TW201223581A

TW201223581A - Devices for delivering at least one active agent to tissue

Info

Publication number: TW201223581A
Application number: TW100139487A
Authority: TW
Inventors: Charles Leahy; Robert F Thompson; Edward Ellis
Original assignee: Vista Scient Llc
Priority date: 2010-10-29
Filing date: 2011-10-28
Publication date: 2012-06-16
Also published as: EP2632532A2; WO2012058382A2; WO2012058382A3; JP2013545521A; AR087932A1

Abstract

A device for delivering an active agent to target tissue at a site that includes a bodily fluid includes a body having a first exterior surface including a first section having a local, discrete recessed area formed in the body for holding the active agent. The body includes a surface flow feature in the form of a canal that is formed in the body and is recessed relative to the exterior surface. The surface flow feature interfaces with the first section and the local recessed area and is configured so as to guide or modify flow of the bodily fluid relative to the body such that fluid communication is provided between the bodily fluid and the local recessed area. The local recessed area is recessed relative to at least a portion of the canal. The device can also be in the form of a device that has an erodible member that releases the active agent over a prescribed period of time.

Description

201223581 六、發明說明：【發明所屬之技術領域】本發明整體而言係關於用於 # 用於傳遞至少一有益活性劑至目才示組織之裝置。更明確但不限帝而3，本發明可應用至位於眼目月之前表面上以將-活性劑傳遞至眼組織之—裝置，其中该活性劑係包含於該裝置中且該裝置具有一經修改施配表面，以輔助將該活性劑 w释放至该目標組織。本發明一般關於用於將活性劑（例如， u妁如，樂品）在延長時間中傳遞至身體組織之裝置。此外，本發个發月係關於控制該活性劑自一裝置之釋放。更明確但不限制^_ ，个丨民制而吕，本發明係關於用於部地傳遞活性劑至眼睛之生物相容性裝置。關於聯邦政府贊助之聲明美國政府擁有本發明之已缴畤哞、 ◦徽秋疔可證且在有限的條件下要求專利持有者基於合理的條王幻條件（如國豕衛生研究所頒發的許可#2 R44EY 013479-04)授予其他人。天相關申請案之交叉參考本申請案主張於2010年11月29a所由^主¥ 卞u月曰所申请之美國專利申士主案序號第61/4〇8,〇16號；於2〇1〇年11月29日所申請之美g 專利申請案序號第61Μ〇8,〇22號；及於2〇1〇年11月8曰所申請之美國專利申請案序號第61/411，〇42號之權利，各個申請案之全文係以引用之方式併入本文中。【先前技術】病患之許多種不植入物，等等。現有用於傳遞活性劑（諸如，藥物）至一同類型之傳遞裝置，包含但不限於膠囊、 I59575.doc 201223581 傳遞裝置之-次_用於傳遞_ 傳遞裝置。活性劑至眼睛之眼部藥物遞裝置’所有的眼部藥物配方中 90%係作爲滴眼液 J尺幻 &仏。除了難以讓病患恰當地插入之外，使用滴眼液會谲& 個主要技術缺點：滴眼液會快速201223581 VI. OBJECTS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention generally relates to apparatus for delivering at least one beneficial agent to a tissue. More specifically, but not limited to the third, the present invention can be applied to a device located on the surface of the eye before the eye to transfer the active agent to the ocular tissue, wherein the active agent is included in the device and the device has a modified application A surface is provided to assist in the release of the active agent w to the target tissue. The present invention is generally directed to devices for delivering an active agent (e.g., a sputum, such as a music product) to body tissue for an extended period of time. In addition, the present invention relates to controlling the release of the active agent from a device. More specifically, but not limited to, the invention relates to a biocompatible device for the delivery of an active agent to the eye. Statement Regarding Federal Government Sponsorship The US Government has the paid, ◦ 疔疔且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且且License #2 R44EY 013479-04) Granted to others. CROSS-REFERENCE TO RELATED APPLICATIONS This application claims to be filed on November 29, 2010 by the main patent of the US Patent Application No. 61/4〇8, 〇16; on 2〇1〇 US Patent Application No. 61Μ〇8, 〇22#, filed on November 29, 2009; and US Patent Application No. 61/411, 〇42, filed on November 8th, 2010 The entire contents of each application are incorporated herein by reference. [Prior Art] Many types of patients do not implant, and so on. There are existing delivery devices for delivering active agents (such as drugs) to a variety of types, including but not limited to capsules, I59575.doc 201223581 delivery devices - for delivery-transfer devices. Active agent to the eye area of the eye Drug delivery device '90% of all eye drug formulas are used as eye drops J-Fantasy & In addition to the difficulty of properly inserting the patient, the use of eye drops will result in & major technical disadvantages: eye drops will be rapid

睛消失且對於目標組織而言，滴眼液生物利用性不佳。因此’由於角臈的淚膜稀釋及消失及可滲透性障壁，、一般而言，所施加劑量的藥物中到達眼内組織的（劑量）遠遠J於百刀之五。JU此’局部眼部藥物溶液經配方濃度高而要、吊f生地配給…主要臨床缺點在於與治療之非相依性’其原因在於需要經常性配給，在與治療應用立刻關聯之後缺乏可偵測症狀減輕、由於需要高濃度藥物及其他原因而產生不希望之系統性副作用。為了解決此等問題’將一固態裝置放置於眼中或眼睛附近以在長時間中傳遞-有益的藥劑之理念已經吸引人們在夕年中付諸大量努力來發展。一般而t，此等裝置之特徵在於作為基質或貯槽類型裝置。基置係由—材料組成且該有益藥劑係包含在整個該材料中。一貯槽裝置在該裝置之一個或一個以上之不同部分包含該藥劑。此等裝置包含具有有益藥劑之一貯槽或包含該有益藥劑之材料之一貯槽亦被稱為藥物貯槽（drug depot)、藥物核心（drug c〇re)、藥品貯槽（medication depot)或簡單地稱為貯槽（dep〇t)。該裝置之本體中之包含該貯槽之空間係由各種術語稱謂，包含，井狀部、袋狀部、貯存部、孔隙、儲液部及腔。頒與 159575.doc 201223581The eye disappears and the bioavailability of the eye drops is poor for the target tissue. Therefore, due to the dilution and disappearance of the tear film and the permeable barrier of the horn, in general, the dose (dose) of the applied dose of the drug reaches the intraocular tissue. JU This 'partial eye drug solution has a high concentration of formula, and it is necessary to hoist it. The main clinical disadvantage lies in the non-dependence of treatment'. The reason is that it requires frequent ration, and it lacks detectability after being immediately associated with the therapeutic application. Symptoms are alleviated, undesired systemic side effects due to the need for high concentrations of drugs and other reasons. In order to solve such problems, the concept of placing a solid-state device in the eye or near the eye for delivery over a long period of time - the concept of a beneficial agent has attracted a great deal of effort to develop in the eve of the year. Typically, these devices are characterized by a device of the type of substrate or tank. The base is composed of a material and the beneficial agent is contained throughout the material. A sump device contains the medicament in one or more different portions of the device. Such devices comprise a reservoir having one of the beneficial agents or a material containing the beneficial agent. The storage tank is also referred to as a drug depot, a drug core, a medication depot or simply It is a storage tank (dep〇t). The space containing the sump in the body of the device is referred to by various terms, including a well, a pocket, a reservoir, a pore, a reservoir, and a cavity. Awarded 159575.doc 201223581

