纤维素酯、聚醚砜、丙烯酸树脂(acrylics)、上述聚合物的衍生物及其组合。 Examples of polymers suitable for use in said polymeric composition include silicone, polyvinyl alcohol, ethylene vinyl acetate, polylactic acid, nylon, polypropylene, polycarbonate, cellulose, cellulose acetate, polyethylene glycol acid, polylactic - glycolic acid, cellulose esters, polyethersulfone, acrylics (acrylics), derivatives of the above polymers, and combinations thereof. 适合的软丙烯的例子在美国专利第5,403,901中有更全面的揭示，该专利已整个包括在本文中。 Examples of suitable soft propylene is more fully disclosed in U.S. Patent No. 5,403,901, which patent is included herein throughout. 所述聚合物组合物最好包括硅氧烷。 The composition preferably comprises a silicone polymer. 当然，所述聚合物组合物还可以包括影响其物理性质的传统材料，其中所述物理性质不构成限制地包括孔隙率、弯曲度、渗透性、刚性、硬度和光滑性。 Of course, said polymeric composition further may comprise conventional materials that affect the physical properties wherein the physical properties do not constitute a limitation, porosity, tortuosity, permeability, rigidity, hardness, and smoothness. 影响这些性质中的其中之一的材料的例子包括传统的可塑剂、填料和润滑剂。 Examples of the material of one of the impact of these properties include conventional plasticizers, fillers, and lubricants. 所述聚合物组合物可以包括其它影响其化学性质的材料，其中的化学性质不构成限制地包括毒性、疏水性和基体21-内核81的相互作用。 The polymer composition may include other materials affect its chemical properties, chemical properties which do not constitute a limitation, the core 81 interacts 21 toxicity, hydrophobicity, and substrate. 基体21最好对于内核81中的药物活性药剂来说是不可渗透的。 For the core base 21 is preferably a pharmaceutical active agent 81 is impermeable. 当基体21由一般的弹性的聚合物组合物制成时，可以使槽20的形状稍微小于内核81的形状。 When the substrate 21 is made of a generally elastic polymeric composition, the shape of the groove 20 is slightly smaller than the shape of the core 81. 这种磨擦配合将内核81固定在槽20中。 Such friction with the fixed core 81 in the groove 20. 在此实施例中，如果要求的话，基体21可以带有或不带保持零件62，内核81可以带有或不带斜边87。 In this embodiment, if desired, the substrate 21 may be with or without a holding part 62, the core 81 may be provided with or without the beveled edge 87.
内核81可以包括任何眼部可接受的药物活性药剂，以便进行局部释放。 Core 81 may comprise any ophthalmically acceptable pharmaceutically active agents, and for local delivery. 适合于内核81的药物活性药剂的例子是抗感染药，不构成限制地包括抗生素、抗病毒药、抗真菌药、抗过敏原的药和乳突细胞稳定剂；类固醇和非类固醇的抗炎药；环氧合酶抑制剂，不构成限制地包括Cox I和Cox II抑制剂；抗感染药和抗炎药的组合；抗青光眼药，不构成限制地包括肾上腺素能剂、β-肾上腺素能阻滞剂、α-肾上腺素能促效药、拟副交感剂、胆碱酯酶抑制剂、碳酸酐酶抑制剂和前列腺素；抗青光眼药的组合；抗氧化剂；营养供给剂；用于治疗囊样黄斑水肿的药物不构成限制地包括非类固醇抗炎药；用于治疗ARMD的药物不构成限制地包括血管生成抑制剂和营养供给剂；用于治疗疱疹感染和CMV眼部感染的药物；用于治疗增生性玻璃体视网膜病变的药物不构成限制地包括抗代谢剂和溶解纤维蛋白；创伤调节药物不构成限制地包括生长素；抗代谢 Examples of pharmaceutically active agents suitable for the core 81 are anti-infectives, does not constitute a limitation, antibiotics, antivirals, antifungals, allergens, drugs and mast cell stabilizers; steroidal and non-steroidal anti-inflammatory drugs ; cyclooxygenase inhibitors, do not constitute a limitation, Cox I and Cox II inhibitors; combinations of anti-infectives and anti-inflammatory agents; anti-glaucoma drugs, do not constitute a limitation, adrenergic agents, adrenergic [beta] blockers, alpha] adrenergic agonists, intended parasympathetic agents, cholinesterase inhibitors, carbonic anhydrase inhibitors, and prostaglandins; combinations of anti-glaucoma agents; antioxidants; nutrient supplying agent; for the treatment of bladder macular edema drugs do not constitute a limitation, non-steroidal anti-inflammatory drugs; drugs for treating ARMD does not constitute a limitation, angiogenesis inhibitors and nutritional supplying agent; medicament for the treatment of herpes infections and CMV ocular infections; with medicament for the treatment of proliferative vitreoretinopathy does not constitute a limitation, antimetabolites and fibrinolytic; wound modulating agent does not constitute a limitation, auxin; antimetabolites ；神经保护药物不构成限制地包括eliprodil；和用于治疗眼后部疾病的血管抑制类固醇，这些眼后部疾病不构成限制地包括ARMD、CNV、视网膜病变、视网膜炎、眼色素层炎、黄斑水肿和青光眼。 ; Neuroprotective drugs do not constitute a limitation, eliprodil; and angiostatic steroids for the treatment of diseases back of the eye, back of the eye diseases which do not constitute a limitation, ARMD, CNV, retinopathies, retinitis, uveitis, macular edema and glaucoma. 这种血管抑制类固醇更完全地揭示于美国专利第5,679,666和第5,770,592号中，这些专利均已完全包括在本文中。 Such angiostatic steroids disclosed more fully in U.S. Patent Nos. 5,679,666 and 5,770,592, these patents are fully included herein. 这种血管抑制类固醇的较优的种类包括4，9(11)-孕双烯-17α，21-二醇-3，20--二酮(4，9(11)-Pregnadien-17α，21-diol-3，20-dione)和4，9(11)-孕双烯-17α，21-二醇-3，20-二酮-21醋酸酯(4，9(11)-Pregnadien-17α，21-diol-3，20-dione-21-acetate)。 This kind of superior angiostatic steroids include 4,9 (11) - diene pregnant -17α, 21- diol -3,20-- dione (4,9 (11) -Pregnadien-17α, 21- diol-3,20-dione) and 4,9 (11) - diene pregnant -17α, 21- diol-3,20-dione acetate -21 (4,9 (11) -Pregnadien-17α, 21 -diol-3,20-dione-21-acetate). 一种优选的用于治疗囊样黄斑水肿的非类固醇抗炎剂是nepafenac。 A preferred for the treatment of cystoid macular edema is a non-steroidal antiinflammatory agents nepafenac. 内核81还可以包括传统的非活性的赋形剂以加强活性药剂或药核的稳定性、溶解性、渗透性或其它特性。 Core 81 may also include conventional inactive excipients to enhance active agent or the drug core stability, solubility, permeability or other properties.
如果内核81是一个药片，它还可以包括传统的制药片需要用的赋形剂，如填料和润滑剂。 If the core 81 is a tablet, it may include a conventional tabletting excipients needed, such as fillers and lubricants. 这种药片可以用传统的制药片方法来生产。 This kind of tablet can be used conventional methods for producing pharmaceutical tablets. 药物活性药剂最好均匀地分布在整个药片中。 Pharmaceutically active agent is preferably distributed evenly throughout the tablet. 除了传统的药片之外，内核81还可以包括一种以控制的速率被生物腐蚀的特殊药片，来释放药物活性药剂。 In addition to conventional tablets, the core 81 may further comprise a special tablet kind of rate control biological corrosion, to release the pharmaceutically active agent. 例如，这种生物腐蚀可通过水解或酶分裂产生。 For example, such bioerosion may be produced by hydrolysis or enzymatic cleavage. 如果内核81是一种水凝胶或其它的胶，这种胶会以控制的速率进行生物腐蚀，并且释放出药物活性药剂。 If the core 81 is a hydrogel or other glue, this glue may be bioerodible at a controlled rate, and release of the pharmaceutically active agent. 另外，这种胶还可以是非生物腐蚀的，但可以扩散药物活性药剂。 Further, this glue may also be non-bioerodible, the pharmaceutically active agent can diffuse.
装置50可以采用传统的聚合物生产方法来制造，这些方法不构成限制地包括注射模塑、压挤模塑、传递模塑和压塑。 Apparatus 50 may be employed conventional production methods for producing polymers, these methods do not constitute a limitation, injection molding, pressing molding, transfer molding and compression molding. 最好，装置50采用传统的注射模塑技术形成。 Preferably, the apparatus 50 using conventional injection molding techniques. 内核81最好在装置50的基体21形成之后配置到槽20中。 The core matrix 81 is preferably arranged in the apparatus 50 into the groove 20 after the formation 21. 保持零件62最好具有足够的弹性，以便让内核81的斜边87插入开口64中并且随后恢复到其原来位置。 Holding part 62 preferably has sufficient elasticity, so that the oblique side 87 of the core 81 inserted into the opening 64 and then return to its original position.
