本發明之一實施形態為一種經皮吸收製劑，其係具備藥物貯留層、黏著劑層及支持體者，上述藥物貯留層具有第1及第2主面，含有藥物；上述黏著劑層設置於上述藥物貯留層之上述第1主面側，含有包含聚有機矽氧烷之矽酮黏著劑；支持體以覆蓋上述藥物貯留層之側面及上述第2主面之方式形成；且上述矽酮黏著劑之含量相對於上述黏著劑層之總質量為20質量%以上，作為經皮吸收製劑整體之透濕度為20 g/m2
・24 hr以上且314 g/m2
・24 hr以下。 本發明之一實施形態之經皮吸收製劑其作為經皮吸收製劑整體之透濕度為20 g/m2
・24 hr以上且314 g/m2
・24 hr以下。作為經皮吸收製劑整體之透濕度之下限值並無特別限定，可為25、30、35、40或100 g/m2
・24 hr。作為經皮吸收製劑整體之透濕度之上限值並無特別限定，可為150、200、250或300 g/m2
・24 hr。 藥物貯留層為含有經皮投予之藥物之層。 藥物貯留層之面積可考慮到藥物量及貼附時間等而任意設定，例如為3～150 cm2
之範圍，較佳為10～100 cm2
之範圍，更佳為10～50 cm2
之範圍。又，藥物貯留層之厚度並無特別限定，就可含有能夠於製劑之貼附期間發揮充分之治療效果之量的藥物、易製造性及製劑強度等方面而言，較佳為25～1000 μm，更佳為50～500 μm，進而較佳為75～250 μm。 藥物只要為能夠經皮投予者則並無特別限定，越為比較容易產生皮膚刺激之藥物，則越容易顯現出本發明之皮膚刺激減輕效果。作為比較容易產生皮膚刺激之藥物，例如可列舉：奧昔布寧、阿塞那平、比索洛爾、利培酮、煙鹼及西酞普蘭等。除此之外，作為比較容易產生皮膚刺激之藥物，可列舉：吲哚美辛、酮洛芬、水楊酸甲酯、水楊酸乙二醇酯、雙氯芬酸鈉、氟比洛芬、聯苯乙酸、美洛昔康及洛索洛芬鈉等非類固醇性消炎鎮痛藥，雌二醇、炔諾酮及雌三醇等激素藥，可多替芬等抗組織胺藥，美金剛、利凡斯的明、多奈哌齊、加蘭他敏等抗阿茲海默症藥，舍曲林、氟西汀、帕羅西汀、氟伏沙明等抗抑鬱藥，替普瑞酮等胃潰瘍治療劑，托特羅定及素立芬新等膀胱過動症治療劑，妥布特羅等支氣管擴張藥，羅替戈汀等帕金森氏病治療劑以及美托洛爾等降血壓劑等。藥物可自例如由奧昔布寧、阿塞那平、比索洛爾、西酞普蘭、雙氯芬酸鈉、美金剛、利凡斯的明、多奈哌齊、加蘭他敏、氟西汀、帕羅西汀、托特羅定及羅替戈汀所組成之群中進行選擇。 藥物貯留層中所包含之藥物可以溶解狀態、飽和狀態、過飽和結晶狀態或分散狀態含有於藥物貯留層中。 藥物貯留層中所包含之藥物之含量之下限值並無特別限定，相對於藥物貯留層之總質量可為1、5、10、15、20、30或40質量%。若為上述下限值以上，則易於獲得藥物之充分之皮膚滲透性。藥物貯留層中所包含之藥物之含量之上限值並無特別限定，相對於藥物貯留層之總質量可為50、60、70、80或85質量%。若為上述上限值以下，則易於確保足以維持藥物貯留層形狀之強度。關於藥物貯留層中所包含之藥物之含量，例如相對於藥物貯留層之總質量可為1～90質量%，亦可為15～85質量%。 藥物貯留層亦可含有乙基纖維素。藉由藥物貯留層含有乙基纖維素，而即便暴露於皮膚應用部位處之發汗及環境中之水分等，藥物貯留層亦能夠維持凝集性，減輕由膨脹破壞所導致之皮膚刺激。藥物貯留層中所包含之乙基纖維素之含量之下限值並無特別限定，相對於藥物貯留層之總質量可為20、25、30、35、40或50質量%。若為上述下限值以上，則易於維持藥物貯留層之凝集性。藥物貯留層中所包含之乙基纖維素之含量之上限值並無特別限定，相對於藥物貯留層之總質量可為70、80、90、95或99質量%。關於藥物貯留層中所包含之乙基纖維素之含量，例如相對於藥物貯留層之總質量可為40～99質量%。 藥物貯留層亦可含有丙烯酸系基劑。藉由藥物貯留層含有丙烯酸系基劑，而即便暴露於皮膚應用部位處之發汗及環境中之水分等，藥物貯留層亦能夠維持凝集性，減輕由膨脹破壞所導致之皮膚刺激。藥物貯留層中所包含之丙烯酸系基劑之含量之下限值並無特別限定，相對於藥物貯留層之總質量可為20、25、30、35、40或50質量%。若為上述下限值以上，則易於維持藥物貯留層之凝集性。藥物貯留層中所包含之丙烯酸系基劑之含量之上限值並無特別限定，相對於藥物貯留層之總質量可為70、80、90、95或99質量%。關於藥物貯留層中所包含之丙烯酸系基劑之含量，例如，相對於藥物貯留層之總質量可為40～99質量%。 作為藥物貯留層中所包含之丙烯酸系基劑，適宜使用烷基之碳數為4～18之(甲基)丙烯酸烷基酯之均聚物或共聚物、或者上述(甲基)丙烯酸烷基酯與其他官能性單體之共聚物。再者，所謂(甲基)丙烯酸意指丙烯酸或甲基丙烯酸。 作為藥物貯留層中所包含之丙烯酸系基劑，較佳為丙烯酸酯共聚物。丙烯酸酯共聚物可自由不具有官能基之丙烯酸酯共聚物、具有羥基之丙烯酸酯共聚物及具有羧基之丙烯酸酯共聚物以及該等之組合所組成之群中進行選擇。 作為不具有官能基之丙烯酸酯共聚物，例如可列舉：Duro-tak(註冊商標，Henkel Corporation)87-9900、Duro-tak(註冊商標)87-9301及GELVA(註冊商標)GMS 3083等。 作為具有羥基之丙烯酸酯共聚物，例如可列舉丙烯酸2-羥基乙酯等丙烯酸羥基烷基酯。上述丙烯酸羥基烷基酯進而可經鹵素原子、烷基、烯基、炔基等取代。作為具有羥基之丙烯酸酯共聚物，例如可列舉：Duro-tak(註冊商標)87-2516、GELVA(註冊商標)GMS 788及GELVA(註冊商標)GMS 737等。 作為具有羧基之丙烯酸酯共聚物，可列舉含有丙烯酸之丙烯酸酯共聚物。作為與丙烯酸進行共聚合之單體成分，只要為能夠與丙烯酸進行共聚合者，則無特別限制，例如可列舉：丙烯酸甲酯、丙烯酸2-乙基己酯等丙烯酸酯；二甲基丙烯醯胺、𠰌啉丙烯醯胺等丙烯醯胺；乙酸乙烯酯；乙烯醇；苯乙烯等。與丙烯酸進行共聚合之單體成分可為單獨1種，亦可為2種以上。作為具有羧基之丙烯酸酯共聚物，例如可列舉：Duro-tak(註冊商標)87-2194、Duro-tak(註冊商標)87-2852及GELVA(註冊商標)GMS 753等。 藥物貯留層只要能夠維持藥物貯留層之凝集性即可，亦可含有除藥物及乙基纖維素以外之其他成分。所謂其他成分，並無特別限定，例如可列舉：藥物之穩定劑、塑化劑、溶解劑、經皮吸收促進劑及油脂等。 穩定劑只要為於經皮吸收製劑中可確認到穩定作用之化合物即可，並無特別限定，例如可列舉：生育酚類、抗壞血酸類、二丁基羥基甲苯、亞硫酸氫鈉及乙二胺四乙酸鹽等。 塑化劑只要為於經皮吸收製劑中可確認到塑化作用之化合物即可，並無特別限定，例如可列舉：液態石蠟、液狀聚丁烯、液狀聚異戊二烯及酯化油類等。 溶解劑只要為對藥物具有溶解作用之化合物即可，並無特別限定，經皮吸收促進劑亦只要為於經皮吸收製劑中可確認到吸收促進作用之化合物，則無特別限定。作為溶解劑及吸收促進劑，例如可列舉：碳鏈數6～20之脂肪酸、脂肪族醇、脂肪酸酯、脂肪酸醯胺、脂肪酸醚類、芳香族系有機酸、芳香族系醇、芳香族系有機酸酯、芳香族系有機酸醚(以上飽和或不飽和皆可，環狀、直鏈狀或支鏈狀皆可)、乳酸酯類、乙酸酯類、單萜系化合物、倍半萜系化合物、氮酮(Azone)、氮酮衍生物、吡咯硫代癸烷、甘油脂肪酸酯類、丙二醇脂肪酸酯類、山梨醇酐脂肪酸酯類(Span系)、聚山梨糖醇酯系(Tween系)、聚乙二醇脂肪酸酯類、聚氧乙烯氫化蓖麻油系(HCO系)、聚氧乙烯烷基醚類、蔗糖脂肪酸酯類及植物油等。具體而言，可列舉：月桂醇、肉豆蔻醇、油醇、異硬脂醇、癸二酸二乙酯、甘油單癸酸酯、甘油單月桂酸酯、甘油單油酸酯、山梨醇酐單月桂酸酯、丙二醇單月桂酸酯、聚氧乙烯月桂醚、吡咯硫代癸烷及肉豆蔻酸異丙酯等。 黏著劑層為設置於藥物貯留層之與皮膚接觸側之第1主面側，發揮防止藥物貯留層直接與皮膚接觸之作用之層。 黏著劑層之面積只要為藥物貯留層之面積以上，則並無特別限定，為了確實地使覆蓋藥物貯留層之支持體得到固定，較佳為面積較藥物貯留層更寬大。黏著劑層之厚度並無特別限定，可任意設定。 黏著劑層含有包含聚有機矽氧烷之矽酮黏著劑。藉由黏著劑層含有包含聚有機矽氧烷之矽酮黏著劑，經皮吸收製劑之透濕度提高。 作為聚有機矽氧烷，例如可使用Dow Corning公司之BIO-PSA 7-4202及BIO-PSA 7-4302等市售品。 矽酮黏著劑中之聚有機矽氧烷之含量之下限值並無特別限定，可為40、50、60、70、80或90質量%。矽酮黏著劑中之聚有機矽氧烷之含量之上限值並無特別限定，可為80、90、95或100質量%。 矽酮黏著劑之含量相對於黏著劑層之總質量為20質量%以上。矽酮黏著劑之含量之下限值相對於黏著劑層之總質量可為30、35或40質量%。矽酮黏著劑之含量之上限值並無特別限定，相對於黏著劑層之總質量可為60、70、80、90或100質量%。 黏著劑層除了含有矽酮黏著劑，較佳為進而含有包含選自由苯乙烯-異戊二烯-苯乙烯嵌段共聚物、黏著賦予樹脂及塑化劑所組成之群中之1種以上之化合物之黏著基劑，更佳為進而含有包含選自由苯乙烯-異戊二烯-苯乙烯嵌段共聚物、黏著賦予樹脂及塑化劑所組成之群中之2種以上之化合物之黏著基劑，進而較佳為進而含有包含苯乙烯-異戊二烯-苯乙烯嵌段共聚物、黏著賦予樹脂及塑化劑之黏著基劑。藉由進而含有上述黏著基劑，能夠提高經皮吸收製劑之皮膚滲透持續性。 上述黏著基劑中之苯乙烯-異戊二烯-苯乙烯嵌段共聚物之含量之下限值並無特別限定，相對於上述黏著基劑之總質量可為1、5、10或20質量%。又，上述黏著基劑中之苯乙烯-異戊二烯-苯乙烯嵌段共聚物之含量之上限值並無特別限定，相對於黏著基劑之總質量可為60、70、80、90或95質量%。 黏著賦予樹脂只要為具有提高黏著力之作用之化合物，則並無特別限定，例如可列舉：脂環族飽和烴樹脂(例如荒川化學工業之Alcon P-100)、松香衍生物(例如松香、松香甘油酯、氫化松香及氫化松香甘油酯)、萜烯樹脂(例如Yasuhara Chemical之Clearon P-125)、脂肪族系烴樹脂(例如Nippon Zeon之Quintone B170)及順丁烯二酸樹脂等。上述黏著基劑中之黏著賦予樹脂之含量之下限值並無特別限定，相對於上述黏著基劑之總質量可為5、10、20、30或40質量%。又，上述黏著基劑中之黏著賦予樹脂之含量之上限值並無特別限定，相對於黏著基劑之總質量可為60、70、80、90或95質量%。 塑化劑如上所述。上述黏著基劑中之塑化劑之含量之下限值並無特別限定，相對於上述黏著基劑之總質量可為1、5、10或20質量%。又，上述黏著基劑中之塑化劑之含量之上限值並無特別限定，相對於黏著基劑之總質量可為60、70、80、90或95質量%。 上述黏著基劑之含量之下限值並無特別限定，相對於黏著劑層之總質量可為5、10、20、30或40質量%。又，上述黏著基劑之含量之上限值並無特別限定，相對於黏著劑層之總質量可為60、70、80、90或95質量%。 於包含上述黏著基劑之情形時，黏著劑層中之矽酮黏著劑與上述黏著基劑之含量之比率可為1：4～7：3，亦可為3：7～7：3。若為上述比率，則存在維持經皮吸收製劑之良好之透濕度，並且提高皮膚滲透持續性之傾向。 黏著劑層亦可進而含有(甲基)丙烯酸酯共聚物。關於(甲基)丙烯酸酯共聚物，例如作為主要單體，可列舉(甲基)丙烯酸之C4～C20烷基酯及(甲基)丙烯酸羥基C4～C20烷基酯等。作為(甲基)丙烯酸酯共聚物之共聚單體，可列舉：(甲基)丙烯酸之C4～C20烷基酯、(甲基)丙烯酸羥基C4～C20烷基酯、(甲基)丙烯酸、乙酸乙烯酯及乙烯基吡咯啶酮等。 黏著劑層亦可含有上述黏著劑及黏著基劑以外之其他成分。所謂其他成分，只要為經皮吸收製劑中廣泛使用者，則並無特別限定，例如可列舉穩定劑等。 支持體為保持藥物貯留層之層。 支持體之面積並無特別限定，可任意設定。支持體之厚度並無特別限定，例如為1～3000 μm，較佳為1～1000 μm，更佳為50～500 μm，進而較佳為100～250 μm。 支持體包含具有不會因藥物貯留層中之藥物等之移行等而膨潤之性質的片材。作為支持體之材質，例如可列舉：聚酯(PET等)、聚烯烴(聚乙烯及聚丙烯等)及聚胺基甲酸酯等。 作為支持體之性狀，例如可列舉：膜、不織布、織布、針織布及多孔質片材等。於支持體為布狀之情形時，亦可實施撥水處理。其原因在於：藉由對支持體進行撥水處理，而存在使藥物貯留層所吸收之環境中之水分等減少，減輕藥物貯留層之膨潤之傾向。作為撥水處理，例如可列舉利用矽酮系撥水劑、氟樹脂系撥水劑、石蠟撥水劑、鋯化合物系撥水劑、伸乙脲系撥水劑、羥甲基醯胺系撥水劑及脂肪族系撥水劑等所進行之處理。 作為支持體之材質及性狀，較佳為PET膜與PET不織布之層壓膜(以下稱作PET/不織布層壓膜)、聚胺基甲酸酯製膜、乙烯-乙酸乙烯酯共聚物膜，更佳為經撥水處理之PET針織布。支持體例如可自由經撥水處理之PET針織布、乙烯-乙酸乙烯酯共聚物膜、PET/不織布層壓膜、聚胺基甲酸酯製不織布、聚胺基甲酸酯製膜及PET膜所組成之群中進行選擇。又，就提高經皮吸收製劑之透濕度之觀點而言，支持體較佳為自由經撥水處理之PET針織布、乙烯-乙酸乙烯酯共聚物膜、聚胺基甲酸酯製不織布及聚胺基甲酸酯製膜所組成之群中進行選擇。進而，就防止藥物之浸透之觀點而言，支持體更佳為經撥水處理之PET針織布或乙烯-乙酸乙烯酯共聚物膜。再者，此處所謂藥物之浸透係指因外部環境所帶來之水分而導致藥物自支持體側脫離之現象。 本發明之經皮吸收製劑可進而經覆蓋材料覆蓋，或者進而積層覆蓋材料。 覆蓋材料由支持體、與積層於其單面之黏著劑層所構成。覆蓋材料包括覆蓋本發明之經皮吸收製劑並固定於皮膚者、及進而積層於經皮吸收製劑者。覆蓋材料例如可用於在藥物之投予期間維持經皮吸收製劑之狀態以及保護經皮吸收製劑遠離由外部環境所帶來之水分(淋浴等)等。 覆蓋材料之支持體較佳為具備適當之強度、透濕性及耐水性等者，較佳為選自聚酯(PET等)、聚烯烴(聚乙烯及聚丙烯等)及聚胺基甲酸酯等中。 