417387 玖、發明說明 (發明說明廊钕昍·Λ 〜β.發明所屬之技術領域、先前技術、内容、實施方式及圖式簡單說明） 本申明案係請求於2002年3月11日提出申請的美國臨 時專利申請案序號為60/363,150之優先權。 【發明所屬之技術領域】 5 發明領域 本發明係有關於一種藥物傳輸系統；更特定言之，本 發明係有關於一種供人類或是其他動物所用的可植入式小 型藥物傳輸裝置。 t 先前 !〇 發明背景 藉由使用一或更多的藥劑，有效地治療人類或動物的 身體内所發生的數種症狀或疾病。針對數種該等症狀及疾 病，係以口服方式服用藥劑。一經吞服，藥劑藉通過胃腸 系統最後移動至症狀或疾病的位置。在其他的情況下，藥 15劑係經由血液流動而傳輸至症狀或疾病的位置。特別地， 藉由一皮下注射器將藥劑注射進入肌肉或軟組織，接著藉 由血液流動運載。在其他的情況下，一般在保健服務設施 ，可使用一 IV drip方式將藥劑直接地置入於血管中。在其 他的情況下，一些類型的外科處置係用以將一特別的藥劑 20 ，置於體内症狀或疾病的位置處或是接近的位置。 頃發現的是’藉由使用針對積體電路之產生所發展的 技術，能夠製成小型的藥物傳輸裝置，用以容納並接著將 樂劑傳輸至人體内症狀或疾病的位置。該等小型藥物植入 裝置的實例，係揭露在以下的美國專利中：美國專利第 5 200417387 玖、發明說明 5’770,076號；美_ #利帛5,797,898號；美目專利第 5,985,328號；美國專利第6，123,861號；以及美國專利第 6,331，3 13號。數種該等小型藥物植入裝置係高度地複雜， 因此，對於製造而言係為困難且昂貴。於是，於業界存在 5著一需求，即一小型、低成本、易於製造的可植入式小型 藥物傳輸裝置，其能用於植入人體或是其他動物體中，用 以將藥劑傳輸至廣泛的位置。 L發明内容】 發明概要 10 纟發明之簡單、低成本、易於製造之可植入式藥物傳 輸系統，使機構能夠植入在人體中，用以將藥劑傳輸至廣 泛的位置。所揭露的系統至少包括一池、井或是開放空間 。該池、井或是開放空間係經配框、圍住、包裝或是構成 在一核心主體中。位在核心主體中的池、井或是開放空間 15或池外殼部分係有足夠的尺寸，用以容納所需量的藥劑， 該量係為慢性症狀或疾病之延長體内治療所需。該等典型 的慢性症狀或疾病，係為所熟知之發生在眼内的慢性症狀 或疾病。 在核心主體的頂部或是底部、或頂部與底部處以一筛 20圍繞覆蓋池、井或是開放空間。該筛係用以控制放置在池 、井或是開放空間中的片劑、粉劑或是漿液之藥物或是藥 劑，釋放或移動進入人體或是動物體中。篩中孔的數目、 尺寸、位置及配置，係為容納在池、井或是開放空間中藥 劑的溶解度、藥劑的溶解率、藥劑的濃度以及藥物的形 6 200417387 玫、發明說明 式-片劑、粉劑、漿液或是該等的結合等之函數。 一或更多的藥劑一旦放入池、井或開口 ·中，並且节、、也 、井或開口係覆以一篩，則該整個藥物或藥劑之結合、構 成池之主體以及筛係植入在身體中。例如，針對發生在眼 5中的症狀或疾病，一種技術係將所揭露的藥物傳輸系統麫 由鞏膜部分嵌入眼中。該所揭露的藥物傳輸裝置一旦正確 地安置在其之所需位置，則可利用數種方法將其固定在適 當位置，包括將縫線通過一構成在核心主體中之孔。 當流體由主體中移經篩中之穿孔進入池中時，藥劑自 10 池、井或開放空間分散而出。此流體流經篩在池内開始溶 解藥劑。該溶解的藥劑將因而緩慢地經由位在篩中之孔向 外滲出，只要在所揭露的藥物傳輸裝置之池中保持藥劑量 ，即可提供對於症狀或疾病的持續治療。 圖式簡單說明 藉由參考圖式可對本發明之可植入式藥物傳輸系統有 較佳的瞭解。 第1圖係為本發明之嵌入人類眼睛中的一具體實施例 之側視圖； 第2A圖係為較佳具體實施例的分解透視圖； 20 第2B圖係為與第2A圖中所示相似的一核心主體的透 視圖， 第2C圖係為與第2A圖中所示相似的一篩的透視圖； 第2D圖係為諸如第2C圖中所示之一篩之一部分的放 大平面圖； 7 200417387 ♦ 暑 玖、發明說明 第3圖係為一第一可交替具體實施例的分解透視圖； 第4A及4B圖係為所揭露的藥物傳輸系統之一第二及 第二可父替具體貫施例的透視圖； 第5圖係為附裝至-支撐件之藥物傳輸系統的側視圖； 5 第6A圖係為包括一銳化邊緣或是解剖刀鼻部分之藥物 傳輸系統的一透視圖； 第6B圖係為第6A圖中所示之具體實施例的一分解視 S3 · 圃， 第6C圖係為與第6A圖中所示相似之包括一銳化邊緣 10 之藥物傳輸系統的一透視圖； 第6 D圖係為在第6 C圖中所示之具體實施例的分解視 圖； 第7圖係為本發明之藥物傳輸系統之核心主體的一可 交替具體實施例的透視圖，其進一步包括一通道用於再供 15 給藥劑至該池中； 第7A圖係為在第7圖中所示之藥物傳輸系統的核心主 體的一可交替具體實施例，其包括一凸緣部分丨以及 第8圖係為藥物傳輸系統的另一可交替具體實施例的 一透視圖，其包括複數之較小的池； 20 帛9圖係為具有-三區劃池的-藥物傳輪系統的一透 視圖，其中在區劃之間包括一内通道用於藥劑移動； 第10圖係為一藥物傳輸系統的一透視圖，其中在一較 大的池中包括二較小的池； 第11圖係為於第10圖中所示之藥物傳輸系統的一可交 8 200417387 t » 玖、發明說明 替具體實施例的一透視圖； 第12圖係為具有-單-池之-藥物傳輪系統的一透視 圖； 弟13圖係為在第12圖中所示之藥物傳輪系統的一第一 5 可交替具體實施例的一透視圖； 第14圖係為在第12圖中所示之藥物傳輪系統的一第二 可交替具體實施例的一透視圖； 第15圖係為在第12圖中所示之藥物傳輪系統的一第三 可交替具體實施例的一透視圖； 10 第16圖係為在第12圖中所示之藥物傳輸系統的一第四 可交替具體實施例的一透視圖； 弟17圖係為在第12圖中所示之藥物傳輸系统的一第五 可交替具體實施例的一透視圖； 弟18圖係為在弟12圖中所示之藥物傳輸系統的一第六 15 可交替具體實施例的一透視圖； 第19圖係為在第12圖中所示之藥物傳輸系統的一第七 可交替具體實施例的一透視圖； 第20圖係為在第12圖中所示之藥物傳輸系統的一第八 可交替具體實施例的一透視圖； 2〇 第21圖係為在第1〇圖中所示之藥物傳輸系統的一第一 可交替具體實施例的一透視圖； 第22圖係為在第1〇圖中所示之藥物傳輸系統的一第二 可交替具體實施例的一透視圖； 第23圖係為利用betaxolol鹽酸鹽片劑的活體外研究（ill 9 200417387 玖、發明說明 vitro study)中，藥物濃度對時間的一曲線；以及 第24圖係為利用nepafenac片劑的活體外研究（in vitro study)中，藥物濃度對時間的一曲線。 【實施方式3 5 具體實施例之說明 於以下的較佳及可交替的具體實施例之說明中，所使 用的代表符號係有助於說明所揭露的發明。於此整個說明 中’與每一具體實施例之相同部分係以相同的個位及十位 數子代表符號標示。而以百位及千位數字的代表符號標示 0 —可交替具體實施例。 於第1圖中可見，所顯示之本發明的一小型可植入式 藥物傳輸系統，其係用於治療對眼睛内在部分造成影響的 症狀或疾病。該等疾病包括但不限制在老年性黃斑部病變 (ARMD)、增殖期糖尿病視網膜病變（pDR)、新生血管性青 光眼、 缺血性及醫源性視網膜病變、後眼發炎及視網膜水 療内眼疾病而加以說明， ，本發明係可在一動物翻 儘管本發明之較佳具體實施例於此餘據其之用於治 但熟知此技藝之人士應暸解的是417387 发明, description of the invention (Invention Gallery Neodymium 昍 · Λ ~ β. Brief description of the technical field, prior art, content, implementation and drawings of the invention) This declaration is a request for application on March 11, 2002 US provisional patent application serial number 60 / 363,150 has priority. [Technical Field to which the Invention belongs] 5 Field of the Invention The present invention relates to a drug delivery system; more specifically, the present invention relates to a small implantable drug delivery device for humans or other animals. t Previous! Background of the Invention By using one or more medicaments, several symptoms or diseases that occur in the human or animal body are effectively treated. For several of these symptoms and diseases, the medication is taken orally. Once swallowed, the medicament finally moves through the gastrointestinal system to the location of the symptoms or disease. In other cases, the medication is transmitted to the location of the symptom or disease via blood flow. Specifically, the medicament is injected into the muscle or soft tissue by a hypodermic syringe, and then carried by blood flow. In other cases, generally in health care facilities, an IV drip method can be used to place the medicament directly into the blood vessel. In other cases, some types of surgical procedures are used to place a particular medicament 20 at or near the location of a symptom or disease in the body. What was discovered was that ‘by using technology developed for the generation of integrated circuits, it is possible to make small drug delivery devices to hold and then deliver lotions to the location of symptoms or diseases in the human body. Examples of such small drug implantation devices are disclosed in the following U.S. patents: U.S. Patent No. 5,200417387, Invention Description No. 5'770,076; US_ # 利 _5,797,898; Meme Patent No. 5,985,328; U.S. Patent No. 6,123,861; and U.S. Patent No. 6,331,313. Several of these small drug implantation devices are highly complex and therefore difficult and expensive to manufacture. Therefore, there is a need in the industry for a small, low-cost, and easy-to-manufacture implantable small drug delivery device that can be implanted into the human body or other animal bodies to deliver medicaments to a wide range s position. SUMMARY OF THE INVENTION [Summary of the Invention] [10] The invention is a simple, low-cost, easy-to-manufacture implantable drug delivery system that enables a mechanism to be implanted in a human body to deliver a medicament to a wide range of locations. The disclosed system includes at least a pool, well, or open space. The pool, well, or open space is framed, enclosed, packed, or formed into a core body. The pool, well, or open space 15 or the shell portion of the core body is of sufficient size to accommodate the required amount of the medicament, which is required for prolonged in vivo treatment of chronic symptoms or diseases. These typical chronic symptoms or diseases are the chronic symptoms or diseases known to occur in the eye. A screen 20 surrounds the pool, well, or open space at the top or bottom of the core body, or at the top and bottom. The sieve is used to control the release or movement of tablets, powders or slurries of drugs or medicines placed in the pool, well or open space into the human or animal body. The number, size, location and configuration of the holes in the sieve are the solubility of the drug, the solubility of the drug, the concentration of the drug, and the shape of the drug contained in the pool, well, or open space. 