CN105392481B - 两性离子性软性隐形眼镜用眼科用组合物 - Google Patents
两性离子性软性隐形眼镜用眼科用组合物 Download PDFInfo
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- CN105392481B CN105392481B CN201480029909.8A CN201480029909A CN105392481B CN 105392481 B CN105392481 B CN 105392481B CN 201480029909 A CN201480029909 A CN 201480029909A CN 105392481 B CN105392481 B CN 105392481B
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- Prior art keywords
- amphoteric ion
- scl
- pranoprofen
- salt
- contact lens
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Abstract
本发明的目的在于，提供在包含普拉洛芬和/或其盐的两性离子性软性隐形眼镜用眼科用组合物中，呈现澄清的外观性状、且抑制普拉洛芬和/或其盐对两性离子性软性隐形眼镜的吸附的技术。通过在包含普拉洛芬和/或其盐的两性离子性软性隐形眼镜用眼科用组合物中，配合氨丁三醇，且将pH值设定为5.5以上，能够实现澄清的外观性状，而且能够有效地抑制普拉洛芬和/或其盐对两性离子性软性隐形眼镜的吸附。
Description
技术领域
本发明涉及呈现澄清的外观性状、能够抑制普拉洛芬和/或其盐对两性离子性软性隐形眼镜的吸附的两性离子性软性隐形眼镜用眼科用组合物。此外，本发明涉及抑制普拉洛芬和/或其盐对两性离子性软性隐形眼镜的吸附的方法。
背景技术
普拉洛芬和/或其盐具有抑制成为炎症、疼痛的原因的前列腺素的生物合成的作用，在眼科领域中，以眼的充血、发痒等症状的缓和、睑缘炎、结膜炎、包括巩膜外层炎的巩膜炎、术后的炎症、前眼部葡萄膜炎等的预防或治疗为目的被广泛使用。此外，对于利用了普拉洛芬和/或其盐的眼科用组合物的制剂处方，也进行了各种报道。例如，专利文献1中报道了，包含普拉洛芬和/或其盐与抗组胺剂的局部用水性液剂能够发挥优异的抗炎症作用和镇痒作用。此外，专利文献2中也报道了，含有普拉洛芬和/或其盐0.01～2.0w/v％和萘甲唑啉等特定的血管收缩剂0.0005～0.1w/v％的滴眼剂能够有效地发挥外眼部充血的消除或减轻作用。
另一方面，近年来，开发了一次性、能够长期连续佩戴的软性隐形眼镜(以下，有时简写为SCL)，SCL佩戴者增加了。此外，目前SCL的素材大多使用显示非离子性的素材、显示阴离子性的素材，近年来，作为能够抑制泪液中的蛋白质、脂质、细胞碎片等对眼镜表面的聚集的SCL素材，显示两性离子性的素材也被实用化。因此，为了提高两性离子性SCL佩戴者的便利性，要求能够在佩戴了两性离子性SCL的状态下使用的滴眼剂(两性离子性SCL用滴眼剂)。对于两性离子性SCL用滴眼剂，除了发挥所期望的药效以外，需要以对两性离子性SCL不产生不良影响的方式进行处方。如果两性离子性SCL用滴眼剂中的药物吸附于SCL，则导致眼镜的变形、使用感的降低等，进一步有时变得不能对眼粘膜发挥所期望的药理效果，因此对于两性离子性SCL用滴眼剂，抑制药物对两性离子性SCL的吸附成为特别重要的课题。
