CN110678185A - 磷脂酰胆碱经皮吸收制剂 - Google Patents
磷脂酰胆碱经皮吸收制剂 Download PDFInfo
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- CN110678185A CN110678185A CN201880035390.2A CN201880035390A CN110678185A CN 110678185 A CN110678185 A CN 110678185A CN 201880035390 A CN201880035390 A CN 201880035390A CN 110678185 A CN110678185 A CN 110678185A
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- Prior art keywords
- phosphatidylcholine
- adhesive layer
- preparation
- present
- transdermal
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Abstract
本发明提供一种在粘合剂层中含有磷脂酰胆碱的磷脂酰胆碱经皮吸收制剂。本发明涉及的磷脂酰胆碱经皮吸收制剂(1),构成为在支撑体(2)的至少一个面上形成的粘合剂层(3)包含磷脂酰胆碱、粘合成分和亲油性成分,所以能将制剂固定在患处,将所谓与液体等的制剂相比具有更好处理性的剂型作为贴剂,除了上述优点之外,由于磷脂酰胆碱可以稳定地存在于粘合剂层(3)中,所以通过贴附在人体等的皮肤等,利用磷脂酰胆碱的经皮吸收可以使皮下脂肪等局部肥胖溶解,能发挥使脂肪减少等效果,从而可以成为作为含有磷脂酰胆碱的减脂剂起作用的贴剂型的经皮吸收制剂(1)。
Description
技术领域
本发明涉及磷脂酰胆碱经皮吸收制剂。更具体而言,本发明涉及在粘合剂层中包含磷脂酰胆碱的贴剂型经皮吸收制剂。
背景技术
磷脂酰胆碱是从大豆种子提取油中获得的大豆卵磷脂的主要成分,其在化妆品和药品等中用作表面活性剂(乳化剂等)、皮肤调理剂等。该磷脂酰胆碱包括是亲水亲油性的都可以穿透脂肪细胞,另外,磷脂酰胆碱等磷脂酸能参与使皮下脂肪等局部肥胖减少的脂肪酸释放路径的活化,因此,可以预期发挥皮下脂肪的溶解效果。
作为皮下脂肪蓄积、肥胖中脂肪过多(具有脂肪层)的肥胖的减轻手段,例如采用直接皮下注入用于除去脂肪的皮下蓄积的组合物的方法,作为该组合物,使用了磷脂酰胆碱制剂等(例如,参照专利文献1)。但是,由于这种磷脂酰胆碱制剂的皮下注入在治疗过程中伴有疼痛。在安全性等方面是有问题的,因此期待开发不需要直接的皮下注入的自给药成为可能的经皮吸收型的制剂(经皮吸收制剂,也称为经皮给药制剂)。因此,提供了包含源自天然物的磷脂酰胆碱、L-肉碱、丙二醇、甘油和水但不包括亲油性基质的经皮用组合物(例如,参照专利文献2)。
现有技术文件
专利文献
专利文献1:日本专利公开第2007-509085号
专利文献2:日本专利第5747820号
发明内容
发明要解决的课题
另外,要求提供一种在粘合剂层中含有磷脂酰胆碱并且使剂型为贴剂的经皮吸收制剂。在粘合剂层中包含磷脂酰胆碱并使剂型为贴剂的经皮吸收制剂,从而得到不是涂布到皮肤等的类型的经皮吸收型制剂等,通过贴附到考虑脂肪的减少等的患部,可以将制剂固定在患部等,具有使剂型为贴剂的优点,除此之外,与液体状或凝胶状的制剂相比,其处理性也好。然而,在上述专利文献2中公开的构成等迄今为止提供的制剂的构成中,难以使剂型为贴剂。
