TWI670088B - 含有阿申那平(asenapine)之貼附劑之製造方法 - Google Patents
含有阿申那平(asenapine)之貼附劑之製造方法 Download PDFInfo
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- TWI670088B TWI670088B TW105123611A TW105123611A TWI670088B TW I670088 B TWI670088 B TW I670088B TW 105123611 A TW105123611 A TW 105123611A TW 105123611 A TW105123611 A TW 105123611A TW I670088 B TWI670088 B TW I670088B
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- acid
- adhesive
- asenapine
- adhesive composition
- adhesive layer
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
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Abstract
本發明提供一種具備支持體、及積層於支持體上之黏著劑層的貼附劑之製造方法,其包括:將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物的步驟;及將黏著劑組合物成形而獲得黏著劑層之步驟。
Description
本發明係關於一種含有阿申那平(ASENAPINE)之貼附劑之製造方法。
阿申那平係作為中樞神經系統疾病、尤其是精神***症之治療藥而為人所知之化合物。含有阿申那平之貼附劑例如係記載於專利文獻1~4中。已知含有阿申那平游離鹼之貼附劑係阿申那平之透皮性優異。
[專利文獻1]國際公開第2010/127674號
[專利文獻2]國際公開第2014/017593號
[專利文獻3]國際公開第2014/017594號
[專利文獻4]國際公開第2014/017595號
另一方面,於貼附劑具備含有(甲基)丙烯酸酯(共)聚合物之黏著劑層之情形時,若於製造貼附劑時使用阿申那平游離鹼,則有阿申那平容易被分解之情況。因此,本發明之目的在於提供一種阿申那平難
以被分解之貼附劑之製造方法。
本發明者等人在研究於製造貼附劑時阿申那平難以被分解之方法的過程中發現,藉由使黏著劑層中含有順丁烯二酸金屬鹽,而減少阿申那平之分解。進而亦發現,於製造貼附劑時,相較於使用含有阿申那平游離鹼及順丁烯二酸金屬鹽之黏著劑組合物之情形,於使用含有阿申那平之酸加成鹽及脫鹽劑之黏著劑組合物之情形時,可減少阿申那平之分解物之生成量。
另一方面,根據本發明者等人之研究,於具備含有橡膠系黏著劑之黏著劑層的貼附劑之製造中,於製造貼附劑時幾乎未觀察到阿申那平之分解。本發明者等人推測,製造貼附劑時之阿申那平之分解恐係因與黏著劑組合物中之其他成分之接觸、暴露於加熱或紫外線等光下而變得容易產生。
因此,本發明提供一種具備支持體、及積層於支持體上之黏著劑層的貼附劑之製造方法,其包括:將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物之步驟;及將黏著劑組合物成形而獲得黏著劑層之步驟。
阿申那平之酸加成鹽之酸較佳為選自由鹽酸、氫溴酸、氫碘酸、磷酸、乙酸、丙酸、乙醇酸、順丁烯二酸、丙二酸、丁二酸、酒石酸、檸檬酸、抗壞血酸、水楊酸及苯甲酸所組成之群中。又,脫鹽劑較佳為選自由鹼金屬氫氧化物、鹼金屬鹽、鹼土金屬氫氧化物、鹼土金屬鹽及低分子胺所組成之群中。
本發明又提供一種使含有(甲基)丙烯酸酯(共)聚合物之黏著劑組合物中之阿申那平穩定化之方法,其包括:將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物之步驟。