装置50最好通过手术直接放置到巩膜100的外表面上，在眼球筋膜101之下，并且使槽20和内核81直接处于黄斑98之上的巩膜100的区域上，其所采用的是以下优选的可用于门诊病人的技术。 Means 50 is preferably surgically placed directly on the outer surface of sclera 100, below Tenon's 101, and the groove 20 and the core 81 directly in the area of ​​sclera 100 above macula 98, which is equipped with the following preferred techniques for outpatient. 外科医生首先在眼90的一个四分体上进行一个8毫米的球结膜环状切开术。 The surgeon first performed on a 8 mm in a quadrant of the eye 90 of the annular conjunctival incision. 最好，外科医生在颞下的四分体上、在眼90的边缘115之后3毫米处进行这种球结膜环状切开术。 Preferably, the surgeon on the temporal quadrant, for such cyclic conjunctival incision 90 after edge 115 mm 3. 一旦形成切口，外科医生就进行一个钝器解剖术以便将眼球筋膜101从巩膜100上分离。 Once the incision, the surgeon proceeds to a blunt dissection to separate Tenon's operation from the sclera 101 100. 采用剪刀或钝器解剖术，在巩膜100的外表面在下斜肌107以下处，最好是顺着侧直肌105的下边缘，在前后方向上形成一个通道。 Using scissors or a blunt dissection technique, the outer surface of the sclera 100 at the lower oblique muscle 107, preferably along the lower edge of the lateral rectus muscle 105, a channel is formed in the longitudinal direction. 然后让下斜肌107与Jamison肌肉钩结合。 Then let the inferior oblique muscle 107 in conjunction with Jamison hook. 然后将该肌肉钩端前移到下斜肌的后面以形成将容纳装置50的横向部分18的通道的一部分。 The front end of the hook is then moved to the next muscle behind the oblique portion of the channel to form a transverse portion 18 of the receiving apparatus 50 will. 一旦该通道形成，外科医生使用Nuggett钳来夹持装置50的横向部分18，使巩膜表面14对着巩膜100，而横向部分18的远端58远离外科医生。 Once the channel is formed, the surgeon uses forceps to Nuggett clamping means 18 transverse portion 50, scleral surface 14 facing sclera 100 and distal end 58 away from the lateral portions 18 of the surgeon. 然后外科医生将把远端58放在前面，在球结膜环状切开术所在层面内将装置50导入该通道。 The surgeon will then be placed in front of the distal end 58, an annular incision in the conjunctiva of the device 50 where the operation level is introduced into the channel. 一旦进入通道，外科医生顺着该通道向着下斜肌107前移装置50，直到止动部分36接触到下斜肌107的前边界。 Once in the channel, the surgeon along the channel 107 toward the oblique advancement device 50, until the stop portion 36 contacts the front border 107 of the inferior oblique muscle. 在可见的下斜肌107的层面内，外科医生在肌肉107以下转动装置50，这样装置50的横向部分18进入到通道正好在下斜肌107之后的部分。 In the level 107 at oblique visible, the surgeon rotates the device 107 in the muscle 50, such device 50 into the transverse portion 18 of the channel portion 107 after the lower right oblique. 当外科医生感到弯曲部分32不能再向前移时，外科医生就在前后方向上稍微移动装置50，以便让下斜肌107容纳于在横向部分18和止动部分36之间的缺口42中。 When the surgeon can no longer feel forward curved portion 32, the surgeon slightly moves in the longitudinal direction of the apparatus 50, so that the oblique cutout 107 accommodated between the lateral portions 18 and 36 of the stopper portion 42. 由于缺口42和槽20的位置靠近横向部分18的远端58，内核81被放置在巩膜100上直接处于黄斑98之上的区域。 Since the position of the notch 42 and the groove 20 near the distal end portion 18 of the lateral 58, the core 81 is placed directly on the sclera 100 above macula 98 in a region. 然后将纵向部分15的近端25缝合到巩膜100上。 The proximal end of longitudinal portion 15 is then sewn to the sclera 25 of 100. 外科医生然后通过将眼球筋膜101和结膜94缝合到巩膜100上来关闭球结膜环状切口。 The surgeon then 101 Tenon's and conjunctiva 94 to sclera 100 by stitching up closed annular conjunctival incision. 关闭之后，外科医生将一个抗生素软膏条放置到外科创口上。 After closing, the surgeon will place a bar antibiotic ointment on the surgical wound. 所有的缝合最好采用7-0Vicryl缝合。 All stapling suturing 7-0Vicryl preferably used. 对于治疗ARMD和CNV来说，内核81中的药物活性药剂最好是美国专利第5,679,666号和第5,770,592号中所揭示的血管抑制类固醇中的一种。 For the treatment of ARMD and CNV, the pharmaceutically active agent in the core 81 is preferably a U.S. Patent Nos. 5,679,666 and No. 5,770,592 disclosed the angiostatic steroids.
装置50的基体21的几何形状包括巩膜表面14的凹陷特性；横向部分18、槽20、开口64、内核81和保持零件62的形状和位置；以及缺口42和止动部分36的形状和位置，都是有利于从内核81中通过巩膜100、脉络膜99到视网膜97中特别是黄斑98中释放有药效剂量的药物活性药剂。 The geometry of the device body 50 of the 21 include recessed characteristic scleral surface 14; transverse portion 18, slot 20, opening 64, the core 81 and maintain the shape and the position of the part 62; and a notch 42 and a stopper shape and location of portion 36, are conducive to the core 81 through sclera 100, choroid 99 into retina 97, macula 98 in particular release pharmaceutical active agents have efficacy dose. 在槽20和巩膜100之间不设聚合物层或膜，将大大有利于加强和简化将一种活性药剂向视网膜97的释放。 No polymer layer or membrane between the sclera 20 and the groove 100, will contribute greatly to simplify and strengthen the release of an active agent to retina 97.
