TW202329923A - 抑制雙氯芬酸吲哚啉酮體之生成之方法 - Google Patents
抑制雙氯芬酸吲哚啉酮體之生成之方法 Download PDFInfo
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- TW202329923A TW202329923A TW111136189A TW111136189A TW202329923A TW 202329923 A TW202329923 A TW 202329923A TW 111136189 A TW111136189 A TW 111136189A TW 111136189 A TW111136189 A TW 111136189A TW 202329923 A TW202329923 A TW 202329923A
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- diclofenac
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Abstract
本發明揭示一種抑制貼附劑中之雙氯芬酸吲哚啉酮體之生成之方法。上述貼附劑係具備支持體層、及積層於上述支持體層上之黏著劑層之貼附劑,上述方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟。又,以上述黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
Description
本發明係關於一種抑制雙氯芬酸吲哚啉酮體之生成之方法。
關於含有作為一種非類固醇性消炎鎮痛劑之雙氯芬酸之貼附劑,已知其具有腰痛症、肩周炎、頸肩腕綜合征、腱/腱鞘炎、腱周圍炎、肱骨外上髁炎(網球肘等)、肌肉痛(肌肉/筋膜性腰痛症等)、及外傷後之腫脹/疼痛等疾病及症狀之鎮痛/消炎、各種癌之鎮痛等功效作用,迄今為止進行了大量研究。例如,專利文獻1中記載有一種貼附劑,其含有雙氯芬酸或其藥學上可容許之鹽、檸檬酸及二甲基亞碸,且雙氯芬酸或其藥學上可容許之鹽與檸檬酸之質量比、雙氯芬酸或其藥學上可容許之鹽與二甲基亞碸之質量比處於特定範圍內。又,專利文獻2中記載有一種含活性物質之黏著性貼附藥,其包含:不滲透性輔助膜;雙氯芬酸或其藥學上可容許之鹽;選自苯乙烯-異戊二烯-苯乙烯嵌段共聚物及乙烯-乙酸乙烯酯共聚物之基質形成聚合物;包含脂肪族烴樹脂及熱塑性萜烯樹脂之黏著性賦予劑;以及選自由油酸及其衍生物、脂肪酸烷基酯、以及N-烷基-吡咯啶酮所組成之群中之1種或1種以上之溶劑;以及可剝離之保護膜。
先前技術文獻
專利文獻
專利文獻1:國際公報第2013/191128號
專利文獻2:日本專利特表2004-508397號公報
[發明所欲解決之問題]
此前研究之含雙氯芬酸之貼附劑大多為含有雙氯芬酸之藥學上可容許之鹽(具體而言為雙氯芬酸鈉)之貼附劑。已知於含有雙氯芬酸之藥學上可容許之鹽之貼附劑中,會生成作為雙氯芬酸之一種分解物之雙氯芬酸吲哚啉酮體。為提供穩定性較高之貼附劑,抑制雙氯芬酸吲哚啉酮體之生成較為重要。因此,本發明之目的在於提供一種抑制貼附劑中之雙氯芬酸吲哚啉酮體之生成之方法。又,本發明之目的還在於提供一種雙氯芬酸吲哚啉酮體之生成得到抑制之貼附劑及其製造方法。
[解決問題之技術手段]
發明人等對含有雙氯芬酸游離酸之貼附劑進行了研究,結果發現,含有特定量之雙氯芬酸游離酸之貼附劑相較於含有雙氯芬酸鈉之貼附劑,更能夠抑制雙氯芬酸吲哚啉酮體之生成,從而完成了本發明。
即,本發明提供一種方法,其係於具備支持體層、及積層於上述支持體層上之黏著劑層的貼附劑中抑制黏著劑層中之雙氯芬酸吲哚啉酮體之生成之方法,該方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟,以黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
本發明還提供一種方法,其係具備支持體層、及積層於上述支持體層上之黏著劑層的貼附劑之製造方法,該方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟,以上述黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%,本發明進而提供一種貼附劑,其具備支持體層、及積層於上述支持體層上之黏著劑層,上述黏著劑層含有雙氯芬酸游離酸及黏著基劑,以上述黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