目前，对于SCL用滴眼剂，为了抑制药物对SCL的吸附，采用了选择难以吸附于SCL的药物、配合抑制药物对SCL的吸附的成分等形成的制剂处方。例如，专利文献3中报道了，作为能够抑制包含具有仲氨基或叔氨基的胺化合物的碱性药物对SCL的吸附的制剂处方，与该碱性药物一起含有氨基酸、氨基酸的盐、酸性粘多糖、酸性粘多糖的盐或环糊精，且将pH值设定为3.5～4.8的SCL用组合物。
现有技术文献
专利文献
专利文献1：日本特开2002-193805号公报
专利文献2：国际公开第01/87304号
专利文献3：国际公开第2007/77783号
发明内容
发明所要解决的课题
然而，在专利文献3中，完全没有着眼于普拉洛芬和/或其盐、关于其对两性离子性SCL的吸附特性的研究。具有仲氨基或叔氨基的胺化合物中包含了多种多样的药物，因而药物对SCL的吸附特性也根据除氨基以外的结构而变化。进一步，根据离子性的有无、离子性的种类等，眼镜表面的特性有很大不同，因此，关于药物对SCL的吸附特性，要求进行与SCL的素材相应的研究。实际上，由本发明人确认了，两性离子性SCL与非离子性SCL、阴离子性SCL不同，具有普拉洛芬和/或其盐的吸附性极高的特有课题(参照后述的试验例1)。
进一步，在专利文献3中，必须将pH值设定为4.8以下，但是由本发明人确认了，如果将包含普拉洛芬和/或其盐的SCL用眼科用组合物调节为pH值4.8以下左右，则存在产生白浊、不能呈现能够实用化的外观性状的问题点(参照后述的试验例2)。
以这样的现有技术为背景，为了将包含普拉洛芬和/或其盐的两性离子性SCL用眼科用组合物实用化，要求在充分考虑普拉洛芬和/或其盐对两性离子性SCL的吸附特性的基础上，来设定呈现澄清的外观性状的制剂处方。
因此，本发明的目的在于，提供在包含普拉洛芬和/或其盐的两性离子性SCL用眼科用组合物中，呈现澄清的外观性状、且抑制普拉洛芬和/或其盐对两性离子性SCL的吸附的技术。
用于解决课题的手段
本发明人为了解决前述课题而进行深入研究，结果发现，在包含普拉洛芬和/或其盐的两性离子性SCL用眼科用组合物中，通过配合氨丁三醇、且将pH值设定为5.5以上，能够实现澄清的外观性状，而且能够有效地抑制普拉洛芬和/或其盐对两性离子性SCL的吸附。本发明是基于相关的见解，通过进一步反复研究而完成的。
即，本发明提供下述公开的形式的发明。
项1.一种两性离子性软性隐形眼镜用眼科用组合物，其特征在于，含有普拉洛芬和/或其可药用的盐、和氨丁三醇，且pH值为5.5以上。
项2.根据项1所述的两性离子性软性隐形眼镜用眼科用组合物，包含氨丁三醇0.0001～5w/v％。
项3.根据项1或2所述的两性离子性软性隐形眼镜用眼科用组合物，pH值为5.5～9。
项4.根据项1～3中任一项所述的两性离子性软性隐形眼镜用眼科用组合物，包含普拉洛芬和/或其可药用的盐0.001～0.5w/v％。
项5.根据项1～4中任一项所述的两性离子性软性隐形眼镜用眼科用组合物，是两性离子性软性隐形眼镜用滴眼剂。
项6.一种抑制普拉洛芬和/或其可药用的盐对两性离子性软性隐形眼镜的吸附的方法，其特征在于，在包含普拉洛芬和/或其可药用的盐的两性离子性软性隐形眼镜用眼科用组合物中，配合氨丁三醇，且将pH值调节为5.5以上。
项7.液剂的用于制造两性离子性软性隐形眼镜用眼科用组合物的应用，所述液剂含有普拉洛芬和/或其可药用的盐、和氨丁三醇，且pH值为5.5以上。
项8.一种抑制普拉洛芬和/或其可药用的盐对两性离子性软性隐形眼镜的吸附的方法，包含下述工序：使含有普拉洛芬和/或其可药用的盐、和氨丁三醇，且pH值为5.5以上的液剂接触两性离子性软性隐形眼镜。
发明的效果
通过本发明的两性离子性SCL用眼科用组合物，能够抑制普拉洛芬和/或其盐对两性离子性SCL的吸附，因此，不会对两性离子性SCL产生不良影响，能够使普拉洛芬和/或其盐的药效有效地发挥。此外，在本发明的两性离子性SCL用眼科用组合物中，通过作为pH调节剂使用的氨丁三醇的配合与pH调节，能够抑制普拉洛芬和/或其盐对两性离子性SCL的吸附，由于能够任意地设定有无其他药理成分、添加剂的配合，所以也具有制剂处方上的制约少的优点。
