201012499 六、發明說明： 【發明所屬之技術領域】 本發明一般相關於數種用於經皮膚傳送治療劑之電離子透入 藥物傳送系統，尤其是指一種電離子透入藥物傳送組裝結構，相關 该等系統之包裝以用於長有效期限及容易組裝使用。該系統包裝 包括電離子透入皮膚貼片組件，其容納一電源、電子設備、數 個電極及-藥物包組件，其攜有一治療劑，該治療劑係作為一 裝入。包裝好之該系統尚提供使用時組裝容易。 ❹201012499 VI. Description of the Invention: [Technical Field] The present invention relates generally to several iontophoretic drug delivery systems for transdermal delivery of therapeutic agents, and more particularly to an iontophoretic drug delivery assembly structure, The packaging of these systems is used for long expiration dates and for easy assembly. The system package includes an iontophoresis skin patch assembly that houses a power source, electronics, electrodes, and a drug pack assembly that carries a therapeutic agent that is loaded as a unit. The packaged system is also easy to assemble when used. ❹
電離子透入療法為眾所熟知，且已發現在具相同電荷的系統 電極部位穿過皮膚傳送帶電離子化合物的重大商業用途。 已有人研發出數個自給式耐用的電離子透入系統，其中電路 結構及電力供應已整合成一單—皮膚貼片。在許多這些裝置中， 藥物離子自裝在電離子透人裝置中的—含水，，藥物，，貯液槽傳送 到身體襄，及相反電荷的反向離子自―”反向，，貯液槽傳送出。 因藥物/離子溶液“大數量儲存在遠處，及在使㈣才引到有 用的電離子透人電極的-吸收層，因此需要額外步驟將藥物離子 及反向離子合併到裝置中n電極會輕易過度裝填或裝填不 足’因此逆方面需要具備良好技術的熟練人員，此外，因藥物溶 液與電極是分_存’因此需要二種存貨的管理。 / 為避免使用者在使用時需要合併含水藥物或離子貯液槽，可 將藥物溶液與-電極預先包裝起來，或可使—貯液槽與—電極組 牛接觸來储存，及在使用時將一乾藥層插到貯液槽。不幸地， 用任配置’ 一電極仍儲存在潮濕環境中，及該組件及其他組 件會禁不起腐钱劣化。 201012499 “為上述及其他理由’電離子透讀㈣藥物傳送貼片與活性 藥物的共同包裝依然是具挑戰性的問題。因電離子透人貼片包含 數個電極及電子設備’及藥物溶液通常本f上是水，因此在含水 環境與電子設備之間不用障蔽，在㈣的有效期限内，可能是兩 年内’電子設備及藥物溶液兩者都將發生劣化。尋求—包裝解決 方法，其在電子設備與藥物溶液之間提供—障蔽且因此滿足有效 期限的要求，又在使料仍容物溶液與電子設備合併在一组 σ裝置中。更想要-解決方法’其不僅提供有效期限穩^以解決 以電極及電子電路環繞共同包裝㈣物水溶液的議題，其亦使操 作人員或使用者較容易啟動及應用該貼片。 【發明内容】 本申請案係以下專利申請案的非臨時申 ，…，申請曰2_年9月5曰，及主張該專== ，先權’該專利中請案全部内容當然亦以制方式併人本申請案 本發明提出-種預先包裝完整的電離子透入藥物傳送系統， 其輕易由包裝狀態加以組合。本發明贱包裝完整的電透 藥物傳送系統包括-電離子透人貼片及—治療劑，兩者皆 用，及享有長的有效期限。該系統包括二主要組件，gp : 包組件，其包含-或多個吸收墊，其中至少—者包含—活性劑. 及-電離子透人貼片組件’其包括數個電極及—電源。藥物及 貼片包裝在-起，但在該系統儲存期間卻是分開的組件，、 藉由使用-内建對準技術立即將它們合併成—組合狀離進 技術利用可採取數個任一形式的一對準結構，盆中的二升, = ^ + 一相連可摺疊平台或支撐結構，其將該等組件攜帶在分 上，及另一形式涉及一分開對準固定物或導引元件的使用。裕 户《ΐ —實施例巾，在設計成依列方式自行摺疊以同時適庫儲 存及使用的一配置中，藉由數個連續支撐格結構將—電離子 201012499 貼片組件及一密封含治療用離子或含活 塑料氣泡罩，，）組件裝載在-區別設置中。㈣為 徵是-摺疊配置或可财切結構。 & ^類型的特 或者，一電離子透入貼片及—密封藥物包可 ίί:包，結構中二及在使用前使用-對準固定物或。 '，δ請準物或㈣元件可為㈣ 、卫 始地黏附到電離子透人貼片或藥物包”任—者。匕裝為初 / m = +雖然大°卩分藥物或治絲子種類通常將以凝膠形式f =包中，但有些可以乾燥狀態裝在治療貼片中，在= 〇 ❹ 合。HI組合時料治療離子種類與該凝膠或其他溶液結 -格可例的特徵是-平台或支#結構中的複數個連續連 、、、°格冰其中'經皮膚電離子透人貼片附著到-分格支料構，及 ^月碟形狀㈣封的治療劑小室或藥物包 式1 支撐配置或平台較佳以且其間有一適當摺線。可摺疊 材料製成，使經皮膚貼片及藥物包附著到該等分格。除 i右=吸水塾外，經皮膚貼片包括—典型電離子透人貼片裝置 所有需要的2帶、襯裡、電子設備及電路元件。 該密封藥物包S使用低濕氣傳輸材料製成，及包含至少一可 U收墊，其吸人—般為凝膠形式的想要藥物溶液，直到使用 ’ :·'止’ 4等藥物吸收塾在有效期限期間仍分開地保護在 封藥物包中。 八姓可摺疊配置包含數個剪下圖樣及摺線以容許及導引各種不同 内摺疊或摆疊在另-者上方，及包括—脫開塗層（其可與 Ί 口塗在背面，以一塗層塗在前側，其具有可施加印刷的一 W4 ^可印刷的塗層表面可包括—傳統黏土材料，經皮膚貼片黏 1 4平台的塗關層或背側上的—第__分格藥物包黏合到可 塗黏土前侧上的相鄰分格。可槽疊系統尚包含依照經皮膚 '分格上的吸收墊形狀及位置的數個剪下圖線，當摺疊該系統 201012499 連準藥物包的内容，如所述，貼片及藥物包 ·〆氣/包罩或藥物小室與貼片電極的對應井對準。 透入實施例中，其中存在與該藥物包組件及該電離子 聯的—可摺疊支揮結構，該可摺疊支樓結構尚 摺属：二狀：：眘其配置成當電離子透入藥物傳送系統處於 如時實體地分開藥物包及電離子透入貼片組件。 述’在此等實施例中’支撐結構可包括—第—分格虚電離子 二= 牛相:：:及一第二分格與藥物包組件相關聯，其中 ^故ίΐ 卜分格構成’如在該第二分格連接到該第 -：多相對的一側上連接到該第二分格，其中此等額外的 子透入與Lifi在該ί統在摺疊儲存狀態時實體地分開電離 華物勺盥目Jb'y G且，该分隔線組件不僅在摺疊儲存狀態令分開 樂物，與貼1組件，亦作為該等系統組件的保護組裝結構。 泡罩或等樂，吸水塾儲存在一通常為隋性密封塑料氣 、容、夜或佯嘈U止内容物與周圍環境互起作用’藉此防止藥物 2或:護在樂物包附近的任何電子設備或其他貼片組件有任何 二的持該等内容物的完整，在儲存期間與藥物溶液直接 ===佳限定為相對隋性材料，此等材料包括一明確形狀 及祕㈣罩或藥物包的蓋子或障蔽層。低渴氣 乙稀基、聚醋、聚酿胺，包括尼龍，或聚烧基如聚 埽及聚丙稀。該材料尚可以是選自以下各物的_材料塗在一或 :料ΐίϊ織物、箱、金屬膜或其他更進-步減少濕氣傳輸 亦應由面對藥物溶液及吸收塾等組件時呈 該篆；匕括鋁/聚合物一合成材料形成的-托盤及蓋子， 一輕易脫除密封層，用於使用時輕易移除，在該實 ，^等吸收墊由合適聚合層及塗層的一疊層組成，該等層 對及接觸藥物溶液時是穩定的。該等吸收塾較佳屬於具有一已 201012499 知凝膠吸收性或發生作用速率的 非織造基質包括棉、聚丙烯、聚乙適用於該能吸收的 收材料是聚丙烯》 •曰纖維，較佳地，該吸 數個替代實施例使用一對準闳金私斗、拔3| _ 件組合該藥物傳送裝置系二=件由數個分開組 或與-經皮膚電離子透人心^ ί件可作為―分開組件供應 -八貼=物包的構造與配合心=二者及類電:子透 ❹ -分格的盘子，露出仍附著到該系統的 二格4樂物吸水墊。貼片組件黏附到-相鄰分格。接著， ^乍人員將該等分格指疊起來’使該等藥物吸水塾盜該等貼片電 極的井緊密接觸’該等貼片電極具備有一黏合環，當貼片電極與 吸水藝兩者接觸時’該黏合環連接 口衣連接到3亥等吸收墊表面的一匹配環 f。？：將該貼片自支撐配置上的一石夕化或其他合適脫開塗 二留下該等藥物吸水墊藉由周邊黏合劑永久地黏附到貼 2該4電極’最後’將貼片敷在病患上。以此基本概念及方式 為中心可想出多個實施例或變化。 〜具有一分開對準固定組件或導引元件的實施例，在一對準固 定物或導引元件上連續具有數個㈣元件的藥物包及電離子透入 貼片支擇結構中，藉由數個標示的對準開口加以組合。藥物包首 先5合到其扁平基板上的導引元件，及如在其他實施例中一般移 除5子，接著，將電離子透入貼片組裝判打開的藥物包上方再 使藥物包的數個凝膠吸收墊對準數個對應電極放置，如此再造成 一合併配置，其中該等藥物吸收墊藉由周邊黏合劑永久地黏合到 該等電極，及其中該組合件可加以分開及敷在一病患身上。在數 個替代實施例中，可將導引元件包裝組合及攜有組合到該合併中 的塑料氣泡罩（或藥物包組件）及電離子透入貼片組件，或可將電 離子透入貼片組件包裝組合到導引元件，然後與藥物包組件結 合0 7 201012499 【實施方式】 請參閱圖1A至圖14所示，本發明係提供一種電離子透入藥 7傳送組裝結構，此外，本發明以―預先包裝藥物傳送系統的形式 提供-功能完全、自給式、容易使用的電離子透入襄置，其享有 一較長的穩定有效期限，該系統包含：—藥物貯液包可摺叠分 格f撐結構構造，及_經皮膚貼片，其包含—電源、電流控制電 子設備，及數個電極。該裝置立即可使用及僅需要-些簡單操作 啟動該貼片及敷在治療職。在―些實_巾，料操作由以下 步驟組成：移除—藥物包障蔽蓋，將該等分格互相摺疊，及自一 脫開塗層剝除該貼片。在其他實施例中，經皮膚貼片及藥物包是 先、、且口在冑準固定物或導引元件上，再將該對準固定物或導引 元件移除U下將說明該等裝置的數個較佳實施例以闡述本發明 的概念’但並不表示此等實施例以任—方式限制本創新概念 圍。 圖ΙΑ、1B及2分別以剖面分解圖、組合剖面圖及上視圖說 明在-打開或水平配置的一可摺叠裝置2〇的一實施例，圖Μ及 9Β分別以侧剖圖及上視圖說明該裝置摺疊在—包裝配置以用於長 期儲存的If形。§錄置由3個主要元件組成：—可擅疊支撑結構 22、-經皮膚電離子透人貼μ 24，及—裝藥物包或塑料氣泡罩 26 ° 可摺疊支撐結構22可包括一紙板（或類似材料），一側塗有 -脫開塗層28及反側塗有-可印刷塗層3G的基板，0 1(：以片 段放大剖面圖說明可摺疊支律結構22的—部分，崎示脫開塗 層28及可印刷塗層30。脫開塗層28可為一石夕化塗層，及可印 刷塗層3G可為-黏土塗層替代可摺疊基板或支撲層可為一 201012499 加熱形成聚合物或類似物。摺^ ^ ^ ^ ^ ^ ^ ^ 32、33及34，其可藉由齒支私構22可包含數個摺疊線 成基板的情形，可在:疊 鍵。依指線數目衫=二、二V4加熱形成數個活動絞 供數個區域則/ 構可分缝個分格，其提 置的各種不同組件，印刷用法說明，及/ 二t'脫開障蔽塗層以用於_分格上裸露的黏合劑，以免在儲 存期間摺疊起來時永久黏在其他分格上。 ΟElectron iontophoresis is well known and has found significant commercial use of electrophoretic compounds through the skin at the system electrode sites of the same charge. Several self-contained and durable iontophoresis systems have been developed in which the circuit structure and power supply have been integrated into a single-skin patch. In many of these devices, the drug ions are self-contained in the ion-permeable device - the water, the drug, the sump is transferred to the body, and the counter-ions of the opposite charge are "reverse", the reservoir Transmitted. Because the drug/ion solution is "large in quantity stored in the distance, and in (4) leads to the useful absorption layer of the ionizing electrode, an additional step is required to incorporate the drug ion and the counter ion into the device. The n-electrode can be easily over-filled or underfilled. Therefore, a skilled person with good technology is required in the reverse direction. In addition, since the drug solution and the electrode are separated, two kinds of inventory management are required. / In order to avoid the need for the user to combine the aqueous drug or ion reservoir during use, the drug solution and the electrode may be pre-packaged, or the reservoir may be contacted with the electrode group for storage, and will be used during use. A dry layer is inserted into the reservoir. Unfortunately, the configuration of an electrode is still stored in a humid environment, and the components and other components can not withstand the deterioration of the money. 