6 200417387 , Powder, slurry, or a combination of these. Once one or more medicaments are placed in the pool, well, or opening, and the joints, wells, or wells are covered with a sieve, the combination of the entire drug or medicament, the body constituting the pool, and the sieve are implanted in In the body. For example, for a symptom or disease that occurs in eye 5, a technique is to embed the disclosed drug delivery system 麫 from the sclera part into the eye. Once the disclosed drug delivery device is properly positioned in its desired position, it can be secured in place using several methods, including passing a suture through a hole formed in the core body. When the fluid moves from the main body through the perforations in the sieve into the pool, the medicine is dispersed from the 10 pools, wells or open spaces. This fluid flows through the screen and begins to dissolve the agent in the tank. The dissolved medicament will therefore slowly leak out through the holes located in the sieve, and as long as the dose is maintained in the pool of the disclosed drug delivery device, a continuous treatment for symptoms or disease will be provided. BRIEF DESCRIPTION OF THE DRAWINGS A better understanding of the implantable drug delivery system of the present invention can be obtained by referring to the drawings. Figure 1 is a side view of a specific embodiment of the present invention embedded in human eyes; Figure 2A is an exploded perspective view of a preferred embodiment; 20 Figure 2B is similar to that shown in Figure 2A Figure 2C is a perspective view of a sieve similar to that shown in Figure 2A; Figure 2D is an enlarged plan view of a portion of a sieve such as that shown in Figure 2C; 7 200417387 ♦ Summer and invention description Figure 3 is an exploded perspective view of a first alternate embodiment; Figures 4A and 4B are one of the disclosed drug delivery systems. A perspective view of an embodiment; FIG. 5 is a side view of a drug delivery system attached to a support; FIG. 6A is a perspective view of a drug delivery system including a sharpened edge or a nasal portion of a scalpel 6B is an exploded view S3 of the specific embodiment shown in FIG. 6A, FIG. 6C is a view of a drug delivery system including a sharpened edge 10 similar to that shown in FIG. 6A Perspective view; Figure 6D is a breakdown of the specific embodiment shown in Figure 6C FIG. 7 is a perspective view of an alternate embodiment of the core body of the drug delivery system of the present invention, which further includes a channel for supplying another 15 doses to the pool; FIG. 7A is An alternate embodiment of the core body of the drug delivery system shown in FIG. 7 includes a flange portion and FIG. 8 is a perspective view of another alternate embodiment of the drug delivery system 20 包括 9 is a perspective view of a drug transfer wheel system with a three-zone pool, in which an inner channel is included between the zones for medicament movement; FIG. 10 A perspective view of a drug delivery system, where two larger pools are included in a larger pool; Figure 11 is a deliverable of the drug delivery system shown in Figure 10 8 200417387 t »玖A description of the invention is a perspective view of a specific embodiment; FIG. 12 is a perspective view of a-single-pool-drug transfer system; Figure 13 is a view of the drug transfer system shown in Figure 12 A perspective of a first 5 alternate embodiment Figure 14 is a perspective view of a second alternate embodiment of the drug transfer system shown in Figure 12; Figure 15 is a drug transfer system shown in Figure 12 A perspective view of a third alternate embodiment of FIG. 10; FIG. 16 is a perspective view of a fourth alternate embodiment of the drug delivery system shown in FIG. 12; FIG. 17 is A perspective view of a fifth alternative embodiment of the drug delivery system shown in FIG. 12; FIG. 18 is a sixth alternative implementation of the drug delivery system shown in FIG. 12 A perspective view of the example; FIG. 19 is a perspective view of a seventh alternate embodiment of the drug delivery system shown in FIG. 12; FIG. 20 is a drug shown in FIG. 12 A perspective view of an eighth alternate embodiment of the delivery system; FIG. 21 is a perspective view of a first alternate embodiment of the drug delivery system shown in FIG. 10; Figure 22 is a second alternate implementation of the drug delivery system shown in Figure 10 Fig. 23 is a graph of drug concentration versus time in an in vitro study (ill 9 200417387 (vitro study) using betaxolol hydrochloride tablets), and Fig. 24 is a graph using nepafenac A curve of drug concentration versus time in an in vitro study of a tablet. [Embodiment Mode 3 5 Description of Specific Embodiments] In the following description of the preferred and alternate specific embodiments, the representative symbols used are used to explain the disclosed invention. Throughout this description, the same portions as those of each specific embodiment are indicated by the same unit and tens digits. And the representative symbols of the hundreds and thousands digits are marked with 0-specific embodiments can be alternated. As can be seen in Figure 1, a small implantable drug delivery system of the present invention is shown for treating symptoms or diseases that affect the inner part of the eye. These diseases include, but are not limited to, senile macular degeneration (ARMD), proliferative diabetic retinopathy (pDR), neovascular glaucoma, ischemic and iatrogenic retinopathy, posterior eye inflammation, and retinal hydrotherapy inner eye disease To illustrate, the present invention can be applied to an animal. Although the preferred embodiments of the present invention are used for treatment, those skilled in the art should understand that
治療而發生之副作用， 位置，用於治療攝護腺癌或是攝護 露的裝置，通常伴隨著攝護腺癌之 諸如潮熱、聲音改變、或是胸部擴 10 200417387 玖、發明說明 大等可顯著地降低，或甚至是消除。此外，熟知此技藝之 人士應暸解的是’可以顯著地降低治療疾病或症狀所需的 藥物或藥劑量，因而減少病患成本。病患遵照的治療型態 係隨著有效地排除頻繁投藥的需求而得以改良。將可減少 5藥師工作量及暴露在有危險的或有毒的製劑中的機會。可 有效地避免藥物對藥物或是藥物對食物相互影響的機會。 並且，增加提供藥物結合療 '法的機會。 假若所揭露的裝置包括以植入於女性體内的避孕劑取 代，亦可獲得相似之優點。其他的具潛力之應用包括以一 10 抗黴菌藥劑治療外陰黴菌感染。 柏金森氏症患者亦等候將所揭露的藥物傳輸裝置植入 腦中’用以緩慢地釋放藥劑用於減少顫抖。具有潰瘍性結 腸炎或是複數種不同的消化系疾病，亦能夠藉由在消化道 中植入所揭露之裝置而得到緩解。 15 如第2A圖中可見，藥物傳輸系統10包括一池14。該池 係構成在池包封容器、配框或是外殼部分12中。為了簡化 說明，池包封容器、配框或是外殼部分係稱作為核心主體 12。於較佳的具體實施例中，核心主體12係由一大體上平 坦剛性的材料件所製成。於第2A圖中所示之池14，具有一 20頂部16以及一底部18。池14之頂部16係與核心主體12的上 表面20相交。於較佳的具體實施例中，池14之底部18與核 心主體12的下表面22相交。圖示的池14實際上係為核心主 體12穿過的一孔。假若頂部16大於底部18，則池14可具有 推拔壁17。 11 200417387 玖、發明說明 藉由參考第2B圖可對核心主體12之構造有較佳的瞭解 。其中，所示之核心主體12具有一拱形改良的跑道式外周 圍。包含於其中的池14完全地經由上表面20通過至下表面 22，並且其之周圍大約平行於核心主體的外周圍。為了對 5所揭露的小尺寸之藥物傳輸系統有較佳的瞭解，核心主體 12的長度係約為9·5公厘，以及寬度係約為5.3公厘。 如第2B圖中所示，池14可位在核心主體12的中心處， 或是較為接近核心主體12的一端部。池14之尺寸係足以容 納複數之不同的藥劑。該等藥劑可包括該等直接或間接的 10神經保護劑、抗氧化劑、抑制細胞凋亡劑、可溶解的生長 因子啟動劑或拮抗劑、抗增生劑、抑制金管增生劑、抗水 腫劑、血管標劑、抗發炎或是抗生素，無論其係為小的有 機分子或生物，諸如蛋白質、核酸型酵素、抗體、抗體碎 片、契合寡聚體（aptameters)、或是核苷酸不足。更特定言 15之適5的藥劑包括但不限定在信號轉導抑制劑、蛋白質 催化拮抗劑、酪胺酸催化拮抗劑、血管内皮生長因子受體 枯抗劑、整合素拮抗劑、基質金屬蛋白酶抑制劑、企漿糖 皮質激素、非類固醇類抗炎藥（NSAIDS)、環氧化酵素 (COX-1及/或cox_2)抑制劑及_〇伽以類固醇。該等每 20 -樂劑係可為粉劑、漿液或是片劑的形式。視疾病的類型 與嚴重性，開立一段期間的藥劑處方，該藥劑量應足以提 供該疾病的充分治療。如有需要，可將複數種不同的添加 劑添加至藥劑，用以增加其之有效性。例如，可將一具親 水性的添加劑，諸如一輔藥濕潤劑，添加至藥劑中為吸 12 200417387 玖、發明說明 引水分子至傳輸裝置嵌入眼中的區域，開始或是有助於藥 劑的溶解或是運送藥劑離開該池丨4。 為了將在池14中形成的小氣泡減至最少，池14之尺寸 及形狀較佳地大體上與放置在池14中的藥劑之尺寸及形狀 5相同’用以將自由空氣量降至最低。 