Behney之㈣專㈣3,3G2,6健揭示—種詩牛血清眼部藥物傳遞之裝置。該裝置具有一由軟膏填充之一袋狀部，其經=鄰近眼睛之角膜表面及鞏膜前表面。更一般而言，該貯槽係位於該裝置之内部且此等類型之裝置之大多數先前技術關注於將該藥物自該貯槽運輸至該裝置之該表面或管理至該施配表面之運輸速率。 z 頒與Ness之美國專利第3,416,53〇號揭示使用具有毛細管作用之穿孔來將藥物自其内部儲液部帶動至該裝置之表面。頒與Zaffaroni之美國專利第4186，184號揭示一種具有一傳遞入口之裝置，該入口通向至該裝置之被認為最適合於作爲目標之該組織之表面。 ®：Graham等人之美國專利第4,973,304號揭示使用水凝膠^將藥物自該儲液部運輸至該裝置之該表面。㈣Chen等人之美國專财請第5,9G2,598號揭示一種具擴政鈿口之裝置’纟用於將藥物自該儲液部運輸至該裝置之該表面。對於許多藥物及傳遞系絲，、、’、提（、長期治療的藥物位準所而要的所有事物僅係具有華物頁樂物之一小袋狀部或具有一小外配表面之一較大袋狀部。 _ ^ 樂物係自此荨系統經由位於该裝置上之緊鄰眼組織之一个U開口或入口而釋放。然㈣度而言’將藥物釋放集令於眼組織之一狭窄 ΒΒ 二需關切的問題，明確而言係關於藥物具有已知副作用 ’ 卞用4如發炎，且明確而言，在該 159575.doc 201223581 裝置相對於該緊鄰組織相對可移動之情形下。因此，在眼部藥物傳遞領域中，f要一種能夠併入一藥物貯槽且自該貯槽在眼組織之一較大部分上擴展藥物釋放 • 2藥物傳遞裝置。理想上’此-裝置應能夠傳遞多種用於 ‘ 療之藥物或有益的物理條件且應相對易於製造。此外，基質裝置之相對平滑表面將得益於眼淚流動特徵，其增大且改良裝置表面積且增加藥物獲得及分散。【發明内容】 Ο . ^ ^ _ 實3例令，一種用於傳遞一活性劑之裝置包含一本體，其具有用於放置於目標組織附近之至少一個表面，該活性劑經傳遞至該目標組織。該目標組織之位置亦包含一體液。該活性劑係與該本體關聯且係由該本體以任何數目之不同方式承載，包含但不限於，設置於形成該本體之該基質内’設置於局部區域中，諸如在一局部凹陷區域(例如，一井狀部、一袋狀部或儲液部）中；沿該本體之一表〇而叹置等專。该裝置之該表面上之物理特徵引導、中斷或以其他方式f多改該體液相對於該本體之流動，使得該體液與該活性劑之間發生接觸，以藉由該液體流而將該活性劑傳遞至目標組織。當該活性劑係設置於該局部凹陷區域内時，該裝置外部之一環境可通過該凹陷區域之—開口該而獲得該活性劑。在—應用中，該裝置係用於一眼部環境中。在此一實施例中，該液體係呈眼内液體（例如，眼淚）之形式且該本體之一表面係放置與該目標組織接觸或鄰近該目標組織，該 159575.doc 201223581 2標組織係呈眼組織之形式，諸如，眼睛之鞏膜或其他區域。該袭置之該表面上之物理特徵弓I導或以其他方式修改 2内液體㈣朝向、跨過及/或遠離包含該活性劑之該部區域。在另-態樣中，本發明整體而言係關於用於將活性劑 (例如’藥品）在延長時間中傳遞至身體組織（目標組織）之 j置。此外，本發明關於控龍活性劑自 =更明確但不限制而言，本發明關於用於將藥品局= 將以眼部插入物、淚管塞目^;此眼部應用中，本發明眼部裝置之组態使用二：部植入物、隱形眼鏡及其他本發明係關於控制自組態用於藥物傳遞。物傳遞裝置…釋：―—基貝類型或-貯槽類型之藥明.箱古…釋具有兩種操作性方法來實踐本發明.一種方法係適用於一藥物之基質構造之裝置。第： = ;，，完全由包含置，其中藥品係在丄到一貯槽類型裝置可為基質類型與貯槽類型局部區域。此外裝將為同時傳遞不Γ 之·"組合。此一裝置之一應用于得遞不同的藥物。本發明之裝置在該裝 △ 放動力學及藥物 ^療持、，期更好地管理釋漸地曝露更多的率：置可經組態以隨著時間流逝逐物，-有限曰^物知配表面積。隨著該裝置開始施配藥因此更大有=旦^限制表面積將被曝露至體液及組織且面上使用具有物將經初始釋放。透過在潛在施配表 s冰度或厚度之生物易蝕性覆蓋物，腐蝕 159575.doc 201223581 將逐漸地造成更大的表面積曝露且因此相較自具有一固定尺寸之-施配表面，可發生釋放速率之一更漸進之減小。在-態樣中’本發明包含—種具有—結構性本體之一藥㈣遞裝置，其中藥品係存在於該整個本體或位於該本體之局部區域内且該藥品通過該本體之一個或一個以上之表面而釋放至該本體外側之環境。【實施方式】〇本申請案揭示用於傳遞一活性劑（可呈藥物及/或一治療劑及/或其他有益藥劑之形式）至目標組織之若干種裝置。 S亥等裝置係意在放置於病患體内之鄰近該活性劑將傳遞至彼處之目標組織。應理解，該等裝置可放置於體内之任何數目之不同位置處且因此，該目標組織可為該病患整個身體内之不同組織。在本發明之一實施例中，該裝置係呈一眼部 (〇phthalmic/ocular)傳遞裝置之形式，該裝置係一局部眼部〇傳遞系統之一部分且該眼部傳遞裝置經設計以將眼淚實體地導向該傳遞裝置之一個或一個以上之施配表面處，以施配該活性劑（藥物及/或治療藥劑等等）。如下文將詳盡描述，當該活性劑係包含於一聚合物基質（其界定該藥物傳遞裝置之一本體及/或該活性劑之一該施配表面）内時，該施配表面可呈該傳遞裝置之一曝露表面之形式及/或該施配表面可為具有一活性劑之一經曝露表面，其經設置於形成於該傳遞裝置之該本體中之一局部凹陷空間（例如，一井狀部、儲存部、艙、腔、儲液部、袋狀部等等）内。以 159575.doc 201223581 此方式’該活性劑可以一織。有控制之方式釋放至該目標組圖1至圖3圖解根據一實施例之用於傳遞一活性置⑽。如上文所述，該傳遞裝置i⑽可相對於該病' 體用於任何不同數目之應用中，身从/口療不同的目標組織位。雖然，本文將該裝置100描述為係一「藥物」（細遞裝置’應理解’該裝置_及本文所揭示及在多個圖中所不之其他裝置並不限於一醫學藥品之傳遞，而是可用於傳遞在技術上並不歸類為一醫學藥物之一活性（治療）藥劑。 ’、一更明確而言，該裝置100及本文所揭示且在多個圖中所不之其他裝置經構造以傳遞一活性劑至目標組織。表達「藥劑」（、agent)用於本文中廣義上包含可自該裝置傳遞以產生有盈且有用之結果之任何化合物、物質之組合物或 f混合物。為了本發明之目的，藥品（medication)、醫學藥劑（medical agent)、治療藥劑（therapeutic 叫61^、有益藥劑（beneficiu agent)或藥物（drug)可視為同義詞。在本發明中所述之裝置包含有效地獲得一所要的局部或系統性生理效果或藥理效果之一活性劑。下列分類之活性劑可併入本發明之裝置中。可與本發明之傳遞裴置配合使用之合適的藥物或活性劑包含（僅藉由舉例之方式，並不限於）：（A)抗感染藥物：諸如，柷生素、包含四環素、氣四環素、桿菌肽 '新黴素、夕黏菌素B、短桿菌肽 '氧四環素、氯黴素及紅黴素；磺 159575.doc -10 - 201223581 醯胺類，包含，乙醯磺胺、磺胺甲二唑、異唑磺胺；喹諾酮類，包含，氧氟沙星、諾氟沙星、塞普沙星、司帕沙星，胺基糖苷類’包含’阿米卡星、妥布黴素、慶大黴 ^ I，頭抱菌素；抗生素之組合；抗病毒藥物，包含，峨苷、二氟尿苷、阿糖腺苷西多福韋、膦曱酸鈉、更昔洛韋納及阿昔洛韋；抗真菌藥物，諸如，兩性黴素B、制黴菌素、氟胞嘧啶、氟康唑、遊黴素、黴康唑及酮康唑；及其他抗感染藥物，包含，呋喃西林及丙酸鈉；（B)抗過敏藥物，諸如，安他唑啉、美沙吡啉、撲爾敏、美吡拉敏及屈米通、依美斯汀、酮咯酸、左卡巴斯汀、洛度沙胺、氣替潑諾、萘甲唑啉/安他唑啉、萘曱唑啉/苯吡胺、奥洛他定及色甘酸鈉；（C)消炎藥：諸如，氫化可的松、醋酸氫化可的松、地塞米松、氟美松21_磷酸酯、氟輕鬆、甲羥松、氫化波尼松、氫化波尼松21_磷酸酯、醋酸潑尼松龍、氟曱龍、醋酸氟米龍、甲羥松、依碳酸氯替潑諾、雙 Q 曱丙醯龍；(D)非固醇類消炎藥：諸如，氟比洛芬、舒洛芬、雙氣芬酸、吲哚美辛、酮洛芬及酮咯酸；解充血藥：諸如，苯福林、萘甲唑啉、羥甲唑啉及四氫唑啉； (F)縮瞳藥及抗膽鹼酯酶：諸如，匹羅卡品、水楊酸毒扁 " 豆域、碳醢膽鹼、二異丙基氟磷酸、碘磷靈滴眼劑及地美溴銨；及（G)散瞳藥：諸如，硫酸阿托品、環戊通；後馬托PO、莨菪域、托吡卡胺、尤卡托品及羥基苯丙胺。此外，下列/舌性劑亦可用於本發明之裝置中：（A)抗青光眼藥劑：諸如，腎上腺素，包含，腎上腺素及地匹福 159575.doc 201223581 林、環领腎上腺素、0_腎倍他洛爾、美替'各爾含’布諾洛爾' 禹替洛爾、噻嗎洛爾、卡替洛爾能激動藥，包含，毛友男上腺素酶抑制藥，包含化胺甲醯膽驗;膽驗酿酶抑制劍，々人臭錄、依可峨®旨；碳酸酐 " 匕3，—氣苯磺胺乙醯唑胺、醋f唑胺、杜突醢胺、布林佐胺、二氯苯磺胺；冑列腺：列素、曲伏前列素、此民义石丨本拉坦則上、馬刖列素，dlconosoids及上述藥物 …諸如’ β-腎上腺抑制劑與破酸野酶抑制劑之二二’及(Β)抗白内障藥物：諸如，醛糖還原酶含，托瑞斯他、司特醇、索比尼爾；抗氧化劑，包^; 壞血病酸、維他命E ;总1 仇鋅。 S養補錢’包含，谷胱甘肽及另-組活性劑係呈潤滑劑之形式：諸如，甘油醇、聚甘油及可選擇性水溶解聚合物，纖： :、—聚乙二醇及生物聚合物，諸如=: 酸及脫乙醯殻多糖。处月貨述之藥劑’可使用本發明之持續性釋放 :置來使用及管理適用於治療、有益於、狀況之其他藥劑。 > 呵眠邛在-示例性應用中，該藥物傳遞裝置1〇〇係根例之-局部眼部藥物傳遞裝置⑽，“，將理解，: 100不僅僅限於用於眼部應用中，而、二以治療身體之其他部位。該藥物傳二 =應由: 本體U0界定，在此特定示例性手由再具有預定之尺 I59575.doc •12· 201223581 寸以允許放置於眼中。該本體110係由一第一表面或第一面及-相對之第二表面或第二面13〇而界定。該本體 110之厚度經界定為該第一表面120與該第二表面13〇之間之-距離。該本體11〇包含一周邊邊緣刚，其在所圖解實施例中顯示為一侧壁。亦將理解’所圖解之本體11G之形狀僅僅係示例性且該本體11G可具有其他形狀。該本體m經形成使得其具有一 Ο 定程度之可撓性’以允許將該本體UG放置於該目標組織所：之目標位置。因此，該本體11〇可具有允許該本體"Ο 至少大體上或實質上適應該目標組織（該本體ιι〇係應用至及目私組織)之形狀之材料特性。例如，當用於眼部應用令時’該本體110可適應眼睛之形狀，下文將予以更詳細之描述。亦將理解，無論該第一表面120或是該第二表面13〇均可放置抵靠該目標組織’且因此相對之表面背離該目標組 Ο 織。在—眼部應用中，該第-表面120或該第二表面13〇可放置抵靠眼睛之該組織，下文將予以更詳盡之描述。將理解，雖然該本體110具有圍繞一中央抽線之對稱性，但該裝置100並不限於具有此一特性，且相反地，該本體110可具有一非對稱構造。本發明之中請人擁有之先前文獻（作品）描述各種眼部藥物傳遞系統。例如’美國專利申請案第10/569 743及 1 1/359，156號，其各者之全文係以引用之方式併i本文中。因此將理解， °亥裝置100及本文所述且在附圖中圖解 159575.doc 201223581 之其他襄置可由此等申 ^ ^ ^ 甲月案中所揭不之材料形成且具有上这申睛案中所揭示之結構特性。具有上根據本發明，該本體11()之—個或_個以上之至少一個表面流動特徵八特徵2GG及/或240 ’以引導或以其他方 =:該本體"〇接觸之一液體之流動，以辅助將該活 =傳遞至該目標H在圖，該表面流動特徵200係 :成於该第-表面12G中，該第—表面12阿為遠離該目標、·且織之表面。。如在圖1中所示，該表面流動特徵2〇〇可呈一局部凹陷區域之形式’其具有諸如，形狀及尺寸及㈣之預定特性，其引導或以其他方式修改與該本體110接觸之液體之流動，以輔助且最佳化該活性劑至該目標組織之傳遞。舉例而。且如下文將更詳細地描述，該表面流動特徵2〇〇可經構造以修改液體流動朝向該施配表面，或遠離該施配表面或朝向或遠離界定於該施配表面上之一特定局部區域。該表面流動特徵200係呈一表面特徵或修改物之形式，其界定沿該襞置之該本體之一流徑’以當該液體沿/跨該裝置之該本體流動時使該液體在該流徑中流動。該表面流動特徵200至少部分地包含該液體。該表面流動特徵200可呈一凹陷開口流槽、凹槽或具有適於引導或修改液體之流動之一形狀及若干尺寸之其他凹陷部。該表面流動特徵 200亦可理解為呈斜坡、流槽、水閘、山谷、半管、卡盤、漆布等等之形狀，逐漸變窄、加寬、轉彎、扭曲等 159575.doc 14 201223581 等，或此等形式之一組合。係呈-至少部分開口之導管之二之，該表面流動特徵200 自-個位置移動至另一液體可流經該導管且七雖然本文中論述該表面流動特徵200係一凹陷流槽，以穷％ 4"論及統一性，將理魅，在本發明之範圍内，哕矣以表面^動特徵200可呈任何數目之不同形狀之凹陷結構之形式。 ^ ^ α 圈所不，该表面流動特徵 2 0 0不限於為一線性構；皮 & 3 _l ?on 疋相反地，該表面流動特徵 Ο 200可具有一個或一個以之’f曲區段且可具如圖所示之一分支構造。因此，該表面流動特徵可沿該本體U0之-個或一個以上之周邊邊緣而開口。例如，該表面流動特徵200可沿該本體U〇之兩個周邊邊緣而開口。在本發明之範圍内，該表面流動特徵200並不沿任何周邊邊緣而開口，如本文圖解及描述。此外’該表面流動特徵200可位於沿該本體11〇之—周邊邊緣之一個以上之位置。亦將理解’該流槽之深度可根據該本體1丨G之特定應用及特性（諸如該本體110之厚度等等）而變動。此外，該表面流動特徵200(流槽）可藉由變動若干深度而界定，其原因在於，該表面流動特徵200之一區域可具有一第一深度（相對於·»亥本體110之該表面），而另一區域可具有不同於該第一床度之一第一深度（相對於該本體110之該表面）^ 如圖1中所示，該表面流動特徵240可呈具有預定特性 (形狀及尺寸及輪廓）之一局部升高區域之形式，諸如，其 I59575.doc 15 201223581 引導、中斷或以其他方式修改與該本體u〇接觸之液體之流動’以辅助且最佳化該活性劑至該目標組織之傳遞。舉例而言且如下文將詳細描述’該表面流動特徵2〇〇可經構造以修改液體流動朝向該施配表面，或遠離該施配表面，或朝向或遠離界定於該施配表面上之—特定局部區域。該表面流動特徵240係呈一表面特徵或修改物之形式，其改變沿該裝置之該本體或沿該流槽之—液體流徑。該表面流動特徵24G係呈—楔形物、墩部或其他升高形狀之形式’其具有適於引#、中斷或以其他方式修改液體之流動之尺寸。該表面流動特徵240亦可理解為呈一斜坡、凸部、柱、以及分割、偏轉或以其他方式中斷及改變眼内液流過該表面之任何其他升高特徵，或呈此等形式之一組合0 在-些實施例中’一升高表面特徵可留駐於一凹陷表面流動特徵内或，且相反地，—凹陷表面流動特徵可留駐於-升高表面流動特徵内或上。此外，一實施例可具有此等之任何組合。然而’如附圖中所圖解，該表面流動特徵可呈不且有表面流動特徵240之一非分支類型。在此實施例中，該表面流動特徵200作用於該體液之流動。具體參考圖1，該表面流動特徵（流槽）2〇〇具有一分支構造’其原因在於，該流槽包含沿該本體丨1〇之—第一邊緣 ill而開口之一第—流槽區段21〇及由與該第—流槽區段 210流體連通之複數個個別分支流槽區段222形成之一第二 I59575.doc -16- 201223581 流槽區段220❶該等分支係藉由該等升高楔形物（升高區段）240形成。該等分支流槽區段222中之各者係沿該本體 110之一第二邊緣113而開口。該第二邊緣lu係與該第一邊緣111相對。在所圖解之實施例中，具有三（3)個分支流槽區段222。將理解，該表面流動特徵（流槽）2〇〇之橫截面形狀可變動且經根據特定的應用而選擇。例如，在一實施例中，該流槽200可藉由至少大體上垂直於一流槽底部22〇之兩個相對的壁210而界定。或者，該流槽2〇〇可藉由相對於該流槽底部220形成一角度之兩個相對壁2〇5而界定。因此，在此實施例中，該等壁205類似於圖1中所示之傾斜壁。該等壁 205所成之角度產生一傾斜流槽且可經組態以改變行進至該流槽中、流出該流槽及在該流槽内行進之液體之流動動力學。例如，該等傾斜壁205辅助液體流過此等壁，以允許液體更容易地流入該流槽2〇〇中及自該流槽2〇〇中流出。此外’將理解，該等個別分支流槽區段222可相對於彼此具有不同的特性且明確而言，該等分支流槽區段222之寬度及/或長度及/或形狀可不同。舉例而言且如圖1所示，一分支流槽區段222可具有一較大的長度；一流槽區段222 可具有一較大的寬度且該等流槽區段222具有不同的形狀。圖1顯示該裝置100 ’其中該活性劑係包含於該本體11〇内（例如’分散遍及形成該本體110之一聚合物基質）且通過該本體110之一個或一個以上之表面（例如，表面12〇)而施 159575.doc 17 201223581 配。當該裝置100係用於放置於眼中（即，一眼部應用）時），該流槽200係用於引導及/或修改眼内液（例如，眼淚）之流動。一較易識別之眼内液係眼淚’眼淚係眼睛之通常潤滑且沖掉顆粒及外來物體所必要。如在此項技術中所理解，一個人的眼中的大多數眼淚係由主要淚腺所產生，該主要淚腺自眼球之中心位於鼻子之上方且稍微靠近太陽穴，或遠離或與鼻子相對。眼淚產生係始於淚腺中且具有沿上眼驗及下眼驗及位於覆蓋眼球之表面之結膜中之多個較小隱秘腺體’其提供油質及黏液至淚膜。儘管眨眼機制在任何眨眼間歇期間於該眼球之一經曝露部分上重建一薄膜，此膜代表眼中之總體眼淚體積之一小分率。習知的眼淚流動遵循自淚腺（源）下行至眼睛之表面，且同時跨過眼睛朝向鼻子（若干排泄孔（淚點）位於此處）之一大體流經。因此，當雙眼眼瞼閉合時，雙眼眼瞼進行朝向鼻子之一輕微閉合運動，藉此在排泄孔之方向推動眼淚。將理解，描述眼淚動之液體機制之上文描述並不限於本發明，而是描述眼淚如何在眼中流動之一已為人接受之機制。因此，該表面流動特徵200作用以導向且引導眼淚沿預定流徑，以輔助且最佳化包含於該本體11〇中之該活性劑之釋放。圖2,4不根據一不同實施例之一裝置1 〇 1，其類似於該裝置00，然而，該裝置1〇1包含具有一局部凹陷區域（空 )(諸如，袋狀部' 儲液部、腔、餘、井狀部、凹槽等 I59575.doc •18- 201223581 等)之一額外特徵。該局部凹陷區域250可具有將提供空間，任何數目之不同形狀及尺寸。其經定位及形成使得其與。亥表面抓動特徵2〇〇流體連通，但相對於該表面流動特徵 2〇0凹陷。更明確而言’該局部凹陷區域250收納或容納該活性劑（在圖2中界定為1〇3)。因此，該等表面流動特徵· 及240之結構性特性及位置經選擇以引導或以其他方式修改眼内液机動朝向、跨過或進入，且遠離該局部凹陷 250。一該活性劑103可呈任何數目之不同形式且可具有任何數目之不同形狀且具有不同的尺寸。將理解，該活性劑1〇3 之形式及尺寸係至少部分地取決於該活性劑本身及特定之應用。例如，該活性劑103可具有下列形式：固態小片；〇 3該活性劑之一聚合物基質、包含位於一離散井狀部中之一液體活性劑之一固態結構 '一凝膠結構、一囊封於一結構中之液體活性劑、一包含於一薄膜之下方之液體、一〇包含位於一薄臈下方之該活性劑之一聚合物基質，或可具有任何其他形式，只要該活性劑103可與該局部區域250流體連通且以一受控制之方式分散即可。在圖2中，該活性劑103係位於該表面流動特徵（流槽）200内且明確而言，該活性劑1 〇3經定位鄰近該第一流槽區段210與該等個別分支流槽區段222之間之介面。此配置允許在該第一流槽區段210内流動之液體（例如，眼内液）與該活性劑103接觸且接著在遠離包含該活性劑1〇3之該局部區域250之一方向上流動。 159575.doc -19- 201223581 對於其他實施例’雖然圖中未繪示，將理解，在各個表面流動特徵200内可具有多個間隔之局部區域25〇。此等區域可容納相同或不同類型之活性劑。亦將理解，在該表面流動特徵2〇〇中之流動方向可為自邊緣111至邊緣113或反之亦然。換言之，液體可在該液體流入該第一流槽區段21〇且接著進入該第二流槽區段22〇或自遠第二流槽區段220至該第一流槽區段21〇之一方向上流動。亦將理解，液體可於沿該表面流動特徵（流槽）2〇〇之長度之任何數目之不同位置處進入該表面流動特徵（流槽）2⑻ 且因此液體並不限於初始僅沿該邊緣丨〗2而流入該流槽2〇〇之該開口端，而是可於介於該流槽2〇〇之該等端中間之若干中間位置而流入該流槽2〇〇中。在應用期間，該裝置100係較佳以使最佳化該液體（例如，眼内液）與該等表面流動特徵200及240之間之相互作用以達成本文所述之目的之定向而放置於該目標位置（例如’眼中）。換言之，較佳定向該裝置⑽使得該等表面流動特徵200及24G之定向係互補與該液體之流動方向及流動特I·生。此導致該液體在該表面流動特徵2〇〇内自然地流動且與該活性劑103接觸。該液體與該活性劑1〇3之間之相互用用以將β亥活性劑有效地施配至眼中且與該目標組織在此情形下，眼組織）接觸之-機制。藉由有效地引導（導 =)存在於該目標位置處之自然液體，該液體之自然流動型樣係用於將該活性劑施配至該目標組織。 I59575.doc -20 = 201223581 因此’該自然液體用作該活性劑之—載體錢該活性劑導向跨過眼睛，以允許更分散且有效地傳遞該活性劑。圖2及一些後續的圖中顯示眼内液體流入及流出該局部凹陷區域250之彎曲方向箭頭係僅僅示例性且在許多情形下，眼内液體可能僅沿該活性劑1〇3之外表面而流動且並不實質上進入該局部凹陷區域25〇中。在該實施例中，該活性劑103係使用若干習知技術而固持於該本體110上（例如，在該凹陷區域中），例如但不限於使用生物相容性黏合劑、該凹陷區域250内之物理特徵、呈圍阻形式之活性劑103的物理特徵等等。圖3顯示一裝置300,除了其一本體31〇之形狀之外其類似於裝置100。更明確而言，該裝置3〇〇具有一圓形本體 3 10且因此類似於一碟或圓盤或類似物。如同該裝置1〇〇，該裝置300包含沿該裝置300之一個或一個以上之表面而形成之一個或一個以上之表面流動特徵2〇〇及24〇 ^在所圖解〇之實施例中’一個表面流動特徵200係沿一第一表面或面 3 12形成。類似於圖2中所示之該表面流動特徵2〇〇，形成於裝置300中之該表面流動特徵2〇〇係呈一個多分支流槽之形式。更明確而言，該表面流動特徵2〇〇係呈一流槽之形式，其包含沿该本體310之一周邊邊緣（圓周邊緣）3丨1之一位置而開口之一第一流槽區段2 10及由與該第一流槽區段 310流體連通之複數個個別分支流槽區段322所形成之一第二流槽區段220。該等分支流槽區段322中之各者係沿該本體310之該周邊邊緣311之不同位置而開口。在所圖解之實 159575.doc -21- 201223581 施例中’具有三（3)個分支流槽區段322。將理解，關於圖1至圖2所述之該等表面流動特徵2〇〇及 240之所有結構性變動及設計細節同樣地適用於形成於本發明中所揭不且附圖中所圖解之任何其他傳遞裝置（包括裝置300)中之該等表面流動特徵2〇〇及。此外如圖所不，該裝置300包含用於容納及包含該活性劑1〇3之該局部區或2 5 0。對於先刖實施例，該活性劑1 〇 3經定位（且因此該局部凹陷區域25〇形成）於與該表面流動特徵2〇〇流體連通之一位置，以允許液體（例如，眼内液）由於該液體之流徑經該表面流動特徵2 〇〇引導或以其他方式修改而與該活性劑103接觸。關於圖2，圖3顯示在一個方向中自該第一流槽區段2丄〇至該第二流槽區段22〇之箭頭，將理解，流動可在一相反的方向，因為該液體可自該第二流槽區段22〇流動至該第一流槽區段21 〇。圖4顯示用於將活性劑傳遞至該目標組織之另一裝置 00圖4至圖20顯示裝置400之許多修改版。該裝置4〇〇經特疋设計且適於眼部藥物傳遞應用且明磘而言，經構造用於藉由將該裝置400放置於人眼之下前鞏膜或上前鞏膜（白色）而插入人眼中或佩戴於人眼中或用於靈長目或四足生物之治療。對於該先前實施例，將理解且在下文將更明顯瞭解到，該裝置400僅係本發明之一示例性實施例且絕非意在被解讀為限制本發明之範疇。 δ亥裝置400包含具有一邊緣頂點輪廓412之一本體41〇， 159575.doc -22- 201223581 該邊緣頂點輪廓係該裝置邊緣之倒角之量及定位且一般經界定為掃過該裝置400之-周長之—半徑剖面。該裝置_ 具有一基座曲線（一般標識為414)，其經界定為各個最高點 (即’垂直及水平）中之主半徑，且係該裝置彻之—般盘掌膜接觸之表面（該裝置之後表面）。在各個最高點處的值係相同的情形下，該基座曲線414經界定為球面基座曲線。在各個最高點處的值係不同之情形下，該後表面係界定為帛面後表面。在任何情形下，該基座曲線特徵係指該後表 y 面之具體曲率’其經選擇以既使該裝置配合至眼球且亦考量到眼驗與該裝置之相互作用，因此，如在隱形眼鏡設叶技術中所理解，使維持恰當位置與一非植入裝置保持在眼環境中之生物相容性所必需之移動間平衡。該裝置彻亦具有-邊緣提起部，其係圍繞鄰近且遵循該邊緣頂點輪廊 412之周長之一區段幾何寬度，於此該基座曲線414係較為平坦（增加）。該邊緣提升部係由半徑漸增及—寬度界定。 ◎《邊緣提升部特徵亦經理解為在該隱形眼鏡設計技術中作為一特別特徵來增強舒適度且允許該裝置在眼組織上移動而不造成刺激或（眼部）發炎。一（一個以上）前曲線418係界定為各個最高點（即，垂直及水沿該本體彻而界定之軸線））處之次級裝置半徑。 °亥等刖曲線產生與眼驗接觸之表面（該裝置之前表面）。在各個最高點處之值係相同之情形下，該前曲線418係界定為球面。在各個最高‘點中之值係不同之情形下，談裝置彻之該前表面係界定為一環面前表面。在一較㈣施例 159575.doc 23· 201223581 * 本^文所揭示$ 士為環面。該裝置4 狀裝置400、該前曲線418係界定衣置4〇〇亦可包含齒鍵，苴之幾何實體，其界定由夕項專式產生换 ' 自一經界定形狀或橫截面至g Μ. 橋接之平滑混合輪廓表面…曰… 至另一者之該裝置彻之眼驗側上之⑽裝在鄰近 ^之該邊緣之厚度之操縱者一晶狀===體 =且-般具有至該主要前彎曲半徑幾何體之=二二 4日日狀體遵循該邊緣頂點輪廓％之在§亥裝置400之周|月囹担似因此 ^ 之周長周圍提供—減小之厚度橫截该裝置400之該本體41 〇經構造及組熊白色部分（鞏膜）之給廒n ' a眼球本身之位署時有助於眼瞼對於_置400之置穩疋性、移動及舒適性之作用該裝置400亦必須维持連^ $ 。 S保持在原位，滯後於眼球之移動。此係為了允許淚膜=二且稍微環’以幫助防止該組織發紅、受刺激 '點曰“體周圍循又別激 '黏附至該組液及其他表面沈積物累積於前表面或後表面上。與眼目^ 相互作用亦由設計決定，且對於_隱料鏡 = 置彻之位置' 穩定性、移動及舒適性/裝识之“相互作用亦可允㈣淚膜在該裝置伽之 ^此有助於清除黏液累積，黏液累積傾向於連同堵截二結膜凹陷處之外來物而發生。 Ί 將理解，本發明之該農置彻可佩戴於角膜上方下方之輩膜上。因此’將理解’本文所述之用於眼部、之該等傳遞裝置可定位於此等兩個位置中〜考'。 159575.doc •24- 201223581 '如本申請案之申請人先前之專利申請公開案中所詳細描述’該裝置400可包含-個或_個以上之凸片415。在此實施例中，該裝置400-般呈-「„亞龄」之形式，其具有一相對薄之中央區段及形成於該裝置之該等端處之兩個相對之凸片區段415。該裝置400之啞鈴形狀使質量遠離該中心朝向該裝置400之該等端而再分佈，且引導至眼驗下方之該鞏臈上之所要的位置且在眼睛上之更大穩定性，同時維〇㈣積。該等凸片415亦提供具有增加之質量（厚度）之區域，該可容納該活性劑且明確而言，各個凸片415可包含用於包含該活性劑之一個或一個以上之局部凹陷區域 250。舉例而言且如圖解，一局部凹陷區域25〇(諸如，一井狀部)係形成於該凸片415中。在圖4中，具有兩個凹陷區域250,各個凸片415具有一凹陷區域25〇,以容納該活性劑。不同於前文之實施例，在圖4中顯示該表面流動特徵2〇〇〇 ϋ不具有一分支構造，其原因在於，該表面流動特徵咖更類似一線性流槽。該表面流動特徵2〇〇延伸橫越該裝置 4〇〇之寬度而自—邊緣到達一相對之邊緣。該表面流動特徵200延伸橫越該凸片415(例如，橫越該凸片415之—頂點）且如其他實施例中，該表面流動特徵2〇〇經設計引導或修改圍繞該裝置400之自然液體（例如，眼淚）之流動。如上文所述，液體之流動方向將取決於該裝置4〇〇之位置及定向，然而，該液體可於該表面流動特徵2〇〇内在任一方向上流動。 159575.doc •25- 201223581 如在其他實施例中，該表面流動特徵200係由可傾斜或直形之相對壁205界定。亦將理解，在本文所述之任何實施例中，該局部凹陷區域相對於該表面流動特徵200之寬度及長度之寬度及長度可變動。s亥流槽之寬度係該兩個相對之側壁之間之距離，而該流槽之長度係自該流槽之一端至該相對端而測量。明確而言，該局部凹陷區域（且因此，該活性劑）之寬度可為該表面流動特徵之該寬度之至少5〇%或可為至少7〇% ;或可為至少9G%。此外，纟—些應用中，該局部凹陷區域之該寬度可小於該表面流動特徵之該寬度之5〇%。在另一實施例中，該局部凹陷區域及該活性劑之該寬度可大於該流槽之該寬度。關於該流槽之該長度，該活性劑較佳沿小於 ^饥槽之i個長度之長度而定位且可僅代表該流槽之整個區域之一分率（例如，小於25%、小於10%等等）。然而，在其他δ又计中，該百分率可更高。圖5 員示裝置401，其極其類似於該裝置4〇〇，且主要不同在於該裝置401僅包含形成於該等&片415中之一者上單表面*動特徵200。該單一表面流動特徵2〇〇所具有刀支類型與圖2中所示之分支類型類似。將理解，該 '片5中之各者可包含一表面流動特徵2〇〇(其包含— :性劑）或與局部凹陷區域250連通。如在本文所述之所有實施例中’該局部凹陷區域250之深度係取決於若干因素’包含該裝置之該本體之尺寸、該活性劑之特性（包含尺寸）、待施配之活性劑之量等等。 159575.doc • 26 - 201223581 在圖5之實施例中，該笤公A、味寻刀支/爪槽區段222終止於一邊緣處或該邊緣之附近。可理解，該等分支流槽區段222可終止於並不位於該裝置之該邊綾虚 ^进緣處或附近之一點處。在此一構造中’該分支流槽區段222夕兮 • 2之該端可包含用於促進液體流出或流入該分支流槽區段222之一構件。例如，該分支流槽區段222之該端可包含另一表面流動特徵、一傾斜表面（斜坡），其用於促使液體流入或流出該分支流槽區段〇 222。對於其他實施例，當該表面流動特徵200具有一分支構造時，可具有兩個或兩個以上之分支流槽區段⑶。在此實施例中，該等分支係由表面流動特徵24〇促成。圖6顯示一裝置403 ’其類似於該等其他裝置4〇〇、4〇1且係由本體410及若干凸片415界定。在此實施例中，各個凸片415〇 3呈刀支流槽形式之一表面流動特徵2〇〇且明確而。，在所圖解之實施例中，該表面流動特徵可具有三個分支（分支流槽區段222)。類似於圖4至圖5，液體係意 Q 在沿該表面流動特徵20〇而流動且將理解，流動之方向可取决於特疋的應用。舉例而言且如圖7中所示，當邊緣係定位鄰近該角膜且與角膜成面對關係時，該液體可在自該第一流槽區段210至該第二流槽區段22〇之一大體方向上流動。然而，在本發明之範疇内，根據該裝置之定向及其他考量，流動可在一相對之方向上。圖8顯示該裝置400之一後（下側）表面4〇9且在此實施例中，一個或一個以上之表面流動特徵2〇〇沿該後表面4〇9而形成。 159575.doc -27- 201223581 將理解’如本文先前所論述’該活性劑可分散遍及形成該裝置400之一聚合物基質或其可定位於一局部凹陷區域 (諸如’區域250)中。對於形成於多個裝置之前表面上之該戊等）表面流動特徵2〇〇,在該後表面上形成該表面流動特徵200係用於引導/修改液體（例如，眼内液）之流動，使得促成將該活性劑傳遞至該目標組織。換言之，與本文所述之任何裝置關聯之該表面流動特徵2〇〇作為一表面流動導官，其中液體流動與關聯於該襞置之該本體之該活性劑接觸。將理解，在本文所述之任何實施例中，表面流動特徵 200及240可形成於該後表面上，且亦可形成於該傳遞裝置之相對之前表面上。將理解’在本文所述之任何實施例中，一表面流動特徵 200可形成於該後表面或前表面上，且該特徵在達到該裝置之s亥周邊邊緣之前而終止’且可使用一斜坡、傾斜部或有用的特徵來允許該液體更容易地流入或流出該表面流動特徵200。圖9中顯示一示例性液體流動型樣。然而，如在其他實施例中，將理解’ 一相反之流動型樣同樣可行。圖9顯示該活性劑103係設置於一局部凹陷區域250(例如，一袋狀部）内。圖10顯示類似於先前實施例（包含圖7之實施例）之另一實施例。在圖1 0之該實施例中，圖解一裝置5〇〇。該裝置 5 00之與其他實施例共有之特徵係用相同的數字標識。不 159575.doc = 28- 201223581 ^於其他實施例，該裝置500之-本體510包含複數個通孔或通路或通道550。該等通孔55〇係呈穿過該裝置5〇〇之該體5 1 〇之開口之形式。例如，一個或一個以上之通孔$ $ 〇經形成與該表面流動特徵200流體連通，以提供用於將該 '舌性劑傳遞至該目標組織之另-或額外構件（例如，可直接地形成於該表面流動特徵内）。在所圖解之實施例中，該等分支流槽區段222中之各者 ^含至少一個通孔550。該等通孔550可形成於該分支流槽區段222内之任何位置，因為此代表一般位於該活性劑103 源之下游之一位置。該等通孔550提供該液體之一次級流徑，因為一些該液體可在該表面流動特徵2〇〇内流動超過該通孔55〇,而一些液體向下流入該通孔中，於此其經引導與該目標組織鄰接。因此，該等通孔550提供用於將活性劑自該活性劑源傳遞至該目標組織之另一構件。現參考圖11，圖解用於傳遞一活性劑之另一裝置6〇〇。該裝置600係類似於本文所述之其他裝置。在此實施例申，各個表面流動特徵2〇〇(例如，流槽）具有一閉合端，因為該表面流動特徵並不如先前實施例中沿該裝置6〇〇之該邊緣之至少兩個區段而開σ。在此實施例中，該表面流動特徵200具有一閉合第一端211及一開口端213。在所圖解之實施例中，該局部凹陷區域（例如，袋狀部或儲液部）250係位於該表面流動特徵2〇〇之該閉合第一端 211處或附近。圖U顯示該表面流動特徵2〇〇具有一分支流 159575.doc -29- 201223581 槽構造且因此，所圖解之表面流動特徵2〇〇係由延伸朝向且終止於該裝置600之-本體㈣之1邊邊緣處或附近之複數個分支流槽區段222形成’以促進活性劑自該源1〇3流動至該目標組織，該裝置_係定位於該目標組織上方附近。該等分支流槽區段222係定位於該活性劑1〇3之源之—側上且因此，眼淚之流動（藉由眼驗之泉送作用及農置連同眨眼之輕微移動而輔助）將使自該裝置釋放之該活性劑朝向該目標組織分佈。圖11中所示之該表面流動特徵扇可具有本文描述且圖解之其他實施狀該表面流動特徵2 G G料之任何特性。顯示眼淚流動之方向箭頭係僅僅示意性且由於具有此設計之該閉合端2U，該液體（眼淚）在與該閉合端211相對二遠離之-方向上流動朝向該本體610之一周邊邊緣，於此由該液體承載之該活性劑係施配至該目標組織。圖12顯不一襄置700，其極其類似於圖11之該裝置600，只不過f表面流動特徵扇並不呈—分支流槽構造之形式而疋絲面流動特徵200具有類似於圖4中所示之更性構造。對於先箭音说y ' 貫施例，該表面流動特徵200具有該活性劑103處或j 4 na人、 _ —，一閉5端211，該活性劑在圖中細顯示為經設置於兮尽如、·工罝於》玄局部凹陷區域25〇(例如，一袋狀部）内。在圖1 2中，太Α m 向前頭指示當該裝置700經放置於眼中付该表面流動特徵2 ^^ + ^ 00在一方向上自眼睛之角膜徑向向外延伸時液體（諸如，目ρ^ 眼淚）之一可行流動型樣，且因此， 159575.doc -30- 201223581 常艮淚抓動垔樣(上文已詳盡描述)導致眼淚進入該表面流動流槽細中且經引導朝向該活性劑⑻。如在其他實施例中艮淚與„亥活性劑接觸且眼淚之繼續流動促進將該活性劑103自其位於本體710中之源施配至該目標組織(即，眼組織）。圖13揭不本發明之另—實施例，其中圖解用於傳遞該活 /·生劑103之裝置_。該裝置8〇〇係類似於圖⑺之該裝置Behney's (four) special (four) 3, 3G2, 6 Jian reveals a kind of poetry serum eye drug delivery device. The device has a pocket filled with an ointment that is adjacent to the corneal surface of the eye and the anterior surface of the sclera. More generally, the sump is located inside the device and most of the prior art of such devices is concerned with transporting the drug from the sump to the surface of the device or to the transport rate of the dispensing surface. U.S. Patent No. 3,416,53, issued to Ness, discloses the use of a perforation having capillary action to drive a drug from its internal reservoir to the surface of the device. U.S. Patent No. 4,186,184 to Zaffaroni discloses a device having a delivery opening leading to the surface of the device which is considered to be the most suitable target. The use of a hydrogel to transport a drug from the reservoir to the surface of the device is disclosed in U.S. Patent No. 4,973,304 to the disclosure of U.S. Pat. (d) Chen et al., U.S. Patent No. 5,9G2,598 discloses a device for expanding a mouthpiece for transporting a drug from the reservoir to the surface of the device. For many drugs and transmission ligatures, ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Large bag. _ ^ The music system is released from this system via a U-open or entrance to the eye tissue located on the device. However, in terms of degree, the drug release is limited to one of the eye tissues. Issues of concern, specifically with regard to the known side effects of the drug' 卞 use 4 as inflamed, and specifically, in the 159,575. Doc 201223581 The device is relatively movable relative to the immediate tissue. Thus, in the field of ocular drug delivery, f is a drug delivery device that can be incorporated into a drug reservoir and that extends drug release from a larger portion of the ocular tissue from the reservoir. Ideally, the device should be capable of delivering a variety of medications or beneficial physical conditions for the treatment and should be relatively easy to manufacture. In addition, the relatively smooth surface of the matrix device will benefit from the tear flow characteristics, which increase and improve the device surface area and increase drug acquisition and dispersion. SUMMARY OF THE INVENTION ^ ^ _ 3, a device for delivering an active agent comprises a body having at least one surface for placement adjacent to a target tissue, the active agent being delivered to the target tissue. The target tissue also contains a body fluid. The active agent is associated with the body and is carried by the body in any number of different ways, including, but not limited to, being disposed within the substrate forming the body in a localized region, such as in a partially recessed region (eg, , in a well, a bag or a liquid storage part; sigh along the surface of the body. The physical features on the surface of the device direct, interrupt, or otherwise modify the flow of the body fluid to the body such that contact occurs between the body fluid and the active agent to The active agent is delivered to the target tissue. When the active agent is disposed in the partially recessed region, an environment external to the device can obtain the active agent through the opening of the recessed region. In an application, the device is used in an eye environment. In this embodiment, the fluid system is in the form of an intraocular fluid (e.g., tears) and one of the surfaces of the body is placed in contact with or adjacent to the target tissue, 159575. Doc 201223581 The standard tissue is in the form of ocular tissue, such as the sclera of the eye or other areas. The physical features on the surface of the attack guide or otherwise modify 2 the liquid (4) toward, across, and/or away from the region containing the active agent. In another aspect, the invention as a whole relates to the delivery of an active agent (e.g., a drug) to body tissue (target tissue) over an extended period of time. In addition, the present invention relates to the control agent of the present invention, which is more clearly but not limited, the present invention relates to the use of an ocular implant, a tear duct, and the eye of the present invention. Configuration of the device uses two: implants, contact lenses, and other aspects of the invention regarding control self-configuration for drug delivery. Material transfer device... Release: ―—Kibei type or - storage type of medicine. Box Gu... has two operational methods to practice the invention. One method is suitable for a device for the construction of a matrix of a drug. The first: =;,, is completely contained, wherein the drug is in a tank type device and can be a local type of substrate type and tank type. In addition, the installation will be a combination of the "&" combination. One of the devices is used to deliver different drugs. The device of the invention can better manage the release rate in the dysfunction and the drug treatment, and can be configured to be used as time lapse, - finite 曰Know the surface area. As the device begins to dispense the drug, it is more likely that the surface area will be exposed to body fluids and tissues and that the surface will have an initial release. Corrosion through the bioerodible covering of the potential distribution table s ice or thickness 159575. Doc 201223581 will gradually result in greater surface area exposure and thus a more gradual reduction in release rate than in a fixed size-dispensing surface. In the aspect of the invention, the invention includes a drug having a structural body, wherein the drug is present in the entire body or in a partial region of the body and the drug passes through one or more of the body The surface is released to the environment outside the body. [Embodiment] This application discloses several devices for delivering an active agent (which may be in the form of a drug and/or a therapeutic agent and/or other beneficial agent) to a target tissue. A device such as S Hai is intended to be placed in the patient's body adjacent to the