CN108883316A - 亮肤、防晒、生成维生素d的组合物 - Google Patents
亮肤、防晒、生成维生素d的组合物 Download PDFInfo
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- CN108883316A CN108883316A CN201780019310.XA CN201780019310A CN108883316A CN 108883316 A CN108883316 A CN 108883316A CN 201780019310 A CN201780019310 A CN 201780019310A CN 108883316 A CN108883316 A CN 108883316A
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- acid
- sunscreen compositions
- topical sunscreen
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Abstract
本发明涉及一种防晒组合物。具体而言、本发明涉及一种涂于皮肤后可防止晒伤、使290nm‑298nm的紫外线B充分渗入皮肤以生成维生素D、同时抑制黑色素生成的防晒组合物。
Description
发明背景
皮肤过度暴露于紫外线辐射(UVR)可导致基底细胞癌和鳞状细胞癌。当紫外线B(290-320nm)和紫外线A(320-400nm)范围内的过多光子通过光化学作用破坏嘧啶二聚体而损伤DNA、并降低胶原蛋白弹性时、可引起皮肤受损和起皱。
人体皮肤受紫外线A(400nm-320nm;UVA)照射与受紫外线B(320nm-290nm;UVB)照射的反应不一样。UVA波长范围内的光线深入皮肤真皮、从而破坏胶原纤维、降低皮肤弹性、产生皱纹、通常还会引发光致老化。波长为350nm的UVA引起皮肤中黑色素的氧化、导致肤色变暗。这种UVA导致的皮肤变暗在阳光照射后2-5小时内极为明显、随后几天内消退。黑色素是导致黑斑和皮肤呈褐色(功能性着色)的色素、然而、接触UVA并不会增加黑色素数量。
与UVA相反、UVB仅渗入皮肤的表皮基底层、从而未影响胶原蛋白。暴露于UVB下可导致黑素生成、该过程通过特殊皮肤细胞(称为:黑色素细胞)增加了皮肤中黑色素的数量、从而导致功能性着色。照射UVB后的48-72小时内、肤色变暗尤为明显、随后于数星期至数月内消退。UVB通过黑素生成而导致皮肤晒黑、出现深色的色素沉着斑、如:黑斑、太阳斑、老年斑、红斑、褐斑、黑斑、老年性雀斑、太阳雀斑和瑕斑等。有趣的是、黑色素也通过吸收UVB而具有过滤UVR的作用。
UVB照射与人体内的维生素D水平也存在相关性。UVB照射使得维生素D前体在皮肤内合成、特别是、波长为290nm-298nm的UVB可破坏类胆固醇分子的强化学键。体内的维生素D水平高可降低各种疾病的发病率、如:多发性硬化、糖尿病、类风湿性关节炎、骨病、心血管疾病和癌症。
维生素D主要在皮肤的棘层和基底层进行合成、而黑素生成则是在基底层下面开始的。290nm-315nm的UVB在被吸收掉之前仅能穿透至表皮的有限深度里。该范围可分为两类:有利于生成维生素D的较短波长(290nm-298nm)、有利于黑素生成的较长波长(299nm-315nm)。波长越长、穿透越深。
通过偶尔暴露于阳光下、人体获得了所需的大部分维生素D。然而、现代生活使人们影响了对产维生素D的有益UVB的接触。UVB来自太阳、在穿过大气臭氧层时已被吸收了90%-95%。仅有10%-5%的UVB到达地球表面、薄雾再将其减弱5%-23%、阴天时会减弱50%-70%、积云将其减弱99%。只有当太阳高挂天空(通常为上午11点至下午1点左右)时、到达地表的UVB数量才足以产生具有生物学意义的、大量维生素D。建筑及车辆玻璃几乎可100%过滤掉UVB照射。此外、人们在户外活动时可接触大量UVB、但这种有益于生成维生素D的接触因人们使用防晒品而受阻。
防晒品由多种UVR过滤剂复合而成、每种UVR过滤剂吸收、阻挡或反射掉独特光谱的光线、并以不同百分比复合不同的UVR过滤剂从而得出不同类型的防晒品。常规防晒品专用于过滤掉UVB、UVA波长范围内的最广泛的UVR。但是这样也就过滤掉了很大一部分、用于人体皮肤进行维生素D合成的UVB。
现代室内生活方式加上大量使用防晒品使得许多国家的维生素D缺乏率上升。维生素D缺乏的定义为:25-羟基维生素D的血液水平低于20ng/ml、21-29ng/mL则为维生素D不足(Holick,MF,维生素D溶液,Hudson Street Press,2010,p.46)。
尽管日光暴露有诸多好处、但在许多文化中以拥有白皙肌肤为较高社会经济地位的象征、并且许多人发现无黑斑的肌肤比满是晒斑的肌肤更美丽。东西方文化中对肌肤明亮性的看法是完全不同的。在亚洲和印度次大陆的许多地方、男人、女人都希望通过重塑肤色来提高社会地位。2004年、Synovate的一项营销研究估计、香港、台湾、韩国、马来西亚和菲律宾约有40%的女性使用美白产品。相应地、这类人群也会主动避免任何日光暴露、因而她们更容易导致维生素D不足。
尽管防晒技术的最新进展能使使用者在防止UVR伤害的同时仍可生成治疗剂量的维生素D(见PCT/IB2009/055881)、但本发明切实引领了功能性着色(褐色肌肤)的发展、功能性着色在许多以白、亮肌肤为美的文化中是不被认可的。
以PCT/IB2009/055881的观点看、本发明的成就是惊人的、因为它不是鼓励功能性着色——这必然会减弱皮肤利用黑色素作为UVR过滤剂阻止UVB波长渗透生成维生素D的能力。本发明的组合物减弱了黑素生成。
发明内容
本发明涉及一种可防止功能性着色(如:晒黑)并保护皮肤免受日晒伤害、同时还可生成维生素D的防晒组合物。这类组合物的开发一开始即存在疑问、且有悖于直觉、因为晒黑和生成维生素D基本上是由相同光谱的UVB光实现的。
因此、本发明的第一个方面即提供了一种可防止UVR导致肌肤损伤、并允许290nm-298nm范围内UVB穿过生成维生素同时抑制黑素生成的局部防晒组合物。
该防晒组合物包括UVR过滤剂、其成分和浓度均根据每种过滤剂的吸收光谱进行调整以选择性过滤UVB和UVA范围内的光、从而防止肌肤损伤、同时使290nm-298nm范围内的UVB穿过生成维生素。
290nm-298nm波长范围很重要、因为这是可被人体皮肤吸收从而产生最多维生素D的UVR波长。
本发明的防晒组合物适用于局部使用、其形式可以是液体、洗液、乳液、摩丝、糊状物、乳膏、血清、喷雾、软膏、凝胶、泡沫或香脂。
为了发挥防晒品的有效性、需充分涂抹于皮肤上。因此、本发明的优选实施例中、该组合物在皮肤上的使用剂量约为0.01mg/cm2-50mg/cm2、或0.05mg/cm2-20mg/cm2或0.05mg/cm2-10mg/cm2或0.05mg/cm2-5mg/cm2。优选地、该组合在皮肤上的使用剂至少约为0.5mg/cm2-2mg/cm2。优选地、该组合在皮肤上的使用剂至少约为0.5mg/cm2。更优选地、该组合在皮肤上的使用剂至少约为1mg/cm2。优选地、该组合在皮肤上的使用剂至少约为1.3mg/cm2-2mg/cm2。更优选地、该组合在皮肤上的使用剂至少约为2mg/cm2。本领域的技术人员都知道、皮肤防晒组合物的使用剂量至少为2mg/cm2才具显著意义、因为该值为使用于受试者皮肤上的假设量、这样才能至少达到欧盟ISO24444的SPF等级及澳大利亚体内试验方法。
某特定防晒组合物的功效可由SPF表示、SPF定义为:使用后皮肤上产生最小红斑量(MED、即:晒伤)所需的UVR能量除以不使用防晒品产生MED所需的UVR能量。MED定义为:在未使用防晒品时、使皮肤产生最小、可察觉晒伤的UVR最短时间间隔或剂量。因此、SPF是用户在使用/或未使用防晒品情况下多长时间出现晒伤二者间的相对值。例如、某人在使用SPF为15的防晒品后、其晒伤出现时间比未使用防晒品的时间要长15倍。SPF越高、防晒组合物对UVR的防护程度越高。
在本发明的一个或多个实施例中、防晒组合物的SFP至少为4、6、8、10、15、20、25、30、40、50。优选地、该组合物的SPF至少为10、更优选为15。在其它优选实施例中、防晒组合物的SPF至少为20、25或30。SPF可根据AS/NZS 2604:2012定义的标准确定、该标准与剂量为2mg/cm2时产品的真实SPF相关。
本领域技术人员均知道、皮肤由不同的层组成、如:表皮、真皮和皮下组织(皮下层)、以及其它细胞类型和成分、如:脂肪组织、毛囊、静脉、动脉、汗腺、神经和纤维。
UVR导致的皮肤损伤是指对皮肤或皮肤细胞、或对皮肤外观或皮肤层细胞的暂时或永久性损伤、如:干性皮肤、红斑(晒伤)、角化病、皱纹、着色过度、过早老化和皮肤细胞DNA损伤。皮肤着色过度可表现为通常所说的太阳斑、老年斑、褐黄斑、老年雀斑、斑点、日光斑和瑕斑。
在本发明的实施例中、组合物包含两种以上UVR过滤剂。根据本发明组合物所需性质、对该组合物中的UVR过滤剂及其浓度进行选择和调整。即:选择UVR过滤剂及调整其浓度、使本发明组合物在UVR辐照时能有效防止UVR导致的皮肤损伤、同时让290nm-298nm范围内的UVB充分渗透以生成维生素D。
在本发明的实施例中、防晒组合物可使波长范围为290nm-298nm(最大程度生成维生素D的波长范围)的UVB穿过量至少为5%、10%、15%或20%。
在本发明的优选实施例中、该防晒组合物允许290nm-298nm范围内的UVB光穿过量约为5%-5%(最大程度生成维生素D的波长范围)。
本发明组合物所使用的UVR过滤剂可以是能吸收、阻挡、或反射掉UVR的任何化合物、其中、UVR的波长约为280nm-400nm。本领域技术人员应知道、该波长范围包含了UVA和UVB波长范围、因此也包括了可导致人体皮肤晒伤的UVR范围。
UVR过滤剂可以是化学防晒剂或物理防晒剂。除上述讨论的外、UVR过滤剂或该组合物所用试剂的选择以下因素的影响、如:欲达到的SPF等级、波长290nm-298nm内欲达到吸收率、安全性、管理因素、试剂是液体或固体、UVR过滤剂结合其它成分形成稳定组合物的能力。
在本发明的实施例中、组合物包含一种或多种UVR过滤剂、这些过滤剂为可吸收UVR的化学防晒剂、选自以下成分:邻氨基苯甲酸薄荷酯、磺基苯甲酮(二苯甲酮-4)、磺基苯甲酮钠(二苯甲酮-5)、二乙氨基羟苯甲酰基苯甲酸己酯、苯甲酸盐、羟苯酮(二苯甲酮-3)、依茨舒(对苯二甲酰二硒酸磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、苯基二钠二苯并咪唑四磺酸盐、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
