CN113950356A - 含罗替戈汀的贴附剂 - Google Patents
含罗替戈汀的贴附剂 Download PDFInfo
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- CN113950356A CN113950356A CN202080043204.7A CN202080043204A CN113950356A CN 113950356 A CN113950356 A CN 113950356A CN 202080043204 A CN202080043204 A CN 202080043204A CN 113950356 A CN113950356 A CN 113950356A
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- Prior art keywords
- rotigotine
- adhesive
- mass
- adhesive layer
- agent layer
- Prior art date
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Abstract
本发明的含罗替戈汀的贴附剂是具备支持体层及粘着剂层，且上述粘着剂层含有罗替戈汀及/或其药学上容许的盐的含罗替戈汀的贴附剂，上述粘着剂层进一步含有脂环族饱和烃树脂、与选自月桂醇、辛基十二烷醇、油醇、及肉豆蔻醇中的至少1种脂肪族醇。
Description
技术领域
本发明涉及一种含罗替戈汀的贴附剂，更详细而言涉及一种含有罗替戈汀及/或其药学上容许的盐的贴附剂。
背景技术
罗替戈汀是化合物(-)-5,6,7,8-四氢-6-[丙基-[2-(2-噻吩基)乙基]-氨基]1-萘酚的国际通用名称。罗替戈汀是D1/D2/D3多巴胺受体激动剂，主要用于帕金森氏症、不宁腿综合症的症状的治疗。
作为用于投予罗替戈汀的制剂，例如，在日本国内外市售有“ニュープロ(注册商标)贴剂”。另外，日本特开2010-159302号公报(专利文献1)中，作为用于治疗不宁腿综合症的经外表皮投予形式，记载有一种具有含有罗替戈汀的自粘合性基质层的经皮吸收治疗***；日本特表2002-509878号公报(专利文献2)中记载有一种经皮治疗***，其包含相对于基质成分呈非活性的衬底层与含有罗替戈汀的自粘合性基质层，且基质以罗替戈汀的溶解度为5％(w/w)以上且非水溶性的丙烯酸酯系或有机硅系的聚合物粘合剂作为基材。进而，国际公开第2012/084969号(专利文献3)中记载有一种经皮吸收***，其具备由含有苯乙烯系聚合物及/或聚异丁烯、罗替戈汀或其制药上可容许的盐、聚乙烯吡咯烷酮或乙烯吡咯烷酮及/或乙酸乙烯酯的粘着剂组合物所形成的粘着剂层。
另外，例如，日本特开2014-177428号公报(专利文献4)中记载有经皮吸收型贴附制剂，其包含：支持体、及含药物层，该含药物层含有包含松香系树脂及橡胶系粘着成分的橡胶系粘着剂以及罗替戈汀或其制药上可容许的盐；日本特开2018-123131号公报(专利文献5)中记载有一种经皮吸收型贴附剂，其包含支持体、含药物层及剥离衬垫，该含药物层含有罗替戈汀、聚异丁烯系粘着剂、液体石蜡及聚乙烯吡咯烷酮。
现有技术文献
专利文献
专利文献1：日本特开2010-159302号公报
专利文献2：日本特表2002-509878号公报
专利文献3：国际公开第2012/084969号
专利文献4：日本特开2014-177428号公报
专利文献5：日本特开2018-123131号公报
发明内容
发明所要解决的课题
然而，本发明者等人针对含有罗替戈汀及/或其药学上容许的盐的含罗替戈汀的贴附剂进行进一步的研究，结果发现以下问题。即，一直以来，作为贴附剂中所含有的粘着赋予剂或药物的经皮吸收促进剂，已知有众多剂，但本发明者等人发现即便含有它们，现有的含有罗替戈汀及/或其药学上容许的盐的含罗替戈汀的贴附剂中，也存在尚未达成充分的罗替戈汀的皮肤透过性的情形。
本发明是鉴于上述课题而成的，其目的在于提供一种罗替戈汀的皮肤透过性优异的贴附剂。
用于解决课题的手段
本发明者等人为了达成上述目的，反复进行锐意研究，结果发现，在具备支持体层及粘着剂层的贴附剂中，通过在上述粘着剂层中在选自罗替戈汀及其药学上容许的盐中的至少1种(以下，视情形称为“罗替戈汀及/或其药学上容许的盐”)中组合含有脂环族饱和烃树脂、及特定的脂肪族醇，从而相较于使用其他粘着赋予剂、经皮吸收促进剂的情形，达成特别高水平的罗替戈汀的皮肤透过性，从而完成了本发明。
即，本发明的含罗替戈汀的贴附剂是具备支持体层及粘着剂层，且上述粘着剂层含有罗替戈汀及/或其药学上容许的盐的含罗替戈汀的贴附剂，
上述粘着剂层进一步含有脂环族饱和烃树脂、及选自月桂醇、辛基十二烷醇、油醇、及肉豆蔻醇中的至少1种脂肪族醇。
本发明的含罗替戈汀的贴附剂中，优选上述粘着剂层中的上述脂肪族醇的含量相对于上述粘着剂层的总质量，为1～15质量％。另外，也优选上述粘着剂层中的罗替戈汀及/或其药学上容许的盐换算成罗替戈汀游离体的含量相对于上述粘着剂层的总质量，为5～15质量％。