此外，根据本发明的两性离子性SCL用眼科用组合物，能够提供虽然含有普拉洛芬和/或其盐，但是能够抑制通过将pH值设定为4.8以下左右而产生的白浊，呈现澄清的外观性状的两性离子性SCL用眼科用组合物。另外，在本说明书中，所谓“澄清”，是指没有由于普拉洛芬和/或其盐而产生白浊的状态，是不限于无色澄清，也包含由于其他含有成分而显色的有色澄清的概念。
具体实施方式
1.两性离子性SCL用眼科用组合物
本发明的两性离子性SCL用眼科用组合物的特征在于，含有普拉洛芬和/或其可药用的盐、和氨丁三醇，且pH值为5.5以上。以下对于本发明的两性离子性SCL用眼科用组合物进行详述。另外，在本说明书中，所谓“两性离子性SCL用眼科用组合物”，表示在眼科领域中使用，在与两性离子性SCL接触的形式下使用的组合物。此外，在本说明书中，各成分的浓度单位“w/v％”表示质量对体积的百分率，与g/100mL含义相同。
本发明的两性离子性SCL用眼科用组合物含有普拉洛芬和/或其盐。所谓普拉洛芬，也称为α-甲基-5H-[1]苯并吡喃并[2,3-b]吡啶-7-乙酸，是在眼科领域已知具有消炎作用的公知的化合物。
作为普拉洛芬的盐，以可药用为限度就无特别限制，可举出例如，钠盐、钾盐、钙盐、镁盐、铝盐等金属盐；三乙胺盐、二乙胺盐、吗啉盐、哌嗪盐等有机碱盐等。这些普拉洛芬的盐可以单独使用1种，此外也可以组合2种以上使用。
在本发明的两性离子性SCL用眼科用组合物中，可以从普拉洛芬及其盐中选择1种单独使用，也可以组合2种以上来使用。普拉洛芬及其盐中，优选可以举出普拉洛芬。
在本发明的两性离子性SCL用眼科用组合物中，对于普拉洛芬和/或其盐的浓度，根据该两性离子性SCL用眼科用组合物的用途等进行适当设定，可举出例如，0.001～0.5w/v％，优选为0.01～0.2w/v％，进一步优选为0.01～0.1w/v％。
本发明的两性离子性SCL用眼科用组合物进一步含有氨丁三醇。所谓氨丁三醇，也称为三(羟甲基)氨基甲烷，是在眼科领域也作为缓冲剂使用的公知的化合物。
在本发明的两性离子性SCL用眼科用组合物中，对于氨丁三醇的浓度，可举出例如，0.0001～5w/v％。特别是从更进一步有效地抑制普拉洛芬和/或其盐对两性离子性SCL的吸附的观点出发，作为氨丁三醇的浓度，可举出优选为0.001～5w/v％，进一步优选为0.001～2w/v％。
本发明的两性离子性SCL用眼科用组合物的pH值设定为5.5以上。对于本发明的两性离子性SCL用眼科用组合物，通过使氨丁三醇与前述普拉洛芬和/或其盐一起共存，且设定为这样的pH范围，可以抑制普拉洛芬和/或其盐对两性离子性SCL的吸附，同时可以抑制白浊而呈现澄清的外观性状。
作为本发明的两性离子性SCL用眼科用组合物的pH值，从更进一步有效地抑制普拉洛芬和/或其盐对两性离子性SCL的吸附、同时使其具备澄清的外观性状的观点出发，可举出优选为5.5～9，更优选为6～8，进一步优选为6.5～8，特别优选为6.5～7.5。
为了将本发明的两性离子性SCL用眼科用组合物的pH值调节到前述范围，使用眼科用组合物中通常使用的pH调节剂即可。作为pH调节剂，可举出例如，氢氧化钠、氢氧化钾等碱；乙酸、柠檬酸、盐酸、磷酸、酒石酸等酸。这些pH调节剂可以单独使用1种，此外可以组合2种以上来使用。
由于本发明的两性离子性SCL用眼科用组合物中包含显示缓冲作用的氨丁三醇，所以即使不包含其他缓冲剂，也能够具备缓冲能力，但是以不妨碍本发明的效果为限度，也可以根据需要包含其他的缓冲剂。作为这样的其他的缓冲剂，可举出例如，磷酸缓冲剂、硼酸缓冲剂、柠檬酸缓冲剂、酒石酸缓冲剂、乙酸缓冲剂、氨基酸等。这些缓冲剂可以单独使用1种，此外可以组合2种以上来使用。