据信，根据所采用的药物活性药剂的具体物理化学特性，装置50可以用来长年向视网膜97释放有药效剂量的药物活性药剂。 It is believed that, depending on the particular physicochemical properties of the pharmaceutically active agent employed, the apparatus 50 may be used with a long release pharmaceutical active agents to the retina 97 dose efficacy. 植入物的物理化学特性包括疏水性、溶解性、溶解速率、扩散系数、分配系数和组织亲和性。 Physicochemical properties of the implant include hydrophobicity, solubility, dissolution rate, diffusion coefficient, partition coefficient, and tissue affinity. 在内核20不再含有活性药剂后，外科医生可以很容易地将装置50移走。 After the core 20 no longer contains active agent, a surgeon may easily remove the device 50. 另外，“以前形成”的通道便于用一个新装置50来替换旧的装置50。 Further channel, "previously formed" facilitating means 50 with a new device 50 to replace the old.
图8显示了一个眼药释放装置60，它对眼药释放装置50稍微作了一些改进，这些改进有利于一些本发明的植入。 Figure 8 shows a release device 60 eyedrops, ophthalmic its release means 50 is slightly made some improvements have a number of beneficial implant of the present invention. 如图8所示，装置60与图7和图9中所示的装置50的几何形状基本相似，其不同之处在于在基体21的眼眶表面12上靠近缺口42的地方增加了一个斜坡45。 As shown, the geometry of the device 50 shown in FIGS. 7 and 60 of FIG. 9 is substantially similar to 8, except that in place close to the base body 42 is increased a notch 45 on the ramp 12 orbital surface 21. 斜坡45是一个倾斜表面，该倾斜表面最好从其第一端的巩膜表面14处延伸到第二端的眼眶表面12处。 45 is an inclined ramp surface, preferably extending from the first end of scleral surface 14 to the surface of the eyes at the second end 12 of the inclined surface. 另外，斜坡45还可以从其第一端的纵向部分15的圆形边缘24处延伸到其第二端的眼眶表面12处。 Further, the ramp 45 may also extend from the circular edge of the first end 15 of longitudinal portion 24 to the second end of the orbital surface 12 thereof. 如上所述，当装置60被植入眼90中时，斜坡45有利于在缺口42中容纳下斜肌107，其中缺口42中处在横向部分18和止动部分36之间。 As described above, when the device 60 is implanted in the eye 90, 45 facilitate oblique ramp 107 is accommodated in the notch 42, wherein between the lateral portions 18 and the stopper portion 36 in the notch 42. 装置60可以采用与装置50基本类似的技术来制造。 60 may be employed with the apparatus 50 is substantially similar techniques.
图12和14示意性地显示了用于人体左眼的眼药释放装置70。 12 and FIG. 14 schematically shows a human eye for ophthalmic release means 70. 装置70的几何形状是用于人体右眼的根据图7和9所述的装置50的几何形状的镜像。 The geometry of the device 70 is a mirror image of the right geometry for the body of the apparatus 79 and 50 according to FIG. 装置70的应用基本上与装置50的应用相同，装置70可以采用与装置50基本类似的技术来制造。 Application of the device 70 is substantially the same application device 50, the device 70 may be employed with the apparatus 50 is substantially similar techniques.
图13显示的是一个用于人体左眼的眼药释放装置75，其中对眼药释放装置70稍微作了一些改进，这些改进有利于一些本发明的植入。 Figure 13 shows a human eye for ophthalmic release means 75, in which the release means 70 is slightly ophthalmic made some improvements have a number of beneficial implant of the present invention. 图13的装置75的几何形状与图8中的装置60的几何形状基本类似，不同之处在于装置75是装置60的镜像。 The geometry of device 75 of FIG. 13 of the device 60 of FIG. 8 geometry substantially similar, except that the device 75 is a mirror image of device 60.
图15显示了一个眼药释放装置30，它对眼药释放装置50稍微作了一些改进，这些改进有利于一些本发明的植入。 Figure 15 shows an ophthalmic release means 30, release means 50 it is slightly ophthalmic made some improvements have a number of beneficial implant of the present invention. 如图15所示，装置30与图7和图9中所示的装置50的几何形状基本相似，其不同之处在于当从边缘24处看时，纵向部分15有逐渐变小的厚度，该逐渐变小厚度的部分开始于位置33处并且延续到近端25处。 As shown, the geometry of the device 50 shown in FIGS. 7 and the device 30 is substantially similar to FIG. 9, 15, except that when seen from the edge 24, the longitudinal portion 15 has a tapered thickness, the It becomes gradually smaller thickness portion beginning at a position at the proximal end 33 and continues to 25. 纵向部分15的该部分配置在眼的前部并且可以被其它人看见。 The portion of the longitudinal portion 15 disposed in the front portion of the eye and others may be seen. 因此，由于这种逐渐变小的厚度，装置30可能变得更舒服，并且在美容方便更容易让患者接受。 Thus, due to this tapered thickness, device 30 may be more comfortable, convenient and easier for cosmetic patients. 装置30的应用基本上与装置50的应用相同，装置30可以采用与装置50基本类似的技术来制造。 Application of the device 30 is substantially the same application device 50, the device 30 may be employed with the apparatus 50 is substantially similar techniques.
