TWI805535B - 含有利多卡因之貼附劑 - Google Patents
含有利多卡因之貼附劑 Download PDFInfo
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- TWI805535B TWI805535B TW111148879A TW111148879A TWI805535B TW I805535 B TWI805535 B TW I805535B TW 111148879 A TW111148879 A TW 111148879A TW 111148879 A TW111148879 A TW 111148879A TW I805535 B TWI805535 B TW I805535B
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- TW
- Taiwan
- Prior art keywords
- mass
- adhesive layer
- adhesive
- lidocaine
- registered trademark
- Prior art date
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- 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
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- 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
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Abstract
本發明係一種貼附劑,其係於支持體上具備黏著劑層者,上述黏著劑層含有利多卡因或其藥學上可容許之鹽、丙二醇、橡膠系黏著基劑及萜烯系樹脂,關於上述黏著劑層中之利多卡因或其藥學上可容許之鹽之含量,以上述黏著劑層之總質量為基準,以利多卡因之游離體換算為2質量%~6質量%,上述黏著劑層中之利多卡因或其藥學上可容許之鹽與丙二醇之質量比以利多卡因之游離體換算為1:0.6~1:1.8,上述黏著劑層中之萜烯系樹脂之含量以上述黏著劑層之總質量為基準,為5質量%~18質量%。
Description
本發明係關於一種含有利多卡因之貼附劑。
已知具有局部麻醉作用之利多卡因以低劑量投予便具有鎮痛效果,故對治療術後疼痛及因神經障礙引起之疼痛有效,並以肌內注射、靜脈內注射、點滴、凝膠、貼附劑等形式進行投予。其中,關於利用貼附劑之經皮投予方法,就投予之容易性、或提昇適應性、效果持續之優點而言,其為有用之投予方法。
關於含有利多卡因之貼附劑,例如,於專利文獻1(國際公開第2013/046335號)中,作為用於以溶解狀態預先調配利多卡因之溶解劑,揭示有一種使用有機酸、多元醇類或界面活性劑之含有利多卡因之非水性貼附劑。又,於專利文獻2(日本公表專利公報第2018-525419號公報)中,揭示有一種含有包含有機酸及多元醇之混合物之溶解劑的非水性貼附劑。
發明所欲解決之問題
本發明人等對含有利多卡因之貼附劑進行了研究,結果發現,於使用多元醇作為利多卡因之溶解劑之情形時,根據多元醇之種類,於製造過程中或剛製造後之貼附劑中結晶析出。析出了藥物結晶之貼附劑經常存在藥物之皮膚透過性降低、不能得到充分之藥效之問題。
又,本發明人等發現於多元醇之含量較多之貼附劑中,具有黏著力降低之傾向,另一方面,存在貼附面彼此較強地黏著而難以剝離之傾向,即,自黏性較強之傾向。關於自黏性較強之貼附劑,若於將貼附劑貼附時誤使貼附面彼此接觸,則會產生難以剝離,不能適當地貼附之問題。
因此,本發明之目的在於提供一種能抑制結晶析出,且抑制自黏性之含有利多卡因之貼附劑。
解決問題之技術手段
本發明人等進行了努力研究,結果發現,於黏著劑層中包含規定量之丙二醇及規定量之萜烯系樹脂之貼附劑能抑制結晶析出,且抑制自黏性,從而完成了本發明。
即,本發明之貼附劑於支持體上具備黏著劑層,上述黏著劑層含有利多卡因或其藥學上可容許之鹽、丙二醇、橡膠系黏著基劑及萜烯系樹脂,關於上述黏著劑層中之利多卡因或其藥學上可容許之鹽之含量,以上述黏著劑層之總質量為基準,以利多卡因之游離體換算為2質量%~6質量%,上述黏著劑層中之利多卡因或其藥學上可容許之鹽與丙二醇之質量比以利多卡因之游離體換算為1:0.6~1:1.8,上述黏著劑層中之萜烯系樹脂之含量以上述黏著劑層之總質量為基準,為5質量%~18質量%。