如第2C圖中所示，將所構成的一第一篩24附裝至核心 主體12的上表面20，用以覆蓋池14之頂部16。可任擇地， 將一第二篩26附裝至核心主體12的下表面22，用以覆蓋池 14之底部18。於較佳的具體實施例中，篩24係如第2C圖中 10所示。特別地，篩24具有一梹形改良的跑道式周圍3 6，其 大約與池14的周圍及核心主體12的周圍平行。篩中構成孔 28的部分23，其之厚度視裝置1〇的構造，可與周圍25的厚 度相同，或是一不同的厚度。 如第2D圖中可見，構成篩24或是篩24、26用以容納該 15複數孔28。於篩24或是篩24、26中孔28的數目、尺寸、位 置以及配置，係為種種因素的函數，包括放置在池14中之 藥物的溶解度、放置在池14中之藥物的溶解率、以及放置 在池14中之藥物的濃度。典型地，孔28的尺寸在任何位置 大體上約從0.2微米至1〇〇微米。然而，所揭露的發明的多 2〇功性，在其他的應用亦可使用不同的孔尺寸。儘管應瞭解 的是，大體上孔28均勻地分佈涵蓋篩24或是篩24、26之表 面，使能夠得到藥劑的最大溶解，但是如以下說明，其他 之孔28的不均勻分佈亦能夠達到相同效果。此外，熟知此 技藝之人士應瞭解的是，當在眼中使用本發明之藥物傳輸 13 200417387 玖、發明說明 糸、、先守β亥專孔必需夠小用以阻止任何會干擾視力之未溶 解的藥劑顆粒通過。 針對每一篩的適當厚度，視打算於目標植入處所投藥 的藥劑量而定，係約從〇·〇5公厘至0·5公厘，而核心主體12 5的適當厚度，係約從0.5公厘至3·〇公厘，較佳地約從1〇公 厘至2.0公厘。 當使用金屬抑或是非金屬材料製造所揭露的藥物傳輸 裝置時，篩24或是篩24、26可利用複數種不同的黏著劑， 固定至核心主體12，包括矽橡膠、氰基丙烯酸、或是通常 10可利用之適合人體使用之室温黏著劑、熱黏著劑、環氧或 是紫外光固化黏著劑。於較佳的具體實施例中，如同核心 主體12，所構成的篩24或是篩24、26大體上亦為平面的。 複數種不同的材料可用以製造核心主體12以及篩24或 是篩24、26。該等材料可自複數種不同之適合人體使用的 15 材料中選出，其包括矽、玻璃、紅寶石、藍寶石、鑽石或 是陶瓷。如為所需，可使用一適合人體使用的材料，用以 構成核心主體12以及師2 4、2 6。該等適合人體使用的材料 包括金、銀、白金、不銹鋼、鎢以及鈦。當使用一適合人 體使用的材料時’篩24或是篩24、26可利用複數種不同的 20 技術熔接至核心主體12，包括雷射熔接、熱電接合，如先 前所示，或是上述的膠及黏著劑。 熟知此技藝之人士應瞭解的是，所揭露的藥物傳輸平 臺的有效性，係於一段預定期間藉由傳輸適當數目之藥劑 分子而決定。因此，在篩中孔28的總和面積，必需能夠自 14 200417387 玖、發明說明 達到所需的藥劑傳輸率。_般地，如此係視為孔密度 。為了此揭露内容，孔密度係為總孔面積除以裝置的總表 面積’甚至是該等未由一篩所覆蓋的面積。 位在一篩之表面上孔的數目、其之尺寸、其之位置以 及其之-般外觀，構成一孔圖案。此孔圖案係經調整用以 確保，在所需的流率下傳輸所需的藥劑量。當在核心主體 帽成複數之池時，於_中複數之孔圖案可用㈣㈣劑 的/败動。例如，孔集中在池之-端部處的-孔圖案，將開 始導致藥劑的一快速流動。但是，當藥劑用盡時，藥劑在 自池14中排出之前行進一段較長的路徑；因此，藥劑離開 藥物傳輸池14的釋放率將超時地急下降。 10 於第3圖中所示的一可交替具體實施例中，池ιΐ4之底Side effects and location of treatment, the device used to treat prostate cancer or propolis, usually accompanied by prostate cancer such as hot flashes, sound changes, or chest enlargement 10 200417387 Can be significantly reduced, or even eliminated. In addition, those skilled in the art should understand that 'can significantly reduce the amount of drugs or medications needed to treat a disease or condition, thereby reducing patient costs. The patient's adherence to the treatment modality has improved with the effective elimination of the need for frequent dosing. Will reduce the workload of 5 pharmacists and exposure to dangerous or toxic preparations. Can effectively avoid drug-to-drug or drug-to-food interaction opportunities. Also, increase the chances of providing drug combination therapy. Similar advantages can be obtained if the disclosed device includes a contraceptive implanted in a woman. Other potential applications include the treatment of vulvar mold infections with an antimycotic agent. People with Parkinson's disease are also waiting for the disclosed drug delivery device to be implanted in the brain 'to slowly release the medicament to reduce tremors. Ulcerative colitis or multiple different digestive diseases can also be alleviated by implanting the disclosed device in the digestive tract. 15 As can be seen in Figure 2A, the drug delivery system 10 includes a pool 14. The cell is formed in a cell-encapsulating container, a frame, or an outer shell portion 12. For simplicity of explanation, the container-enclosed container, frame, or shell part is referred to as the core body 12. In a preferred embodiment, the core body 12 is made of a substantially flat rigid piece of material. The pool 14 shown in FIG. 2A has a top 20 and a bottom 18. The top 16 of the pool 14 intersects the upper surface 20 of the core body 12. In a preferred embodiment, the bottom 18 of the pool 14 intersects the lower surface 22 of the core body 12. The pool 14 shown is actually a hole through which the core body 12 passes. If the top 16 is larger than the bottom 18, the pool 14 may have a push wall 17. 11 200417387 发明 Description of the invention A better understanding of the structure of the core body 12 can be obtained by referring to FIG. 2B. Among them, the core body 12 shown has an arched modified runway-type periphery. The pool 14 contained therein passes completely through the upper surface 20 to the lower surface 22, and its periphery is approximately parallel to the outer periphery of the core body. In order to better understand the small-sized drug delivery system disclosed in 5, the length of the core body 12 is about 9.5 mm and the width is about 5.3 mm. As shown in FIG. 2B, the pool 14 may be located at the center of the core body 12 or closer to one end of the core body 12. The size of the cell 14 is sufficient to accommodate a plurality of different medicaments. The agents may include such direct or indirect 10 neuroprotective agents, antioxidants, inhibitors of apoptosis, soluble growth factor initiators or antagonists, antiproliferative agents, inhibitors of gold tube proliferation, antiedema agents, blood vessels Standards, anti-inflammatory, or antibiotics, regardless of whether they are small organic molecules or organisms, such as proteins, nucleic acid-type enzymes, antibodies, antibody fragments, aptamers, or lack of nucleotides. More specifically, 15 to 5 agents include, but are not limited to, signal transduction inhibitors, protein catalytic antagonists, tyrosine catalytic antagonists, vascular endothelial growth factor receptor antagonists, integrin antagonists, and matrix metalloproteinases Inhibitors, glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDS), inhibitors of epoxidizing enzymes (COX-1 and / or cox_2), and steroids. The 20-percent can be in the form of a powder, a slurry, or a tablet. Depending on the type and severity of the disease, a prescription for the medication should be prescribed for a period of time sufficient to provide adequate treatment for the disease. If desired, a number of different additives can be added to the agent to increase its effectiveness. For example, a hydrophilic additive, such as an adjuvant humectant, can be added to the medicament to absorb 12 200417387 发明, the description of the invention introduces water molecules to the area of the delivery device embedded in the eye, to start or help the dissolution or It is the medicine that leaves the pool. To minimize the formation of small bubbles in the pool 14, the size and shape of the pool 14 is preferably substantially the same as the size and shape of the medicament placed in the pool 14 'to minimize the amount of free air. As shown in Figure 2C, a first screen 24 is attached to the upper surface 20 of the core body 12 to cover the top 16 of the pool 14. Optionally, a second screen 26 is attached to the lower surface 22 of the core body 12 to cover the bottom 18 of the pool 14. In a preferred embodiment, the screen 24 is shown as 10 in Fig. 2C. In particular, the sieve 24 has a rounded modified runway-like periphery 36 which is approximately parallel to the periphery of the pool 14 and the periphery of the core body 12. The thickness of the portion 23 of the sieve constituting the hole 28 may be the same as that of the surrounding 25 or a different thickness depending on the structure of the device 10. As can be seen in FIG. 2D, the sieve 24 or the sieves 24, 26 are used to accommodate the 15 plurality of holes 28. The number, size, position, and configuration of holes 