本發明提供一種於具備含有阿申那平之黏著劑層的貼附劑之製造過程中抑制阿申那平之分解的方法,其包括:將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物之步驟;及將黏著劑組合物成形而獲得黏著劑層之步驟。
根據本發明之貼附劑之製造方法,可減少製造貼附劑時阿申那平之分解物之生成量。
圖1係表示阿申那平之分解物之生成量之圖表。
圖2係表示阿申那平之分解物之生成量之圖表。
圖3係表示阿申那平之分解物之生成量之圖表。
於本說明書中,「(甲基)丙烯酸」之用詞係指丙烯酸及甲基丙烯酸之任一者或兩者,類似表述亦係同樣地定義。
以下示出本發明之實施形態,對本發明詳細地進行說明。
本發明之一實施形態為具備支持體、及積層於支持體上之黏著劑層的貼附劑。貼附劑可藉由包括如下步驟之方法而製造:將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物之步驟;及將黏著劑組合物成形而獲得黏著劑層之步驟。
支持體只要為可維持貼附劑、尤其是黏著劑層之形狀者即可。作為支持體之材質,例如可列舉:聚乙烯、聚丙烯、聚丁二烯、乙烯-氯乙烯共聚物、聚氯乙烯、尼龍等聚醯胺、聚酯、纖維素衍生物、聚胺基甲酸酯等合成樹脂。支持體之性狀為例如膜、片材、片狀多孔質體、片狀發泡體、織布、針織布、不織布等布、及其等之積層體等。支持體之厚度並無特別限制,通常較佳為2~3000μm左右。
黏著劑層係由將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合
物及脫鹽劑混合而獲得之黏著劑組合物所形成。黏著劑層較佳為不含橡膠系黏著劑。作為橡膠系黏著劑,例如可列舉:天然橡膠、聚異丁烯、烷基乙烯基醚(共)聚合物、聚異戊二烯、聚丁二烯、苯乙烯-丁二烯共聚物、苯乙烯-異戊二烯共聚物、苯乙烯-異戊二烯-苯乙烯嵌段共聚物、聚矽氧橡膠等。
黏著劑層之厚度並無特別限制,亦可為30~300μm。若黏著劑層之厚度超過300μm,則於被覆之裝卸時等貼附劑變得容易脫落。
阿申那平為亦被稱為(3aRS,12bRS)-5-氯-2-甲基-2,3,3a,12b-四氫-1H-二苯并[2,3:6,7]氧[4,5-c]吡咯之化合物,係由以下之化學式表示。阿申那平具有複數種光學異構物,可為任一光學異構物,亦可為外消旋體等光學異構物之混合物。作為加成於阿申那平上之酸,只要為藥學上可容許之酸,則並無特別限制。阿申那平之酸加成鹽亦可為酐,亦可為水合物。
作為酸,例如可列舉:鹽酸、氫溴酸、氫碘酸、磷酸、乙酸、丙酸、乙醇酸、順丁烯二酸、丙二酸、丁二酸、酒石酸、檸檬酸、抗壞血酸、水楊酸、苯甲酸等。例如,阿申那平順丁烯二酸鹽係作為精神***症之治療藥而市售。
脫鹽劑只要為藉由與阿申那平之酸加成鹽之鹽交換反應而可將阿申那平之酸加成鹽變換為阿申那平游離鹼者即可。即,所謂脫鹽劑,係指將阿申那平之酸加成鹽變換為阿申那平游離鹼之成分。作為脫鹽劑,例如可列舉:鹼金屬氫氧化物、鹼金屬鹽、鹼土金屬氫氧化
物、鹼土金屬鹽、低分子胺等。作為鹼金屬氫氧化物,可列舉:氫氧化鋰、氫氧化鈉、氫氧化鉀。作為鹼金屬鹽,可列舉:碳酸鈉、碳酸鉀、碳酸氫鈉、磷酸三鈉、磷酸氫二鈉、磷酸二氫鈉、磷酸三鉀、磷酸氫二鉀、磷酸二氫鉀、乳酸鈉、檸檬酸鈉、酒石酸二鈉、酒石酸氫鈉、油酸鈉等。低分子胺係分子量為30~300之胺,例如可列舉:單乙醇胺、二乙醇胺、三乙醇胺、異丙醇胺、二異丙醇胺等。脫鹽劑只要考慮加成於阿申那平上之酸之pKa而選擇即可。若脫鹽劑為氫氧化鈉,則於製造貼附劑時藥物之分解更少。
(甲基)丙烯酸酯(共)聚合物係對黏著劑層賦予黏著性之成分,例如為1種或2種以上之(甲基)丙烯酸烷基酯之(共)聚合物。作為(甲基)丙烯酸烷基酯,例如可列舉:(甲基)丙烯酸丁酯、(甲基)丙烯酸異丁酯、(甲基)丙烯酸己酯、(甲基)丙烯酸辛酯、(甲基)丙烯酸2-乙基己酯、(甲基)丙烯酸癸酯等。
(甲基)丙烯酸酯(共)聚合物亦可為由(甲基)丙烯酸烷基酯(主單體)與共聚單體形成之(共)聚合物。共聚單體只要為可與(甲基)丙烯酸烷基酯共聚合之成分即可。作為共聚單體,例如可列舉:(甲基)丙烯酸羥基烷基酯、乙烯、丙烯、苯乙烯、乙酸乙烯酯、N-乙烯基吡咯啶酮、(甲基)丙烯醯胺等。共聚單體可為單獨1種或將2種以上組合而成者。
