1267386 A7 B7 五、發明說明（1 技術領域 本發明爲有關以羊毛脂及水爲必要成分使用之含水 性熱融型粘著劑之外用貼劑，及其製法，詳言之，爲有關 含水性熱融型粘著劑膏體，其對皮膚之剌激性低，且膏 體中含有之水溶性藥物不析出結晶而充分發揮樂效之 外用貼劑。 發明背景 以往含水性外用製劑有軟膏劑、洗劑、水性貼劑 等。這些製劑中，軟膏劑和洗劑難將含有之藥物持續又 定量地投與，且有塗布時附著在患部外等污染之問題。 水性貼劑雖決解這些問題而使藥物持續經皮吸收，作 爲貼劑膏劑之物性上，欲貼在肘、膝等屈曲部，須以外 科膠帶固定等手段。 非水性貼劑有以天然橡膠、合成橡膠等爲基劑之粘 著劑，或以丙烯酸酯系粘著劑爲膏體之粘著劑。此貼劑 粘著力強，可開發爲彌補水性貼劑之缺點。 但在通常當作外用貼劑之藥物溶解劑之多羥醇、二 請 先 閱 讀 背 面 之 注 意 事 項 再 $1 本 頁 經濟部智慧財產局員工消費合作社印製 含時 欲物 物 藥 之 溶 不 乎 藥弓， 性晶 溶結 水出 合析 配齊 幾其著 類尤粘 酯。在 及難而 類困分 醇種充 經 起 在因，皮 一一g= 種 有 時 劑 貼 性 水 非 不 性問 解等 溶化 之惡 劑性 溶收 對吸 題 開 特 在 如 例 用 使 案 提 劑 溶 助 爲 作 題 問 些 這 決 解 爲 劑 著 24粘 6 1 性2 Ξ -3水 4非 平於 東 民 他 羅 克 之 示 揭 足 己 酉 周 1三口 中 澧 勤 仍。 肩物 }藥 on之 t效 藥 現 呈 以 m 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公爱） 1267386 A7 --— ____B7 _ 五、發明說明（2 ) (請先閱讀背面之注意事項再填寫本頁) 水性貼劑之調製上，將水溶性藥物溶在膏體時，若該 藥物爲酸性藥物，則將二異丙醇胺溶在配來離子化來溶 解之手段。這種技術應用在製造之非水性貼劑雖然可 會g，但在須乾燥工程之溶劑系貼劑，或須高熱處方之熱 融型粘劑等，則水分被蒸除，使在膏體中多以結晶析 出。 作爲熱融型粘著劑成分雖也有用界面活性劑來使水 分混合之手段，但因界面活性劑會誘發剌激皮膚之問 題。 此外，雖可考慮用吸水性或水溶性高分子化合物賦予 膏體吸水融能力，但在連續生產工程，爲熔融其次之粘 著劑而加熱時，蒸發水分，而有析出高分子化合物，異構 化等問題。又因水分在粘著劑中以被高分子包圍之形 態存在於膏體中，故活性成分之藥物在粘著劑中之移動 擴散被抑制，結果也藥物之利用率惡化等問題。 經濟部智慧財產局員工消費合作社印製 鑑於上述現狀，本發明如何提供將水溶性藥物安定 地配合，從粘著劑之藥物釋放性良好，且基於其經皮吸 收之生物利用性高之含水性熱融型粘著劑膏體，用以製 造外用貼劑爲其課題。 發明之揭示 爲解決上述課題，本發明基本上提供以苯乙烯-異戊 二烯-苯乙烯嵌段共聚物，賦粘樹脂，抗氧化劑，羊毛脂及 水爲必要成分之含水性熱融型粘著劑膏體配合之外用 貼劑。 -4- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 12673861267386 A7 B7 V. INSTRUCTION DESCRIPTION OF THE INVENTION (1) Field of the Invention The present invention relates to a hydrothermal hot-melt adhesive for use as a necessary component of lanolin and water, and a method for preparing the same, and more specifically, relates to water content The hot-melt adhesive paste has a low irritation to the skin, and the water-soluble drug contained in the paste does not precipitate crystals, and the patch for external use is fully exerted. BACKGROUND OF THE INVENTION Conventional aqueous external preparations have ointments , lotions, water-based patches, etc. Among these preparations, ointments and lotions are difficult to continuously and quantitatively administer the drug, and there is a problem of contamination such as adhesion to the affected part during application. The problem is that the drug continues to be percutaneously absorbed. As a patch ointment, it should be attached to the flexion of the elbow, knee, etc., and must be fixed by surgical tape. Non-aqueous patches are based on natural rubber and synthetic rubber. An adhesive, or an adhesive with an acrylate-based adhesive as a paste. The adhesive has strong adhesion and can be developed to compensate for the shortcomings of the aqueous patch. However, it is usually used as a drug dissolution agent for external patches. Many Alcohol, please read the notes on the back and then $1. On the one hand, the Ministry of Economic Affairs, the Intellectual Property Bureau, the employee consumption cooperative, printed the time-dependent drug, the drug is not dissolved in the medicine bow, and the crystal clear water is combined with the combination. Viscous esters. In the difficult and difficult to dilute the alcohol species to fill up the cause, the skin one g = the kind of time, the adhesive water, the non-information, the dissolution of the evil agent, the dissolution of the problem For example, use the solution to dissolve the solution as a problem. Ask this solution as a solution. 