作為覆蓋材料之支持體之性狀，例如可列舉：膜(較佳為胺基甲酸酯膜)、不織布、織布、針織布及多孔質片材等，就促進將經皮吸收製劑應用於皮膚時產生之汗等水分之揮發之方面而言，較佳為布狀，更佳為針織布。於支持體為布狀之情形時，為了提高其防水性，可實施撥水處理。作為撥水處理，例如可列舉利用矽酮系撥水劑、氟樹脂系撥水劑、石蠟撥水劑、鋯化合物系撥水劑、伸乙脲系撥水劑、羥甲基醯胺系撥水劑及脂肪族系撥水劑等所進行之處理。 覆蓋材料之黏著劑層於覆蓋經皮吸收製劑並固定於皮膚者之情形時，具備用以將經皮吸收製劑固定於皮膚之接著性，於進而積層於經皮吸收製劑之情形時，具備用以接著於經皮吸收製劑之接著性。覆蓋材料較佳為進而具備良好之透濕性。 作為覆蓋材料之黏著劑層中所含有之黏著基劑，例如可列舉：丙烯酸系黏著劑、矽酮黏著劑及橡膠系黏著劑等。作為丙烯酸系黏著劑，例如可列舉含有(甲基)丙烯酸酯共聚物者。關於(甲基)丙烯酸酯共聚物，例如作為主要單體，可列舉(甲基)丙烯酸之C4～C20烷基酯及(甲基)丙烯酸羥基C4～C20烷基酯等。作為(甲基)丙烯酸酯共聚物之共聚單體，可列舉：(甲基)丙烯酸之C4～C20烷基酯、(甲基)丙烯酸羥基C4～C20烷基酯、(甲基)丙烯酸、乙酸乙烯酯及乙烯基吡咯啶酮等。 作為矽酮黏著劑，例如可列舉聚二甲基矽氧烷等。 作為橡膠系黏著劑，例如可列舉：聚異丁烯(PIB)、聚異戊二烯及苯乙烯-異戊二烯-苯乙烯嵌段共聚物(SIS)等。 覆蓋材料之黏著劑層亦可含有上述黏著劑以外之其他成分。所謂其他成分，只要為經皮吸收製劑中廣泛使用者即可，並無特別限定，例如可列舉：黏著賦予樹脂、塑化劑及穩定劑等。 覆蓋材料可與經皮吸收製劑分開提供，於施用經皮吸收製劑時合併使用，亦可以預先與經皮吸收製劑接合之形態提供。 本發明之經皮吸收製劑之黏著劑層或覆蓋材料之黏著劑層亦可由用以於應用於皮膚之前保護黏著劑層之層，例如由包含剝離襯墊之層覆蓋。 關於剝離襯墊，例如可列舉：聚酯(PET等)、聚氯乙烯、聚偏二氯乙烯、尼龍及聚烯烴(聚乙烯及聚丙烯等)等膜，道林紙及玻璃紙等紙，道林紙或者玻璃紙等與聚烯烴之層壓膜等。 剝離襯墊可藉由於與黏著劑層接觸之面塗佈矽酮樹脂或氟樹脂等而實施易剝離處理。 剝離襯墊亦可由複數個斷片形成。又，剝離襯墊至少為能夠覆蓋經皮吸收製劑之黏著劑層或覆蓋材料之黏著劑層其整體的大小，亦可延伸至較各黏著劑層之外側。 作為本發明之經皮吸收製劑等之基本製造方法，例如可列舉如下方法。 經皮吸收製劑之製造例 秤取藥物等並混合，將所得者藉由添加溶劑或進行熔融等方法使其流化而製成片狀後，藉由去除溶劑等使其固化，裁剪成適宜形狀，藉此獲得藥物貯留層。其次，對藥物貯留層進行加熱使其軟化後接合至支持體。 藉由常規方法於剝離襯墊上形成含有矽酮黏著劑之黏著劑層後，於黏著劑層上積層藥物貯留層，裁剪成適宜形狀而獲得經皮吸收製劑。 成為覆蓋材料之片材係藉由如下方式獲得：藉由常規方法於剝離襯墊上形成黏著劑層後，於黏著劑層積層支持體，裁剪成適宜形狀。 於由覆蓋材料覆蓋經皮吸收製劑之情形時，自覆蓋材料片材剝離去除剝離襯墊，於所露出之覆蓋材料片材之黏著劑層之黏著面接合經皮吸收製劑之支持體層，根據需要裁剪成適宜形狀。進而於由剝離襯墊被覆經皮吸收製劑之黏著劑層之情形時，根據需要剝離去除附著於經皮吸收製劑之剝離襯墊，轉而由剝離襯墊被覆覆蓋材料片材之黏著面側，使其片材化後，裁剪成適宜形狀。 [實施例] [試驗1] 黏著劑層之基劑組成之比較 作為黏著劑層之基劑，針對以特定比率含有包含聚有機矽氧烷之矽酮系黏著劑、與包含苯乙烯-異戊二烯-苯乙烯嵌段共聚物(SIS)、黏著賦予樹脂及塑化劑之黏著基劑(以下亦表示為「含SIS之黏著基劑」)的經皮吸收製劑(實施例1～7及比較例1)，比較透濕度及藥物之皮膚滲透持續性。 實施例1～7及比較例1之製造 關於藥物貯留層，秤取比索洛爾40質量%及乙基纖維素60質量%，添加適量溶劑(甲醇)進行溶解，而獲得塗佈液。將塗佈液塗佈於剝離襯墊上，乾燥去除溶劑，而獲得厚度為150 g/m2
之片材。將該片材裁剪成圓形(38 cm2
)，而獲得藥物貯留層。秤取表1之各成分，添加適量溶劑(甲苯或乙酸乙酯)進行溶解，而獲得塗佈液。將塗佈液塗佈於剝離襯墊上，乾燥去除溶劑，而獲得厚度為75 g/m2
之黏著劑層。於黏著劑層上接合藥物貯留層，剝離去除藥物貯留層之剝離襯墊，於所露出之面積層支持體(經撥水處理之PET針織布)，以藥物貯留層為大致中心裁剪成圓形(38 cm2
)，而獲得經皮吸收製劑。 [表1]
評價方法 (1)透濕度試驗方法 關於經皮吸收製劑之透濕度，根據由JIS Z 0208：1976所規定之防潮包裝材料之透濕度試驗方法(杯式法)，測定於溫度：40±0.5℃、相對濕度：90±2%下之水分之滲透速度(MVTR)g/m2
・24 hr。 透濕度試驗之評價基準 ◎：透濕度為40 g/m2
・24 hr以上＝透濕度較高，幾乎不會對皮膚產生刺激 ○：透濕度為20 g/m2
・24 hr以上～未達40 g/m2
・24 hr＝透濕度稍高，不易對皮膚產生刺激 ×：透濕度未達20 g/m2
・24 hr＝透濕度較低，容易對皮膚產生刺激 (2)體外(in vitro)人皮膚滲透試驗方法 於人皮膚切片之角質層側貼附經皮吸收製劑(應用面積3 cm2
)，以皮膚真皮側為受體槽側之方式，將皮膚切片安裝於使32℃之溫水循環而保溫之流出型擴散槽中。其次，於受體槽中裝滿磷酸鹽緩衝液，一面以一定流速進行置換，一面每隔6小時自受體槽採集溶液直至168小時後。藉由高效液相層析法測定所採集之溶液中之藥物(比索洛爾)濃度。 其次，根據濃度測定值而算出各時段所滲透之藥物量，求出各時段藥物之皮膚滲透速度(μg/cm2
/hr)。進而，作為表現藥物之皮膚滲透持續性之指標，用168小時後之皮膚滲透速度Jlast
除以最大皮膚速度Jmax
而算出Jlast
/Jmax
值。若Jlast
/Jmax
值較大，則表示藥物之皮膚滲透持續性較高。 體外人皮膚滲透試驗之評價基準 ◎：Jlast
/Jmax
值為0.60以上 ○：Jlast
/Jmax
值為0.30以上且未達0.60 ×：Jlast
/Jmax
值未達0.30 實施例1～7及比較例1之評價結果 [表2]
若黏著劑層中之包含聚有機矽氧烷之矽酮系黏著劑之比率增加，則可見經皮吸收製劑之透濕度增強之傾向。藥物之皮膚滲透持續性隨著包含聚有機矽氧烷之矽酮系黏著劑之比率增加而稍有下降，但仍維持充分值。實施例1～7、尤其實施例2～7之經皮吸收製劑其透濕度及藥物之皮膚滲透持續性皆比較良好。 再者，將實施例1及4之藥物貯留層中之比索洛爾分別變更為奧昔布寧、阿塞那平、西酞普蘭、雙氯芬酸鈉、美金剛、利凡斯的明、多奈哌齊、加蘭他敏、氟西汀、帕羅西汀、托特羅定及羅替戈汀之經皮吸收製劑亦透濕度及藥物之皮膚滲透持續性皆比較良好。 [試驗2] 經皮吸收製劑之支持體之比較 針對使用經撥水處理之PET針織布、乙烯-乙酸乙烯酯共聚物膜、PET/不織布層壓膜、聚胺基甲酸酯製不織布或聚胺基甲酸酯製膜作為支持體之經皮吸收製劑(實施例8～12)，比較透濕度。又，針對使用經撥水處理之PET針織布、乙烯-乙酸乙烯酯共聚物膜或PET膜作為支持體之經皮吸收製劑(實施例8～9及29)、及未積層支持體之經皮吸收製劑(比較例2)，比較防藥物浸透性。 實施例8～12、29及比較例2之製造 關於藥物貯留層，秤取比索洛爾40質量%及乙基纖維素60質量%，藉由與試驗1中所記載之方法相同之方法而製得。關於黏著劑層，秤取包含聚有機矽氧烷之矽酮系黏著劑100質量%，藉由與試驗1中所記載之方法相同之方法而製得。於黏著劑層上接合藥物貯留層，剝離去除藥物貯留層之剝離襯墊，於所露出之面積層表3之支持體(比較例2中不積層支持體)，以藥物貯留層為大致中心裁剪成圓形(38 cm2
)，而獲得經皮吸收製劑。 [表3]
評價方法 (1)透濕度試驗方法 關於經皮吸收製劑之透濕度，根據由JIS Z 0208：1976所規定之防潮包裝材料之透濕度試驗方法(杯式法)，測定於溫度：40±0.5℃、相對濕度：90±2%下之水分之滲透速度(MVTR)g/m2
・24 hr。 透濕度試驗之評價基準 ◎：透濕度為40 g/m2
・24 hr以上＝透濕度較高，幾乎不會對皮膚產生刺激 ○：透濕度為20 g/m2
・24 hr以上～未達40 g/m2
・24 hr＝透濕度稍高，不易對皮膚產生刺激 ×：透濕度未達20 g/m2
・24 hr＝透濕度較低，容易對皮膚產生刺激 實施例8～12之評價結果 [表4]
由此可見，使用PET針織布(撥水處理)、乙烯-乙酸乙烯酯共聚物膜、聚胺基甲酸酯製不織布及聚胺基甲酸酯製膜作為支持體之經皮吸收製劑存在透濕度較高之傾向。 (2)防藥物浸透性試驗方法 將實施例8～9、29及比較例2之經皮吸收製劑之支持體側浸沒於900 mL之水中，靜置15分鐘後，測定水分中之藥物含有率。 防藥物浸透性之評價基準 ○：幾乎未確認到藥物自支持體側之浸透。 ×：確認到藥物自支持體側之浸透。 實施例8～9、29及比較例2之評價結果 [表5]
由此可見，使用PET針織布(撥水處理)、乙烯-乙酸乙烯酯共聚物膜及PET膜作為支持體之經皮吸收製劑存在防藥物浸透性較高之傾向。 [試驗3] 藥物貯留層之比較 針對藥物貯留層中含有乙基纖維素(EC)、丙烯酸系基劑或羥丙基纖維素(HPC)之經皮吸收製劑(實施例13～28)，比較藥物貯留層之凝集性。 實施例13～28之製造 秤取表6之各成分，藉由與試驗1中所記載之方法相同之方法獲得藥物貯留層。 秤取包含聚有機矽氧烷之矽酮系黏著劑100質量%(BIO-PSA 7-4202/BIO-PSA 7-4302＝50/50)，藉由與試驗1中所記載之方法相同之方法獲得黏著劑層。 於黏著劑層上接合藥物貯留層，剝離去除藥物貯留層之剝離襯墊，於所露出之面積層支持體(PET/不織布層壓膜)，以藥物貯留層為大致中心裁剪成近似正方形(13.4 cm2
)，而獲得經皮吸收製劑。 [表6]
凝集性之評價方法 準備含有瓊脂2質量%之膠貼，剝離去除上述所得之實施例13～28之經皮吸收製劑之黏著劑層之剝離襯墊，以所露出之黏著面與膠貼接觸之方式於膠貼上積層經皮吸收材，靜置24小時。自膠貼剝離經皮吸收製劑，使經皮吸收製劑之黏著面上所附著之水分風乾後，藉由指觸黏性法，根據以下基準而評價藥物貯留層之凝集性。 凝集性之評價基準 ○：藥物貯留層未出現凝集破壞 △：藥物貯留層略有凝集破壞 ×：藥物貯留層出現凝集破壞 實施例13～28之評價結果 [表7]
於含有HPC作為藥物貯留層之基劑之實施例21～23之經皮吸收製劑中，藥物貯留層因水分而膨潤，將經皮吸收製劑自膠貼剝離時可見藥物貯留層出現凝集破壞之傾向。 另一方面，於含有乙基纖維素作為藥物貯留層之基劑之實施例13～20之經皮吸收製劑、含有丙烯酸系基劑作為藥物貯留層之基劑之實施例24～28中，可見藥物貯留層之凝集破壞經抑制、凝集性得以維持之傾向。尤其於實施例13～17、19～20及24～28之經皮吸收製劑中，藥物貯留層未出現凝集破壞，凝集性良好。One embodiment of the present invention is a percutaneously absorbable preparation comprising a drug storage layer, an adhesive layer, and a support. The drug storage layer has first and second main surfaces and contains a drug; the adhesive layer is provided on The first main surface side of the drug storage layer contains a silicone adhesive containing polyorganosiloxane; the support is formed to cover the side surface of the drug storage layer and the second main surface; and the silicone is adhered The content of the agent is 20% by mass or more relative to the total mass of the adhesive layer, and the moisture permeability of the entire transdermal absorption preparation is 20 g/m 2 ·24 hr or more and 314 g/m 2 ·24 hr or less. The transdermal absorption preparation of one embodiment of the present invention has a moisture permeability of 20 g/m 2 ·24 hr or more and 314 g/m 2 ·24 hr as the entire transdermal absorption preparation. The lower limit of the moisture permeability of the entire transdermal absorption preparation is not particularly limited, and it may be 25 , 30, 35, 40, or 100 g/m 2 · 24 hr. The upper limit of the moisture permeability of the entire transdermal absorption preparation is not particularly limited, and may be 150, 200 , 250, or 300 g/m 2 · 24 hr. The drug storage layer