上表汇编了批准用于澳大利亚、美国、欧洲、日本等国的UVR过滤剂。随时间推移、该表可能有所变动、如:排除了某些化合物或添加了新的化合物。列表添加了所有化合物均适用于本发明所用的UVR过滤剂。
本发明实施例中、该组合物至少包括两种选至以下成分的UVR过滤剂:邻氨基苯甲酸薄荷酯、磺基苯甲酮(二苯甲酮-4)、磺基苯甲酮钠(二苯甲酮-5)、二乙氨基羟基苯甲酰基苯甲酸己酯、羟苯酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、苯基二苯并咪唑四磺酸二钠、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明的实施例中、该组合物至少包括选自以下成分中的两种UVR过滤剂:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括选自以下成分中的至少三种UVR过滤剂:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括选自以下成分中的至少三种UVR过滤剂:邻氨基苯甲酸薄荷酯、磺基苯甲酮(二苯甲酮-4)、磺基苯甲酮钠(二苯甲酮-5)、二乙氨基羟基苯甲酰基苯甲酸己酯、羟苯酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、苯基二苯并咪唑四磺酸二钠、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括浓度约为0.5%-7%(w/w)的邻氨基苯甲酸薄荷酯。在本发明的优选实施例中、该组合物包括浓度约为1%-4%(w/w)的邻氨基苯甲酸薄荷酯。
在本发明的实施例中、该组合物包括浓度约为0.5%-10%(w/w)的磺基苯甲酮(二苯甲酮-4)。在本发明的优选实施例中、该组合物包括浓度约为1%-4%(w/w)的磺基苯甲酮(二苯甲酮-4)。
在本发明的实施例中、该组合物包括浓度约为0.5%-10%(w/w)的磺基苯甲酮钠(二苯甲酮-5)。在本发明的实施例中、该组合物包括浓度约为1%-4%(w/w)的磺基苯甲酮钠(二苯甲酮-5)。
在本发明的实施例中、该组合物包括浓度约为0.5%-10%(w/w)的二乙氨基羟基苯甲酰基苯甲酸己酯。在本发明的优选实施例中、该组合物包括浓度约为1%-5%(w/w)的二乙氨基羟基苯甲酰基苯甲酸己酯。
在本发明的实施例中、该组合物包括浓度约为0.5%-8%(w/w)的羟苯甲酮(二苯甲酮-3)。在本发明的优选实施例中、该组合物包括浓度约为1%-4%(w/w)的羟苯甲酮(二苯甲酮-3)。
在本发明的实施例中、该组合物包括浓度约为0.5%-10%(w/w)的依莰舒(对苯二甲酰亚胺二磺酸)。在本发明的优选实施例中、该组合物包括浓度约为1%-9%(w/w)的依莰舒(对苯二甲酰亚胺二磺酸)。
在本发明的实施例中、该组合物包括浓度约为0.5%-10%(w/w)的奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)。在本发明的优选实施例中、该组合物包括浓度约为1%-7%(w/w)的奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)。
在本发明的实施例中、该组合物包括浓度约为0.5%-7%(w/w)的丁基甲氧基二苯甲酰甲烷(阿伏苯宗)。在本发明的优选实施例中、该组合物包括浓度约为1%-5%(w/w)的丁基甲氧基二苯甲酰甲烷(阿伏苯宗)。
在本发明的实施例中、该组合物包括浓度约为0.5%-5%(w/w)的聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)。在本发明的优选实施例中、该组合物包括浓度约为1%-3%(w/w)的聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)。
在本发明的实施例中、该组合物包括浓度约为0.5%-5%(w/w)的苯基二苯并咪唑四磺酸二钠。在本发明的优选实施例中、该组合物包括浓度约为1%-3%(w/w)的苯基二苯并咪唑四磺酸二钠。
在本发明的实施例中、该组合物包括浓度约为0.5%-5%(w/w)的PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)。在本发明的优选实施例中、该组合物包括浓度约为2%-3%(w/w)的PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)。
在本发明的实施例中、该组合物包括浓度约为0.5%-15%(w/w)的甲基水杨醇(水杨酸高孟酯)。在本发明的优选实施例中、该组合物包括浓度约为1%-13%(w/w)的甲基水杨醇(水杨酸高孟酯)。在本发明的其它优选实施例中、该组合物包括浓度约为0.5%-6%(w/w)的甲基水杨醇(水杨酸高孟酯)。
在本发明的其它优选实施例中、该组合物包括浓度约为0.5%-10%(w/w)的水杨酸辛酯(水杨酸乙基己酯)。在本发明的优选实施例中、该组合物包括浓度约为0.5%-8%(w/w)的水杨酸辛酯(水杨酸乙基己酯)。在本发明的其它优选实施例中、该组合物包括浓度约为0.5%-6%(w/w)的水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括选自下组成分中的至少两种:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)、其中、本发明组合物按浓度计包括:约0.5%-8%(w/w)的氧苯酮(二苯甲酮-3)、约0.5%-10%(w/w)的依莰舒(对苯二甲酰亚胺二磺酸磺酸)、约0.5%-10%(w/w)的奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、约0.5%-7%(w/w)的丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、约0.5%-15%的甲基水杨醇(水杨酸高孟酯)、约0.5%-10%(w/w)的水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括选自以下成分中的至少三种UVR过滤剂:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)、其中、本发明组合物按浓度计包括:约0.5%-8%(w/w)的氧苯酮(二苯甲酮-3)、约0.5%-10%(w/w)的依莰舒(对苯二甲酰亚胺二磺酸磺酸)、约0.5%-10%(w/w)的奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、约0.5%-7%(w/w)的丁基甲氧基二苯甲酰基甲烷(阿伏苯宗)、约0.5%-15%(w/w)的甲基水杨醇(水杨酸高孟酯)、约0.5%-10%(w/w)的水杨酸辛酯(水杨酸乙基己酯)。
在本发明的优选实施例中、该组合物包括选自下组成分中的至少两种UVR过滤剂:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)、其中、本发明组合物按浓度计包括:约1%-4%(w/w)的氧苯酮(二苯甲酮-3)、约1%-9%(w/w)的依莰舒(对苯二甲酰亚胺二磺酸)、约1%-7%(w/w)的奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、约1%-5%(w/w)的丁基甲氧基二苯甲酰基甲烷(阿伏苯宗)、约0.5%-6%(w/w)的甲基水杨醇(水杨酸高孟酯)、约0.5%-6%(w/w)的水杨酸辛酯(水杨酸乙基己酯)。
在本发明的优选实施例中、该组合物包括选自以下成分中的至少三种UVR过滤剂:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酰亚胺二磺酸)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)、其中、本发明组合物按浓度计包括:约1%-4%(w/w)的羟苯甲酮(二苯甲酮-3)、约1%-9%(w/w)的依莰舒(对苯二甲酰亚胺二磺酸磺酸)、约1%-7%(w/w)的奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、约1%-5%(w/w)的丁基甲氧基二苯甲酰基甲烷(阿伏苯宗)、约0.5%-6%(w/w)的甲基水杨醇(水杨酸高孟酯)、约0.5%-6%(w/w)的水杨酸辛酯(水杨酸乙基己酯)。
一般而言、本发明组合物所用的UVR过滤剂可分为主要吸收UVA的过滤剂、如:邻氨基苯甲酸薄荷酯、二乙氨基羟基苯甲酰基己基苯甲酸酯、依莰舒(对苯二甲酰亚胺二磺酸)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、二苯基二苯并咪唑四磺酸二钠;主要吸收UVB的过滤剂、如:磺基苯甲酮(二苯甲酮-4)、磺基苯甲酮钠(二苯甲酮-5)、羟苯酮(二苯甲酮-3)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括选自以下成分中的至少一种:邻氨基苯甲酸薄荷酯、二乙氨基羟基苯甲酰基苯甲酸己酯、依莰舒(对苯二甲酰亚胺二磺酸)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)和苯基二苯并咪唑四磺酸二钠。
在本发明实施例中、该组合物包括选自下组成分中的至少一种UVB过滤剂:磺基苯甲酮(二苯甲酮-4)、磺基苯甲酮钠(二苯甲酮-5)、羟苯酮(二苯甲酮-3)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括选自以下成分中的至少两种UVB过滤剂:磺基苯甲酮(二苯甲酮-4)、磺基苯甲酮钠(二苯甲酮-5)、羟苯酮(二苯甲酮-3)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括选自以下成分中的至少三种UVB过滤剂:磺基苯甲酮(二苯甲酮-4)、磺基苯甲酮钠(二苯甲酮-5)、羟苯酮(二苯甲酮-3)、奥克立林(2-乙基己基α-氰基-β-苯基肉桂酸酯)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)。
在本发明实施例中、该组合物包括一种UVA过滤剂和至少一种UVB过滤剂。例如、该组合物可包含阿伏苯宗和甲基水杨醇、或阿伏苯宗和奥克立林、或阿伏苯宗和水杨酸辛酯、或邻氨基苯甲酸薄荷酯和甲基水杨醇、或二乙氨基羟基苯甲酰基苯甲酸己酯和甲基水杨醇、或依莰舒和辛基水杨酸、或二苯基二苯并咪唑四磺酸二钠和磺基苯甲酮、或邻氨基苯甲酸薄荷酯和奥克立林、或依莰舒和甲基水杨醇。