进而，本发明的含罗替戈汀的贴附剂中，优选上述粘着剂层中的上述脂环族饱和烃树脂的含量相对于上述粘着剂层的总质量，为5～80质量％，另外，也优选上述粘着剂层进一步含有苯乙烯系热塑性弹性体。作为上述粘着剂层中的上述苯乙烯系热塑性弹性体的含量，更优选相对于上述粘着剂层的总质量为5～50质量％。
进而，本发明的含罗替戈汀的贴附剂中，优选上述粘着剂层进一步含有增塑剂，更优选上述粘着剂层中的上述增塑剂的含量相对于上述粘着剂层的总质量为4～50质量％。
发明的效果
根据本发明，可提供一种罗替戈汀的皮肤透过性特别优异的含罗替戈汀的贴附剂。
具体实施方式
以下，根据优选的实施方式详细地说明本发明。本发明的含罗替戈汀的贴附剂是具备支持体层及粘着剂层，且上述粘着剂层含有罗替戈汀及/或其药学上容许的盐的含罗替戈汀的贴附剂，
上述粘着剂层进一步含有脂环族饱和烃树脂、及选自月桂醇、辛基十二烷醇、油醇、及肉豆蔻醇中的至少1种脂肪族醇。
本发明的含罗替戈汀的贴附剂具备支持体层及粘着剂层。作为上述支持体层，只要可支持后述的粘着剂层，则无特别限制，作为贴附剂的支持体层，可适当采用公知的支持体层。作为本发明涉及的支持体层的材质，例如可例举：聚乙烯、聚丙烯等聚烯烃；乙烯-乙酸乙烯酯共聚物、乙酸乙烯酯-氯乙烯共聚物、聚氯乙烯等；尼龙等聚酰胺；聚对苯二甲酸乙二醇酯(PET)、聚对苯二甲酸丁二醇酯、聚萘二甲酸乙二醇酯等聚酯；纤维素衍生物；聚氨酯等合成树脂、或铝等金属。它们之中，就药物非吸附性或药物非透过性的观点而言，优选聚酯、聚对苯二甲酸乙二醇酯。作为上述支持体层的形态，例如可例举：膜；片材、片状多孔质体、片状发泡体等片材类；机织布、针织布、无纺布等布帛；箔；及它们的叠层体。另外，上述支持体层的厚度无特别限制，就贴附贴附剂时的作业容易性及制造容易性的观点而言，优选在5～1000μm的范围内。
本发明的含罗替戈汀的贴附剂也可在上述粘着剂层的与上述支持体层相反的面上进一步具备剥离衬垫。作为上述剥离衬垫，可例举由聚乙烯、聚丙烯等聚烯烃；乙烯-乙酸乙烯酯共聚物、乙酸乙烯酯-氯乙烯共聚物、聚氯乙烯等；尼龙等聚酰胺；聚对苯二甲酸乙二醇酯等聚酯；纤维素衍生物；聚氨酯等合成树脂、或铝、纸等材质形成的膜或片材及它们的叠层体。作为这些剥离衬垫，优选为对与该粘着剂层接触侧的面实施了含有机硅化合物涂布或含氟化合物涂布等脱模处理以使剥离衬垫能够容易地从上述粘着剂层剥离的剥离衬垫。
＜罗替戈汀及其药学上容许的盐＞
本发明涉及的粘着剂层含有选自罗替戈汀及其药学上容许的盐中的至少1种作为药物。在本发明中，作为上述粘着剂层中所含有的罗替戈汀的形态，可为游离体(自由体)也可为其药学上容许的盐，也可为制造过程中及/或制造完成的制剂中，罗替戈汀的药学上容许的盐经脱盐而成的自由体，也可为它们中的1种或2种以上的混合物。作为罗替戈汀的药学上容许的盐，可例举酸加成盐，作为上述酸加成盐的酸，例如可例举：盐酸、硫酸、硝酸、磷酸、亚磷酸、氢溴酸、马来酸、苹果酸、抗坏血酸、酒石酸、月桂酸、硬脂酸、棕榈酸、油酸、肉豆蔻酸、月桂基硫酸、亚麻酸、富马酸。它们之中，作为本发明涉及的粘着剂层，优选以游离体的形态含有罗替戈汀。
在本发明中，作为上述粘着剂层中所含有的罗替戈汀及/或其药学上容许的盐的含量(罗替戈汀的含量或罗替戈汀的药学上容许的盐的含量、或者在两者均含有的情形时为其合计含量，以下相同)，以罗替戈汀游离体换算，相对于上述粘着剂层的总质量，优选为5～15质量％，更优选为7～14质量％，进一步优选为7～12质量％，进一步更优选为8～12质量％，特别优选为8～10质量％。若罗替戈汀及/或其药学上容许的盐的含量未达上述下限，则存在罗替戈汀的皮肤透过性下降的倾向，另一方面，若超过上述上限，则存在罗替戈汀及/或其药学上容许的盐的结晶析出，或产生非晶质型，或粘着剂层的粘着力变得容易下降的倾向。
＜脂环族饱和烃树脂＞
本发明涉及的粘着剂层进一步含有脂环族饱和烃树脂。在本发明中，通过上述粘着剂层组合含有上述脂环族饱和烃树脂与下述特定的脂肪族醇，从而达成特别高水平的皮肤透过性。已知上述脂环族饱和烃树脂主要作为粘着基剂的粘着赋予剂发挥功能，但若本发明涉及的粘着剂层中含有其他粘着赋予剂代替上述脂环族饱和烃树脂，则存在罗替戈汀的皮肤透过性下降的倾向。
本发明涉及的上述所谓脂环族饱和烃树脂，是指作为脂环族饱和烃单体的均聚物或共聚物的脂环族系氢化石油树脂。作为上述脂环族饱和烃树脂，重均分子量优选为1,000～1,500，更优选为1,200～1,400。作为本发明涉及的脂环族饱和烃树脂，可单独使用它们中的1种，也可组合2种以上使用。作为上述脂环族饱和烃树脂，更具体而言，可例举：アルコンP-70、アルコンP-85、アルコンP-90、アルコンP-100、アルコンP-115、アルコンP-125(以上为商品名，荒川化学工业株式会社制造)。