24 sticks, 6 1 sex, 2 Ξ -3 water, 4 non-flat, and Dongmin, he is a sign of the singer. The shoulder medicine} medicine on the t-effect is now in m. This paper scale applies the Chinese National Standard (CNS) A4 specification (210 X 297 public) 1267386 A7 --- ____B7 _ five, invention description (2) (please Read the precautions on the back and fill out this page. In the preparation of the water-based patch, when the water-soluble drug is dissolved in the paste, if the drug is an acidic drug, the diisopropanolamine is dissolved in the ionization to dissolve. Means. This technology is applied in the manufacture of non-water Although the patch may be g, in the solvent-based patch to be dried, or the hot-melt adhesive which requires a high heat, the water is distilled off, so that the crystal is mostly precipitated in the paste. Although the type of the adhesive agent is also a means for mixing the water with a surfactant, the surfactant may induce a problem of irritating the skin. In addition, it is considered that the water-absorbing or water-soluble polymer compound can be used to impart a sorption of the paste. Capability, but in continuous production engineering, when heating to melt the next adhesive, it evaporates water, and there are problems such as precipitation of polymer compound, isomerization, etc., and moisture is surrounded by the polymer in the adhesive. When it exists in a paste, the movement|distribution of the drug of an active ingredient in an adhesive agent is suppressed, and it is also the problem of the deterioration of the utilization rate of a drug. According to the above situation, how does the present invention provide a stable combination of a water-soluble drug, a drug release property from an adhesive, and a high bioavailability based on transdermal absorption; A hot-melt adhesive paste for the manufacture of a topical patch is a subject. DISCLOSURE OF THE INVENTION In order to solve the above problems, the present invention basically provides a water-containing hot-melt type adhesive having a styrene-isoprene-styrene block copolymer, a tackifying resin, an antioxidant, lanolin and water as essential components. The paste is used in combination with a patch. -4- This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) 1267386
五、發明說明（3 ) 具體而言，本發明爲於將水溶性藥物配合於上述含 水性熱融型粘著劑之外用貼劑。 尤其本發明宜爲含水〇 . 1〜3 0%之外用貼劑。 也即本發明之特徵在使用於以苯乙烯-異戊二烯-苯 乙烯嵌段共聚物，賦粘樹脂，抗氧化劑，羊毛脂及水爲必 要成分之含水性熱融型粘著劑，於此含水性熱融型粘著 劑膏配合水溶性藥物，用這種含水性熱融型粘著劑之外 用貼劑兼具經時優異之藥物安定性及藥物釋放性，又可 解決上述種種問題。 實施本發明之最佳形態 次就本發明提供之外用貼劑所配合之原料及其配合 量更詳細說朋。 本發明之外用貼劑所用之羊毛脂爲將附著在羊毛之 分泌物洗淨時回收精製者，加2〜3倍量水也不喪失軟 膏樣之粘稠度，而易溶於***、氯仿、石油、輕質汽油 等之膽固醇脂肪。本發明爲利用這種羊毛脂之特徵之 含水性熱融型粘著劑製造外用貼劑。 經濟部智慧財產局員工消費合作社印製 本發明之貼劑所用苯乙烯-異戊二烯-苯乙烯嵌段共 聚物（以下稱SIS )爲成貼著劑之基本骨架之合成橡 膠，使用苯乙烯/橡膠比爲14/86者。通常製造用SIS之 粘著劑時之熔融溫度爲120〜160°C，本發明之含水性熱 融型粘著劑爲含有水分，須在約9 0 °C捏合之處方設計頗 爲重要。 故S I S之配合量宜爲1 〇〜2 5 % (對熱融型粘著劑全 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） I267386V. INSTRUCTION DESCRIPTION OF THE INVENTION (3) Specifically, the present invention relates to a patch for use in combination with a water-soluble drug or a water-containing hot-melt adhesive. In particular, the present invention is preferably a hydrazine. 1 to 30% of the external patch. That is, the present invention is characterized in that it is used in a hydrated hot-melt adhesive containing styrene-isoprene-styrene block copolymer, tackifying resin, antioxidant, lanolin and water as essential components. The water-containing hot-melt adhesive paste is combined with a water-soluble drug, and the water-containing hot-melt adhesive and the external patch have excellent drug stability and drug release properties, and can solve the above problems. . BEST MODE FOR CARRYING OUT THE INVENTION Next, the present invention provides a raw material to which the external patch is blended, and a blending amount thereof. The lanolin used in the external patch of the present invention is used for recovering and purifying the secretions attached to the wool, and adding 2 to 3 times the amount of water does not lose the viscosity of the ointment, and is easily soluble in ether, chloroform, Cholesterol fat such as petroleum and light gasoline. The present invention is an external patch for the use of a hydrothermal hot-melt adhesive characterized by such lanolin. The styrene-isoprene-styrene block copolymer (hereinafter referred to as SIS) used in the patch of the present invention printed on the patch of the present invention is a synthetic rubber which is a basic skeleton of the adhesive, and styrene is used. / Rubber ratio is 14/86. The melting temperature of the SIS adhesive is usually 120 to 160 ° C. The hydrothermal adhesive of the present invention is important in that it contains water and is kneaded at about 90 ° C. Therefore, the amount of S I S should be 1 〇~2 5 %. (For the hot-melt adhesive, the paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm). I267386
、發明說明（ 請 先 閱 讀 背 面 之 注 意 事 項 再 填 本 頁 重量之重量％，以下同），尤宜1 5〜2 Ο %，若不滿1 ο % , 則不能保持粘著劑之凝聚力，易發生殘糊；又若超2 5 % , 則粘著劑膏體變硬，難捏合，成爲粘著力低之膏體。 本發明之外用貼劑所用賦粘樹脂可用芳族樹脂、脂 族樹脂、脂環族石油樹脂、松香脂、松香脂酯、萜系 樹脂等，其配合量宜15〜35%，尤宜20〜30%，若不滿 15%，則不易呈現粘著性，凝聚力下降，易發生殘糊；又若 超過35%，則粘著劑膏體變硬，難捏合，成爲粘著力低之 膏體。 本發明之外用貼劑所用抗氧化劑乃爲防止粘著劑之 捏合中及製品保存中防止氧化劣化而配合者，可爲如二 丁羥基甲苯、異戊四醇-肆[3- (3，5-二第三丁基-4-羥 苯基）丙酸酯、乙酸生育酚等，這種抗氧化劑宜配合 0 · 1 〜2 % 〇 經濟部智慧財產局員工消費合作社印製 本發明所用羊毛脂具有保持粘著劑中水分之作用，也 當作粘著劑之軟化劑，其配合量取決於所配合之水分量 與其他油脂、液態橡膠等軟化劑之配合量之平衡，宜5 〜4 0 %，尤宜1 0〜3 0 %，若不滿5 %，則不能保持水分安 定；又若超過40%，則粘著劑成糊而不宜。 本發明所用水爲溶解藥物而對膏體賦予冷卻感而配 合者，其配合量取決於主藥配合量與羊毛脂配合量之 平衡，宜〇 · 1〜3 0 %，尤宜1〜2 0 %，若不滿0 · 1 %，則不符 配合之目的；若超過3 0%，則不能保持粘著劑之必要物 性而不宜。 -6_ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 經濟部智慧財產局員工消費合作社印製 1267386 A7 ________Β7___ 五、發明說明（7 ) 處方製造粘著劑膏體。墊子採用經矽酮處理之聚酯膜， 基布採用聚酯纖維織布。粘著劑膏體之塗布量均爲 10 0 g/m2 〇 第1表：實施例1〜5之粘著劑膏體處方 原料名 實施例No. 1 2 3 4 5 SIS 14.0 18.0 16.0 17.0 16.0 脂環族飽和石油樹脂 25.0 松香脂酯樹脂 22.0 萜樹脂 24.0 25.0 24.0 聚丁烯 7.0 19.0 6.0 液態石蠟 13.0 6.0 17.0 8.5 聚乙二醇-400 10.0 5.0 二丁羥基甲苯 1.0 1.0 1.0 1.0 1.0 羊毛脂 24.0 25.0 10.0 10.0 25.0 精製水 9.0 9.0 1.0 1.0 9.0 精製水（主藥溶解用） 1.0 1.0 1.0 1.0 1.0 二異丙醇胺 5.0 5.0 5.0 5.0 10.0 克羅他尼東 2.5 2.5 2.5 2.5 2.5 BPAA 5.0 5.0 5.0 5.0 5.0 1-盏醇 0.5 0.5 0.5 0.5 0.5 十四酸異丙酯 5.0 比較例1〜4 用無配合水分之熱融型粘著劑及市售丙烯酸酯系粘 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁) ip- # 1267386 發明說明（ 者劑製造外用貼劑，各比較例之處方如下第2表。 第2表··比較例1〜4，杜宴翻丨暮鹛南卡 原料名 _ 比較例No. 1 2 3 4 SIS 18.0 20.0 萜樹脂 29.0 31.0 聚丁烯 15.0 15.0 液態石蠟 ----- 9.0 15.0 聚乙二醇-400 5.0 5.0 5.0 5.0 二丁羥基甲苯 1.0 1.0 市售丙烯酸酯A 72.0 市售丙烯酸酯B 72.0 羊毛脂 10.0 10.0 10.0 二異丙醇胺 5.0 5.0 5.0 5.0 克羅他尼東 2.5 2.5 2.5 2.5 BPAA 5.0 5.0 5.0 5.0 1-盏醇 0.5 0.5 0.5 0.5 (請先閱讀背面之注意事項再填寫本頁) 0 I ϋ I -II 訂·! 1111 經濟部智慧財產局員工消費合作社印製 % 但市售丙烯酸酯系粘著劑A採用丙烯酸-2-乙基己酯 j -乙酸乙烯酯共聚物，市售丙烯酸酯系粘著劑B採用丙 | 嫌酸-2 -乙基己酯-乙嫌基吡略[}定酮共聚物。 I 試驗例1 :藥物诱渦件胃式厓命 ] 以市售之含BPAA水性貼劑爲對照，就前述實施例及 比較例之貼劑，實行體外皮膚透過性試驗來評價藥物透 | 過性。 ! I I -ίο- ! 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公爱） 1267386 經濟部智慧財產局員工消費合作社印製 A7 B7 五、發明說明（9) 方法： 將裸鼠腹部皮膚用外科刀及剪切取，固定在接受器側 裝滿生理食鹽水之豎形擴散池，其護套內循環約3 5 °C之 溫水。 裸鼠之皮膚上貼各種藥劑後，經時採樣接受器液，將 24小時後之藥物透過量以HPLC定量。 糸吉果: 結果如第3表，對照之市售含BPAA水性貼劑其透 過量爲 66.0/zg/cm 2。 第3表：鼠皮膚透過性試驗結果 黏著劑 實施例1 實施例2 實施例3 實施例4 實施例5 透過量// g/cm2 58.2 74.6 62.4 81.5 65.8 黏著劑No. 比較例1 比較例2 比較例3 比較例4 透過量// g/cm2 29.8 21.5 43.7 3 1.6 由第3表之結果得知，本發明實施例之貼劑與比較例 之貼劑相較，其皮膚透過性較高，藥物釋放性較佳。 試驗例2 :安定件試驗 將前述實施例之貼劑與比較例之貼劑分別投入聚乙 烯-鋁袋，在40 °C保存6個月，檢查從製劑有無結晶析 出。 結果雖在實施例之貼劑不見結晶之析出，但在比較例 之貼劑則在第1個月己析出結晶，不能從墊子剝離或粘 著力極端下降。在所有製劑均不見主藥含量之下降。 -11- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -I ϋ ϋ ϋ ϋ f. ϋ ^ ϋ ϋ -I I ^ ϋ I I ϋ . 一-0, I ϋ ^ ϋ ϋ ϋ I I ϋ ϋ 1.— I I —.1 ϋ J ^ ^1 1— I ^ I I ϋ I I ϋ I H I · (請先閱讀背面之注音？事項再填寫本頁) 1267386 A7 五、發明說明（1G) 上述保存安定後，貼劑之結晶析出之有無，及其粘著 力測定結果如下第4及5表。 粘著力測定爲電木板1 8 0 °剝離，單位：g/2 5匪。 第 4表：安定性試驗結果（: 竇施例 1〜5) 實施例1 實施例2 實施例3 實施例4 實施例5 初期 結晶 Μ >fnrr 挑 Μ ^\\\ Μ 1II γ (製造即後）粘著力 780 890 540 690 750 40°C 結晶 Μ >fml /fnT Μ 無 Μ j\\\ 1個月 粘著力 750 870 610 710 770 40°C 結晶 Μ 並 Μ Mill! 3個月 粘著力 760 890 590 680 730 40°C 結晶 無 >fnr 無 >fnT Μ： 4nt 6個月 粘著力 740 790 620 690 750 第 5表：安定性試驗結果（比較例 1〜4) 比較例1 比較例2 比較例3 比較例4 初期 結晶 dnt 挑 Μ ^\\\ 無 並 j\\\ (製造即後）粘著力 2340 1780 2540 1520 40°C 結晶 有 有 有 有 1個月 粘著力 1580 320 410 280 40°C 結晶 有 有 有 有 3個月 粘著力 1460 380 340 250 40°C 結晶 有 有 有 有 6個月 粘著力 1390 350 390 280 -12- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注音？