is a layer containing drugs administered percutaneously. The area of the drug storage layer can be arbitrarily set in consideration of the amount of drug and the application time, etc., for example, the range is 3 to 150 cm 2 , preferably 10 to 100 cm 2 , more preferably 10 to 50 cm 2 . In addition, the thickness of the drug storage layer is not particularly limited. In terms of the amount of the drug that can exhibit a sufficient therapeutic effect during the application of the preparation, the ease of manufacturability and the strength of the preparation, it is preferably 25 to 1000 μm. , More preferably 50-500 μm, still more preferably 75-250 μm. The drug is not particularly limited as long as it can be administered transdermally. The more easily a drug that causes skin irritation, the easier it is to exhibit the skin irritation reduction effect of the present invention. Examples of drugs that are relatively prone to skin irritation include oxybutynin, asenapine, bisoprolol, risperidone, nicotine, and citalopram. In addition, as drugs that are more prone to skin irritation, include: indomethacin, ketoprofen, methyl salicylate, ethylene glycol salicylate, diclofenac sodium, flurbiprofen, biphenyl Non-steroidal anti-inflammatory analgesics such as acetic acid, meloxicam and loxoprofen sodium, hormones such as estradiol, norethindrone and estriol, antihistamines such as codotifen, memantine, rivan Anti-Alzheimer's drugs such as stigmine, donepezil, and galantamine, antidepressants such as sertraline, fluoxetine, paroxetine, fluvoxamine, treatment agents for gastric ulcer such as teprenone, Todt Therapeutic agents for overactive bladder such as Rodine and Surifenxin, bronchodilators such as tobuterol, therapeutic agents for Parkinson's disease such as rotigotine, and blood pressure lowering agents such as metoprolol. The drug can be selected from, for example, oxybutynin, asenapine, bisoprolol, citalopram, diclofenac sodium, memantine, rivastigmine, donepezil, galantamine, fluoxetine, paroxetine, tropoxetine Choose from the group consisting of Terodine and Rotigotine. The drug contained in the drug storage layer may be contained in the drug storage layer in a dissolved state, a saturated state, a supersaturated crystalline state, or a dispersed state. The lower limit of the content of the drug contained in the drug storage layer is not particularly limited, and may be 1, 5, 10, 15, 20, 30, or 40% by mass relative to the total mass of the drug storage layer. If it is more than the above lower limit, it is easy to obtain sufficient skin permeability of the drug. The upper limit of the content of the drug contained in the drug storage layer is not particularly limited, and may be 50, 60, 70, 80, or 85% by mass relative to the total mass of the drug storage layer. If it is less than the above upper limit, it is easy to ensure the strength sufficient to maintain the shape of the drug storage layer. Regarding the content of the drug contained in the drug storage layer, for example, it may be 1 to 90% by mass, or 15 to 85% by mass relative to the total mass of the drug storage layer. The drug storage layer may also contain ethyl cellulose. Since the drug storage layer contains ethyl cellulose, even if it is exposed to sweating at the skin application site and moisture in the environment, the drug storage layer can maintain agglomeration and reduce skin irritation caused by swelling and destruction. The lower limit of the content of ethyl cellulose contained in the drug storage layer is not particularly limited, and can be 20, 25, 30, 35, 40, or 50% by mass relative to the total mass of the drug storage layer. If it is more than the above lower limit, it is easy to maintain the agglutinating property of the drug storage layer. The upper limit of the content of ethyl cellulose contained in the drug storage layer is not particularly limited, and may be 70, 80, 90, 95, or 99% by mass relative to the total mass of the drug storage layer. Regarding the content of ethyl cellulose contained in the drug storage layer, for example, it may be 40 to 99% by mass relative to the total mass of the drug storage layer. The drug storage layer may also contain an acrylic base. Since the drug storage layer contains an acrylic base, even if it is exposed to sweating at the skin application site and moisture in the environment, the drug storage layer can maintain agglomeration and reduce skin irritation caused by swelling and destruction. The lower limit of the content of the acrylic base contained in the drug storage layer is not particularly limited, and it can be 20, 25, 30, 35, 40, or 50% by mass relative to the total mass of the drug storage layer. If it is more than the above lower limit, it is easy to maintain the agglutinating property of the drug storage layer. The upper limit of the content of the acrylic base contained in the drug storage layer is not particularly limited, and may be 70, 80, 90, 95, or 99% by mass relative to the total mass of the drug storage layer. Regarding the content of the acrylic base contained in the drug storage layer, for example, it may be 40 to 99% by mass relative to the total mass of the drug storage layer. As the acrylic base contained in the drug storage layer, a homopolymer or copolymer of alkyl (meth)acrylate having 4 to 18 carbon atoms in the alkyl group, or the above-mentioned alkyl (meth)acrylate Copolymer of ester and other functional monomers. In addition, the so-called (meth)acrylic acid means acrylic acid or methacrylic acid. The acrylic base contained in the drug storage layer is preferably an acrylate copolymer. The acrylate copolymer can be selected from the group consisting of an acrylate copolymer without a functional group, an acrylate copolymer with a hydroxyl group, an acrylate copolymer with a carboxyl group, and combinations thereof. As an acrylate copolymer having no