本发明正是鉴于上述问题而完成的发明,其提供一种在粘合剂层中包含磷脂酰胆碱的贴剂型的磷脂酰胆碱经皮吸收制剂。
用于解决课题的手段
为了解决上述问题,本发明涉及的经皮吸收制剂,其特征在于,具有支撑体和在该支撑体的至少一个面上形成的粘合剂层,其中,上述粘合剂层含有磷脂酰胆碱、粘合成分和亲油性成分。
本发明涉及的经皮吸收制剂,其特征在于,在上述的本发明中,上述粘合成分是苯乙烯系热塑性弹性体。
本发明涉及的经皮吸收制剂,其特征在于,在上述的本发明中,进一步含有肉碱。
本发明涉及的经皮吸收制剂,其特征在于,在上述的本发明中,磷脂酰胆碱的含量是相对于整个粘合剂层为2.5~8.0质量%。
本发明涉及的经皮吸收制剂,其特征在于,在上述的本发明中,上述亲油性成分含有矿油。
本发明涉及的经皮吸收制剂,其特征在于,在上述的本发明中,其还包含具有支化结构的聚烯烃。
本发明涉及的经皮吸收制剂,其特征在于,在上述的本发明中,上述具有支化结构的聚烯烃是氢化C6-14烯烃聚合物。
发明效果
本发明涉及的磷脂酰胆碱经皮吸收制剂,在支撑体的至少一个面上形成的粘合剂层包含磷脂酰胆碱、粘合成分和亲油性成分而构成。由此,可以将制剂固定于患部,与液状等的制剂相比处理性良好,有使剂型为贴剂的优点,除此之外,磷脂酰胆碱能稳定地存在于粘合剂层中,因此通过贴附于人体等的皮肤等,利用磷脂酰胆碱的经皮吸收,使皮下的脂肪等局部肥胖溶解,可以发挥使脂肪减少等效果,制成作为含有磷脂酰胆碱的减脂剂起作用的贴剂型的经皮吸收制剂。
附图说明
图1是表示本发明涉及的经皮吸收制剂的一个实施方式的前视图。
图2是图1的A―A线剖视图。
具体实施方式
(I)经皮吸收制剂1的构成
以下,对本发明涉及的磷脂酰胆碱经皮吸收制剂1的一个实施方式进行说明。图1是表示本发明涉及的经皮吸收制剂1的一个实施方式的前视图,图2是图1的A―A线剖视图。在图中,1表示磷脂酰胆碱经皮吸收制剂(经皮吸收制剂),2表示支撑体,3表示粘合剂层,4表示剥离片,41表示切痕。
本发明涉及的磷脂酰胆碱经皮吸收制剂(经皮吸收制剂)1,是具有支撑体2和在该支撑体2的至少一面上形成的粘合剂层3的经皮吸收制剂1,其基本构成为上述的试剂层3包含磷脂酰胆碱、粘合成分和亲油性成分。需要说明的是,在图1和图2中,作为经皮吸收性制剂1的构成的一例,示出了在支撑体2的一个面形成有粘合剂层3且在粘合剂层3的表面贴附有剥离片4的构成。
(II)支撑体2
在本发明中,支撑体2只要其可以使用作为经皮吸收制剂1的贴剂的支撑体用途通常使用的支撑体,就没有特别限制,例如可以举出含有聚乙烯、聚丙烯等的伸缩性或非伸缩性的织布、无纺布,聚乙烯、聚丙烯等聚烯烃,聚对苯二甲酸乙二醇酯(PET)、聚萘二甲酸乙二醇酯(PEN)等聚酯,乙烯-乙酸乙烯酯共聚物、氯乙烯等的薄膜或片材(在本发明中,“薄膜”和“片材”同义,以下相同。),或氨基甲酸酯、聚氨酯等的发泡性片材等(以上也可称为“片状物”)。上述的物质可以单独使用1种,也可以组合使用2种以上(混合或层叠)。另外,为了防止静电在支撑体2上蓄积,可以使构成支撑体2的上述织布、无纺布等片状物等中含有抗静电剂等。
经皮吸收制剂1中的支撑体2的厚度,例如优选为200~280μm,特别优选为240~260μm左右,但并不特别限定于该范围。
此外,本发明的经皮吸收制剂1可以如图1和图2所示采用粘合剂层3被支撑体2和剥离片4夹持的构成。作为剥离片4,也可以具备通常在贴剂领域中使用的剥离片4。作为剥离片4,例如可以使用聚乙烯、聚丙烯等聚烯烃、聚对苯二甲酸乙二醇酯(PET)、聚萘二甲酸乙二醇酯(PEN)等聚酯、聚苯乙烯等的树脂片,玻璃纸、铝片,发泡聚乙烯片或发泡聚丙烯片等,或者上述中2种以上的层叠体。另外,可以使用对它们实施硅酮加工的片材、实施了氟树脂加工的片材、实施了压花加工、亲水性加工、疏水性加工等的片材等。
