1243689 03777twf2.doc/006 修正日期 93.5.18 玖、發明說明： 本發明是有關於一種經皮吸收貼劑（Transdermal Absorbed Patch)，且特別是有關於一種以親水性高分子 (Hydrophilic Polymer)爲間質(Matrix)之經皮吸收貼劑。 新藥物的發明或發現到批准上市需要花費數年甚至數 十年的時間。而有些藥物因給藥之途徑不正確，使大部分 之藥物在達到標的物之前，其成分就被其它組織所吸收甚 至破壞，因而降低其療效。因此改良既有藥物之劑型，使 藥物能正確地導向標的物，充分發揮藥效，且對於其他組 織的影響降至最低是目前醫藥發展的趨勢之一。其中藥物 控制釋放(Drug Controlled Release)爲將藥物放置在儲存體 (Reservoir)，於適當的環境中，儲存體的結構產生變化， 同時藥物藉由擴散作用釋放到儲存體之外，因而延長藥物 在體內停留之時間。經皮吸收爲一種藥物控制釋放模式， 儲存體則是黏附在皮膚，藥物由儲存體釋放而滲入皮膚， 以達到全身或是局部之治療’其主要的優點爲使用方便， 且爲非侵入(Non-invaded)式之投藥方式。 經皮吸收貼劑可分爲雨種型式：一種是儲存體爲囊狀 物，藥物裝塡在其中，儲存體之另一面爲具有黏性之半透 膜，此半透膜控制藥物的釋放速率。另一種則以高分子間 質爲儲存體，混合或是在其外添加黏著劑，以增加對皮膚 之黏附性，控制釋放之功能爲高分子間質。 理想的親水性高分子間質之條件爲：對皮膚之刺激性 小，低過敏性且具吸水膨潤性（Swelling)，但不會崩裂散 扣‘。’‘ 修正日期93.5.18 1243689 03777twf2.d〇c/006 開。水膠（Hydrogel)具有上述之特性，其主要的種類有聚 丙烯酸(Polyacrylate)、聚乙稀醇(Polyvinyl Alcohol)、聚丙 細酸胺（Polyacrylamide)、聚乙嫌比略垸嗣（Polyvinyl1243689 03777twf2.doc / 006 Modification date 93.5.18 发明, Description of the invention: The present invention relates to a transdermal absorbent patch, and in particular to a kind of hydrophilic polymer (Hydrophilic Polymer) Matrix (Matrix) transdermal absorption patch. It can take years or even decades for a new drug to be discovered or discovered before it can be approved for marketing. And some drugs are not properly administered, so that most of the drugs' components are absorbed or even destroyed by other tissues before reaching the target, thus reducing their efficacy. Therefore, it is one of the current trends in the development of medicine to improve the dosage forms of existing medicines so that the medicines can be properly directed to the target substance and give full play to the effects of medicines, and minimize the impact on other organizations. The Drug Controlled Release is to place the drug in a reservoir (Reservoir). In a suitable environment, the structure of the reservoir changes, and at the same time, the drug is released outside the reservoir by diffusion, thus prolonging the drug's Time spent in the body. Transdermal absorption is a controlled release mode of the drug, and the storage body is adhered to the skin. The drug is released from the storage body and penetrates the skin to achieve systemic or local treatment. Its main advantages are ease of use and non-invasive (Non -invaded). Transdermal absorption patches can be divided into rain types: one is the storage body is a capsule, the drug is contained therein, and the other side of the storage body is a viscous semipermeable membrane, which controls the drug release rate . The other type uses the polymer interstitial substance as a storage body, mixes or adds an adhesive to the outside to increase the adhesion to the skin, and the function of controlling release is the polymer interstitial substance. The ideal conditions for the hydrophilic polymer interstitial are: low irritation to the skin, hypoallergenicity, and water absorption and swelling (Swelling), but it will not break apart. ‘‘ Revision date 93.5.18 1243689 03777twf2.d〇c / 006. Hydrogel has the above characteristics. Its main types are Polyacrylate, Polyvinyl Alcohol, Polyacrylamide, Polyvinyl, etc.