functional group, for example, Duro-tak (registered trademark, Henkel Corporation) 87-9900, Duro-tak (registered trademark) 87-9301, GELVA (registered trademark) GMS 3083, and the like can be cited. Examples of acrylate copolymers having a hydroxyl group include hydroxyalkyl acrylates such as 2-hydroxyethyl acrylate. The above-mentioned hydroxyalkyl acrylate may be further substituted with a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, and the like. Examples of the acrylate copolymer having a hydroxyl group include Duro-tak (registered trademark) 87-2516, GELVA (registered trademark) GMS 788, and GELVA (registered trademark) GMS 737. As the acrylate copolymer having a carboxyl group, an acrylate copolymer containing acrylic acid can be cited. The monomer component to be copolymerized with acrylic acid is not particularly limited as long as it can be copolymerized with acrylic acid. Examples include acrylic acid esters such as methyl acrylate and 2-ethylhexyl acrylate; dimethyl acrylate Allylamines such as amines and pyridine acrylamides; vinyl acetate; vinyl alcohol; styrene, etc. The monomer component to be copolymerized with acrylic acid may be one type alone or two or more types. Examples of the acrylate copolymer having a carboxyl group include Duro-tak (registered trademark) 87-2194, Duro-tak (registered trademark) 87-2852, and GELVA (registered trademark) GMS 753. The drug storage layer only needs to be able to maintain the agglutinating properties of the drug storage layer, and may also contain other ingredients besides the drug and ethyl cellulose. The other components are not particularly limited, and examples include drug stabilizers, plasticizers, solubilizers, transdermal absorption enhancers, and oils and fats. The stabilizer is not particularly limited as long as it is a compound whose stabilizing effect can be confirmed in the transdermal absorption preparation, and examples thereof include tocopherols, ascorbic acids, dibutylhydroxytoluene, sodium bisulfite, and ethylenediamine Tetraacetate and so on. The plasticizer is not particularly limited as long as it is a compound whose plasticizing effect can be confirmed in the transdermal absorption preparation, and examples include liquid paraffin, liquid polybutene, liquid polyisoprene, and esterification. Oil etc. The dissolving agent is not particularly limited as long as it is a compound having a dissolving effect on the drug, and the transdermal absorption enhancer is not particularly limited as long as it is a compound whose absorption promoting effect can be confirmed in the transdermal absorption preparation. Examples of dissolving agents and absorption promoters include: fatty acids with 6 to 20 carbon chains, aliphatic alcohols, fatty acid esters, fatty acid amides, fatty acid ethers, aromatic organic acids, aromatic alcohols, aromatics Organic acid esters, aromatic organic acid ethers (the above are saturated or unsaturated, cyclic, linear or branched), lactates, acetates, monoterpenoids, sesquiterpenes Series compounds, azone (Azone), azone derivatives, pyrrole thiodecane, glycerin fatty acid esters, propylene glycol fatty acid esters, sorbitan fatty acid esters (Span series), polysorbate esters (Tween series) ), polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oil series (HCO series), polyoxyethylene alkyl ethers, sucrose fatty acid esters and vegetable oils. Specifically, examples include: lauryl alcohol, myristyl alcohol, oleyl alcohol, isostearyl alcohol, diethyl sebacate, glycerol monocaprate, glycerol monolaurate, glycerol monooleate, sorbitol anhydride Monolaurate, propylene glycol monolaurate, polyoxyethylene lauryl ether, pyrrole thiodecane and isopropyl myristate, etc. The adhesive layer is a layer provided on the first main surface side of the skin contact side of the drug storage layer, and plays a role of preventing the drug storage layer from directly contacting the skin. The area of the adhesive layer is not particularly limited as long as it is greater than the area of the drug storage layer. In order to securely fix the support covering the drug storage layer, the area is preferably larger than the drug storage layer. The thickness of the adhesive layer is not particularly limited and can be set arbitrarily. The adhesive layer contains a silicone adhesive containing polyorganosiloxane. Since the adhesive layer contains a silicone adhesive containing polyorganosiloxane, the moisture permeability of the transdermal absorption preparation is improved. As the polyorganosiloxane, for example, commercially available products such as BIO-PSA 7-4202 and BIO-PSA 7-4302 of Dow Corning can be used. The lower limit of the polyorganosiloxane content in the silicone adhesive is not particularly limited, and it can be 40, 50, 60, 70, 80, or 90% by mass. The upper limit of the polyorganosiloxane content in the silicone adhesive is not particularly limited, and it can be 80, 90, 95 or 100% by mass. The content of the silicone adhesive is 20% by mass or more relative to the total mass of the adhesive layer. The lower limit of the content of the silicone adhesive can be 30, 35 or 40% by mass relative to the total mass of the adhesive layer. The upper limit of the content of the silicone adhesive is not particularly limited, and it can be 60, 70, 80, 90 or 100% by mass relative to the total mass of the adhesive layer. In addition to the silicone adhesive, the adhesive layer preferably further contains one or more selected from the group consisting of styrene-isoprene-styrene block copolymers, adhesion-imparting resins and plasticizers The adhesive base of the compound, more preferably, further contains an adhesive base containing two or more compounds selected from the group consisting of styrene-isoprene-styrene block copolymers, adhesion-imparting resins and plasticizers The agent preferably further contains an adhesive