發明之效果
根據本發明,可提供一種能抑制結晶析出,抑制自黏性,且黏著力優異之含有利多卡因之貼附劑。
以下,示出本發明之實施方式,對本發明進行詳細說明。
本發明之一實施方式之貼附劑於支持體上具備黏著劑層,上述黏著劑層含有利多卡因或其藥學上可容許之鹽、丙二醇、橡膠系黏著基劑及萜烯系樹脂,關於上述黏著劑層中之利多卡因或其藥學上可容許之鹽之含量,以上述黏著劑層之總質量為基準,以利多卡因之游離體換算為2質量%~6質量%,上述黏著劑層中之利多卡因或其藥學上可容許之鹽與丙二醇之質量比以利多卡因之游離體換算為1:0.6~1:1.8,關於上述黏著劑層中之萜烯系樹脂之含量,以上述黏著劑層之總質量為基準,為5質量%~18質量%。
支持體只要可維持貼附劑,特別是黏著劑層之形狀即可。作為支持體之材質,例如可例舉: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。關於支持體之性狀,例如為膜、片材、片狀多孔質體、片狀發泡體、織布、編織布、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 μm~3000 μm左右。支持體之單位面積重量例如為30 g/m
2~200 g/m
2。於本說明書中,支持體之厚度及單位面積重量基於JIS L 1906:2000之標準而測定。
黏著劑層係由混合利多卡因或其藥學上可容許之鹽、丙二醇、橡膠系黏著基劑、萜烯系樹脂、及下述之任意成分而得之黏著劑組合物所形成。黏著劑層之每單位面積之質量並無特別限制,可為15 g/m
2~400 g/m
2,亦可為50 g/m
2~300 g/m
2、100 g/m
2~200 g/m
2、或130 g/m
2~170 g/m
2。若黏著劑層之每單位面積之質量超過400 g/m
2,則於被覆之脫離時等,貼附劑容易脫落。若黏著劑層之每單位面積之質量未達15 g/m
2,則貼附劑之黏著力容易降低。
利多卡因之藥學上可容許之鹽意指於利多卡因之酸加成鹽中,可用作醫藥者。作為有機酸,例如可例舉:甲酸、乙酸、己二酸、檸檬酸、酒石酸、甲磺酸、富馬酸、馬來酸等。作為無機酸,例如可例舉:鹽酸、硫酸、硝酸、磷酸等。利多卡因之藥學上可容許之鹽較佳為鹽酸利多卡因。利多卡因或其藥學上可容許之鹽可為酸酐,亦可為水合物。
關於利多卡因或其藥學上可容許之鹽之含量,以黏著劑層之總質量為基準,可為2質量%~6質量%,亦可為3質量%~5質量%。再者,上述質量%意指於為黏著劑層中含有利多卡因之藥學上可容許之鹽的貼附劑之情形時,利多卡因之游離體換算之質量%。
丙二醇抑制於製造過程中或剛製造後之貼附劑析出結晶。黏著劑層中之利多卡因或其藥學上可容許之鹽與丙二醇之質量比可為1:0.6~1:1.8,亦可為1:0.75~1:1.75。利多卡因或其藥學上可容許之鹽與丙二醇之質量比為上述範圍內之貼附劑能抑制結晶析出,且能抑制自黏性。丙二醇之含量以黏著劑層之總質量為基準,可為1.2質量%~7質量%,亦可為1.8質量%~7質量%,亦可為3質量%~7質量%。
橡膠系黏著基劑對黏著劑層賦予黏著性。作為橡膠系黏著基劑,可例舉:苯乙烯-丁二烯嵌段共聚物、苯乙烯-丁二烯-苯乙烯嵌段共聚物、苯乙烯-異戊二烯嵌段共聚物、苯乙烯-異戊二烯-苯乙烯嵌段共聚物、聚異丁烯、天然橡膠、烷基乙烯基醚(共)聚合物、聚異戊二烯、聚丁二烯等,可單獨使用該等中之1種,亦可組合2種以上而使用。
作為本實施方式之橡膠系黏著基劑,就存在可發揮黏著劑層之更充分之黏著力的傾向之觀點而言,較佳為包含選自由苯乙烯-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,更佳為包含苯乙烯-異戊二烯-苯乙烯嵌段共聚及聚異丁烯。
作為苯乙烯-異戊二烯-苯乙烯嵌段共聚物之具體例,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(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,巴斯夫公司製造)、JSR(註冊商標)Butyl065、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)Butyl065、065S、068、068S、268、268S、365、365S(商品名,Exxon Mobile公司製造)等。