在本发明中，作为上述粘着剂层中所含有的上述脂环族饱和烃树脂的含量(在组合2种以上的上述脂环族饱和烃树脂的情形时为它们的合计含量，以下相同)，相对于上述粘着剂层的总质量，优选为5～80质量％，更优选为10～70质量％，进一步优选为10～60质量％，进一步更优选为20～60质量％，特别优选为20～50质量％。若上述脂环族饱和烃树脂的含量未达上述下限，则存在粘着剂层的粘着力或向皮肤的附着性下降的倾向，另一方面，若超过上述上限，则存在罗替戈汀的经皮吸收性或粘着剂层的保形性下降的倾向。就罗替戈汀的经皮吸收性的观点而言，作为上述脂环族饱和烃树脂的含量，也优选为10～50质量％。
＜脂肪族醇＞
本发明涉及的粘着剂层进一步含有选自月桂醇、辛基十二烷醇、油醇、及肉豆蔻醇中的至少1种脂肪族醇。需要说明的是，在本发明中，所谓脂肪族醇，是指饱和或不饱和的直链状或支链状的1元或2元以上的脂肪族醇。含罗替戈汀的贴附剂中，存在即便使用这4种以外的脂肪族醇，也不会发挥充分的罗替戈汀的皮肤透过性的倾向，进而，在使用碳原子数为6以下的脂肪族醇的情形时，由于沸点变低，故存在难以将制剂中的含量保持恒定，经时稳定性下降的倾向。
在本发明中，作为上述粘着剂层中所含有的上述脂肪族醇的含量(在组合2种以上的上述脂肪族醇的情形时为它们的合计含量，以下相同)，相对于上述粘着剂层的总质量，优选为1～15质量％，更优选为1～10质量％，进一步优选为2～10质量％，进一步更优选为2～7质量％，特别优选为3～7质量％。若上述脂肪族醇的含量未达上述下限，则存在罗替戈汀的皮肤透过性下降的倾向，另一方面，若超过上述上限，则存在与粘着基剂或其他成分的相容性下降的倾向。
另外，在本发明中，作为上述粘着剂层中所含有的上述脂环族饱和烃树脂的含量与上述脂肪族醇的含量的质量比(脂环族饱和烃树脂的含量：脂肪族醇的含量)，优选为17：1～2：1，更优选为12：1～3：1，进一步优选为10：1～5：1。若上述脂环族饱和烃树脂的含量相对于上述脂肪族醇的含量未达上述下限，则存在粘着剂层的粘着力或向皮肤的附着性下降的倾向，另一方面，若超过上述上限，则存在罗替戈汀的经皮吸收性下降的倾向。就罗替戈汀的经皮吸收性的观点而言，上述质量比也优选为10：1～2：1。
＜粘着基剂＞
本发明涉及的粘着剂层含有粘着基剂。作为上述粘着基剂，无特别限定，可例举：橡胶系粘着基剂、丙烯酸系粘着基剂、及有机硅系粘着基剂，可单独使用它们中的1种，也可组合2种以上使用，优选至少含有橡胶系粘着基剂。
(橡胶系粘着基剂)
作为上述橡胶系粘着基剂，可例举：苯乙烯系热塑性弹性体、异戊二烯橡胶、聚异丁烯(PIB)、聚丁烯等，可单独使用它们中的1种，也可组合2种以上使用，它们之中，特别优选苯乙烯系热塑性弹性体。上述所谓苯乙烯系热塑性弹性体，是指若加热则软化而表现出流动性，若冷却则表现出回复至橡胶状弹性体的热塑性的苯乙烯系弹性体。其中，就充分的粘着性赋予及经时稳定性的观点而言，优选苯乙烯系嵌段共聚物。
作为上述苯乙烯系嵌段共聚物，具体而言，可例举：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(SBS)、苯乙烯-异戊二烯嵌段共聚物、苯乙烯-异戊二烯-苯乙烯嵌段共聚物(SIS)、苯乙烯-乙烯/丁烯嵌段共聚物、苯乙烯-乙烯/丁烯-苯乙烯嵌段共聚物、苯乙烯-乙烯/丙烯嵌段共聚物、苯乙烯-乙烯/丙烯-苯乙烯嵌段共聚物、苯乙烯-异丁烯嵌段共聚物、苯乙烯-异丁烯-苯乙烯嵌段共聚物等，可单独使用它们中的1种，也可组合2种以上使用。需要说明的是，上述中，“乙烯/丁烯”表示乙烯及丁烯的共聚物嵌段，“乙烯/丙烯”表示乙烯及丙烯的共聚物嵌段。它们之中，作为本发明涉及的苯乙烯系热塑性弹性体，更优选为苯乙烯-异戊二烯-苯乙烯嵌段共聚物。
作为上述苯乙烯-异戊二烯-苯乙烯嵌段共聚物，粘度平均分子量优选为30,000～2,500,000，更优选为100,000～1,700,000。若上述粘度平均分子量未达上述下限值，则存在贴附剂的制剂物性(尤其是粘着剂层的凝集力)下降的倾向，另一方面，若超过上述上限值，则存在与粘着剂层中所含有的其他成分的相容性下降，导致贴附剂的制造变得困难的倾向。
在本发明中，当在上述粘着剂层中含有上述苯乙烯系热塑性弹性体作为上述粘着基剂时，作为其含量(在组合2种以上的上述苯乙烯系热塑性弹性体的情形时为它们的合计含量，以下相同)，相对于上述粘着剂层的总质量，优选为5～50质量％，更优选为10～40质量％，进一步优选为10～30质量％。若上述苯乙烯系热塑性弹性体的含量未达上述下限，则存在粘着剂层的凝集力或保形性等下降的倾向，另一方面，若超过上述上限，则存在粘着剂层的凝集力过度地增加，导致粘着剂层的粘着力下降或相容性下降的倾向。
另外，作为上述橡胶系粘着基剂，就存在进一步提高粘着剂层的粘着性及凝集力的倾向的观点而言，更优选为苯乙烯系热塑性弹性体(更优选苯乙烯-异戊二烯-苯乙烯嵌段共聚物)及聚异丁烯的组合，进一步优选上述苯乙烯系热塑性弹性体与聚异丁烯的质量比(苯乙烯系热塑性弹性体的质量：PIB的质量)为1：2～30：1(进一步优选为1：1～10：1的范围)。
在本发明中，当在上述粘着剂层中含有橡胶系粘着基剂作为上述粘着基剂时，作为其含量(在2种以上的组合的情形时为它们的合计含量，以下相同)，相对于上述粘着剂层的总质量，优选为1～60质量％，更优选为5～50质量％，进一步优选为10～40质量％。