本发明的两性离子性SCL用眼科用组合物中，除了前述成分以外，可以根据需要含有普拉洛芬和/或其盐以外的药理成分。作为这样的药理成分，可举出例如，甘草酸二钾、尿囊素、ε-氨基己酸、溴芬酸、酮咯酸氨丁三醇、奈帕芬胺、盐酸小檗碱、硫酸小檗碱、薁磺酸钠、硫酸锌、乳酸锌、盐酸溶菌酶等消炎剂；马来酸氯苯那敏、盐酸苯海拉明等抗组胺剂；色甘酸钠、酮替芬富马酸盐、阿扎司特、氨来呫诺、吡嘧司特钾、曲尼司特、异丁司特等抗变态反应剂；诺氟沙星、氧氟沙星、洛美沙星、左氧氟沙星、庆大霉素、加替沙星等抗菌剂；抗坏血酸、黄素腺嘌呤二核苷酸钠、氰钴胺素、盐酸吡哆素、生育酚乙酸酯、视黄醇乙酸酯、视黄醇棕榈酸酯、泛醇、泛酸钙、泛酸钠等维生素类；天冬氨酸、牛磺酸、硫酸软骨素钠等氨基酸类，新斯的明甲基硫酸盐等抗胆碱酯酶剂；萘甲唑啉、四氢唑啉、肾上腺素、麻黄碱、去氧肾上腺素、dl-甲基麻黄碱等血管收缩剂；透明质酸钠等角膜结膜上皮障碍治疗药；磺胺嘧啶、磺胺异唑、磺胺索嘧啶、磺胺二甲氧哒嗪、磺胺甲氧哒嗪、磺胺甲唑、磺胺乙二唑、磺胺托嘧啶、磺胺苯吡唑、磺胺脒、酞磺胺噻唑、琥珀磺胺噻唑等磺胺剂等。这里示例的化合物，以可药用为限度，可以是盐的形态，此外也可以是其他的盐的形态。这些药理成分可以单独使用1种，此外也可以组合使用2种以上。
对于这些药理成分的浓度，根据药理成分的种类、两性离子性SCL用眼科用组合物的用途等进行适当设定。
此外，本发明的两性离子性SCL用眼科用组合物中，除了前述成分以外，可以根据需要含有等张剂、助溶剂、粘稠剂、螯合剂、清凉剂、防腐剂、稳定剂、表面活性剂等添加剂。
作为等张剂，可举出山梨糖醇、葡萄糖、甘露糖醇等糖类；甘油、丙二醇等多元醇类；氯化钠等盐类；硼酸等。这些等张剂可以单独使用1种，此外也可以组合使用2种以上。
作为助溶剂，可举出例如，聚氧乙烯失水山梨糖醇单油酸酯、聚氧乙烯硬化蓖麻油、泰洛沙泊、普朗尼克(Pluronic)等非离子性表面活性剂；甘油、聚乙二醇(macrogol)等多元醇等。这些助溶剂可以单独使用1种，此外也可以组合使用2种以上。
作为粘稠剂，可举出例如，聚乙烯吡咯烷酮、聚乙二醇、聚乙烯醇、羧基乙烯基聚合物、黄原胶、硫酸软骨素钠、透明质酸钠等水溶性高分子；羟丙甲纤维素、羟乙基纤维素、甲基纤维素、羟丙基纤维素、羟丙基甲基纤维素、羧甲基纤维素钠等纤维素类等。这些粘稠剂可以单独使用1种，此外也可以组合使用2种以上。
作为螯合剂，可举出例如，乙二胺四乙酸盐、柠檬酸或其盐等。这些螯合剂可以单独使用1种，此外也可以组合使用2种以上。
作为清凉剂，可举出例如，l-薄荷醇、冰片、樟脑、桉树油等。这些清凉剂可以单独使用1种，此外也可以组合使用2种以上。
作为防腐剂，可举出例如，山梨酸或其盐、苯甲酸或其盐、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、氯丁醇、氯己定葡糖酸盐、硼酸、脱氢乙酸或其盐、苯扎氯铵、苄索氯铵、苯甲醇、氯化锌、对氯间二甲苯酚、氯甲酚、苯乙醇、泊利氯铵、硫柳汞、二丁基羟基甲苯等。这些防腐剂可以单独使用1种，此外也可以组合使用2种以上。
作为稳定剂，可举出例如，聚乙烯吡咯烷酮、亚硫酸盐、单乙醇胺、甘油、丙二醇、环糊精、葡聚糖、抗坏血酸、乙二胺四乙酸盐、牛磺酸、生育酚、二丁基羟基甲苯等。这些稳定剂可以单独使用1种，此外也可以组合使用2种以上。
作为表面活性剂，可举出例如，泰洛沙泊、聚氧乙烯硬化蓖麻油、聚氧乙烯聚氧丙烯嵌段共聚物、聚氧乙烯失水山梨糖醇脂肪酸酯、辛苯聚醇(octoxynol)等非离子性表面活性剂；烷基二氨基乙基甘氨酸、月桂基二甲基氨基乙酸甜菜碱等两性表面活性剂；烷基硫酸盐、N-酰基牛磺酸盐、聚氧乙烯烷基醚磷酸盐、聚氧乙烯烷基醚硫酸盐等阴离子表面活性剂；烷基吡啶盐、烷基胺盐等阳离子表面活性剂等。这些表面活性剂可以单独使用1种，此外也可以组合使用2种以上。