[發明之效果]
根據本發明,可於貼附劑中抑制雙氯芬酸吲哚啉酮體之生成(尤其是保存時之雙氯芬酸吲哚啉酮體之生成)。
以下,示出本發明之實施方式來詳細地說明本發明。
本發明之一實施方式之貼附劑具備支持體層、及積層於上述支持體層上之黏著劑層。上述黏著劑層含有雙氯芬酸游離酸及黏著基劑,以上述黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
支持體層保持黏著劑層。支持體層較佳為將纖維製成布狀(織布、不織布、或編織布)而成者之單層體或積層體、或者無孔性或多孔性之膜(片材)之單層體或積層體。支持體層之材質較佳為選自聚酯(聚對苯二甲酸乙二酯、聚間苯二甲酸乙二酯、聚對苯二甲酸丙二酯、聚間苯二甲酸丙二酯、聚對苯二甲酸丁二酯、或聚萘二甲酸乙二酯等)、聚烯烴(乙烯、丙烯、乙酸乙烯酯、或丙烯腈等乙烯基系單體之聚合物或共聚物)、聚醯胺(尼龍或蠶絲等)、聚胺酯、或纖維素(棉紗或麻等)中之1種以上之材質。布(織布、不織布、或編織布)上可塗佈橡膠組合物。橡膠組合物包含橡膠系黏著基劑。橡膠系黏著基劑例如為聚異戊二烯、聚異丁烯、聚丁二烯、苯乙烯-丁二烯-苯乙烯嵌段共聚物、苯乙烯-異戊二烯-苯乙烯嵌段共聚物、苯乙烯-丁二烯橡膠、苯乙烯-異戊二烯橡膠、或該等之組合。橡膠組合物可包含黏著賦予樹脂。黏著賦予樹脂例如為脂環族飽和烴樹脂、氫化松香甘油酯、萜烯系樹脂、或該等之組合。又,橡膠組合物亦可進而包含塑化劑、填充劑等添加劑。支持體層之厚度例如為0.1 mm~2 mm。支持體層之單位面積重量例如為30 g/m
2~200 g/m
2。於本說明書中,支持體層之厚度及單位面積重量係依據JIS L 1906:2000之標準進行測定。
支持體層之透濕度較佳為400 g/m
2・24小時以上,更佳為1000 g/m
2・24小時以上,進而較佳為4000 g/m
2・24小時以上。若使用此種高透濕度之支持體層,則二甲基亞碸自應用於皮膚之貼附劑中逐漸揮散,因此貼附劑之黏著性提高,即便長時間應用貼附劑,亦不易剝落。透濕度之上限值可為20000 g/m
2・24小時。若支持體層之透濕度處於此種範圍內,則二甲基亞碸更易自黏著劑層中揮散,故而對貼附劑之黏著性之提高更有效。再者,支持體層之透濕度係指JIS Z0208:1976之標準(防濕包裝材料之透濕度試驗方法(杯式法))中定義之40℃下之透濕度。
於支持體層為布狀之情形時,支持體層之縱向(材料流動方向)及橫向(材料寬度方向)中之任一方向之50%模數(JIS L 1018:1999)均較佳為1 N/50 mm~12 N/50 mm。於50%模數為12 N/50 mm以下之情形時,由於皮膚之伸縮,貼附劑所受到之應力更小,因此對皮膚之附著性良好。
於支持體層為膜之情形時,材質較佳為如聚胺酯之高透濕性(高二甲基亞碸透過性)。包含聚胺酯之膜由於伸縮性優異,故而就提高貼附劑對皮膚之附著性及伸縮追隨性之觀點而言較佳。
支持體層較佳為例如包含聚胺酯之不織布或膜、包含聚對苯二甲酸乙二酯之編織布、不織布或膜、經橡膠組合物塗佈之聚酯之布、或該等之組合。更具體而言,支持體層更佳為包含聚胺酯之膜與包含聚胺酯之不織布之積層體、包含聚對苯二甲酸乙二酯之編織布或不織布、或經橡膠組合物塗佈之聚酯之布。
黏著劑層係由將雙氯芬酸游離酸、黏著基劑、及後述之任意成分混和所得之黏著劑組合物形成。就使貼附劑適當地黏著於皮膚之觀點而言,黏著劑層整體之膏體質量較佳為10 g/m
2~1000 g/m
2,更佳為30 g/m
2~300 g/m
2,進而較佳為100 g/m
2~250 g/m
2。
雙氯芬酸游離酸係亦稱為2-[(2,6-二氯苯基)胺基]苯乙酸之化合物。以黏著劑層之總質量為基準,雙氯芬酸游離酸之含量為0.5質量%~8質量%,亦可為1質量%~7質量%、1質量%~5質量%或1質量%~4.65質量%。
黏著基劑係用於對黏著劑層賦予黏著性者,例如可例舉:橡膠系黏著基劑、丙烯酸系黏著基劑、矽酮系黏著基劑等。黏著基劑較佳為選自由橡膠系黏著基劑、丙烯酸系黏著基劑及矽酮系黏著基劑所組成之群中之1種以上。黏著基劑較佳為不含水(非水系黏著基劑)。黏著基劑可為橡膠系黏著基劑、丙烯酸系黏著基劑及矽酮系黏著基劑中之任一者,亦可為該等之組合。以黏著劑層之總質量為基準,黏著基劑之總含量可設為10質量%~90質量%,亦可為20質量%~90質量%。