target tissue to which the active agent will be delivered. It should be understood that the devices can be placed at any number of different locations within the body and, therefore, the target tissue can be a different tissue throughout the body of the patient. In one embodiment of the invention, the device is in the form of an 〇 phthalmic/ocular delivery device that is part of a partial ocular delivery system and the ocular delivery device is designed to tear Physically directed to one or more dispensing surfaces of the delivery device to dispense the active agent (drug and/or therapeutic agent, etc.). As will be described in detail below, when the active agent is contained within a polymeric matrix defining one of the body of the drug delivery device and/or the dispensing surface of one of the active agents, the dispensing surface can be in the delivery device One of the exposed surface forms and/or the dispensing surface can be an exposed surface having an active agent disposed in a partially recessed space (eg, a well, stored in the body formed in the transfer device) Inside the department, cabin, cavity, liquid storage, bag, etc.). To 159575. Doc 201223581 This method 'the active agent can be woven. Release to the target group in a controlled manner. Figures 1 through 3 illustrate the transfer of an active device (10) in accordance with an embodiment. As described above, the delivery device i (10) can be used to treat different target tissue locations in any different number of applications relative to the disease. Although the device 100 is described herein as being a "drug" (the fine delivery device 'should understand" that the device - and other devices disclosed herein and not in the plurality of figures are not limited to the delivery of a medical drug, It is useful for delivering an active (therapeutic) agent that is not technically classified as a medical drug. ', and more specifically, the device 100 and other devices disclosed herein and not in the plurality of figures Constructed to deliver an active agent to a target tissue. An expression "agent" is used herein to broadly encompass any compound, composition of matter, or mixture of substances that can be delivered from the device to produce a profitable and useful result. For the purposes of the present invention, a medicament, a medical agent, a therapeutic agent (therapeutic called 61^, a beneficiu agent, or a drug) may be considered synonymous. The device described in the present invention comprises An active agent which effectively obtains one of the desired local or systemic physiological effects or pharmacological effects. The following classified active agents can be incorporated into the device of the present invention. Suitable drugs or active agents for use in conjunction with the delivery include (by way of example only, without limitation): (A) anti-infective drugs: such as, for example, vitamins, tetracycline, gas tetracycline, bacitracin Neomycin, oxymyxin B, gramicidin 'oxytetracycline, chloramphenicol and erythromycin; sulfonate 159575. Doc -10 - 201223581 Indoleamines, including, acesulfame, sulfamethoxazole, isoxazolidine; quinolones, including ofloxacin, norfloxacin, capefloxacin, sparfloxacin, amine Glycosides 'comprising' amikacin, tobramycin, gentamicin ^ I, cephalosporin; combination of antibiotics; antiviral drugs, including, glucoside, difluorouridine, adenosine Dofovir, sodium phosphinate, ganciclovir and acyclovir; antifungal drugs such as amphotericin B, nystatin, flucytosine, fluconazole, natamycin, mycoconazole And ketoconazole; and other anti-infectives, including, nitrofurazone and sodium propionate; (B) anti-allergic drugs, such as, anoxazoline, mesalpin, chlorpheniramine, mepyramine, and cimetidine, Imestatin, ketorolac, levocabastine, lodosamide, gasteprine, naphazoline/antazozoline, naphthyloxaline/pizopiramide, olopatadine and cromolyn Sodium; (C) anti-inflammatory drugs: such as hydrocortisone, hydrocortisone acetate, dexamethasone, dexamethasone 21-phosphate, fluocinolone, hydroxybutazone, hydrogenation Ponisone, hydrogenated prednisone 21_phosphate, prednisolone acetate, fluorometholone, fluorometholone acetate, hydroxybutazone, loteprednol citrate, double Q 曱醯醯 ;; (D) non Sterol anti-inflammatory drugs: such as flurbiprofen, suprofen, difenfen, indomethacin, ketoprofen and ketorolac; decongestants: such as phenylephrine, naphazoline, hydroxymethyl Oxazoline and tetrahydrozoline; (F) miotic and anticholinesterase: for example, pilocarpine, salicylic acid " bean domain, carbachol, diisopropylfluorophosphate, Iodophos eye drops and diammonium bromide; and (G) mydriatic drugs: such as atropine sulfate, cyclopentane; posthorse PO, sputum domain, tropicamide, eucatropine and hydroxy amphetamine. In addition, the following / lingual agents can also be used in the device of the invention: (A) anti-glaucoma agents: such as, epinephrine, including, adrenaline and dipyridamole 159,575. Doc 201223581 Lin, ring-negative adrenaline, 0_ kidney betaxolol, medi's ol's containing 'bunolor' tilalolol, timolol, carteolol agonist, including, Mao Younan Adrenergic enzyme inhibitor, including amide guanidine test; biliary test enzyme inhibiting sword, swearing scent, yoke 峨®; carbonic anhydride " 匕3, benzene sulfonamide, oxazolamide, vinegar Fazozinamide, tromethamine, brinzolamide, dichlorobenzenesulfonamide; sputum gland: linsin, travoprost, prasaldine, merinostat, dlconosoids and above Drugs such as 'β-adrenal inhibitors and acid-degrading enzyme inhibitors 22' and (Β) anti-cataract drugs: such as aldose reductase, torstastat, stetol, sobinil; Antioxidant, package ^; scurvy acid, vitamin E; total 1 hate zinc. S raises money' contains, glutathione and another group of active agents are in the form of lubricants: such as, glycerol, polyglycerol and selectively water-soluble polymers, fiber: :, - polyethylene glycol and Biopolymers such as =: acid and chitosan. The monthly drug described herein can be used with the sustained release of the present invention: it is used to manage and manage other agents suitable for treatment, benefit, and condition. > Hypnotic 邛 In an exemplary application, the drug delivery device 1 is a local ocular drug delivery device (10), ", it will be understood that: 100 is not limited to use in eye applications, but Second, to treat other parts of the body. The drug passed two = should be: The body U0 is defined, in this particular example hand by the predetermined ruler I59575. Doc •12· 201223581 inches to allow placement in the eye. The body 110 is defined by a first surface or first surface and - opposite second or second surface 13". The thickness of the body 110 is defined as the distance between the first surface 120 and the second surface 13〇. The body 11A includes a peripheral edge, which is shown as a side wall in the illustrated embodiment. It will also be understood that the shape of the illustrated body 11G is merely exemplary and that the body 11G may have other shapes. The body m is formed such that it has a degree of flexibility 'to allow the body UG to be placed at the target location of the target tissue. Thus, the body 11 can have material properties that allow the body to conform at least substantially or substantially to the shape of the target tissue (the body is applied to the tissue). For example, when applied to an eye application, the body 110 can be adapted to the shape of the eye, as will be described in more detail below. It will also be understood that either the first surface 120 or the second surface 13A can be placed against the target tissue' and thus the opposing surface faces away from the target tissue. In an ocular application, the first surface 120 or the second surface 13 can be placed against the tissue of the eye, as described in more detail below. It will be understood that while the body 110 has symmetry around a central draw line, the device 100 is not limited to having such a characteristic, and conversely, the body 110 can have an asymmetrical configuration. The prior literature (work) owned by the present inventors describes various ocular drug delivery systems. For example, U.S. Patent Application Serial Nos. 10/569,743, the entire disclosure of each of which is incorporated herein by reference. Therefore, it will be understood that the device 100 is described herein and illustrated in the drawings and is 159,575. The other devices of doc 201223581 can be formed from the materials disclosed in the case of the ***, and have the structural characteristics disclosed in the above-mentioned application. In accordance with the present invention, at least one surface flow characteristic of the body 11() is characterized by eight features 2GG and/or 240' to guide or otherwise: the body "〇 contact one of the liquids Flowing to assist in the transfer of the activity to the target H is in the figure, the surface flow feature 200 is formed in the first surface 12G, the first surface 12 being away from the target, and the surface of the weave. . As shown in FIG. 1, the surface flow feature 2 can be in the form of a partially recessed region having a predetermined characteristic such as shape and size and (d) that directs or otherwise modifies contact with the body 110. The flow of liquid to aid and optimize the delivery of the active agent to the target tissue. For example. As will be described in greater detail below, the surface flow feature 2 can be configured to modify the flow of liquid toward the dispensing surface, or away from the dispensing surface or toward or away from a particular localized area defined on the dispensing surface. The surface flow feature 200 is in the form of a surface feature or modification that defines a flow path ' along the body of the body to cause the liquid to flow in the flow path as the liquid flows along the body of the device Flowing in. The surface flow feature 200 at least partially comprises the liquid. The surface flow feature 200 can be a recessed open flow channel, groove or other recess having one shape and several dimensions suitable for directing or modifying the flow of liquid. The surface flow feature 200 can also be understood as being in the shape of a slope, a trough, a sluice, a valley, a half pipe, a chuck, a varnish, etc., which is gradually narrowed, widened, turned, twisted, etc. 159,575. Doc 14 201223581 et al., or a combination of these forms. Two of the at least partially open conduits, the surface flow feature 200 moving from one position to another through which the liquid can flow and seven although the surface flow feature 200 is discussed herein as a recessed flow trough % 4" Regarding unity, it will be appreciated that within the scope of the present invention, the surface features 200 may be in the form of any number of differently shaped recessed structures. ^^ α圈, the surface flow characteristic 2 0 0 is not limited to a linear configuration; skin & 3 _l ?on 疋 Conversely, the surface flow characteristic Ο 200 may have one or one 'f curved section And can have a branch structure as shown. Thus, the surface flow feature can open along one or more peripheral edges of the body U0. For example, the surface flow feature 200 can be opened along both peripheral edges of the body U〇. Within the scope of the present invention, the surface flow feature 200 does not open along any peripheral edges, as illustrated and described herein. Further, the surface flow feature 200 can be located at more than one location along the perimeter edge of the body 11. It will also be understood that the depth of the flow channel can vary depending on the particular application and characteristics of the body 1G, such as the thickness of the body 110, and the like. Moreover, the surface flow feature 200 (flow cell) can be defined by varying a number of depths because one of the surface flow features 200 can have a first depth (relative to the surface of the body 110) And another region may have a first depth different from the first bed (relative to the surface of the body 110). As shown in FIG. 1, the surface flow feature 240 may have a predetermined characteristic (shape and One of the dimensions and contours) is a form of locally elevated area, such as its I59575. Doc 15 201223581 directs, interrupts, or otherwise modifies the flow of liquid in contact with the body u to assist and optimize delivery of the active agent to the target tissue. For example and as will be described in detail below, the surface flow feature can be configured to modify the flow of liquid toward the dispensing surface, or away from the dispensing surface, or toward or away from a particular localized region defined on the dispensing surface. . The surface flow feature 240 is in the form of a surface feature or modification that changes the liquid flow path along the body of the device or along the flow channel. The surface flow feature 24G is in the form of a wedge, a pier or other elevated shape that has dimensions suitable for inducing, interrupting, or otherwise modifying the flow of the liquid. The surface flow feature 240 can also be understood as a slope, a protrusion, a column, and any other elevated feature that divides, deflects, or otherwise interrupts and alters the flow of liquid in the eye through the surface, or in one of these forms. Combination 0 In some embodiments, an elevated surface feature may reside within a concave surface flow feature or, conversely, a concave surface flow feature may reside within or on the elevated surface flow feature. Moreover, an embodiment can have any combination of these. However, as illustrated in the drawings, the surface flow feature may be of a non-branched type of one of the surface flow features 240. In this embodiment, the surface flow feature 200 acts on the flow of the bodily fluid. Referring specifically to FIG. 1, the surface flow feature (flow channel) 2〇〇 has a branching structure' because the flow cell includes a first-flow groove region along the first edge ill of the body 丨1〇 The segment 21〇 and the plurality of individual branch flow channel segments 222 in fluid communication with the first flow channel segment 210 form a second I59575. Doc - 16 - 201223581 The runner section 220 ❶ these branches are formed by the raised wedges (elevating sections) 240. Each of the branch flow channel sections 222 is open along a second edge 113 of the body 110. The second edge lu is opposite the first edge 111. In the illustrated embodiment, there are three (3) branch flow channel segments 222. It will be appreciated that the cross-sectional shape of the surface flow feature (fluid) 2〇〇 is variable and selected for a particular application. For example, in one embodiment, the flow cell 200 can be defined by two opposing walls 210 that are at least substantially perpendicular to the bottom portion 22 of the first stage trough. Alternatively, the launder 2 can be defined by two opposing walls 2〇5 forming an angle with respect to the bottom 220 of the launder. Thus, in this embodiment, the walls 205 are similar to the inclined walls shown in FIG. The angle formed by the walls 205 creates an inclined flow channel and can be configured to vary the flow kinetics of the liquid traveling into, out of, and traveling within the flow channel. For example, the inclined walls 205 assist in the flow of liquid through the walls to allow liquid to flow more easily into and out of the flow cells 2 . Moreover, it will be understood that the individual branch runner segments 222 may have different characteristics with respect to one another and, in particular, the width and/or length and/or shape of the branch runner segments 222 may vary. For example and as shown in FIG. 1, a branch trough section 222 can have a relatively large length; the first trough section 222 can have a larger width and the trough sections 222 have different shapes. 1 shows the device 100' wherein the active agent is contained within the body 11 (eg, 'dispersed throughout a polymer matrix forming one of the bodies 110) and passes through one or more surfaces of the body 110 (eg, a surface) 12〇) and 159575. Doc 17 201223581 with. When the device 100 is intended to be placed in the eye (i.e., an eye application), the flow cell 200 is used to direct and/or modify the flow of intraocular fluid (e.g., tears). A more easily identifiable intraocular fluid tears. The tears are usually lubricated and necessary to wash away particles and foreign objects. As understood in the art, most of the tears in a person's eye are produced by the main lacrimal gland, which is located above the nose from the center of the eye and slightly adjacent to the temple, or away from or opposite the nose. The tear production system begins in the lacrimal gland and has a plurality of smaller cryptic glands along the upper and lower eye examinations and in the conjunctiva covering the surface of the eyeball, which provide oily and mucus to the tear film. Although the blinking mechanism rebuilds a film on one of the exposed portions of the eye during any blink interval, the film represents a small fraction of the overall tear volume in the eye. The flow of conventional tears follows from the lacrimal gland (source) down to the surface of the eye, and at the same time across the eye toward the nose (where several drainage holes (puncture points) are located) generally flows through. Therefore, when the eyelids are closed, the eyelids are slightly closed toward one of the noses, thereby pushing the tears in the direction of the drain holes. It will be understood that the above description of the liquid mechanism describing tears is not limited to the present invention, but rather a mechanism for describing how tears flow in the eye is accepted. Thus, the surface flow feature 200 acts to direct and direct the tear along a predetermined flow path to assist and optimize the release of the active agent contained in the body 11〇. 2, 4 is not according to a different embodiment of the device 1 〇 1, which is similar to the device 00, however, the device 1 包含 1 comprises a partial recessed area (empty) (such as the pocket portion of the reservoir) , cavity, remainder, well, groove, etc. I59575. Doc •18- 201223581, etc.) One of the additional features. The partially recessed region 250 can have any shape and size that will provide space, any number. It is positioned and formed to make it with. The surface gripping feature 2 is in fluid communication but is recessed relative to the surface flow characteristic 2〇0. More specifically, the partially recessed region 250 contains or houses the active agent (defined as 1〇3 in Fig. 2). Accordingly, the structural characteristics and locations of the surface flow features and 240 are selected to direct or otherwise modify the intraocular fluid to maneuver, cross or enter, and away from the local depression 250. An active agent 103 can be in any number of different forms and can have any number of different shapes and of different sizes. It will be understood that the form and size of the active agent 1〇3 will depend, at least in part, on the active agent itself and the particular application. For example, the active agent 103 can have the following form: a solid tablet; a polymer matrix of one of the active agents, a solid structure comprising one of the liquid active agents in a discrete well, a gel structure, a capsule a liquid active agent encapsulated in a structure, a liquid contained under a film, a polymer matrix comprising one of the active agents under a thin crucible, or may have any other form as long as the active agent 103 It can be in fluid communication with the localized region 250 and can be dispersed in a controlled manner. In FIG. 2, the active agent 103 is located within the surface flow feature (flow cell) 200 and, in particular, the active agent 1 〇 3 is positioned adjacent to the first flow channel segment 210 and the individual branch flow regions The interface between segments 222. This configuration allows liquid (e.g., intraocular fluid) flowing within the first flow channel section 210 to contact the active agent 103 and then flow in a direction away from one of the local regions 250 containing the active agent 1〇3. 159575. Doc -19-201223581 For other embodiments, although not shown in the drawings, it will be understood that there may be a plurality of spaced partial regions 25 within each surface flow feature 200. These areas can accommodate the same or different types of active agents. It will also be appreciated that the flow direction in the surface flow feature 2 can be from edge 111 to edge 113 or vice versa. In other words, the liquid may flow into the first trough section 21 and then into the second trough section 22 or from the far second trough section 220 to the first trough section 21 flow. It will also be appreciated that the liquid can enter the surface flow feature (flow channel) 2 (8) at any number of different locations along the surface flow feature (flow channel) 2〇〇 and thus the liquid is not limited to initially only along the edge. And flowing into the open end of the flow cell 2, but flowing into the flow cell 2 at a plurality of intermediate positions intermediate the ends of the flow cell 2〇〇. During application, the device 100 is preferably placed to optimize the interaction between the liquid (e.g., intraocular fluid) and the surface flow features 200 and 240 for the purposes described herein. The target location (eg 'in the eye'). In other words, the device (10) is preferably oriented such that the orientations of the surface flow features 200 and 24G are complementary to the flow direction and flow of the liquid. This causes the liquid to naturally flow within the surface flow feature 2 and contact the active agent 103. The interaction between the liquid and the active agent 1〇3 serves to effectively administer the β-ly active agent to the eye and to contact the target tissue in this case, the ocular tissue. The natural flow pattern of the liquid is used to dispense the active agent to the target tissue by effectively directing (conducting) the natural liquid present at the target location. I59575. Doc -20 = 201223581 Thus the natural liquid is used as a carrier for the active agent. The active agent is directed across the eye to allow for more dispersed and efficient delivery of the active agent. 