对于这些添加剂的浓度，根据添加剂的种类、两性离子性SCL用眼科用组合物的用途等进行适当设定。
对于本发明的两性离子性SCL用眼科用组合物的制剂形态，只要是包含水作为基剂的制剂形态即可，例如，可以是水溶液状、乳液状等中的任一种，但是优选为可举出水溶液状。
本发明的两性离子性SCL用眼科用组合物，只要根据其用途，按照自身公知的调制法制造即可，例如，可以使用第16改正日本药典制剂总则所记载的方法来制造。
本发明的两性离子性SCL用眼科用组合物作为即使在佩戴两性离子性SCL中也能够滴眼的滴眼剂(两性离子性SCL用滴眼剂)；即使在佩戴两性离子性SCL中也能够洗眼的洗眼剂(两性离子性SCL用洗眼剂)；两性离子性SCL用佩戴液、两性离子性SCL用多功能护理液、两性离子性SCL用洗涤液、两性离子性SCL用保存液等隐形眼镜护理用品来使用。其中，可举出优选为两性离子性SCL用滴眼剂、两性离子性SCL用洗眼剂，进一步优选为两性离子性SCL用滴眼剂。
所谓成为本发明的适用对象的两性离子性SCL，是以含有包含阳离子性基团的单体和包含阴离子性基团的单体作为离子性单体的聚合物作为构成素材的SCL。作为两性离子性SCL，具体地可举出以包含季铵盐等阳离子性基团，和羧基、磺酸基、磷酸基等阴离子性基团的聚合物为构成素材的SCL，对于该素材、制法，例如，日本特开平10-197831号公报等有所记载。
此外，成为本发明的适用对象的两性离子性SCL，可以是高含水率或低含水率中的任一种，但是可举出优选为高含水率，即美国食品药品局(FDA)中分类为组IV(离子性单体1摩尔％以上，含水率50％以上)的SCL。
2.抑制普拉洛芬和/或其盐对两性离子性SCL的吸附的方法(1)
此外，本发明提供抑制普拉洛芬和/或其盐对两性离子性SCL的吸附的方法，其特征在于，在包含普拉洛芬和/或其可药用的盐的两性离子性SCL用眼科用组合物中，配合氨丁三醇，且将pH值调节为5.5以上。该抑制吸附的方法在赋予两性离子性SCL用眼科用组合物抑制普拉洛芬和/或其盐对两性离子性SCL的吸附的作用方面是有用的。
在本发明的抑制吸附的方法中，对于所使用的普拉洛芬和/或其可药用的盐的种类、浓度、氨丁三醇的浓度、两性离子性SCL用眼科用组合物的pH、配合在两性离子性SCL用眼科用组合物中的药理成分、添加剂的种类、两性离子性SCL用眼科用组合物的制剂形态、用途、成为适用对象的两性离子性SCL的种类等，如前述“1.两性离子性SCL用眼科用组合物”项所记载的那样。
3.抑制普拉洛芬和/或其盐对两性离子性SCL的吸附的方法(2)
此外，本发明提供抑制普拉洛芬和/或其盐对两性离子性SCL的吸附的方法，该方法包含使含有普拉洛芬和/或其可药用的盐、和氨丁三醇，且pH值为5.5以上的液剂接触两性离子性SCL的工序。
在本发明的抑制吸附的方法中，对于所使用的普拉洛芬和/或其可药用的盐的种类、浓度、氨丁三醇的浓度、液剂的pH、配合到液剂中的药理成分、添加剂的种类、液剂的制剂形态、用途、成为适用对象的两性离子性SCL的种类等，如前述“1.两性离子性SCL用眼科用组合物”项所记载的那样。此外，在本发明的抑制吸附的方法中，使前述液剂接触两性离子性SCL的方法，只要根据该液剂的用途进行适当设定即可。例如，在前述液剂为滴眼剂的情况下，只要对佩戴两性离子性SCL的眼睛滴加前述液剂即可。
实施例
以下举出实施例对本发明进行具体地说明，但本发明不受这些任何限定。另外，在以下的试验例中，普拉洛芬使用株式会社エーピーアイコーポレーション制的普拉洛芬，氨丁三醇使用日本药典外药品标准氨丁三醇(UE-E)(关东化学株式会社制)或特级三(羟甲基)氨基甲烷(ナカライテスク株式会社制)。