在本发明实施例中、该组合物包括至少一种UVA过滤剂和至少两种UVB过滤剂。例如、该组合物可包含阿伏苯宗、甲基水杨醇和奥克立林、或阿伏苯宗、奥克立林和水杨酸辛酯、或阿伏苯宗、水杨酸辛酯和四基水杨醇、或邻氨基苯甲酸薄荷酯、甲基水杨醇和奥克立林、或二乙氨基羟基苯甲酰基己基苯甲酸酯、甲基水杨醇和羟苯甲酮、或依莰舒、水杨酸辛酯和甲基水杨醇、或苯基二苯并咪唑四磺酸二钠、磺胺苯酮和聚硅氧烷-15、或邻氨基苯甲酸薄荷酯、奥克立林和PEG-25PABA、或依莰舒、甲基水杨醇和水杨酸辛酯。
在本发明实施例中、该组合物包括至少一种UVA过滤剂和至少三种UVB过滤剂。例如、该组合物可包括:阿伏苯宗、甲基水杨醇、水杨酸辛酯和奥克立林、或阿伏苯宗、奥克立林、羟苯甲酮和水杨酸辛酯、或阿伏苯宗、磺基苯甲酮、水杨酸辛酯和甲基水杨醇、或邻氨基苯甲酸薄荷酯、羟苯甲酮、甲基水杨醇和奥克立林、或二乙氨基羟基苯甲酰基己基苯甲酸酯、甲基水杨醇、PEG-25PABA和羟苯甲酮、或依莰舒、水杨酸辛酯、聚硅氧烷-15和甲基水杨醇、或苯基二苯并咪唑四磺酸二钠、磺异苯酮、奥克立林和聚硅氧烷-15、或邻氨基苯甲酸薄荷酯、羟苯甲酮、奥克立林和PEG-25PABA、或阿莰舒、甲基水杨醇、奥克立林和水杨酸辛酯。
在本发明实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约0.5%-5%(w/w)的阿伏苯宗、约0.5%-8%(w/w)的甲基水杨醇、约0.5%-6%(w/w)的水杨酸辛酯和约0.5%-7%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约1%-5%(w/w)的阿伏苯宗、约1%-8%(w/w)的甲基水杨醇、约1%-8%(w/w)的水杨酸辛酯、约1%-9%(w/w)的奥克立林和约1%-10%(w/w)的羟苯甲酮。
在本发明的优选实施例中、该组合物按浓度计包括:约1%-5%(w/w)的阿伏苯宗、约1%-8%(w/w)的甲基水杨醇、约1%-8%(w/w)的水杨酸辛酯、约1%-9%(w/w)的奥克立林和约1%-7%(w/w)的阿莰舒。
在本发明的更优选实施例中、该组合物按浓度计包括:约0.5%-4%(w/w)的阿伏苯宗、约0.5%-6%(w/w)的甲基水杨醇、约0.5%-3%(w/w)的水杨酸辛酯和约0.5%-4%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约1%-5%(w/w)的阿伏苯宗、约1%-8%(w/w)的甲基水杨醇、约1%-8%(w/w)的水杨酸辛酯和约1%-9%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约3%-5%(w/w)的阿伏苯宗、约4.9%-7%(w/w)的甲基水杨醇、约2.3%-5%(w/w)的水杨酸辛酯和约2.7%-7%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约3%(w/w)的阿伏苯宗、约4.9%(w/w)的甲基水杨醇、约2.3%(w/w)的水杨酸辛酯和约2.7%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约3%(w/w)的阿伏苯宗、约4.9%(w/w)的甲基水杨醇、约3.7%(w/w)的水杨酸辛酯和约5%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约3%(w/w)的阿伏苯宗、约6%(w/w)的甲基水杨醇、约4%(w/w)的水杨酸辛酯和约7%(w/w)的奥克立林。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-8%(w/w)的羟苯甲酮、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约3%-5%(w/w)的阿伏苯宗、约2%-4%(w/w)的羟苯甲酮、约2%-6%(w/w)的水杨酸辛酯和约2%-7%(w/w)的奥克立林。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的磺异苯酮。
在本发明的优选实施例中、该组合物按浓度计包括:约3%-5%(w/w)的阿伏苯宗、约2%-6%(w/w)的甲基水杨醇、约2%-6%(w/w)的水杨酸辛酯和约2%-5%(w/w)的磺异苯酮。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的邻氨基苯甲酸薄荷酯、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-8%(w/w)的羟苯甲酮和约0.5%-10%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约2%-4%(w/w)的邻氨基苯甲酸薄荷酯、约2%-6%(w/w)的甲基水杨醇、约2%-4%(w/w)的羟苯甲酮和约2%-7%(w/w)的奥克立林。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-10%(w/w)的阿莰舒、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的羟苯甲酮和约0.5%-10%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约1%-4%(w/w)的阿茨舒、约2%-6%(w/w)的甲基水杨醇、约2%-4%(w/w)的羟苯甲酮和约2%-%(w/w)的奥克立林。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-10%(w/w)的二乙氨基羟基苯甲酰基苯甲酸己酯、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林。
在本发明的优选实施例中、该组合物按浓度计包括:约2%-5%(w/w)的二乙氨基羟基苯甲酰基苯甲酸己酯、约2%-4.9%(w/w)的甲基水杨醇、约1%-2.9%(w/w)的水杨酸辛酯和约2%-5%(w/w)的奥克立林。
该组合物还可包含稳定剂和抗氧化剂、以帮助维持UVR过滤剂在该组合物中的稳定性、如:浓度约为0.5%-4%(w/w)的苯并三唑基十二烷基对甲酚(Tinogard TL或BDC)、浓度约为0.5%至7%(w/w)的二乙基己基丁香醛丙二酸酯(DEHSM)。
本发明的防晒组合物抑制黑素生成、因此、尽管该组合物允许一定比例的、波长为290nm-298nm的UVB被皮肤吸收产生维生素D、但皮肤不生成黑色素、且不会被晒黑(即:功能性着色)。其有利方面为、个人可长时间使用本发明组合物、且不影响其通过持续日晒而生成维生素的能力。
黑色素负责皮肤着色、它是通过一系列氨基酸酪氨酸和酶酪氨酸酶的氧化反应形成的。酪氨酸酶将酪氨酸转化为L-3,4-二羟基苯丙氨酸(L-DOPA或DOPA)、然后转化为多巴醌。随后、多巴醌经自氧化转化为多巴色素、然后再转化为二羟基吲哚(二羟基吲哚-2-羧酸或DHICA)、最后形成真黑素(黑褐色肌肤色素)。后一个反应是在多巴铬互变异构酶和DHICA氧化酶存在条件下发生的。多巴醌在半胱氨酸或谷胱甘肽存在条件下转化为半胱氨酰DOPA或谷胱甘肽DOPA。随后形成褐黑素(黄红皮肤色素)。
本发明防晒组合物所用的黑素生成抑制剂可破坏这些反应中的其中一个、即:抑制黑色素合成和皮肤色素沉着。最重要的是、这种可抑制黑素生成的优选化合物不会明显阻断、吸收和反射掉可生成维生素D的波长范围的UVR、尤其是波长为290-298nm的UVR。
在本发明实施例中、该组合物包括一种施于皮肤后即可通过抑制酪氨酸酶活性来抑制黑素生成的化合物。
对于适用于本发明组合物的、可抑制酪氨酸酶活性的化合物、其非限制性实例包括:L-抗坏血酸-2-磷酸镁、甘草根及乌拉甘草的甘草提取液(包括:光甘草定)、N-十一碳烯酰基苯丙氨酸、1-甲基乙内酰脲-2-酰亚胺、苯乙基间苯二酚、反式-4-氨基甲基环己烷羧酸、乳酸、甘氨酸锌、葡萄糖酸、二硫代辛二醇、葡糖胺、N-乙酰基-D-葡糖胺、寡肽-34、曲酸、4-羟基苯基-α-D-吡喃葡萄糖苷、红藻萃取液、乙醇酸、烟酰胺及其衍生物、羟基均二苯乙烯及其衍生物、芦荟素和羟基醌及其衍生物。
在本发明实施例中、该组合物包括一种施用于皮肤后即可通过抑制黑素体转移来抑制黑素生成的化合物。
对于适用于本发明组合物的、可抑制黑素体转移的化合物、其非限制性实例包括:烟酰胺、红藻萃取液、类黄酮衍生物如5,7,3'-三羟基-3,6,4'-三甲氧基黄酮和抑制PAR-2通路的大豆提取物。
在本发明实例中、该组合物包括浓度为0.5%-10%(w/w)的烟酰胺。在本发明的优选实施例中、该组合物包括浓度约为1%-5%(w/w)的烟酰胺。
在本发明的实施例中、该组合物包括浓度约为0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。在本发明的优选实施例中、该组合物包括浓度约为1%-4.5%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物包括来自甘草根及乌拉甘草的、含光甘草定的甘草提取液、其浓度约为0.1%-5%(w/w)。在本发明的优选实施例中、该组合物包括来自甘草根及乌拉甘草的、含光甘草定的甘草提取液、其浓度约为1%-2.5%(w/w)。
在本发明的实施例中、该组合物包括浓度约为0.5%-6%(w/w)的红藻萃取液。在本发明的优选实施例中、该组合物包括浓度约为1%-3%(w/w)的红藻萃取液。
在本发明的实施例中、该组合物包括浓度约为0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸。在本发明的优选实施例中、该组合物包括浓度约为0.25%-2.5%(w/w)的N-十一碳烯酰基苯丙氨酸。
在本发明的实施例中、该组合物包括浓度约为0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺。在本发明的优选实施例中、该组合物包括浓度约为0.25%-3%(w/w)的1-甲基乙内酰脲-2-酰亚胺。
在本发明的实施例中、该组合物包括浓度约为0.05%-7%(w/w)的苯乙基间苯二酚。在本发明的优选实施例中、该组合物包括浓度约为0.1%-3%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物包括浓度约为0.5%-8%(w/w)的大豆提取物。在本发明的优选实施例中、该组合物包括浓度约为1%-6%(w/w)的大豆提取物。
在本发明实施例中、该组合物包括浓度约为0.5%-3%(w/w)的反式-4-氨基甲基环己烷羧酸。在本发明的优选实施例中、该组合物包括浓度约为1%-2%(w/w)的反式-4-氨基甲基环己烷羧酸。
在本发明的实施例中、该组合物包括浓度约为1%-25%(w/w)的乳酸或其衍生物。在本发明的优选实施例中、该组合物包括浓度约为4%-10%(w/w)的乳酸或其衍生物。