28 in the sieve 24 or in the sieve 24, 26 are functions of various factors, including the solubility of the drug placed in the pool 14, the dissolution rate of the drug placed in the pool 14, And the concentration of the drug placed in the tank 14. Typically, the size of the holes 28 is generally from about 0.2 microns to 100 microns at any location. However, the multi-functionality of the disclosed invention can also be used in other applications with different hole sizes. Although it should be understood that, in general, the holes 28 are evenly distributed to cover the surface of the sieve 24 or the sieve 24, 26, so that the maximum dissolution of the drug can be obtained. effect. In addition, those skilled in the art should understand that when using the drug delivery of the present invention in the eye 13 200417387 玖, invention description 糸, the pre-beta pores must be small enough to prevent any undissolved The medicament particles pass. The appropriate thickness for each sieve depends on the dosage of the drug intended to be administered in the target implantation space, from about 0.05 mm to 0.5 mm, and the appropriate thickness of the core body 12 5 is from about 0.5 mm to 3.0 mm, preferably from about 10 mm to 2.0 mm. When metal or non-metal materials are used to make the disclosed drug delivery device, the sieve 24 or the sieve 24, 26 can be fixed to the core body 12 using a plurality of different adhesives, including silicone rubber, cyanoacrylic acid, or generally 10 Available room temperature adhesives, thermal adhesives, epoxy or UV curing adhesives suitable for human use. In a preferred embodiment, like the core body 12, the formed screen 24 or screens 24, 26 are also generally planar. A plurality of different materials can be used to make the core body 12 and the screens 24 or 24,26. These materials can be selected from a number of different materials suitable for human use, including silicon, glass, ruby, sapphire, diamond or ceramic. If necessary, a material suitable for the human body can be used to constitute the core body 12 and the divisions 24, 26. These materials suitable for human use include gold, silver, platinum, stainless steel, tungsten, and titanium. When using a material suitable for the human body, the sieve 24 or sieves 24, 26 can be welded to the core body 12 using a plurality of different 20 technologies, including laser welding, thermoelectric bonding, as shown previously, or the glue described above. And adhesives. Those skilled in the art should understand that the effectiveness of the disclosed drug delivery platform is determined by the delivery of an appropriate number of drug molecules over a predetermined period of time. Therefore, the total area of the holes 28 in the sieve must be able to achieve the required drug transmission rate from 14 200417387 发明. Generally, this is regarded as the pore density. For the purpose of this disclosure, the pore density is the total pore area divided by the total surface area of the device 'or even those areas not covered by a sieve. The number of holes located on the surface of a sieve, its size, its location, and its general appearance constitute a hole pattern. This hole pattern is adjusted to ensure that the required dose is delivered at the required flow rate. When the cap is formed into a plurality of pools in the core body, the pattern of the plurality of holes in _ can be used by the tincture / defeat. For example, a -hole pattern where the holes are concentrated at the -end of the pool will start to cause a rapid flow of the medicament. However, when the medicament is exhausted, the medicament travels a long path before being discharged from the tank 14; therefore, the release rate of the medicament from the drug delivery tank 14 will drastically decrease over time. 10 In an alternate embodiment shown in Figure 3, the bottom of the pool 4
crpl 1 8本身了構成為一篩，因此排除使用及附裝如於第2 A 圖中所不的-第二_26之需求。於其他的應用中，如於第 15 3囷中所示亦有可能使池Π 4具有一實體底部。當池114 具有一實體底部時，在池114之頂部116上僅使用一單一篩 124。 儘管幸乂佳的具體實施例顯示一改良的跑道周圍3 6，將 池14較接近末端15，以及一縫孔3〇係配置在近側端^，熟 20知此技藝之人士應瞭解的是，複數種其他的可植入式藥物 傳輸平臺的設計係為可行，不致背離本發明之範疇。例如 ，藥物傳輸平臺可構成具有複數的縫孔3〇,或是構成平直 的側邊，諸如在第4A圖中所示的三角形狀310。可交替地 ，方形形狀、環形形狀、槳形狀或是任一其他合宜的形狀 15 200417387 玖、發明說明 可欲入通過眼睛中或是位在身體中之一部分的一小切口， 該處係為確定藥劑可最有效地使用的位置。 由於所揭露之發明的適應性可構形為複數種不同的形 狀，特別是假若核心主體及篩係以適合人體使用的材料製 5成’則所揭露裝置如第4B圖中所示可構成為一環或為一圓 筒380。當以此方式裝配時，裝置可環繞著一腱、一韌帶 、一肌纖維、一血管、一神經束或是身體的任一其他部分 等對局部投藥有良好反應之部分捲曲。同樣地，該圓筒 380能夠在安置身體内的一管性導管中，膨脹抑或是縫合 10 用以固定其之位置。 如有需要，不同類型的藥劑可放置在具有不同形狀或是 不同顏色的不同核心主體中。在不同形狀或是顏色的核心主 體中使用不同的藥劑，使外科醫生能夠藉由包含藥劑之裝置 的形狀及顏色而區別不同的藥劑，降低藥劑之混淆。 15 於特疋的狀況，可相關於受治療的症狀或疾病而需將 蕖物傳輸裝置定向在一特定位置。於該狀況下，如第5圖 中所示，藥物傳輸裝置41〇係可附裝至一支撐件432，使核 心主體412位在所需方向上。 於第6A及6B圖中所示之藥物傳輸平臺51〇的另一具體 2〇貫施例中，製作核心主體512、上篩524、以及一下篩525 ，用以構成一銳化邊緣534。儘管如於第2A、3、及4八圖 中所示的一薄平面具體實施例，係適於嵌入眼睛之玻璃體 中，但其他應用係需貫穿軟組織。當構成核心主體512致 使構成的核心主體512之周圍邊緣536的一部分，包括一銳 16 200417387 玖、發明說明 化邊緣534時，核心主體512本身係可用以製成一開始切口 ，或是將一切口擴大讓藥物傳輪裝置51〇通過安置。於此 具體貫把例中，上筛524之前緣係為部分的銳化邊緣，其 係用以針對產生所揭露藥物傳輸裝置可喪入通過的一開口 5 造成初始接觸。 於另可父替的具體實施例610中，如第6(：及61)圖中 所示，銳化邊緣係可安置在坐落於池614下方的一實體件 625之邊緣上的一部分上。 儘官可將足夠的藥劑放置在核心主體之池中，用以治 H)療症狀或疾病持續-段最短或是延長期間，但是假若症狀 或疾病係特別地頑固，則其必需實際地更換藥劑。儘管可 更換整個裝置，但頃發現的是，當裝置在病患體内使用持 續一段延長時間時，諸如一年或更長，如第7圖中所示， 核心主體712内的池714係可藉由使用_自核心主體712之 15周圍邊緣736行經進人池714的—通道川而再灌滿。由於 核。主體712的小尺寸，所以無法自周圍邊緣736至池crpl 1 8 itself is constructed as a sieve, so the need to use and attach as shown in Figure 2A-the second _26 is excluded. In other applications, it is also possible to make the pool Π 4 have a solid bottom, as shown in 153. When the pool 114 has a solid bottom, only a single screen 124 is used on the top 116 of the pool 114. Although the specific embodiment of Xing Yijia shows an improved runway around 36, the pool 14 is closer to the end 15 and a slot 30 is arranged at the proximal end ^, those skilled in the art should know that The design of a plurality of other implantable drug delivery platforms is feasible without departing from the scope of the present invention. For example, the drug delivery platform may be formed with a plurality of slits 30, or may be formed with straight sides, such as a triangular shape 310 as shown in FIG. 4A. Alternately, square, ring, paddle, or any other suitable shape 15 200417387 玖, description of the invention A small incision that can be passed through the eye or a part of the body, where it is determined The place where the medicament can be used most effectively. As the adaptability of the disclosed invention can be configured into a plurality of different shapes, especially if the core body and the sieve are made of 50% of materials suitable for human use, the disclosed device can be configured as shown in FIG. 4B A ring or a cylinder 380. When assembled in this manner, the device can curl around a tendon, ligament, muscle fiber, blood vessel, nerve bundle, or any other part of the body that responds well to topical administration. Similarly, the cylinder 380 can be inflated or sutured in a tubular catheter placed in the body to fix its position. If needed, different types of medicaments can be placed in different core bodies with different shapes or different colors. The use of different medicaments in core bodies of different shapes or colors enables the surgeon to distinguish between different medicaments by the shape and color of the device containing the medicament, reducing the confusion of medicaments. 