试验例1
通过将表1所示的各成分用常法混合，来调制试验液。通过观察所得到的各试验液的外观，且测定浊度(660nm的吸光度)来评价白浊的有无。
此外，将各试验液2mL放入小瓶中，在其中浸渍SCL1片，在25℃下振荡2小时以上。此外，将各试验液2mL放入小瓶中在不浸渍SCL的状态下，在25℃下振荡2小时以上。通过液相色谱测定振荡后各试验液中的普拉洛芬含量，按照下述式，算出普拉洛芬对SCL的吸附量。另外，由于如果在将SCL浸渍于试验液的条件下振荡，则2小时以内普拉洛芬对SCL的吸附达到平衡状态，所以如果将振荡时间设定为2小时以上，则可以确认对普拉洛芬对SCL的吸附量的测定值无影响。
[数1]
吸附于1片SCL的普拉洛芬量(μg)＝(CC-CT)×V
CC：未浸渍SCL的试验液中的普拉洛芬含量(μg/mL)
CT：浸渍了SCL的试验液中的普拉洛芬含量(μg/mL)
V：试验中使用的试验液的量(mL)
另外，本试验中，使用下述4种SCL，求出普拉洛芬对各SCL的吸附量。
眼镜1：组IV，商品名“シード1dayPure”(注册商标)株式会社シード社制)，两性离子性，眼镜素材：甲基丙烯酸2-羟基乙酯(HEMA)、含有季铵基的甲基丙烯酸酯系化合物、含有羧基的甲基丙烯酸酯系化合物、甲基丙烯酸甲酯(MMA)、乙二醇二甲基丙烯酸酯(EGDMA)
眼镜2：组IV，商品名“シード1dayPure UP(うるおいプラス)”(注册商标)株式会社シード社制)，两性离子性，眼镜素材：甲基丙烯酸2-羟基乙酯(HEMA)、含有季铵基的甲基丙烯酸酯系化合物、含有羧基的甲基丙烯酸酯系化合物、甲基丙烯酸甲酯(MMA)、乙二醇二甲基丙烯酸酯(EGDMA)
眼镜3：组IV，商品名“ワンデーアキュビュー(注册商标)”(ジョンソンエンドジョンソンメディカル社制)，阴离子性，USAN名：etafilcon A
眼镜4：硅水凝胶隐形眼镜，组I，商品名“エアオプティクス2ウィーク(注册商标)”(チバビジョン社制)，USAN名：lotrafilcon B
将所得的结果示于表1。从该结果确认，在pH7.5下，所有的试验液均呈现无色澄清且良好的外观性状。此外，在不含氨丁三醇的试验液(比较例1)中，对于阴离子性SCL和非离子性的SCL，普拉洛芬几乎未被吸附，与此相对，对于两性离子性SCL，观察到普拉洛芬的吸附强，表明两性离子性SCL具有容易吸附普拉洛芬这样的特有特性。与此相对，在与普拉洛芬一起含有氨丁三醇、且pH值为7.5的试验液(实施例1～5)中，能够抑制普拉洛芬对两性离子性SCL的吸附。
[表1]
试验例2
通过将表2所示的各成分用常法混合来调制试验液。通过观察所得的各试验液的外观，且测定浊度(660nm的吸光度)来评价白浊的有无。此外，对于所得的各试验液，通过与前述试验例1同样的方法，测定普拉洛芬对两性离子性SCL的吸附量。
将所得的结果示于表2。从该结果确认，如果pH值变为4.5以下，则试验液产生白浊，观察到外观性状的恶化；但pH值为5.5以上时，呈现澄清的外观性状。此外，与pH值变高相伴，观察到普拉洛芬对两性离子性SCL的吸附量增加的倾向，但对于包含氨丁三醇的试验液，能够有效地抑制普拉洛芬对两性离子性SCL的吸附。从以上的结果确认，通过与普拉洛芬一起含有氨丁三醇、且将pH值设定为5.5以上，可以呈现澄清的外观性状，能够抑制普拉洛芬对两性离子性SCL的吸附。
[表2]
试验例3
通过将表3所示的各成分用常法混合来调制试验液。通过观察所得的各试验液的外观，且测定浊度(660nm的吸光度)来评价白浊的有无。此外，对于所得的各试验液，通过与前述试验例1同样的方法，测定普拉洛芬对两性离子性SCL的吸附量。另外，对于本试验，使用前述试验例1中使用的眼镜2(组IV，两性离子性)作为两性离子性SCL来进行。