2 and some subsequent figures show that the arrow of the direction of the flow of the intraocular fluid into and out of the partially recessed region 250 is merely exemplary and in many cases, the liquid in the eye may only be along the outer surface of the active agent 1〇3. It flows and does not substantially enter the local recessed area 25〇. In this embodiment, the active agent 103 is retained on the body 110 (eg, in the recessed region) using a number of conventional techniques, such as, but not limited to, the use of a biocompatible adhesive within the recessed region 250. Physical characteristics, physical characteristics of the active agent 103 in a containment form, and the like. Figure 3 shows a device 300 which is similar to device 100 except for the shape of its body 31〇. More specifically, the device 3 has a circular body 3 10 and is thus similar to a dish or disc or the like. As with the device, the device 300 includes one or more surface flow features 2 and 24 formed along one or more surfaces of the device 300 in the illustrated embodiment. The surface flow feature 200 is formed along a first surface or face 312. Similar to the surface flow feature 2 shown in Figure 2, the surface flow feature 2 formed in the apparatus 300 is in the form of a multi-branched flow cell. More specifically, the surface flow feature 2 is in the form of a first-class groove that includes one of the openings 3 1 along one of the peripheral edges (circumferential edges) of the body 310 and opens one of the first trough sections 2 10 And a second flow channel section 220 formed by a plurality of individual branch flow channel sections 322 in fluid communication with the first flow channel section 310. Each of the branch flow channel segments 322 opens at a different location along the peripheral edge 311 of the body 310. In the illustrated reality 159575. Doc - 21 - 201223581 The embodiment has three (3) branch flow trough sections 322. It will be understood that all structural variations and design details of the surface flow features 2 and 240 described with respect to Figures 1 through 2 are equally applicable to any of the embodiments illustrated in the drawings and illustrated in the drawings. These surface flow features are included in other transfer devices, including device 300. Further, as shown, the device 300 includes the localized region or 250 for containing and containing the active agent 1〇3. For the prior embodiment, the active agent 1 〇 3 is positioned (and thus the partially recessed region 25 〇 is formed) in a position in fluid communication with the surface flow feature 2 , to allow liquid (eg, intraocular fluid) The active agent 103 is contacted by the flow path of the liquid being guided or otherwise modified by the surface flow feature 2 . With respect to Figure 2, Figure 3 shows the arrows from the first trough section 2 to the second trough section 22 in one direction, it will be understood that the flow can be in the opposite direction because the liquid can be self-contained The second flow channel section 22〇 flows to the first flow channel section 21〇. Figure 4 shows another device for delivering an active agent to the target tissue. 00 Figures 4 through 20 show many modified versions of the device 400. The device 4 is specifically designed and suitable for ocular drug delivery applications and, in the case of alum, is configured to be placed under the human eye by the anterior sclera or the anterior sclera (white). Inserted into the human eye or worn in the human eye or used for the treatment of primates or quadruped creatures. It is to be understood that the device 400 is merely an exemplary embodiment of the invention and is not intended to limit the scope of the invention. The AH device 400 includes a body 41〇, 159575 having an edge apex profile 412. Doc -22- 201223581 The edge apex profile is the amount and location of the chamfer of the edge of the device and is generally defined as the radius profile of the circumference of the device 400. The device _ has a pedestal curve (generally designated 414) that is defined as the major radius of each of the highest points (ie, 'vertical and horizontal') and is the surface of the device that is generally in contact with the palm of the hand (this Surface behind the device). The pedestal curve 414 is defined as a spherical base curve where the values at the respective highest points are the same. In the case where the values at the respective highest points are different, the rear surface is defined as the rear surface of the kneading surface. In any case, the pedestal curve characteristic refers to the specific curvature of the y-plane of the posterior table, which is selected to allow the device to fit into the eyeball and also to account for the interaction of the eye exam with the device, thus, as in stealth As understood in the spectacles setting technique, the balance necessary to maintain proper position and maintain the biocompatibility of a non-implanted device in the ocular environment is balanced. The device also has an edge lifter that surrounds a geometrical width of a section adjacent to and following the perimeter of the edge vertex porch 412, where the pedestal curve 414 is relatively flat (increased). The edge lift is defined by an increasing radius and a width. ◎ The edge lift feature is also understood to be a special feature in the contact lens design technique to enhance comfort and allow the device to move over the ocular tissue without causing irritation or (eye) inflammation. One (one or more) front curve 418 is defined as the secondary device radius at each of the highest points (i.e., the axis perpendicular to and defined by the water along the body). The 亥刖刖 curve produces a surface that is in contact with the eye (the front surface of the device). The front curve 418 is defined as a spherical surface in the case where the values at the respective highest points are the same. In the case where the values in the respective highest ‘points are different, it is said that the front surface is defined as a front surface of the ring. In a more (four) application 159575. Doc 23· 201223581 * This article reveals that the $shi is a torus. The device 4 device 400, the front curve 418 defines the clothing 4 can also include a tooth key, the geometrical entity of the ,, which is defined by the eve of the special shape from a defined shape or cross section to g Μ. Smoothly blending the contoured surface of the bridge...曰... The device to the other is on the side of the eye (10) The operator who is attached to the thickness of the edge of the edge is a crystal ===body=and generally has The main front bending radius geometry = 22nd and 4th day, the celestial body follows the edge apex contour % in the week of the § hai device 400 | 囹囹 like the circumference of the ^ ^ provided - reduced thickness cross section of the device 400 The body 41 is constructed and the bear white portion (sclera) is given to the eyeball itself, which helps the eyelids to stabilize the movement, comfort and comfort of the device 400. Must also maintain the connection ^ $. S remains in place, lags behind the movement of the eye. This is to allow the tear film to be = two and slightly ringed 'to help prevent the tissue from reddening and irritating 'points' around the body and not to spurt 'adhesion to the group of liquids and other surface deposits accumulated on the front or back surface The interaction with the eye ^ is also determined by the design, and for the _ hidden lens = the location of the 'stability, movement and comfort / assembly of the interaction" can also allow (four) tear film in the device gamma ^ This helps to clear the accumulation of mucus, which tends to occur in conjunction with obstruction of the conjunctiva. Ί It will be understood that the present invention can be worn on the film above the cornea. Thus, it will be understood that the delivery devices described herein for the eye can be positioned in such two locations as the test. 159575. Doc. 24 - 201223581 'The apparatus 400 may include more than one or more tabs 415 as described in detail in the applicant's prior patent application publication of the present application. In this embodiment, the device 400 is generally in the form of "adolescent" having a relatively thin central section and two opposing tab sections 415 formed at the ends of the apparatus. The dumbbell shape of the device 400 redistributes the mass away from the center toward the ends of the device 400 and directs to the desired position on the sclera below the eye exam with greater stability on the eye while dimensioning 〇 (four) product. The tabs 415 also provide an area of increased mass (thickness) that can accommodate the active agent and, in particular, each tab 415 can comprise one or more partially recessed regions 250 for containing the active agent. . By way of example and as illustrated, a partially recessed region 25, such as a well, is formed in the tab 415. In Fig. 4, there are two recessed regions 250, each tab 415 having a recessed area 25〇 to accommodate the active agent. Unlike the previous embodiment, it is shown in Figure 4 that the surface flow feature 2 〇〇 ϋ does not have a branched configuration because the surface flow feature is more like a linear flow cell. The surface flow feature 2 〇〇 extends across the width of the device 4 from the edge to an opposite edge. The surface flow feature 200 extends across the tab 415 (eg, across the apex of the tab 415) and, as in other embodiments, the surface flow feature 2 is designed to guide or modify the nature surrounding the device 400. The flow of liquid (eg, tears). As noted above, the direction of flow of the liquid will depend on the position and orientation of the device, however, the liquid may flow in either direction within the surface flow feature 2〇〇. 159575. Doc • 25- 201223581 As in other embodiments, the surface flow feature 200 is defined by opposing walls 205 that are tiltable or straight. It will also be understood that in any of the embodiments described herein, the width and length of the width and length of the partially recessed region relative to the surface flow feature 200 can vary. The width of the s-flow cell is the distance between the two opposing side walls, and the length of the flow cell is measured from one end of the flow cell to the opposite end. In particular, the width of the partially recessed region (and therefore the active agent) may be at least 5% or may be at least 7% of the width of the surface flow signature; or may be at least 9G%. Moreover, in some applications, the width of the partially recessed region may be less than 5% of the width of the surface flow feature. In another embodiment, the partially recessed region and the width of the active agent can be greater than the width of the flow channel. With respect to the length of the launder, the active agent is preferably positioned along a length less than i of the length of the stagnation tank and may represent only a fraction of the entire area of the launder (eg, less than 25%, less than 10%) and many more). However, in other delta counts, the percentage can be higher. Figure 5 shows the device 401, which is very similar to the device 4'', and the main difference is that the device 401 includes only one of the surface & motion features 200 formed in one of the & The single surface flow feature 2 has a knife type similar to the branch type shown in Figure 2. It will be understood that each of the 'sheets 5' may include a surface flow feature 2 (which includes - a sexual agent) or be in communication with the partially recessed region 250. As in all embodiments described herein, 'the depth of the partially recessed region 250 depends on a number of factors' including the size of the body of the device, the characteristics of the active agent (including dimensions), the active agent to be dispensed Quantity and so on. 159575. Doc • 26 - 201223581 In the embodiment of Fig. 5, the ram A, the hunch knife/claw section 222 terminates at or near an edge. It will be appreciated that the branch flow channel sections 222 may terminate at a point not at or near the edge of the edge of the device. In this configuration, the end of the branch trough section 222 can include a member for facilitating the outflow or inflow of liquid into the branch trough section 222. For example, the end of the branch flow channel section 222 can include another surface flow feature, an inclined surface (slope) that is used to cause liquid to flow into or out of the branch flow channel section 222. For other embodiments, when the surface flow feature 200 has a branched configuration, there may be two or more branch flow channel segments (3). In this embodiment, the branches are facilitated by surface flow features 24A. Figure 6 shows a device 403' which is similar to the other devices 4, 4 and 1 and is defined by a body 410 and a plurality of tabs 415. In this embodiment, each of the tabs 415 〇 3 has a surface flow characteristic in the form of a knife branching groove and is unambiguous. In the illustrated embodiment, the surface flow feature can have three branches (branch flow channel segments 222). Similar to Figures 4 through 5, the liquid system is intended to flow along the surface flow feature 20 且 and it will be understood that the direction of flow may depend on the particular application. For example and as shown in FIG. 7, when the edge is positioned adjacent to the cornea and in confronting relationship with the cornea, the liquid may be from the first trough section 210 to the second trough section 22 Flowing in a general direction. However, within the scope of the present invention, the flow may be in an opposite direction depending on the orientation of the device and other considerations. Figure 8 shows a rear (lower) surface 4〇9 of the device 400 and in this embodiment one or more surface flow features 2〇〇 are formed along the back surface 4〇9. 159575. Doc -27-201223581 It will be understood that the active agent may be dispersed throughout a polymer matrix forming one of the devices 400 or may be positioned in a partially recessed region (such as 'region 250) as previously discussed herein. The surface flow feature 200 formed on the surface of the front surface of the plurality of devices is formed on the rear surface for guiding/modifying the flow of the liquid (eg, intraocular fluid) such that Facilitating delivery of the active agent to the target tissue. In other words, the surface flow feature 2 associated with any of the devices described herein acts as a surface flow director wherein the liquid flow contacts the active agent associated with the body of the device. It will be understood that in any of the embodiments described herein, surface flow features 200 and 240 can be formed on the back surface and can also be formed on opposing front surfaces of the transfer device. It will be understood that in any of the embodiments described herein, a surface flow feature 200 can be formed on the back or front surface and the feature terminates before reaching the peripheral edge of the device and a slope can be used A slope or useful feature to allow the liquid to flow into or out of the surface flow feature 200 more easily. An exemplary liquid flow pattern is shown in FIG. However, as in other embodiments, it will be understood that the opposite flow pattern is equally feasible. Figure 9 shows that the active agent 103 is disposed within a partially recessed region 250 (e.g., a pocket). Figure 10 shows another embodiment similar to the previous embodiment (including the embodiment of Figure 7). In the embodiment of Fig. 10, a device 5 is illustrated. Features of the device 500 that are common to other embodiments are identified by the same numerals. Not 159575. Doc = 28-201223581 ^ In other embodiments, the body 510 of the device 500 includes a plurality of vias or vias or channels 550. The through holes 55 are in the form of openings through the body 5 1 of the device 5 . For example, one or more through holes $$ can be formed in fluid communication with the surface flow feature 200 to provide additional or additional components for delivering the 'tongue agent to the target tissue (eg, directly Formed within the surface flow feature). In the illustrated embodiment, each of the branch flow channel segments 222 includes at least one via 550. The through holes 550 can be formed anywhere within the branch flow channel section 222 because this represents a location generally downstream of the source of the active agent 103. The through holes 550 provide a secondary flow path of the liquid because some of the liquid can flow in the surface flow feature 2〇〇 beyond the through hole 55〇, and some liquid flows downward into the through hole, Guided to the target organization. Thus, the through holes 550 provide another means for delivering the active agent from the source of active agent to the target tissue. Referring now to Figure 11, another apparatus 6 for delivering an active agent is illustrated. The device 600 is similar to other devices described herein. In this embodiment, each surface flow feature 2 (e.g., a flow cell) has a closed end because the surface flow feature is not as good as at least two of the edge of the device 6 in the prior embodiment. And open σ. In this embodiment, the surface flow feature 200 has a closed first end 211 and an open end 213. In the illustrated embodiment, the partially recessed region (e.g., pocket or reservoir) 250 is located at or near the closed first end 211 of the surface flow feature 2''. Figure U shows that the surface flow feature 2〇〇 has a branch flow 159575. Doc -29-201223581 Slot construction and, therefore, the illustrated surface flow feature 2 is formed by a plurality of branch flow channel segments 222 that extend toward and terminate at or near one edge of the body (four) of the device 600. 'To facilitate the flow of active agent from the source 1〇3 to the target tissue, the device is positioned near the target tissue. The branch trough sections 222 are positioned on the side of the source of the active agent 1〇3 and, therefore, the flow of tears (assisted by the eye test and the slight movement of the farm with the blink) will The active agent released from the device is distributed toward the target tissue. The surface flow feature fan shown in Figure 11 can have any of the characteristics of the surface flow feature 2 G G described and illustrated herein. The direction arrow showing the flow of tears is merely schematic and due to the closed end 2U of this design, the liquid (tears) flows in a direction away from the closed end 211 in a direction away from one of the peripheral edges of the body 610, The active agent carried by the liquid is dispensed to the target tissue. Figure 12 shows a device 700 that is very similar to the device 600 of Figure 11, except that the f-surface flow feature fan is not in the form of a - branch flow channel configuration and the wire surface flow feature 200 has a similar appearance to that of Figure 4. The more detailed structure shown. For the first arrow sound, the surface flow feature 200 has the active agent 103 or j 4 na human, _, a closed 5 end 211, and the active agent is shown in the figure as being set in the 兮As long as the work is done in the area of the partial depression of the ridge (for example, a bag). In Fig. 12, the forehead m indicates the liquid (such as the target ρ) when the device 700 is placed in the eye and the surface flow feature 2 ^^ + ^ 00 is extended radially outward from the cornea of the eye in one direction. ^ One of the possible flow patterns of tears, and therefore, 159575. Doc -30- 201223581 A regular tear-like grip (described in detail above) causes tears to enter the surface flow trough and is directed toward the active agent (8). As in other embodiments, the tears are in contact with the active agent and the continued flow of tears promotes dispensing the active agent 103 from its source in the body 710 to the target tissue (ie, ocular tissue). Another embodiment of the present invention, wherein the device for transferring the living agent 103 is illustrated. The device 8 is similar to the device of Figure (7).