该剥离片4的厚度例如优选为80~120μm,特别优选为90~110μm,但并不特别限定于该范围。
需要说明的是,为了容易从粘合剂层3剥离,优选在剥离片4上形成切痕(狭缝)41。在图1所示的构成中,示出形成两个曲线形状的切痕41而剥离片4被分成三个的实施方式。
(III)粘合剂层3
粘合剂层3包含磷脂酰胆碱、粘合成分和亲油性成分。磷脂酰胆碱(Phosphatidylcholine)大多数情况下是具有胆碱形成磷酸酯键作为甘油磷脂的亲水部分且甘油骨架的2个脂肪酸形成酯键作为疏水部分的结构的磷脂的总称。磷脂酰胆碱是从大豆种子提取物油中获得的大豆卵磷脂的主要成分,并且通过渗入脂肪细胞,而参与使皮下脂肪等的局部肥胖减少的脂肪酸释放路径的活化,发挥皮下脂肪的溶解效果。需要说明的是,磷脂酰胆碱根据2个脂肪酸的选择而具有不同的磷脂名称,当选择2个棕榈酸作为脂肪酸时,称为二棕榈酰磷脂酰胆碱;当选择两个亚油酸作为脂肪酸时,称为DL磷脂酰胆碱,当选择2个棕榈酸作为脂肪酸时,称为二棕榈酰磷脂酰胆碱;当选择棕榈酸和油酸作为脂肪酸时,称为PO磷脂酰胆碱。
作为磷脂酰胆碱,例如可以举出以往公知的蛋黄磷脂酰胆碱、大豆磷脂酰胆碱、蛋黄溶血磷脂酰胆碱、大豆溶血磷脂酰胆碱、氢化蛋黄磷脂酰胆碱、氢化大豆磷脂酰胆碱、氢化蛋黄溶血磷脂酰胆碱、氢化大豆溶血磷脂酰胆碱等,这些可以单独使用1种,还可以组合使用2种以上。
粘合剂层3中的磷脂酰胆碱的含量,优选相对于整个粘合剂层3(指设粘合剂层3的总质量为100质量%;以下相同)为1.0~9.0质量份%。通过将磷脂酰胆碱的含量设定在该范围内,可以作为贴剂型的经皮吸收制剂而高效地发挥通过磷脂酰胆碱的经皮吸收来使皮下脂肪等局部肥胖减轻的效果。磷脂酰胆碱的含量特别优选相对于粘合剂层3整体为2.5~8.0质量%。
需要说明的是,肉碱可以添加到磷脂酰胆碱中。通过肉碱的存在,可以提高粘合剂层3中的磷脂酰胆碱的稳定性等,可以更有效地发挥含有磷脂酰胆碱的效果。在此,作为肉碱,例如可以举出L-肉碱、DL-肉碱、乙酰基-L-肉碱等,这些可以单独使用1种,也可以组合使用2种以上。在本发明中,优选使用L-肉碱。此外,作为肉碱,可以使用内盐、盐酸盐或钠盐等无机盐、酒石酸盐、草酸盐或富马酸盐等有机酸盐等。
就肉碱相对于磷脂酰胆碱的添加量而言,当将磷脂酰胆碱设为100质量份时,肉碱的添加量优选为8.5~12.0质量份,特别优选为9.0~10.5质量份。
接下来,作为形成粘合剂层3的粘合成分,例如,优选使用热塑性弹性体。在此,“热塑性弹性体”通常是表现出所谓通过加热而软化并表现出流动性同时通过冷却恢复成橡胶状弹性体这样的热塑性的弹性体的总称。作为这种热塑性弹性体,例如可以举出苯乙烯系、氨基甲酸酯系、丙烯酸系、烯烃系等的热塑性弹性体。在本发明中,优选使用可以使磷脂酰胆碱稳定地存在于粘合剂层3中且具有充分的皮肤粘合性和低皮肤刺激性的苯乙烯系热塑性弹性体(包括氢化苯乙烯系热塑性弹性体),特别优选使用苯乙烯系嵌段共聚物等苯乙烯系共聚物(包括氢化的共聚物)。
作为热塑性弹性体的苯乙烯系嵌段共聚物(包括氢化的共聚物,以下相同),具体可以举出包括苯乙烯-丁二烯嵌段共聚物、氢化苯乙烯-丁二烯嵌段共聚物、苯乙烯-丁二烯-苯乙烯嵌段共聚物、氢化苯乙烯-丁二烯-苯乙烯嵌段共聚物、苯乙烯-异戊二烯嵌段共聚物、氢化苯乙烯-异戊二烯嵌段共聚物、苯乙烯-异戊二烯-苯乙烯嵌段共聚物、氢化苯乙烯-异戊二烯-苯乙烯嵌段共聚物等。另外,还可以举出苯乙烯-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、以及它们的氢化后的嵌段共聚物等。这些苯乙烯系嵌段共聚物可以单独使用1种,还可以组合使用2种以上。