201012499 "For the above and other reasons, 'ion ion read through (4) drug delivery patch and active drug co-packaging is still a challenging problem. Because iontophoresis patch contains several electrodes and electronic devices' and drug solutions usually This f is water, so there is no barrier between the aqueous environment and the electronic equipment. Within the validity period of (4), it may be that within two years, both electronic equipment and drug solution will deteriorate. Seeking-packaging solution, Providing a barrier between the electronic device and the drug solution and thus meeting the requirement of the expiration date, and combining the material solution and the electronic device in a set of sigma devices. More desirable-solutions, which not only provide an effective period of stability ^ to solve the problem of surrounding the common packaging (four) aqueous solution with electrodes and electronic circuits, which also makes it easier for the operator or the user to activate and apply the patch. [Invention] This application is a non-provisional application of the following patent application. ,..., application 曰 2 _ September 5 曰, and claim that the special ==, first right 'the entire content of the patent in the patent is also based on the system and the application The present invention provides a pre-packaged complete iontophoretic drug delivery system that can be easily assembled from a packaged state. The present invention comprises a fully packaged electrodialysis drug delivery system comprising an iontophoretic patch and a therapeutic agent. Both are used and have a long expiration date. The system consists of two main components, gp: package assembly, which contains - or multiple absorbent pads, at least one of which contains - the active agent. The tablet assembly 'which includes several electrodes and a power supply. The drug and patch are packaged, but are separate components during storage of the system, and are immediately combined into one by using - built-in alignment techniques. The detachment technique utilizes an alignment structure of any of a number of forms, two liters in the basin, = ^ + a connected foldable platform or support structure, which carries the components on the sub-section, and another form Involving the use of a separate alignment fixture or guide element. The ΐ 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施 实施structure Load the -ion ion 201012499 patch assembly and a seal containing therapeutic ions or bubble caps containing live plastics in the -differential setting. (d) for the sign-fold configuration or the cut-off structure. Or, an iontophoret patch and a sealed drug pack can be ίί: package, structure 2 and use before the use - alignment fixture or . ', δ please be the object or (4) component can be (four), Wei Shi Adhere to the ion-ion patch or drug pack. Armored as initial / m = + although large ° 卩 points of drug or ruler type will usually be in the form of gel f = package, but some can be placed in the treatment patch in a dry state, at = 〇 ❹. HI combined with the treatment of ion species and the gel or other solution knot - grid can be characterized by - a plurality of continuous connections in the platform or branch structure, , ° ° ice in which 'transdermal ionized patch The therapeutic agent chamber or the drug pack 1 support configuration or platform attached to the -divided material structure and the ^4 dish shape (4) is preferably provided with an appropriate fold line therebetween. The foldable material is made to attach the transdermal patch and the drug pack to the compartments. In addition to i right = sputum sputum, transdermal patches include - typical ion-ion transmissive devices all the required 2 bands, linings, electronics and circuit components. The sealed drug package S is made of a low moisture transmission material, and comprises at least one U-receiving pad, which absorbs a desired drug solution in the form of a gel until a drug absorption such as ':·' The 塾 is still protected separately in the package during the expiration date. The eight-fold foldable configuration includes a plurality of cut patterns and fold lines to allow and guide various inner folds or stacks over the other, and includes a release coating (which can be applied to the back with a sputum) The coating is applied to the front side and has a W4^printable coating surface to which printing can be applied. The surface may include a conventional clay material, which is adhered to the coating layer or the back side of the skin patch through the skin patch. The drug pack is bonded to the adjacent compartment on the front side of the coatable clay. The slot stack system also includes several cut lines according to the shape and position of the absorbent pad on the skin's compartment, when folding the system 201012499 The contents of the quasi-drug pack, as described, the patch and the drug pack/helium/envelope or the drug chamber are aligned with the corresponding well of the patch electrode. In the embodiment, wherein the drug pack component and the ionization are present Sub-joined-foldable branch structure, the foldable branch structure is still genus: two-shaped:: carefully configured to separate the drug pack and iontophoresis when the iontophoresis drug delivery system is in the same time Sheet assembly. In the embodiments, the support structure can be Including - the first-divided virtual ion II = cow phase::: and a second cell associated with the drug pack component, wherein the ^ ΐ ΐ 分 构成 构成 构成 如 如 如 如 如 如 如 如 如 如 如 如 如 如a plurality of opposite sides connected to the second compartment, wherein the additional sub-transparent and Lifi are physically separated from each other in the folded storage state to ionize the Chinese material spoon Jb'y G and The dividing line assembly not only separates the music in the folded storage state, but also acts as a protective assembly structure for the components of the system. The blister or the like, the squeegee is stored in a normally sealed plastic gas, capacity, Night or 止U stop the content interacting with the surrounding environment' thereby preventing the drug 2 or any electronic device or other patch component in the vicinity of the music bag from having any two of the contents intact. The storage period and the drug solution directly === are preferably defined as relatively alkaline materials, such materials include a clear shape and a secret (4) cover or a cover or barrier layer of the drug pack. Low-taste ethylene, polyester, polyamine , including nylon, or polyalkyl groups such as polyfluorene and polypropylene. It can also be a material selected from the following: a material: a material, a box, a metal film or other further step-by-step reduction of moisture transport should also be present in the face of components such as drug solutions and absorbents. Included in aluminum/polymer-synthetic material--tray and lid, an easy-to-remove sealing layer for easy removal during use, in this case, a stack of suitable polymeric layers and coatings The layer composition is stable when it is in contact with the drug solution. Preferably, the absorption enthalpy belongs to a nonwoven substrate having a gel absorption or action rate of 201012499, including cotton, polypropylene, and poly(ethylene). The absorbable material is polypropylene 曰 曰 fiber, preferably, the sucking alternative embodiment uses an aligning sheet metal, plucking 3| _ pieces combination of the drug delivery device system Separate group or with - through the skin ionization can be used as a "separate component supply - eight stickers = the structure of the package and the coordination of the heart = both and electric: sub-transparent - separate plate, exposed still A two-piece 4 music absorbent pad attached to the system. The patch assembly is attached to the adjacent cell. Then, the 乍 乍 将该 将该 将该 ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 该 该 该 该 该 该 该 该 该 该 该 该 该 该 该 该 该 该 该When contacting, the adhesive ring is connected to a matching ring f on the surface of the absorbent pad such as 3H. ? : attaching the patch to the self-supporting configuration or other suitable disengagement coating to leave the