在本发明的实施例中、该组合物包括浓度约为0.05%-6%(w/w)的甘氨酸锌。在本发明的优选实施例中、该组合物包括浓度约为0.1%-4%(w/w)的甘氨酸锌。
在本发明的实施例中、该组合物包括浓度约为0.05%-5%(w/w)的葡糖酸。在本发明的优选实施例中、该组合物包括浓度约为0.5%-3%(w/w)的葡糖酸。
在本发明的实施例中、该组合物包括浓度约为0.5%-6%(w/w)的二硫代辛二醇。在本发明的优选实施例中、该组合物包括浓度约为1%-3%(w/w)的二硫代辛二醇。
在本发明的实施例中、该组合物包括浓度约为0.5%-6%(w/w)的葡糖胺。在本发明的优选实施例中、该组合物包括浓度约为1%-4%(w/w)的葡糖胺。
在本发明的实施例中、该组合物包括浓度约为0.5%-6%(w/w)的N-乙酰基-D-葡糖胺。在本发明的优选实施例中、该组合物包括浓度约为0.75%-5%(w/w)的N-乙酰基-D-葡糖胺。
在本发明的实施例中、该组合物包括浓度约为0.1%-4%(w/w)的寡肽-34。在本发明的优选实施例中、该组合物包括浓度约为1%-2%(w/w)的寡肽-34。
在本发明的实施例中、该组合物包括浓度约为0.5%-4%(w/w)的曲酸及其衍生物。在本发明的优选实施例中、该组合物包括浓度约为1%-3%(w/w)的曲酸及其衍生物。
在本发明的实施例中、该组合物包括浓度约为0.1%-3%(w/w)的羟基均二苯乙烯及其衍生物。在本发明的优选实施例中、该组合物包括浓度约为0.25%-2%(w/w)的羟基均二苯乙烯及其衍生物。
在本发明的实施例中、该组合物包括浓度约为0.1%-3%(w/w)的芦荟素。在本发明的优选实施例中、该组合物包括浓度约为0.25%-2%(w/w)的芦荟素。
在本发明的实施例中、该组合物包括浓度约为0.1%-3%(w/w)的类黄酮衍生物、如:5,7,3-三羟基-3,6,4-三甲氧基黄酮。在本发明的优选实施例中、该组合物包括浓度约为0.25%-2%(w/w)的类黄酮衍生物、如:5,7,3-三羟基-3,6,4-三甲氧基黄酮。
在本发明的实施例中、该组合物包括浓度约为0.1%-3%(w/w)的氢醌单苯甲醚及香豆素。在本发明的优选实施例中、该组合物包括浓度约为0.25%-2%(w/w)的氢醌单苯甲醚及香豆素。
在本发明的实施例中、该组合物至少一种选自以下成分的、抑制黑素生成的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁。
在本发明的优选实施例中、该组合物至少两种选自以下成分的、抑制黑素生成的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁。
例如:该组合物可包含1-甲基乙内酰脲-2-酰亚胺和烟酰胺、或苯乙基间苯二酚和N-十一碳烯酰基苯丙氨酸、或N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁、或1-甲基乙内酰脲-2-酰亚胺和苯乙基间苯二酚、或N-十一碳烯酰基苯丙氨酸和N-乙酰基-D-葡糖胺、或L-抗坏血酸-2-磷酸镁和烟酰胺、或烟酰胺和N-乙酰基-D-葡糖胺、或L-抗坏血酸-2-磷酸镁和甲基乙内酰脲-2-酰亚胺。
在本发明的实施例中、该组合物至少包括一种选自以下成分、且抑制黑素生成的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺、L-抗坏血酸-2-磷酸镁、其中、该组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物至少包括两种选自以下成分、且抑制黑素生成的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺、L-抗坏血酸-2-磷酸镁、其中、该组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物至少包括三种选自以下成分、且抑制黑素生成的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺、L-抗坏血酸-2-磷酸镁、其中、该组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.05%-7%(w/w)的苯乙基间苯二酚和约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸和约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺。
在本发明的实施例中、该组合物按浓度计包括:约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-10%(w/w)的烟酰胺和约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺。
在本发明的实施例中、该组合物按浓度计包括:约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁和约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺。
在本发明的优选实施例中、该组合物包括至少三种选至以下成分并可抑制黑素生成的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁。
例如:该组合物可包括:1-甲基乙内酰脲-2-酰亚胺、烟酰胺和苯乙基间苯二酚、或N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁、或1-甲基乙内酰脲-2-酰亚胺、苯乙基间苯二酚和N-十一碳烯酰基苯丙氨酸、或N-乙酰基-D-葡糖胺、L-抗坏血酸-2-磷酸镁和烟酰胺、或烟酰胺、苯乙基间苯二酚和N-乙酰-D-葡糖胺、或L-抗坏血酸-2-磷酸镁、1-甲基乙内酰脲-2-酰亚胺和烟酰胺、或苯乙基间苯二酚、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁、或苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸和L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的优选实施例中、该组合物按浓度计包括:约0.05%-2%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-5%(w/w)的烟酰胺和约0.05%-2%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.05%-7%(w/w)的苯乙基间苯二酚和约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺、约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚和约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺。
在本发明的实施例中、该组合物按浓度计包括:约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁、约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.05%-7%(w/w)的苯乙基间苯二酚、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物包括一种以上UVR过滤剂和一种以上可抑制黑素生成的化合物、并精心选择和调整过滤剂和化合物浓度、使得该组合物在用于皮肤上时具有防止UVR导致皮肤损伤、且允许290-298nm范围内UVB充分穿过皮肤产生维生素D、并抑制黑色素形成的作用。
在本发明实施例中、该组合物包括一种或多种可吸收UVR的UVR过滤剂、这些过滤剂均为化学防晒剂、它们选自以下成分:邻氨基苯甲酸薄荷酯、磺胺苯二酮(二苯甲酮-4)、磺胺苯二酮钠(二苯甲酮-5)、二乙氨基羟基苯甲酰基苯甲酸酯、羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酸二苯甲醚磺酸)、奥克立林(2-乙基己基-α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、聚硅氧烷-15(二甲基二苯甲醛丙二酸酯)、苯基二苯并咪唑四磺酸二钠、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯);以及一种或多种可抑制黑素生成、且选自以下成分的化合物:L-抗坏血酸-2-磷酸镁、来自甘草根和乌拉甘草的、含光甘草定的甘草提取物、N-十一碳烯酰基苯丙氨酸、1-甲基乙内酰脲-2-酰亚胺、苯乙基间苯二酚、反式-4-氨基甲基环己烷羧酸、乳酸、甘氨酸锌、葡萄糖酸、二硫辛二醇、葡糖胺、N-乙酰-D-葡萄糖胺、寡肽-34、曲酸及其衍生物、羟基均二苯乙烯及其衍生物、芦荟素、羟基醌及其衍生物、烟酰胺、红藻萃取物、类黄酮衍生物如5,7,3'-三羟基-3,6,4'-三甲氧基黄酮和抑制PAR-2通路的大豆提取物。
在本发明的实施例中、该组合物包含选自以下成分的至少一种UVA过滤剂:邻氨基苯甲酸薄荷酯、二乙氨基羟基苯甲酰基苯甲酸酯、依莰舒(对苯二甲酸二苯甲醚磺酸)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、苯基二苯并咪唑四磺酸二钠;选自以下成分的至少一种UVB过滤剂:磺胺苯二酮(二苯甲酮-4)、磺胺苯二酮钠(二苯甲酮-5)、羟苯甲酮(二苯甲酮-3)、奥克立林(2-乙基己基-α-氰基-β-苯基肉桂酸酯)、聚硅氧烷-15(二甲基二苯甲醛丙二酸酯)、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯);以及至少一种可抑制黑素生成且选自以下成分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物包含选自以下成分的、至少一种UVA过滤剂:邻氨基苯甲酸薄荷酯、二乙氨基羟基苯甲酰基苯甲酸酯、依莰舒(对苯二甲酸二苯甲醚磺酸)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、苯基二苯并咪唑四磺酸二钠;选自以下成分的至少两种UVB过滤剂:磺胺苯二酮(二苯甲酮-4)、磺胺苯二酮钠(二苯甲酮-5)、羟苯甲酮(二苯甲酮-3)、奥克立林(2-乙基己基-α-氰基-β-苯基肉桂酸酯)、聚硅氧烷-15(二甲基二苯甲醛丙二酸酯)、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯);以及至少两种可抑制黑素生成且选自以下成分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁。