Pyrrolidone)及它們的衍生物。 因此本發明的目的就是在提供一種以親水性高分子爲 間質之經皮吸收貼劑，利用其高分子側鏈之帶電荷之官能 基與汗液中之電解質的交互作用，而改變間質的孔洞結 構，以達到控制釋放之作用。 根據本發明之上述目的，提出一種以親水性高分子爲 間質之經皮吸收貼劑，其組成包括：親水性高分子、增黏 劑、塡充劑以及活性物質(Active Substance)，所形成之膠 狀物可直接黏覆於皮膚上。 爲讓本發明之上述和其他目的、特徵、和優點能更明 顯易懂，下文特舉一較佳實施例，並配合所附圖式，作詳 細說明如下= 圖式之簡單說明： 第1圖是本發明之較佳實施例之一種經皮吸收貼劑之 製備流程圖。 實施例 請參照第1圖，爲本發明之較佳實施例之一種經皮吸 收貼劑之製備流程圖。 首先加入適量的水，使親水性高分子膨潤，形成A溶 液。所使用之親水性高分子例如是BFGoodrich公司所製 造的Carbopol®樹脂，其爲一種聚丙烯酸共聚物 修正日期93·5·18 1243689 03777twf2.doc/006 (Polyacrylate Copolymer)，具熱穩定性、抗囷性與生物相 容性（Biocompability)。 另配製B溶液，其組成包括增黏劑、交聯劑、塡充劑 與活性物質。其中增黏劑可提高貼劑與皮膚的黏著性’其 材質例如是聚丙烯酸鈉與聚乙烯比咯烷酮；交聯劑會與親 水性高分子之官能基形成交互作用，增加親水性高分子之 機械強度，其材質爲多醇類例如甘油；塡充劑是爲了維持 貼劑之形狀，其材質例如是高嶺土與二氧化鈦；活性物質 則包括親水性的有機化合物，例如非類固醇抗發炎藥或是 香料。 然後將A溶液與B溶液充分攪拌混合，形成膠狀物’ 其各成分之重量百分比如第一表所示。 第一表 _ 組成 ---—— 重量百分比（％)_一 聚丙烯酸共聚物 0.5-10 _. 聚丙烯酸鈉 0.5-10 聚乙烯比咯烷酮 0.5-10___ 甘油 1.0-50 __ 高嶺土 _ 0.1-10 __- 二氧化鈦 0.1-10 活性物質 _1-Q-1Q 一_— 接著將膠狀物塗佈在支撐物例如不織布上，然後在膠 狀物上覆上離型紙，置於室溫中約24小時，使膠狀物熟 化(Curring)，形成親水性的高分子貼劑。在熟化的過程中， 1243689 03777twf2.doc/006 修正日期 93.5.18 親水性的高分子之孔洞變小，而將活性物質局限在孔洞 中。 使用時先除去離型紙，然後將高分子貼劑黏附於皮膚’ 因爲由皮膚之毛細孔所排出之汗液含有尿素與無機鹽類等 電解質，會破壞高分子鏈之間所形成之鍵結（Bonding) ’使 高分子之孔洞變大，而局限在孔洞之活性物質因濃度梯度 而向外擴散至皮膚中，同時貼劑中的高分子增黏劑其分子 鏈亦會伸展開，使貼劑的黏度增加，因而提高貼劑對皮膚 之附著性。 第二表爲本發明所製成之貼劑與市售貼劑包覆非類固 醇抗發炎藥ketoprofen，以人皮爲藥物穿透模式，量測藥 物釋放之累積量。 第二表Pyrrolidone) and their derivatives. Therefore, the object of the present invention is to provide a transdermal absorption patch with a hydrophilic polymer as an interstitial substance, and use the interaction between a charged functional group of a polymer side chain and an electrolyte in sweat to change the interstitial substance. Hole structure to achieve controlled release. According to the above object of the present invention, a transdermal absorption patch with a hydrophilic polymer as an interstitial substance is proposed. The composition includes: a hydrophilic polymer, a tackifier, a filler, and an active substance. The gel can be directly adhered to the skin. In order to make the above and other objects, features, and advantages of the present invention more comprehensible, a preferred embodiment is exemplified below in conjunction with the accompanying drawings, and the detailed description is as follows = Brief description of the drawings: FIG. 1 It is a preparation flow chart of a transdermal absorption patch according to a preferred embodiment of the present invention. Examples Please refer to FIG. 1, which is a flowchart of the preparation of a transdermal absorption patch according to a preferred embodiment of the present invention. First, an appropriate amount of water is added to swell the hydrophilic polymer to form an A solution. The hydrophilic polymer used is, for example, Carbopol® resin manufactured by BFGoodrich, which is a polyacrylic acid copolymer. Modified date is 93.5.18 1243689 03777twf2.doc / 006 (Polyacrylate Copolymer), which is thermally stable and resistant to rubidium. And biocompatibility. Solution B is also prepared, and its composition includes a thickener, a cross-linking agent, a filler, and an active substance. Among them, the tackifier can improve the adhesion between the patch and the skin. Its material is, for example, sodium polyacrylate and polyvinylpyrrolidone; the cross-linking agent will interact with the functional group of the hydrophilic polymer to increase the hydrophilic polymer. Its mechanical strength is made of polyalcohols such as glycerin; tincture is used to maintain the shape of the patch, and its materials are kaolin and titanium dioxide; active substances include hydrophilic organic compounds such as non-steroidal anti-inflammatory drugs or spices. Then, the solution A and the solution B are thoroughly stirred and mixed to form a gelatin substance. The weight percentages of the components are shown in the first table. The first table _ composition ------- weight percent (%) _ a