drug absorbent pad permanently adhered to the sticker 2 by the peripheral adhesive. Finally, the patch is applied to the disease. Suffering. A number of embodiments or variations can be devised based on this basic concept and manner. An embodiment having a separate alignment fixing assembly or guiding element, in a drug package and an iontophoresis patch-receiving structure having a plurality of (four) elements continuously on an alignment fixture or guiding element, by A number of labeled alignment openings are combined. The drug pack is first 5 joined to the guiding element on its flat substrate, and as in other embodiments, 5 is generally removed, and then the ion is penetrated into the patch assembly to determine the number of the drug pack. The gel absorbent pads are placed in alignment with a plurality of corresponding electrodes, such that a combined configuration is achieved, wherein the drug absorbent pads are permanently bonded to the electrodes by a peripheral adhesive, and wherein the assembly can be separated and applied A sick person. In a number of alternative embodiments, the guiding element package can be packaged and carried with a plastic bubble cap (or drug pack component) and iontophoresis patch assembly incorporated into the combination, or can be iontophoresed. The sheet assembly package is combined with the guiding member and then combined with the drug pack assembly. 0 7 201012499 [Embodiment] Referring to FIG. 1A to FIG. 14 , the present invention provides an iontophoresis 7 transport assembly structure, and further, the present invention Provided in the form of a "prepackaged drug delivery system" - a fully functional, self-contained, easy-to-use iontophoresis device that enjoys a long, stable expiration date, the system includes: - a drug reservoir package foldable Grid structure, and _ skin patch, which contains - power, current control electronics, and several electrodes. The device is ready for use and requires only a few simple operations to activate the patch and apply it to therapist. In the case of "real", the material operation consists of removing the drug packet barrier cover, folding the cells into each other, and stripping the patch from a release coating. In other embodiments, the transdermal patch and the drug pack are first, and the mouth is placed on the fixture or the guiding member, and then the alignment fixture or the guiding member is removed. The several preferred embodiments are intended to illustrate the concept of the invention, but are not intended to limit the inventive concept in any way. ΙΑ, 1B and 2 respectively illustrate an embodiment of a foldable device 2〇 in an open or horizontal configuration in a cross-sectional exploded view, a combined cross-sectional view and a top view, respectively, with side and top views, respectively. The device is folded in a -pack configuration for long-term storage of the If shape. § Recording consists of three main components: - an ergonomic support structure 22, a transcutaneous iontophoresis μ 24, and a drug pack or plastic bubble cover 26 ° The collapsible support structure 22 may comprise a cardboard ( Or a similar material), one side coated with a release coating 28 and the opposite side coated with a -printable coating 3G substrate, 0 1 (: a fragmentary enlarged sectional view illustrating the portion of the collapsible branch structure 22, The release coating 28 and the printable coating 30. The release coating 28 can be a stone coating, and the printable coating 3G can be a clay coating instead of a foldable substrate or a puff layer can be a 201012499 Heating to form a polymer or the like. Folding ^ ^ ^ ^ ^ ^ ^ 32, 33 and 34, which can be composed of a plurality of folding lines into a substrate by the dental support 22 can be: Number of finger lines = two, two V4 heating to form a number of activities twisted for several areas / structure can be divided into a compartment, the various components of its installation, printing instructions, and / two t' detachment barrier coating The layer is used for the bare adhesive on the _ compartment to avoid permanent sticking to other compartments when folded up during storage.
斤不在基板的脫開塗層侧上，經皮膚電離子透入貼片24 以黏合劑黏_摺疊支撐結構22的—第—分格3βΑ，經皮膚電 離子透入貼片24包括-泡棉膠帶層38、—閉塞雙面膠帶層4〇， 、電極子组合件層42，其由—電源、電子設備及數個電極組成用 以操作該貼片（未顯示）’及—上娜帶層44。如圖ΐβ所示，泡 棉的黏合面及上鄉帶黏附到支撑結構的脫開塗層侧。 ，如圖2所示，泡棉膠帶層38及摺疊支撐結構22層中的數個 剪下圖樣產生一陽極空井46或凹處及一陰極空井48，其在組合 /啟動期間對準用以收納對應的陽極及陰極藥物吸收墊，較佳是 凝勝塾。陽極及陰極剪下圖樣46、48分別暴露下方的電極，包 括陽極50及陰極52 ’圖2中亦顯示藉由在第一分格36a打齒孔 以產生—半格脫開襯裡54，半格脫開襯裡54用以在啟動後將貼 片自支撐結構的臨時層剝掉。 該半格脫開襯裡為使撓性貼片變硬以助於敷用，及另外容許 '作人員谷易操作貼片’使貼片不會黏在操作人員手指上。較 佳’未由半格脫開襯裡54蓋住的一半貼片先附著到病患皮膚 上’隨後藉由在半格脫開襯裡的凸出塊54A將半格脫開襯裡剝下 移除’最後，將貼片的另一半附著到病患皮膚上。 201012499 在第一分格36A上，一條雙面膠帶的黏合條56黏附到摺疊 支撐結構22的可印刷面，黏合條56具有雙功能，一是如圖9A 所示藉由暫時黏合在一脫開塗層面而在其長期儲存情形期間使該 結構保持密閉，第二功能是當該等零件如圖3C所示摺疊起來以 轉移陽極凝膠墊60及陰極凝膠墊62時永久地黏合到摺疊支撐結 構22的一第二分格36B上，以便無法再打開第一分格36A。 如圖9A所示，摺疊支撐結構22亦包括個別的第三分格36C 及第四分格36D，第三分格36C及第四分格36D全體構成一分隔 線組件，其在電離子透入藥物傳送系統存在於摺疊儲存階段時， 配置成實體地分開藥物包及電離子透入貼片組件。支撐結構22 的第三及第四分格36C及36D摺疊時產生一脫開塗層障蔽，其在 長期儲存期間防止經皮膺電離子透入貼片24中的閉塞膠帶40接 觸到藥物包或塑料氣泡罩26的具明確形狀蓋子層64且永久黏 住。 如圖2所示，當該系統存在於儲存前的預先摺疊狀態時，藥 物包組件存在於支撐結構的中央區域中，由電離子透入貼片組件 在一第一側及支撐結構的分隔線組件在第一側對面的一第二側由 兩側相接，該分隔線組件同時提供系統儲存時結構上的分開及外 部保護。 在摺疊支撐結構22的可印刷面上，一第二片雙面膠帶66黏 附到第二半格36B，用以將藥物包或塑料氣泡罩26永久地黏合 到摺疊支撐結構22，或者，例如不用雙面膠帶66，可藉由在裝 藥包底部或支撐結構的可印刷側上塗上一加熱密封塗層，如此使 藥物包或塑料氣泡罩26加熱密封到摺疊支撐結構22。 如圖1B及圖3A所示，藥物包或塑料氣泡罩26具備有一明 201012499 確形狀障蔽蓋64，該障蔽蓋64具低濕氣滲透性，一大致扁平底 層68，其含有二分隔凝膠位置，一位置包含一非織造陽極凝膠吸 收墊60，另一位置包括一非織造陰極凝膠吸收墊62。有明確形 狀的低濕氣可滲透之障蔽蓋64之形狀以圖1B所示較佳，大致扁 平底層68由鋁箔合成膜構成，該薄膜在接觸凝膠墊的該側可包 含一加熱密封塗層（未顯示）。若使用一加熱密封塗層，較佳是一 - 立即可剝除塗層，係以凝膠吸收墊是由一合成或層疊非織造材料 構成，陽極及陰極凝膠分配在該等墊上且浸透到該合成非織造材 〇 射° 具明確形狀的低濕氣可滲透障蔽蓋64已成功地由可冷形成 的鋁合成材料構成，該障蔽蓋64是由產品接觸下側上的一密封 層及對面上的一尼龍層所組成，或者，例如產品接觸面可由聚氯 乙烯（PVC)組成，不需密封層，若利用一密封層，較佳是可剝除 的加熱密封塗層。陽極空腔72及陰極空腔74分別可利用鐵弗龍 (聚四氟乙烯）插頭的傳統冷形成工具作業或藉助真空或壓力用機 械形成。若使用一替代材料，包括薄片或薄膜形成的其他含氟塑 Q 料，如以商標名Aclar販售的材料、聚二氯乙烯（PVDC)，及其 他低濕氣傳輸障蔽加熱形成包裝材料，則該材料可為加熱形成。 圖7A及7B分別以上視圖及側剖圖繪示一實施例陽極72或 陰極74合成墊材料的結構，如所示，陽極72或陰極74合成墊 材料較佳屬於非織物結構以維持結構中裝藥材料的連貫，及可包 括複數個材料層，可能高達三層，這些層可包括一針衝厚聚丙烯 層76、一可滲透薄聚乙烯網狀層，及一閉塞薄聚丙烯層80。該 等層可不需黏合劑加以熱熔接起來，所有三層切割成具有相同外 緣形狀。閉塞薄聚丙烯層80切割成一依然完整無缺及閉塞的周 201012499 邊環形狀，在該環内， 以便内才5塞薄聚丙稀層80完全剪下或穿孔， 中疑㈣I 為可滲制。當組合使賴裝置時，藉由容 Π 過此層及卿該㈣極的全部面積，使可滲透區域 =㈣狀與陽極5Q (如圖2所示）及陰極52電極的形狀相符。 要地’閉塞-聚丙烯層8〇提供一障蔽以用於凝膠移動，因此 外部表面在儲存期間依_為乾燥，有助於該裝置啟動期間藥物 吸收墊的黏合轉移。 在實施例中，陽極72及陰極74合成墊兩者形狀類似，當 然’該等電極可為任何方便的形狀，及在—已知貼月實施例中的◎ 電極可為相同或不同形狀。圖8A及8β以正視圖及剖面圖說明由 合成非織造材料86製成的-陽極及/或陰極任一者的一替代形 狀，此實施例具有製成-定形狀的一周邊環88，具有可渗透的内 部區90。圖10以上視圖說明一替代實施例，顯示一裝置1〇〇， 其具有-藥物包102，藥物包i 02具有不同形狀的陽極及陰極明 確形狀空腔，分別為1 〇 4及1 〇 6，在類似方式中，相異但具對應 形狀的數個陽極及陰極明確形狀空腔反映在泡棉層、摺疊支撐結 構22及閉塞層114及116中的陽極1〇8及陰極11〇中。僅有在❹ 一組合式裝置中一起組裝的對應組件需要具相同形狀。 本發明的一重要方面涉及共同包裝的電離子透入裝置的有效 期限穩疋性’基於此類裝置的歷史’此方面主要的影響係該尊類 裝置因有效期限的限制而在商業上不易成功。如所述，共同包裝 技術己包括努力在長期儲存期間使濕的藥物凝膠直接接觸電極加 以包裝，及努力透過低濕氣可滲透（高障蔽）材料以隔離同一包震 内的電源及電子設備。濕凝膠僅直接接觸電極加以包裝，及在使 用時藉由一電纜或其他連接器連接到一電源及電子設備，如所 12 201012499 述，這些裝置各充滿長期穩定性的挑戰，例如，最終濕凝膠會使 電極、電源及電子設備中的金屬劣化，再輪到此等劣化又污染及 劣化凝膠的穩定性。 ❹ ❹ 在本發明中，實現穩定的長期共同包裝是藉由提供陽極及陰 極凝膠-儲存容器，形式是具有產品接觸層的一分開密封地密： 藥物包或㈣氣泡罩空腔，其不讀出進人凝雜⑽起反應 =收，膠。由於凝膠材料本身未具形狀，因此使用—載體基板材 =以提供凝膠形狀及結構，當組裝制該㈣時又提供—穩定支 :成膠自長期儲存容器中移出。該載體基板應由不會將凝 :辦其〜起反應或吸收的材料構成，較佳塑料氣泡罩空腔及 載體基板應由穩定、較隋 ω ^ g 材枓如聚丙烯及聚乙烯製成，可基於 凝膠的性質使用及選擇任何合適㈣。 土於 性而限穩定性會因貼片組件的構造及貼片組成的整體穩定 性而有所不同，貼片有 ^ T, At ^ 双朋限疋依黏合品質的保持及電路組件特 疋功能的維持而定，該裝 卞行 裝置應具有至少2年的穩定有效期限。 一獎-至>5E根據本發明以逐步剖面圖說明形成、填充及密封 入Bi:法或藥物包的方法’圖6以上視圖說明圖5的藥物包組 合時的情形，诵堂以！ ± ., 120表示。