在上文中,“乙烯/丁烯”的表述是指乙烯和丁烯的共聚物嵌段,“乙烯/丙烯”的表述是指乙烯和丙烯的共聚物嵌段。
在上述的苯乙烯系嵌段共聚物中,从具有良好的皮肤粘合性和低的皮肤刺激性且容易获得和易于处理的观点出发,优选使用从由苯乙烯-丁二烯嵌段共聚物、氢化苯乙烯-丁二烯嵌段共聚物、苯乙烯-异戊二烯嵌段共聚物、氢化苯乙烯-异戊二烯嵌段共聚物、苯乙烯-异戊二烯-苯乙烯嵌段共聚物、氢化苯乙烯-异戊二烯-苯乙烯嵌段共聚物构成的组中选择的至少一种。
另外,作为苯乙烯-丁二烯嵌段共聚物(包括氢化的共聚物),优选共聚物中苯乙烯成分的含量为5~55质量%,特别优选为10~50质量%。此外,通过凝胶过滤色谱法等测得的重均分子量(以下的重均分子量与之相同)优选为10000~5500000,特别优选为15000~500000。
另外,作为苯乙烯-异戊二烯嵌段共聚物(包括氢化的共聚物),优选共聚物中苯乙烯成分的含量为5~55质量%,特别优选为10~50质量%。此外,重均分子量优选为10000~5500000,特别优选为15000~500000。
进而,作为苯乙烯-异戊二烯-苯乙烯嵌段共聚物(包括氢化的共聚物),优选共聚物中苯乙烯成分的含量为5~65质量%,特别优选为10~60质量%。此外,重均分子量优选为18000~5500000,特别优选为20000~500000。
粘合剂层3中热塑性弹性体等粘合成分的含量,优选相对于整个粘合剂层3为20.0~35.0质量%。如果粘合成分的含量小于20.0质量%,则有时难以维持粘合剂层3的形状,如果超过35.0质量%,则有时对皮肤的粘合性不足,所以不优选。粘合剂层3中热塑性弹性体等粘合成分的含量特别优选相对于整个粘合剂层3为25.0~30.0质量%。
需要说明的是,出于改善粘合剂层3的硬度、透明度、改善使用感、使粘合剂层3的各成分的混合、分散等良好的目的,优选配合具有支化结构的聚烯烃。作为这种聚烯烃,例如可以举出氢化C6-14烯烃聚合物、聚丁烯、氢化聚异丁烯、(C7、8)异链烷烃、(C8、9)异链烷烃、(C9-11)异链烷烃、(C10-13)异链烷烃、(C11、12)异链烷烃、(C11-13)异链烷烃、(C13、14)异链烷烃、(C13-16)异链烷烃、(C18-70)异链烷烃等异链烷烃类,烯烃低聚物、氢化聚癸烯等。其中,从粘合剂层3的透明性、附着性等使用性的观点出发,特别优选氢化C6-14烯烃聚合物、聚丁烯和氢化聚异丁烯。这些可以单独使用1种,还可以组合使用2种以上。
粘合剂层3中具有支化结构的聚烯烃的含量,优选相对于整个粘合剂层3为2.0~15.0质量%,特别优选为4.0~10.0质量%。
另外,亲油性成分在本发明中是对于将上述磷脂酰胆碱、粘合成分制成粘合剂层3有效的成分,例如可以举出橄榄油(橄榄果油)、橙子油(橙子果油)、矿油等植物油、动物油和矿物油。通过在它们以及下述的亲油性成分中含有矿油,可以更有效地发挥经皮吸收磷脂酰胆碱的效果。
进而,作为亲油性成分,例如可以举出棕榈酸、油酸、硬脂酸等脂肪酸类;鳄梨油、亚麻籽油、杏仁油、紫苏子油、榧子油、菜籽油、橄榄油、玉米油、蓖麻油、红花油、葵花籽油、棉籽油、霍霍巴油、夏威夷核果油、小麦胚芽油、大豆油、花生油、椰子油、棕榈油、棕榈仁油、山茶油、月见草油等植物油类;貂油、鱼油、猪油、牛油等动物油类;液体石蜡、角鲨烯、角鲨烷、聚丁烯、氢化聚异丁烯等烃类;己二酸二异丁酯、己二酸2-己基癸酯、己二酸二-2-庚基十一烷基酯、单异硬脂酸N-烷基乙二醇酯、异硬脂酸异鲸蜡酯、三异硬脂酸三羟甲基丙烷、2-乙基己酸鲸蜡酯、二-2-乙基己