關於橡膠系黏著基劑之含量,以黏著劑層之總質量為基準,可為10質量%~80質量%,亦可為15質量%~60質量%,亦可為15質量%~40質量%。
黏著劑層除橡膠系黏著基劑以外,可包含選自由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。關於黏著基劑之總含量,以黏著劑層之總質量為基準,可為10質量%~95質量%,亦可為20質量%~90質量%。
丙烯酸系黏著基劑例如為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」之用語係指丙烯酸及甲基丙烯酸中之任一者或兩者,類似之表達亦被同樣地定義。
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種以上而使用。共聚單體只要是可與(甲基)丙烯酸烷基酯共聚合之成分即可。作為共聚單體,例如可例舉:(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。
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所含有之丙烯酸系高分子等。作為此種丙烯酸系黏著基劑,作為具體例,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(Cosmedy Pharma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)、ultrasole(註冊商標)系列(Aica Kogyo股份有限公司製造)。
關於丙烯酸系黏著基劑之含量,以黏著劑層之總質量為基準,可為10質量%~50質量%,亦可為10質量%~20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 Silicone Adhesive、MD7-4602 Silicone Adhesive等MD系列(Dupont・Toray・Specialty・Material股份有限公司製造);BIO-PSA(註冊商標) 7-4301 Silicone Adhesive、BIO-PSA(註冊商標) 7-4302 Silicone Adhesive、BIO-PSA(註冊商標) 7-4201 Silicone Adhesive、BIO-PSA(註冊商標) 7-4202 Silicone Adhesive、BIO-PSA(註冊商標) 7-4101 Silicone Adhesive、BIO-PSA(註冊商標) 7-4102 Silicone Adhesive、BIO-PSA(註冊商標) 7-4601 Silicone Adhesive、BIO-PSA(註冊商標) 7-4602 Silicone Adhesive、BIO-PSA(註冊商標) 7-4501 Silicone Adhesive、BIO-PSA(註冊商標) 7-4502 Silicone Adhesive、BIO-PSA(註冊商標) 7-4401 Silicone Adhesive、BIO-PSA(註冊商標) 7-4402 Silicone Adhesive等BIO-PSA系列(Dupont・Toray・Specialty・Material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。
關於矽酮系黏著基劑之含量,以黏著劑層之總質量為基準,可為10質量%~50質量%,亦可為10質量%~20質量%。
萜烯系樹脂作為黏著賦予樹脂發揮功能。關於萜烯系樹脂之含量,以黏著劑層之總質量為基準,可為5質量%~18質量%,亦可為9質量%~14質量%。萜烯系樹脂之含量為上述範圍內之貼附劑可發揮充分之黏著力並且亦可抑制自黏性。
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)。
黏著劑層亦可進而任意地含有其他添加劑。作為其他添加劑,例如可例舉:除萜烯系樹脂以外之黏著賦予樹脂、塑化劑、吸收促進劑、除丙二醇以外之溶解劑、穩定劑、填充劑、香料等。