在圖5Α至5Ε的方法中，該裝藥 包在倒轉位置中组人， ^ 分 、，口 開始組合時先提供一低濕氣傳送材料製成 的—蓋子或覆蓋薄膜199 ^ ’其形狀用以在特定間隔及深度分別產 &陰極凝膠空腔形狀124及126，接著將-陽極整128放 ”月確开ν狀的陽極空腔124，及以相同方式將—陰極墊⑽放 "狀的陰極空腔126。該等墊可具有與圖7Α至7Β及 層132 Β所不者類似的結構，將陽極及陰極塾定向以便各閉塞 134放置成朝向空腔内及接觸對應具明確形狀空腔的底 201012499 部。使陽極及陰極墊定出剛好放入具形狀空腔底部的大小，依此 方式，具明確雜空雌著初始地提供該等墊套準到具明確形狀 的蓋子或覆蓋薄膜122。 以-時間順序執行的其餘步驟將如以下說明，該組件可容許 打開時間由墊滲透作用的速率判定，該速率與所使用凝勝的黏度 有關。 - 在時間t = t0，如圖5C所示’分配一數量具黏性的铜陽極凝、 膠136用以均勻地覆蓋陽極墊128的中央可渗透區域84 (圖μ 所示），類似地，分配一數量具黏性的陰極凝膠138用以均勻地 覆蓋陰極塾130的-可渗透區域。亦如圖5C所示，陽極及陰極 凝膠兩者依一方式分配，以便一旦分配一已知數量凝膠墊加上 凝膠高度的總高度有點超過具明確形狀陽極或陰極空腔124或 126的深度。該凝膠為在裝置組合期間維持其形狀/高度一必要期 間，必須屬一較高黏度範圍。在t<t〇<1;l，施加一平底或載體基 板層140(圖5D)及加熱密封到具明確形狀蓋子或覆蓋薄膜122。 亦如圖5D所示，平載體基板層140的施加接觸及壓緊陰極凝膠 138A、陽極凝膠136A，令凝膠弄濕平載體基板層u〇的内表面 ◎ 及舖開來。 或者，在另一實施例（未顯示）中，可形成該平底層類似於具 明確形狀的覆蓋薄膜層，以產生一嵌套配置，在該例子中，可設 計凝膠加上墊高度，當組合底層及蓋子層時，以便凝膠將以所述 實施例的類似方式與平載體基板接觸。 在此程序中’ t = t0至t = tl的一段時間期間定義為，所分配 的陽極及陰極凝膠浸濕通過其各別墊及開始濕到蓋子層具明確形 狀空腔的底部所需時間。時間是一要素，原因是已發現若在施加 14 201012499 平載體基板層前，凝膠完全浸濕通過各別墊及弄濕底部或具明確 形狀覆蓋薄膜空腔的内表面，則該等墊一旦吸滿會優先地黏在具 明確形狀蓋子的内側。人們在試著組合該系統時當然不想要發生 此情況，因為吸飽的凝膠墊會黏著到蓋子或覆蓋薄膜122而非載 體基板層140。t = tO至t = tl的一段時間期間亦定義，當施加基 ' 板層140時凝膠會適當地維持其高度以便凝膠會弄濕及黏著到該 - 層内表面的時間。 為上述理由，凝膠制定在較佳黏度範圍以提供正確流動速率 0 及表面張力，例如一 1 00, 000釐泊凝膠可具有大約2至4分鐘 的時間窗，這在正常組裝時發生是適當的。 在此過程中，凝膠初始地接觸及弄濕基板層140，此在基板 層140與陽極墊128及陰極墊130之間的凝膠的表面張力超過 吸收墊上的引力時，容許凝膠作為黏合劑，因此，當陽極墊128 及陰極墊130緩慢地吸收凝膠時，不管裝置的定向如何，該等墊 將黏著到載體基板及拉向載體基板。因此，如圖5E所示，在密 封底層及蓋子層後，受壓縮的凝膠分別吸收（浸透）到陽極及陰極 Q 墊中，產生吸收完全的非織造陽極墊128A及吸收完全的陰極墊 130A。如上述，吸收完全的陽極及陰極凝膠墊繼續黏著到基板層 140，藉此亦如圖5Έ所示，在該包裝中分別產生陽極及陰極頂部 空間142及144。已發現，由於凝膠的高表面張力及較佳高黏 度，吸收完全的墊將依然暫存在其個別具明確形狀蓋子空腔上， 及如所示在裝置的整個預期有效期間黏附到載體基板層。 應了解，為使過量凝膠減到最少，加到各空腔的凝膠量應與 各凝膠的吸收率匹配，凝膠的量及黏度較佳使吸收的凝膠不弄濕 貼片上的閉塞環的外表面，依此方式，閉塞環146、148的外表 15 201012499 面應依然較乾燥，在啟動期間有助於凝膠吸收墊的黏合轉移及黏 合附著到經皮膚貼片的對應陽極及陰極空井中，在陽極及陰極頂 部空間142及144區域中，具明確形狀蓋子空腔的内表面應依然 無凝膠及較乾燥。 為使此組裝概念起作用，必須制定凝膠具有一較佳黏度，較 佳範圍是在8, 000至120,000釐泊之間，但只要該過程能成功 遵循亦不加限定。制定系統中的有用的凝膠可藉由在水中溶解一- 適量藥物或生理鹽水及加入一凝膠形成劑如HpMC(羥丙基甲基纖 維素），以便產生一適量黏度的傳導性凝膠，亦可使用其他凝膠❹ 形成劑如PVP(聚乙烯吼咯酮）、pE〇(聚氧化乙烯）或pVA(聚乙烯 醇），以重量計2%的HPMC粉末已制定出成功的凝膠。 依有用處的凝膠形成劑及期望貼片劑量及計晝施加期間而 · 定，該凝膠中的-活化劑濃度可大大不同，通常，濃度範圍將從 約〇· 2%至10%(重量）。 圖3A至3D以剖面圖逐步地說明一較佳實施例如何啟動及展 開到療部位，圖4以上視圖說明圖3A在移除塑料氣泡罩或 藥物包障蔽蓋64後的情形。圖9A及9β分別以側面圖及上視冑〇 說明一包裝完全的裝置。 、、由圖9A及9B包裝完全的裝置開始，將說明一展開或組裝方 法’首先，藉由扯開凸出塊18使黏合條56自第四分格㈣的脫 開襯裡塗裝侧脫開，以打開及展開包裝完全的裝置。第二，將具 月確形狀覆蓋障蔽蓋64自扁平底層68移除或剥去，露出非織造 陽極及陰極凝膠吸收墊6G、62，其如圖3A所示經由凝膠的表面 張力黏著到扁平底層68。剝除動作是藉由剝開具明確形狀障蔽蓋 b4構件上的凸出塊is (圖2)開始。 16 201012499 接著，如圖3C所示，將第一分格36A在摺疊線32摺疊到第 —分格36B上，藉此使陽極及陰極凝膠墊、62的閉塞層8〇 的閉塞區域與經皮膚電離子透入貼片24的閉塞雙面膠帶層4〇永 久黏合接觸，而且，使黏合條與摺疊支撐結構22的可印刷塗層 接觸且永久地黏著到第二分格36B，藉此防止第一分格36a被重 新打開。圖3B _示由動作的中間圖示，較佳按壓經皮膚貼片的 - 外表面以確保閉塞雙面膠帶層40永久黏合到凝膠墊上的閉塞區 域的情形良好。 © 最後，在凸出塊54八將半個脫開襯裡54自支撐結構剥下， 帶著組裝完成的經皮膚貼片隨它剝下，露出的一半貼片黏合劑可 塗到治療位置，及接著在凸出塊54β(圖9B)將半個脫開襯裡自經 皮膚貼片剝下，其餘半個貼片黏著到治療位置。 圖11A至11C繪示一替代實施例，其包括一對準固定物或導 引元件，及繪示該實施例的啟動，圖12以上視圖說明圖UB完 全相似實施例，圖UA至11C的剖面圖採取自該實施例。如圖 11A令最佳可見’該裝置2 〇 〇，如包裝時，包括三個主要組件： © 一導引元件202，其具有數個間隔凸起的對準構件2〇4、2〇6 ; 一藥物包208設置，及一經皮膚貼片組件21〇。該等主要組件設 計成分開儲存在一共同包裝中，及在預備使用該裝置時加以組 合。 藥物包包括一平卡基板層212，其設計有數個間隔的對準開 口 214及216，此等開口在組合期間與對準構件2〇4及2〇6套 準。非織造陽極及陰極凝膠吸收墊218及22〇依圖5A至5E上 述實施例的方式分別裝載在一底層222上及與藥物包蓋子224分 開，藥物包208如藉由一雙面膠帶層226黏著到平卡基板層 17 201012499 212。 經皮膚貼片組件210利用間隔的對準開口 23〇及232及如 前述實施例的半個脫開襯裡234安裝在一平卡基板層228上貼 片組件具有類似上述泡棉層236、256及雙面膠帶238 '電極子 組合件層240及上襯膠帶層242的結構。 在使用時，個別組件使用一組件自行對準到毗鄰組件的特點 互相對準及組合，依此方式，如圖11A所示，導引元件2〇2可利 用間隔的對準構件204、206朝上地定位在一扁平表面上。接 著，藉由對準構件204套準到藥物包中的對準開口 214及對準構 件206套到對準開口 216，將塑料氣泡藥物包2〇8組合到對準固 定物或導引元件202。接著可將蓋子224自藥物包208剝掉，分 別露出非織造陽極及陰極凝膠吸收墊218及220，接著，再使用 對準構件204及206對準開口 230及232將該經皮膚貼片組件 21 0組&到藥物包2 0 8，藉此使該等凝膠吸收塾與對應電極對準 放置，此造成圖11B的剖面圖及圖12的上視圖所示合併配置， 藥物包2 0 8及經皮膚貼片組件21 〇以連續套準方式組合在導引元 件202上。 在此堆疊情形中，組合好的貼片預備好分開以放置在病患患 處，如圖lie所示，藉由簡單地將半個脫開襯裡234自該卡片剝 下可完成分離，藉此使該裝置與平卡基板層228分開及帶著組裝 成的經皮膚貼片2 5 0。如上述實施例的說明，接著貼片預備好 供病患使用。 應了解，除了此實施例中的平卡基板層是數個分開的扁平構 件而非數個摺疊連接的分格外，藥物包208及經皮膚貼片組件 210在構造上類似上述實施例，平卡基板層212、228包括數個 201012499 對準開口 ’其對應到導引元件202上的對準構件204及206，及 此等層不需矽或其他脫開塗層，以便兩側可包含一可印刷黏土塗 層材料或類似物（如圖1 2所示）。 平卡基板層212、228亦可由任何合適聚合物材料構成，導 引凡件202的對準構件204及206亦較佳由一合適聚合物材料 加熱形成或射出模製。 圖13以剖面分解圖說明圖11A至llc所示實施例的一替代 實施例’其中以具有對準構件304及306的一導引元件302在 © 藥物包308中取代平卡基板層212，除此之外，藥物包類似於上The jin is not on the disengaged coating side of the substrate, and the skin iontophoresis into the patch 24 is adhered to the adhesive-folding support structure 22 - the first compartment 3βΑ, and the transdermal iontophoresis patch 24 includes the foam The tape layer 38, the occlusive double-sided tape layer 4, and the electrode sub-assembly layer 42 are composed of a power source, an electronic device and a plurality of electrodes for operating the patch (not shown) and the upper layer 44. As shown in Fig. ΐ, the bonding surface of the foam and the upper layer of the foam adhere to the side of the release coating of the support structure. As shown in FIG. 2, a plurality of cut patterns in the foam tape layer 38 and the folded support structure 22 layer produce an anode hollow 46 or a recess and a cathode open well 48 which are aligned during assembly/starting for storage. The anode and cathode drug absorption pads are preferably condensed. The anode and cathode shear patterns 46, 48 respectively expose the underlying electrodes, including the anode 50 and the cathode 52'. Figure 2 also shows the perforation in the first compartment 36a to create a semi-lattice lining 54, half-grid The lining 54 is detached to strip the patch from the temporary layer of the support structure after activation. The half-lattice lining is used to stiffen the flexible patch to aid in application, and additionally allows the user to operate the patch so that the patch does not stick to the operator's fingers. Preferably, the half patch that is not covered by the semi-detached lining 54 is attached to the patient's skin first. Then the detached lining is peeled off by the bulging block 54A in the half-plain lining. Finally, attach the other half of the patch to the patient's skin. 201012499 On the first compartment 36A, a double-sided tape adhesive strip 56 is adhered to the printable side of the folded support structure 22, and the adhesive strip 56 has a dual function, one being temporarily bonded as shown in Figure 9A. The coated side retains the structure during its long-term storage condition, and the second function is to permanently bond to the fold when the parts are folded as shown in Figure 3C to transfer the anode gel pad 60 and the cathode gel pad 62. A second compartment 36B of the support structure 22 is provided so that the first compartment 36A can no longer be opened. As shown in FIG. 9A, the folded support structure 22 also includes an individual third compartment 36C and a fourth compartment 36D. The third compartment 36C and the fourth compartment 36D collectively form a separation line assembly for iontophoresis. The drug delivery system is configured to physically separate the drug pack and the iontophoretic patch assembly when present in the folded storage phase. The third and fourth compartments 36C and 36D of the support structure 22 are folded to create a release coating barrier that prevents the occlusive tape 40 in the percutaneous sputum ion penetration into the patch 24 from contacting the drug pack or during long term storage. The plastic bubble cover 26 has a well-defined cover layer 64 and is permanently adhered. As shown in FIG. 2, when the system is present in a pre-folded state before storage, the drug pack component is present in a central region of the support structure, and the iontophores penetrates the patch