(丙烯酸系粘着基剂)
作为上述丙烯酸系粘着基剂，可例举：“医药品添加物事典2016(日本医药品添加剂协会编集)”中作为粘着剂收录的丙烯酸/丙烯酸辛酯共聚物、丙烯酸2-乙基己酯/乙烯吡咯烷酮共聚物、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-乙基己酯共聚树脂、丙烯酸2-乙基己酯/丙烯酸甲酯/丙烯酸/甲基丙烯酸缩水甘油酯共聚物、丙烯酸2-乙基己酯/乙酸乙烯酯/丙烯酸羟基乙酯/甲基丙烯酸缩水甘油酯共聚物、丙烯酸2-乙基己酯/二丙酮丙烯酰胺/甲基丙烯酸乙酰乙酰氧基乙酯/甲基丙烯酸甲酯共聚物、丙烯酸乙酯/甲基丙烯酸甲酯共聚物、丙烯酸树脂烷醇胺液中所含有的丙烯酸系高分子等，可单独使用它们中的1种，也可组合2种以上使用。
(有机硅系粘着基剂)
作为上述有机硅系粘着基剂，可例举：聚二甲基硅氧烷(基于ASTM D-1418的表述中表示为MQ的聚合物等)、聚甲基乙烯基硅氧烷(基于ASTM D-1418的表述中表示为VMQ的聚合物等)、聚甲基苯基硅氧烷(基于ASTM D-1418的表述中表示为PVMQ的聚合物等)等，可单独使用它们中的1种，也可组合2种以上使用。
在本发明中，当在上述粘着剂层中含有上述丙烯酸系粘着基剂及/或有机硅系粘着基剂作为上述粘着基剂时，作为其含量(在2种以上的组合的情形时为它们的合计含量，以下相同)，相对于上述粘着剂层的总质量，优选为10质量％以下。
＜其他成分＞
作为本发明的粘着剂层，在不损害本发明的效果的范围内，也可进一步含有罗替戈汀及其药学上容许的盐以外的其他药物；上述脂环族饱和烃树脂以外的其他粘着赋予剂；上述脂肪族醇以外的其他吸收促进剂；吸附剂、脱盐剂、增塑剂、溶解剂、填充剂、稳定剂、保存剂等添加剂。
(其他药物)
作为上述罗替戈汀及其药学上容许的盐以外的其他药物，例如可例举：非甾体性消炎镇痛剂(双氯芬酸、吲哚美辛、酮洛芬、联苯乙酸、氯索洛芬、布洛芬、氟比洛芬、噻洛芬、阿西美辛、舒林酸、依托度酸、托美汀、吡罗昔康、美洛昔康、安吡昔康、萘普生、阿扎丙宗、水杨酸甲酯、水杨酸乙二醇酯、伐地昔布、塞来昔布、罗非昔布、氨芬酸等)、解热镇痛药(乙酰氨基酚等)、抗组胺剂(苯海拉明、氯苯那敏、美喹他嗪、高氯环嗪等)、降血压剂(地尔硫卓、尼卡地平、尼伐地平、美托洛尔、比索洛尔、群多普利等)、抗帕金森药(培高利特、罗匹尼罗、溴麦角环肽、司来吉兰等)、支气管扩张剂(妥布特罗、异丙肾上腺素、沙丁胺醇等)、抗过敏药(酮替芬、氯雷他定、氮卓斯汀、特非那定、西替利嗪、阿扎司特等)、局部麻醉剂(利多卡因、狄布卡因等)、神经障碍性疼痛治疗药(普瑞巴林等)、非麻药性镇痛药(丁基原啡因、曲马多、喷他佐辛)、麻醉系镇痛剂(***、羟考酮、芬太尼等)、泌尿器官用剂(奥昔布宁、坦索罗辛等)、精神神经用剂(丙嗪、氯丙嗪等)、甾体激素剂(***、***、炔诺酮、可的松、氢化可的松等)、抗抑郁药(舍曲林、氟西汀、帕罗西汀、西酞普兰等)、抗痴呆药(多奈哌齐、卡巴拉汀、加兰他敏等)、抗精神病药(利培酮、奥氮平等)、中枢神经***(哌醋甲酯等)、骨质疏松症治疗药(雷洛昔芬、阿仑膦酸盐等)、乳癌预防药(他莫昔芬等)、抗肥胖药(马吲哚、***等)、失眠症改善药(褪黑素等)、抗风湿药(阿克他利等)，可单独使用它们中的1种，也可组合2种以上使用。
在本发明中，当在上述粘着剂层中进一步含有这些其他药物时，作为其含量，在为2种以上的情形时以合计来计，相对于上述粘着剂层的总质量，优选为10质量％以下。
(其他粘着赋予剂)
作为上述脂环族饱和烃树脂以外的其他粘着赋予剂，例如可例举：上述脂环族饱和烃树脂以外的石油系树脂、萜烯系树脂、松香系树脂、酚系树脂及二甲苯系树脂，可单独使用它们中的1种，也可组合2种以上使用。
作为上述脂环族饱和烃树脂以外的石油系树脂，例如可例举：脂环族系氢化石油树脂、脂肪族系石油树脂(脂肪族烃树脂等)、脂肪族系氢化石油树脂、芳香族系石油树脂，更具体而言，可例举：エスコレッツ8000(商品名，エッソ石油化学株式会社制造)等。作为这样的石油系树脂，可单独使用它们中的1种，也可组合2种以上使用。
作为上述萜烯系树脂，例如可例举：蒎烯聚合物(α-蒎烯聚合物、β-蒎烯聚合物等)、萜烯聚合物、双戊烯聚合物、萜烯-酚聚合物、芳香族改性萜烯聚合物、蒎烯-酚共聚物，更具体而言，可例举：YSレジン(YSレジンPXN(1150N、300N)、YSレジンPX1000、YSレジンTO125、YSレジンTO105等)、クリアロンP105、クリアロンM115、クリアロンK100(以上为商品名，ヤスハラケミカル株式会社制造)、タマノル901(商品名，荒川化学工业株式会社制造)，可单独使用它们中的1种，也可组合2种以上使用。
作为上述松香系树脂，例如可例举：氢化松香甘油酯、超浅色松香、超浅色松香酯、酸改性超浅色松香，更具体而言，可例举：パインクリスタル(KE-311、PE-590、KE-359、KE-100等)(商品名，荒川化学工业株式会社制造)等，可单独使用它们中的1种，也可组合2种以上使用。