将所得的结果示于表3。如表3表明的那样，即使使用除了氨丁三醇以外的缓冲剂成分，也不能充分地减少普拉洛芬对两性离子性SCL的吸附量。即，本试验结果表明，抑制普拉洛芬对两性离子性SCL的吸附是通过选择氨丁三醇作为含有成分，且将pH值设定为5.5以上而实现的特有的效果。
[表3]
表3
表中，各配合成分的配合量的单位是“w/v％”。
#1所谓HEPES，是2-[4-(2-羟基乙基)哌嗪-1-基]乙磺酸的简称。
Claims (6)
1.一种两性离子性软性隐形眼镜用眼科用组合物，其特征在于，含有0.001～0.5w/v％的普拉洛芬和/或其可药用的盐、和1～2w/v％的氨丁三醇，且pH值为5.5～9。
2.根据权利要求1所述的两性离子性软性隐形眼镜用眼科用组合物，是两性离子性软性隐形眼镜用滴眼剂。
3.一种抑制普拉洛芬和/或其可药用的盐对两性离子性软性隐形眼镜的吸附的方法，其特征在于，在包含0.001～0.5w/v％的普拉洛芬和/或其可药用的盐的两性离子性软性隐形眼镜用眼科用组合物中，配合氨丁三醇使其为0.0001～5w/v％，且将pH值调节为5.5～9。
4.液剂的用于制造两性离子性软性隐形眼镜用眼科用组合物的应用，所述液剂含有0.001～0.5w/v％的普拉洛芬和/或其可药用的盐、和1～2w/v％的氨丁三醇，且pH值为5.5～9。
5.根据权利要求4所述的应用，所述液剂是两性离子性软性隐形眼镜用滴眼剂。
6.一种非治疗目的抑制普拉洛芬和/或其可药用的盐对两性离子性软性隐形眼镜的吸附的方法，包含下述工序：使含有0.001～0.5w/v％的普拉洛芬和/或其可药用的盐、和0.0001～5w/v％的氨丁三醇，且pH值为5.5～9的液剂接触两性离子性软性隐形眼镜。
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| JP (1) | JP6401699B2 (zh) |
| CN (1) | CN105392481B (zh) |
| HK (1) | HK1217901A1 (zh) |
| RU (1) | RU2669570C2 (zh) |
| TW (1) | TWI623314B (zh) |
| WO (1) | WO2014192738A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TWI630931B (zh) * | 2017-04-10 | 2018-08-01 | 明基材料股份有限公司 | 眼用鏡片及其製造方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007008928A (ja) * | 2005-06-01 | 2007-01-18 | Rohto Pharmaceut Co Ltd | アシタザノラスト含有水性組成物 |
| CN101351199A (zh) * | 2005-12-27 | 2009-01-21 | 狮王株式会社 | 软性接触镜用组合物及吸附抑制方法 |
| JP2011098960A (ja) * | 2009-10-09 | 2011-05-19 | Rohto Pharmaceutical Co Ltd | 水性組成物 |
| JP2013010754A (ja) * | 2011-06-02 | 2013-01-17 | Rohto Pharmaceutical Co Ltd | トラニラストを含有する水性組成物 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3170619B2 (ja) * | 1995-04-20 | 2001-05-28 | 参天製薬株式会社 | 有機アミンを配合したプラノプロフェン点眼液 |