500且包3對表面流動特徵200，該對表面流動特徵2〇〇經形成橫越且至少部分地位於該裝置咖之該本體81〇之該等凸片415内。各個表面流動特徵200係一分支流槽類型且由沿該本體 81〇之-周邊邊緣而開口 < _第一流槽區段21〇及由複數個分支流槽區段222界定之一第二流槽區段而界定。該表面流動特徵200係由包含可為直形或傾斜之邊緣2〇5之若干壁界疋該等分支流槽區段222係沿或鄰近該本體之另一周邊邊緣而開口。雖然圖13中所示之該表面流動特徵2〇〇係分支流槽類型，將理解，該表面流動特徵2〇〇可為一非分支類型且本質上比先前圖中所示更顯線性。根據此實施例，一蓋825經形成橫越該表面流動特徵2〇〇之一部分或區段。該蓋825較佳位於該活性劑1 〇3之上方，以進一步包含該活性劑103且藉由經導向液體（諸如，在該表面流動特徵200内行進之眼内液體）而進一步影響該活性劑1 03之施配。其亦用於進一步防止眼組織與該局部凹陷 159575.doc -31 _ 201223581 區域250(見圖Η))之間之直接接觸且防止可能出現其中之令活性劑103之濃度過高（見圖ι〇)。 μ 此外’該等方"頭顯㈣體之__性流動型樣且並不限制本發明。如本文所提及’流動型樣之方向及性係取決於某些因素，諸如，㈣置_之定向。實際上’ -隨道狀環境係藉由將該蓋奶設置於該表面流動特徵細(例如，流槽)上方而產生且此輔助引導該液體與該活性劑接觸且遠離該活性劑朝向該目標組織。儘管圖中未繪示，在-些實施例中，該蓋可由該蓋防與該表面流動特徵200之間之若干柱狀物進一步支撐。在一實施例中，該蓋825係由與該本體81〇之剩餘部分之 :料不同之材料製成且可具有不同的材料特性。例如，該蓋825可由—Μ材料形成’使得其在-預定時段中腐蝕腐#時間框可與該活性劑之釋放之動力學協調。圖14顯不用於傳遞_活性劑之另一裝置_。該裝置_ 類似於其他實施例且包含_對凸片化。在此實施例中， =等&片415中之—者包含相對於本體91〇之經曝露表面凹陷之表面•動特徵920且係由一平坦表面925(底部）及一對相對之侧922而界定。料側922可相對於該底部奶垂直或形成一角度。該表面流動特徵920並不延伸至該本體之周邊邊緣，而是大體上限於位於該凸片415内。該表面抓動特徵920之端係開口且允許液體流流人及流出該表面流動特徵920。在此實施例申該局部凹陷區域250係自該本體9 1 〇之外 i59575.doc -32· 201223581 表面（此處該前表面）進一步凹陷且因此該活性劑經進一步凹陷。圖15顯不裝置900在另一凸片415中包含一第二表面流動特徵920。對於其他的實施例，該表面流動特徵92〇經構造以增加將邊活性劑施配至該目標組織之效率，且利用眼瞼之重複泵送作用而在淚液緩慢地流過該裝置時混合流過該活性劑 103之淚液。圖16顯示用於傳遞該活性劑ι〇3之另一裝置1〇〇〇。在此實施例中，該裝置1000係呈一隱形眼鏡或此類物之形式，因為其係由包含一光學元件區域或區1〇2〇之一本體1〇1〇形成。如圖所示，光學元件區域丨〇2〇係位於中心，使得當該裝置1000經佩戴於眼中時，光學元件區域1〇2〇位於角膜上。如在先前實施例中’該裝置1000包含一表面流動特徵 200 ’該表面流動特徵200係形成於該本體1010中位於該光學元件區域1020之外側之若干位置。在先前實施例中，該表面流動特徵200促成自然體液（在此情形下眼内液體（眼淚））與該活性劑103之間之接觸，以促成該活性劑103之施配且增加該活性劑1 03之施配效率。如在先前實施例中，該表面流動特徵200可呈一流槽之形式，其沿該光學元件區域1020之該外侧之該本體1010之一周邊邊緣而形成。在所圖解之實施例中，該表面流動特徵200係呈包含兩個流槽區段之一流槽結構之形式，該兩個流槽區段共享形成於該本體1〇1〇之該周邊邊緣處之一共 I59575.doc -33- 201223581 有開口 221。該兩個流槽區段沿該本體1〇1〇之該周邊邊緣在相對之方向上延伸且各者終止於沿該周邊邊緣之一位置處之一開口 223處。因此，該兩個流槽區段本質上係拱形 (彎曲）。在先則實施例中，s亥專流槽區段係與該活性劑1 〇 3流體連通，以允許液體（眼淚）接觸該活性劑且輔助施配且傳遞該活性劑⑻至該目標組織。雖然圖解之實施例顯示該活 ί·生劑103係位於由一流槽交又之一局部凹陷區域㈣（袋狀部）中，將理解，該活性劑可由該本體以本文所提及之其他方式承載’包含設置於一基質中。將理解，各個流槽區段可具有一分離開口，而非共享一共有開口 22 1。在此構造中，兮法播 °〆/瓜槽之各個端於兩個不同的位置開口通向該周邊邊緣。此外，該裝置觀可經構造以僅具有—個流槽且因含該活性劑103之一個局部離散區域。文所述S'1亥W生劑103至邊目標組織，該裝置⑽。與本、八他裝置以相同或類似之方式發揮作用；唯 =在於’其經構造而佩戴於眼中且包含光學元件區域門實:例中，該表面流動特徵在某種程度上係1 二冓，因為該表面流動特徵之至少—個端係開口，、允許液體在任-方向上穿過其令朝向該以遠離該裝置之該本體之-方向上 & ^本體或在且古$钵朝向該裝置之外部。茈盥具有連續且閉合端之一導管相反。此與 159575.doc -34- 201223581 虽β亥活性劑經設置於一離散凹陷區域（袋狀部或儲液部）中時，將理解，該活性劑可填充整個凹陷區域或可填充少於整個凹陷區域之區域且可甚至過度填充該凹陷區域，因為該活性劑可設置於該開口上方進入該凹陷區域中(即，一部分之該活性劑可部分地延伸進入該表面流動特徵（可位於該表面流動特徵之周圍底部之上方）中 Ο500 and a pair of surface flow features 200, the pair of surface flow features 2 are formed transversely and at least partially within the tabs 415 of the body 81 of the device. Each of the surface flow features 200 is a branch flow cell type and is defined by a second flow along the peripheral edge of the body 81 and the opening < _ first flow channel segment 21 〇 and by a plurality of branch flow channel segments 222 Defined by the groove section. The surface flow feature 200 is opened by a plurality of walls including edges 〇5 that may be straight or slanted, and the branch runner segments 222 are open along or adjacent to another peripheral edge of the body. Although the surface flow feature 2 is shown in Figure 13 as a branch flow cell type, it will be appreciated that the surface flow feature 2 can be a non-branched type and is substantially more linear than previously shown. According to this embodiment, a cover 825 is formed to form a portion or section of the flow feature 2〇〇 across the surface. The cover 825 is preferably positioned over the active agent 1 〇 3 to further comprise the active agent 103 and further affect the active agent by directing a liquid, such as an intraocular fluid traveling within the surface flow feature 200. 1 03 distribution. It is also used to further prevent direct contact between the ocular tissue and the local depression 159575.doc -31 _ 201223581 area 250 (see Figure Η) and to prevent possible concentration of the active agent 103 (see Figure ι). 〇). μ In addition, the 'the other party' is a sexual flow pattern and does not limit the present invention. As mentioned herein, the direction and nature of the flow pattern depends on certain factors, such as the orientation of (iv). In fact - the on-channel environment is created by placing the cap milk over the surface flow feature (eg, a launder) and this assists in directing the liquid into contact with the active agent and away from the active agent toward the target organization. Although not shown in the figures, in some embodiments, the cover may be further supported by the cover against a plurality of posts between the surface flow features 200. In one embodiment, the cover 825 is made of a different material than the remainder of the body 81 and may have different material properties. For example, the cover 825 can be formed from a "ruthenium material" such that it occludes the kinetics of the release of the active agent for a predetermined period of time. Figure 14 shows that it is not used to transfer another device to the active agent. The device _ is similar to other embodiments and includes _pairing. In this embodiment, the =etc & sheet 415 includes a surface-moving feature 920 that is recessed relative to the exposed surface of the body 91 and is comprised of a flat surface 925 (bottom) and a pair of opposing sides 922. And defined. The material side 922 can be perpendicular or at an angle relative to the bottom milk. The surface flow feature 920 does not extend to the peripheral edge of the body, but is generally limited to being located within the tab 415. The end of the surface gripping feature 920 is open and allows liquid to flow to and from the surface flow feature 920. In this embodiment, the partial recessed region 250 is further recessed from the surface of the body 9 1 i i59575.doc -32· 201223581 (here the front surface) and thus the active agent is further recessed. The display device 900 of FIG. 15 includes a second surface flow feature 920 in the other tab 415. For other embodiments, the surface flow feature 92 is configured to increase the efficiency of dispensing the active agent to the target tissue and to utilize the repeated pumping action of the eyelid to mix the flow as the tear slowly flows through the device. The tear fluid of the active agent 103. Figure 16 shows another device 1 for delivering the active agent ι 3 . In this embodiment, the device 1000 is in the form of a contact lens or the like because it is formed by a body comprising an optical element region or region 1〇1〇. As shown, the optical element region 位于2 is centered such that when the device 1000 is worn in the eye, the optical element region 1〇2〇 is located on the cornea. As in the previous embodiment, the device 1000 includes a surface flow feature 200. The surface flow feature 200 is formed in the body 1010 at a number of locations on the outer side of the optical component region 1020. In the previous embodiment, the surface flow feature 200 facilitates contact between the natural body fluid (in this case the intraocular fluid (tears)) and the active agent 103 to facilitate dispensing of the active agent 103 and increase the active agent. 1 03 distribution efficiency. As in the previous embodiment, the surface flow feature 200 can be in the form of a first-class slot formed along a peripheral edge of the body 1010 of the outer side of the optical element region 1020. In the illustrated embodiment, the surface flow feature 200 is in the form of a flow channel structure comprising one of the two flow channel segments, the two flow channel segments being shared at the peripheral edge of the body 1〇1〇 One of the total I59575.doc -33- 201223581 has an opening 221. The two flow channel segments extend in opposite directions along the peripheral edge of the body 1〇1〇 and each terminate at an opening 223 at one of the locations along the peripheral edge. Therefore, the two flow channel sections are substantially arched (bent). In a prior embodiment, the sigma channel section is in fluid communication with the active agent 1 〇 3 to allow liquid (tears) to contact the active agent and assist in dispensing and delivering the active agent (8) to the target tissue. Although the illustrated embodiment shows that the living agent 103 is located in a partially recessed area (four) (pocket) from the first-class groove intersection, it will be understood that the active agent may be from the body in other manners as referred to herein. The carrier 'includes is disposed in a matrix. It will be understood that each of the flow channel sections may have a separate opening instead of sharing a common opening 22 1 . In this configuration, each end of the tamper-evident/melon groove opens to the peripheral edge at two different locations. Moreover, the device view can be constructed to have only one flow cell and a partially discrete region of the active agent 103. Said S'1H W agent 103 to the side target tissue, the device (10). Acting in the same or similar manner as the present and the eight devices; only = is that it is constructed and worn in the eye and contains the optical element region: in this case, the surface flow characteristic is to some extent Because at least one end of the surface flow feature is open, allowing the liquid to pass through it in any direction - toward the direction away from the body of the device - < ^ body or at Outside the device.之一 One of the continuous and closed ends of the conduit is opposite. This and 159575.doc -34- 201223581, although the beta agent is placed in a discrete recessed area (pocket or reservoir), it will be understood that the active agent can fill the entire recessed area or can be filled less than the entire a region of the recessed region and may even overfill the recessed region because the active agent may be disposed over the opening into the recessed region (ie, a portion of the active agent may partially extend into the surface flow feature (which may be located on the surface) Above the bottom of the flow feature)