base containing a styrene-isoprene-styrene block copolymer, an adhesion imparting resin, and a plasticizer. By further containing the above-mentioned adhesive base, the skin penetration durability of the transdermal absorption preparation can be improved. The lower limit of the content of the styrene-isoprene-styrene block copolymer in the adhesive base is not particularly limited, and it can be 1, 5, 10 or 20 mass relative to the total mass of the adhesive base %. In addition, the upper limit of the content of the styrene-isoprene-styrene block copolymer in the adhesive base is not particularly limited, and it can be 60, 70, 80, 90 relative to the total mass of the adhesive base. Or 95% by mass. The adhesion-improving resin is not particularly limited as long as it is a compound that has the effect of improving adhesion. Examples include: alicyclic saturated hydrocarbon resin (such as Alcon P-100 from Arakawa Chemical Industry), rosin derivatives (such as rosin, rosin) Glycerides, hydrogenated rosin, and hydrogenated rosin glycerides), terpene resins (for example, Clearon P-125 from Yasuhara Chemical), aliphatic hydrocarbon resins (for example, Quintone B170 from Nippon Zeon) and maleic acid resins. The lower limit of the content of the adhesion-imparting resin in the adhesive base is not particularly limited, and may be 5, 10, 20, 30, or 40% by mass relative to the total mass of the adhesive base. Moreover, the upper limit of the content of the adhesion-imparting resin in the adhesive base is not particularly limited, and can be 60, 70, 80, 90, or 95% by mass relative to the total mass of the adhesive base. The plasticizer is as described above. The lower limit of the content of the plasticizer in the adhesive base is not particularly limited, and it can be 1, 5, 10, or 20% by mass relative to the total mass of the adhesive base. In addition, the upper limit of the content of the plasticizer in the adhesive base is not particularly limited, and can be 60, 70, 80, 90, or 95% by mass relative to the total mass of the adhesive base. The lower limit of the content of the adhesive base is not particularly limited, and it can be 5, 10, 20, 30, or 40% by mass relative to the total mass of the adhesive layer. In addition, the upper limit of the content of the adhesive base is not particularly limited, and it can be 60, 70, 80, 90, or 95% by mass relative to the total mass of the adhesive layer. In the case of containing the above-mentioned adhesive base, the ratio of the content of the silicone adhesive in the adhesive layer to the above-mentioned adhesive base may be 1:4-7:3, or 3:7-7:3. If it is the above ratio, there is a tendency to maintain the good moisture permeability of the transdermal absorption preparation and increase the durability of skin penetration. The adhesive layer may further contain a (meth)acrylate copolymer. Regarding the (meth)acrylate copolymer, for example, as main monomers, C4-C20 alkyl esters of (meth)acrylic acid and hydroxy C4-C20 alkyl esters of (meth)acrylic acid can be cited. As the comonomers of (meth)acrylate copolymers, examples include: (meth)acrylic acid C4-C20 alkyl esters, (meth)acrylic hydroxy C4-C20 alkyl esters, (meth)acrylic acid, and acetic acid Vinyl ester and vinyl pyrrolidone etc. The adhesive layer may also contain components other than the above-mentioned adhesive and adhesive base. The other components are not particularly limited as long as they are widely used in transdermal absorption preparations, and examples thereof include stabilizers. The support is the layer that holds the drug storage layer. The area of the support is not particularly limited and can be set arbitrarily. The thickness of the support is not particularly limited. For example, it is 1 to 3000 μm, preferably 1 to 1000 μm, more preferably 50 to 500 μm, and still more preferably 100 to 250 μm. The support includes a sheet having the property of not being swollen due to migration of drugs and the like in the drug storage layer. Examples of the material of the support include polyester (PET, etc.), polyolefin (polyethylene, polypropylene, etc.), and polyurethane. Examples of the properties of the support include films, non-woven fabrics, woven fabrics, knitted fabrics, and porous sheets. When the support is cloth-shaped, water repellent treatment can also be implemented. The reason is that by water-repellent treatment of the support, there is a tendency to reduce the moisture in the environment absorbed by the drug storage layer and reduce the swelling of the drug storage layer. As the water repellent treatment, for example, the use of silicone water repellents, fluororesin water repellents, paraffin water repellents, zirconium compound water repellents, urea-based water repellents, and methylolamide-based water repellents can be cited. Treatment of water and aliphatic water repellents. The material and properties of the support are preferably a laminate film of PET film and PET nonwoven fabric (hereinafter referred to as PET/nonwoven fabric laminate film), polyurethane film, ethylene-vinyl acetate copolymer film, More preferably, it is a PET knitted fabric with water repellent treatment. Supports such as PET knitted fabrics, ethylene-vinyl acetate copolymer films, PET/non-woven fabric laminate films, polyurethane non-woven fabrics, polyurethane films and PET films that can be freely treated with water repellency Choose from the group. In addition, from the viewpoint of increasing the moisture permeability of the transdermal absorption preparation, the support is preferably a PET knitted fabric freely subjected to water repellent treatment, an ethylene-vinyl acetate copolymer film, a non-woven fabric made of polyurethane, and a poly Choose from the group of urethane films. Furthermore, from the viewpoint of preventing penetration of the drug, the support is more preferably a water-repellent treated