在本发明的优选实施例中、该组合物包含选自以下成分的、至少两种UVR过滤剂:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酸二苯甲醚磺酸)、奥克立林(2-乙基己基-α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)、其中、本发明组合物按浓度计包括:约1%-4%(w/w)的羟苯甲酮(二苯甲酮-3)、约1%-9%(w/w)的依莰舒(对苯二甲酸二苯甲醚磺酸)、约1%-7%(w/w)的奥克立林(2-乙基己基-α-氰基-β-苯基肉桂酸酯)、约1%-5%(w/w)的丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、约0.5%-6%(w/w)的甲基水杨醇(水杨酸高孟酯)和约0.5%-6%(w/w)的水杨酸辛酯(水杨酸乙基己酯);本发明组合物至少包括一种可抑制黑素生成且选自以下组分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺、L-抗坏血酸-2-磷酸镁。其中、本发明组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的优选实施例中、该组合物包含选自以下成分的、至少三种UVR过滤剂:羟苯甲酮(二苯甲酮-3)、依莰舒(对苯二甲酸二苯甲醚磺酸)、奥克立林(2-乙基己基-α-氰基-β-苯基肉桂酸酯)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、甲基水杨醇(水杨酸高孟酯)和水杨酸辛酯(水杨酸乙基己酯)、其中、本发明组合物按浓度计包括:约1%-4%(w/w)的羟苯甲酮(二苯甲酮-3)、约1%-9%(w/w)的依莰舒(对苯二甲酸二苯甲醚磺酸)、约1%-7%(w/w)的奥克立林(2-乙基己基-α-氰基-β-苯基肉桂酸酯)、约1%-5%(w/w)的丁基甲氧基二苯甲酰甲烷(阿伏苯宗)、约0.5%-6%(w/w)的甲基水杨醇(水杨酸高孟酯)和约0.5%-6%(w/w)的水杨酸辛酯(水杨酸乙基己酯);本发明组合物至少包括两种可抑制黑素生成且选自以下组分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺、L-抗坏血酸-2-磷酸镁、其中、本发明组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括至少一种可抑制黑素生成且选自以下组分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-7%(w/w)的苯乙基间苯二酚和约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
在本发明的实施例中、该组合物按浓度计包括:约为0.5%-7%(w/w)的阿伏苯宗、浓度约为0.5%-15%(w/w)的甲基水杨醇、浓度约为0.5%-10%(w/w)的水杨酸辛酯、浓度约为0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、浓度约为0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸和约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.5%-10%(w/w)的烟酰胺和约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁和约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%至约10%(w/w)的水杨酸辛酯、约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-2%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-5%(w/w)的烟酰胺和约0.05%-2%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰葡糖胺和约0.1%-12%(w/w)的镁-L-抗坏血酸-2-磷酸酯。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.05%-7%(w/w)的苯乙基间苯二酚和约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.5%-6%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.1%-12%(w/w)的镁-L-抗坏血酸-2-磷酸酯和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚和约0.5%-6%(w/w)的N-十一碳烯酰基苯丙氨酸。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.1%-12%(w/w)的镁-L-抗坏血酸-2-磷酸酯、约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺和约0.5%-10%(w/w)的烟酰胺。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸和约0.1%-12%(w/w)的镁-L-抗坏血酸-2-磷酸酯。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-7%(w/w)的苯乙基间苯二酚、约0.5%-6%(w/w)的N-十一碳烯酰基苯丙氨酸和约0.1%-12%(w/w)的镁-L-抗坏血酸-2-磷酸酯。
在本发明的实施例中、该组合物包含至少一种选自下组的UVA过滤剂:邻氨基苯甲酸薄荷酯、二乙氨基羟基苯甲酰基苯甲酸己酯、依茨舒(对苯二甲酰亚胺二磺酸磺酸)、丁基甲氧基二苯甲酰甲烷(阿伏苯宗)和二苯基二苯并咪唑四磺酸二钠;至少一种选自下组的UVB过滤剂:磺异苯酮(二苯甲酮-4)、磺异苯酮钠(二苯甲酮-5)、氧苯酮(二苯甲酮-3)、氰双苯丙烯酸辛酯(α-氰基-β-苯基肉桂酸2-乙基己酯)、聚硅氧烷-15(二甲基二乙基苯甲醛丙二酸酯)、PEG-25PABA(乙氧基化4-氨基苯甲酸乙酯)、甲基水杨醇(水杨酸三甲环己酯)和水杨酸辛酯(水杨酸乙基己酯)、此外还包括浓度约0.05%-5%的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-8%(w/w)的氧苯酮、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的阿伏苯宗、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的磺异苯酮、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-7%(w/w)的邻苯二甲酸薄荷酯、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-8%(w/w)的氧苯酮和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和-约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-10%(w/w)的依茨舒、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的磺异苯酮和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
在本发明的实施例中、该组合物按浓度计包括:约0.5%-10%(w/w)的二乙氨基羟基苯甲酰基苯甲酸己酯、约0.5%-15%(w/w)的甲基水杨醇、约0.5%-10%(w/w)的水杨酸辛酯和约0.5%-10%(w/w)的奥克立林、此外还包括约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺和约0.05%-7%(w/w)的苯乙基间苯二酚。
可以理解的是、任何能够有效过滤290nm-298nm范围内的UVB的浓度下的化合物或组分都不适合包含在本发明的组合物中。
类似地、任何有效促进皮肤中黑色素形成的化合物或组分都不适合包含在本发明的组合物中。
以下是黑色素生成抑制剂的非限制性实例、在一定浓度下、它们可能不适合于本发明的防晒剂组合物、因为它们在皮肤用来制造维生素D的范围内有效地过滤UVB。
不适合包含在本发明组合物中的黑素生成抑制剂包括类维生素A及其衍生物、ronaflair Softshade、皮质类固醇包括局部类固醇、如氟轻松、5,7-二羟基-6,8-二甲基-3-(4-甲氧基苄基)苯并二氢吡喃-4-酮、羟基肉桂酸是苯丙素、人参和西洋参提取物、2,5-二氢苯甲酸、3,4,5-三羟基苯甲酸、4-(苄氧基)苯酚、N-乙酰基-4-S-半胱氨酰苯酚和N-丙酰基-4-S-半胱氨酰基苯酚、4-羟基茴香醚、水杨酸和乙酰水杨酸、芦荟、山茶花提取物、yitis Vinifera提取物。不适当的UV过滤剂