作為橡膠系黏著基劑,例如可例舉: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、苯乙烯-丁二烯-苯乙烯嵌段共聚物等。橡膠系黏著基劑可單獨使用該等中之1種,亦可組合2種以上使用。其中,作為本實施方式之橡膠系黏著基劑,就傾向於可發揮出黏著劑層之更充分之黏著力之觀點而言,較佳為選自由苯乙烯-異戊二烯-苯乙烯嵌段共聚物及聚異丁烯所組成之群中之至少1種以上,更佳為苯乙烯-異戊二烯-苯乙烯嵌段共聚物、或者苯乙烯-異戊二烯-苯乙烯嵌段共聚物及聚異丁烯。
作為橡膠系黏著基劑之具體例,可例舉:Quintac(註冊商標)3570C(商品名,日本瑞翁股份有限公司製造)、SIS5002、SIS5229、SIS5505、SIS5505P(商品名,JSR股份有限公司製造)、SIBSTAR(註冊商標)T102(商品名,Kaneka股份有限公司製造)等,又,聚異丁烯亦包含所謂之丁基橡膠(異丁烯-異戊二烯橡膠),作為具體例,可例舉:Oppanol(註冊商標)N50、N80、N100、N150、B11、B12、B50、B80、B100、B120、B150、B220(商品名,BASF公司製造)、JSR(註冊商標)Butyl 065、268、365(商品名,JSR股份有限公司製造)、X_Butyl(註冊商標)RB100、101-3、301、402(商品名,ARLANXEO公司製造)、Exxon(註冊商標)Butyl 065、065S、068、068S、268、268S、365、365S(商品名,Exxon Mobile公司製造)等。
以黏著劑層之總質量為基準,橡膠系黏著基劑之含量可設為10質量%~90質量%,亦可為15質量%~60質量%、15質量%~40質量%、15質量%~30質量%。於使用苯乙烯-異戊二烯-苯乙烯嵌段共聚物及聚異丁烯之混合物作為橡膠系黏著基劑之情形時,兩者之質量比較佳為4:1~1:4、3:1~1:1、或3:1~2:1。
丙烯酸系黏著基劑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,例如可例舉:(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。再者,於本說明書中,「(甲基)丙烯酸」這一用語係指丙烯酸及甲基丙烯酸之任一者或兩者,類似表達以同樣之方式來定義。
丙烯酸系黏著基劑可為由(甲基)丙烯酸烷基酯(主單體)與共聚單體所形成之共聚物。作為主單體,例如可例舉:(甲基)丙烯酸甲酯、(甲基)丙烯酸乙酯、(甲基)丙烯酸丁酯、(甲基)丙烯酸己酯、(甲基)丙烯酸庚酯、(甲基)丙烯酸辛酯、(甲基)丙烯酸2-乙基己酯等,可單獨使用該等中之1種,亦可組合2種以上使用。共聚單體只要為可與(甲基)丙烯酸烷基酯共聚之成分即可。作為共聚單體,例如可例舉:(甲基)丙烯酸羥烷基酯、乙烯、丙烯、苯乙烯、乙酸乙烯酯、N-乙烯基吡咯啶酮、(甲基)丙烯酸、(甲基)丙烯醯胺等。共聚單體可為單獨1種或組合2種以上而成者。
作為丙烯酸系黏著基劑之具體例,可例舉:丙烯酸/丙烯酸辛酯共聚物、丙烯酸2-乙基己酯/乙烯基吡咯啶酮共聚物溶液、丙烯酸酯/乙酸乙烯酯共聚物、丙烯酸2-乙基己酯/甲基丙烯酸2-乙基己酯/甲基丙烯酸十二烷基酯共聚物、丙烯酸甲酯/丙烯酸2-乙基己酯共聚樹脂乳液、丙烯酸樹脂烷醇胺液中含有之丙烯酸系高分子等。作為此種丙烯酸系黏著基劑之具體例,可例舉:DURO-TAK(註冊商標)387-2510、DURO-TAK(註冊商標)87-2510、DURO-TAK(註冊商標)387-2287、DURO-TAK(註冊商標)87-2287、DURO-TAK(註冊商標)87-4287、DURO-TAK(註冊商標)387-2516、DURO-TAK(註冊商標)87-2516、DURO-TAK(註冊商標)87-2074、DURO-TAK(註冊商標)87-900A、DURO-TAK(註冊商標)87-901A、DURO-TAK(註冊商標)87-9301、DURO-TAK(註冊商標)87-4098等DURO-TAK系列(Henkel公司製造);GELVA(註冊商標)GMS 788、GELVA(註冊商標)GMS 3083、GELVA(註冊商標)GMS 3253等GELVA系列(Henkel公司製造);MAS811(商品名)、MAS683(商品名)等MAS系列(CosMED Pharmaceutical股份有限公司製造);Eudragit(註冊商標)系列(Evonik公司製造)、Nikasol(註冊商標)系列(日本電石工業股份有限公司製造)、ULTRAZORU(註冊商標)系列(Aica Kogyo股份有限公司製造)。