G 根據本發明之一態樣，一種用於施配活性劑之裝置可由形成一载體（本體）及藥物包含空間（藥物貯槽）之本體組 j，且一㈣-個以上之施酉己表面經併入該裝置之若干特定表面上或中。該藥物貯槽可由包含一個或一個以上之藥物包含媒體之該裝置中或上之一個三維空間組成。本發明之裝置可用於控制由待分佈至淚膜中之物質組成之眼部藥物之傳遞，以使該藥物更好地分散至該等眼組織。宜設計技術利用由眨眼及眼睛移動而產生之物理力且促成地交換鄰近該藥物貯槽之施配表面處之淚液之連續交換。其設計亦可已3減少或消除該等施配表面與相鄰之組織之間之直接接觸之物理特徵。裝置組態係用於可能造成局部刺激、充血或色素沈著之藥物(諸如，前列腺素類似物)之釋放。該裝置亦用於若干狀況中，包含，先眼艮睛乾溫、感 ’：、表障礙及術後癒纟。該裝置尤其適合於將青 (治療）藥物直接釋放進入該淚膜令又 μ ^ M ^ ^ ^ U此糟由鉍貫角膜路 -將樂物供應至前區段中’且藉由一橫貫結眼球之外側之廣泛環繞分佈，鄰近虹膜根部但在（= 之外)以達成在整個眼球周圍渗透，到達圍繞= 159575.doc -35· 201223581 目標，毛體及/或鞏膜外層區域。當經有效地分佈至治療之目標之該整個前區段時，青光眼藥物更有效。藥物之此傳遞不同於習知之藥物傳遞裝置自一裝置直接針對該組織集中藥物釋放，因爲料置之—藥物㈣直接立於組織之局部區域上方。當通過流動的動態淚膜而分佈 2該眼表面之大區域時，作用於眼表面之許多眼睛乾溫藥物亦更有效。因此，向需要該活性劑之該整個眼表面更均句地分佈改良經釋放之-給定量之料.治療效果，同時減小對緊鄰該藥物貯槽之該開口之組織明用於一眼部環境中時，本發明致力於藉由混合該樂物貯槽上方之淚液且將該藥物汲出該藥物貯槽，且經由 :淚膜將該藥物呈送至目標組織至大區域達成更統一之藥釋放速率，從而使用淚膜作為_無端儲槽及活性劑分散 =體。此淚液傳遞純依賴於該淚膜與該目標組織之間之漠度梯度，以幫助驅動該活性劑朝向該目標組織，而非依賴於-嚴袼局部化之濃度梯度，其限制自藥物貯槽至位 tr眼部裝置之藥物貯槽表面與該目標組織之間之緊鄰近端部分之間之該局部區域之傳遞。或者，此傳遞可減小充血、發炎及色素沈著之此等不希望的副作用，A等副作料歸因於將藥物集中局部地傳遞 ^鄰近遭受此等副作用之一組織，在青光眼病患眼中重複局部施加前列腺素類似物滴液時可發生此等副作用。該裝置持續藥物傳遞可避免传用邈避充使用滴眼液，因此導致改良之病患又從性、便利性及後續之效率。裝置經製造時可併入該藥 i59575.d〇c -36- 201223581 物，因此產生藥物裝載貯槽，且該等貯槽之開口係位於前表面、側向表面或與最鄰近該局部眼部藥物傳遞裝置之鞏膜及球形結膜表面遠離之任何表面。 . 將理解，本文所揭示之任何傳遞裝置（包含圖1至圖16中所示之該專傳遞裝置）可經形成使得該活性劑103並非經設置於該局部凹陷區域25GH活性劑1G3可沿該表面流動特徵200之該底部而設置。在一構造中，該活性劑1〇3可沿〇該底部相對於該底部自身以一非凹陷方式而設置（但相對於該裝置之該本體之形成有該表面流動特徵2〇〇之表面凹陷）、換。之，該活性劑103可設置於該表面流動特徵200 之一平坦或非平坦底表面上且相對於該表面流動特徵2〇〇之尺寸而構造，使得其不會負面地阻礙或影響液體在該表面流動特徵200内之流動。因此，該活性劑1〇3可呈沿該表面流動特徵200之該底部之一長度而設置之一膜或此類物之形式。因此，自然液體（眼内液體）流過該活性劑1〇3且該 Ο $性劑藉此得以承載或者以其他方式施配至該目標組織。在此構造中，該活性劑可佔據之面積小於該表面流動特徵 200之該底部之整個表面積且因此形成於沿該底部之一局部離散區域中。或者，該活性劑可形成於沿該底部之複數個局部離散區域（例如，該活性劑之若干間隔區域）中。該構造亦適用於下文參考圖17至圖20所述之裝置。如上文所述，在本發明之另一態樣中，一種用於傳遞活性劑之裝置可經構造使得該活性劑在一延長時段中傳遞至身體組織（目標組織）。更明確但不限制而言，本發明係關 159575.doc -37- 201223581 於用於將活性劑局部地傳遞至眼睛之生物相容性裝置。將理解’本文參考圖17A至圖2G所揭示之實施例可併入具有圖1至圖16中所述之特徵之裝置中或者其可併入缺乏此等特徵之裝置中。現參考圖17A及圖17B，在-示例性應用令，用於傳遞一活性劑（例如’―藥物）之—裝置胸係呈根據本實施例之-局部眼部藥物傳遞裝置11〇〇之形式；然而，將理解，該裝置mo並不限於僅用於眼部應用中，而是可用於其他應用中療身體之其他區域。藥物傳遞裝置11 〇〇係由本體1110界S ’在此特^示例性應用中，該本體11且有允許放置於眼中之尺寸。該本體mo係由面1120及-相對之第二表面或面ιΐ3〇界定。該本體⑴〇之 -厚度係界定為該第一表面! 12〇與該第二表面i Η。之間之一距離。該本體U1G包含-周邊邊緣114G，在所圖解之實施例中其顯示為-側壁。該本體Ul〇包含容納一活性劑之一藥物貯槽1103。如太古私、+. _ ^ 如本文所述，該藥物貯槽11〇3代表該活性劑之源且可呈任何數目之不同實體形式。該藥物貯槽⑽可由僅藥物或—材料組成，諸如包含藥物之-基質、包含藥物之一鍵劑或包含藥物之一經封閉液體。因此’該藥物貯槽1103之形式可與本文所述之該活性劑⑻之形式相同。根據本發明，該藥物貯槽⑽之一個或一個以j之表面包含由具有一均勻或變動厚度⑴$之易蝕表面覆k之至少-個表面。在點U4(^u5〇處或沿該整個長度之-狹窄條帶，該厚度可漸縮至零，使得藥物釋放在 I59575.doc -38- 201223581 放置於合適的位置之後可立刻開始。亦將理解，所圖解之本體丨丨丨0之形狀係僅僅示例性且該本體1110可具有其他形狀。該本體111〇經形成使得其具有一定程度之可撓性，以允許將該本體1110放置於該目標組織所處之目標位置。因此，該本體丨丨丨0可具有允許該本體 1110至少大體上或實質上適應應用有該本體111〇之該目標組織之形狀之材料特性。例如，當用於眼部應用中，該本 ❹ 體1110可適應眼睛之形狀，如下文將更詳細地描述。將理解，該第一表面1120或第二表面1130可經放置抵靠目標組織，且因此相對之表面遠離該目標組織。在一局部眼部應用中，該第一表面1120或第二表面1130可經放置抵靠眼睛之組織，下文將更詳細地描述。將理解，雖然該本體1110具有相對一中央軸線之對稱性’該裝置1100並不限於此一特性且相反地，該本體111〇可具有一非對稱構造。〇因此，將理解，該裝置1100及本文所述且在附圖中圖解之其他裝置可由在先前所併入之申請案中所揭示之材料製成且可具有上文申請案中所揭示之結構特性。圖1 9顯示根據一不同實施例之一裝置丨3〇〇，六丫 I體 U10包含具有一局部凹陷區域（空間）1350(諸如，袋狀部、井狀部、儲液部、艙等等）之一額外特徵。將理解，該较置1300看起來類似於本文所揭示之該等裝置且該局部凹陷區域1350可與本文先前所述之該局部凹陷區域25〇相同類似。 & 159575.doc -39- 201223581 該局部凹陷區域1350經定位及形成使得其與該表面流體連通更月確而5，§亥局部凹陷區域13 5 0收納且容納該活性劑或藥物貯槽，在圖2中其經標識為12〇3。該活性劑 1203經放置於定位於該袋狀部内之一藥物貯槽1中，但並不填充該局部凹陷區域135〇。該貯槽可僅由藥物或一材料組成，諸如，包含藥物之一基質 '包含藥物之一錠劑或包含藥物之一經封閉液體。該貯槽之幾何形狀在體積方面隨著袋狀部深度而變動；也就是說，該貯槽之體積在接近該局部凹陷區域135〇之頂部處最小，且在接近該局部凹陷區域13 50之底部處最大。一可生物分解材料經放置於該袋狀部中位於該貯槽之「上方」以填充產生一複合結構136〇 ^該袋狀部，該可生物分解材料複合結構實質上不允許該貝丁槽中之該藥物滲透。經修改之藥物貯槽接著具有一大體上平坦頂部1370，且該藥物貯槽12〇3之一小部分包括該局部凹陷區$ 1350之一部分之經曝露表面，《一大體平坦部刀137〇，其完全由該可生物分解材料複合結構136〇組成，其完全蓋住該藥物貯槽12〇3於下方。圖2〇顯不裝置1400，其令該活性劑係包含於本體141〇内 (例如，分散遍及形成該本體141〇之一聚合物基質）且通過該本體1410之表面之由具有均勻或變動厚度143〇之一易蝕表面覆蓋之任何經曝露部分而施配。在點144〇及145〇處， °玄厚度可漸縮至零，使得在放置於合適的位置之後，藥物釋放可立刻開始。將理解，在本發明之此態樣中，揭示控制自一基質類型 i59575.doc •40· 201223581 遞裝置之一之藥物釋放。具有兩種法：一種適用於完全由—包含藥物二種方法涉及到一種該藥物局部地置。在該裝置本體完全由包含藥物之基質組成之裝置構造可包含另外兩個元件，即⑴該裝置基質本體，I 具有適於其在哺乳動物身體内之預期放置位置之—結構及According to one aspect of the invention, a device for dispensing an active agent can be formed by a body group (body) and a drug containing space (drug storage tank), and one (four) or more of the surface of the substrate On or in several specific surfaces of the device. The drug reservoir can be comprised of a three dimensional space in or on the device comprising one or more drugs comprising a medium. The device of the present invention can be used to control the delivery of ocular drugs consisting of substances to be distributed into the tear film to better distribute the drug to the ocular tissues. The design technique utilizes the physical forces generated by the blinking and movement of the eye and facilitates the exchange of tears at the dispensing surface adjacent to the drug reservoir. It is also designed to reduce or eliminate the physical characteristics of the direct contact between the dispensing surface and adjacent tissue. The device configuration is for the release of drugs (such as prostaglandin analogs) that may cause local irritation, congestion or pigmentation. The device is also used in a number of conditions, including: dry eye, dryness, sensation, and dysfunction. The device is particularly suitable for direct release of the cyan (therapeutic) drug into the tear film to cause μ ^ M ^ ^ ^ U to be supplied to the anterior segment by the keratoconus - and by a transverse junction The outer circumference of the eyeball is widely distributed around the root of the iris but outside (=) to achieve penetration around the entire eyeball, reaching the target around the 159575.doc-35·201223581, the outer region of the hair and/or sclera. Glaucoma medications are more effective when effectively distributed throughout the anterior segment of the target of treatment. This delivery of the drug is different from conventional drug delivery devices that concentrate drug release directly from the device against the tissue because the drug (4) is placed directly over a localized area of the tissue. When a large area of the surface of the eye is distributed by the flowing dynamic tear film, many eye dry warming drugs acting on the surface of the eye are also more effective. Thus, the more uniform distribution of the entire ocular surface in need of the active agent improves the release-giving amount of the therapeutic effect while reducing the tissue adjacent to the opening of the drug reservoir for use in an ocular environment In the meantime, the present invention aims to achieve a more uniform drug release rate by mixing the tear fluid above the music storage tank and scooping the drug out of the drug storage tank, and delivering the drug to the target tissue via the tear film to a large area. The tear film is used as the _ endless tank and the active agent dispersion = body. This tear delivery is purely dependent on the gradient of the gradient between the tear film and the target tissue to help drive the active agent toward the target tissue, rather than relying on a concentration gradient that is localized, which is limited from the drug reservoir to The transfer of the localized region between the surface of the drug reservoir of the tr eye device and the immediately adjacent end portion between the target tissue. Alternatively, this delivery may reduce such undesirable side effects of congestion, inflammation, and pigmentation, and A and other by-products are attributed to localized delivery of the drug to the tissue adjacent to one of these side effects, repeating in the eye of the glaucoma patient These side effects can occur when a prostaglandin analog drop is applied topically. The device continues to deliver drugs to avoid the use of eye drops, thus resulting in improved patient sex, convenience and subsequent efficiency. The device may be incorporated into the drug i59575.d〇c-36-201223581, thereby producing a drug loading reservoir, and the openings of the reservoirs are located on the front surface, the lateral surface, or the drug delivery closest to the local eye. The surface of the sclera and spherical conjunctiva of the device is far from any surface. It will be understood that any of the delivery devices disclosed herein (including the specialized delivery device illustrated in Figures 1-16) can be formed such that the active agent 103 is not disposed in the localized recessed region 25GH, the active agent 1G3 can be along the The bottom of the surface flow feature 200 is disposed. In one configuration, the active agent 1〇3 can be disposed in a non-recessed manner along the bottom of the crucible relative to the bottom itself (but with respect to the surface of the apparatus, the surface of the surface is characterized by a surface depression. ),change. The active agent 103 can be disposed on one of the flat or non-flat bottom surfaces of the surface flow feature 200 and configured relative to the surface flow feature 2〇〇 such that it does not negatively obstruct or affect the liquid. The flow within the surface flow feature 200. Thus, the active agent 1〇3 can be in the form of a film or the like disposed along the length of one of the bottoms of the surface flow feature 200. Thus, a natural fluid (intraocular fluid) flows through the active agent 1〇3 and the steroid is thereby carried or otherwise dispensed to the target tissue. In this configuration, the active agent can occupy an area that is less than the entire surface area of the bottom of the surface flow feature 200 and is thus formed in a discrete portion of the bottom portion. Alternatively, the active agent can be formed in a plurality of discrete regions along the bottom (e.g., several spaced regions of the active agent). This configuration is also applicable to the apparatus described below with reference to Figs. 17 to 20. As described above, in another aspect of the invention, a device for delivering an active agent can be configured such that the active agent is delivered to body tissue (target tissue) for an extended period of time. More specifically, but not by way of limitation, the present invention is directed to 159,575.doc-37-201223581 for use in a biocompatible device for the topical delivery of an active agent to the eye. It will be understood that the embodiments disclosed herein with reference to Figures 17A-2G may be incorporated into a device having the features described in Figures 1-16 or may be incorporated into a device that lacks such features. Referring now to Figures 17A and 17B, in an exemplary application, an apparatus for delivering an active agent (e.g., a "drug") is in the form of a topical ocular drug delivery device 11 according to the present embodiment. However, it will be understood that the device mo is not limited to use only in eye applications, but may be used in other applications to treat other areas of the body. The drug delivery device 11 is exemplified by the body 1110, which has dimensions that allow placement in the eye. The body mo is defined by a face 1120 and an opposite second face or face ΐ3ΐ. The body (1) is defined as the first surface! 12〇 and the second surface i Η. A distance between them. The body U1G includes a peripheral edge 114G, which in the illustrated embodiment is shown as a - sidewall. The body U1 contains a drug reservoir 1103 containing an active agent. As for Taikoo, +. _ ^ As described herein, the drug reservoir 11〇3 represents the source of the active agent and can be in any number of different physical forms. The drug reservoir (10) may be composed of only a drug or a material, such as a matrix containing a drug, a one containing a drug, or one containing a drug via a blocking liquid. Thus, the form of the drug reservoir 1103 can be the same as that of the active agent (8) described herein. According to the invention, one or one of the drug reservoirs (10) comprises at least one surface of the erodible surface covering k having a uniform or varying thickness (1). At point U4 (^u5〇 or along the entire length of the narrow strip, the thickness can be tapered to zero, so that drug release can begin immediately after I59575.doc -38 - 201223581 is placed in the appropriate position. It is understood that the illustrated shape of the body 丨丨丨0 is merely exemplary and the body 1110 can have other shapes. The body 111 is formed such that it has a degree of flexibility to allow placement of the body 1110 therein. The target location at which the target tissue is located. Thus, the body 丨丨丨0 can have material properties that allow the body 1110 to at least substantially or substantially conform to the shape of the target tissue to which the body 111〇 is applied. For example, when used In ocular applications, the body 1110 can be adapted to the shape of the eye, as will be described in more detail below. It will be appreciated that the first surface 1120 or the second surface 1130 can be placed against the target tissue, and thus the opposing surface Away from the target tissue. In a partial ocular application, the first surface 1120 or the second surface 1130 can be placed against the tissue of the eye, as will be described in more detail below. It will be understood that although The body 1110 has symmetry with respect to a central axis. The device 1100 is not limited to this feature and, conversely, the body 111 can have an asymmetrical configuration. Thus, it will be understood that the device 1100 and the Other devices illustrated in the drawings can be made from the materials disclosed in the previously incorporated application and can have the structural features disclosed in the above application. Figure 1 shows a device according to a different embodiment. 3〇〇, the six-body I U10 includes an additional feature having a partially recessed area (space) 1350 (such as a pocket, a well, a reservoir, a tank, etc.). It will be understood that the comparison 1300 It appears similar to the devices disclosed herein and the partially recessed region 1350 can be similarly similar to the partially recessed region 25A previously described herein. &159575.doc -39- 201223581 The partially recessed region 1350 is positioned and Formed such that it is in fluid communication with the surface, and the localized recessed area 1300 is received and houses the active agent or drug reservoir, which is identified as 12〇3 in Figure 2. The active agent 1203 is placed Placed in a drug storage tank 1 positioned in the pocket, but not filling the partial depression area 135. The storage tank may be composed only of a drug or a material, such as one containing a drug The agent or one of the drugs comprises a closed liquid. The geometry of the sump varies in volume with the depth of the pocket; that is, the volume of the sump is minimal near the top of the partially recessed region 135, and is close The bottom portion of the partially recessed region 135 is at a maximum. A biodegradable material is placed in the pocket above the "slot" of the sump to fill to create a composite structure 136, the bag-like portion, the biodegradable material The composite structure substantially does not allow penetration of the drug in the betty tank. The modified drug reservoir then has a generally flat top 1370, and a small portion of the drug reservoir 12〇3 includes an exposed surface of a portion of the partially recessed area $1350, "a large flat knife 137〇, which is completely It consists of the biodegradable material composite structure 136, which completely covers the drug storage tank 12〇3 below. 2 shows a device 1400 that includes the active agent in a body 141 (eg, dispersed throughout a polymer matrix forming the body 141) and has a uniform or varying thickness through the surface of the body 1410. One of the exposed surfaces covered by the 143 易 opaque surface is dispensed. At points 144 and 145, the thickness of the crease can be tapered to zero so that drug release can begin immediately after placement in the proper position. It will be appreciated that in this aspect of the invention, the release of drug from one of the substrate types i59575.doc • 40· 201223581 is disclosed. There are two methods: one for completely consisting of - containing drugs, and two methods involving a partial localization of the drug. The device configuration in which the body of the device consists entirely of a drug-containing matrix may comprise two additional components, namely (1) the device matrix body, I having a structure suitable for its intended placement in the body of the mammal.