具體之(甲基)丙烯酸酯(共)聚合物之例可例示:DURO-TAK(註冊商標)87-900A、DURO-TAK 87-2510、DURO-TAK 87-4287、DURO-TAK 87-2194(商品名,Henkel公司製造)等。DURO-TAK 87-2510及DURO-TAK 87-4287於其化學結構中具有羥基,DURO-TAK 87-2194於其化學結構中具有羧基。
(甲基)丙烯酸酯(共)聚合物之含量以黏著劑層之總質量為基準而為50~98質量%,較佳為70~96質量%。(甲基)丙烯酸酯(共)聚合物之
含量係基於固形物成分之質量進行計算。
黏著劑層亦可進而含有其他添加劑。作為其他添加劑,例如可列舉:增黏樹脂、塑化劑、吸收促進劑、溶解劑、穩定劑、填充劑、香料等。
增黏樹脂係調整黏著劑層之黏著性之成分。作為增黏樹脂,例如可列舉:脂環族飽和烴樹脂;松香、松香之甘油酯、氫化松香、氫化松香之甘油酯、松香之季戊四醇酯、順丁烯二醯化松香等松香衍生物;萜烯系增黏樹脂;石油系增黏樹脂等。增黏樹脂可單獨使用1種,亦可將2種以上組合使用。
吸收促進劑係調整阿申那平或阿申那平之酸加成鹽之透皮性的成分。作為吸收促進劑,只要為先前可見對皮膚之吸收促進作用之化合物則並無特別限定,例如可列舉:碳數6~20之脂肪族醇、碳數6~20之脂肪族醚、碳數6~20之脂肪酸、碳數6~20之脂肪酸酯、碳數6~20之脂肪酸醯胺、甘油、甘油脂肪酸酯類、丙二醇類、丙二醇脂肪酸酯類、聚乙二醇及聚乙二醇脂肪酸酯類、芳香族系有機酸、芳香族系醇、芳香族系有機酸酯、芳香族系有機醚(以上化合物可為飽和及不飽和之任一種,可為直鏈狀及分支狀之任一種,亦可為包含環狀結構者)、乳酸酯類、乙酸酯類、單萜烯系化合物、倍半萜烯系化合物、1-十二烷基氮雜環庚烷-2-酮(Azone(商品名))及其衍生物、山梨醇酐脂肪酸酯類(Span(註冊商標)系)、聚山梨醇酯系(Tween(註冊商標)系)、聚氧乙烯氫化蓖麻油類、聚氧乙烯烷基醚類、蔗糖脂肪酸酯類、植物油。作為吸收促進劑之具體例,可列舉:辛酸、癸酸、己酸、月桂酸、肉豆蔻酸、棕櫚酸、硬脂酸、異硬脂酸、油酸、亞麻油酸、次亞麻油酸、月桂醇、肉豆蔻醇、油醇、異硬脂醇、鯨蠟醇、月桂酸甲酯、月桂酸己酯、月桂酸二乙醇醯胺、肉豆蔻酸異丙酯、肉豆蔻酸肉豆蔻酯、肉豆蔻酸辛基十二烷基酯、棕櫚酸鯨蠟酯、棕櫚酸異
丙酯、水楊酸、水楊酸甲酯、水楊酸乙二醇酯、肉桂酸、肉桂酸甲酯、甲酚、乳酸鯨蠟酯、乳酸月桂酯、乙酸乙酯、乙酸丙酯、香葉草醇、瑞香草酚、丁香油酚、松脂醇、l-薄荷腦、冰片、d-檸檬烯、異丁香油酚、異冰片、橙花醇、dl-樟腦、甘油單辛酸酯、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、蔗糖單月桂酸酯、聚山梨醇酯20、丙二醇、丙二醇單月桂酸酯、聚乙二醇單月桂酸酯、聚乙二醇單硬脂酸酯、聚氧乙烯月桂醚、Nikkol(註冊商標)HCO-60、Pyrrothiodecane(註冊商標)、橄欖油及山梨醇酐單油酸酯。作為吸收促進劑,就顯著提高阿申那平之透皮性之方面而言,較佳為丙二醇單月桂酸酯、棕櫚酸異丙酯,更佳為棕櫚酸異丙酯。吸收促進劑可單獨使用1種,亦可將2種以上組合使用。
於黏著劑層含有吸收促進劑之情形時,吸收促進劑之含量較佳為以黏著劑層整體之質量為基準而為2~40質量%。若吸收促進劑之含量為2質量%以上,則有阿申那平之透皮性變得更高而顯示出充分之藥理作用的傾向。又,若吸收促進劑之含量為40質量%以下,則有不顯示皮膚刺激性之傾向。
溶解劑係使阿申那平及其酸加成鹽容易溶解於黏著劑組合物中之成分。
穩定劑只要為可抑制因紫外線等光線、熱或活性化學種之作用而產生的自由基之生成及其鏈反應之進行者即可。藉由含有穩定劑,可使製造貼附劑時之阿申那平之穩定性進一步提高。作為穩定劑,例如可列舉:維生素E及其酯衍生物、抗壞血酸及其酯衍生物、二丁基羥基甲苯、丁基羥基苯甲醚、2-巰基苯并咪唑等。穩定劑可單獨使用1種,亦可將2種以上組合使用。作為穩定劑,就作為貼附劑之物性(成形性、外觀等)變合之適方面、及使阿申那平更穩定化之方面而言,較佳為二丁基羥基甲苯。