酸乙二醇酯、二-2-乙基己酸新戊二醇酯、三-2-乙基己酸甘油酯、三-2-乙基己酸三羟甲基丙烷、四-2-乙基己酸季戊四醇酯、辛酸鲸蜡酯、辛基十二烷基胶酯、油酸油酯、油酸辛基十二烷基酯、油酸癸酯、二癸酸新戊二醇酯、柠檬酸三乙酯、琥珀酸2-乙基己酯、乙酸戊酯、乙酸乙酯、乙酸丁酯、硬脂酸异鲸蜡酯、硬脂酸丁酯、癸二酸二异丙酯、癸二酸二-2-乙基己酯、乳酸鲸蜡酯、乳酸肉豆蔻酯、棕榈酸异丙酯、棕榈酸2-乙基己酯、棕榈酸2-己基癸酯、棕榈酸2-庚基十一烷基酯、12-羟基硬脂酸胆固醇酯、二季戊四醇脂肪酸酯、肉豆蔻酸异丙酯、肉豆蔻酸2-辛基十二烷基酯、肉豆蔻酸2-己基癸酯、肉豆蔻酸肉豆蔻酯、二甲基辛酸己基癸酯、月桂酸乙酯、月桂酸己酯、N-月桂酰-L-谷氨酸-2-辛基十二烷基酯、苹果酸二异硬脂基酯等酯类;二甲基聚硅氧烷、甲基苯基聚硅氧烷、甲基氢聚硅氧烷、八甲基环四硅氧烷、十甲基环五硅氧烷、十二甲基环六硅氧烷、四甲基四氢环四硅氧烷、氟改性的聚硅氧烷等有机硅类;全氟癸烷、全氟辛烷、全氟聚醚等氟系油剂类。上述举出的亲油性成分可以单独使用1种,也可以组合使用2种以上。
粘合剂层3中亲油性成分的含量,优选相对于整个粘合剂层3为30.0~85.0质量%,进一步优选为40.0~75.0质量%,特别优选为40~60质量%。
在具有上述构成的粘合剂层3中,作为任意成分,可以根据需要在不影响发明的目的和效果的范围内适当地配合抗氧化剂、增塑剂、填充剂、药物溶解助剂、抗菌剂、皮肤刺激减少剂、赋形剂等。
作为抗氧化剂,没有特别限制,例如可以举出抗坏血酸棕榈酸酯、抗坏血酸四异棕榈酸酯等抗坏血酸衍生物,依地酸钠等螯合剂,亚硫酸钠,丁基羟基茴香醚、丁基羟基甲苯、生育酚等生育酚和生育酚衍生物,硫酸羟基喹啉等喹啉和喹啉衍生物等。
作为增塑剂,没有特别限定,例如可以举出乙二醇、二甘醇、三甘醇、丙二醇、聚乙二醇、聚丙二醇等二醇类;橄榄油、蓖麻油、角鲨烯、羊毛脂等油脂类;液体石蜡等烃类;己二酸二异丙酯、己二酸二异丁酯、苯甲酸苄酯、2-乙基己酸鲸蜡酯、油酸油酯、油酸癸酯、乙酸苄酯、癸二酸二异丙酯、癸二酸二乙酯、三油酸山梨糖醇酯、三硬脂酸山梨糖醇酯、棕榈酸鲸蜡酯、肉豆蔻酸辛基十二烷基酯、肉豆蔻酸鲸蜡酯、肉豆蔻酸肉豆蔻酯、肉豆蔻酸异丙酯等脂肪酸酯类等,这些可以单独使用1种,也可以组合使用2种以上。
作为填充剂,没有特别限制,例如可以举出高岭土、膨润土和二氧化钛等。另外,作为药物溶解助剂,没有特别限制,例如可以举出α-环糊精、β-环糊精、γ-环糊精等环糊精(也可以用作后述的赋形剂)等。作为抗菌剂,没有特别限制,例如可以举出苯扎氯铵、苯甲酸、对羟基苯甲酸甲酯等。作为皮肤刺激减少剂,没有特别限制,例如可以举出硅酸酐等。作为赋形剂,没有特别限制,例如可以举出环糊精、乳糖、纤维素系粉末等(环糊精等赋形剂通常预先与肉碱等混合后使用)。
为了获得本发明的经皮吸收制剂1,例如,将构成粘合剂层3的成分中磷脂酰胆碱、热塑性弹性体等粘合成分和根据需要添加的成分分别与亲油性成分加以混合,使其分散,根据需要使其在丙酮、乙酸乙酯或甲苯等溶剂混合乃至分散,来制备用于形成粘合剂层3的涂布液。接着,将得到的涂布液涂布在支撑体2的形成粘合剂层3的面上,然后进行干燥(在与溶剂混合等时,使溶剂飞散),由此可以制造。粘合剂层3的厚度优选干燥后为约150~300μm左右。
此外,在使用剥离片4的情况下,可以在涂布于支撑体2之后的粘合剂层3上压接剥离片4,将粘合剂层3夹在支撑体2与剥离片4之间并进行层叠。或者,可以在剥离层4上涂布粘合剂层3的涂布液,进行干燥,使溶剂飞散,在剥离片4的表面上形成粘合剂层3,然后将支撑体2压接于粘合剂层3上而贴合。