’及(2)4本體上之—保形塗層’且該塗層係由具有變動之深度之易飯材料製成。該保形塗層將具有位於該塗層中之-個或-個以上之「孔」（開σ/穿孔），立使下伏之基質曝露。該等「孔」之數目及大小將取決於該裝置之幾何形狀、基質材料、該藥物之化學本f、藥物濃度及所所要的釋放剖面而變動。或者，該保形塗層之厚度可非And (2) 4 on the body - conformal coating ' and the coating is made of an easy-to-eat material having a varying depth. The conformal coating will have one or more "holes" (open σ/perforation) in the coating to expose the underlying substrate. The number and size of such "holes" will vary depending on the geometry of the device, the matrix material, the chemical composition of the drug, the concentration of the drug, and the desired release profile. Or the thickness of the conformal coating is not

均勻且當該塗層之最薄部分首先開始分解時，下伏之基質表面將經曝露。 AUniform and when the thinnest portion of the coating begins to decompose first, the underlying substrate surface will be exposed. A

或藥物貯槽類型藥物傳實踐本發明之操作性方之基質構造之裝置，帛位於裝置本體内之—裝「此裝置構造之原理在於，初始藥物釋放將通過該等「孔」中之經曝露基質發生或當塗層之該最薄層分解以曝、之基質表面時發生。此將大大減小或消除習知基質裝置中常見之初始藥物釋放「突釋效應」。該保形塗層將緩慢，腐钱’從而曝露更多之下伏基質表面，因此允許更多的藥物與經曝露之基質表面積大略成比例而釋放。以此方式可以使釋放速率在該裝置之整個壽命週期中更恆定之方式來控制藥物釋放動力學。除了針對基質類型裝置所述之此等兩個元件，一額外元 159575.doc -41- 201223581 件可用於構造-儲槽類型裝置中；—選用非易蚀障壁（實質上不允許該基質中之藥物滲透），其覆蓋該裝置之一些表面部分。在該裝置本體由局部地位於該裝置本體内包含藥物之貯槽組成之情形下，該裂置構造可包含至少四個元件：⑴該裝置本體，其具有適合於其在哺乳動物身體内之預期放置位置之—結構及幾何形狀；⑺一袋狀部（局部凹陷區域），該I置本體中鄰近該表面，且該袋狀部具有通向外 ::二―部分。該袋狀部可呈-孔、孔隙、井狀部、腔或具有多種簡單或複雜形狀之凹部之形式，且可包含諸如暫倒釣、狹槽、凹槽、螺紋'環、拉耳或凸塊之特徵，以寶助包含且穩定包含於其物其定位於該袋狀部内，但不殖右兮…丄w帛物貯槽’ 藥°該貯槽可由僅 & # 一包含藥物之基質、-包含藥物之錠劑或包含藥物之一在雜積上可根據袋狀部深声而㈣槽之幾何形狀雜積在接近该袋狀部之就是說’該貯槽之部處最大。若形成一二且在位於該袋狀部之底可《解此界定之實例且明確而…：個間皁的幾何形狀其平放於該袋狀部中側向τ 4 ^圓錐形貯槽，半體’其平放於該袋狀部中侧向下。二::貯槽之- 藥物貯槽具有到達或接近該袋狀部之二：什該 W-可生物分解材料丨之頂敎-小部分；及「上方」，以填充，代办1置於該袋狀部中該貯槽之 u1此產生實質上不允許該貯 159575.doc -42. 201223581 ，甲之藥物渗透之_可生物分解材料複合結構。該經修改樂物貯槽可具有—大體上平坦頂部，且該藥物貯槽之-小卩刀匕括4袋狀部頂部之表面積之—部分，或具有完全位於下方之藥物貯槽上方之一大體上平坦頂部。除了此等四個元件，另外兩個元件可用於一貯槽類型裝置之構&中.⑴一選用薄膜（membrane或thin film)，其經放置於该袋狀部之開口上，以進一步調整藥物自該袋狀部 0 <釋放，且該薄膜完全地或部分地覆蓋該袋狀部之開口；及⑺根據4藥物貯槽之構造及用於構造該裝置本體之該聚 σ材料必的是4吏該袋狀部之壁及底部不彳允許該藥物擴散渗透。此將阻止該藥物不希望地擴散進入該裝置本體中且引導藥物通過該袋狀部之該頂部而釋放且進入眼部環境中。該裝置之本體可完全由包含藥物之基質組成或該裝置可包含一局部藥物貯槽。在任一情形下，一般地，該裝置之 Q 该本體係由一非易蝕聚合材料製成，較佳本質上具有彈性。在該裝置本體完全係一包含藥物之基質之情形下，選擇聚合材料之主要原因在於聚合材料能夠提供所要的釋放動力學。對於具有一局部藥物貯槽之裝置，可以更大的自由度選擇該本體材料自身。在此情形下，該本體材料之一重要方面在於其阻止該藥物自所包含之袋狀部擴散進入該本體中之能力。可用於實踐本發明中之聚合材料之實例包含但不限於，聚丙烯酸及甲基丙烯酸酯、醚聚氣乙烯、聚烯烴、聚醯胺、聚氯乙烯、含氟聚合物、聚胺酯、聚酯、 159575.doc -43- 201223581 聚矽氧烷及聚苯乙烯。雖然-般而言，該裳置之本體係由非W材料製成，續本體亦由比該等藥物貯槽袋狀部中之該基質裝置之保形塗層或該可生物分解材料具有更大之抗腐㈣之可生物分解材料製成。將理解，該貯槽1IG3可為本文所揭示且在先前實施例中參考活性劑103所論述之任何活性劑。在本發明之背景中’易料料係界定為可崩解為通常在體内存在之簡單化學物之有機材料。更明確而言，術語可生物分解通常用於描述在接觸體液時崩解之聚合物，如下文所界定。生物分解係材料藉由曝露至一生理環境而發生之化學崩解。s亥等材料可為有機材料’諸如，聚合物，或無機材料’諸如某些陶瓷或矽酸鹽’且分解機制可為水解作用、 _催化反應或該二者之一組合。此外，分解過程亦對環境之PH(值）極其敏感。為了本發明之目的，術語易蝕的 (erodible)、可分解的（degradable)、可生物腐触 (bioerodible)及可生物分解（biodegradable)均係指上文界定之過程。下列係可用於本發明中之一類可生物分解聚合物：合成之可生物分解聚合物，包含但不限於，聚酯；聚原酸酯；聚酐；聚醯胺；聚二惡烷酮；聚草酸；聚縮醛；聚亞胺碳酸；聚胺酯；苷酸-氰丙烯酸酯；聚磷腈；及天然可生物分解聚合物，包含但不限於’澱粉、透明質酸、肝填脂、 1595754ο, • 44 - 201223581 明膠、清蛋白、右旋糖酐及脫乙醯殼多糖。 Ο Ο 通常用於適用於實踐本發明中之藥物傳遞中之可生物分解聚合物之實例包含但不限於：聚乳酸、聚乙醇酸、乳酸/ 乙醇酸共聚物、聚已酸内酯、聚羥基丁酸、聚經基戍酸酯、聚二惡烷酮、聚亞胺碳酸、聚原酸酯、聚醋針、聚醢胺、聚正_氰丙烯酸酯、順丁烯二酸酐共聚物、丙烯醯胺· Ν，Ν’-甲叉雙丙稀醯胺、Ν-乙烯基吡咯烷酮_Ν，Ν，_曱又雙丙稀醯胺、反丁烯二酸/聚乙烯乙二醇_N_乙烯基吡咯烷酮、反丁烯二酸乙醇酸-N-乙烯基吡咯烷酮、反丁烯二酸/氧代丙二酸-N-乙烯基吡咯烷酮、反丁烯二酸/氧代戊二酸_n_烯基吡咯烷酮、聚（胺基酸）、偽胺基酸、聚磷腈、澱粉、透明質酸、肝鱗脂、明膠、清蛋白、右旋糖肝及脫乙酿殼多糖。可生物分解聚合物可基於其所資借而分解之機制或過程而分類成兩組。此等過程係體分解及表面分解。對於聚人物，發生體分解。水向該基質中渗透之速率係大於聚合：分解之速率。該過程係一均勻 J J迫程其中分解在整個聚合物基質中以一均勻之速率發士生相反地，水滲透進入該基貝中之速率小於聚合物分解鮮之速率之一實例之材料係聚針。因此’此過程係非均勻，面岸且刀解限於聚合物之一薄表 ^壯32 較佳为解方法係通過在將该裝置安裝於眼中之後持續腐餘表面層。旦該裝置經構造，一選遲户Μ ,、選擇在於將一薄膜附接至該袋狀邛上，以調整藥物自該袋狀之釋放。該溥臈係完全或部 159575.doc -45. 201223581 分地覆蓋該袋狀部。此缝 — 此薄膜（membrane或film)可選自在一疋程度上可允許該筚、上^ Μ Λ樂物貯槽中之藥物滲透之聚合物。根據坆個疋義，該薄膜限制藥物 — 』樂物自該袋狀部之通量。該薄臈係用於叮制該藥物之釋放剖面。 _ t . 霄見之薄膜包含乙稀基醋酸乙烯（EVA)聚合物，辛功备Q & A夕軋及聚（甲基）丙烯酸酯。另外亦可使用其他聚合物作為薄膜。預期之藥物擴散路徑係自該經曝露藥物貯槽表面直接到眼部環境或通過切㈣物貯槽表面與眼料境之間之一釋放控制薄膜。將理解，除非阻止藥物自該貯槽（釋放）’藥物將擴散至該藥物貯槽之所有表面之外。由於擴散進入邊裝置之主體中，此將導致藥物損失。該裝置之該本體中之藥物接著對該病患大體上不具有治療價值。必須使此非生產性藥物擴散消除或至少減小—量值，以使通過鄰近眼部環境之該藥物貯槽表面之藥物通量最大。若該藥物衣狀部係呈一圓柱體之形式’則必要的是在該圓柱體之侧表面及平坦底面上放置一障壁。此將允許藥物僅僅自頂擴散此頂面接著將經放置鄰近該裝置表面，以引導藥物流出該裝置且進入該眼部環境中。、提供該藥物之方向性流動之技術係將該貯槽鑄造成一塑膠容器，諸如具有一開口頂部之一桶。具有可用作優良障壁之許多塑膠，舉例而言，聚曱基丙烯酸甲酯、聚醯亞月女來四氟乙烯⑧及聚丙烯。此方法之一缺點在於，該塑膠容器將難以製造，因為需要小尺寸。另一缺點在於，任何塑膠容器之實體大小將增加該藥物貯槽之總體體積。考 I59575.doc -46- 201223581 慮到眼部裝置自身之尺寸小，此不合需要。另—方法係藉由採用該障壁之一極薄之膜來在該藥物貯槽之周圍形成擴散障壁。可藉由化學方式在該藥物貯槽上施加一薄的氧化矽塗層，但此係一高成本過程。在該藥物貯槽上產生一障 n較佳方法係施加聚對二甲苯，其係廣為人知之障壁薄臈。聚對二f苯係用作濕氣障壁及介電質障壁之多種化學氣相沈積聚(對二歹苯)聚合物之商品名。在此等聚合物 0 巾’ Paryiene c係最受歡迎’因為其集障壁性能佳、成本低及其他處理優點於一身。Paryiene係自我起始(無需起始劑）且無終端（無需一終端基），且無需溶劑或催化劑。其聚合化發生在極低的壓力及接近室溫的溫度下。整個過程係稱為CVD或化學氣相沈積。所生成之派瑞林模（在沈積過程中已鍵合）成為一厚度以微米計之保護性薄塗層。派瑞林依形於幾乎任何經曝露表面且不同於典型之液體塗層，其渗透小^縫及非均句塗布表面，諸如，尖銳點、㈣、〇彡緣、角落及甚至微孔。此外，派瑞林提供障壁保護，防止有機化合物及無機化合物進入。本發明之該等裝置可由基於聚合物之材料製作。對於一基質裝置，言玄藥物或藥劑可在此聚合物基質内i分解及/ 或分散狀態。在-實施例中’該藥物或藥劑化合成一預成形聚合物，其中該預成形聚合物可呈溶解或分散狀態。接著該裝置有包含此藥物之聚合物形成。有用之聚合物材料之實例係乙烯基醋酸乙烯及丙烯酸基聚合物材料。在另— 實施例中，該藥物或藥劑可化合成一反應體系統。該體係 159575.doc •47· 201223581 可為一單體或大分子單體，其中該藥物或藥劑係呈分解或分散狀態。接著將液體放置於呈該裝置之形狀之一模具中。聚合化該體系（一般係透過uv、可見光、熱或此等方式之一組合）接著形成該裝置。有用之反應性體系之實例包含使用液體丙烯酸單體或反應性聚矽氧預聚合物。用於產生本發明之該基質藥物傳遞裝置之一較佳製程係澆鑄模製。在此製程中，一藥物或藥劑經分解及/或分散於-單體混合物中且放置於呈該眼部裂置之幾何形狀之一塑膠澆鑄模具中。熱曝露、uv曝露或二者之一粗人均可聚合該單體。該裝置接著自該模具移除。可能需要後續處理，例如，邊緣修整。該可生物分解塗層接著應用至該經修改基質裝置。本發明之該等裝置亦可經構造在該裝置本體中之鄰近該 f:面處之一袋狀部或開口，且該袋狀部具有通向該裝置外 t環境之—部分。該袋狀部將部分地由-藥物貯槽填 :该袋狀部之開口係由_可生物分解聚合物部分或完蓋。 P方了由一樂物釋放控制薄膜覆貯：Γ裝置可包含多個袋狀部。各個袋狀部可由-藥物 τ二“也填充，各者具有用於填充該袋狀部之開口之深物分解聚合物。經此態之情形下，該農置 k t、藥物之後續個別突釋， — 4 + 1 釋而非在該裝置應用之後開始次大規模突釋。或者，今望低間夕且 Μ專^狀部可由具有不同腐蝕時間之易蝕材料覆蓋且此亦 ^ τ 抚供後續之釋放特性。該裝置亦 159575.doc -48- 201223581 可經組態傳遞多種藥物。此等組態亦可經組合使得該裝置開始釋放-種藥物且在後_次釋放—不同藥物。由於具有多個衣狀。P ’该裝置亦可經組態以使不同藥物之釋放之時刻改變或重疊。本發明之該等I置亦可經構造具有—藥物貯槽，其完全封閉於該裝置之本體内且能夠將藥物自該貯槽運輸至本體之表面之至少一些部分。Or drug storage tank type drug delivery device for practicing the matrix construction of the present invention, the device is located in the body of the device - "The principle of the device configuration is that the initial drug release will pass through the exposed matrix in the "hole" Occurs or occurs when the thinnest layer of the coating decomposes to expose the surface of the substrate. This will greatly reduce or eliminate the "bursting effect" of the initial drug release that is common in conventional matrix devices. The conformal coating will be slow and rotted to expose more of the surface of the substrate, thus allowing more of the drug to be released in proportion to the surface area of the exposed substrate. In this way, the drug release kinetics can be controlled in such a way that the release rate is more constant throughout the life of the device. In addition to the two components described for the matrix type device, an additional element 159575.doc -41 - 201223581 can be used in the construction-slot type device; - a non-erodible barrier is selected (substantially not allowed in the matrix) Drug penetration), which covers some of the surface portions of the device. Where the device body is comprised of a reservoir that is partially contained within the body of the device, the disrupting configuration can comprise at least four components: (1) the device body having an appropriate placement suitable for its presence within the body of the mammal Position—structure and geometry; (7) a pocket (a partially recessed area) adjacent to the surface of the body, and the pocket has an outward-facing: two-part. The pocket may be in the form of a bore, a void, a well, a cavity or a recess having a plurality of simple or complex shapes, and may include, for example, a temporary fishing, a slot, a groove, a threaded ring, a lug or a convex The characteristics of the block, which are contained in Baosuke and are stably contained in the bag, are located in the pocket, but do not colonize the right 兮丄帛帛贮 ' 药该该该该该该该该该该该该该该该该该该该该该该该一One of the tablets containing the drug or one of the contained drugs may be deep in the pocket according to the deep sound of the bag and the geometry of the groove may be close to the bag portion, that is, the portion of the tank is the largest. If one or two are formed and located at the bottom of the bag, the example of the definition can be solved and the shape of the soap is flat: the lateral τ 4 ^ conical sump is placed flat in the pocket, half The body 'places flat on the side of the pocket. 2:: Storage tank - The drug storage tank has two or the closest to the bag: the W-biodegradable material is the top part - the small part; and the "above" to fill, the agent 1 is placed in the bag In the part, the u1 of the storage tank substantially does not allow the storage of the 159575.doc-42. 201223581, a drug-infiltrated _ biodegradable material composite structure. The modified music sump may have a substantially flat top and the squeegee of the drug sump includes a portion of the surface area of the top of the 4 pockets or a substantially flat one above the drug reservoir completely below top. In addition to these four components, the other two components can be used in a sump type device. (1) A membrane or thin film is placed on the opening of the pocket to further adjust the drug. Released from the pocket 0 < and the film completely or partially covers the opening of the pocket; and (7) according to the configuration of the 4 drug reservoir and the polysigma material used to construct the body of the device must be 4 The wall and bottom of the bag are not allowed to diffuse and penetrate the drug. This will prevent the drug from undesirably diffusing into the body of the device and directing the drug to be released through the top of the pocket and into the ocular environment. The body of the device may consist entirely of a matrix containing the drug or the device may comprise a local drug reservoir. In either case, generally, the device Q is made of a non-erodible polymeric material, preferably elastic in nature. In the case where the body of the device is entirely a substrate containing a drug, the primary reason for selecting the polymeric material is that the polymeric material provides the desired release kinetics. For devices having a localized drug reservoir, the bulk material itself can be selected with greater freedom. In this case, one of the important aspects of the bulk material is its ability to prevent the drug from diffusing into the body from the contained pockets. Examples of polymeric materials that can be used in the practice of the invention include, but are not limited to, polyacrylic acid and methacrylate, ether polyethylene, polyolefins, polyamines, polyvinyl chlorides, fluoropolymers, polyurethanes, polyesters, 159575.doc -43- 201223581 Polyoxane and polystyrene. Although in general, the present system is made of a non-W material, the continuation body is also larger than the conformal coating or the biodegradable material of the substrate device in the bag of the drug sump. Made of biodegradable material resistant to corrosion (4). It will be appreciated that the sump 1IG3 can be any of the active agents disclosed herein and referenced to the active agent 103 in the previous examples. In the context of the present invention, a readily available material is defined as an organic material that can disintegrate into simple chemicals that are typically present in the body. More specifically, the term biodegradable is commonly used to describe polymers that disintegrate upon contact with body fluids, as defined below. Biodegradable materials are chemically disintegrated by exposure to a physiological environment. The material such as shai may be an organic material such as a polymer, or an inorganic material such as certain ceramics or silicates and the decomposition mechanism may be hydrolysis, _catalytic reaction or a combination of the two. In addition, the decomposition process is extremely sensitive to the pH (value) of the environment. For the purposes of the present invention, the terms "erodible", "degradable", "bioerodible" and "biodegradable" refer to the process defined above. The following series can be used in the present invention as a biodegradable polymer: synthetic biodegradable polymer, including but not limited to, polyester; polyorthoester; polyanhydride; polydecylamine; polydioxanone; Oxalic acid; polyacetal; polyimine carbonate; polyurethane; glycoside-cyanoacrylate; polyphosphazene; and natural biodegradable polymer, including but not limited to 'starch, hyaluronic acid, liver fat, 1595754ο, 44 - 201223581 Gelatin, albumin, dextran and chitosan. Ο 实例 Examples of biodegradable polymers generally used in the practice of drug delivery in the present invention include, but are not limited to, polylactic acid, polyglycolic acid, lactic acid/glycolic acid copolymer, polycaprolactone, polyhydroxyl Butyric acid, polypyridyl phthalate, polydioxanone, polyimine carbonic acid, polyorthoester, polyacetate, polydecylamine, poly-n-cyanoacrylate, maleic anhydride copolymer, propylene Amidoxime, hydrazine, Ν'-methylidene acetophenamide, hydrazine-vinylpyrrolidone Ν, hydrazine, hydrazine, acetoin, methacrylic acid/polyethylene glycol _N_ethylene Pyrrolidone, fumaric acid-N-vinylpyrrolidone, fumaric acid/oxomalonic acid-N-vinylpyrrolidone, fumaric acid/oxoglutaric acid_n-ene Pyrrolidone, poly(amino acid), pseudo amino acid, polyphosphazene, starch, hyaluronic acid, liver squama, gelatin, albumin, dextrose liver and deacetylated chitin. Biodegradable polymers can be classified into two groups based on the mechanism or process by which they are decomposed. These processes are decomposed and decomposed by the surface. For agglomerates, body decomposition occurs. The rate of penetration of water into the matrix is greater than the rate of polymerization: decomposition. The process is a homogeneous JJ process in which the decomposition of the material in a polymer matrix at a uniform rate is reversed, and the rate at which water penetrates into the matrix is less than the rate at which the polymer decomposes. needle. Therefore, this process is non-uniform, and the surface is not limited to one of the polymers. It is preferred that the solution is to continue the surface layer after the device is installed in the eye. Once the device is constructed, a late household is selected, and a film is attached to the bag to adjust the release of the drug from the bag. The tether is completely or partially covered by 159575.doc -45. 201223581 to cover the pocket. This slit - the membrane or film may be selected from polymers which allow the penetration of the drug in the sputum, the upper sputum reservoir. According to the deficiencies, the film limits the flux of the drug from the pocket. The thin tether is used to tanning the release profile of the drug. _ t . The film of 霄包含 contains ethylene vinyl acetate (EVA) polymer, 辛功备Q & A rolling and poly (meth) acrylate. Other polymers may also be used as the film. The intended drug diffusion path is from a surface of the exposed drug reservoir directly to the ocular environment or through a release control film between the surface of the sump and the ocular environment. It will be understood that unless the drug is prevented from being released (released) from the reservoir, the drug will diffuse out of all surfaces of the drug reservoir. This will result in drug loss due to diffusion into the body of the side device. The drug in the body of the device then has substantially no therapeutic value for the patient. This non-productive drug must be spread to eliminate or at least reduce the amount of drug to maximize drug flux through the surface of the drug reservoir adjacent to the ocular environment. If the drug-like portion is in the form of a cylinder, it is necessary to place a barrier on the side surface and the flat bottom surface of the cylinder. This will allow the drug to spread only from the top of the top surface and then be placed adjacent to the surface of the device to direct the drug out of the device and into the ocular environment. The technique of providing directional flow of the drug is to cast the sump into a plastic container, such as a bucket having an open top. There are many plastics that can be used as good barriers, for example, polymethyl methacrylate, poly fluorene, and tetrafluoroethylene 8 and polypropylene. One disadvantage of this method is that the plastic container will be difficult to manufacture because of the small size required. Another disadvantage is that the physical size of any plastic container will increase the overall volume of the drug reservoir. Test I59575.doc -46- 201223581 This is not necessary considering the small size of the eye unit itself. Another method is to form a diffusion barrier around the drug reservoir by using an extremely thin film of the barrier. A thin yttria coating can be applied chemically to the drug reservoir, but this is a costly process. A preferred method of creating a barrier on the drug reservoir is the application of parylene, which is a well-known barrier. Poly-p-diphenyl is a trade name for a variety of chemical vapor deposited poly(p-quinone) polymers used as moisture barriers and dielectric barriers. In these polymers, the 'Paryiene c is the most popular' because of its good barrier properties, low cost and other processing advantages. Paryiene is self-starting (no starter required) and has no termination (no need for a terminal base) and does not require solvents or catalysts. Its polymerization occurs at extremely low pressures and temperatures close to room temperature. The entire process is called CVD or chemical vapor deposition. The resulting parylene module (which has been bonded during the deposition process) becomes a protective thin coating in microns. Parylene is shaped on almost any exposed surface and differs from typical liquid coatings in that it penetrates small and non-uniform coated surfaces such as sharp points, (d), enamel edges, corners and even micropores. In addition, Parylene provides barrier protection against the ingress of organic compounds and inorganic compounds. The devices of the present invention can be made from polymer based materials. For a matrix device, the drug or agent can be decomposed and/or dispersed within the polymer matrix. In the embodiment, the drug or pharmaceutical compound is a preformed polymer, wherein the preformed polymer can be in a dissolved or dispersed state. The device is then formed with a polymer comprising the drug. Examples of useful polymeric materials are vinyl acetate and acrylic based polymeric materials. In another embodiment, the drug or agent can be converted to a reactant system. The system 159575.doc • 47· 201223581 can be a monomer or a macromonomer in which the drug or agent is in a decomposed or dispersed state. The liquid is then placed in a mold in the shape of the device. The system is polymerized (typically by uv, visible light, heat or a combination of such means) and the device is subsequently formed. Examples of useful reactive systems include the use of liquid acrylic monomers or reactive polyoxynized prepolymers. One of the preferred process lines for producing the matrix drug delivery device of the present invention is cast molding. In this process, a drug or agent is decomposed and/or dispersed in a monomer mixture and placed in a plastic casting mold in the geometry of the ocular fissure. The monomer can be polymerized by heat exposure, uv exposure, or both. The device is then removed from the mold. Subsequent processing may be required, for example, edge trimming. The biodegradable coating is then applied to the modified matrix device. The apparatus of the present invention may also be constructed in a portion of the apparatus body adjacent the f: face or opening, and the pocket has a portion leading to the environment outside the apparatus. The pocket will be partially filled with a - drug sump: the opening of the pocket is partially or completely covered by a biodegradable polymer. The P side is covered by a piece of music release control film: the device can include a plurality of pockets. Each of the pockets may be "filled with" drug τ2, each having a deep decomposition polymer for filling the opening of the pocket. In this case, the agricultural kt, the subsequent individual burst of the drug , — 4 + 1 release rather than starting a large-scale burst release after the application of the device. Or, the current low-lying and Μ Μ 可由 can be covered by erodible materials with different corrosion times and this is also Subsequent release characteristics. The device is also 159575.doc -48- 201223581 can be configured to deliver multiple drugs. These configurations can also be combined so that the device begins to release the drug and release it after the drug. There are a plurality of garments. The device can also be configured to change or overlap the timing of release of different drugs. The I-positions of the present invention can also be constructed with a drug reservoir that is completely enclosed by the device. The body is capable of transporting the drug from the reservoir to at least some portion of the surface of the body.