PET knitted fabric or an ethylene-vinyl acetate copolymer film. Furthermore, the so-called penetration of the drug here refers to the phenomenon that the drug is detached from the side of the support due to the moisture brought by the external environment. The transdermal absorption preparation of the present invention may be further covered with a covering material, or a covering material may be further laminated. The covering material is composed of a support and an adhesive layer laminated on one side of the support. Covering materials include those covering the transdermal absorption preparation of the present invention and fixing it to the skin, and those that are further laminated on the transdermal absorption preparation. The covering material can be used, for example, to maintain the state of the transdermal absorption preparation during the administration of the drug and to protect the transdermal absorption preparation from moisture (shower, etc.) brought by the external environment. The support of the covering material is preferably one with appropriate strength, moisture permeability, water resistance, etc., preferably selected from polyester (PET, etc.), polyolefin (polyethylene and polypropylene, etc.) and polyurethane Ester etc. The properties of the support of the covering material include, for example, films (preferably urethane films), non-woven fabrics, woven fabrics, knitted fabrics, and porous sheets, which promote the application of transdermal absorption preparations to the skin In terms of the volatilization of moisture such as sweat generated from time to time, it is preferably cloth-like, and more preferably knitted cloth. When the support is cloth-like, in order to improve its waterproofness, water-repellent treatment can be implemented. As the water repellent treatment, for example, the use of silicone water repellents, fluororesin water repellents, paraffin water repellents, zirconium compound water repellents, urea-based water repellents, and methylolamide-based water repellents can be cited. Treatment of water and aliphatic water repellents. The adhesive layer of the covering material has adhesiveness to fix the transdermal absorption preparation to the skin when it covers the transdermal absorption preparation and fixes it to the skin, and when it is further laminated on the transdermal absorption preparation, it has the In order to adhere to the percutaneous absorption preparation. The covering material preferably further has good moisture permeability. Examples of the adhesive base contained in the adhesive layer of the covering material include acrylic adhesives, silicone adhesives, and rubber-based adhesives. Examples of acrylic adhesives include those containing (meth)acrylate copolymers. Regarding the (meth)acrylate copolymer, for example, as main monomers, C4-C20 alkyl esters of (meth)acrylic acid and hydroxy C4-C20 alkyl esters of (meth)acrylic acid can be cited. As the comonomers of (meth)acrylate copolymers, examples include: (meth)acrylic acid C4-C20 alkyl esters, (meth)acrylic hydroxy C4-C20 alkyl esters, (meth)acrylic acid, and acetic acid Vinyl ester and vinyl pyrrolidone etc. As a silicone adhesive, polydimethylsiloxane etc. are mentioned, for example. Examples of rubber-based adhesives include polyisobutylene (PIB), polyisoprene, and styrene-isoprene-styrene block copolymer (SIS). The adhesive layer of the covering material may also contain other ingredients besides the above-mentioned adhesive. The other components are not particularly limited as long as they are widely used in transdermal absorption preparations, and examples thereof include adhesion-imparting resins, plasticizers, stabilizers, and the like. The covering material can be provided separately from the transdermal absorption preparation, and used in combination when the transdermal absorption preparation is applied, or it can be provided in the form of being combined with the transdermal absorption preparation in advance. The adhesive layer of the transdermal absorption preparation of the present invention or the adhesive layer of the covering material may also be covered by a layer for protecting the adhesive layer before application to the skin, for example, a layer containing a release liner. For release liners, for example, films such as polyester (PET etc.), polyvinyl chloride, polyvinylidene chloride, nylon and polyolefins (polyethylene and polypropylene, etc.), paper such as forest paper and cellophane, etc. Laminated films such as forest paper or cellophane and polyolefin. The release liner can be easily peeled off by coating silicone resin or fluororesin on the surface in contact with the adhesive layer. The release liner can also be formed from a plurality of pieces. In addition, the release liner is at least the size that can cover the adhesive layer of the transdermal absorbent preparation or the adhesive layer of the covering material as a whole, and it may extend to the outside of each adhesive layer. As a basic manufacturing method of the percutaneous absorption preparation etc. of this invention, the following methods are mentioned, for example. Manufacturing example of transdermal absorption preparations Weigh and mix medicines, etc., fluidize the obtained by adding a solvent or melting to form a sheet, then solidify by removing the solvent, etc., and cut into a suitable shape , Thereby obtaining the drug storage layer. Next, the drug storage layer is heated to soften it and then joined to the support. After forming an adhesive layer containing a silicone adhesive on the release liner by a conventional method, a drug storage layer is laminated on the adhesive layer and cut into a suitable shape to obtain a transdermal absorption preparation. The sheet used as the covering material is obtained by forming the adhesive layer on the release liner by a conventional method, and