图16显示了一个眼药释放装置40，它对眼药释放装置50稍微作了一些改进，这些改进有利于一些本发明的植入。 Figure 16 shows some ophthalmic implant of the present invention, a release means 40, release means 50 it is slightly ophthalmic made some improvements have beneficial. 如图16所示，装置40与图7和图9中所示的装置50的几何形状基本相似，其不同之处在于装置40的纵向部分15的长度相对于装置50来说被缩短了。 16, the geometry of the device 50 shown in FIGS. 7 and 40 of the device 9 is substantially similar, except that the length of its longitudinal portion 15 of the device 40 with respect to the apparatus 50 is to be shortened. 与装置30类似，这种纵向部分15的缩短，使得装置40变得更舒服，并且在美容方便更容易让患者接受。 Similar to the device 30, this shortening of longitudinal part 15, 40 so that the device becomes more comfortable, convenient and easier for cosmetic patients. 装置40的应用基本上与装置50的应用相同，装置40可以采用与装置50基本类似的技术来制造。 Application of device 40 is substantially the same application device 50, the device 40 may be employed with the apparatus 50 is substantially similar techniques.
图17显示了一个眼药释放装置80，它对眼药释放装置40稍微作了一些改进，这些改进有利于一些本发明的植入。 Figure 17 shows some ophthalmic implant of the present invention, a release means 80, release means 40 it ophthalmic made some slight improvements have beneficial. 如图17所示，装置80与图16中所示的装置40的几何形状基本相似，其不同之处在于在基体21的眼眶表面12上靠近缺口42的地方增加了一个斜坡45。 As shown in FIG. 17, the geometry of the device 16 shown in FIG. 40, the device 80 is substantially similar, except that in which the base body 42 near where the gap 45 is increased a ramp 12 on orbital surface 21. 斜坡45是一个倾斜表面，该倾斜表面最好从其第一端的巩膜表面14处延伸到第二端的眼眶表面12处。 45 is an inclined ramp surface, preferably extending from the first end of scleral surface 14 to the surface of the eyes at the second end 12 of the inclined surface. 另外，斜坡45还可以从其第一端的纵向部分15的边缘24上一点处延伸到其第二端的眼眶表面12处。 Further, the ramp 45 may extend therefrom at a point 24 on the edge of the first longitudinal end portion 15 of the orbital surface of the second end 12 thereof. 如以上根据装置50所述，当装置80被植入眼90中时，斜坡45有利于在缺口42中容纳下斜肌107，其中缺口42中处在横向部分18和止动部分36之间。 As described above, according to the apparatus 50, when the device 80 is implanted in the eye 90, 45 facilitate oblique ramp 107 is accommodated in the notch 42, in which the gap 42 between the lateral portions 18 and the stopper portion 36. 装置80可以采用与装置50基本类似的技术来制造。 Apparatus 80 may be employed with the apparatus 50 is substantially similar techniques.
图18示意性地显示了根据本发明第二优选实施例的、用于人体右眼的眼药释放装置65。 18 schematically shows a preferred embodiment according to the second embodiment of the present invention, the release of human eye for ophthalmic apparatus 65. 装置65可以用在任何需要采用局部释放药物活性药剂给眼睛的情况。 Device 65 may be used in any case need to partially release pharmaceutical active agents in the eye. 装置65特别适应于将活性药剂释放到眼后部的情况。 The apparatus 65 is especially suitable for release of active agent to the case back of the eye. 装置65的一个优选的应用是将药物活性药剂释放到靠近黄斑的视网膜上，以便治疗ARMD、脉络膜新血管形成(CNV)、视网膜病变、视网膜炎、眼色素层炎、黄斑水肿、青光眼和神经病变。 One preferred application device 65 is to release the pharmaceutically active agent onto the retina near the macula, so that the treatment of ARMD, choroidal neovascularization (the CNV), retinopathies, retinitis, uveitis, macular edema, glaucoma, and neuropathies .