事項再填寫本頁) 訂· 經濟部智慧財產局員工消費合作社印製 1267386 A7 B7 12 五、發明說明（ 過性試驗來評價藥物透過性。 方法： (請先閱讀背面之注音？事項再填寫本頁) 將裸鼠各組6隻在腹部皮膚用外科刀及剪切取，固定 在接受器側裝滿生理食鹽水之豎形擴散池，其護套內循 環約3 5 °C之溫水。 各裸鼠之皮膚上貼實施例6或7之貼劑後之2, 4, 6, 8及24小時經時採樣接受器液，將之藥物透過量以 HPLC定量。 結果： 就各實施例之貼劑，將藥物之透過量列在如第7表。 第7表 實施例 6之貼著劑：硫酸砂路布達磨之鼠皮膚透過性 試驗（各小時藥物透過量）（// g/cm2) 小時 0 2 4 6 8 24 透過量 0 2.17 3.18 5.56 7.29 20.9 實施例7之貼著劑：鹽酸普羅布拉諾羅之鼠皮膚透過 性試驗（各小時藥物透過量）（// g/cm2) 小時 0 2 4 6 8 24 透過量 0 2.4 1 9.84 19.27 25.82 59.76 經濟部智慧財產局員工消費合作社印製 由第7表之結果得知，本發明實施例之貼劑爲皮膚透 過性高，藥物釋放性佳之貼劑。 產業上之利用可能性 如上所述，本發明之使用以苯乙烯-異戊二烯-苯乙 儲嵌段共聚物，賦粘樹脂，抗氧化劑，羊毛脂及水爲必要 14- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） 1267386 A7 _B7 13 五、發明說明（） 成分之含水性熱融型粘著劑膏體之外用貼劑兼具經時 優異之藥物安定性及藥物釋放性，且粘著力不下降之 優異製劑。於這種含水性熱融型粘著劑中配合配合經 皮吸收性藥物之貼劑爲尤其在醫療上優異之製劑。 (請先閱讀背面之注意事項再填寫本頁) · ϋ I ·ϋ · ---•訂--------- 經濟部智慧財產局員工消費合作社印製 LI — — — — — — · _ ·1 %| ϋ ϋ ! ϋ — 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） ο 申請曰期 案 號 ^ f 類 別 以上各欄由本局填註） Α4 C4 1267386,, d1/! *) β (2006年08月07日修正) ||墨專利説明書 中 文 發明 新型 名稱 外用貼劑用之含水性熱融型粘著劑膏體 其製造方法及外用貼劑 英 文 HYDROUS HOT MELT TYPE BINDER PASTE, METHOD FOR PREPARING IT AND AN EXTERNAL E，LA..S.X£J?__ 姓 名 國 川地敏邦 裝 發明 創作 人 住、居所 姓 名 (名稱） 日本 香川縣大川郡大內町三殿136-104 帝國製藥股份有限公司 (帝國製藥株式會社） 訂 經濟部智慧財產局員工消費合作社印製 線 國 籍 申請人 住、居所 (事務所） 代表人 姓 名 日本 香川縣大川郡大內町三本松567番地 赤澤庄三 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 1267386, invention description (please read the note on the back and then fill the weight of the weight of the page, the same below), especially 1 5~2 Ο %, if less than 1 ο %, can not maintain the cohesive force of the adhesive, prone to occur Remnant paste; if it exceeds 25%, the adhesive paste becomes hard and difficult to knead, and becomes a paste with low adhesion. The tackifying resin used in the external patch of the present invention may be an aromatic resin, an aliphatic resin, an alicyclic petroleum resin, a rosin fat, a rosin ester, an anthraquinone resin, etc., and the compounding amount thereof is preferably 15 to 35%, particularly preferably 20~ 30%, if less than 15%, it is not easy to exhibit adhesiveness, cohesiveness is reduced, and residual paste is liable to occur; and if it exceeds 35%, the adhesive paste becomes hard and difficult to knead, and becomes a paste with low adhesion. The antioxidant used in the external patch of the present invention is for preventing the oxidative degradation during the kneading of the adhesive and during the preservation of the product, and may be, for example, dibutylhydroxytoluene or pentaerythritol-肆[3- (3,5). -Di-tert-butyl-4-hydroxyphenyl)propionate, tocopherol acetate, etc., this antioxidant should be combined with 0 · 1 ~ 2 % 〇 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed lanolin used in the present invention It has the function of retaining moisture in the adhesive and also acts as a softener for the adhesive. The blending amount depends on the balance of the combined amount of water and other softeners, liquid rubber and other softeners, preferably 5 to 4 0 %, especially 1 0~3 0 %, if it is less than 5%, it can not maintain moisture stability; if it exceeds 40%, the adhesive is not suitable for paste. The water used in the present invention is a solution for dissolving a drug and imparting a cooling sensation to the paste. The amount of the mixture is determined by the balance between the amount of the main drug and the amount of the lanolin, and is preferably 1 to 30%, particularly preferably 1 to 2 0. %, if it is less than 0 · 1%, it does not match the purpose of the cooperation; if it exceeds 30%, it is not suitable to maintain the necessary properties of the adhesive. -6_ This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) Printed by the Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative 1267386 A7 ________Β7___ V. Invention Description (7) Prescription adhesive paste. The mat is made of a