then laminating the support on the adhesive layer and cutting it into a suitable shape. When the transdermal absorption preparation is covered by the covering material, the release liner is peeled off from the covering material sheet, and the support layer of the transdermal absorption preparation is joined to the adhesive surface of the adhesive layer of the exposed covering material sheet, as required Cut into suitable shapes. Furthermore, when the adhesive layer of the transdermal absorption preparation is covered by the release liner, the release liner attached to the transdermal absorption preparation is peeled off as necessary, and the adhesive surface side of the covering material sheet is covered by the release liner instead. After making it into a sheet, it is cut into a suitable shape. [Example] [Experiment 1] Comparison of the base composition of the adhesive layer As the base of the adhesive layer, a silicone-based adhesive containing polyorganosiloxane and styrene-isoamyl containing at a specific ratio Diene-styrene block copolymer (SIS), adhesion-imparting resin and plasticizer adhesive base (hereinafter also referred to as "SIS-containing adhesive base") transdermal absorption preparation (Examples 1-7 and Comparative example 1) compares the moisture permeability and the persistence of drug skin penetration. Production of Examples 1 to 7 and Comparative Example 1 Regarding the drug storage layer, 40% by mass of bisoprolol and 60% by mass of ethyl cellulose were weighed, and an appropriate amount of solvent (methanol) was added to dissolve to obtain a coating liquid. The coating liquid was applied to the release liner, and the solvent was removed by drying to obtain a sheet with a thickness of 150 g/m 2 . The sheet was cut into a circle (38 cm 2 ) to obtain a drug storage layer. Each component in Table 1 was weighed out, and an appropriate amount of solvent (toluene or ethyl acetate) was added to dissolve to obtain a coating liquid. The coating liquid is applied on the release liner, and the solvent is removed by drying to obtain an adhesive layer with a thickness of 75 g/m 2 . Join the drug storage layer on the adhesive layer, peel off the release liner to remove the drug storage layer, and cut the exposed area layer support (water-repellent PET knitted fabric) into a circle with the drug storage layer as the center (38 cm 2 ) to obtain a transdermal absorption preparation. [Table 1] Evaluation method (1) Moisture permeability test method Regarding the moisture permeability of transdermal absorption preparations, the moisture permeability test method for moisture-proof packaging materials (cup method) specified by JIS Z 0208:1976 is measured at temperature: 40±0.5℃ , Relative humidity: Moisture penetration rate (MVTR) g/m 2 ·24 hr under 90±2%. Evaluation criteria for the moisture permeability test ◎: The moisture permeability is 40 g/m 2 ·24 hr or more = The moisture permeability is high, and it hardly irritates the skin ○: The moisture permeability is 20 g/m 2 ·24 hr or more ~ not reached 40 g/m 2 · 24 hr = slightly higher moisture permeability, less irritation to the skin ×: less than 20 g/m 2 · 24 hr = low moisture permeability, easy to irritate the skin (2) In vitro (in in vitro) Human skin penetration test method. A transdermal absorption preparation (application area 3 cm 2 ) is attached to the stratum corneum side of a human skin slice, and the dermal side of the skin is the receptor groove side. The skin slice is installed at a temperature of 32°C. In the outflow type diffusion tank where warm water is circulated and insulated. Secondly, fill the receptor tank with phosphate buffer, and while replacing at a certain flow rate, collect the solution from the receptor tank every 6 hours until 168 hours later. The concentration of the drug (bisoprolol) in the collected solution was determined by high performance liquid chromatography. Next, calculate the amount of drug permeated at each time period based on the measured concentration value, and obtain the skin penetration rate of the drug at each time period (μg/cm 2 /hr). Furthermore, as an indicator of the durability of skin penetration of the drug, the value of J last /J max is calculated by dividing the skin penetration rate J last after 168 hours by the maximum skin velocity J max . If the value of J last /J max is larger, it means that the skin penetration of the drug is persistent. Evaluation criteria for in vitro human skin penetration test ◎: J last /J max value is 0.60 or more ○: J last /J max value is 0.30 or more and less than 0.60 ×: J last /J max value is less than 0.30 Examples 1-7 And the evaluation results of Comparative Example 1 [Table 2] If the ratio of the silicone adhesive containing polyorganosiloxane in the adhesive layer increases, the moisture permeability of the transdermal absorption preparation tends to increase. The skin penetration persistence of the drug decreases slightly as the ratio of silicone-based adhesives containing polyorganosiloxane increases, but still maintains a sufficient value. The transdermal absorption preparations of Examples 1-7, especially Examples 2-7, have relatively good moisture permeability and continuity of skin penetration of drugs. Furthermore, the bisoprolol in the drug storage layers of Examples 1 and 4 was changed to oxybutynin, asenapine, citalopram, diclofenac sodium, memantine, rivastigmine, donepezil, and carbazide, respectively. The transdermal absorption preparations of lantamamine, fluoxetine, paroxetine, tolterodine and rotigotine also have relatively good moisture permeability and persistence of drug skin penetration. [Test 2] The comparison of the support for transdermal absorption preparations is based on the use of water-repellent treated PET knitted fabric, ethylene-vinyl acetate copolymer film, PET/non-woven fabric laminated film, polyurethane non-woven fabric or