15 Depending on the condition of the person, the object delivery device may need to be directed to a specific location in relation to the symptoms or illness being treated. In this state, as shown in Fig. 5, the drug delivery device 41 is attachable to a support 432 so that the core body 412 is positioned in a desired direction. In another specific embodiment of the drug delivery platform 51 shown in FIGS. 6A and 6B, a core body 512, an upper screen 524, and a lower screen 525 are made to form a sharpened edge 534. Although the thin-plane embodiment shown in Figures 2A, 3, and 48 is suitable for embedding in the vitreous body of the eye, other applications need to penetrate soft tissue. When the core body 512 is formed so that a part of the surrounding edge 536 of the core body 512 is formed, including a sharp 16 200417387, and the illustrated edge 534, the core body 512 itself can be used to make an initial cut or cut all Enlargement allows the drug transfer device 51 to pass through. In this specific example, the leading edge of the upper sieve 524 is a partially sharpened edge, which is used to make an initial contact with an opening 5 through which the disclosed drug delivery device can pass through. In the alternative embodiment 610, as shown in Figures 6 (: and 61), the sharpened edge may be placed on a part of the edge of a solid piece 625 located below the pool 614. Adequate agents can be placed in the pool of the core subject to treat the symptoms or diseases for a short period of time or for an extended period of time, but if the symptoms or diseases are particularly stubborn, they must be physically changed . Although the entire device can be replaced, it has been found that when the device is used in the patient for an extended period of time, such as one year or more, as shown in Figure 7, the pool 714 in the core body 712 can be replaced. It is refilled by using the channel __ which passes from the edge 736 around the core body 712-15 into the pond 714. Thanks to the nuclear. The small size of the main body 712, so it cannot reach from the surrounding edge 736 to the pool
鑽出通道。於該等狀況中，需由二相配件712a、7i2B 構成核心主體712，每一相配件包括一部分的通道。當其 中邛刀放置在另一部分頂部上時，該等二部分的通道不 w疋尺平或是垂直地一起構成一小孔738，由周圍邊緣736 至池714·。 ;另具體貫施例810中，通道838之端部可附裝至一 凸緣840。凸緣84〇係有助於開口的位置，藉使用一皮下注 射為（未顯示）以一藥劑將池814再灌滿。再者，使用凸緣 17 200417387 玖、發明說明 840可防止或是降低污染。凸緣84〇係可配置在核心主體 812之側邊上，或是距離一段短距離，並藉由一小管842連 接。如第7A圖中所示，通道838可構成為一迂迴曲折的路 徑。 5 於複雜的狀況下，必需將多種藥劑放置在接近症狀或 疾病的位置。於該等狀況下，在核心主體943、945中可構 成複數之池。如於第8圖中所示，該核心主體912至少包括 一較小的近側端池943，以及一較小的末端池945。由於不 同的藥劑，必需以一篩覆蓋近侧端943及末端945，包括不 10同數目及不同尺寸之孔覆蓋該每一近側端943及末端945較 小池。 以下說明在第9至23圖中所示之揭露的藥物傳輸平臺 的其他具體實施例。 第9圖中顯示藥物傳輸裝置1010的一具體實施例，其 15 包括一近側端池1043、一中間池1045以及一末端池1〇47。 近侧端池1043係藉使用一第一分隔件1041而與中間池1〇45 分開，中間池1045係藉使用一第二分隔件1〇49而與末端池 1047分開。如有需要，藉由在分隔件1〇41、1049中構成的 通道1048，係有助於藥劑在不同的小池之間傳送或移動。 20 亦應注意的是，在核心主體1012之上表面1020上的第一筛 1024，以及在核心主體1012之下表面1024上的第二篩中的 孔圖案，係製作用以控制釋放藥劑。特別地，在末端1〇 15 處包括一 U形狀圖案1050，以及在近側端1〇 13處包括一拱 形圖案1052。此具體實施例在需將三種藥劑Ml、M2及M3 18 200417387 玖、發明說明 放置在動物體内時係特別地有用。可交替地，該等分隔件 1041及1049可為實心的或是不滲透性的，用以將藥劑mi 、M2及M3分開。 第ίο圖係圖示一具體實施例1110，用於將二藥劑Μι 5及M2於體内消散。因此，核心主體丨丨丨2係利用一實心的 或是不滲透性的分隔件1141，於其間劃分成一近側端小池 1143，以及一末端小池1147。藥劑M2的釋放係藉由在上 篩1124與下篩1126中篩孔U50的一 u形狀圖案覆蓋末端池 1147而控制。一梯形圖案的篩孔1154係配置覆蓋近侧端池 10 1143，用於控制藥劑Μ1之釋放。 於第11圖中，所示係為另一二區劃可植入式藥物傳輸 平臺1210。應注意的是，所具有的一第一篩孔圖案1256係 覆蓋整個末端池1247，以及一第二篩孔圖案1258係覆蓋整 個近側端池1243，二者係分別地容納藥劑m2及Ml。 15 於第12圖中所示，一具體實施例1310其具有一用於容 納一藥劑Μ的單一池1314。該單一池1314係藉由二核心主 體件1312Α及1312Β結合在一起而構成。核心主體件U12A 、1312Β中的每一核心主體件包括一完整的篩孔圖案136〇 ’用以覆蓋在核心主體之二部分1312Α、1312Β間所構成 20 的池 1314。 於弟13圖中所示，係為包括一單一池Mi#的另一具體 實施例1410。於此具體實施例141〇中，核心主體1412包括 一下篩1426係由一上篩1424所覆蓋。應注意的是，上篩 1424完全地覆蓋核心主體1412，並係裝配一完整的篩孔圖 19 200417387 玖、發明說明 案1460’用以覆蓋整個池1414。 於第14圖中所示，係為另一單一池具體實施例1510。 於此具體實施例中，上篩1524具有一周長Μ%，其係與構 成在核心主體1512中的池1514之内周圍的内部配合。 5 於第15圖中所示，係為具有一單-井1614的另-具體 實施例關。於此具體實施例161〇中，上筛觀包括一向 下懸垂的凸緣1662，其係建構並配置用以與構成在核心主 體1612中之池1614之周圍内部壓入配合。可交替地，如第 18圖中所示，凸緣係可配置在核心主體1612上，用以向上 10延伸與一篩1624中的一凹入部分嚙合。 於第16圖中所示，係為具有一單一池1714的另一具體 實施例1710。單一池1714的係構成在一核心主體i7i2中， 其進一步地與一核心主體支架1712(：内部配合。核心主體 支架1712C包括一開放部分1712(：1，將核心主體1712牢固 15地固持於其中。一上篩1724覆蓋位在核心主體1712中的池 1714。核心主體1712的底部部分係構成為一篩。 於第17圖中所示，係圖示一與第16圖中所示之具體實 施例1710相似的一具體實施例181〇。然而，將核心主體支 架1812D構成具有二分支，於其間構成一開放空間1812D1 20 ，而非具有一連續周圍的核心主體支架U12D。建構並配 置該開放空間1812D.1，用以接受該核心主體1812。一溝 槽1864接受核心主體支架is 12D之二分支。再一次，將核 心主體1812以一篩1824覆蓋，並且將核心主體1812的底部 構成為一篩。 20 20041738 玖、發明說明 於第18圖中所示，所揭露的具體實施例1910包括一核 心主體1912 ’其具有一向上延伸的凸緣1966係與上篩1924 配合，因此该上篩1924可配置在核心主體1912上覆蓋池 1914 〇 5 於第19圖中所示，一具體實施例2010包括一大體上中 空的核心主體2012。一下篩2026係配置在大體上中空的核 心主體2012之底部表面2022上，以及一上篩2〇26係位在核 心主體之頂部表面2020上。 於第20圖中所示，一具體實施例211 〇包括一近侧端小 10 池2143，以及一末端小池2147。將近側端小池2143與末端 小池2147分開的分隔件2141，具有構成於其中的通道2148 ，供藥劑移動通過。藉由構成在上篩2124與下篩2126中的 拱形的孔圖案2152，控制藥劑Ml、M2的釋放。可交替地 ，分隔件2141可沿著池2114之長軸分佈，用以構成並列的 15 小池。 於第21圖中所示，另一具體實施例2210包括一近側端 小池2243，以及一末端小池2247。一分隔件2241將位在核 心主體2212中的近側端小池2243與末端小池2247分開。上 篩2224與下篩2226二者在末端2215處包含一 U形狀的孔圖 20 案2250，以及在近側端2213處包含一完整的孔圖案2260。 於第22圖中所示，係為一橢圓形變厚的具體實施例 2310，其包括環形篩2324、2326，配置在核心主體23 12之 上表面2320與下表面2322上。 實例 21 玖、發明說明 將與第15圖中所示相似 蘭白兔中。利用矽黏著劑將篩附裝至核心主體。該對側的 眼睛係使用作為-對照物。在二日時，將—隻兔子自研究 中取出在個月時，測試三隻兔子，在三個月時，測試 其餘的四隻兔子。在-個月及三個㈣，執行病理組織學 觀察H㈣’其中三隻兔子在玻璃體中出現小數目 的、田胞毛X。5亥等二隻兔子的其中之一隻亦在鋸齒緣中出 現發炎症狀。最後兔子已最低限度地增長晶狀體纖維。針 對此群組的毒理學觀察係為不顯著的。 10 15 20 的該等裝置，植入於八隻紐西 於一活體外研究中，betax〇l〇l鹽酸鹽，一相對的高水 、11物貝係為總重22毫克的片劑，其中具有1 〇%微晶的 纖維素以及0.4%的硬脂酸鎮。betax〇1〇1鹽酸鹽片劑係嵌入 在’與第15圖中所示之具體實施例相似的藥物傳輸裝置的 中"亥等裝置在池之一側邊上係使用一 8微米1%孔隙率 的師。所有孔的面積對篩之面積的比值係約為〇18%。藥 物傳輸衣置上的所有孔的面積對所有表面之面積的比值係 、、、勺為0.02 /〇本發明之負載的藥物傳輸裝置係放置在一 4mL的高效液相層析（HpLC)小玻璃瓶中，内有磷酸鹽/生 理鹽水緩衝劑，接著湘-小㈣棒㈣。該等小玻璃瓶 係疋』地針對藥物濃度’ II由高$文液相層析法取樣 及刀析如第24圖中所示，係為一藥物濃度對時間的圖表 ’說明該釋放量變曲線。 於一第二活體外研究中，使用一具有相對低水溶性物 貝的另一第一藥物製劑，nepafenac片劑，亦在一與第^ 5圖 22 200417387 玖、發明說明 中所圖示之具體實施例相似的一裝置中研究。該等片劑亦 包含10%微晶的纖維素以及0·40%的硬脂酸鎂。一片劑係 放置在一二側式14微米25%孔隙率裝置中。所有孔的面積 對篩之面積的比值係約為4·5%。藥物傳輸裝置上的所有孔 5的面積對所有表面之面積的比值係約為0.48%。一第二片 劑係放置在-二側式14微米1%裝置中。所有孔的面積對 篩之面積的比值係約為〇·18%。藥物傳輸裝置上的所有孔 的面積對所有表面之面積的比值係約為0.02%。如上所述 ^地執行藥物釋放研究。如第25圖中所示，曲線“Α”係顯示 侍自於一側式14微米25%孔隙率之裝置的釋放量變曲線。 、本Β係顯示彳于自於一側式丨4微米1 %孔隙率之裝置的釋 1憂曲線。藉由自一側式14微米1 %孔隙率之裝置更換 磷酸鹽/生理鹽水緩衝劑而執行第三實驗，並重新開始實 行實驗。此實驗係以曲線“c”標示。 15手術 體内的症狀或疾病一經確認並定位，醫師將確定是否 可以將-藥劑放置在極接近症狀或疾病的方式治療該症狀 或是藥物治療。假若決定以將一藥劑放置在極接近症狀或 )疾病的方式治療該症狀或是疾病，則因必需實際地將藥劑 放置在接近症狀或是疾病位置。於其他的應用中，係需一 段短距離治療症狀或是疾病。該短距離治療係需來自於藥 物傳輸裝置之持續程度的藥劑流動。 於第1圖中所示的具體實施例10中，症狀或疾病係存 在於-病患的眼中。例如’外科醫師藉由在輩膜中產生的 23 玖、發明說明 刀口，可將一可植入式裝置嵌入至病患的玻璃狀房中 。藥物傳輸平臺U)接著㈣切口嵌人，並|^通過在核心 主如中的縫孔30加以縫合，並將縫合的其他部分附裝至 $眼睛，而固定在適當的位置。將該平臺定向致使植入式平 室維持偏離自晶狀體至網膜的光線路徑。 為防止該植入式裝置受細胞覆蓋，而阻礙藥劑自池通 過師孔之流動，可在篩及核心主體上使用抗增生塗料。同 樣地，諸如石夕的材料可構成晶片，俾便防止鑿平該筛，以 及可以一物質覆蓋核心主體用以防止鑾平。 1〇 如先前所提及，儘管所示較佳具體實施例係針對嵌入 藥劑用以治療眼内的症狀或疾病，但熟知此技藝之人士應 瞭解的是，所揭露之可植入式藥物傳輸平臺1〇可在動物體 内，以一植入式藥劑對症狀或疾病作最佳治療的任一位置 處使用。 15 根據所揭露之較佳的及可交替的具體實施例，熟知此 技藝之人士現可瞭解本發明。熟知此技藝之人士應瞭解的 是，本發明之複數的其他具體實施例，亦可藉由前述的揭 露内容加以具體化。該等其他的具體實施例應包括在附加 的申請專利範圍之範疇與意義内。 