以黏著劑層之總質量為基準,丙烯酸系黏著基劑之含量可設為10質量%~90質量%,亦可為20質量%~90質量%。
矽酮系黏著基劑為具有有機聚矽氧烷骨架之化合物。作為矽酮系黏著基劑,例如可例舉:二甲基聚矽氧烷、聚甲基乙烯基矽氧烷、聚甲基苯基矽氧烷。作為具體之矽酮系黏著基劑,例如可例舉:MD7-4502矽酮黏合劑(Silicone Adhesive)、MD7-4602矽酮黏合劑等MD系列(DuPont Toray Specialty Materials股份有限公司製造);BIO-PSA(註冊商標)7-4301矽酮黏合劑、BIO-PSA(註冊商標)7-4302矽酮黏合劑、BIO-PSA(註冊商標)7-4201矽酮黏合劑、BIO-PSA(註冊商標)7-4202矽酮黏合劑、BIO-PSA(註冊商標)7-4101矽酮黏合劑、BIO-PSA(註冊商標)7-4102矽酮黏合劑、BIO-PSA(註冊商標)7-4601矽酮黏合劑、BIO-PSA(註冊商標)7-4602矽酮黏合劑、BIO-PSA(註冊商標)7-4501矽酮黏合劑、BIO-PSA(註冊商標)7-4502矽酮黏合劑、BIO-PSA(註冊商標)7-4401矽酮黏合劑、BIO-PSA(註冊商標)7-4402矽酮黏合劑等BIO-PSA系列(DuPont Toray Specialty Materials股份有限公司製造)、Dow Corning(註冊商標)7-9800A、Dow Corning(註冊商標)7-9800B、Dow Corning(註冊商標)7-9700A、Dow Corning(註冊商標)7-9700B。
以黏著劑層之總質量為基準,矽酮系黏著基劑之含量可設為10質量%~90質量%,亦可為20質量%~90質量%。
出於使雙氯芬酸游離酸溶解以提高其皮膚透過性等目的,黏著劑層可進而含有二甲基亞碸。以黏著劑層之總質量為基準,二甲基亞碸之含量較佳為1質量%~20質量%、1質量%~7質量%、2質量%~10質量%、3質量%~10質量%、或4質量%~8質量%。
就提昇雙氯芬酸游離酸之皮膚透過性之觀點、及防止雙氯芬酸之結晶析出之觀點而言,雙氯芬酸游離酸與二甲基亞碸之比較佳為1:0.3~1:14、1:0.4~1:7、1:0.6~1:3、或1:0.7~1:3。
黏著劑層可進而任意含有其他添加劑。作為其他添加劑,例如可例舉:黏著賦予樹脂、塑化劑、吸收促進劑、溶解劑、穩定劑、填充劑、香料等。
黏著賦予樹脂係調整黏著劑層之黏著性之成分。作為黏著賦予樹脂,例如可例舉:石油系樹脂、萜烯系樹脂、松香系樹脂、酚系樹脂及二甲苯系樹脂等。作為石油系樹脂,例如可例舉脂環族系石油樹脂(脂環族飽和烴樹脂等)、脂肪族系石油樹脂(脂肪族烴樹脂等)、芳香族系石油樹脂等,更具體而言,可例舉:Arkon P-70、Arkon P-85、Arkon P-90、Arkon P-100、Arkon P-115、Arkon P-125、Arkon M-70、Arkon M-85、Arkon M-90、Arkon M-100、Arkon M-115、Arkon M-125(以上為商品名,荒川化學工業股份有限公司製造)、Escorez 8000(商品名,埃索(Esso)石油化學股份有限公司製造)等。作為萜烯系樹脂,例如可例舉:蒎烯聚合物(α-蒎烯聚合物、β-蒎烯聚合物等)、萜烯聚合物、雙戊烯聚合物、萜烯-苯酚聚合物、芳香族改性萜烯聚合物、蒎烯-苯酚共聚物,更具體而言,可例舉:YS Resin(YS Resin PXN(1150N、300N)、YS Resin PX1000、YS Resin TO125、YS Resin TO105等)、Clearon P105、Clearon M115、Clearon K100(以上為商品名,Yasuhara Chemical股份有限公司製造)、Tamanol 901(商品名,荒川化學工業股份有限公司製造)。作為松香系樹脂,例如可例舉:氫化松香甘油酯、超淺色松香、超淺色松香酯、酸改性超淺色松香,更具體而言,可例舉:Pine Crystal(KE-311、PE-590、KE-359、KE-100等)(商品名,荒川化學工業股份有限公司製造)等。黏著賦予樹脂可單獨使用該等中之1種,亦可組合2種以上使用。其中,較佳為脂環族飽和烴樹脂、萜烯系樹脂、氫化松香甘油酯或該等之組合,更佳為脂環族飽和烴樹脂、氫化松香甘油酯或該等之組合。於黏著劑層含有黏著賦予樹脂之情形時,以黏著劑層之總質量為基準,黏著賦予樹脂之含量可設為15質量%~80質量%,亦可為30質量%~65質量%。於使用脂環族飽和烴樹脂及氫化松香甘油酯作為黏著賦予樹脂之情形時,兩者之質量比較佳為4:1~1:4、4:1~2:3、或3:1~2:1。