poly A transdermal absorption preparation (Examples 8-12) made of a urethane film as a support was compared with the moisture permeability. In addition, for transdermal absorption preparations using water-repellent treated PET knitted fabrics, ethylene-vinyl acetate copolymer films or PET films as supports (Examples 8-9 and 29), and transdermal non-laminated supports The absorption preparation (Comparative Example 2) compares drug penetration resistance. Preparation of Examples 8-12, 29 and Comparative Example 2 Regarding the drug storage layer, 40% by mass of bisoprolol and 60% by mass of ethyl cellulose were weighed and prepared by the same method as the method described in Test 1 Got. Regarding the adhesive layer, 100% by mass of the silicone-based adhesive containing polyorganosiloxane was weighed and prepared by the same method as the method described in Test 1. Join the drug storage layer on the adhesive layer, peel off the release liner to remove the drug storage layer, and cut the support on the surface 3 of the exposed area (the support is not laminated in Comparative Example 2) with the drug storage layer as the approximate center. It is round (38 cm 2 ) to obtain a transdermal absorption preparation. [table 3] Evaluation method (1) Moisture permeability test method Regarding the moisture permeability of transdermal absorption preparations, the moisture permeability test method for moisture-proof packaging materials (cup method) specified by JIS Z 0208:1976 is measured at temperature: 40±0.5℃ , Relative humidity: Moisture penetration rate (MVTR) g/m 2 ·24 hr under 90±2%. Evaluation criteria for the moisture permeability test ◎: The moisture permeability is 40 g/m 2 ·24 hr or more = The moisture permeability is high, and it hardly irritates the skin ○: The moisture permeability is 20 g/m 2 ·24 hr or more ~ not reached 40 g/m 2 · 24 hr = slightly higher moisture permeability, less irritation to the skin ×: less than 20 g/m 2 · 24 hr = lower moisture permeability, easy to cause skin irritation Examples 8-12 Evaluation results [Table 4] It can be seen that the percutaneous absorption preparations that use PET knitted fabric (water repellent treatment), ethylene-vinyl acetate copolymer film, polyurethane non-woven fabric, and polyurethane film as the support have permeability. Tendency to higher humidity. (2) Drug penetration resistance test method The support side of the transdermal absorption preparations of Examples 8-9, 29 and Comparative Example 2 were immersed in 900 mL of water, and after standing for 15 minutes, the drug content in the water was measured . Evaluation criteria for drug penetration prevention ○: The penetration of the drug from the support side was hardly confirmed. ×: Penetration of the drug from the support side was confirmed. Evaluation results of Examples 8-9, 29 and Comparative Example 2 [Table 5] It can be seen that percutaneous absorption preparations using PET knitted fabric (water repellent treatment), ethylene-vinyl acetate copolymer film, and PET film as a support tend to have higher drug penetration resistance. [Test 3] Comparison of drug storage layer For transdermal absorption preparations (Examples 13-28) containing ethyl cellulose (EC), acrylic base or hydroxypropyl cellulose (HPC) in the drug storage layer, comparison Coagulation of drug storage layer. Production of Examples 13 to 28 The components in Table 6 were weighed, and the drug storage layer was obtained by the same method as the method described in Experiment 1. Weigh 100% by mass of silicone adhesive containing polyorganosiloxane (BIO-PSA 7-4202/BIO-PSA 7-4302 = 50/50) by the same method as the method described in Test 1 Obtain an adhesive layer. Join the drug storage layer on the adhesive layer, peel off the release liner to remove the drug storage layer, and cut the exposed area layer support (PET/non-woven laminate film) into an approximate square with the drug storage layer as the approximate center (13.4 cm 2 ) to obtain a transdermal absorption preparation. [Table 6] Evaluation method of agglutination: Prepare an adhesive patch containing 2% by mass of agar, and peel off the release liner from which the adhesive layer of the transdermal absorption preparations of Examples 13-28 obtained above is removed, and contact the adhesive with the exposed adhesive surface Method: Put a layered transdermal absorbent material on the glue and let it stand for 24 hours. After peeling off the transdermal absorption preparation from the adhesive tape and allowing the moisture attached to the adhesive surface of the transdermal absorption preparation to air dry, the agglutinating property of the drug storage layer was evaluated by the finger-touch method according to the following criteria. Criteria for evaluation of agglutination ○: No agglutination failure occurred in the drug storage layer △: Agglomeration failure occurred slightly in the drug storage layer ×: Agglomeration failure occurred in the drug storage layer Evaluation results of Examples 13-28 [Table 7] In the transdermal absorption preparations of Examples 21 to 23 containing HPC as the base of the drug storage layer, the drug storage layer swelled due to moisture. When the transdermal absorption preparation was peeled from the adhesive tape, the drug storage layer showed a tendency to agglutinate and destroy . On the other hand, in the transdermal absorption preparations of Examples 13-20 containing ethyl cellulose as the base of the drug storage layer, and Examples 24-28 containing the acrylic base as the base of the drug storage layer, it can be seen The agglutination destruction of the drug storage layer is inhibited and the agglutination tends to be maintained. In particular, in the transdermal absorption preparations of Examples 13-17, 19-20, and 24-28, the drug storage layer did not undergo agglutination failure, and the agglutination was good.