在二進-步態樣中，本發明包括一眼部藥物傳遞裝置，其匕3具有-表面之—本體，其係、用於放置鄰近輩媒及一袋狀部或孔隙，其具有通向鞏膜表面之一開口。包括醫藥活性劑之一藥物貯槽係設置於該袋狀部中。可生物分解 (可生物腐#)材料可經設置橫越且覆蓋該藥物貯槽且該可生物分解材料之厚度可非均句(在該裝置之該袋狀部之若干邊緣處較厚）（圖18A及圖18Β)β可在不存在該可生物分解材料處提供一視窗，於此曝露該藥物貯槽。在一進一步態樣中，本發明包括一種傳遞艮青之方法’眼睛具有鞏膜、肋臊及目艮後段。提供一種包括-本體之藥物傳遞裝置’ 一眼部活性劑，其經設置於該本體中。該裝置經設置於鞏膜一联及外表面上，位於眼琢肋膜之下方且鄰近該眼後段。該裝置本體可藉由-模製製程由—聚合材料製成。此將包含但不限於’㈣模製、標準注射·、液體注射模製、壓縮模製及轉移模製。該包含藥物之基質貯槽可獨立於該裝 ~所要的 159575.doc •49· 201223581 構形來製造且然後放置在該袋狀部中。或者，該包含藥物之基質貯槽可在該袋狀部中原位形成。在任一情況中，— 旦該包含藥物之基質貯槽位在該袋狀部中時，該生物可分解聚合物便可被引入至該袋狀物中以至少部分地覆蓋該貯槽之曝露表面。在此時，若可行，可將釋放控制薄膜經由該袋狀物之開口而施加至該裝置表面。用於製造該裝置本體（尤其具有一袋狀物）之另一方法係模製。此將包含但不限於，澆鑄模製、標準注射模製、液體注射模製、壓縮模製及轉移模製。可能需要後續處理，例如，邊緣修整。對於一眼部裝置，較佳使用聚丙烯漁鑄模具。一較佳材料係具有高於2 之-炼融流動指數之—聚丙烯樹脂。—聚丙稀樹脂係pp 1901-01，其具有約34 g/1〇 _之一熔融流動指數。在熔融*動指數大於20 gm/i〇 min之情形下，形狀複雜之澆鑄模具可經射出模製且部件尺寸可良好地複製。製作本發明之該等藥物傳遞裝置之另—較佳製程係液體、出模製其尤其適合於矽氧烷材料。矽氧烷預聚物係與 -聚合化催化劑纟室溫下混合，且接著注射於一熱模具中，以固化。在經固化之後，該裝置係自該模具移除。有時需要後續處理以移除飛邊及/或刻劃分模線之輪廓對於本發明之局部裝置，邊緣剖面在提供裝置舒適性及配合中至關重要。可使用當前在眼科工業中使用之標準化拋光技術來設定此等裝置之該等邊緣及輪廓。較佳的是使用雷射修邊，以形成—光滑、輪廊良好之邊緣。 159575.doc 201223581 性劑且在一些情形下，圖解丄固鮮顯不接觸該活性劑之體液之示例性體液流動型樣；【圖式簡單說明】圖1至圖16係根據本發明之劑傳遞至目標組織之各種袭置不同實施例之用於將一活性之視圖’該等裝置包含一活圖17A係用於在一延長時段中傳遞一活性劑至一目標組織之一示例性裝置之一俯視圖； ΟIn a binary-step pattern, the present invention includes an ocular drug delivery device, the 匕3 having a surface-body for locating a proximity medium and a pocket or aperture having a path One of the scleral surfaces is open. A drug storage tank including one of the pharmaceutically active agents is disposed in the pocket. a biodegradable (biocidal #) material can be disposed across and covering the drug reservoir and the thickness of the biodegradable material can be non-uniform (thicker at some edges of the pocket of the device) 18A and Fig. 18Β) β provides a window in the absence of the biodegradable material, where the drug reservoir is exposed. In a further aspect, the invention includes a method of delivering indigo, the eye having a sclera, a rib, and a posterior segment. There is provided a drug delivery device comprising an ontology, an ocular active agent, disposed in the body. The device is disposed on the sclera and on the outer surface, below the eyelid rib membrane and adjacent to the posterior segment of the eye. The device body can be made of a polymeric material by a molding process. This will include, but is not limited to, '(4) molding, standard injection, liquid injection molding, compression molding, and transfer molding. The drug-containing substrate storage tank can be manufactured independently of the desired configuration of 159575.doc • 49· 201223581 and then placed in the pocket. Alternatively, the drug-containing substrate reservoir can be formed in situ in the pocket. In either case, the biodegradable polymer can be introduced into the pouch to at least partially cover the exposed surface of the reservoir when the drug containing substrate storage tank is positioned in the pocket. At this time, if possible, a release control film can be applied to the surface of the device through the opening of the bag. Another method for making the body of the device, especially having a bag, is molded. This will include, but is not limited to, cast molding, standard injection molding, liquid injection molding, compression molding, and transfer molding. Subsequent processing may be required, for example, edge trimming. For an eye device, a polypropylene fishing mold is preferably used. A preferred material has a polypropylene resin having a smelting flow index of greater than 2. - Polypropylene resin pp 1901-01 having a melt flow index of about 34 g / 1 〇 _. In the case where the melt *motion index is greater than 20 gm/i 〇 min, the casting mold of complicated shape can be injection molded and the part size can be well reproduced. Another preferred process for making such drug delivery devices of the present invention is liquid, which is particularly suitable for use in oxoxane materials. The decane prepolymer is mixed with the -polymerization catalyst at room temperature and then injected into a hot mold to cure. After curing, the device is removed from the mold. Subsequent processing is sometimes required to remove the flash and/or to divide the contour of the mold line. For the partial device of the present invention, the edge profile is critical in providing device comfort and fit. The edges and contours of such devices can be set using standard polishing techniques currently used in the ophthalmic industry. It is preferred to use a laser trim to form a smooth, well-rounded edge. 159575.doc 201223581 The agent and in some cases, illustrates an exemplary body fluid flow pattern of sputum sputum that is not in contact with the body fluid of the active agent; [Simplified Schematic] Figures 1 to 16 are agents delivered according to the present invention. Various exemplary embodiments of the various embodiments of the target tissue for use in the view of an activity comprising one of the devices of FIG. 17A for delivering an active agent to a target tissue for an extended period of time Top view; Ο

圖17B係圖17A之該裝置之—側視圖；圖18A係-種用於在延長時段中傳遞一活性劑至一目標組織之一單一經修改藥物貯槽之一俯視圖，該貯槽係由該傳遞裝置支撐；圖18B係圖18A之該經修改藥物貯槽之一橫截面側視圖；圖19係用於在一延長時段中傳遞一活性劑至目標組織之一示例性裝置之一透視圖；及圖20係用於傳遞一活性劑至一目標組織之一示例性裝置之一代表圖。【主要元件符號說明】 100 裝置 101 裝置 103 活性劑 110 本體 111 第一邊緣 113 第二邊緣 159575.doc • 51 · 201223581 120 130 140 200 205 210 211 213 220 221 222 223 240 250 300 310 311 312 322 400 401 403 407 409 第一表面或面第二表面或面周邊邊緣表面流動特徵壁第一流槽區段閉合第一端開口端第二流槽區段共有開口分支流槽區段開口表面流動特徵局部凹陷區域裝置本體周邊邊緣（圓周邊緣）第一表面或面分支流槽區段裝置裝置裝置邊緣後（下側）表面 159575.doc -52- 201223581Figure 17B is a side elevational view of the device of Figure 17A; Figure 18A is a top plan view of a single modified drug reservoir for delivering an active agent to a target tissue over an extended period of time, the reservoir being utilized by the delivery device Figure 18B is a cross-sectional side view of one of the modified drug reservoirs of Figure 18A; Figure 19 is a perspective view of one exemplary device for delivering an active agent to a target tissue over an extended period of time; and Figure 20 A representation of one of the exemplary devices used to deliver an active agent to a target tissue. [Main component symbol description] 100 device 101 device 103 active agent 110 body 111 first edge 113 second edge 159575.doc • 51 · 201223581 120 130 140 200 205 210 211 213 220 221 222 223 240 250 300 310 311 312 322 400 401 403 407 409 first surface or surface second surface or surface peripheral edge surface flow characteristic wall first flow channel section closed first end open end second flow channel section common opening branch flow channel section opening surface flow feature local depression Peripheral edge of the device body (circumferential edge) Surface of the first surface or face branching trough section device device device (lower side) 159575.doc -52- 201223581

410 本體 412 邊緣頂點輪廓 414 基座曲線 415 凸片 418 前曲線 500 裝置 510 本體 550 通道 600 裝置 610 本體 700 裝置 710 本體 800 裝置 810 本體 825 蓋 900 裝置 910 本體 920 表面流動特徵 922 側 925 平坦表面（底部） 1000 裝置 1010 本體 1020 光學區域 1100 裝置 159575.doc -53- 201223581 1103 藥物貯槽 1110 本體 1115 厚度 1120 第一表面或面 1130 第二表面或面 1140 周邊邊緣 1150 點 1203 活性劑 1300 裝置 1310 本體 1350 局部凹陷區域 1360 複合結構 1370 平坦頂部 1400 裝置 1410 本體 1430 厚度 1440 點 1450 點 159575.doc410 Body 412 Edge Vertex Profile 414 Base Curve 415 Tab 418 Front Curve 500 Device 510 Body 550 Channel 600 Device 610 Body 700 Device 710 Body 800 Device 810 Body 825 Cover 900 Device 910 Body 920 Surface Flow Feature 922 Side 925 Flat Surface ( Bottom) 1000 Device 1010 Body 1020 Optical Zone 1100 Device 159575.doc -53- 201223581 1103 Drug Tank 1110 Body 1115 Thickness 1120 First Surface or Face 1130 Second Surface or Face 1140 Peripheral Edge 1150 Point 1203 Active Agent 1300 Device 1310 Body 1350 Partially recessed area 1360 composite structure 1370 flat top 1400 unit 1410 body 1430 thickness 1440 point 1450 point 159575.doc

Claims

201223581 VII. Patent Application Range: 1. A device for delivering an active agent to a target tissue at a portion including a unitary liquid, the device comprising: a body having a first outer surface; a body formed on the body a partially recessed region, the partially recessed region opening along the first outer surface; an active agent disposed in the partially recessed region such that the active agent is accessible along the first outer surface; a surface flow feature in the form of an open flow channel formed in the body and recessed relative to the outer surface, the flow channel intersecting the local recessed region and configured to direct or modify the body fluid phase for the body The flow causes the body fluid to be in fluid communication with the active agent to improve the dispensing of the active agent from the body to the target tissue; wherein the partially recessed region is recessed relative to at least a portion of the flow channel. 2. The device of claim </RTI> wherein the active agent comprises at least one of a drug and a lubricant. 3. The device of claim 1, wherein the body is configured to be placed in the eye and the body fluid comprises tears. 4. The device of claim 1, wherein the flow cell is positioned and oriented within the body to achieve contact between the body fluid and the active agent and to move away from the active agent after the body fluid has contacted the active agent At least one of them. 5. The device of claim 4 wherein the active agent is positioned along an intermediate section of the flow cell to allow the flow cell to direct the body fluid to contact the active agent 159575.doc 201223581 or to include activity The body fluid of the agent is directed from the localized recessed area to the target tissue. 6. The device of claim 1, wherein the first outer surface comprises a surface that faces away from the target tissue. 7. The device of claim 1 wherein the first outer surface comprises a surface in contact with the target tissue. 8. The device of claim 1, wherein the partially recessed region comprises a well portion to contain the active agent. 9. The device of claim 1, wherein the flow cell comprises at least one open end. The device of claim 1, wherein the flow channel is defined by a first segment and a first segment, and the partial recessed region is formed in the first segment of the flow channel, the flow The slot is recessed from the bottom surface relative to the first outer surface and the partially recessed region is recessed relative to the bottom portion. 11. The device of claim 10, wherein the second segment comprises a branch flow channel segment defined by at least two branch flow channel segments, each branch flow channel segment having one of fluid communication with the localized depression region a first end and an opposite second open end, wherein the branch flow channel sections are divided by a partition wall to determine a device 1 wherein the first segment of the flow channel is along the one The peripheral edge is open and the second section of the flow channel is open at different locations along the edge of the edge. The apparatus of the invention is wherein the member extends across the domain-opening end while maintaining the structure of one of the components of the flow cell to further guide the local depression W under the member. 201223581 Move. 14. If the request item is on the other hand, the local four-trap area 1 is intended to contain two or two cores containing two active cells and the body and two or more flow cells. 15. Formed as a part of claim 1 to:: the body comprises a bottom through the trough and the body: a dip such that it opens along the bottom and is configured in the hole two = The two outer surfaces are open at opposite ends, and the body fluid flows from the flow channel to the opposite second outer surface.忍丨 . . 如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如如a surface flow feature in the form of a first-class groove formed in the body to be recessed relative to the first outer surface, the surface flow feature interfacing with the first segment and the partially recessed region and configured to guide or Modifying the flow of the body fluid to the body such that fluid communication is provided between the body fluid and the partially recessed region; wherein the partially recessed region is recessed relative to at least a portion of the flow channel. 1 7. A device for delivering an active agent to a target tissue at a site comprising a unitary fluid, comprising: a body having an outer surface and a first segment for applying the active agent And to the target tissue; and 159575.doc 201223581 - a surface flow feature in the form of an open-sigmoid trough formed in the body, the surface flow feature being configured to direct or modify the body fluid phase for the body Flowing such that the bodily fluid is in fluid communication with the active agent of the first-section scarf 'continued, 23⁄4: HM, HM", L-channel-discontinuous structure having the flow cell providing the device and At least one open end of the liquid exchange between the outer portions is configured to dispense the active agent to the target tissue m through the flow path through the body of the device, the flow path performing at least the following (five) actions (1) directing the body fluid to contact the active agent and (2) directing the body fluid from the source of the active agent in the first section. 18. A device for delivering an active agent to a target tissue during a predetermined period of time - the device comprises: a body; a sump containing the active agent and supported by the body, the sump comprising a first surface; And an erodible member disposed at least along the first surface of the sump with a varying thickness across the first surface of the sump to control release of the active agent from the sump for a predetermined period of time . The device of Moon Springs 18, wherein the body is configured to be placed in the eye and the member is formed from a material that is rotted in the liquid in the eye over time. 20. The apparatus of claim 18, wherein the body comprises a partially recessed region, the reservoir having the erodible member therein, the partially recessed region being exposed along the exterior of the beta body. 21. The device of claim 18, wherein the first surface has a convex shape, and the 159575.doc 201223581 erodible member is located at one of the vertices of one of the sumpes. 22, as claimed in claim 18 A device of the invention, wherein the erodible member has a large thickness at a plurality of peripheral edges of the sump. 23. The request item is a <only& device having a plurality of reservoirs and a plurality of associated members. The members of the (four) members have different cross-sectional profiles, and the profiles are released with different activity-times. Ο 24. ΐΓΓΓ, the device, wherein at least one of the easy-to-use components is constructed in a dispenser.匕3 immediately after one part of the body fluid of the right stem is dispensed with the activity. 25. The device of claim 8, wherein the first surface of the remaining component - the inner surface essence I = non-tank and the storage tank is not Thousands of tandem with respect to the surface: opposite one of the profiles' and the outer surface of the easy-to-use member is at least substantially flat. The device of claim 18, wherein the first surface has H and the stomach οιο οο οο ο ο ο ο ο ο The material may be made of a material in the =_: component, and at least a portion of the conduit is corroded to an open skin: passing through the braided member and reaching the outside to stop the active agent from passing through the easy # member. 28) The apparatus of claim 18, the straight section, ~,; 1 component is selected with a release rate of a non-uniform cross-section. The pre-existing time & the required device 29, such as the device of claim 18, the stable outer side of the body and representing 3 = the component is the device J 〇 is placed in the body 159575.doc 201223581 a part One of the inserts in the recessed area. The device of claim 29, wherein an outer surface of the body of the device comprises a recessed open flow channel formed therein, the flow channel opening along at least one end and opening along a top thereof, the flow A groove intersects the partially recessed area to direct bodily fluids in contact with the erodible member. 159575.doc 6 =