於黏著劑層含有穩定劑之情形時,穩定劑之含量較佳為以黏著劑層整體之質量為基準而為0.1~3質量%。若穩定劑之含量為0.1~3質量%,則有貼附劑中之各成分之穩定性優異之傾向。
貼附劑亦可進而具備剝離襯墊。剝離襯墊係對黏著劑層積層於與支持體為相反側之面。若具備剝離襯墊,則有於保管時可減少對黏著劑層之污物等之附著的傾向。
作為剝離襯墊之素材,並無特別限定,可使用業者通常所知之襯墊。作為剝離襯墊之材質,例如可列舉:聚對苯二甲酸乙二酯、聚萘二甲酸乙二酯等聚酯;聚乙烯、聚丙烯等聚烯烴;聚氯乙烯、聚偏二氯乙烯等之膜;道林紙與聚烯烴之層壓膜;尼龍(商品名)、鋁等之膜等。作為剝離襯墊之材質,較佳為聚丙烯或聚對苯二甲酸乙二酯。
<貼附劑之製造方法>
本發明之貼附劑例如可藉由以下方法進行製造。首先,將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合,視需要添加溶劑、其他添加劑等進行混合,獲得均勻之黏著劑組合物。繼而,將所獲得之黏著劑組合物以特定之厚度塗佈於支持體之單面上後,視需要進行加溫而將溶劑乾燥去除,並裁剪成所需大小,藉此而獲得貼附劑。再者,作為加溫之條件,可根據上述溶劑而適當選擇,作為溫度條件,較佳為60~120℃,加溫時間例如為2~30分鐘。
於製造具備剝離襯墊之貼附劑之情形時,亦可於將黏著劑組合物塗佈於支持體上後,將溶劑乾燥去除後積層剝離襯墊。又,於製造具備剝離襯墊之貼附劑之情形時,亦可將黏著劑組合物以特定之厚度塗佈於剝離襯墊之單面上後,視需要進行加溫而將溶劑乾燥去除,積層支持體,並剪裁成所需之大小,藉此而獲得貼附劑。
於上述製造方法中使用之黏著劑組合物含有阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑,視需要進而含有溶劑、其
他添加劑等。
溶劑只要為不與黏著劑組合物中所含之其他成分發生反應者即可,係為了調整黏著劑組合物之黏性而添加。作為溶劑,例如可列舉:甲苯、乙醇、甲醇、乙酸乙酯等。溶劑可單獨使用1種,亦可將2種以上組合使用。溶劑之含量只要考慮黏著劑組合物之黏性而調整即可。
黏著劑組合物中之阿申那平之酸加成鹽之含量以黏著劑組合物整體之質量為基準而較佳為0.5~50質量%,更佳為4.2~21質量%。
黏著劑組合物中之(甲基)丙烯酸酯(共)聚合物之含量以黏著劑組合物整體之質量為基準而較佳為50~98質量%,更佳為70~96質量%。若(甲基)丙烯酸酯(共)聚合物之含量為50質量%以上,則有凝聚力不下降而黏著力不下降之傾向。
黏著劑組合物中之脫鹽劑之含量以黏著劑組合物整體之質量為基準而較佳為0.05~20質量%,更佳為0.1~10質量%。
[實施例]
以下示出實施例與比較例,對本發明更詳細地進行說明。再者,DURO-TAK 87-2516、DURO-TAK 87-4287、DURO-TAK 87-2194、DURO-TAK 87-900A及DURO-TAK 87-2510係基於固形物成分之質量進行計算。
(1)貼附劑之製造
分別稱取表1中記載之成分,視需要添加溶劑進行混合,而獲得黏著劑組合物。將所獲得之黏著劑組合物塗佈於聚酯製之剝離襯墊上並將溶劑乾燥去除,藉此而形成黏著劑層。於所獲得之黏著劑層上積層聚酯膜(支持體)並適當剪裁,而獲得所需之貼附劑。再者,表1中之數字係指質量%。
(2)分解物之生成量測定
將所獲得之貼附劑之黏著劑層浸漬於四氫呋喃(高效液相層析法用等級)10mL中進行萃取,添加下述作為移動相而記載之溶劑40mL並進行過濾後,於以下之分析條件下利用高效液相層析法測定阿申那平之分解物之生成量。阿申那平之分解物之生成量係於所獲得之層析圖中,以對應於阿申那平之分解物之波峰之曲線下面積相對於對應於阿申那平之波峰之曲線下面積的值表示。阿申那平之分解物之生成量係將對應於阿申那平之波峰之曲線下面積設為100而算出。
<分析條件>
管柱:TSK-gel ODS-80Ts
移動相:甲醇:0.1%磷酸(添加10mM十二烷基硫酸鈉)=75:25
測定波長:210nm