装置65通常包括基体29，该基体29有一个凸的、圆顶形的眼眶表面12和一个凹的、圆顶形的巩膜表面14(没有显示)。 Device 65 generally includes a base 29, the base 29 has a convex dome shaped orbital surface 12 and a concave, dome-shaped scleral surface 14 (not shown). 所设计的巩膜表面14的曲率半径便于它与巩膜100直接接触。 The radius of curvature of the scleral surface 14 is designed to facilitate it in direct contact with sclera 100. 更好是使巩膜表面14的曲率半径等于平常人眼90的曲率半径91。 More preferably scleral surface 14 of radius of curvature equal to the radius of curvature of 90 normal human eye 91. 眼眶表面12最好被设计成具有便于植入到眼球筋膜101以下的曲率半径。 Orbital surface 12 is preferably designed with a radius of curvature to facilitate sub-Tenon implantation of 101 or less. 当从上面看时，基体21最好有一个大概为“C-形”的几何形状，其中有纵向部分17、横向部分18和其间的弯曲部分32。 When viewed from above, the substrate 21 preferably has an approximately "the C-shaped" geometry with a longitudinal part 17 in which the curved portion 18 and lateral portions 32 therebetween. 纵向部分17和横向部分18最好在弯曲部分32处相连，以形成一个约为九十度的角度。 Longitudinal portion 17 and transverse portion 18 is preferably connected to the curved portion 32, to form an angle of approximately ninety degrees. 纵向部分17有一个近端25、一个圆形边缘24。 Longitudinal portion 17 has a proximal end 25, a rounded edge 24. 一个止动部分37形成了C形的“下”部并且该止动部分最好比通常凸起的眼眶表面12的其余部分升高一些。 A stopper portion 37 formed in a portion "of" C-shaped and the stop portion is preferably longer than the remainder generally convex orbital surface 12 increases a number. 一个缺口42位于纵向部分17处，并且由横向部分18和止动部分37所确定。 A notch 42 is located at a longitudinal portion 17, and portion 37 is defined by lateral portions 18 and the stopper. 与图7和图9所示的装置50的缺口42类似，装置65的缺口42被设计用来容纳下斜肌107的起始端部。 Gap device 50 shown in FIGS. 7 and 9 is similar to FIG. 42, the notch 42 of device 65 is designed to receive the lower portion of the starting end 107 of oblique. 与装置50的止动部分36类似，止动部分37通过与下斜肌107的前边界相接触，防止装置65向视觉神经96过分前移。 Similar to the apparatus 50, the stopper portion 36, the stopper portion 37 by contact with the front oblique lower boundary 107, over-prevention device 6596 to advance the optic nerve. 横向部分18有一个远端58、一个圆形边缘28和一个在巩膜表面14(没有显示)上有开口64(没有显示)的槽或空腔20，以便夹持住与以上根据图10和图11所描述的内核相似的内核。 Transverse portion 18 has a distal end 58, a rounded edge 28 and a (not shown) on the scleral surface 14 has an opening 64 (not shown) of the groove or cavity 20, clamped to the above FIG. 10 and FIG. the core 11 is similar to the kernel described. 槽20和开口64最好大概为椭圆形。 Groove 20 and the opening 64 is preferably roughly elliptical.
装置65的应用基本上与上述装置50的应用相同。 Application of device 65 is substantially the same application device 50 described above. 装置65可以采用与装置50基本类似的技术来制造。 Device 65 may be employed with the apparatus 50 is substantially similar techniques.
图19显示了一个眼药释放装置67，它对眼药释放装置65稍微作了一些改进，这些改进有利于一些本发明的植入。 FIG 19 shows some ophthalmic implant of the present invention a release device 67, it is slightly ophthalmic release means 65 made some improvements have beneficial. 如图19所示，装置67与图19中所示的装置65的几何形状基本相似，其不同之处在于在基体29的眼眶表面12上靠近缺口42的地方增加了一个斜坡45。 19, the geometry of the device 65 of the apparatus 67 shown in FIG. 19 is substantially similar, except that in which the base body 42 near where the gap 45 is increased a ramp 12 on the surface 29 of the orbital. 斜坡45是一个倾斜表面，该倾斜表面最好从其第一端的巩膜表面14处延伸到第二端的眼眶表面12处。 45 is an inclined ramp surface, preferably extending from the first end of scleral surface 14 to the surface of the eyes at the second end 12 of the inclined surface. 另外，斜坡45还可以从其第一端的纵向部分17的边缘24上一点处延伸到其第二端的眼眶表面12处。 Further, the ramp 45 may extend therefrom at a point 24 on the longitudinal edge of the first end portion 17 to the second end surface of the eyes 12. 如以上根据装置50所述，当装置67被植入眼90中时，斜坡45有利于在缺口42中容纳下斜肌107，其中缺口42处在横向部分18和止动部分37之间。 As described above, according to the apparatus 50, when the device 67 is implanted in the eye 90, 45 facilitate oblique ramp 107 is accommodated in the notch 42, in which the gap 42 between the lateral portion 37 and the stopper portion 18. 装置67可以采用与装置50基本类似的技术来制造。 Device 67 may be employed with the apparatus 50 is substantially similar techniques.
图20示意性地显示了根据本发明的第三优选实施例的、用于人体右眼的眼药释放装置52。 FIG 20 schematically shows an embodiment according to a third preferred embodiment of the present invention, the human eye for ophthalmic release means 52. 装置65可以用在任何需要采用局部释放药物活性药剂给眼睛的情况。 Device 65 may be used in any case need to partially release pharmaceutical active agents in the eye. 装置65特别适应于将活性药剂释放到眼后部的情况。 The apparatus 65 is especially suitable for release of active agent to the case back of the eye. 装置65的一个优选的应用是将药物活性药剂释放到靠近黄斑的视网膜上，以便治疗ARMD、脉络膜新血管形成(CNV)、视网膜病变、视网膜炎、眼色素层炎、黄斑水肿、青光眼和神经病变。 One preferred application device 65 is to release the pharmaceutically active agent onto the retina near the macula, so that the treatment of ARMD, choroidal neovascularization (the CNV), retinopathies, retinitis, uveitis, macular edema, glaucoma, and neuropathies .