黏著賦予樹脂為調整黏著劑層之黏著性之成分。黏著劑層除萜烯系樹脂以外,例如亦可含有石油系樹脂、松香系樹脂、酚系樹脂及二甲苯系樹脂等黏著賦予樹脂。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,Esso石油化學股份有限公司製造)等。作為松香系樹脂,例如可例舉:氫化松香甘油酯、超淡色松香、超淡色松香酯、酸改性超淡色松香,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。除萜烯系樹脂以外,可單獨使用該等黏著賦予樹脂中之1種,亦可組合2種以上而使用。於黏著劑層還含有除萜烯系樹脂以外之黏著賦予樹脂之情形時,關於黏著賦予樹脂之含量(除去萜烯系樹脂之含量),以黏著劑層之總質量為基準,可為5質量%~50質量%,亦可為10質量%~40質量%。
作為塑化劑,例如可例舉:液態石蠟、輕質液態石蠟、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、桉樹油、荷荷芭油、白樟油、葵花籽油、橙皮油等)、油脂類(鄰苯二甲酸二丁酯、鄰苯二甲酸二辛酯等)、及液態橡膠(液態聚丁烯、液態異戊二烯橡膠等)等。該等塑化劑可單獨使用1種,亦可組合2種以上而使用。於黏著劑層含有塑化劑之情形時,其含量以黏著劑層之總質量為基準,例如為3質量%~50質量%、10質量%~50質量%、或20質量%~50質量%。
吸收促進劑只要是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:有機酸酯(例如脂肪酸酯、肉桂酸酯)、有機酸醯胺(例如脂肪醯胺)、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、直鏈狀或分枝狀之化學結構。又,吸收促進劑亦可為單萜烯系化合物、倍半萜烯系化合物、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種以上而使用。
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。
脂肪族醇意指碳原子數6~20之脂肪族醇。作為脂肪族醇,例如可例舉:月桂醇、肉豆蔻醇、油醇、異硬脂醇、鯨蠟醇。
脂肪族醚意指具有碳原子數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。
作為單萜烯系化合物,例如可例舉:香葉草醇、瑞香草酚、萜品醇、l-薄荷腦、龍腦、d-檸檬烯、異龍腦、橙花醇、dl-樟腦。作為單萜烯系化合物,可使用薄荷油。
於黏著劑層含有吸收促進劑之情形時,吸收促進劑之含量以黏著劑層之總質量為基準,可為0.5質量%~20質量%。
溶解劑係使利多卡因或其藥學上可容許之鹽容易溶解於黏著劑組合物中之成分。黏著劑層除丙二醇以外,例如亦可含有脂肪酸多元醇酯(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)等溶解劑。除丙二醇以外,還可單獨使用該等溶解劑中之1種,亦可組合2種以上而使用。於黏著劑層含有丙二醇以外之溶解劑之情形時,溶解劑之含量(丙二醇之含量除外)以黏著劑層之總質量為基準,可為2質量%~10質量%。
穩定劑只要可抑制因紫外線等光線、熱或活性化學種之作用而發生之自由基之生成及其連鎖反應之進行即可。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(BHT)、丁基羥基甲氧苯(BHA)、2-硫醇基苯并咪唑等。穩定劑可單獨使用1種,亦可組合2種以上而使用。於黏著劑層含有穩定劑之情形時,穩定劑之含量以黏著劑層之總質量為基準,可為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、氫氧磷灰石、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)之粉末或包含其等之樹脂之短纖維。填充劑可單獨使用1種,亦可組合2種以上而使用。於黏著劑層含有填充劑之情形時,填充劑之含量以黏著劑層之總質量為基準,可為0.1質量%~20質量%。
貼附劑亦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相反側之面。若具備剝離襯墊,則具有於保管時,可減少污物等附著於黏著劑層之傾向。剝離襯墊之與黏著劑層接觸之面較佳為經矽酮或氟化聚烯烴等進行了離型處理。
剝離襯墊之素材並無特別限定,可使用業者通常已知之襯墊。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。剝離襯墊亦可為道林紙與聚烯烴之層壓薄膜。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製之膜。