| JP4919666B2 (ja) * | 2005-01-26 | 2012-04-18 | ロート製薬株式会社 | プラノプロフェン含有組成物 |
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2014
- 2014-05-27 CN CN201480029909.8A patent/CN105392481B/zh not_active Expired - Fee Related
- 2014-05-27 RU RU2015154023A patent/RU2669570C2/ru not_active IP Right Cessation
- 2014-05-27 JP JP2015519868A patent/JP6401699B2/ja not_active Expired - Fee Related
- 2014-05-27 WO PCT/JP2014/063960 patent/WO2014192738A1/ja active Application Filing
- 2014-05-29 TW TW103118779A patent/TWI623314B/zh not_active IP Right Cessation
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2016
- 2016-05-23 HK HK16105849.4A patent/HK1217901A1/zh unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007008928A (ja) * | 2005-06-01 | 2007-01-18 | Rohto Pharmaceut Co Ltd | アシタザノラスト含有水性組成物 |
| CN101351199A (zh) * | 2005-12-27 | 2009-01-21 | 狮王株式会社 | 软性接触镜用组合物及吸附抑制方法 |
| JP2011098960A (ja) * | 2009-10-09 | 2011-05-19 | Rohto Pharmaceutical Co Ltd | 水性組成物 |
| JP2013010754A (ja) * | 2011-06-02 | 2013-01-17 | Rohto Pharmaceutical Co Ltd | トラニラストを含有する水性組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2669570C2 (ru) | 2018-10-12 |
| CN105392481A (zh) | 2016-03-09 |
| RU2015154023A3 (zh) | 2018-03-14 |
| WO2014192738A1 (ja) | 2014-12-04 |
| JP6401699B2 (ja) | 2018-10-10 |
| HK1217901A1 (zh) | 2017-01-27 |
| RU2015154023A (ru) | 2017-07-06 |
| TW201517904A (zh) | 2015-05-16 |
| JPWO2014192738A1 (ja) | 2017-02-23 |
| TWI623314B (zh) | 2018-05-11 |
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