装置52通常包括基体39，该基体39有一个凸的、圆顶形的眼眶表面12和一个凹的、圆顶形的巩膜表面14(没有显示)。 Apparatus 52 generally includes a base 39, the base 39 has a convex dome shaped orbital surface 12 and a concave, dome-shaped scleral surface 14 (not shown). 所设计的巩膜表面14的曲率半径便于它与巩膜100直接接触。 The radius of curvature of the scleral surface 14 is designed to facilitate it in direct contact with sclera 100. 更好是使巩膜表面14的曲率半径等于平常人眼90的曲率半径91。 More preferably scleral surface 14 of radius of curvature equal to the radius of curvature of 90 normal human eye 91. 眼眶表面12最好被设计成具有便于植入到眼球筋膜101以下的曲率半径。 Orbital surface 12 is preferably designed with a radius of curvature to facilitate sub-Tenon implantation of 101 or less. 当从上面看时，基体39最好有一个大概为“L-形”的几何形状，其中有纵向部分15、横向部分18和其间的弯曲部分32。 When viewed from above, the substrate 39 preferably has an approximately "L-shaped" geometry with a longitudinal part 15 in which the curved portion 18 and lateral portions 32 therebetween. 纵向部分15和横向部分18最好在弯曲部分32处相连，以形成一个约为九十度的角度。 Longitudinal portion 15 and transverse portion 18 is preferably connected to the curved portion 32, to form an angle of approximately ninety degrees. 与图7和图9的装置50的缺口42相似，装置52的区域43被设计用来容纳下斜肌107的起始端。 The notch 50 is similar to the device 42 of FIG. 7 and FIG. 9, the region 43 of device 52 is designed to receive the starting end 107 of oblique. 纵向部分15有一个近端25、一个圆形边缘24。 Longitudinal portion 15 has a proximal end 25, a rounded edge 24. 横向部分18有一个远端58、一个圆形边缘28和一个在巩膜表面14上有开口64(没有显示)的槽或空腔20，以便夹持住与以上根据图10和图11所描述的内核相似的内核。 Transverse portion 18 has a distal end 58, a rounded edge 28 and an opening 64 on the scleral surface 14 (not shown) of the groove or cavity 20, so clamped as described above in accordance with FIGS. 10 and 11 similar kernel kernel. 槽20和开口64最好为椭圆形。 Groove 20 and the opening 64 is preferably elliptical.
装置52的应用基本上与上述装置50的应用相同，装置52可以采用与装置50基本类似的技术来制造。 Application of device 52 is substantially the same using the above apparatus 50, the apparatus 52 may be employed with the apparatus 50 is substantially similar techniques.
图21显示了一个眼药释放装置54，它对眼药释放装置52稍微作了一些改进，这些改进有利于一些本发明的植入。 Figure 21 shows some ophthalmic implant of the present invention, a release means 54, release means 52 it is slightly ophthalmic made some improvements have beneficial. 如图21所示，装置54与图20中所示的装置52的几何形状基本相似，其不同之处在于在基体29的眼眶表面12上靠近区域43的地方增加了一个斜坡45。 As shown, the geometry of the device 52 and the device 54 illustrated in FIG. 20 in 21 is substantially similar, except that it adds a ramp 45 near the local area 43 on the orbital surface 12 of the base 29. 斜坡45是一个倾斜表面，该倾斜表面最好从其第一端的巩膜表面14处延伸到第二端的眼眶表面12处。 45 is an inclined ramp surface, preferably extending from the first end of scleral surface 14 to the surface of the eyes at the second end 12 of the inclined surface. 另外，斜坡45还可以从其第一端的纵向部分15的边缘24上一点处延伸到其第二端的眼眶表面12处。 Further, the ramp 45 may extend therefrom at a point 24 on the edge of the first longitudinal end portion 15 of the orbital surface of the second end 12 thereof. 如以上根据装置50所述，当装置54被植入眼90中时，斜坡45有利于在区域43中容纳下斜肌107。 As described above, according to the apparatus 50, when the device 54 is implanted in the eye 90, 45 facilitate oblique ramp 107 at the receiving area 43. 装置54可以采用与装置50基本类似的技术来制造。 Device 54 may be employed with the apparatus 50 is substantially similar techniques.
由上所述，可以体会到本发明提供了改进的装置和方法，以便安全、有效、控制速率地局部释放各种药物活性药剂给眼睛，特别是给眼睛后部，以抵抗ARMD、CNV、视网膜病变、视网膜炎、眼色素层炎、黄斑水肿、青光眼和神经病变。 From the above, we can appreciate that the present invention provides an improved apparatus and methods for safe, effective, controlled release rate of various drugs locally active pharmaceutical agent to the eye, especially to the back of the eye, against ARMD, CNV, retinal disease, retinitis, uveitis, macular edema, glaucoma, and neuropathies. 植入该装置的外科操作是安全、简便、迅速并且可以给门诊患者实施。 Surgical procedure implanting the devices is safe, simple, quick, and can give an outpatient embodiment. 这种装置在制造上也是方便和经济的。 This device is also convenient and economical in manufacture. 另外，因为它们能够释放各种药物活性药剂，这些装置在临床研究中可用于释放各种眼药以便为患者产生一种特殊的身体状态。 Further, since they can release a variety of pharmaceutically active agents, such devices may be used in clinical studies for the release of various ophthalmic produce a special physical state of the patient.