assembly on a first side and the separation line of the support structure. The second side of the assembly opposite the first side is joined by the sides, and the dividing line assembly simultaneously provides structural separation and external protection during system storage. On the printable side of the folded support structure 22, a second sheet of double-sided tape 66 is adhered to the second half-frame 36B for permanently bonding the drug pack or plastic bubble cover 26 to the folded support structure 22, or, for example, without The double-sided tape 66 can be heat sealed to the folded support structure 22 by applying a heat seal coating to the printable side of the charge pack or to the printable side of the support structure. As shown in FIG. 1B and FIG. 3A, the drug pack or plastic bubble cover 26 is provided with a 201012499 shape mask 64 having a low moisture permeability and a substantially flat bottom layer 68 containing two separate gel positions. One location includes a nonwoven anode gel absorbent pad 60 and the other location includes a nonwoven cathode gel absorbent pad 62. The shape of the low moisture permeable barrier cover 64 having a well-defined shape is preferably as shown in FIG. 1B, and the substantially flat bottom layer 68 is composed of an aluminum foil synthetic film which may include a heat seal coating on the side contacting the gel pad. (not shown). If a heat seal coating is used, preferably an immediate peelable coating, wherein the gel absorbent pad is comprised of a synthetic or laminated nonwoven material on which the anode and cathode gels are dispensed and impregnated The synthetic nonwoven material has a well-defined low moisture permeable barrier cover 64 that has been successfully constructed from a cold formable aluminum composite material that is contacted by a sealing layer on the underside of the product and opposite The upper nylon layer is formed, or, for example, the product contact surface may be composed of polyvinyl chloride (PVC) without a sealing layer. If a sealing layer is used, a peelable heat sealing coating is preferred. The anode cavity 72 and the cathode cavity 74 can each be formed using a conventional cold forming tool of a Teflon (polytetrafluoroethylene) plug or by vacuum or pressure. If an alternative material is used, including other fluoroplastic Q materials formed from flakes or films, such as those sold under the trade name Aclar, polydichloroethylene (PVDC), and other low moisture transport barriers to form packaging materials, This material can be formed by heating. 7A and 7B are respectively a top view and a side cross-sectional view showing the structure of a composite pad material of an anode 72 or a cathode 74. As shown, the composite material of the anode 72 or the cathode 74 is preferably a non-woven structure to maintain the structure. The consistency of the medicinal material, and may include a plurality of layers of material, possibly up to three layers, which may include a needle-punched polypropylene layer 76, a permeable thin polyethylene mesh layer, and a occluded thin polypropylene layer 80. The layers can be thermally welded without the need for a bond, and all three layers are cut to have the same outer edge shape. The occluded thin polypropylene layer 80 is cut into a still intact and occluded week 201012499. The shape of the side ring is within the ring so that the inner layer of the thin polypropylene layer 80 is completely cut or perforated, and the suspected (four) I is permeable. When the device is combined, the permeable region = (tetra) is conformed to the shape of the electrodes of the anode 5Q (shown in Figure 2) and the cathode 52 by accommodating the entire area of the layer and the (four) pole. The 'occlusion-polypropylene layer 8" provides a barrier for gel movement so that the outer surface is dry during storage to aid in the transfer of the drug absorption pad during activation of the device. In the embodiment, both the anode 72 and the cathode 74 composite pads are similar in shape, although the electrodes may be of any convenient shape, and in the known past embodiment, the electrodes may be the same or different shapes. 8A and 8β illustrate, in a front view and a cross-sectional view, an alternative shape of either an anode and/or a cathode made of synthetic nonwoven material 86, this embodiment having a peripheral ring 88 formed into a shaped shape having Permeable inner zone 90. Figure 10 is a top view showing an alternative embodiment showing a device 1 having a drug pack 102 having different shapes of anode and cathode well-defined cavities, 1 〇 4 and 1 〇 6, respectively. In a similar manner, a plurality of anode and cathode well-defined cavities that are distinct but corresponding in shape are reflected in the anode layer 1 and the cathode 11 of the foam layer, the folded support structure 22, and the occlusion layers 114 and 116. Only the corresponding components assembled together in a combined device need to have the same shape. An important aspect of the invention relates to the effective shelf life of a co-packaged iontophoresis device based on the history of such devices. The main impact of this aspect is that the device of the class is not commercially successful due to limitations in the expiration date. . As noted, co-packaging techniques include efforts to package wet drug gels directly into the electrodes during long-term storage, and efforts to isolate power and electronics within the same package through low moisture permeable (high barrier) materials. . The wet gel is only packaged directly in contact with the electrode and is connected to a power source and electronic device by a cable or other connector during use, as described in 12 201012499, each of which is full of long-term stability challenges, such as final wetness The gel degrades the metal in the electrodes, power supplies, and electronics, and it is the turn to degrade and contaminate and degrade the stability of the gel. ❹ ❹ In the present invention, a stable long-term co-packaging is achieved by providing an anode and a cathode gel-storage container in the form of a separate seal with a product contact layer: a drug pack or (iv) a bubble cap cavity, which is not Read into the person condensed (10) from the reaction = receipt, glue. Since the gel material itself is not shaped, the carrier-based sheet material is used to provide the gel shape and structure, and when the assembly (4) is assembled, a stable branch is provided: the gel-forming material is removed from the long-term storage container. The carrier substrate should be composed of a material that does not react or absorb. Preferably, the plastic bubble cap cavity and the carrier substrate are made of a stable, relatively 隋ω^g material such as polypropylene and polyethylene. It can be used and selected according to the nature of the gel (4). Soil properties and stability will vary depending on the structure of the patch components and the overall stability of the patch composition. The patch has ^ T, At ^ double-pound retention and retention of circuit components and circuit component features. Depending on the maintenance, the installation device should have a stable expiration date of at least 2 years. One Prize-to-5E illustrates a method of forming, filling, and sealing a Bi: method