作為塑化劑,例如可例舉:石蠟油(液態石蠟等)、角鯊烷、角鯊烯、植物油類(橄欖油、山茶油、蓖麻油、妥爾油、花生油、綠薄荷油、桉葉油、荷荷芭油、白樟油、葵花籽油、橙油等)、油脂類(鄰苯二甲酸二丁酯、鄰苯二甲酸二辛酯等)、及液狀橡膠(液狀聚丁烯、液狀異戊二烯橡膠等)。較佳之塑化劑為液態石蠟。塑化劑可單獨使用1種,亦可組合2種以上使用。於黏著劑層含有塑化劑之情形時,以黏著劑層之總質量為基準,塑化劑之含量例如為3質量%~50質量%、5質量%~30質量%、或7質量%~20質量%。
吸收促進劑只要為先前已知具有經皮吸收促進作用之化合物即可。作為吸收促進劑,例如可例舉:有機酸及其鹽(例如,碳原子數為6~20之脂肪族羧酸(以下,亦稱為「脂肪酸」)及其鹽、肉桂酸及其鹽)、有機酸酯(例如,脂肪酸酯、肉桂酸酯)、有機酸醯胺(例如,脂肪酸醯胺)、脂肪族醇、多元醇、醚(例如,脂肪族醚、聚氧乙烯烷基醚)等。該等吸收促進劑可具有不飽和鍵,亦可為環狀、直鏈狀或支鏈狀之化學結構。又,吸收促進劑可為單萜系化合物、倍半萜系化合物、及植物油(例如,橄欖油)。該等吸收促進劑可單獨使用1種,亦可組合2種以上使用。
作為相關有機酸,可例舉:脂肪族(單、二或三)羧酸(例如,乙酸、丙酸、異丁酸、己酸、辛酸、脂肪酸、乳酸、馬來酸、丙酮酸、草酸、琥珀酸、酒石酸等)、芳香族羧酸(例如,苯二甲酸、水楊酸、苯甲酸、乙醯水楊酸等)、肉桂酸、烷烴磺酸(例如,甲磺酸、乙磺酸、丙磺酸、丁磺酸)、烷磺酸衍生物(例如,聚氧乙烯烷基醚磺酸、N-2-羥乙基哌𠯤-N'-2-乙磺酸)、膽酸衍生物(例如,去氫膽酸等)。該等有機酸可為鈉鹽等鹼金屬鹽。其中,較佳為脂肪族羧酸、芳香族羧酸或該等之鹽,尤佳為乙酸或乙酸鈉。作為脂肪酸,例如可例舉月桂酸、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。
於另一實施方式中,黏著劑層不含檸檬酸(包括檸檬酸酐)及其鹽。具備不含檸檬酸及其鹽之黏著劑層之貼附劑能夠進一步抑制雙氯芬酸吲哚啉酮體之生成。
作為有機酸酯,例如可例舉:乙酸乙酯、乙酸丙酯、乳酸鯨蠟酯、乳酸月桂酯、水楊酸甲酯、乙二醇水楊酸酯、肉桂酸甲酯、脂肪酸酯。作為脂肪酸酯,例如可例舉:月桂酸甲酯、月桂酸己酯、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、棕櫚酸異丙酯、棕櫚酸鯨蠟酯。脂肪酸酯可為甘油脂肪酸酯、丙二醇脂肪酸酯、山梨醇酐脂肪酸酯、聚乙二醇山梨醇酐脂肪酸酯、聚乙二醇脂肪酸酯、蔗糖脂肪酸酯、或聚氧乙烯氫化蓖麻油。作為脂肪酸酯之具體例,可例舉: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、聚山梨糖醇酯20、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、Span40、Span60、Span80、Span120(商品名,Croda Japan股份有限公司製造)、Tween(註冊商標)20、Tween(註冊商標)21、Tween(註冊商標)40、Tween(註冊商標)60、Tween(註冊商標)80、NIKKOL(註冊商標)HCO-60(商品名,Nikko Chemicals股份有限公司製造)。
作為有機酸醯胺,例如可例舉:脂肪酸醯胺(例如,月桂酸二乙醇醯胺)、六氫-1-十二烷基-2H-氮呯-2-酮(亦稱為Azone)及其衍生物、吡咯硫代癸烷。
脂肪醇係指碳原子數為6~20之脂肪族醇。作為脂肪醇,例如可例舉:月桂醇、肉豆蔻醇、油醇、異硬脂醇、鯨蠟醇。作為多元醇,例如可例舉丙二醇。
脂肪醚係指具有碳原子數為6~20之脂肪族基(例如,烷基、烯基)之醚。作為聚氧乙烯烷基醚,例如可例舉聚氧乙烯月桂醚。
作為單萜系化合物,例如可例舉:香葉草醇、瑞香草酚、松油醇、l-薄荷腦、冰片、d-檸檬烯、異冰片、橙花醇、dl-樟腦。作為單萜系化合物,亦可使用薄荷油。
於黏著劑層含有吸收促進劑之情形時,以黏著劑層之總質量為基準,吸收促進劑之含量可設為2質量%~40質量%。