用于形成粘合剂层3的涂布液的涂布,例如可以使用辊涂机、模头涂布机、凹版辊涂机、反向辊涂机、轻触辊涂机、浸入辊涂机、棒涂机、刮刀涂布机、喷涂机等以往公知的涂布机来进行。涂布液的干燥优选在例如约40~160℃左右的温度下进行。
如以上说明所述,本发明涉及的磷脂酰胆碱经皮吸收制剂1,构成为在支撑体2的至少一面上形成的粘合剂层3含有磷脂酰胆碱、粘合成分和亲油性成分。由此,有所谓可以将制剂固定于患部且与液状等的制剂相比处理性更好的剂型被设为贴剂的优点,除此之外,磷脂酰胆碱可以在粘合剂层3中稳定地存在,因此通过贴附于人体等的皮肤等,利用磷脂酰胆碱的经皮吸收来熔解皮下脂肪等局部肥胖溶解,可以发挥使脂肪减少等效果,由此成为作为含有磷脂酰胆碱的减脂剂起作用的贴剂型经皮吸收制剂1。
需要说明的是,本发明的磷脂酰胆碱经皮吸收制剂1,采用的构成是使用了含有亲油性成分代替亲水性成分的粘合剂层3的贴剂,由此从皮肤良好地经皮吸收作为药物的磷脂酰胆碱,但作为其渗透机理,认为如下所示。
即,推测原因如下:通过将作为贴剂的经皮吸收制剂1贴附于皮肤,磷脂酰胆碱利用皮肤的浓度梯度从皮肤表面(皮脂膜)依次渗透到皮肤(肌肤)的深部。另外,除了支撑体2之外,利用基于亲油性成分等的密封效果(密封疗法(ODT:Occlusive Dressing Therapy)效果)来抑制皮肤角质层中水分的蒸散,角质层发生溶胀并且作为粘合成分的热塑性弹性体等高分子变软(高分子的增塑),由此磷脂酰胆碱向皮肤的通过变得良好,在对皮肤的渗透性得以增强的状态下通过皮肤吸收磷脂酰胆碱。
进而,关于经皮吸收的机制,低分子成分透过角质层,但高分子成分与其不同,汗腺、毛囊等已经存在于皮肤表面的孔的内壁细胞是主要的透过路径。低分子成分在亲油性基质(粘合剂层3)的内部和角质层中扩散,分布在表皮内部,接着在真皮内扩散,被吸收到细胞内、毛细血管,另一方面,高分子成分在亲油性基质内以及上述孔中扩散,分布到孔的内壁细胞,不经由角质层到达真皮层。在本发明中,认为利用亲油性成分等的密封效果使角质层溶胀,从而促进了在上述孔中的扩散,提高了有效成分的透过效率。
本发明涉及的经皮吸收制剂1,可以预期通过磷脂酰胆碱的经皮吸收使皮下脂肪等局部肥胖溶解而减少脂肪等的效果,按照贴附于想要减少人体等的皮下脂肪的患部(的皮肤)的方式来使用。需要说明的是,贴附经皮吸收性制剂1的频率可以根据粘合剂层3中的磷脂酰胆碱等的含量、其他构成成分的种类和含量等来适当确定,但认为通过大概每周3~6次左右(不特别限于该范围)的贴附可以高效发挥其效果。
需要说明的是,以上说明的实施方式示出了本发明的一个实施方式,本发明并不限于上述的实施方式,具有本发明的构成且可以实现目的和效果的范围内的变形和改良当然包含在本发明的内容中。此外,实施本发明时的具体结构以及形状等,在能够实现本发明的目的和效果的范围内当然可以作为其他结构或形状等。本发明不限于上述的各实施方式,在能够实现本发明的目的的范围内的变形和改良包括在本发明中。
例如,在上述的实施方式中,作为经皮吸收制剂1的构成,如图1所示,示出了在剥离片4上形成有两条曲线形状的切痕41的实施方式并进行说明,但切痕41的形状是任意形状,另外,也可以不形成切痕41。除此之外,可以仅使用支撑体2和粘合剂层3而不使用剥离片41。
在上述的实施方式中,作为经皮吸收性制剂1的构成的一例,使用图2、图3对在支撑体2的一面形成粘合剂层3且在粘合剂层3的表面贴附有剥离片4的构成进行了说明。但粘合剂层3可以形成在支撑体2的两面上,还可以根据需要在粘合剂层3的表面贴附剥离片4。