or a drug pack in a stepwise sectional view in accordance with the present invention. FIG. 6 is a view showing the case of the combination of the medicine pack of FIG. ± ., 120 indicates. In the method of FIGS. 5A to 5A, the charging bag is assembled in the inverted position, and the mouth is combined to provide a low moisture conveying material, a cover or a cover film 199 ^ ' The cathode cavities 124 and 126 are respectively produced at specific intervals and depths, and then the anodes are fixed to the anode cavity 124, and the cathode pads (10) are placed in the same manner. a cathode cavity 126. The pads may have a structure similar to that of Figures 7A through 7A and 132, with the anode and cathode being oriented such that each occlusion 134 is placed toward the cavity and the contact is clear The bottom of the shape cavity is 201012499. The anode and cathode pads are set to just the size of the bottom of the shaped cavity. In this way, the clear dorms are initially provided to the cover with a clear shape. Or covering the film 122. The remaining steps performed in a time sequence will be as explained below, the component can allow the opening time to be determined by the rate of pad osmosis, which is related to the viscosity of the used condensate - at time t = t0, As shown in Figure 5C A quantity of viscous copper anode condensate, glue 136 is dispensed to uniformly cover the central permeable region 84 of the anode pad 128 (shown in Figure 51), similarly, a quantity of viscous cathode gel 138 is dispensed for Uniformly covering the permeable region of the cathode crucible 130. As also shown in Figure 5C, both the anode and cathode gels are dispensed in a manner such that once a known amount of gel pad is dispensed plus the total height of the gel height is somewhat Exceeding the depth of the anode or cathode cavity 124 or 126 having a well-defined shape. The gel must be in a higher viscosity range for maintaining its shape/height during device assembly. At t<t〇<1;l Applying a flat or carrier substrate layer 140 (Fig. 5D) and heat sealing to a clear shaped cover or cover film 122. As also shown in Fig. 5D, the flat carrier substrate layer 140 is applied to contact and compress the cathode gel 138A, anode. The gel 136A is such that the gel wets the inner surface of the flat carrier substrate layer ◎ and spreads out. Alternatively, in another embodiment (not shown), the flat bottom layer may be formed to resemble a clear film having a clear shape. Layer to create a nested configuration In this example, the gel plus pad height can be designed when the bottom layer and the cover layer are combined so that the gel will contact the flat carrier substrate in a similar manner to the described embodiment. In this procedure 't = t0 to t The period of time = tl is defined as the time required for the dispensed anode and cathode gel to wet through the respective pads and begin to wet to the bottom of the lid layer with a well-defined cavity. Time is an element because it has been found If the gel is completely wetted through the respective pads and wet the bottom or the inner surface of the film cavity with a clear shape before applying the 14 201012499 flat carrier substrate layer, the pads will preferentially adhere to each other once they are filled. The inside of the shape cover. This is of course not desirable when trying to combine the systems because the saturated gel pad will adhere to the cover or cover film 122 instead of the carrier substrate layer 140. The period of time from t = tO to t = tl is also defined as the time at which the gel will properly maintain its height when the base layer 140 is applied so that the gel will wet and adhere to the inner surface of the layer. For the above reasons, the gel is formulated at a preferred viscosity range to provide a correct flow rate of 0 and surface tension. For example, a 1 000 000 centipoise gel can have a time window of about 2 to 4 minutes, which occurs during normal assembly. appropriate. During this process, the gel initially contacts and wets the substrate layer 140, which allows the gel to adhere as the surface tension of the gel between the substrate layer 140 and the anode pad 128 and the cathode pad 130 exceeds the attractive force on the absorbent pad. Thus, when the anode pad 128 and the cathode pad 130 slowly absorb the gel, the pads will adhere to the carrier substrate and to the carrier substrate regardless of the orientation of the device. Thus, as shown in Figure 5E, after sealing the bottom layer and the cover layer, the compressed gel is separately absorbed (soaked) into the anode and cathode Q pads, resulting in a fully absorbed nonwoven anode pad 128A and a fully absorbed cathode pad 130A. . As described above, the fully absorbed anode and cathode gel pads continue to adhere to the substrate layer 140, thereby also creating anode and cathode top spaces 142 and 144 in the package, as shown in Figure 5A. It has been found that due to the high surface tension of the gel and the preferred high viscosity, the fully absorbed pad will remain temporarily on its individual well-defined lid cavity and adhere to the carrier substrate layer as indicated throughout the intended life of the device. . It should be understood that in order to minimize excess gel, the amount of gel added to each cavity should match the absorption rate of each gel, and the amount and viscosity of the gel are preferably such that the absorbed gel does not wet the patch. The outer surface of the occlusive ring, in this manner, the outer surface of the occlusive ring 146, 148 15 201012499 should still be relatively dry, facilitating the adhesion transfer and adhesion of the gel absorbent pad to the corresponding anode of the transdermal patch during activation. In the cathode anomalous, in the region of the anode and cathode headspaces 142 and 144, the inner surface of the cavity having a well-defined cover should remain gel-free and drier. In order for this assembly concept to work, it is necessary to formulate a gel having a preferred viscosity, preferably in the range of 8,000 to 120,000 centipoise, provided that the process is successfully followed or not. A useful gel in the system can be prepared by dissolving a proper amount of the drug or physiological saline in water and adding a gel forming agent such as HpMC (hydroxypropyl methylcellulose) to produce a proper amount of conductive gel. Other gel 形成 forming agents such as PVP (polyvinyl ketone), pE 聚 (polyethylene oxide) or pVA (polyvinyl alcohol) may be used, and 2% by weight of HPMC powder has developed a successful gel. . The concentration of the activator in the gel may vary greatly depending on the gel forming agent in use and the desired amount of tablet and the application period, and generally, the concentration will range from about 〇 2% to 10% ( weight). Figures 3A through 3D illustrate, in cross-section, a preferred embodiment of how a preferred embodiment can be activated and deployed to a treatment site. Figure 4 above illustrates the situation of Figure 3A after removal of the plastic bubble shield or drug packet barrier cover 64. Figures 9A and 9B illustrate a fully packaged device in a side view and a top view, respectively. Starting from the complete package of Figures 9A and 9B, an unfolding or assembly method will be described. First, the adhesive strip 56 is detached from the detached lining side of the fourth compartment (4) by tearing the projection 18. To open and unpack the complete device. Second, the monthly cover cover 64 is removed or stripped from the flat bottom layer 68 to expose the nonwoven anode and cathode gel absorbent pads 6G, 62 which are adhered via the surface tension of the gel as shown in Figure 3A. Flat bottom layer 68. The stripping action begins by stripping the raised block is (Fig. 2) on the b4 member with the clear shape baffle cover. 