溶解劑係使雙氯芬酸游離酸容易溶解於黏著劑組合物中之成分。作為溶解劑,例如可例舉:脂肪酸烷基酯(例如,肉豆蔻酸異丙酯、棕櫚酸異丙酯)、脂肪酸多元醇酯(例如,單月桂酸丙二醇酯、單月桂酸甘油酯、單油酸甘油酯、山梨醇酐單月桂酸酯)、脂肪酸醯胺(例如,月桂酸二乙醇醯胺)、脂肪族醇(例如,辛基十二烷醇、異硬脂醇、油醇)、多元醇(例如,丙二醇、二丙二醇、聚乙二醇)、吡咯啶酮衍生物(例如,N-甲基-2-吡咯啶酮)、胺(例如,三乙醇胺、二乙醇胺、單乙醇胺、二異丙醇胺、胺丁三醇、葡甲胺)。溶解劑可單獨使用1種,亦可組合2種以上使用。於黏著劑層含有溶解劑之情形時,以黏著劑層之總質量為基準,溶解劑之含量可設為2質量%~40質量%。
穩定劑只要為可抑制因紫外線等光線、熱或活性化學物種之作用而產生之自由基之生成及其連鎖反應之進行者即可。作為穩定劑,例如可例舉:維生素E及其酯衍生物、抗壞血酸及其酯衍生物、2,6-二丁基羥基甲苯、丁基羥基甲氧苯、2-硫醇基苯并咪唑等。穩定劑可單獨使用1種,亦可組合2種以上使用。於黏著劑層含有穩定劑之情形時,以黏著劑層之總質量為基準,穩定劑之含量可設為0.05質量%~3質量%,亦可為0.05質量%~1質量%、0.05質量%~0.25質量%或0.1質量%~0.25質量%。
作為填充劑,例如可例舉:金屬化合物(氧化鋁、氫氧化鋁、氧化鋅、氧化鈦、碳酸鈣等)、陶瓷(滑石、黏土、高嶺土、二氧化矽、羥磷石灰、合成矽酸鋁、矽酸鋁鎂等)或有機化合物(纖維素粉末、硬脂酸鹽等)之粉末或包含該等之樹脂之短纖維。填充劑可單獨使用1種,亦可組合2種以上使用。於黏著劑層含有填充劑之情形時,以黏著劑層之總質量為基準,填充劑之含量可設為0.1質量%~20質量%。
貼附劑可進而具備剝離襯墊。剝離襯墊積層於黏著劑層之與支持體為相反側之面。若具備剝離襯墊,則傾向於可減少保存時污物等附著於黏著劑層之情況。剝離襯墊之與黏著劑層相接之面較佳為已利用矽酮或氟化聚烯烴等進行離型處理。
作為剝離襯墊之素材,並無特別限定,可使用本領域技術人員公知之襯墊。作為剝離襯墊,例如可例舉:紙;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、尼龍、鋁等之膜。剝離襯墊可為高級紙與聚烯烴之層壓膜。作為剝離襯墊之材質,較佳為由聚丙烯或聚對苯二甲酸乙二酯製造之膜。
本發明之一實施方式之貼附劑之製造方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟。更具體而言,貼附劑例如可藉由以下方法進行製造。首先,將構成黏著劑層之各成分以特定之比率混合而獲得均勻之溶解物(黏著劑組合物)。然後,使黏著劑組合物以特定之膏體質量於可剝離之膜(剝離襯墊)或支持體層上延展而形成黏著劑層。繼而,以黏著劑層夾於可剝離之膜與支持體層之間之方式,將黏著劑層壓接於支持體層或可剝離之膜。最後,切斷為所需之形狀,藉此可獲得貼附劑。於此情形時,剝離襯墊於應用貼附劑時去除。
本發明之一實施方式之抑制黏著劑層中之雙氯芬酸吲哚啉酮體之生成之方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟。更具體而言,可藉由與上述之貼附劑之製造方法相同之方法來實施。
貼附劑之面積可為5~200 cm
2,亦可為30~100 cm
2。貼附劑之形狀及尺寸例如可為短邊3~14 cm且長邊7~20 cm之矩形、或直徑1~10 cm之圓形。
[實施例]
實驗1:使用橡膠系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
按照下述表1,混合各成分,獲得黏著劑組合物。以每單位面積之膏體質量為214 g/m
2之方式,使所得之黏著劑組合物於剝離襯墊(經實施離型處理之聚對苯二甲酸乙二酯製膜)上延展,形成黏著劑層。於所得之黏著劑層之與上述相反之面上積層支持體層(聚對苯二甲酸乙二酯製編織布),獲得依序積層有支持體層/黏著劑層/剝離襯墊之貼附劑。
2.雙氯芬酸吲哚啉酮體含量之測定
雙氯芬酸吲哚啉酮體之含量係使用剛製造後之貼附劑、及製造後於60℃下在鋁製包裝袋中保存1週後之貼附劑,按以下順序進行測定。
首先,取出貼附劑之黏著劑層,浸漬於2 mL丙酮中,提取有機物。
然後,加入6 mL稀釋溶液(0.1%磷酸水溶液/甲醇=60/40(v/v)),使總量為8 mL,過濾不溶物後,藉由以下之分析條件下之高效液相層析法來獲得雙氯芬酸游離酸及雙氯芬酸吲哚啉酮體之峰分離之層析圖。雙氯芬酸吲哚啉酮體之含量係將雙氯芬酸游離酸之理論量設為100,根據雙氯芬酸吲哚啉酮體所對應之峰曲線下面積之值而算出。
<分析條件>
管柱:YMC-PacK Pro C8
流動相:0.1%磷酸水溶液/甲醇=60/40(v/v)
測定波長:275 nm
流量:1 mL/min
試樣注入量:30 μL
管柱溫度:40℃
[表1]