ketone-treated polyester film, and the base fabric is woven with polyester fiber. The amount of the adhesive paste applied was 100 g/m 2 〇 Table 1: Adhesive Paste of Examples 1 to 5 Prescription Material Name Example No. 1 2 3 4 5 SIS 14.0 18.0 16.0 17.0 16.0 Grease Ring saturated petroleum resin 25.0 Rosin ester resin 22.0 Tantalum resin 24.0 25.0 24.0 Polybutene 7.0 19.0 6.0 Liquid paraffin 13.0 6.0 17.0 8.5 Polyethylene glycol-400 10.0 5.0 Dibutylhydroxytoluene 1.0 1.0 1.0 1.0 1.0 Lanolin 24.0 25.0 10.0 10.0 25.0 Refined water 9.0 9.0 1.0 1.0 9.0 Refined water (for dissolution of main drug) 1.0 1.0 1.0 1.0 1.0 Diisopropanolamine 5.0 5.0 5.0 5.0 10.0 Crotstate East 2.5 2.5 2.5 2.5 2.5 BPAA 5.0 5.0 5.0 5.0 5.0 1- Sterol 0.5 0.5 0.5 0.5 0.5 isopropyl myristate 5.0 Comparative Examples 1 to 4 The hot-melt adhesive without moisture and the commercially available acrylate-based adhesive paper scale are applicable to the Chinese National Standard (CNS) A4 specification ( 210 X 297 mm) (Please read the precautions on the back and fill out this page) ip- # 1267386 Description of the invention (The external preparation for the preparation of the agent, the respective comparison examples are as follows. Table 2. Table 2 · Comparative Example 1~4, Duyan丨暮鹛南卡材料名_Comparative Example No. 1 2 3 4 SIS 18.0 20.0 Tantalum resin 29.0 31.0 Polybutene 15.0 15.0 Liquid paraffin----- 9.0 15.0 Polyethylene glycol-400 5.0 5.0 5.0 5.0 Dibutoxyl Toluene 1.0 1.0 Commercially available acrylate A 72.0 Commercially available acrylate B 72.0 Lanolin 10.0 10.0 10.0 Diisopropanolamine 5.0 5.0 5.0 5.0 Crothonia East 2.5 2.5 2.5 2.5 BPAA 5.0 5.0 5.0 5.0 1-decyl alcohol 0.5 0.5 0.5 0.5 (Please read the note on the back and fill out this page) 0 I ϋ I -II Booking·! 1111 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing % However, commercially available acrylate adhesive A uses acrylic acid-2- Ethylhexyl ester j-vinyl acetate copolymer, commercially available acrylate-based adhesive B is a copolymer of propylene tert-butyl-2-ethylhexyl ester-ethylpyrrolidone. I Test Example 1: Drug Inducing Vortex Gastric Cliff Life] Using a commercially available BPAA-containing aqueous patch as a control, the in vitro skin permeability test was carried out to evaluate drug penetration in the above-mentioned examples and comparative examples. . ! II -ίο- ! This paper size applies to China National Standard (CNS) A4 specification (210 X 297 public) 1267386 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed A7 B7 V. Invention description (9) Method: Will nude mice The abdominal skin is surgically cut and cut, and fixed in a vertical diffusion tank filled with physiological saline on the receiving side, and a warm water of about 35 ° C is circulated in the sheath. After the various drugs were applied to the skin of the nude mice, the receiver solution was sampled over time, and the drug permeation amount after 24 hours was quantified by HPLC.糸吉果: The results are as shown in Table 3, and the commercially available BPAA-containing aqueous patch has a dialysis excess of 66.0/zg/cm 2 . Table 3: Mouse Skin Permeability Test Results Adhesive Example 1 Example 2 Example 3 Example 4 Example 5 Permeation amount / / g / cm 2 58.2 74.6 62.4 81.5 65.8 Adhesive No. Comparative Example 1 Comparative Example 2 Comparison Example 3 Comparative Example 4 Permeation amount / / g / cm 2 29.8 21.5 43.7 3 1.6 As a result of the third table, the patch of the embodiment of the present invention has higher skin permeability and drug than the patch of the comparative example. Release is preferred. Test Example 2: Stabilizer test The patch of the above-mentioned example and the patch of the comparative example were respectively placed in a polyethylene-aluminum bag, and stored at 40 ° C for 6 months, and the presence or absence of crystal precipitation from the preparation was examined. As a result, although the crystal of the patch of the example was not precipitated, the patch of the comparative example precipitated crystals in the first month, and was not peeled off from the mat or the adhesion was extremely lowered. No decrease in the main drug content was observed in all the formulations. -11- This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) -I ϋ ϋ ϋ ϋ f. ϋ ^ ϋ ϋ -II ^ ϋ II ϋ . One-0, I ϋ ^ ϋ ϋ ϋ II ϋ ϋ 1.