貼附劑例如可藉由以下方法進行製造,但不限定於此,可使用公知之方法。首先,將構成黏著劑層之各成分以規定之比率進行混合而得到均勻之溶解物(黏著劑組合物)。其次,於可剝離之膜(剝離襯墊)上以規定之厚度使黏著劑組合物延展而形成黏著劑層。進而,以使黏著劑層夾於剝離襯墊與支持體間之方式將支持體壓接於黏著劑層。最後,藉由裁剪成所需之形狀及尺寸,可得到貼附劑。於該情形時,剝離襯墊於應用貼附劑時被去除。貼附劑之面積可為5 cm
2~200 cm
2,亦可為50 cm
2~150 cm
2。貼附劑之形狀及尺寸例如可為短邊2 cm~10 cm且長邊3 cm~15 cm之矩形、或直徑1 cm~8 cm之圓形。
實施例
1.貼附劑之製備
按照表1~3,混合各成分而得到黏著劑組合物。將所得到之黏著劑組合物於剝離襯墊(經離型處理之聚對苯二甲酸乙二酯製膜)上以每單位面積之質量成為150 g/m
2之方式延展,而形成黏著劑層。於所得到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,厚度550 μm,單位面積重量110 g/m
2),而得到依序積層有支持體層/黏著劑層/剝離襯墊之貼附劑。
2.評價方法
按照以下之評價方法對所得到之貼附劑進行評價。
(a)結晶析出
無:於製造過程中或剛製造後之貼附劑中未確認到結晶析出。
有:於製造過程中或剛製造後之貼附劑中確認到結晶析出。
(b)自黏性
將所製造之貼附劑裁剪成20 mm×70 mm之尺寸,於拉伸試驗機以夾頭間距離成為30 mm之方式設置貼附劑後,將夾頭間距離設為5 mm,使黏著面彼此附著。然後,以50 mm/分鐘之速度拉伸貼附劑,測定0 mm~25 mm之積分平均負載(N)的3次之平均值作為剝離各貼附劑之黏著面所需之力。剝離黏著面所需之力為1.3 N以下之貼附劑即使貼附面彼此黏著,亦可容易地剝離。
(c)黏著力
藉由傾斜式滾球黏性試驗法(日本藥典第十八修訂版,一般試驗法6.12黏著力試驗法),將No.30(直徑15/16英吋)以下之球自傾斜板之上端滾動時,將停止之最大之球編號評價為各貼附劑之黏著力。停止之最大之球編號較大之製劑意味著黏著力優異。
[表1]
質量%
實施例1 | 比較例1 | 比較例2 | 比較例3 | |
利多卡因 | 4.0 | 4.0 | 4.0 | 4.0 |
丙二醇 | 3.0 | - | - | - |
聚乙二醇 (PEG400) | - | 4.0 | - | - |
聚丙二醇 (聚丙二醇2000) | - | - | 4.0 | - |
甘油 | - | - | - | 4.0 |
萜烯系樹脂 | 14.0 | 14.0 | 14.0 | 14.0 |
苯乙烯-異戊二烯-苯乙烯嵌段共聚物 | 26.5 | 26.5 | 26.5 | 26.5 |
聚異丁烯 | 11.2 | 11.2 | 11.2 | 11.2 |
液態石蠟 | 40.4 | 39.4 | 39.4 | 39.4 |
其他 | 0.9 | 0.9 | 0.9 | 0.9 |
合計 | 100.0 | 100.0 | 100.0 | 100.0 |
結晶析出 | 無 | 有 | 有 | 有 |
自黏性:黏著面彼此剝離所需之力(N) | 1.18 | - | - | - |
黏著力(停止之最大之球No.) | 30 | 30 | 29 | 30 |
於含有丙二醇作為多元醇之貼附劑(實施例1)中,結晶未析出,相對於此,於含有聚乙二醇、聚丙二醇或甘油作為多元醇之貼附劑(比較例1~3)中,結晶析出。再者,比較例1~3之貼附劑中由於析出了結晶,故不進行自黏性之評價。
[表2]
質量%
比較例4 | 比較例5 | 實施例1 | 實施例2 | 比較例6 | 比較例7 | |
利多卡因 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 |
丙二醇 | - | 2.0 | 3.0 | 7.0 | 8.0 | 14.0 |
萜烯系樹脂 | 14.0 | 14.0 | 14.0 | 14.0 | 14.0 | 14.0 |
苯乙烯-異戊二烯-苯乙烯嵌段共聚物 | 26.5 | 26.5 | 26.5 | 26.5 | 26.5 | 26.5 |
聚異丁烯 | 11.2 | 11.2 | 11.2 | 11.2 | 11.2 | 11.2 |
液態石蠟 | 43.4 | 41.4 | 40.4 | 36.4 | 35.4 | 29.4 |