比較例1 | 實施例1 | 實施例2 | 實施例3 | 實施例4 | 比較例2 | |
雙氯芬酸游離酸 | - | 1.00 | 3.00 | 4.65 | 7.00 | 10.00 |
雙氯芬酸鈉 | 5.00 | - | - | - | - | - |
苯乙烯-異戊二烯-苯乙烯嵌段共聚物 | 19.15 | 20.89 | 20.32 | 19.85 | 19.18 | 18.33 |
聚異丁烯 | 8.21 | 8.96 | 8.71 | 8.51 | 8.24 | 7.86 |
脂環族飽和烴樹脂 | 27.00 | 29.45 | 28.65 | 27.99 | 27.05 | 25.84 |
氫化松香甘油酯 | 10.00 | 10.00 | 10.00 | 10.00 | 10.00 | 10.00 |
液態石蠟 | 12.53 | 13.66 | 13.30 | 12.99 | 12.55 | 11.99 |
油酸 | 5.00 | 5.00 | 5.00 | 5.00 | 5.00 | 5.00 |
二甲基亞碸 | 7.00 | 7.00 | 7.00 | 7.00 | 7.00 | 7.00 |
檸檬酸酐 | 2.11 | - | - | - | - | - |
其他 | 4.00 | 4.04 | 4.02 | 4.01 | 4.0 | 3.98 |
合計 | 100 | 100 | 100 | 100 | 100 | 100 |
剛製造後之吲哚啉酮體之生成率(%) | 0.84 | 0.13 | 0.15 | 0.21 | 0.22 | 0.42 |
於60℃下保存1週後之吲哚啉酮體之生成率(%) | 2.18 | 0.33 | 0.55 | 0.65 | 1.36 | 2.57 |
確認到,相較於含有雙氯芬酸鈉之比較例1之貼附劑,含有雙氯芬酸游離酸之實施例1~4之貼附劑更能夠抑制雙氯芬酸吲哚啉酮體之生成。又,確認到,於比較例2之貼附劑之情形時,無法抑制雙氯芬酸吲哚啉酮體之生成,於上述比較例2之貼附劑中,以黏著劑層之總質量為基準,雙氯芬酸游離酸之含量為10質量%。
實驗2:使用丙烯酸系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
按照下述表2,混合各成分,獲得黏著劑組合物。以每單位面積之膏體質量為120 g/m
2之方式,使所得之黏著劑組合物於剝離襯墊(經實施離型處理之聚對苯二甲酸乙二酯製膜)上延展,將溶劑乾燥去除而形成黏著劑層。於所得之黏著劑層之與上述相反之面上積層支持體層(聚對苯二甲酸乙二酯製膜),獲得依序積層有支持體層/黏著劑層/剝離襯墊之貼附劑。
2.雙氯芬酸吲哚啉酮體含量之測定
以與實驗1相同之方式進行測定。
[表2]
比較例3 | 實施例5 | |
雙氯芬酸游離酸 | - | 4.65 |
雙氯芬酸鈉 | 5.00 | - |
丙烯酸系黏著基劑(MAS811B) | 77.89 | 80.35 |
油酸 | 5.00 | 5.00 |
二甲基亞碸 | 7.00 | 7.00 |
檸檬酸酐 | 2.11 | - |
其他 | 3.00 | 3.00 |
合計 | 100 | 100 |
剛製造後之吲哚啉酮體之生成率(%) | 0.09 | 0.06 |
於60℃下保存1週後之吲哚啉酮體之生成率(%) | 2.05 | 0.84 |
確認到,即便於使用丙烯酸系黏著基劑之情形時,相較於含有雙氯芬酸鈉之比較例3之貼附劑,含有雙氯芬酸游離酸之實施例5之貼附劑亦更能夠抑制雙氯芬酸吲哚啉酮體之生成。
實驗3:使用矽酮系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
以與實驗2相同之方式,按照下述表3之組成製造貼附劑。但是,於本實施例中,以每單位面積之膏體質量為160 g/m
2之方式進行延展。
2.雙氯芬酸吲哚啉酮體含量之測定
以與實驗1相同之方式進行測定。
[表3]
比較例4 | 實施例6 | |
雙氯芬酸游離酸 | - | 4.65 |
雙氯芬酸鈉 | 5.00 | - |
矽酮系黏著基劑(BIO-PSA 7-4202) | 77.89 | 80.35 |
油酸 | 5.00 | 5.00 |
二甲基亞碸 | 7.00 | 7.00 |
檸檬酸酐 | 2.11 | - |
其他 | 3.00 | 3.00 |
合計 | 100 | 100 |
剛製造後之吲哚啉酮體之生成率(%) | 0.21 | 0.06 |
於60℃下保存1週後之吲哚啉酮體之生成率(%) | 5.32 | 1.23 |