— II —.1 ϋ J ^ ^1 1— I ^ II ϋ II ϋ IHI · (Please read the phonetic note on the back first and then fill out this page) 1267386 A7 V. Description of invention (1G) After the preservation and stability, the presence or absence of crystal precipitation of the patch, and the measurement results of the adhesion force are shown in Tables 4 and 5 below. The adhesion was measured as 1 80 ° peeling of the electric board, and the unit was g/2 5 匪. Table 4: Stability test results (: sinus application examples 1 to 5) Example 1 Example 2 Example 3 Example 4 Example 5 Initial crystallization Μ > fnrr Provocation ^\\\ Μ 1II γ (Manufacture After) Adhesion 780 890 540 690 750 40°C Crystalline Μ >fml /fnT Μ No Μ j\\\ 1 month adhesion 750 870 610 710 770 40°C Crystalline Μ and Μ Mill! 3 months adhesion 760 890 590 680 730 40°C crystallization no > fnr no > fnT Μ: 4nt 6 months adhesion 740 790 620 690 750 Table 5: Stability test results (Comparative Examples 1 to 4) Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Initial Crystallization dnt Provocation ^\\\ No and j\\\ (Made in and after) Adhesion 2340 1780 2540 1520 40°C Crystallization There is a 1 month adhesion 1580 320 410 280 40 °C Crystallization has 3 months adhesion 1460 380 340 250 40 °C Crystallization has 6 months adhesion 1390 350 390 280 -12- This paper scale applies to China National Standard (CNS) A4 specifications ( 210 X 297 mm) (Please read the phonetic notes on the back first? Then fill out this page) Property Bureau Staff Consumer Cooperative Printed 1267386 A7 B7 12 V. Invention Description (Over-test to evaluate drug permeability. Method: (Please read the phonetic on the back? Please fill out this page again) Place 6 nude mice in each group The skin is surgically cut and cut, and fixed in a vertical diffusion tank filled with physiological saline on the receiving side, and the jacket is circulated with warm water of about 35 ° C. The skin of each nude mouse is attached with the embodiment 6 or The receptor liquid was sampled over 2, 4, 6, 8 and 24 hours after the patch of 7 and the drug permeation amount was quantified by HPLC. Results: For the patches of the respective examples, the amount of drug permeation was listed as Table 7. The adhesion agent of Example 6 of Table 7: Skin permeability test of sulphate sandpaper Dharma (permeation of drug per hour) (//g/cm2) hour 0 2 4 6 8 24 Permeation amount 0 2.17 3.18 5.56 7.29 20.9 Adhesive of Example 7: Skin permeability test of probronol hydrochloride (drug permeation per hour) (//g/cm2) hours 0 2 4 6 8 24 Permeation amount 0 2.4 1 9.84 19.27 25.82 59.76 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed by the seventh table That result, the patch of the embodiment of the present invention embodiments through the high-permeability, good release of the drug is a skin patch. INDUSTRIAL APPLICABILITY As described above, the use of the present invention is styrene-isoprene-phenethyl block copolymer, tackifying resin, antioxidant, lanolin and water as necessary. China National Standard (CNS) A4 Specification (210 X 297 mm) 1267386 A7 _B7 13 V. INSTRUCTIONS () Ingredients Water-containing hot-melt adhesive paste Externally applied patch and excellent drug stability over time And an excellent preparation that has drug release properties and does not decrease in adhesion. A patch