16 201012499 Next, as shown in FIG. 3C, the first compartment 36A is folded over the first line 36B on the fold line 32, thereby occluding the occlusion area and the occlusion area of the anode and cathode gel pads 62. The occluded double-sided tape layer 4 of the skin ionizing penetration patch 24 is permanently bonded and the adhesive strip is brought into contact with the printable coating of the folded support structure 22 and permanently adhered to the second compartment 36B, thereby preventing The first compartment 36a is reopened. Figure 3B shows an intermediate view of the action, preferably pressing the outer surface of the dermal patch to ensure that the occlusive double-sided tape layer 40 is permanently bonded to the occlusive region of the gel pad. © Finally, the semi-detached lining 54 is peeled off from the support structure at the bulging block 54 and the assembled dermal patch is peeled off with it, and the exposed half of the patch adhesive can be applied to the treatment site, and A half of the detached lining is then peeled off from the transdermal patch at the bulge 54[beta] (Fig. 9B) and the remaining half of the patch is adhered to the treatment site. 11A to 11C illustrate an alternative embodiment including an alignment fixture or guiding element, and illustrating the activation of the embodiment. Figure 12 above illustrates a completely similar embodiment of Figure UB, and the profiles of Figures UA through 11C The figure is taken from this embodiment. As best seen in Figure 11A, the device 2, if packaged, includes three main components: a guiding element 202 having a plurality of spaced apart alignment members 2〇4, 2〇6; A drug pack 208 is provided, and once through the skin patch assembly 21〇. The main component design components are stored in a common package and combined when the device is ready for use. The drug pack includes a flat card substrate layer 212 that is designed with a plurality of spaced alignment openings 214 and 216 that are aligned with alignment members 2〇4 and 2〇6 during assembly. The nonwoven anode and cathode gel absorbent pads 218 and 22 are respectively mounted on a bottom layer 222 and separated from the drug pack lid 224 in the manner of the above-described embodiments of Figures 5A through 5E, such as by a double-sided tape layer 226. Adhered to the flat card substrate layer 17 201012499 212. The transdermal patch assembly 210 is mounted on a flat card substrate layer 228 using spaced alignment openings 23 and 232 and a half release liner 234 as in the previous embodiment. The patch assembly has a similar foam layer 236, 256 and double The surface tape 238' has the structure of the electrode sub-assembly layer 240 and the upper tape layer 242. In use, the individual components are aligned and combined with each other using a component that aligns itself to adjacent components. In this manner, as shown in FIG. 11A, the guiding elements 2〇2 can be aligned toward the alignment members 204, 206. The upper ground is positioned on a flat surface. Next, the plastic bubble package 2〇8 is assembled to the alignment fixture or guiding element 202 by the alignment member 204 registering the alignment opening 214 in the drug pack and the alignment member 206 to the alignment opening 216. . The lid 224 can then be peeled from the drug pack 208 to expose the nonwoven anode and cathode gel absorbent pads 218 and 220, respectively, and the dermal patch assembly can then be aligned using the alignment members 204 and 206 to align the openings 230 and 232. 21 0 & to the drug pack 208, thereby aligning the gel enthalpy with the corresponding electrode, which results in the cross-sectional view of FIG. 11B and the merged configuration shown in the top view of FIG. 12, the drug pack 20 8 and the transdermal patch assembly 21 are combined in a continuous register on the guiding element 202. In this stacking situation, the assembled patches are ready to be placed separately for placement in the patient's affected area, as shown by lie, by simply peeling off the half of the release liner 234 from the card to complete the separation, thereby enabling The device is separated from the flat card substrate layer 228 and carries the assembled transdermal patch 250. As explained in the above embodiment, the patch is then ready for use by the patient. It should be understood that the drug pack 208 and the transdermal patch assembly 210 are similar in construction to the above embodiment, except that the flat card substrate layer in this embodiment is a plurality of separate flat members instead of a plurality of folded joints. The substrate layers 212, 228 include a plurality of 201012499 alignment openings 'which correspond to the alignment members 204 and 206 on the guiding member 202, and such layers do not require snagging or other release coating so that both sides can include one A clay coating material or the like is printed (as shown in Figure 126). The flat card substrate layers 212, 228 may also be constructed of any suitable polymeric material, and the alignment members 204 and 206 of the guide member 202 are also preferably formed by heating or injection molding of a suitable polymeric material. Figure 13 illustrates an alternative embodiment of the embodiment of Figures 11A through 11c in a cross-sectional exploded view in which a flat member substrate 212 is replaced by a guiding member 302 having alignment members 304 and 306 in the drug pack 308. In addition, the drug pack is similar to the above
述藥物包，及一蓋子324。經皮膚貼片組件310亦類似於圖11A 所不者及包括具有數個間隔的對準開口 330及332的基板328 及半片脫開層334，藥物包308藉由雙面膠帶326黏合到導引元 件 302。 組合及啟動類似於圖11A至11C所示實施例的組合及啟動， 因此’移除藥物包蓋子324，及使用對準開口 330及332在對準 構件304及306之上對準經皮膚貼片組件31〇與藥物包，之後 © 依圖lie方式剝掉該組合貼片。 圖14以剖面分解圖說明本發明裝置的又一實施例，其代表 圖11A至11C所示者的另一替代例，在此實施例中，具有對準構 件404及406的對準固定物402取代與經皮膚貼片組件41〇相 關聯的脫開平卡基板228。該對準固定物包括上表面上的一矽酮 脫開塗層，其塗在貼片移除前黏著的該側。此實施例依該等上述 實施例類似方式組合及塗裝’因此移除藥物包4〇8的蓋子424， 半片脫開層412旁的對準開口 414及416與對準構件4〇4及4〇6 對準，及以圖11C的方式剝掉完全對準裝置。 19 201012499 尚應了解，應用&丨 面尺寸，如從㈣大約了使用者的纽合裝置或貼片可屬於任何方 分，尺寸可依處理的分X 2公分到大約15公分⑽公 /化劑及待治療情況而大大不同。 此藝者廊用：:：細即說明本發明以遵守專利法令，及提供熟-此=應㈣_❹以建造及 範 = 本發明自身的範圍可完=:特別不同裝置實施’及不背離 【圖式簡單說明】 〇 一實圖：…]面分解圖說明-可摺叠電離子透入藥物傳迸系統的 圖1B :是圖1A所示裝置的組合圖； 祕圖沾二以錢特別放大剖面圖說明圖1A及1B的可摺疊支撐 μ構的顯示脫開塗層及可印刷層； ®2:以上視圖說明圖1Α及⑺所示實施例； 圖3Α至3D .以剖面圖說明圖4裝置的—逐步啟動及展開； 〇 圖4 :以上視圖說明圖3Α至3D中的實施例圖中顯示具明確 形狀的蓋子自藥物包移除； 圖5A至5E .以剖面圖說明將藥物及生理鹽水凝膠包裝在非織 造吸收墊上的逐步方法及設計； 圖6 :以上視圖說明圖5A至5E如組合時所顯示的實施例； 圖7A及7B .分別以上視圖及剖面圖說明圖6實施例的吸收 勢； 圖8A及8B :分別以上視圖及剖面圖說明一吸收墊的一替代實 施例； 20 201012499 圖9A :根據本發明以側面圖說明在摺疊包裝（儲存）配置中的一 可摺疊電離子透入藥物傳送系統； 圖9B :以上視圖說明圖9A的包裝配置； 圖10 :以上視圖說明該裝置在一打開、水平配置中的一替代實 施例； 圖11A:以剖面分解圖說明本發明裝置的一替代實施例，具有 ' 分開的電離子透入貼片及藥物包組件及一導引元件； 圖11B :以剖面圖說明圖11A的分解零件組合一起的情形； 〇 圖11C :說明用於圖11A及11B的組合式經皮膚電離子透入藥 物傳送系統的分開情形； 圖12 :以上視圖說明圖11B的組件； 圖13 :以剖面分解圖說明圖11A至11C所示實施例的另一替 代實施例，藥物包由導引元件攜帶；及 圖14 :以剖面分解圖說明圖11A至11C所示實施例的再一替 代實施例。 