在本发明中，当在上述粘着剂层中进一步含有这些其他粘着赋予剂时，作为其含量，在2种以上的情形时以合计来计，相对于上述粘着剂层的总质量，优选为10质量％以下。
(其他吸收促进剂(经皮吸收促进剂))
作为上述吸收促进剂，可例举上述特定的脂肪族醇以外的具有药物经皮吸收促进作用的物质，例如可例举：上述特定的脂肪族醇以外的脂肪族醇、碳原子数6～20的脂肪酸、脂肪酸酯、脂肪酰胺、或脂肪族醇醚；芳香族有机酸；芳香族醇；芳香族有机酸酯或醚；POE氢化蓖麻油类；卵磷脂类；磷脂；大豆油衍生物；甘油三乙酸酯，可单独使用它们中的1种，也可组合2种以上使用。
作为上述特定的脂肪族醇以外的脂肪族醇，例如可例举：异丙醇、己醇、鲸蜡醇、硬脂醇、异硬脂醇、次亚麻醇、己基癸醇，可单独使用它们中的1种，也可组合2种以上使用。
作为上述脂肪族醇以外的吸收促进剂，例如可例举：碳原子数6～20的脂肪酸、脂肪酸酯、脂肪酰胺、或脂肪族醇醚；芳香族有机酸；芳香族醇；芳香族有机酸酯或醚；POE氢化蓖麻油类；卵磷脂类；磷脂；大豆油衍生物；甘油三乙酸酯，可单独使用它们中的1种，也可组合2种以上使用。
在本发明中，当在上述粘着剂层中进一步含有这些其他吸收促进剂时，作为其含量，在2种以上的情形时以合计来计，相对于上述粘着剂层的总质量，优选为10质量％以下。
(添加剂)
[吸附剂]
作为上述吸附剂，可例举：具有吸湿性的无机及/或有机物质，更具体而言，可例举：滑石、高岭土、膨润土等矿物；热解法二氧化硅(アエロジル(注册商标)等)、含水二氧化硅等硅化合物；氧化锌、干燥氢氧化铝凝胶等金属化合物；乳酸、乙酸等弱酸；糊精等糖；聚乙烯吡咯烷酮(非交联PVP)、交联聚乙烯吡咯烷酮(也称为“交联聚维酮”、“交联PVP”)、甲基丙烯酸氨基烷基酯共聚物、羧乙烯基聚合物及甲基丙烯酸丁酯-甲基丙烯酸甲酯共聚物等高分子聚合物，可单独使用它们中的1种，也可组合2种以上使用。
作为上述交联聚乙烯吡咯烷酮，可例举交联的N-乙烯基吡咯烷酮聚合物。作为上述N-乙烯基吡咯烷酮聚合物，可为均聚物，也可为共聚物，例如可例举：N-乙烯基吡咯烷酮的均聚物、N-乙烯基吡咯烷酮与多官能单体的共聚物。它们之中，作为本发明涉及的交联聚乙烯吡咯烷酮，优选为1-乙烯基-2-吡咯烷酮的交联均聚物。作为上述交联聚乙烯吡咯烷酮，也可使用コリドンCL、コリドンCL-M(BASF Japan株式会社制造)；ポリプラスドンXL、ポリプラスドンXL-10、ポリプラスドンINF-10(ISP Japan株式会社制造)等市售品。
在本发明中，当在上述粘着剂层中进一步含有这些吸附剂时，作为其含量，在2种以上的情形时以合计来计，相对于上述粘着剂层的总质量，优选为10质量％以下。
另外，在本发明中，通过使上述粘着剂层中含有上述交联聚乙烯吡咯烷酮(优选以与上述罗替戈汀及/或其药学上容许的盐的含量的质量比(罗替戈汀及/或其药学上容许的盐的罗替戈汀游离体换算含量：交联聚乙烯吡咯烷酮含量)计为10：3～1：3)，从而可抑制罗替戈汀及/或其药学上容许的盐的结晶的析出，但就罗替戈汀的特别优异的皮肤透过性的观点而言，上述粘着剂层中优选不含上述交联聚乙烯吡咯烷酮，作为其含量，相对于上述粘着剂层的总质量，优选为10质量％以下，更优选为8质量％以下(例如，3～8质量％)。
[脱盐剂]
上述脱盐剂主要以将碱性药物的全部或一部分转化为游离体为目的而混配。作为这样的脱盐剂，无特别限定，例如，在混配药物的酸加成盐作为上述药物而获得含有游离体的药物的制剂的情形时，优选碱性物质，更优选含金属离子的脱盐剂、含碱性氮原子的脱盐剂。作为上述含金属离子的脱盐剂，可例举：乙酸钠(包括无水乙酸钠)、氢氧化钠、氢氧化钾、氢氧化镁、碳酸氢钠、碳酸氢钾、柠檬酸钠、乳酸钠等，可单独使用它们中的1种，也可组合2种以上使用。需要说明的是，作为本发明涉及的粘着剂层，也可进一步含有源自上述碱性药物及上述脱盐剂的化合物(例如，在组合盐酸罗替戈汀与乙酸钠的情形时为盐酸钠)。在本发明中，当在上述粘着剂层中进一步含有这些脱盐剂、以及源自碱性药物及脱盐剂的化合物的情形时，作为其含量，在2种以上的情形时以合计来计，相对于上述粘着剂层的总质量，优选为10质量％以下。
[增塑剂]
上述增塑剂主要以调整上述粘着剂层的粘着物性、上述粘着剂层的制造过程中的流动特性、上述药物的经皮吸收特性等为目的而混配。作为这样的增塑剂，例如可例举：硅油；石蜡系加工处理油、环烷系加工处理油及芳香族系加工处理油等石油系油；角鲨烷、角鲨烯；橄榄油、山茶油、蓖麻油、妥尔油及花生油等植物系油；邻苯二甲酸二丁酯及邻苯二甲酸二辛酯等二元酸酯；聚丁烯及液状异戊二烯橡胶等液状橡胶；二乙二醇、聚乙二醇、丙二醇、二丙二醇等，可单独使用它们中的1种，也可组合2种以上使用。它们之中，作为上述增塑剂，优选为选自硅油、液体石蜡、及液状聚丁烯中的至少1种。在本发明中，当在上述粘着剂层中进一步含有这些增塑剂时，作为其含量，就提高粘着剂层的粘着力及/或缓和剥离时的局部刺激性的观点而言，在2种以上的情形时以合计来计，相对于上述粘着剂层的总质量，优选为4～50质量％，更优选为5～30质量％，进一步优选为10～20质量％，进一步更优选为15～20质量％。就罗替戈汀的经皮吸收性的观点而言，作为上述增塑剂的含量，也优选为15～50质量％。