在上述的实施方式中,作为经皮吸收性制剂1的形状,如图1所示,以四个角略圆的大致矩形的形状为例进行了说明,但作为经皮吸收性制剂1的形状是任意形状,可以采用三角形、四边形、五边形等多边形、圆形、椭圆形或几何形状等任何形状。另外,经皮吸收性制剂1的大小也是任意尺寸,可以根据涂布部位等适当确定。在如图1所示的大致矩形的形状(四边形)的情况下,例如可以将一边(在四个角倒圆的情况下,在倒圆之前)设置为例如50~200mm左右即可,但不特别限于该范围。
另外,实施本发明时的具体结构以及形状等可以在能实现本发明的目的的范围内为其他结构等。
实施例
以下根据实施例和参考例进一步详细说明本发明,但本发明不限于此。
[实施例1、实施例2和参考例1]
经皮吸收制剂的制造:
使用下述方法,制备图1和2所示的构成的作为贴剂的经皮吸收制剂。需要说明的是,在表1中,示出了实施例1、实施例2和参考例1的粘合剂层的组成(成分和含量(质量%))。另外,表1的数值(含量)是将粘合剂层整体设为100质量%时的各成分的值(质量%)。需要说明的是,参考例1不含磷脂酰胆碱。
(成分的组成)
[表1]
(含量:质量%)
(经皮吸收制剂的制造方法)
首先,在表1所示的成分中除亲油性成分以外的成分中,将亲油性成分和根据需要添加的成分分别混合并分散在亲油性成分中,形成构成粘合剂层的混合溶液。将该混合溶液混合或分散在丙酮等溶剂中,以制备粘合剂层形成用的涂布液。
用市售的模头涂布机将该涂布液涂布于作为支撑体的厚度为250μm的无纺布上并使其厚度为250μm,然后将作为剥离片的厚度为100μm的PET片进行压接,在60℃下干燥8小时,使溶剂飞散后,将尺寸切成110mm×135mm(如图1所示将四个角倒圆),以获得经皮吸收制剂。
[试验例1]
稳定性的确认:
将所获得的实施例1和实施例2的经皮吸收制剂置于温度为50℃的恒温槽中,确认了稳定性(外观、颜色和气味的变化)。需要说明的是,放置期为2周。2周后在经皮吸收制剂中未观察到异常,并且稳定性良好。
[试验例2]
经皮吸收制剂的减脂效果的确认:
将得到的实施例1和实施例2的经皮吸收性制剂以长边垂直短边水平的方向以受试者(各8名女性(实施例1为受试者1~8,实施例2为受试者9~16),表2示出受试者的年龄(岁))的肚脐为中心左右各贴附2片。贴附以受试者的就寝时间(贴附时间为7~8小时)计,将其连续使用一周。通过对使用前后的“(1)脐上周围”和“(2)皮下脂肪(面积)”的测定结果进行比较,确认了是否存在减脂效果。结果示于表2(表2的“差”中的“▲”表示试验后的值比试验前的值减少了(差为负))。
需要说明的是,(1)的量测使用市售的卷尺(尺:messure)进行(量测的单位为cm)。另外,(2)的测定基于使用腹部断层图像测定/全身X射线CT装置“Asteion(注册商标)Super4”(东芝医疗系统株式会社制)得到的图像而进行(面积的单位为cm2)。
(评价结果)
[表2]
如表2所示,可以确认实施例1和实施例2的经皮吸收制剂均具有减脂效果,并且磷脂酰胆碱含量高的实施例1的经皮吸收制剂在减脂效果方面通常更为优异(实施例2在(1)中可见效果,但在(2)中没有得到与实施例1大致相同的结果;实施例1中的结果比实施例2中的结果优异。)。
产业上的可利用性
本发明可以有利地用作提供在粘合剂层中含有磷脂酰胆碱作为有效成分的具有减脂效果的贴剂型经皮吸收制剂(磷脂酰胆碱经皮吸收制剂)的手段,产业上的可利用性高。
符号说明
1...经皮吸收制剂(磷脂酰胆碱经皮吸收制剂)
2...支撑体
3...粘合剂层
4...剥离片
41...切痕(狭缝)
Claims (7)
1.一种经皮吸收制剂,其特征在于,具有支撑体和在所述支撑体的至少一面上形成的粘合剂层,
所述粘合剂层包含磷脂酰胆碱、粘合成分和亲油性成分。
2.根据权利要求1所述的经皮吸收制剂,其特征在于,