Q 【主要元件符號說明】 18凸出塊 20 可摺疊裝置 22摺疊支撐結構 24 經皮膚電離子透入貼片 26、120、408 藥物包或塑料氣泡罩 28 脱開塗層 30 可印刷塗層 32、33、34 摺疊線 36A第一分格 21 201012499 36B第二分格 36C第三分格 36D第四分格 38 泡棉膠帶層 40 閉塞雙面膠帶層 42、240 電極子組合件層 44、242 上襯膠帶層 46 陽極空井（陽極剪下圖樣） 48 陰極空井（陰極剪下圖樣） 50、108 陽極 52、110 陰極 54、234、334 脫開襯裡 54A、54B、160 凸出塊 56、66、238、326 雙面膠帶 60、218非織造陽極凝膠吸收墊 62、220非織造陰極凝膠吸收墊 64 障蔽蓋 68 扁平底層 70 吸凝膠墊 72、124 陽極空腔 74、126 陰極空腔 76 針衝聚丙烯層 78 可滲透聚乙烯網狀層 80 閉塞薄聚丙烯層 84 可滲透區域 86 非織造合成材料 88 周邊環 90 内部區 100、200 裝置 102藥物包 201012499 104 具明確形狀的陽極空腔 106 具明確形狀的陰極空腔 114、116、132、134 閉塞層 122、224、324、424 蓋子（或覆蓋薄膜） 128 陽極墊 128A非織造陽極墊 - 130 陰極墊 130A 吸收完全的陰極墊 136、136A 陽極凝膠 138、138A 陰極凝膠 〇 140基板層 142 陽極頂部空間 144 陰極頂部空間 146、148 閉塞環 170、250 組裝完全的經皮膚貼片 202、302 導引元件 204、206、304、306、404、406 對準構件 208、308、408 藥物包 210 經皮膚貼片組件 212、228 平卡基板層 間隔的對準開口 214、216、230 ' 232、330 ' 332、414、416 222 底層 226 雙面膠帶層 236、256 泡棉層 238、326雙面膠帶 240電極子組合件層 242上襯膠帶層 250皮膚貼片 310、410 經皮膚貼片組件 324、424 蓋子 23 201012499 328 基板 334、412 半片脫開層 402 對準固定物Said drug pack, and a lid 324. The transdermal patch assembly 310 is also similar to the substrate 328 and the half-release layer 334 having a plurality of spaced alignment openings 330 and 332, and the drug pack 308 is bonded to the guide by a double-sided tape 326. Element 302. Combining and activating a combination and activation similar to the embodiment shown in Figures 11A through 11C, thus 'removing the drug pack cover 324, and using the alignment openings 330 and 332 to align the transdermal patches over the alignment members 304 and 306 The component 31 is smeared with the drug pack, and then the combined patch is peeled off according to the figure. Figure 14 illustrates a further embodiment of the apparatus of the present invention in a cross-sectional exploded view, which represents another alternative to that shown in Figures 11A through 11C, in this embodiment, an alignment fixture 402 having alignment members 404 and 406. Instead of disengaging the flat card substrate 228 associated with the transdermal patch assembly 41A. The alignment fixture includes a ketone ketone release coating on the upper surface that is applied to the side to which the patch adheres prior to removal of the patch. This embodiment combines and coats in a similar manner to the above-described embodiments. Thus, the cover 424 of the drug pack 4〇8 is removed, the alignment openings 414 and 416 next to the half-release layer 412 and the alignment members 4〇4 and 4 〇6 Align and strip the full alignment device in the manner of Figure 11C. 19 201012499 It should be understood that the application & face size, such as from (4) about the user's button or patch can belong to any square, the size can be processed according to the point of X 2 cm to about 15 cm (10) public / chemical The agent and the condition to be treated are greatly different. This artist's gallery uses::: fine to illustrate the invention to comply with the patent law, and to provide cooked-this = should (4) _ ❹ to build and Fan = the scope of the invention itself can be completed =: special different device implementation 'and not deviate from the map Brief description of the formula: 〇一实图: ...] surface decomposition diagram description - foldable iontophoresis into the drug delivery system Figure 1B: is a combination of the device shown in Figure 1A; 1A and 1B show the disengageable coating and printable layer of the foldable support structure; ®2: The above view illustrates the embodiment shown in Figs. 1A and (7); Figs. 3A to 3D. Figure 7: The above view illustrates the embodiment of Figures 3A to 3D showing the cover with a clear shape removed from the drug pack; Figures 5A to 5E. The drug and saline are illustrated in cross section. Step-by-step method and design of a gel package on a nonwoven absorbent pad; Figure 6: The above view illustrates the embodiment shown in Figures 5A through 5E as shown in combination; Figures 7A and 7B. The above view and cross-sectional views illustrate the embodiment of Figure 6 Absorption potential; Figures 8A and 8B: respectively, the above view and section BRIEF DESCRIPTION OF THE DRAWINGS An alternative embodiment of an absorbent pad; 20 201012499 FIG. 9A is a side view of a foldable iontophoretic drug delivery system in a folded package (storage) configuration in accordance with the present invention; FIG. 9B: 9A package configuration; Figure 10: The above view illustrates an alternative embodiment of the device in an open, horizontal configuration; Figure 11A: An alternate embodiment of the device of the present invention is illustrated in a cross-sectional exploded view with 'separated iontophoresis Into the patch and drug pack assembly and a guiding component; FIG. 11B is a cross-sectional view illustrating the combination of the exploded components of FIG. 11A; FIG. 11C: illustrating the combined transdermal iontophoresis for FIGS. 11A and 11B Separate Situation of Drug Delivery System; Figure 12: The above view illustrates the assembly of Figure 11B; Figure 13: illustrates another alternative embodiment of the embodiment illustrated in Figures 11A through 11C in a cross-sectional exploded view, with the medication pack carried by the guiding element; Figure 14 is a cross-sectional exploded view showing still another alternative embodiment of the embodiment shown in Figures 11A through 11C. Q [Main component symbol description] 18 protruding block 20 Folding device 22 folding support structure 24 Transdermal iontophoresis patch 26, 120, 408 Drug package or plastic bubble cover 28 Release coating 30 Printable coating 32 , 33, 34 folding line 36A first compartment 21 201012499 36B second compartment 36C third compartment 36D fourth compartment 38 foam tape layer 40 occluding double-sided tape layer 42, 240 electrode sub-assembly layer 44, 242 Lining tape layer 46 anode hole (anode cutting pattern) 48 cathode hole (cathode cutting pattern) 50, 108 anode 52, 110 cathode 54, 234, 334 detaching lining 54A, 54B, 160 protruding block 56, 66, 238, 326 double-sided tape 60, 218 non-woven anode gel absorbent pad 62, 220 non-woven cathode gel absorbent pad 64 baffle cover 68 flat bottom layer 70 suction gel pad 72, 124 anode cavity 74, 126 cathode cavity 76 Needle punched polypropylene layer 78 permeable polyethylene mesh layer 80 occluded thin polypropylene layer 84 permeable region 86 non-woven synthetic material 88 peripheral ring 90 inner region 100, 200 device 102 drug pack 201012499 104 a well-shaped anode cavity 106 with clear Cathode cavities 114, 116, 132, 134 occlusive layers 122, 224, 324, 424 cover (or cover film) 128 anode pads 128A non-woven anode pads - 130 cathode pads 130A fully absorbed cathode pads 136, 136A Glue 138, 138A Cathode Gel 〇 140 Substrate Layer 142 Anode Headspace 144 Cathode Headspace 146, 148 Occlusion Rings 170, 250 Assembly of Complete Transdermal Patches 202, 302 Guide Elements 204, 206, 304, 306, 404, 406 Alignment members 208, 308, 408 drug pack 210 through skin patch assembly 212, 228 flat card substrate layer alignment openings 214, 216, 230 ' 232, 330 ' 332, 414, 416 222 bottom layer 226 double-sided tape Layer 236, 256 foam layer 238, 326 double-sided tape 240 electrode sub-assembly layer 242 lining tape layer 250 skin patch 310, 410 dermal patch assembly 324, 424 cover 23 201012499 328 substrate 334, 412 half-piece off Layer 402 alignment fixture