[溶解剂、填充剂]
作为上述溶解剂，例如可例举：乙酸等有机酸、表面活性剂，可单独使用它们中的1种，也可组合2种以上使用。另外，上述填充剂主要以调整上述粘着剂层的粘着力的目的而混配，作为该填充剂，例如可例举：氢氧化铝、碳酸钙、碳酸镁；硅酸铝或硅酸镁等硅酸盐；硅酸、硫酸钡、硫酸钙、锌酸钙、氧化锌、氧化钛，可单独使用它们中的1种，也可组合2种以上使用。
[稳定剂]
作为上述稳定剂，例如可例举：抗坏血酸或其金属盐或者酯(优选钠盐、棕榈酸酯)、异抗坏血酸或其金属盐(优选钠盐)、乙二胺四乙酸或其金属盐(优选钙二钠盐、四钠盐)、半胱氨酸、乙酰半胱氨酸、2-巯基苯并咪唑、二丁基羟基甲苯、丁基羟基苯甲醚、没食子酸丙酯、四[3-(3,5-二叔丁基-4-羟基苯基)丙酸]季戊四醇酯、3-巯基-1,2-丙二醇、生育酚乙酸酯、百里香酚、大豆卵磷脂、芸香苷、二羟基苯甲酸、二氯异氰尿酸钾、五羟黄酮、对苯二酚、羟基甲亚磺酸金属盐(优选钠盐)、焦亚硫酸金属盐(例如钠盐)、亚硫酸金属盐(优选钠盐)、硫代硫酸金属盐(优选钠盐)，可单独使用它们中的1种，也可组合2种以上使用。上述中，作为金属盐，例如可例举：钠盐、钾盐、钙盐、镁盐。另外，作为酯，可例举：棕榈酸酯、硬脂酸酯、肉豆蔻酸酯等。
在本发明中，存在通过使上述粘着剂层中进一步含有上述稳定剂，从而进一步提高经时稳定性的倾向，但就罗替戈汀的特别优异的皮肤透过性的观点而言，上述粘着剂层中优选不含上述稳定剂(例如，2-巯基苯并咪唑)，作为其含量，相对于上述粘着剂层的总质量，优选为3质量％以下，更优选为2质量％以下，进一步优选为0.25质量％以下(例如，0.005～0.25质量％)。
[保存剂]
作为上述保存剂，例如可例举：对羟基苯甲酸衍生物、苄醇、苯酚、甲酚等，可单独使用它们中的1种，也可组合2种以上使用。
当在上述粘着剂层中进一步含有上述添加剂时，作为其含量，在2种以上的情形时以合计来计，相对于上述粘着剂层的总质量，优选为40质量％以下，更优选为30质量％以下。
作为本发明涉及的粘着剂层，虽无特别限制，但每单位面积(贴附面的面积)的质量优选为20～200g/m2，更优选为30～100g/m2，进一步优选为30～70g/m2。另外，作为本发明的粘着剂层的贴附面的面积，可根据治疗的目的或应用对象适当进行调整，无特别限制，通常在0.5～200cm2的范围。
本发明的含罗替戈汀的贴附剂无特别限制，可通过适当采用公知的贴附剂的制造方法而制造。例如，首先，依据惯常方法，将罗替戈汀及/或其药学上容许的盐、上述脂环族饱和烃树脂、上述特定的脂肪族醇、上述粘着基剂、及视需要的溶剂或上述其他成分进行混练，而获得均匀的粘着剂层组合物。在使用罗替戈汀游离体作为上述罗替戈汀及/或其药学上容许的盐的情形时，可为其I型结晶，可为II型结晶，可为非晶质型，也可为I型结晶、II型结晶、及非晶质型中的至少2种以上的混合物。另外，作为上述罗替戈汀及/或其药学上容许的盐，也可使用溶解于上述溶剂的罗替戈汀及/或其药学上容许的盐。作为上述溶剂，可例举：无水乙醇、甲苯、庚烷、甲醇、乙酸乙酯、己烷、及它们中的至少2种以上的混合液等。
继而，将该粘着剂层组合物以成为所需的每单位面积的质量的方式，涂布于上述支持体层的面上(通常为一面上)后，视需要进行加温，使上述溶剂干燥去除，形成粘着剂层，进而视需要切割为所需的形状，由此可获得本发明的贴附剂。
另外，作为本发明的含罗替戈汀的贴附剂的制造方法，也可进一步包括在上述粘着剂层的与上述支持体层相反的面上贴合上述剥离衬垫的步骤，首先将上述粘着剂层组合物以成为所需的每单位面积的质量的方式涂布于上述剥离衬垫的一面上而形成粘着剂层后，在上述粘着剂层的与上述剥离衬垫相反的面上贴合上述支持体层，视需要切割为所需的形状，由此也可获得本发明的贴附剂。进而，所获得的贴附剂也可视需要封入至保存用包装容器(例如铝层压袋)中，而制成包装体。
实施例
以下，基于实施例及比较例，对本发明更具体地进行说明，但本发明并不受以下实施例限定。需要说明的是，各实施例及比较例中，利用以下所示的方法进行皮肤透过试验。
＜皮肤透过试验(体外(in vitro)无毛小鼠皮肤透过试验)＞
首先，剥离无毛小鼠躯体部的皮肤，去除脂肪而获得脂肪去除皮肤片，在该脂肪去除皮肤片的角质层侧切割出1.0cm2的正方形，并贴附去除了剥离衬垫的贴附剂，以此制成试验样品。以真皮侧与受体液接触的方式，将上述试验样品设置于流通式扩散槽中，在上述槽中装满受体溶液(磷酸盐缓冲生理盐水)。继而，以受体溶液保温于32℃的方式，一边使加温的循环水在外周部循环一边以约5mL/hr的流速输送受体溶液，每2小时采集受体溶液直至24小时。利用高效液相色谱法测定所采集的受体溶液中的罗替戈汀浓度，分别根据以下式：
罗替戈汀皮肤透过量(μg/cm2)＝{受体溶液中的罗替戈汀浓度(μg/mL)×流量(mL)}/贴附剂面积(cm2)
算出粘着剂层的每单位面积中的罗替戈汀皮肤透过量，求出每1小时的皮肤透过量(皮肤透过速度(μg/cm2/hr))。测定是分别对2个试验样品进行，将24小时内各皮肤透过速度的最大值的平均值作为最大皮肤透过速度(Jmax)。