20 【圖式簡單說明】 弟1圖係為本發明之欣入人類眼睛中的一呈體實施例 之側視圖； 第2 A圖係為較佳具體實施例的分解透視圖； 第2B圖係為與第2 A圖中所示相似的一核心主體的透 24 200417387 玖、發明說明 視圖； 第2C圖係為與第2A圖中所示相似的一篩的透視圖； 第2D圖係為諸如第2C圖中所示之一篩之一部分的放 大平面圖； 5 第3圖係為一第一可交替具體實施例的分解透視圖； 第4A及4B圖係為所揭露的藥物傳輸系統之一第二及 一第三可交替具體實施例的透視圖； 第5圖係為附裝至一支撐件之藥物傳輸系統的侧視圖； 第6A圖係為包括一銳化邊緣或是解剖刀鼻部分之藥物 10 傳輸系統的一透視圖； 第6B圖係為第6A圖中所示之具體實施例的一分解視 第6 C圖係為與第6 A圖中所示相似之包括_銳化邊緣 之樂物傳輸糸統的一透視圖； 15 第6D圖係為在第6C圖中所示之具體實施例的分解視 圖； 統之核心主體的一可 包括一通道用於再供 第7圖係為本發明之藥物傳輸系 交替具體實施例的透視圖，其進一步 給藥劑至該池中； 20 第7A圖係為在第7圖中所示之藥物傳輸系統的核 心主 體的一可交替具體實施例，其包括一凸緣部分； 第8圖係為藥物傳輸系統的另一 、、 』又θ具體實施例的 一透視圖，其包括複數之較小的池； 第9圖係為具有一三區劃池的—藥物傳輸系統的一透 以及 25 200417387 玖、發明說明 視圖，其中在區劃之間包括一内通道用於藥劑移動； 第10圖係為一藥物傳輸系統的_透視圖，其中在_較 大的池中包括二較小的池； 第11圖係為於第10圖中所示之蘊％ 口 τ π不 < 樂物傳輸系統的一可交 5 替具體實施例的一透視圖； 第12圖係為具有一單一池之一藥物傳輸系統的一透視 圖； 第13圖係為在第12圖中所示之藥物傳輸系統的一第一 可交替具體實施例的一透視圖； 10 第14圖係為在第12圖中所示之藥物傳輸系統的一第二 可交替具體實施例的一透視圖； 第15圖係為在弟12圖中所示之藥物傳輸系统的一第三 可交替具體實施例的一透視圖； 第16圖係為在第12圖中所示之藥物傳輸系統的一第四 15 可交替具體實施例的一透視圖； 第17圖係為在第12圖中所示之藥物傳輸系統的一第五 可交替具體實施例的一透視圖； 第18圖係為在第12圖中所示之藥物傳輪系統的一第六 可交替具體實施例的一透視圖； 20 第19圖係為在第12圖中所示之藥物傳輪系統的一第七 可交替具體實施例的一透視圖； 第20圖係為在第12圖中所示之藥物傳輸系統的一第八 可交替具體實施例的一透視圖； 第21圖係為在第10圖中所示之藥物傳輸系統的一第一 26 200417387 玖、發明說明 可交替具體實施例的一透視圖； 第22圖係為在第10圖中所示之藥物傳輸系統的一第二 可交替具體實施例的一透視圖； 第23圖係為利用betaxolol鹽酸鹽片劑的活體外研究（in 5 vitro study)中，藥物濃度對時間的一曲線；以及 第24圖係為利用nepafenac片劑的活體外研究（in vitro study)中，藥物濃度對時間的一曲線。 【圖式之主要元件代表符號表】 10…可植入式藥物傳輸系統 23···篩的部分 12 、 412 、 512 、 712 、 812 24、1024···第一篩 、912 、 1012 、 1112 、 25、36、1536•"周 圍 1412 、 1512 、 1612 、 1712 26…第二篩 、1812 、 1912 、 2012 、 2 8 · · ·孑L 2212、2312···核心主體 30…縫孔 13、1013、2213···近侧端 38 、 838 、 1048 、 2148 … 14、114、614、714、814 通道 、1314 、 1414 、 1514 、 110、610…可交替的具體 1914、2114 …池 實施例 15、1015、2215···末端 124 、 1624 、 1824· ··篩 16、116…頂部 3 10…三角形狀 17…推拔壁 380…圓筒 18、118…底部 410、1010···藥物傳輪裝置 20、1020、2320···上表面 432…支撐件 22、2322…下表面 510、1210···藥物傳輪平臺 27 200417387 玖、發明說明 524、 1124、1424、1524 、1634 、 1724 、 1924 、 2124、2224···上篩 525、 1126、1426、2026 、2126、2226···下篩 5 3 4…銳化邊緣 536、736…周圍邊緣 625···實體件 712A，B…相配件 810 、 1110 、 1310 、 1410 、 1510、1610、1710、1810 、1910 、 2010 、 2110 、 2210、2310…具體實施例 840、1662、1966···凸緣 842…小管 943、1043、1243 …近侧 端池 945、1047、1247…末端池 1041…第一分隔件 10 4 5…中間池 1141、2141、2241···分隔件 1143、2143、2243···近側 端小池 1147、2147、2247···末端 小池 1150、1154··· _ 孔 1256…第一篩孔圖案 1258…第二篩孔圖案 13 12A，B…核心主體件 1360、1460···完整的篩孔 圖案 1614…井 1712C、1812D…支架 1712C.1…開放部分 1812D.1…開放空間 1864…溝槽 2020…頂部表面 2022…底部表面 2152…拱形的孔圖案 2250…U形狀的孔圖案 1049…第二分隔件 2260···完整的孔圖案 1050…U形狀圖案 2324、2326…環形篩 1052…拱形圖案 28Get out of the tunnel. In these situations, the core body 712 needs to be composed of two-phase fittings 712a, 7i2B, and each phase fitting includes a part of the channel. When the trowel is placed on top of the other part, the channels of these two parts are not flat or vertical together to form a small hole 738, from the surrounding edge 736 to the pool 714 ·. In another specific embodiment 810, the end of the channel 838 may be attached to a flange 840. The flange 84 is used to help the opening position, and the pool 814 is refilled with a potion by using a subcutaneous injection shot (not shown). Furthermore, the use of flange 17 200417387 玖, invention description 840 can prevent or reduce pollution. The flange 84 may be arranged on the side of the core body 812, or a short distance, and connected by a small tube 842. As shown in Figure 7A, the passage 838 may be configured as a tortuous path. 5 In complex situations, multiple agents must be placed close to the symptoms or illness. Under these circumstances, a plurality of pools can be formed among the core subjects 943 and 945. As shown in Figure 8, the core body 912 includes at least a smaller proximal end pool 943 and a smaller end pool 945. Due to different medicaments, it is necessary to cover the proximal end 943 and the end 945 with a sieve, including different numbers and different sizes of holes to cover each of the proximal end 943 and the end 945 with a small pool. Other specific embodiments of the drug delivery platform disclosed in Figures 9 to 23 are described below. A specific embodiment of the drug delivery device 1010 is shown in FIG. 9, which includes a proximal end cell 1043, an intermediate cell 1045, and an end cell 1047. The proximal end pool 1043 is separated from the intermediate pool 1045 by using a first divider 1041, and the intermediate pool 1045 is separated from the end pool 1047 by using a second divider 1049. If necessary, the passage 1048 formed in the partitions 1041 and 1049 helps to transfer or move the medicine between different cells. It should also be noted that the hole pattern in the first sieve 1024 on the upper surface 1020 of the core body 1012 and the second sieve on the lower surface 1024 of the core body 1012 are made to control the release of the medicament. Specifically, a U-shaped pattern 1050 is included at the distal end 1015, and an arched pattern 1052 is included at the proximal end 1013. This specific example is particularly useful when the three agents M1, M2, and M3 18 200417387 are required to be placed in an animal's body. Alternatively, the partitions 1041 and 1049 may be solid or impermeable to separate the medicaments mi, M2, and M3. Figure 8 shows a specific embodiment 1110, which is used to dissipate the two agents M5 and M2 in the body. Therefore, the core body 2 uses a solid or impermeable divider 1141, which is divided into a proximal end pond 1143 and an end end pond 1147. The release of the medicament M2 is controlled by covering the end pool 1147 with a u-shaped pattern of the sieve holes U50 in the upper screen 1124 and the lower screen 1126. A trapezoid-shaped screen opening 1154 is configured to cover the proximal end cell 10 1143 for controlling the release of the drug M1. In Figure 11, another two-region implantable drug delivery platform 1210 is shown. It should be noted that a first screen pattern 1256 covers the entire end pool 1247, and a second screen pattern 1258 covers the entire proximal end pool 1243, both of which contain the medicaments m2 and Ml, respectively. 15 As shown in FIG. 12, a specific embodiment 1310 has a single pool 1314 for containing a medicament M. The single pool 1314 is formed by combining two core bodies 1312A and 1312B. Each of the core bodies U12A, 1312B includes a complete screen pattern 136 ′ to cover a pool 1314 formed between the two parts of the core body 1312A, 1312B. As shown in FIG. 13, it is another specific embodiment 1410 including a single pool Mi #. In this specific embodiment 1410, the core body 1412 includes a lower screen 1426 covered by an upper screen 1424. It should be noted that the upper screen 1424 completely covers the core body 1412 and is equipped with a complete screen hole. Figure 19 200417387 (ii) Description of the invention 1460 'is used to cover the entire pool 1414. As shown in FIG. 14, it is another specific embodiment 1510 of a single pool. In this specific embodiment, the upper sieve 1524 has a weekly length of M%, which cooperates with the interior formed around the inside of the pool 1514 in the core body 1512. 