確認到,即便於使用矽酮系黏著基劑之情形時,相較於含有雙氯芬酸鈉之比較例4之貼附劑,含有雙氯芬酸游離酸之實施例6之貼附劑亦更能夠抑制雙氯芬酸吲哚啉酮體之生成。
實驗4:不含聚異丁烯之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
以與實驗1相同之方式,按照下述表4之組成製造貼附劑。
2.雙氯芬酸吲哚啉酮體之含量之測定
以與實驗1相同之方式進行測定。
[表4]
實施例7 | |
雙氯芬酸游離酸 | 4.65 |
苯乙烯-異戊二烯-苯乙烯嵌段共聚物 | 22.76 |
聚異丁烯 | - |
脂環族飽和烴樹脂 | 32.10 |
氫化松香甘油酯 | 10.00 |
液態石蠟 | 14.89 |
油酸 | 5.00 |
二甲基亞碸 | 7.00 |
其他 | 3.60 |
合計 | 100 |
剛製造後之吲哚啉酮體之生成率(%) | 0.17 |
於60℃下保存1週後之吲哚啉酮體之生成率(%) | 1.03 |
確認到,即便於不含聚異丁烯之情形時,相較於含有雙氯芬酸鈉之比較例1之貼附劑,含有雙氯芬酸游離酸之實施例7之貼附劑亦更能夠抑制雙氯芬酸吲哚啉酮體之生成。又,確認到實施例7之貼附劑與實施例1~4之貼附劑相比,雙氯芬酸吲哚啉酮體之生成率亦為同等程度。
實驗5:使用丙烯酸系黏著基劑或矽酮系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
以與實驗2相同之方式,按照下述表5之組成製造實施例8~9之貼附劑。又,以與實驗3相同之方式,按照下述表5之組成製造實施例10~11之貼附劑。
2.雙氯芬酸吲哚啉酮體之含量之測定
以與實驗1相同之方式進行測定。
[表5]
實施例8 | 實施例9 | 實施例10 | 實施例11 | |
雙氯芬酸游離酸 | 1.00 | 7.00 | 1.00 | 4.65 |
丙烯酸系黏著基劑(MAS811B) | 84.00 | 78.00 | - | - |
矽酮系黏著基劑(BIO-PSA 7-4202) | - | - | 90.00 | - |
矽酮系黏著基劑(BIO-PSA 7-4502) | - | - | - | 80.35 |
油酸 | 5.00 | 5.00 | 5.00 | 5.00 |
二甲基亞碸 | 7.00 | 7.00 | 1.00 | 7.00 |
其他 | 3.00 | 3.00 | 3.00 | 3.00 |
合計 | 100 | 100 | 100 | 100 |
剛製造後之吲哚啉酮體之生成率(%) | 0.00 | 0.04 | 0.00 | 0.18 |
於60℃下保存1週後之吲哚啉酮體之生成率(%) | 0.29 | 1.34 | 0.57 | 0.48 |
確認到,即便於使用丙烯酸系黏著基劑或矽酮系黏著劑之情形時,實施例8~10之貼附劑與含有雙氯芬酸鈉之比較例3或4之貼附劑相比,亦能夠抑制雙氯芬酸吲哚啉酮體之生成,於上述實施例8~10中,使以黏著劑層之總質量為基準之雙氯芬酸游離酸之含量於0.5質量%~8質量%之範圍內變化。又,確認到,使用有與實施例6不同之矽酮系黏著基劑之實施例11之貼附劑相較於含有雙氯芬酸鈉之比較例4之貼附劑,更能夠抑制雙氯芬酸吲哚啉酮體之生成。
Claims (3)
- 一種方法,其係於具備支持體層、及積層於上述支持體層上之黏著劑層的貼附劑中抑制黏著劑層中之雙氯芬酸吲哚啉酮體之生成之方法, 該方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟, 以上述黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
- 一種方法,其係具備支持體層、及積層於上述支持體層上之黏著劑層的貼附劑之製造方法, 該方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟, 以上述黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
- 一種貼附劑,其具備支持體層、及積層於上述支持體層上之黏著劑層,上述黏著劑層含有雙氯芬酸游離酸及黏著基劑,以上述黏著劑層之總質量為基準,上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
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