polyacrylic acid copolymer 0.5-10 _. Sodium polyacrylate 0.5-10 polyvinyl polypyrrolidone 0.5-10 ___ glycerol 1.0-50 __ kaolin _ 0.1- 10 __- Titanium dioxide 0.1-10 Active substance_1-Q-1Q __ Next, the glue is coated on a support such as a non-woven fabric, and then the glue is covered with a release paper and placed at room temperature for about 24 When the gelatin is cured for hours, a hydrophilic polymer patch is formed. During the aging process, 1243689 03777twf2.doc / 006 amendment date 93.5.18 The pores of the hydrophilic polymer become smaller, and the active substance is confined to the pores. Remove the release paper before use, and then attach the polymer patch to the skin. 'The sweat discharged from the pores of the skin contains electrolytes such as urea and inorganic salts, which will destroy the bond formed between the polymer chains (Bonding ) 'Make the pores of the polymer larger, and the active substance confined in the pores diffuses out into the skin due to the concentration gradient, and at the same time, the molecular chain of the polymer thickener in the patch will also stretch out, making the patch's The viscosity increases, thereby improving the adhesion of the patch to the skin. The second table shows the non-steroidal anti-inflammatory drug ketoprofen prepared by the patch and the commercially available patch. The human skin is used as the drug penetration mode to measure the cumulative amount of drug release. Second table
Ketoprofen 累積量（pg/cm2) 時間（小時） 含聚丙烯酸共聚物之貼劑 市售貼劑 2 21.44 5.17 4 45.74 13.60 6 63.92 21.70 8 89.21 32.59 12 128.86 54.56 24 216.99 105.84 _1 -- 由第二表可看出，本發明之含聚丙烯酸共聚物貼劑之 藥物釋放速率明顯地較市售貼劑爲佳，在兩小時之釋放速 率約爲市售貼劑之四倍，且經過二十四小時仍可維持較高 1243689 〇37? 7tvvf2.doc/006 且如檫定之釋放速率。Ketoprofen Cumulative amount (pg / cm2) Time (hours) Commercially available patches containing polyacrylic acid copolymers 2 21.44 5.17 4 45.74 13.60 6 63.92 21.70 8 89.21 32.59 12 128.86 54.56 24 216.99 105.84 _1-Available from the second table It can be seen that the drug release rate of the polyacrylic acid copolymer-containing patch of the present invention is significantly better than that of the commercially available patch, and the release rate in two hours is about four times that of the commercial patch, and it remains after 24 hours. It can maintain a high release rate of 1243689 〇37? 7tvvf2.doc / 006.
修正日期93.5.18 _占由上述本發明較佳實施例可知，應用本發明具有下列 1 .貼劑中含有增黏劑，因此可直接貼在皮膚上，不需 Μ〜層黏著層’減少活性物質滲透皮膚之阻礙。 2·貼劑所使用之高分子具有對皮膚之刺激性小，且使 後不會發生殘膠或有沾黏異物之惡感。 3·貼劑具有快速之活性物質釋放速率，並可維持穩定 之釋放量。 4·本發明所製備之高分子物質除了包覆藥物外，亦可 包覆香料或農藥，作爲化妝品或殺蟲劑，用途廣泛。 雖然本發明已以一較佳實施例揭露如上，然其並非用 以限定本發明’任何熟習此技藝者，在不脫離本發明之精 神和範圍內，當可作各種之更動與潤飾，因此本發明之保 護範圍當視後附之申請專利範圍所界定者爲準。Correction date 93.5.18 _According to the above-mentioned preferred embodiments of the present invention, it can be known that the application of the present invention has the following 1. The patch contains a tackifier, so it can be directly applied to the skin, without the need for an adhesive layer to reduce the activity Barriers to substance penetration into the skin. 2. The polymer used in the patch has little irritation to the skin, and it will not cause the residue of glue or the feeling of sticking foreign matter. 3. The patch has a fast release rate of the active substance and can maintain a stable release amount. 4. In addition to coating drugs, the polymer materials prepared by the present invention can also be coated with perfumes or pesticides, and are widely used as cosmetics or pesticides. Although the present invention has been disclosed as above with a preferred embodiment, it is not intended to limit the present invention. 'Any person skilled in the art can make various changes and decorations without departing from the spirit and scope of the present invention. The scope of protection of the invention shall be determined by the scope of the attached patent application.