5 is shown in FIG. 15 as another embodiment with a single-well 1614. In this specific embodiment 1610, the upper sieve view includes a downwardly suspending flange 1662, which is constructed and configured to press-fit with the interior of the pool 1614 formed in the core body 1612. Alternatively, as shown in FIG. 18, the flange system may be disposed on the core body 1612 to extend upwardly to engage a recessed portion in a screen 1624. As shown in Fig. 16, another embodiment 1710 having a single pool 1714 is shown. The unit of the single pool 1714 is formed in a core body i7i2, which further cooperates with a core body bracket 1712 (: internal. The core body bracket 1712C includes an open portion 1712 (: 1), which holds the core body 1712 firmly and 15 therein An upper screen 1724 covers the pool 1714 in the core body 1712. The bottom part of the core body 1712 is configured as a screen. As shown in FIG. 17, it is a specific implementation shown in FIG. 1 and FIG. 16 Example 1710 is a specific embodiment 1810. However, the core body bracket 1812D is configured with two branches, and an open space 1812D1 20 is formed therebetween instead of a core body bracket U12D having a continuous surrounding. The open space is constructed and configured. 1812D.1 is used to receive the core body 1812. A groove 1864 receives the core body support is 12D bis branch. Once again, the core body 1812 is covered with a screen 1824, and the bottom of the core body 1812 is formed as a screen 20 20041738 发明 The invention is illustrated in FIG. 18. The disclosed specific embodiment 1910 includes a core body 1912 'having an upwardly extending flange 1966. In cooperation with the upper screen 1924, the upper screen 1924 can be configured on the core body 1912 to cover the pool 1914. As shown in FIG. 19, a specific embodiment 2010 includes a substantially hollow core body 2012. The lower screen 2026 series It is disposed on the bottom surface 2022 of the substantially hollow core body 2012, and an upper screen 2026 is located on the top surface 2020 of the core body. As shown in FIG. 20, a specific embodiment 211 includes a near The side 10 small pool 2143 and one end small pool 2147. The partition 2141 separating the proximal small pool 2143 and the end small pool 2147 has a channel 2148 formed therein for the medicine to move through. The arched hole pattern 2152 in the sieve 2126 controls the release of the medicaments M1 and M2. Alternatively, the partitions 2141 can be distributed along the long axis of the pond 2114 to form a parallel 15 ponds. As shown in Figure 21 As shown, another specific embodiment 2210 includes a proximal end pond 2243, and a distal end pond 2247. A partition 2241 separates the proximal end pond 2243 and the distal end pond 2247 located in the core body 2212. The upper screen 2224 and The sieve 2226 includes a U-shaped hole at the end 2215 and a pattern 2250 at the proximal end, and a complete hole pattern 2260 at the proximal end 2213. As shown in FIG. 22, it is an elliptical thickened concrete Embodiment 2310 includes an annular screen 2324, 2326, and is arranged on the upper surface 2320 and the lower surface 2322 of the core body 2312. Example 21 (ii) Description of the invention The blue and white rabbit will be similar to that shown in FIG. The sieve is attached to the core body with a silicon adhesive. The opposite eye was used as a -control. At two days, one rabbit was taken from the study. Three rabbits were tested at one month, and the remaining four rabbits were tested at three months. At -month and three tadpoles, histopathology was performed to observe H㈣ ', in which three rabbits showed a small number of field hairs X in the vitreous. One of the two rabbits, such as Wu Hai, also developed inflammation in the serrated margin. Finally the rabbit has minimally grown lens fibers. The toxicological observations for this group are not significant. The devices of 10 15 20 were implanted in eight New Zealand in an in vitro study, betax001 hydrochloride, a relatively high water, 11 shellfish series of tablets with a total weight of 22 mg, It has 10% microcrystalline cellulose and 0.4% stearic acid. The betax〇1〇1 hydrochloride tablet is embedded in a drug delivery device similar to the specific embodiment shown in Figure 15 " Hai and other devices use an 8 micron 1% on one side of the pool Porosity Division. The ratio of the area of all the holes to the area of the sieve is about 0.018%. The ratio of the area of all pores to the area of all surfaces on the drug delivery garment is 0.02 / 0. The loaded drug delivery device of the present invention is placed on a 4 mL high performance liquid chromatography (HpLC) shot glass In the bottle, a phosphate / saline buffer was added, followed by the Xiang-Xiao ㈣ stick ㈣. These vials are based on the drug concentration 'II. Samples and analysis by high-performance liquid chromatography are shown in Figure 24. It is a graph of drug concentration versus time', which illustrates the release curve. . In a second in vitro study, another first pharmaceutical preparation with relatively low water solubility, nepafenac tablets, was also used as shown in Fig. 22 and 200417387. The example is studied in a device similar to the example. These tablets also contain 10% microcrystalline cellulose and 0.40% magnesium stearate. One tablet was placed in a two-sided 14 micron 25% porosity device. The ratio of the area of all holes to the area of the sieve is about 4.5%. The ratio of the area of all holes 5 on the drug delivery device to the area of all surfaces is about 0.48%. A second tablet was placed in a two-sided 14 micron 1% device. The ratio of the area of all the holes to the area of the sieve is about 0.18%. The ratio of the area of all holes in the drug delivery device to the area of all surfaces is about 0.02%. Drug release studies were performed as described above. As shown in Figure 25, the curve "A" is a curve showing the amount of release from a device with a side porosity of 14 micron and 25% porosity. 2. This B series shows the release curve for a device with a porosity of 4 micron and 1% porosity. A third experiment was performed by replacing the phosphate / saline buffer with a 14 micron 1% porosity device from one side, and the experiment was restarted. This experiment is indicated by the curve "c". 