流速:1.0mL/分
管柱溫度:40℃
試樣注入量:10μL
將具有較阿申那平之保持時間短之保持時間的波峰作為「阿申那平之分解物1」,將具有較阿申那平之保持時間長之保持時間的波峰
作為「阿申那平之分解物2」。
將結果示於表2及圖1。實施例1及2之貼附劑與比較例1~5之貼附劑相比較,阿申那平之分解物顯著減少。
(3)貼附劑之製造
分別稱取表3中記載之成分,視需要添加溶劑進行混合,而獲得黏著劑組合物。將所獲得之黏著劑組合物塗佈於聚酯製之剝離襯墊上,並將溶劑乾燥去除,形成厚度為約100μm之黏著劑層。於所獲得之黏著劑層上積層聚酯膜(支持體),並進行適當剪裁,而獲得所需之貼附劑。再者,表3中之數字係指質量%。
(4)分解物之生成量測定
將所獲得之貼附劑之黏著劑層浸漬於四氫呋喃(高效液相層析法用等級)10mL中進行萃取,添加上述作為移動相而記載之溶劑40mL並進行過濾後,於上述分析條件下藉由高效液相層析法測定阿申那平
之分解物之生成量。
將結果示於表4及圖2。實施例3及4之貼附劑與比較例6~11之貼附劑相比較,阿申那平之分解物顯著減少。
(5)貼附劑之製造
分別稱取表5中記載之成分,視需要添加溶劑進行混合,而獲得黏著劑組合物。將所獲得之黏著劑組合物塗佈於聚酯製之剝離襯墊上,並將溶劑乾燥去除,藉此形成黏著劑層。於所獲得之黏著劑層上積層聚酯膜(支持體),並進行適當剪裁,而獲得所需之貼附劑。再者,表5中之數字係指質量%。
(6)分解物之生成量測定
將所獲得之貼附劑之黏著劑層浸漬於四氫呋喃(高效液相層析法用等級)10mL中進行萃取,添加上述作為移動相而記載之溶劑40mL
並進行過濾後,於上述分析條件下藉由高效液相層析法測定阿申那平之分解物之生成量。
將結果示於表6及圖3。實施例5及6之貼附劑與比較例12~17之貼附劑相比較,阿申那平之分解物顯著減少。
(7)脫鹽劑之研究
製備於實施例1之貼附劑中使用等莫耳量之氫氧化鉀代替氫氧化鈉之貼附劑(實施例7)。對實施例7之貼附劑測定阿申那平之分解物之生成量,結果分解物之生成量降低。進而,製備於實施例1之貼附劑中使用等莫耳量之碳酸鈉(實施例8)、碳酸氫鈉(實施例9)、碳酸鉀(實施例10)、碳酸氫鉀(實施例11)代替氫氧化鈉之貼附劑。
(8)貼附劑之製造
分別稱取表7中記載之成分,視需要添加溶劑進行混合,而獲得黏著劑組合物。將所獲得之黏著劑組合物塗佈於聚酯製之剝離襯墊上,並將溶劑乾燥去除,形成厚度為約100μm之黏著劑層。於所獲得之黏著劑層上積層聚酯膜(支持體),並進行適當剪裁,而獲得所需之貼附劑。再者,表7中之數字係指質量%。
(9)分解物之生成量測定
將結果示於表8。實施例12~14之貼附劑與比較例18之貼附劑相比較,阿申那平之分解物顯著減少。表8中,「N.D.」係指未達檢測極限。
(10)貼附劑之製造
分別稱取表9中記載之成分,視需要添加溶劑進行混合,而獲得黏著劑組合物。將所獲得之黏著劑組合物塗佈於聚酯製之剝離襯墊上,並將溶劑乾燥去除,形成厚度為約100μm之黏著劑層。於所獲得之黏著劑層上積層聚酯膜(支持體),並進行適當剪裁,而獲得所需之貼附劑。再者,表9中之數字係指質量%。
(11)分解物之生成量測定
將結果示於表10。實施例15~20之貼附劑中,阿申那平之分解物顯著減少。
Claims (5)
- 一種貼附劑之製造方法,該貼附劑具備支持體、及積層於支持體上之黏著劑層,該方法包括將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物的步驟;及將黏著劑組合物成形而獲得黏著劑層之步驟;且黏著劑層不含橡膠系黏著劑。
- 如請求項1之方法,其中阿申那平之酸加成鹽中之酸係選自由鹽酸、氫溴酸、氫碘酸、磷酸、乙酸、丙酸、乙醇酸、順丁烯二酸、丙二酸、丁二酸、酒石酸、檸檬酸、抗壞血酸、水楊酸及苯甲酸所組成之群中。
- 如請求項1或2之方法,其中脫鹽劑係選自由鹼金屬氫氧化物、鹼金屬鹽、鹼土金屬氫氧化物、鹼土金屬鹽及低分子胺所組成之群中。
- 一種使含有(甲基)丙烯酸酯(共)聚合物之黏著劑組合物中之阿申那平穩定化之方法,其包括:將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物之步驟;且黏著劑組合物不含橡膠系黏著劑。