containing a transdermally absorbable drug in such a water-containing hot-melt adhesive is a medically excellent preparation. (Please read the note on the back and then fill out this page) · ϋ I ·ϋ · ---•订--------- Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed LI — — — — — — · _ ·1 %| ϋ ϋ ! ϋ — This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) ο Application for the case number ^ f Category above the column is filled by this Bureau) Α 4 C4 1267386 ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, HYDROUS HOT MELT TYPE BINDER PASTE, METHOD FOR PREPARING IT AND AN EXTERNAL E,LA..SX£J?__ Name Kawasaki Minami-ken, invention, creator, residence name (name) Sanno-cho, Okawa-gun, Kagawa-gun, Kagawa Prefecture, Japan 136-104 Imperial Pharmaceutical Co., Ltd. (Imperial Pharmaceutical Co., Ltd.) Ministry of Economic Affairs, Intellectual Property Office, Employees, Consumer Cooperatives, Printing Line, Nationality Applicant, Residence, Office (Office) Representative Name, San Bensong, 567, Ogawa-gun, Ogawa-gun, Kagawa Prefecture, Japan Akazawa Zhuang San This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) 1267386
五、發明説明（5) 本發明之外用貼劑所用藥物只要爲能經皮吸收之水 溶性藥物則無特定，可爲如消炎止痛劑、降血壓劑、利 尿劑、抗過敏劑、抗氣喘劑、冠狀動脈舒張劑、支氣 管舒張劑、/3遮斷藥等。 其中消炎止痛劑可爲如柳酸甲酯、柳酸乙二醇、吲 口朵美他辛、酮普羅芬、氟必普羅芬、依布普羅芬、二 氯非納克鈉、美非納酸、氟非納酸、依布非納克、阿 氯非納克、羅奇索普羅芬、吡咯奇西甘、納普羅奇 仙，噚普羅畊、史林達克、非路必納克（4 -聯苯基乙 酸，以下稱BPAA )等。 降血壓劑可爲如克羅尼啶、鹽酸克羅尼啶、阿貼諾 維、普羅布拉諾羅、鹽酸普羅布拉諾羅（propranolol hydrochloride)、鹽酸尼卡奇平、普氟拉諾羅、酒石酸 美多普羅路、卡不多普力路、茚羅路、尼巴奇平等。 利尿劑可爲如乙醯達唑醯胺、嵌列酸鉀、氯大利 酮、螺內酯、三氯美噻疊氮等。 抗過敏劑可爲如鹽酸二芬氫胺、鹽酸西普羅庚烷、 鹽酸全氯西克力啶、富馬酸克列馬斯丁、馬來酸氯非 尼拉民、美奇達阱等。 抗氣‘喘劑（止咳劑）可爲如鹽酸麻黃素、鹽酸甲基麻黃 素、檸檬酸戊氧基別林、氫溴酸右旋美多芳、硫酸對 布達松、鹽酸異丙貼列醇等。 冠狀動脈舒張劑可爲如***油、硝化乙二醇、硝 酸異山梨醇、二吡噠磨、磨利西多民等。 -7- 1267386 fl r)t] 五、發明説明（6 ) 支氣管舒張劑可爲如鹽酸三甲氧對苯二酚、鹽酸原 兒茶酚、鹽酸麻布貼羅、硫酸砂路布達磨（salbutamol sulfate)、茶驗、注羅布貼羅等。 此外，本發明之粘著劑中又可依所望而配合吸收促 進劑、淸涼劑、防腐劑、殺菌劑、顏料等。 本發明之外用貼劑可用如上述粘著劑成分而依如下 方法製造。例如在約1 5 0 °C加熱之捏合機中將S I S、賦 粘樹脂、抗氧化劑、羊毛脂及軟化劑熔融捏合成粘著 劑後·以空冷或水冷使粘著劑之溫度冷卻至約9 0 °C。然 後徐徐添加加熱之水及主藥溶液（含水），混合攪拌 所得粘著劑膏體以規定厚度塗在墊子而貼上基布後，裁 斷成所欲大小之製品。 或將上述粘著劑一旦在另外容器製造作成粘著劑塊， 將必要量在約9 0 °C熔融，與水其主藥溶液混合攪拌。 添加含水主藥溶液和水時之粘著劑溫度超過1 〇〇。(：， 則水分蒸發激烈，製品中殘存之水分顯著下降而析出主 藥之結晶等；又若不滿80°C，則粘著劑成分固化，粘性過 高而難攪拌，成分之分散不充分。故主藥溶液添加混合 時之製造溫度須80°C以上，l〇〇°C以下。 實施例 下面詳細說明實施例，但本發明不限於此，依本文適 當變更處方均屬本發明之技術範圍。 實施例1〜5 有效成分選擇消炎止痛藥BP A A，依如下第！表所示V. DESCRIPTION OF THE INVENTION (5) The drug used for the external patch of the present invention is not particularly specific as long as it is a water-soluble drug capable of percutaneous absorption, and may be, for example, an anti-inflammatory analgesic agent, a blood pressure lowering agent, a diuretic, an anti-allergic agent, and an anti-asthmatic agent. Coronary artery relaxant, bronchodilator, /3 amputation, etc. The anti-inflammatory analgesic agent may be, for example, methyl salicylate, salicylic acid glycol, ditopolacin, ketoprofen, flurbiprofen, ebprofen, diclofenac sodium, melibina , flufenamic acid, ibbufenac, aclofenac, roche soprofen, pyrrolizine, naprochis, 噚 罗 耕, 斯林达克, 非路必纳克 (4 -biphenylacetic acid, hereinafter referred to as BPAA). The blood pressure lowering agent may be, for example, clonidine, clonidine hydrochloride, atropinide, probranoro, propranolol hydrochloride, nicardipine hydrochloride, and prevalanol. , tartaric acid, Medopoulu, Kadido Puli Road, Miluo Road, Nibaki equal. The diuretic may be, for example, acetazolamide, potassium acetate, clodrolixone, spironolactone, trichloromethazine azide or the like. The antiallergic agent may be, for example, diphenhydramine hydrochloride, ciprofen hydrochloride, perchlorhexidine hydrochloride, klemastatin fumarate, chlorpheniramine maleate, Mickey trap, and the like. Anti-gas 'asthma (cough suppressant) can be ephedrine hydrochloride, methyl ephedrine hydrochloride, valeroxy citrate, dextromethorphan hydrobromide, bundazone sulfate, isopropyl sulfate Sticking alcohol and the like. The