其他 | 0.9 | 0.9 | 0.9 | 0.9 | 0.9 | 0.9 |
合計 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
利多卡因:丙二醇 | - | 1:0.5 | 1:0.75 | 1:1.75 | 1:2 | 1:3.5 |
結晶析出 | 有 | 有 | 無 | 無 | 無 | 無 |
自黏性:黏著面彼此剝離所需之力(N) | 1.03 | 1.13 | 1.18 | 1.30 | 1.36 | 1.26 |
黏著力(停止之最大之球No.) | - | 30 | 30 | 30 | 29 | - |
利多卡因與丙二醇之質量比為1:0.6~1:1.8之範圍內的貼附劑(實施例1~2)中結晶未析出,自黏性得到抑制,且黏著力優異。
不含丙二醇之貼附劑(比較例4)中由於析出了結晶,故不進行黏著力之評價。比較例7之貼附劑由於丙二醇的量較多,故產生所謂之滲出(液態成分向黏著劑層表面之浸出),故不適合作為製劑。因此,不對比較例7之貼附劑之黏著力進行評價。利多卡因與丙二醇之質量比為1:0.5之貼附劑(比較例5)中結晶析出。利多卡因與丙二醇之質量比為1:2之貼附劑(比較例6)之自黏性較強,且黏著力較差。
[表3]
質量%
實施例1 | 比較例8 | 比較例9 | 實施例3 | 實施例2 | 比較例10 | 比較例11 | |
利多卡因 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 |
丙二醇 | 3.0 | 4.0 | 7.0 | 7.0 | 7.0 | 7.0 | 7.0 |
萜烯系樹脂 | 14.0 | - | 4.0 | 9.0 | 14.0 | 19.0 | 24.0 |
氫化松香甘油酯 | - | 14.0 | - | - | - | - | - |
苯乙烯-異戊二烯-苯乙烯嵌段共聚物 | 26.5 | 26.5 | 26.5 | 26.5 | 26.5 | 26.5 | 26.5 |
聚異丁烯 | 11.2 | 11.2 | 11.2 | 11.2 | 11.2 | 11.2 | 11.2 |
液態石蠟 | 40.4 | 39.4 | 39.4 | 41.4 | 36.4 | 31.4 | 26.4 |
其他 | 0.9 | 0.9 | 0.9 | 0.9 | 0.9 | 0.9 | 0.9 |
合計 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 |
利多卡因:丙二醇 | 1:0.75 | 1:1 | 1:1.75 | 1:1.75 | 1:1.75 | 1:1.75 | 1:1.75 |
結晶析出 | 無 | 無 | 無 | 無 | 無 | 無 | 無 |
自黏性:黏著面彼此剝離所需之力(N) | 1.18 | 0.60 | 0.83 | 1.07 | 1.30 | 2.47 | 3.71 |
黏著力(停止之最大之球No.) | 30 | 26 | 29 | 30 | 30 | 30 | 30 |
萜烯系樹脂之含量為5質量%~18質量%之貼附劑(實施例1~3)中結晶未析出,自黏性得到抑制,且黏著力優異。含有氫化松香甘油酯代替萜烯系樹脂之貼附劑(比較例8)之黏著力顯著較差。萜烯系樹脂之含量為4質量%之貼附劑(比較例9)之黏著力較差。萜烯系樹脂之含量為19質量%~24質量%之貼附劑(比較例10~11)之自黏性較強。
Claims (3)
- 一種貼附劑,其係於支持體上具備黏著劑層者, 上述黏著劑層含有利多卡因或其藥學上可容許之鹽、丙二醇、橡膠系黏著基劑及萜烯系樹脂, 關於上述黏著劑層中之利多卡因或其藥學上可容許之鹽之含量,以上述黏著劑層之總質量為基準,以利多卡因之游離體換算為2質量%~6質量%, 上述黏著劑層中之利多卡因或其藥學上可容許之鹽與丙二醇之質量比以利多卡因之游離體換算為1:0.6~1:1.8, 上述黏著劑層中之萜烯系樹脂之含量以上述黏著劑層之總質量為基準,為5質量%~18質量%。
- 如請求項1之貼附劑,其中上述黏著劑層中之丙二醇之含量以上述黏著劑層之總質量為基準,為1.2質量%~7質量%。
- 如請求項1或2之貼附劑,其中上述黏著劑層中之萜烯系樹脂之含量以上述黏著劑層之總質量為基準,為9質量%~14質量%。
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