本发明在此是通过实施例说明的，对于本领域内的技术人员来说可以进行各种不同的改进。 The invention herein is illustrated by way of example, those skilled in the art, it may be various modifications. 例如，虽然上述的本发明涉及一种从顶部看具有“F-形”，“C-形”，或“L-形”几何形状的眼药释放装置，但也可以采用其它的几何形状，特别是当该装置被植入到人眼的巩膜外表面上以及眼球筋膜之下时，所采用的几何形状有利于该装置被植入到下斜肌以下并且使药物活性药剂在黄斑之上时尤其如此。 For example, although the above-described present invention relates to a seen from the top with "F- shape", "the C-shaped", or "L-shaped" geometry ophthalmic release means, but other geometries may be employed, particularly when the device is implanted beneath the outer surface of the sclera of a human eye and Tenon, the geometry employed in favor of the device is implanted under the oblique and the pharmaceutically active agent over the macula when This is particularly true.
可以相信本发明的操作和结构将从以上描述中变得显而易见。 It is believed that the operation and construction of the present invention will become apparent from the foregoing description. 在以上所显示和描述的设备和方法已经被作为优选实施例加以说明的同时，各种变形和改进都可以在不脱离以下的权利要求所确定的本发明的实质和范围的条件下实行。 The above and simultaneously display apparatus and method embodiments have been described as a preferred embodiment to be described, various modifications and improvements can be practiced at the spirit and scope of the present invention without departing from the following claims as defined.
1.一种用于人眼的药物释放装置，所述眼有一个巩膜、多块眼外肌，其中包含一块下斜肌和一个黄斑，所述装置包括：一种药物活性药剂；和一个具有一个几何形状的基体，该几何形状有利于将所述装置植入到所述巩膜的一个外表面上，在所述下斜肌的下面，并且所述药物活性药剂配置在所述黄斑之上，并且不需要断开或切开所述多块眼外肌中的任何一块。 A human eye means for releasing medicament, the eye has a sclera, a plurality of extraocular muscles, which comprises a lower oblique and a macula, said device comprising: a pharmaceutically active agent; and having a a geometric shape of the matrix, which facilitates the geometry of the device is implanted into an outer surface of the sclera, below the lower oblique muscle, and the pharmaceutically active agent disposed above the macula, and does not require any opening or cutting a plurality of the outer muscles of the eye.
2.根据权利要求1的药物释放装置，其特征在于：所述基体包括一个巩膜表面和一个眼眶表面；并且在从所述巩膜表面或所述眼眶表面看时，所述几何形状是一个F-形的几何形状。 2. A drug release device according to claim 1, wherein: said base comprises a scleral surface and a orbital surface; and when viewed from the scleral surface or the surface of the eyes, the geometric shape is a F- shaped geometry.
3.根据权利要求1的药物释放装置，其特征在于：所述基体包括一个巩膜表面和一个眼眶表面；并且在从所述巩膜表面或所述眼眶表面看时，所述几何形状是一个C-形的几何形状。 3. A drug release device according to claim 1, wherein: said base comprises a scleral surface and a orbital surface; and when viewed from the scleral surface or the surface of the eyes, the geometric shape is a C- shaped geometry.
4.根据权利要求1的药物释放装置，其特征在于：所述基体包括一个巩膜表面和一个眼眶表面；并且在从所述巩膜表面或所述眼眶表面看时，所述几何形状是一个L-形的几何形状。 4. A drug release device as claimed in claim 1, wherein: said base comprises a scleral surface and a orbital surface; and when viewed from the scleral surface or the surface of the eyes, the geometric shape is an L- shaped geometry.
5.根据权利要求1的药物释放装置，其特征在于：所述人眼包括一个眼球筋膜，而所述基体包括一个眼眶表面，该眼眶表面的曲率半径便于将所述装置植入到所述眼球筋膜下。 According to claim 1, wherein the drug release means, wherein: said eye comprises a sub-Tenon, and said matrix comprises a orbital surface, the radius of curvature of the orbital surface of the device is implanted to facilitate the Tenon down.
6.根据权利要求5的药物释放装置，其特征在于：所述眼眶表面还包括一个缺口，在植入所述装置时，所述缺口便于容纳所述下斜肌。 6. A medicament according to claim 5, wherein the release means, wherein: said orbital surface further comprises a notch, in implanting the device, said receiving notch facilitates the inferior oblique.
7.根据权利要求6的药物释放装置，其特征在于：所述缺口包括一个斜坡。 7. A medicament according to claim 6, wherein the release means, wherein: said notch comprises a ramp.
8.根据权利要求1的药物释放装置，其特征在于：所述基体具有一个巩膜表面，所述巩膜表面的曲率半径等于所述人眼的曲率半径。 According to claim 1, wherein the drug release means, wherein: said base body having a scleral surface, the radius of curvature of the scleral surface is equal to the radius of curvature of the human eye.
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