- 一種於具備含有阿申那平之黏著劑層的貼附劑之製造過程中抑制阿申那平之分解的方法,其包括:將阿申那平之酸加成鹽、(甲基)丙烯酸酯(共)聚合物及脫鹽劑混合而獲得黏著劑組合物的步驟;及將黏著劑組合物成形而獲得黏著劑層之步驟;且黏著劑組合物不含橡膠系黏著劑。
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CN115813888A (zh) | 2016-12-20 | 2023-03-21 | 罗曼治疗***股份公司 | 包含阿塞那平的透皮治疗*** |
ES2971449T3 (es) | 2017-02-24 | 2024-06-05 | Hisamitsu Pharmaceutical Co | Parche cutáneo adhesivo y producto envasado del mismo |
BR112019027037B1 (pt) * | 2017-06-26 | 2022-04-05 | Lts Lohmann Therapie-Systeme Ag | Sistema terapêutico transdérmico contendo asenapina e polímero híbrido acrílico de silicone, e processo para fabricar uma camada contendo asenapina para uso no referido sistema |
AU2018392686A1 (en) | 2017-12-20 | 2020-07-09 | Corium Pharma Solutions, Inc. | Transdermal adhesive composition comprising a volatile liquid therapeutic agent having low melting point |
US20210251914A1 (en) * | 2018-06-20 | 2021-08-19 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
CN110958876B (zh) * | 2018-06-20 | 2020-12-18 | 罗曼治疗***股份公司 | 含有阿塞那平的透皮治疗*** |
CN112789039B (zh) | 2018-10-01 | 2023-10-24 | 久光制药株式会社 | 含有阿塞那平的贴剂 |
KR102574287B1 (ko) | 2018-10-01 | 2023-09-01 | 히사미쯔 제약 주식회사 | 아세나핀 함유 첩부제 |
US20240122898A1 (en) * | 2019-10-28 | 2024-04-18 | Hisamitsu Pharmaceutical Co., Inc. | Method for suppressing production of asenapine-n-oxide |
DE102020207642A1 (de) | 2020-06-19 | 2021-12-23 | Lts Lohmann Therapie-Systeme Ag | Verfahren zur herstellung von asenapin in form seiner freien base |
CN116406262A (zh) * | 2020-11-16 | 2023-07-07 | 久光制药株式会社 | 含有阿塞那平的贴剂 |
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TW201410271A (zh) * | 2012-07-26 | 2014-03-16 | Hisamitsu Pharmaceutical Co | 貼附劑 |