15 Surgery Once a symptom or disease in the body is identified and localized, the physician will determine if the agent can be placed in close proximity to the symptom or disease to treat the symptom or disease. If it is decided to treat a symptom or disease in such a way that a medicine is placed in close proximity to the symptom or disease, it is necessary to actually place the medicine close to the symptom or disease. In other applications, a short distance is needed to treat symptoms or diseases. The brachytherapy requires a continuous flow of medication from a drug delivery device. In the specific example 10 shown in Fig. 1, the symptoms or diseases are present in the eyes of the patient. For example, a surgeon can insert an implantable device into a patient's glass-like room by using a knife-edge created in the membrane. The drug delivery platform U) is then inserted into the incision and sutured through a suture hole 30 in the core core, and the other parts of the suture are attached to the eye and fixed in place. Orienting the platform causes the implantable chamber to maintain a deviating light path from the lens to the omentum. In order to prevent the implantable device from being covered by cells and hindering the flow of the medicament from the pool through the orifice, anti-proliferative coatings can be used on the sieve and the core body. Similarly, a material such as Shi Xi can form a wafer to prevent the sieve from being flattened, and a substance can be used to cover the core body to prevent flattening. 10 As previously mentioned, although the preferred embodiment shown is directed to an embedded drug for treating symptoms or diseases in the eye, those skilled in the art should understand that the disclosed implantable drug delivery The platform 10 can be used anywhere in the animal with an implantable agent for optimal treatment of symptoms or diseases. 15 Based on the disclosed preferred and alternative embodiments, those skilled in the art will now understand the invention. Those skilled in the art should understand that a plurality of other specific embodiments of the present invention can also be embodied by the foregoing disclosure. These other specific embodiments should be included in the scope and meaning of the scope of additional patent applications. 20 [Brief Description of the Drawings] Figure 1 is a side view of an embodiment of the present invention that is readily incorporated into human eyes; Figure 2A is an exploded perspective view of a preferred embodiment; Figure 2B is Figure 2A is a perspective view of a core subject similar to that shown in Figure 2A. Figure 2C is a perspective view of a sieve similar to that shown in Figure 2A. Figure 2D is a view such as An enlarged plan view of a portion of a sieve shown in Figure 2C; 5 Figure 3 is an exploded perspective view of a first alternate embodiment; Figures 4A and 4B are one of the disclosed drug delivery systems. Perspective views of the second and third alternate embodiments; Figure 5 is a side view of a drug delivery system attached to a support; Figure 6A is a diagram including a sharpened edge or a scalpel nose A perspective view of the drug 10 delivery system; Figure 6B is an exploded view of the specific embodiment shown in Figure 6A. Figure 6C is similar to that shown in Figure 6A. A perspective view of the music transmission system; 15 Figure 6D is the specific shown in Figure 6C An exploded view of the embodiment; one of the core subjects of the system may include a channel for resupply. Figure 7 is a perspective view of an alternate embodiment of the drug delivery system of the present invention, which further administers the agent to the pool; 20 FIG. 7A is an alternate embodiment of the core body of the drug delivery system shown in FIG. 7, which includes a flange portion; FIG. 8 is another example of the drug delivery system. A perspective view of an embodiment, which includes a plurality of smaller pools; FIG. 9 is a penetrating drug delivery system with a three-zoned pool and 25 200417387 发明, invention explanatory view, including a The inner channel is used for medicament movement. Figure 10 is a perspective view of a drug delivery system, in which two smaller pools are included in a larger pool. Figure 11 is a plot shown in Figure 10. % Τ τ π not < a perspective view of an interchangeable embodiment of a fun animal delivery system; FIG. 12 is a perspective view of a drug delivery system with a single pool; FIG. 13 is a Drug delivery system shown in Figure 12 A perspective view of a first alternate embodiment; 10 FIG. 14 is a perspective view of a second alternate embodiment of the drug delivery system shown in FIG. 12; FIG. 15 is a view at A perspective view of a third alternate embodiment of the drug delivery system shown in Figure 12; Figure 16 is a fourth 15 alternate embodiment of the drug delivery system shown in Figure 12 Figure 17 is a perspective view of a fifth alternate embodiment of the drug delivery system shown in Figure 12; Figure 18 is a drug transfer shown in Figure 12 A perspective view of a sixth alternate embodiment of the wheel system; 20 FIG. 19 is a perspective view of a seventh alternate embodiment of the drug delivery system shown in FIG. 12; 20 The figure is a perspective view of an eighth alternate embodiment of the drug delivery system shown in FIG. 12; FIG. 21 is a first 26 200417387 of the drug delivery system shown in FIG. 10透视 、 A perspective view of the embodiment of the invention that can be alternated; FIG. 22 is A perspective view of a second alternate embodiment of the drug delivery system shown in FIG. 10; FIG. 23 is a view of drug concentration in an in vitro study using betaxolol hydrochloride tablets A graph of time versus time; and Figure 24 is a graph of drug concentration versus time in an in vitro study using nepafenac tablets. [Representative symbol table of main elements of the figure] 10 ... Implantable drug delivery system 23 ... Parts 12 of the sieve 12, 412, 512, 712, 812 24, 1024 ... The first sieve, 912, 1012, 1112 , 25, 36, 1536 • " Around 1412, 1512, 1612, 1712 26 ... Second screen, 1812, 1912, 1912, 2012, 2 8 ·· 孑 L 2212, 2312 ··· Core body 30 ... 1013, 2213 ... Proximal ends 38, 838, 1048, 2148 ... 14, 114, 614, 714, 814 Channels, 1314, 1414, 1514, 110, 610 ... Specific alternate 1914, 2114 ... Pool embodiment 15 1015, 2215 ... End 124, 1624, 1824 ... Sieve 16, 116 ... Top 3 10 ... Triangle 17 ... Push wall 380 ... Cylinder 18, 118 ... Bottom 410, 1010 ... Drug transfer wheel Device 20, 1020, 2320 ... Upper surface 432 ... Support 22, 2322 ... Lower surface 510, 1210 ... Drug transfer platform 27 200417387 玖, Invention description 524, 1124, 1424, 1524, 1634, 1724, 1924 , 2124, 2224 ... Upper sieve 525, 1126, 1426, 2026, 2126 , 2226 ·· Lower sieve 5 3 4 ... Sharpened edges 536, 736 ... Peripheral edges 625 ... Solid parts 712A, B ... Phase accessories 810, 1110, 1310, 1410, 1510, 1610, 1710, 1810, 1910, 2010, 2110, 2210, 2310 ... specific embodiments 840, 1662, 1966 ... flange 842 ... small tubes 943, 1043, 1243 ... proximal end pools 945, 1047, 1247 ... end pools 1041 ... first divider 10 4 5… Intermediate cells 1141, 2141, 2241 ... · Dividers 1143, 2143, 2243 ... Proximal end cells 1147, 2147, 2247 ... End cells 1150, 1154 ... _ Hole 1256 ... First sieve Pattern 1258 ... Second sieve pattern 13 12A, B ... Core body 1360, 1460 ... Complete sieve pattern 1614 ... Well 1712C, 1812D ... Bracket 1712C.1 ... Open part 1812D.1 ... Open space 1864 ... Groove Slot 2020 ... top surface 2022 ... bottom surface 2152 ... arched hole pattern 2250 ... U-shaped hole pattern 1049 ... Second divider 2260 ... Complete hole pattern 1050 ... U-shaped pattern 2324, 2326 ... Ring screen 1052 ... Arch pattern 28