下列UVR过滤剂在一定浓度下不适合包含在本发明的组合物中、因为它们基本上过滤维生素D生产范围内的UVR。这些不合适的UV过滤剂包括但不限于:二苯甲酮(二苯基甲酮)、二苯甲酮-1(2,4-二羟基二苯甲酮)、二苯甲酮-2(2,2',4,4'-四羟基二苯甲酮)、二苯甲酮-6(2,2'-二羟基-4,4'-二甲氧基二苯甲酮)、二苯甲酮-8(2,2'-二羟基-4-甲氧基二苯甲酮)、二苯甲酮-12(2-羟基-4-辛氧基二苯甲酮)、二苯甲酮-7(5-氯-2-羟基二苯甲酮)、二苯甲酮-11(双(2,4-异羟基苯基)甲酮)、4-甲基亚苄基樟脑(Uvinul MBC 95或3-(4-甲基苄基)樟脑)、西诺沙酯(2-乙氧基对-甲氧基肉桂酸酯)、桂皮酸盐(甲氧基肉桂酸辛酯或甲氧基肉桂酸乙基己酯)、二乙醇胺对甲氧基、对甲氧基肉桂酸异戊酯(Neo Heliopan E1000)、阿魏酸、二苯甲酰基甲烷(苯甲酰甲烷)、Bisoctrizole(Tinosorb M、亚甲基双苯并三唑基四甲基丁基苯酚或MBBT)、氧化锌(ZnO)、二氧化钛(氧化钛(IV)或TiO2)、氧化铈(IV)(CeO2)、恩索利唑(2-苯基苯并咪唑-5-磺酸或Parsol HS)、苯基苯并咪唑茶磺酸、苯基苯并咪唑磺酸钠、2-苯基苯并咪唑、氨基苯甲酸(4-氨基苯甲酸、对氨基苯甲酸或PABA)、二甲胺基苯甲酸戊酯-0(乙基己基二甲基PABA或2-乙基己基4-二甲基氨基苯甲酸酯)、二甲胺基苯甲酸戊酯-A(对二甲氨基苯甲酸戊酯或戊基二甲基PABA)、氨基苯甲酸甘油酯(1-4-氨基苯甲酸甘油酯或甘油PABA)、乙基己基三嗪酮(辛基三嗪酮或乙基己基三嗪酮)、水杨酸三乙醇胺(三乙醇胺水杨酸酯或TEA水杨酸酯)、甲酚曲唑三硅氧烷(Mexoryl XL或2-(2-羟基-5-甲基苯基)苯并三唑)、双乙基己氧基苯酚甲氧基苯三嗪(Tinosorb S或双乙基己基氧基苯酚甲氧基苯基三嗪)、异三嗪醇(二乙基己基丁酰氨基三嗪酮或Uvasorb HEB)、二没食子酰三油酸酯(5-(3,3-二甲基2-正硼烷)-3-戊烯-2-酮或没食子酸)、樟脑苯甲酸铵甲基硫酸盐、(Mexoryl S01)、苄叉樟脑磺酸、聚丙烯酰胺甲基苄叉樟脑、6,7-二羟基香豆素(秦皮乙素)、7-羟基香豆素(伞形酮)、褐藻多酚(BAPs)、乙基-4-[双(羟基丙基)]氨基苯甲酸酯(对氨基苯甲酸酯或罗塞二酸酯的丙氧基酯)、肉桂酸乙酯、乙基二羟基丙基PABA、肉桂酸二异丙酯乙酯、甲氧基肉桂酸乙酯、乙基PABA(苯佐卡因)、尿刊酸乙酯、乙基己酸甘油酯酯二甲氧基、甘油辛酸酯二甲氧基、水杨酸异丙基、异戊基三硅氧烷、异戊基三甲氧基肉桂酸酯三硅氧烷、甲氧基肉桂酸异丙酯、二异丙基肉桂酸甲酯、指甲花醌、硅酸镁铝、水杨酸薄荷酯、2,4-二羟基-N-(3-羟丙基)-3,3-二甲基丁酰胺酯、水杨酸苄酯、凡士林软膏、Quicksun Clear和Quicksun Matte提取物、以及尿刊酸(4-咪唑丙烯酸);甘油二酯类似物、毛喉素、异丁基甲基黄嘌呤和促黑细胞刺激素。
本领域技术人员应当理解、本发明的组合物还可以包括防腐剂、保湿剂、润肤剂、润肤霜、稠度因子、螯合剂、香料、活性剂、赋形剂、稀释剂和着色剂。
本发明组合物中使用的保湿剂和润肤剂剂可以使皮肤更柔软、更柔韧和更厚、从而增强皮肤产生维生素D的能力。在优选实施例中、本发明的组合物包括甘油和/或泛酰醇和/或其衍生物。甘油的浓度可为约0.1%至约8%(w/w)。泛酰醇的浓度可以为约0.05%至约7%(w/w)。
用于本发明的防晒组合物的其他适当的润肤霜和保湿剂包括、但不限于:水、氨基酸、神经酰胺、神经酰胺2、透明质酸、脂肪酸、甘油三酸酯、磷脂、糖鞘脂类、亚油酸、葡萄糖胺聚糖、甘油(AKA甘油)、粘多糖、吡咯烷酮羧酸、α-羟基酸、羊毛脂、脂类、杏油、菜籽油、玉米油、荷荷巴油、荷荷巴蜡、卵磷脂、橄榄油、红花油、芝麻油、大豆油、菜籽油、亚麻油、甜杏仁油、核桃油、棕榈油、亚麻子油、大麻籽油、角鲨烷、丙二醇二癸酸酯/二氢吡啶、十六醇、十六烷基硫酸钠、十六烷基醇、癸二醇、十六烷基羟乙基纤维素、甘油三酯、丙烯酸酯/硬脂酸-20甲基丙烯酸酯共聚物、泛醇、泛酸钙、泛酸、去水山梨糖醇单硬脂酸酯、具有活性细菌培养的益生菌、以及硅酮衍生的成分、如环甲基、聚二甲基硅氧烷交联聚合物、硅酮和二甲基硅酮。
本发明的组合物还可包括下列一种或多种适当的赋形剂、稀释剂、润肤剂、增稠剂、防腐剂、增塑剂和载体:硅华-5、SymGlucan、β-葡聚糖、燕麦β-葡聚糖、戊二醇、越桔(越桔)提取物、霍霍巴油、蔓越莓籽油、柳兰提取物、黑加仑油、喜阴悬钩子(黑莓)、椴树属科尔多瓦(菩提树)花提取物、牡丹根提取物、甘氨酸大豆油、玻璃苣籽油、尿囊素、巴拉圭冬青(巴拉圭茶)提取物、洋橄榄树(橄榄)果油、氢化橄榄油、耐冬山茶花、金银花提取物、棕榈酰三肽-5、棕榈酰四肽-7、水蓼、神经酰胺2、肌肽、榄仁树、莳萝提取物、水解糖胺聚糖、黄花龙胆提取物、牛蒡、高山火绒草提取物、葛根、亚麻籽油、没药醇、柳叶菜属植物提取物、染料木黄酮、茯苓酸提取物(fu ling)、墨角藻(海藻)提取物、鳄梨(鳄梨)油、积雪草(雷公根)胚轴提取物、鞘糖脂或天然保湿因子(NMF)、角鲨烯、油棕(棕榈)油、乳过氧化物酶、鞣花酸、天竺葵提取物、紫花苜蓿(苜蓿)提取物、油菜籽油、水孔蛋白、卵磷脂、杏仁油、左旋肉碱、摩洛哥坚果(阿甘树)油、莲花种子提取物、矢车菊提取物、蛋黄、菜籽油、神经酰胺、黑莓提取物、姜黄根(姜黄)、亚麻籽油、西番莲籽油、肌醇、齐墩果酸、番茄红素、石榴提取物、悬钩子属植物和覆盆子(波森莓)浆果提取物、帚石楠花(石楠)提取物、叶黄素、棉花糖提取物、糖胺聚糖、花生(花生)提取物、洋甘菊、母菊(洋甘菊)油、叶黄素、Cucurbitea peponis(南瓜)、紫草、壳聚糖、罗望子种子提取物、磷脂(脑磷脂)、辛酸/癸酸甘油三酯、β-谷甾醇、heolen(蘑菇)、刺梨(栗子)玫瑰提取物、蜂蜜、谷氨酰胺、绣线菊提取物、玉米油、肌酸、枇杷提取物、谷胱甘肽、牛蒡根提取物、巴西莓提取物、杏仁油、甜瓜(蜜瓜)果实提取物、咖啡树(咖啡)种子提取物、咖啡酸、棕榈油、芒果印度(芒果)种子黄油、夏威夷坚果油、月见草油、丝兰提取物、单宁酸、角叉菜胶(海藻)口香糖、花生醇、刺槐豆胶、沸石、聚山梨醇酯、聚山梨醇酯80、聚山梨醇酯20、双-PEG-18甲基醚二甲基硅烷、水解小麦蛋白、十六烷基硫酸钠、十六/十八醇、癸二醇、PPG-20甲基葡萄糖醚、油醇聚醚10、VP/十六烷共聚物、马铃薯淀粉提取物、三指拉瑞阿(小榭树)提取物、明胶、乙二胺四乙酸(EDTA)、EDTA二钠、油酸、水解丝、红6色淀、植酸、碳酸二辛酯、PEG橄榄油羧酸钠、蜜二糖、环甲硅油、木鲁星果棕籽油、新戊基乙二醇二丙酸酯/二癸酸酯、麦角酰胺、焦糖、米糠油、乙基香草醛、甲基丙二醇、山茱萸提取物、诺丽果汁、碳酸二乙基己酯、红33、胭脂红、美国榛子油、磷酸甘油酯、PEG-12牛烯-16、PEG-26牛顿-26、聚二甲基硅氧烷交联聚合物、聚二甲基硅氧烷、硅酮、十六烷基羟乙基纤维素、甘油三酯、丙烯酸酯/硬脂醇聚醚-20甲基丙烯酸酯共聚物、泛酸钙(泛酸)、脱水山梨糖醇硬脂酸酯、三辛基十二烷基柠檬酸酯、小球藻(藻类)、二PPG-3肉豆蔻基醚己二酸酯、PPG-2肉豆蔻基醚丙酸酯、酪蛋白(牛奶蛋白质)、美丽伊谷草(藻类)提取物、月桂醇、氢化二癸烷、脱氢醋酸钠、紫云英(黄芪)根、大麻种子油、巴西果(巴西坚果)提取物、环四硅氧烷、甲基葡萄糖-20、C13-14异链烷烃、偏苯三酸十三烷基酯、蓖麻油、肉豆蔻酸甘油酯、对羟基苯甲酸酯(包括对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯和对羟基苯甲酸乙酯)、镁、PEG-19油菜籽甾醇、七叶皂甙、磷酸钾、蝙蝠醇、聚异丁烯、膨润土、氯氧化铋、氮化硼、碳酸钙、巴西棕榈蜡、瓷土(高岭土)、巴西棕榈、玉米淀粉、漂白土、蒙脱石、尼龙-12、钾、大米淀粉、二氧化硅、硅酸盐、蚕丝粉、淤泥、碳酸钠、双二甘油基多聚己二酸酯、红皮藻、鲸蜡硬脂醇聚醚-20、乙酰六肽-3、核桃油、脱水山梨糖醇倍半油酸酯、依替膦酸四钠、山核桃油、月桂酸丙二醇酯、丙二醇硬脂酸酯、丙二醇、聚二甲基硅氧烷、纯净水、软化水、可溶性鱼胶原蛋白、卡波姆钠、异硬脂酸酯酸、PEG-14丁醚、泊洛沙姆184、椰油脂酸甘油酯、纳豆胶、油酸癸酯、月桂醇聚醚-13羧酸钠、月桂醇聚醚-4、初乳、瓜尔胶、羟丙基瓜尔胶、菌类植物胶、苄氯酚、西门木炔酸、山萮酸、氨甲基庚基丙醇、糊精、壬基酚聚醚、甘油三月桂酸酯、甲基丙烯多聚甘油、聚丙烯酰胺、硬脂酸甘油酯、癸二酸、PEG-32、六偏磷酸钠、赤藓酮糖、脱水山梨糖醇油酸酯、二聚亚油酸二异丙酯、鲸腊醇、硬脂醇聚醚-20、植烷三醇、甘油聚醚-26、甘油聚醚-26磷酸酯、乙基己基甘油、二羟基丙酮(DHA)、甘油硬脂酸酯、保湿剂(鲸蜡硬脂醇)、三油酸甘油酯、果胶、月桂基醚硫酸铵、维生素D3、丙烯酸酯/C 10-30烷基丙烯酸酯交联聚合物、黄色5,1,2-己二醇、PEG/PPG-17/6共聚物、磷酸、小麦胚芽油、小麦蛋白、丙二醇异硬脂酸酯、蓖麻油酸酯、乙酰酪氨酸、聚甘油单硬脂酸酯、月桂基PEG-9聚二甲基硅氧基乙基二甲基硅油、乳清蛋白、二甲基癸酰胺、山崳基三甲基氯化铵、氢化聚异丁烯、癸酸酯/六水合物、丙烯酸酯共聚物、木糖、丙烯酸钠/丙烯酰基二甲基牛磺酸钠共聚物、C18-36酸甘油酯、作品蜡、月桂醇聚醚、山梨糖醇、硬脂基聚甲基硅氧烷、肉豆蔻醇聚醚硫酸酯钠盐、乙酸丁酯、PEG-80脱水山梨糖醇月桂酸酯、硝酸硼、十八烷醇、己二酸二异丙酯、硅氧烷、十三烷醇硬脂酸酯、甘油油酸酯、甘油异硬脂酸酯、鲸蜡醋酸盐、黄原胶、辛乙二醇、氯二甲苯酚、羧乙烯聚合物、弹性蛋白、异十二烷、聚丁烯、异硬脂酰胺DEA、合成鲸蜡、EDTA四钠、聚乙烯、PEG/PPG-20/15二甲聚硅氧烷、蜡大戟、山梨酸、月桂醇聚醚-23、硬脂酸辛酯、山梨酸钾、PEG 90M、PEG-12二甲聚硅氧烷、钙化醇、鼠尾草酸、三乙醇胺、碧萝芷、甘油二硬脂酸酯、C20-40pareth-40、聚山梨醇酯60、二甲聚硅氧烷/PEG-10/15交联聚合物、聚甘油-6失水山梨醇异硬脂酸酯、芝麻油、PEG-10二甲聚硅氧烷、PEG/PPG-18/4共聚物、十六烷基PEG/PPG-101-二甲聚硅氧烷、PEG-8、硬脂酸辛酯、双甘油磷酸酯二钠、石蜡、EDTA三钠、PEG-10二甲聚硅氧烷/乳化剂、葡聚糖、NaPCA、叶酸、乙二醇硬脂酸酯、木糖醇、异十六烷、泛醇、椰油酰胺DEA和MEA和氯氧化铋。
在本发明的实施方案中、除UVR过滤剂和黑素生成抑制剂外、本发明的组合物还可包含一种或多种选自下组的化合物、按浓度计分别包括:约0.1%-7%的甘油、约0.05%-7%的泛醇、约0.25%-5%的丙烯酸酯/丙烯酸C 10-30烷基酯交联聚合物、约0.25%-5%的辛酸/癸酸甘油三酯、约0.25%-5%的卡波姆、约0.25%-5%的聚二甲基硅氧烷、约0.25%至5%的二甲基癸酰胺、约0.25%至5%的EDTA二钠、约0.25%至5%的乙基己基甲氧基丙烯酸、约0.25%-5%的棕榈酸乙基己酯、约0.25%-5%的乙基己基甘油、约0.25%-5%的苯氧乙醇、约0.25%-5%的脱水山梨糖醇倍半油酸、约0.25%-5%的硬脂酸、约0.25%-5%的硬脂醇和约0.25%-5%的三乙醇胺。
定义
除非上下文明确要求、否则在整个说明书和权利要求书中、词语“包括”、“包含”等应以包含性的意义解释、而不是排他性或穷举性的意义;也就是说、在“包括但不限于”的意义上。
在本说明书的上下文中、术语“约”将被理解为表示熟练的收件人将与给定值相关联的通常容差。
在本说明书的上下文中、其中陈述了参数的范围、应当理解、该参数包括所述范围内的所有值、包括该范围的所述端点。
在整个说明书中、除非另外特别说明或上下文另有要求、否则提及单一步骤、物质组成、步骤组或物质组合物组应包括一个和多个(即一个或多个)那些步骤、物质组合物、步骤组或物质组合物组。
本领域技术人员将理解、除了具体描述的那些之外、本文描述的发明易于进行变化和修改。应理解、本发明包括所有这些变化和修改。本发明还包括本说明书中单独或共同提及或指出的所有步骤、特征、组合物和化合物、以及任何和所有组合或所述步骤或特征中的任何两个或更多个。
该发明的详细说明