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WO2009107476A1 (ja) * | 2008-02-27 | 2009-09-03 | 久光製薬株式会社 | 貼付製剤 |
WO2010127674A1 (en) * | 2009-05-06 | 2010-11-11 | Sunin K/S | Transdermal compositions of asenapine for the treatment of psychiatric disorders |
US20130053357A1 (en) * | 2010-04-28 | 2013-02-28 | Hisamitsu Pharmaceutical Co., Inc. | Skin irritation suppressant and transdermal preparation |
AR082640A1 (es) * | 2011-08-25 | 2012-12-19 | Amarin Technologies S A | Un dispositivo para la administracion transdermal de compuestos alcalinos susceptibles a la degradacion en su forma no salificada |
US10493156B2 (en) * | 2012-07-26 | 2019-12-03 | Hisamitsu Pharmaceutical Co., Inc. | Patch and method for producing the same |
AR097544A1 (es) * | 2014-09-03 | 2016-03-23 | Amarin Tech S A | Un dispositivo para la administración transdermal de compuestos farmacéuticamente activos, líquidos a temperaturas cercanas a la ambiente, que presentan funcionalidad alcalina en su forma de base libre, método |
US10806705B2 (en) * | 2015-07-27 | 2020-10-20 | Hisamitsu Pharmaceutical Co., Inc. | Asenapine-containing patch |
JP6639513B2 (ja) * | 2015-09-30 | 2020-02-05 | 帝國製薬株式会社 | 粘着性ポリマーおよび医療用貼付剤 |
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TW201410271A (zh) * | 2012-07-26 | 2014-03-16 | Hisamitsu Pharmaceutical Co | 貼附劑 |
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TW201707692A (zh) | 2017-03-01 |
CN107847488A (zh) | 2018-03-27 |
KR102005201B1 (ko) | 2019-07-29 |
JP6462880B2 (ja) | 2019-01-30 |
US20180207108A1 (en) | 2018-07-26 |
WO2017018321A1 (ja) | 2017-02-02 |
JPWO2017018321A1 (ja) | 2018-01-18 |
CN112843023A (zh) | 2021-05-28 |
EP3329914A4 (en) | 2019-04-03 |
EP3329914A1 (en) | 2018-06-06 |
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