所述粘合成分是苯乙烯系热塑性弹性体。
3.根据权利要求1或2所述的经皮吸收制剂,其特征在于,
进一步含有肉碱。
4.根据权利要求1~3中任一项所述的经皮吸收制剂,其特征在于,
相对于整个粘合剂层,磷脂酰胆碱的含量为2.5~8.0质量%。
5.根据权利要求1~4中任一项所述的经皮吸收制剂,其特征在于,
所述亲油性成分含有矿油。
6.根据权利要求1~5中任一项所述的经皮吸收制剂,其特征在于,
进一步包含具有支化结构的聚烯烃。
7.根据权利要求6所述的经皮吸收制剂,其特征在于,
所述具有支化结构的聚烯烃为氢化C6-14烯烃聚合物。
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PCT/JP2018/017312 WO2019150594A1 (ja) | 2018-01-31 | 2018-04-27 | ホスファチジルコリン経皮吸収製剤 |
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JPS5553649A (en) | 1978-10-13 | 1980-04-19 | Hitachi Ltd | Humidifier |
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JPS5955819A (ja) * | 1982-09-24 | 1984-03-31 | Nitto Electric Ind Co Ltd | 粘着性貼付製剤用膏体 |
JP3313891B2 (ja) * | 1994-06-21 | 2002-08-12 | ポーラ化成工業株式会社 | 経皮吸収促進剤及び皮膚外用剤 |
US20040018237A1 (en) * | 2002-05-31 | 2004-01-29 | Perricone Nicholas V. | Topical drug delivery using phosphatidylcholine |
DE10349979B4 (de) | 2003-10-24 | 2006-05-18 | Sanofi-Aventis Deutschland Gmbh | Medikamentöse gezielte lokale Lipolyse |
US20090028806A1 (en) * | 2005-02-25 | 2009-01-29 | Shigeo Suzuki | Medicine for External Application Containing Anti-Inflammatory Agent and Soy Lecithin |
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ITVR20070150A1 (it) | 2007-10-23 | 2009-04-24 | Phytonature Sas | Prodotto cosmetico per la lipolisi non invasiva del grasso sottocutaneo ed il trattamento della cellulite |
US8568746B2 (en) | 2009-08-25 | 2013-10-29 | Medrx Co., Ltd. | Transdermal composition of phosphatidylcholine and method for producing same |
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