coronary relaxant may be, for example, nitroglycerin, nitroethylene glycol, isosorbide nitrate, dipyridamole, and silliman. -7- 1267386 fl r)t] V. Description of the invention (6) The bronchodilator can be, for example, trimethoxy hydroquinone hydrochloride, protocatechol hydrochloride, sulphate hydrochloride, salbutamol sulfate , tea inspection, note Luo Bu Luo and so on. Further, in the adhesive of the present invention, an absorption enhancer, a cooling agent, a preservative, a bactericide, a pigment or the like can be blended as desired. The external patch of the present invention can be produced by the following method using the above-mentioned adhesive component. For example, after the SIS, the tackifying resin, the antioxidant, the lanolin and the softener are melt-kneaded into an adhesive in a kneader heated at about 150 ° C, the temperature of the adhesive is cooled to about 9 by air cooling or water cooling. 0 °C. Then, the heated water and the main drug solution (aqueous) are slowly added, and the obtained adhesive paste is applied to the mat with a predetermined thickness and attached to the base fabric, and then cut into a desired size. Alternatively, once the above-mentioned adhesive is produced as an adhesive block in another container, the necessary amount is melted at about 90 ° C, and the main drug solution is mixed with water and stirred. The temperature of the adhesive when adding the aqueous main drug solution and water exceeds 1 〇〇. (:, the water evaporates rapidly, the water remaining in the product is remarkably lowered to precipitate the crystal of the main drug, and if it is less than 80 ° C, the adhesive component is solidified, the viscosity is too high, the stirring is difficult, and the dispersion of the component is insufficient. Therefore, the manufacturing temperature of the main drug solution to be mixed and mixed must be 80 ° C or more, l ° ° C or less. EXAMPLES Hereinafter, the examples are described in detail, but the present invention is not limited thereto, and the prescriptions are appropriately changed according to the present invention. Examples 1 to 5 Active ingredients The anti-inflammatory analgesic BP AA was selected as shown in the following table!
1267386 五、發明説明（11 ) 實施例6及7 : 含有硫酸砂路布達磨（salbuta mol sulfate)及鹽酸普 羅布拉諾羅（ProPrano101 hydrochl〇ride)之外用貼劑1267386 V. INSTRUCTIONS (11) Examples 6 and 7: Patches containing salbuta mol sulfate and Probrano 101 hydrochl〇ride
選擇支氣管舒張劑硫酸砂路布達磨，及作爲狹心症治 療用/3遮斷劑鹽酸普羅布拉諾羅，依如下第6表所示處 方製造粘著劑膏體。墊子採用經矽酮處理之聚酯膜，基 布採用聚酯纖維織布。粘著劑膏體之塗布量均爲 1 0 0 g/m 2 。 第6表：比較例6及7之粘著劑膏體處方 原料名 實施例6 實施例7 SIS 22.0 20.0 脂環族飽和石油樹脂 25.0 25.0 聚丁烯 8.0 7.0 羥脂 20.0 25.0 聚乙二醇-400 3.0 3.0 克羅他尼東 2.0 2.0 二丁羥基甲苯 1.0 1.0 十六酸二乙酯 3.0 齡 油酸 - 1.0 精製水 10.0 10.0 硫酸砂路布達磨（活性成分） 6.0 讎 鹽酸普羅布拉諾羅（活性成分） - 6.0 試驗例3 :藥物透過性試驗The bronchodilator sulfuric acid sandbinder was selected, and as a treatment for the treatment of the nucleus/3, the probronol hydrochloride was prepared, and the adhesive paste was prepared as shown in the following Table 6. The mat was treated with a ketone-treated polyester film, and the base fabric was woven with polyester fiber. The amount of the adhesive paste applied was 100 g/m 2 . Table 6: Adhesive Paste of Comparative Examples 6 and 7 Prescription Material Name Example 6 Example 7 SIS 22.0 20.0 Cycloaliphatic saturated petroleum resin 25.0 25.0 Polybutene 8.0 7.0 Hydroxyl ester 20.0 25.0 Polyethylene glycol-400 3.0 3.0 Crotstate East 2.0 2.0 Dibutylhydroxytoluene 1.0 1.0 Diethyl hexadecanate 3.0 Age oleic acid - 1.0 Refined water 10.0 10.0 Sulfuric acid sand road Buda mill (active ingredient) 6.0 普Probranol hydrochloride (active Ingredients) - 6.0 Test Example 3: Drug permeability test
就前述實施例6及7所得外用貼劑，實行體外皮膚透 -13-The external patch obtained in the foregoing Examples 6 and 7 was subjected to in vitro skin permeation- 13-