(实施例1)
首先，将罗替戈汀(游离体)9.0质量份、苯乙烯-异戊二烯-苯乙烯嵌段共聚物15.4质量份、聚异丁烯6.6质量份、脂环族饱和烃树脂(アルコンP-100，荒川化学工业株式会社制造)48.4质量份、液体石蜡17.6质量份、及月桂醇3质量份添加至适量的溶剂(无水乙醇及甲苯)中并加以混合，而获得粘着剂层组合物。继而，将所获得的粘着剂层组合物涂布于剥离衬垫(实施了脱模处理的聚对苯二甲酸乙二醇酯制的膜)上，将溶剂干燥去除，以每单位面积的质量成为50g/m2的方式形成粘着剂层。在所获得的粘着剂层的与上述剥离衬垫相反的面上叠层支持体层(聚对苯二甲酸乙二醇酯制的膜)，获得依序叠层有支持体层/粘着剂层/剥离衬垫的贴附剂。
(实施例2～4、比较例1～18)
将粘着剂层组合物的组成以成为下述表1或表2所示的组成的方式进行设定，除此以外，以与实施例1相同的方式获得了各贴附剂。
对实施例1～4及比较例1～18中所获得的贴附剂实施了皮肤透过试验。将结果与各实施例及比较例的粘着剂层组合物的组成(溶剂除外)一并分别示于表1及表2。
[表1]
[表2]
如表1及表2所示，在使用了月桂醇、辛基十二烷醇、油醇、或肉豆蔻醇的本发明的贴附剂(实施例1～4)中，确认到达成了优异的罗替戈汀的皮肤透过性，尤其是与使用了碳原子数与它们接近或碳原子数共同的其他脂肪族醇(例如，比较例2～4)的情形相比，也达成了特别优异的皮肤透过性。
(实施例5、比较例19～20)
将粘着剂层组合物的组成以成为下述表3所示的组成的方式进行设定，除此以外，以与实施例1相同的方式获得了各贴附剂。表3中，作为萜烯系树脂，使用了“YSレジンPX1150N(ヤスハラケミカル株式会社制造)”，作为氢化松香酯，使用了“KE-311(荒川化学工业株式会社制造)”。
对实施例5及比较例19～20中所获得的贴附剂实施了皮肤透过试验。将结果与各实施例及比较例的粘着剂层组合物的组成(溶剂除外)一并分别示于表3。
[表3]
如表3所示，在使用了辛基十二烷醇及脂环族饱和烃树脂的本发明的贴附剂(实施例5)中，确认到达成了优异的罗替戈汀的皮肤透过性，即便进一步含有吸附剂、稳定剂，也达成了充分的皮肤透过性。另一方面，在使用了作为其他粘着赋予剂的萜烯系树脂或氢化松香酯代替脂环族饱和烃树脂的情形时(比较例19、20)，确认到罗替戈汀的皮肤透过性下降。
(实施例6～7)
将粘着剂层组合物的组成以成为下述表4所示的组成的方式进行设定，除此以外，以与实施例1相同的方式获得了各贴附剂。对实施例6～7中所获得的贴附剂实施了皮肤透过试验。将结果与各实施例的粘着剂层组合物的组成(溶剂除外)一并分别示于表4。
[表4]
如表4所示，确认到即便本发明涉及的脂肪族醇的含量为10质量份或15质量份，本发明的贴附剂(实施例6～7)也达成了优异的罗替戈汀的皮肤透过性。
(实施例8～10)
将粘着剂层组合物的组成以成为下述表5所示的组成的方式进行设定，除此以外，以与实施例1相同的方式获得了各贴附剂。对实施例8～10中所获得的贴附剂实施了皮肤透过试验。将结果与各实施例的粘着剂层组合物的组成(溶剂除外)一并分别示于表5。
[表5]
如表5所示，确认到即便罗替戈汀的含量为11.3质量份或13.5质量份，本发明的贴附剂(实施例8～10)也达成了优异的罗替戈汀的皮肤透过性。
(实施例11～15)
将粘着剂层组合物的组成以成为下述表6所示的组成的方式进行设定，除此以外，以与实施例1相同的方式获得了各贴附剂。对实施例11～15中所获得的贴附剂实施了皮肤透过试验。将结果与各实施例的粘着剂层组合物的组成(溶剂除外)一并分别示于表6。另外，表6中也一并示出上述实施例8的结果。
[表6]
如表6所示，确认到即便脂环族饱和烃树脂的含量为12.5质量份或60质量份，另外，即便液体石蜡的含量为11.6质量份或47.5质量份，本发明的贴附剂(实施例11～14)也达成了优异的罗替戈汀的皮肤透过性。进而，确认到即便不含有聚异丁烯，本发明的贴附剂(实施例15)也达成了优异的罗替戈汀的皮肤透过性。
产业上的可利用性
如上述所说明的那样，根据本发明，可提供一种罗替戈汀的皮肤透过性特别优异的含罗替戈汀的贴附剂。
Claims (8)
1.一种含罗替戈汀的贴附剂，其是具备支持体层及粘着剂层，且上述粘着剂层含有罗替戈汀及/或其药学上容许的盐的含罗替戈汀的贴附剂，
上述粘着剂层进一步含有脂环族饱和烃树脂、和选自月桂醇、辛基十二烷醇、油醇及肉豆蔻醇中的至少1种脂肪族醇。
2.如权利要求1所述的含罗替戈汀的贴附剂，其中上述粘着剂层中的上述脂肪族醇的含量相对于上述粘着剂层的总质量，为1～15质量％。
3.如权利要求1或2所述的含罗替戈汀的贴附剂，其中上述粘着剂层中的罗替戈汀及/或其药学上容许的盐换算成罗替戈汀游离体的含量相对于上述粘着剂层的总质量，为5～15质量％。
4.如权利要求1～3中任一项所述的含罗替戈汀的贴附剂，其中上述粘着剂层中的上述脂环族饱和烃树脂的含量相对于上述粘着剂层的总质量，为5～80质量％。
5.如权利要求1～4中任一项所述的含罗替戈汀的贴附剂，其中上述粘着剂层进一步含有苯乙烯系热塑性弹性体。
6.如权利要求5所述的含罗替戈汀的贴附剂，其中上述粘着剂层中的上述苯乙烯系热塑性弹性体的含量相对于上述粘着剂层的总质量，为5～50质量％。
7.如权利要求1～6中任一项所述的含罗替戈汀的贴附剂，其中上述粘着剂层进一步含有增塑剂。
8.如权利要求7所述的含罗替戈汀的贴附剂，其中上述粘着剂层中的上述增塑剂的含量相对于上述粘着剂层的总质量，为4～50质量％。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006082888A1 (ja) * | 2005-02-03 | 2006-08-10 | Kyorin Pharmaceutical Co., Ltd. | 経皮吸収型製剤 |
| WO2012084969A1 (en) * | 2010-12-22 | 2012-06-28 | Hexal Ag | Adhesive composition containing rotigotine and transdermal therapeutic system comprising the adhesive composition |
| JP2013079220A (ja) * | 2011-10-05 | 2013-05-02 | Yutoku Yakuhin Kogyo Kk | ロチゴチン含有経皮吸収型貼付剤 |
| JP2014177428A (ja) * | 2013-03-15 | 2014-09-25 | Yutoku Yakuhin Kogyo Kk | ロジン系樹脂を含有するロチゴチン経皮吸収型貼付製剤 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE19814084B4 (de) | 1998-03-30 | 2005-12-22 | Lts Lohmann Therapie-Systeme Ag | D2-Agonist enthaltendes transdermales therapeutisches System zur Behandlung des Parkinson-Syndroms und Verfahren zu seiner Herstellung |
| CN1195506C (zh) * | 1999-11-29 | 2005-04-06 | Lts勒曼治疗***股份公司 | 具有改良稳定性的经皮治疗***及其制备方法 |
| DE10220230A1 (de) | 2002-05-06 | 2003-11-27 | Sanol Arznei Schwarz Gmbh | Verwendung von Rotigotine zur Behandlung des Restless Leg Syndroms |
| KR102032405B1 (ko) | 2010-02-15 | 2019-10-16 | 프로덕티브 리서치 엘엘씨 | 성형가능한 경량 복합 재료 시스템 및 방법 |
| TW201431570A (zh) * | 2012-11-22 | 2014-08-16 | Ucb Pharma Gmbh | 用於經皮投服羅替戈汀（Ｒｏｔｉｇｏｔｉｎｅ）之多天式貼片 |
| CN110198715A (zh) | 2017-02-03 | 2019-09-03 | 考司美德制药株式会社 | 含有罗替戈汀的透皮吸收型贴剂 |
| US11607394B2 (en) * | 2017-12-19 | 2023-03-21 | Hisamitsu Pharmaceutical Co., Inc. | Rotigotine-containing patch |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006082888A1 (ja) * | 2005-02-03 | 2006-08-10 | Kyorin Pharmaceutical Co., Ltd. | 経皮吸収型製剤 |
| WO2012084969A1 (en) * | 2010-12-22 | 2012-06-28 | Hexal Ag | Adhesive composition containing rotigotine and transdermal therapeutic system comprising the adhesive composition |
| JP2013079220A (ja) * | 2011-10-05 | 2013-05-02 | Yutoku Yakuhin Kogyo Kk | ロチゴチン含有経皮吸収型貼付剤 |
| JP2014177428A (ja) * | 2013-03-15 | 2014-09-25 | Yutoku Yakuhin Kogyo Kk | ロジン系樹脂を含有するロチゴチン経皮吸収型貼付製剤 |
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