尽管已经参考本文详述的某些实施例描述了本发明、但是其他实施例可以实现相同或相似的结果。对于本领域技术人员来说、本发明的变化和修改是显而易见的、并且本发明旨在覆盖所有这些修改和等同物。
通过以下非限制性实施例进一步描述本发明。
本发明的组合物
根据以下方法制备本发明组合物的实例。
1.)通过将1-甲基乙内酰脲-2-酰亚胺、乙基己基甲氧基丙烯酸乙酯、棕榈酸乙基己酯、丙烯酸酯/丙烯酸C 10-30烷基酯交联聚合物、三乙醇胺、脱水山梨糖醇倍半油酸酯、阿伏苯宗、甲基水杨醇、水杨酸辛酯和奥克立林混合在一起、在分散到油相中之前干燥混合成薄片状或粉末状成分。
2.)在单独的容器中、通过将二甲基神经酰胺、辛酸/癸酸甘油三酯、二甲聚硅氧烷、EDTA二钠、卡波姆、苯乙基间苯二酚、烟酰胺、甘油、泛醇、、苯氧基乙醇和乙基己基甘油混合在一起而分散到水相中。
3.)将油相和水相混合在一起、并向混合物中加入硬脂醇和硬脂酸、然后缓慢加热至47至82℃之间、同时继续混合直至产物均匀。
4.)使最终产品冷却至室温并密封在容器中。初步研究
进行初步研究以测试使用本发明的防晒组合物的三种可能的UV过滤剂组合的能力、以有效地过滤有害的UVR并防止阳光损害。该研究使用美国食品和药物管理局(FDA21CFR第201和310部分)规定的方案进行、以确定SPF值、并由美国加利福尼亚州托兰斯的Bioscreen测试服务公司进行。
本研究中包含的组合物:
样品A(SPF15):3%(w/w)阿伏苯宗、4.9%(w/w)甲基水杨醇、2.3%(w/w)水杨酸辛酯和2.7%(w/w)奥克立林。
样品B(SPF30):3%(w/w)阿伏苯宗、4.9%(w/w)甲基水杨醇、3.7%(w/w)水杨酸辛酯和2.7%(w/w)奥克立林。
样品C(SPF50):3%(w/w)阿伏苯宗、6%(w/w)甲基水杨醇、4%(w/w)水杨酸辛酯和7%(w/w)奥克立林。
样品D(对照;SPF30):8%(w/w)甲氧肉桂酸辛酯、3.5%(w/w)4-甲基苄叉樟脑、2%(w/w)阿伏苯宗和2%(w/w)奥克立林。
样品E(对照;SPF30):25%(w/w)锌氧化物25%、6%(w/w)甲氧肉桂酸辛酯和1%(w/w)4-甲基苄叉樟脑。
样品F(对照;SPF50):9%(w/w)奥克立林、5.7%(w/w)二氧化钛、5%(w/w)氧苯酮、4.5%(w/w)阿伏苯宗、4.5%(w/w)水杨酸辛酯、4.5%(w/w)甲基水杨醇和1.5%(w/w)苯并三嗪醇。样品G(对照;SPF50):8%(w/w)奥克立林、3%(w/w)辛基三嗪酮、4%(w/w)丁基甲氧基二苯甲酰甲烷和8%(w/w)甲基水杨醇。
将组合物A、B或C均匀地涂在10名成人受试者的背部、剂量为2mg/cm2并允许干燥15-30分钟。然后将受试者暴露于氙弧模拟器的1个最小红斑剂量(MED)。受试者在暴露后16至24小时返回场所、此时技术人员在视觉上对暴露部位进行红斑评分。每种组合物都可预防红斑。
组合物A至G也涂在透明的二氧化硅板上、灯发出的UVB光透过组合物、检测通过板的光的百分比并在另一端记录。通过上述每个板透射的波长为295nm的UVB光的百分比为:样品A 23.1%、样品B 15.8%、样品C 13.8%、样品D 0.8%、样品E 0.2%、样品F 0.3%和样品G 1.0%。
初步研究还检验了与常规防晒剂(组合物D、E、F和G)相比、组合物A、B和C允许维生素D产生的能力。这项维生素D生产研究是在澳大利亚悉尼的Dermatest、Pty Ltd的实验室进行的原始体外实验。
维生素D的摄入量通常以国际单位(III)来衡量。中午阳光的一个最小红斑剂量(MED)直接照射到具有健康的I型或II型皮肤的中年人的大部分身体上(即、高加索人)将产生10,000至20,000IU的维生素D。根据这项研究的结果、可以计算出接受相同MED的同一中年高加索人在穿着测试组合物时会产生以下量的维生素D:样品A介于2310和4620IU之间、样品B介于1580和3160IU之间、样品C介于1380和2760IU之间、样品D介于80和160IU之间、样品E介于20和40IU之间、样品G介于90和180IU之间。
研究1
迈克尔F.Holick博士(医学博士)在波士顿大学医学中心的医学系维生素D皮肤和骨骼研究实验室进行了一项题为“用于维生素D生产的皮肤美白产品的比较性能”的研究。本研究使用SPF 30的本发明的防晒组合物、其目的是确定该组合物是否允许在实验条件下有效地合成普利霉素D。
材料和方法:使用具有高紫外线输出的荧光灯照射含有维生素D前体7-脱氢胆固醇(7-DHC)的硼硅酸盐安瓿、其中聚乙烯(Saran)包裹层下面含有2mg/cm2的下列组合物:
配方1000:3%(w/w)阿伏苯宗、4.9%(w/w)甲基水杨醇、2.3%(w/w)水杨酸辛酯、2.7%(w/w)奥克立林、1.5%(w/w)1-甲基乙内酰脲-2-酰亚胺、1%(w/w)苯乙基间苯二酚、3%(w/w)烟酰胺、3.5%(w/w)甘油、0.5%(w/w)泛醇、水、二甲基癸酰胺、乙基己基甲氧基丙烯、棕榈酸乙基己酯、辛酸/癸酸甘油三酯、硬脂醇、硬脂酸、聚二甲基硅氧烷、EDTA二钠、丙烯酸酯/丙烯酸C 10-30烷基酯交联聚合物、苯氧乙醇、卡波姆、三乙醇胺、脱水山梨糖醇倍半油酸酯和乙基己基甘油。
配方2000:3%(w/w)阿伏苯宗、4.9%(w/w)甲基水杨醇、2.3%(w/w)水杨酸辛酯、2.7%(w/w)奥克立林、1.5%(w/w)1-甲基乙内酰脲-2-酰亚胺、1%(w/w)苯乙基间苯二酚、3%(w/w)烟酰胺、1.75%(w/w)甘油、0.25%(w/w)泛醇、水、二甲基癸酰胺、乙基己基甲氧基丙烯、棕榈酸乙基己酯、辛酸/癸酸甘油三酯、硬脂醇、硬脂酸、聚二甲基硅氧烷、EDTA二钠、丙烯酸酯/丙烯酸C 10-30烷基酯交联聚合物、苯氧基乙醇、卡波姆、三乙醇胺、脱水山梨糖醇倍半油酸酯和乙基己基甘油;或
配方3000:3%(w/w)阿伏苯宗、4.9%(w/w)甲基水杨醇、2.3%(w/w)水杨酸辛酯、2.7%(w/w)奥克立林、1.5%(w/w)1-甲基乙内酰脲-2-酰亚胺、1%(w/w)苯乙基间苯二酚、3%(w/w)烟酰胺、7%(w/w)甘油、1%(w/w)泛醇、水、二甲基癸酰胺、乙基己基甲氧基丙烯、棕榈酸乙基己酯、辛酸/癸酸甘油三酯、硬脂醇、硬脂酸、聚二甲基硅氧烷、EDTA二钠、丙烯酸酯/丙烯酸C 10-30烷基酯交联聚合物、苯氧乙醇、卡波姆、三乙醇胺、脱水山梨糖醇倍半油酸酯和乙基己基甘油。
在15分钟的时间间隔进行45分钟的时间暴露。用高效液相色谱(HPLC)分析安瓿含量。取两份样品并取平均值。结果显示通过聚合物膜暴露于UVB辐射的安瓿含量的代表性色谱图、其中任一种配方局部施用、其中可以从相关色谱图的曲线下面积计算前维生素D3的产生。在使用配方2000(1.24、2.58和3.39)和配方1000(1.24、2.34和3.17)和配方3000(1.21、2.3和2.59)后、并暴露于UVB 15分钟、30分钟和45分钟后、转化为前维生素D3的曲线面积较大。
研究2
利用本发明的防晒组合物、即:根据上述1000、2000和3000配方以及以下对照品、我们进行了进一步研究、其名称为:“五种局部配方的美白、去斑、去皱效果:健康成年男士、女士的盲法、安慰剂对照临床试验”。
配方4000(仅为黑素生成抑制剂):1.5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、1%(w/w)的苯乙基间苯二酚、3%(w/w)的烟酰胺、水、二甲基癸酰胺、乙基己基甲氧基丙烯酸酯、乙基己基棕榈酸酯、辛酸/癸酸甘油三酯、硬脂醇、硬脂酸、聚二甲基硅氧烷、EDTA二钠、丙烯酸酯/C IQ-30烷基丙烯酸酯交联聚合物、苯氧乙醇、卡波姆、三乙醇胺、脱水山梨糖醇倍半油酸酯和乙基己基甘油。
配方5000(无活性成分):3.5%(w/w)的甘油、0.5%(w/w)的泛醇、水、二甲基癸酰胺、乙基己基甲氧基丙烯酸、乙基己基棕榈酸酯、辛酸/癸酸甘油三酯、硬脂醇、硬脂酸、聚二甲基硅氧烷、EDTA二钠、丙烯酸酯/C 10-30丙烯酸烷基酯交联聚合物、苯氧基乙醇、卡波姆、三乙醇胺、脱水山梨糖醇倍半油酸酯和乙基己基甘油。
对象及方法:年龄在18-79岁之间、皮肤类型为I-V的健康男性和女性。受试者于在五种组合物中随机选择一种、于每天早晚将0.8g组合物涂于后背(活性手)、而另一只手则什么也不涂(对照手)、持续12周。皮肤变化记录如下:“美白”包括:亮肤、肤色“黑斑”包括:老年斑、太阳斑和褐黄斑;“皱纹”包括细纹、皱纹数量和皱纹大小。通过主观评分、受试者用纸或电子日志形式记录下12周内的皮肤表面变化、评分为-3分(肤色较深、斑点较深或皱纹较多)至+3分(皮肤较亮、斑点较浅、皱纹较少)。
结果:将12周中每一周的“美白”、“黑斑”分数进行求和和平均。配方1000中、n=3;配方2000中、n=2;配方3000中、n=2;配方4000中、n=4;配方5000中、n=3。通过组内方差分析查看以下结果、组内方差分析比较了每个配方中活性手和对照手在不同时期的差异。也可用组间方差分析查看结果、组间方差分析比较了配方5000和配方4000及其它三个活性配方组在不同时期的差异。
配方1000组的每周美白均值:
活性手:第1周(Wk1)0、Wk2 0、Wk3 0.66、Wk4 0.66、Wk5 0.66、Wk6 0.66、Wk7 1、Wk80.66、Wk9 1.33、Wk10 1.66、Wk11 1.5和Wk12 1.5
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方2000组的每周美白均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0.5、Wk10 0.5、Wk11 1和Wk12 1
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方3000组的每周美白均值:
活性手:Wk1 0、Wk2 0、Wk3 0,Wk4 0.5、Wk5 1、Wk6 0.5、Wk7 0.5、Wk8 0.5、Wk9 0.5、Wk10 2、Wk11 2和Wk12 2
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方4000组的每周美白均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0.25、Wk8 0、Wk9 0.33、Wk100、Wk11-0.33和Wk12-0.33
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7-.025、Wk8 0、Wk9 0、Wk10 0、Wk11-0.33和Wk12-0.33
配方5000组的每周美白均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方1000组的每周黑斑均值:
活动手:第1周(Wk1)0、Wk2 0、Wk3 0.5、Wk4 1、Wk5 1、Wk6 0.66、Wk7 1、Wk8 1、Wk91.33、Wk10 1.66、Wk11 1.5和Wk12 1.5
对照手:第1周(Wk1)0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk100、Wk11 0和Wk12 0
配方2000组的每周黑斑均值:
活动手:Wk1 0、Wk2 0、Wk3 0.5、Wk4 0,Wk5 0.5、Wk6 0、Wk7 0、Wk8 0.5、Wk9 0.5、Wk101、Wk11 1和Wk12 1
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方3000组的每周黑斑均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0.5、Wk5 0.5、Wk6 0.5、Wk7 0.5、Wk8 0.5、Wk9 0.5、Wk10 2、Wk11 2和Wk12 2
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方4000组的每周黑斑均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0.25、Wk8 0、Wk9 0.33、Wk10-0.33、Wk11-0.33和Wk12-0.33
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8-0.25、Wk9 0、Wk10 0、Wk11-0.33和Wk12-0.33
配方5000组的每周黑斑均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方1000组的每周皱纹均值:
活性手:第1周(Wk1)0、Wk2 0.33、Wk3 0.66、Wk4 0.66、Wk5 0.66、Wk6 0.66、Wk7 0.33、Wk8 0.66、Wk9 0.66、Wk10 0.66、Wk11 0.33和Wk12 0.33
对照手:第1周(Wk1)0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk100、Wk11 0和Wk12 0
配方2000组的每周皱纹均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方3000组的每周皱纹均值:
活性手:Wk1 0.5、Wk2 0.5、Wk3 0.5、Wk4 1、Wk5 1、Wk6 1、Wk7 0.5、Wk8 0.5、Wk9 0.5、Wk10 2、Wk11 2和Wk12 2
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
配方4000组的每周平均皱纹值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0.25、Wk8 0、Wk9 0.33、Wk10-0.33、Wk11-0.33和Wk12-0.33
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0.25、Wk8 0、Wk9 0.33、Wk100.33、Wk11 0和Wk12 0
配方5000组的每周皱纹均值:
活性手:Wk1 0、Wk2 0、Wk3 0、Wk4 0.33、Wk5 0、Wk6 0.33、Wk7 0.33、Wk8 0.33、Wk90.33、Wk10 0.33、Wk11 0.33和Wk12 0.33
对照手:Wk1 0、Wk2 0、Wk3 0、Wk4 0、Wk5 0、Wk6 0、Wk7 0、Wk8 0、Wk9 0、Wk10 0、Wk110和Wk12 0
综上所述、受试者日志表明、活性手(配方1000、2000和3000)在3-4周内其美白、黑斑均值有所改善、至第12周、这些改善更为明显、但对照组则基本无变化。未报道有不良事件研究3
澳大利亚悉尼Pty LTD的皮肤咨询部受委托进行了一项研究、名为“产维生素D波长通过护肤乳液的渗透率”。研究测量了不同波长的UVR穿过十种局部配方的数量。
本研究组合物为配方1000(SPF15)、配方2000(SPF 15)和配方4000(如研究1所述)、SPF如下的五种市售美白产品为:
i.SPF15的Gamier活性BB再生霜(奥昔康酯4%、二氧化钛2.1%、抗坏血酸葡萄糖苷)
ii.SPF30的Peter Thomas Roth CC修护霜(二氧化钛10.26%、氧化锌5.76%、对苯二酚-α-D-吡喃葡萄糖苷和疑拟香桃木)。
iii.SPF30的Diorsnow亮肤霜(氧化锌18.7%、奥西诺酯7.49%、二氧化钛2.13%、羟苯甲酮2%、抗坏血酸葡萄糖苷)。
iv.SPF30的Neutrogena大豆精华去斑霜(阿伏苯宗3%、胡萝卜素12%、水杨酸辛酯5%、奥克立林1.7%、羟苯甲酮3%、甘氨酸大豆种子提取物、云母)。
v.SPF30的La Roche-Posay CC肌肤修护日霜(奥西诺酯3%、水杨酸辛酯3.5%、奥克立林4.5%、二氧化钛6.2%、云母)。
可生成维生素D但无增白剂的防晒对照品包括:
vi.SPF15的Solar D防晒霜(配方DP100-181B阿伏苯宗3%、甲基水杨醇4.9%、水杨酸辛酯2.3%、奥克立林2.7%)。
将1.3mg/cm2本研究组合物精确、均匀涂于透明基板(模压PMMA 6um Helioscreen基板)的粗糙面上。每个产品均准备四种不同浓度的样本进行研究。让紫外光穿过涂了本品的基板、在另一端用仪器(配有积分球装置的Shimadzu UV-2450分光光度计)测量紫外光穿透样本的百分比。每种研究产品均测量16次。测定每种290-400nm波长的平均渗透率。
结果:配方1000、2000中、波长为290nm-298nm的UVR的渗透率分别约为23%和21.5%。配方4000(无SPF)提供安全的防晒防护、波长为290nm-298nm的UVR的渗透率为64.9%。
五种商业比较产品均无法使渗透的、产维生素D的波长在数量上具有生物显著意义。配方(i)中、波长为290nm-298nm的UVR渗透率仅为1.8%。配方(ii)中、波长为290nm-298nm的UVR渗透率仅为1%。配方(iii)中、波长为290nm-298nm的UVR渗透率仅为1%。配方(iv)中、波长为290nm-298nm的UVR渗透率仅为5.3%。配方(v)中、波长为290nm-298nm的UVR渗透率仅为3.5%。
配方(vi)中、波长为290nm-298nm的UVR渗透率约为23.5%。配方1000、2000和(v)的结果几乎没有差别、这表明、配方1000、2000中的黑素生成抑制剂和其它非活性成分未显著抑制产维生素D的波长通过。
Claims (30)
1.一种局部防晒组合物,可防止UVR导致的皮肤损伤、并适合于波长为290nm-298nm的UVB充分渗透产生维生素D、同时还可抑制黑素生成。
2.权利要求1中任一项所述的局部防晒组合物、该组合物允许至少5%的、波长范围为290nm-298nm的UVB光穿过。
3.权利要求1中任一项所述的局部防晒组合物、该组合物至少允许10%的、波长范围为290nm-298nm的UVB光穿过。
4.权利要求1中任一项所述的局部防晒组合物、该组合物至少允许15%的、波长范围为290nm-298nm的UVB光穿过。
5.权利要求1-5中任一项所述的局部防晒组合物、其中该组合物包括一种或多种选自以下成分的UVR过滤剂:邻氨基苯甲酸薄荷酯、磺异苯酮、磺异苯酮钠、二乙氨基羟基苯甲酰基己基苯甲酸酯、羟苯甲酮、阿莰舒、奥克立林、丁基甲氧基二苯甲酰甲烷、聚硅氧烷-15、苯基二苯并咪唑四磺酸二钠、PEG-25PABA、甲基水杨醇和水杨酸辛酯。
6.权利要求1-5中任一项所述的局部防晒组合物、其中该组合物包括两种或多种选自以下成分的UVR过滤剂:邻氨基苯甲酸薄荷酯、磺异苯酮、磺异苯酮钠、二乙氨基羟基苯甲酰基己基苯甲酸酯、羟苯甲酮、阿莰舒、奥克立林、丁基甲氧基二苯甲酰甲烷、聚硅氧烷-15、苯基二苯并咪唑四磺酸二钠、PEG-25PABA、甲基水杨醇和水杨酸辛酯。
7.权利要求1-5中任一项所述的局部防晒组合物、其中该组合物包括三种或多种选自以下成分的UVR过滤剂:邻氨基苯甲酸薄荷酯、磺异苯酮、磺异苯酮钠、二乙氨基羟基苯甲酰基己基苯甲酸酯、羟苯甲酮、阿莰舒、奥克立林、丁基甲氧基二苯甲酰甲烷、聚硅氧烷-15、苯基二苯并咪唑四磺酸二钠、PEG-25PABA、甲基水杨醇和水杨酸辛酯。
8.权利要求1-7中任一项所述的局部防晒组合物、其中该组合物包括至少两种或多种选自以下成分的UVR过滤剂:羟苯甲酮、阿莰舒、奥克立林、丁基甲氧基二苯甲酰甲烷、甲基水杨醇和水杨酸辛酯、其中、本发明组合物按浓度计包括:约0.5%-8%(w/w)的羟苯甲酮、约0.5%-10%(w/w)阿莰舒、约0.5%-10%(w/w)的奥克立林、约0.5%-7%(w/w)丁基甲氧基二苯甲酰甲烷、约0.5%-15%(w/w)的甲基水杨醇和约0.5%-10%(w/w)的水杨酸辛酯。
9.权利要求1-8中任一项所述的局部防晒组合物、其中该组合物包括至少三种或多种选自以下成分的UVR过滤剂:羟苯甲酮、阿莰舒、奥克立林、丁基甲氧基二苯甲酰甲烷、甲基水杨醇和水杨酸辛酯、其中、本发明组合物按浓度计包括:约0.5%-8%(w/w)的羟苯甲酮、约0.5%-10%(w/w)阿莰舒、0.5%-10%(w/w)的奥克立林、约0.5%-7%(w/w)丁基甲氧基二苯甲酰甲烷、0.5%-15%(w/w)的甲基水杨醇和约0.5%-10%(w/w)的水杨酸辛酯。
10.权利要求1-8中任一项所述的局部防晒组合物、其中该组合物包括至少三种或多种选自以下成分的UVR过滤剂:羟苯甲酮、阿莰舒、奥克立林、丁基甲氧基二苯甲酰甲烷、甲基水杨醇和水杨酸辛酯、其中、本发明组合物按浓度计包括:约1%-4%(w/w)的羟苯甲酮、约1%-9%(w/w)阿莰舒、约1%-7%(w/w)的奥克立林、约1%-5%(w/w)丁基甲氧基二苯甲酰甲烷、约0.5%-6%(w/w)的甲基水杨醇和约0.5%-6%(w/w)的水杨酸辛酯。
11.权利要求1-10中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.5%-6%(w/w)的水杨酸辛酯。
12.权利要求1-11中任一项所述的局部防晒组合物、其中该组合物包括浓度为1%-4%(w/w)的羟苯甲酮。
13.权利要求1-12中任一项所述的局部防晒组合物、其中该组合物包括浓度为1%-5%(w/w)的丁基甲氧基二苯甲酰甲烷。
14.权利要求1-13中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.5%-6%(w/w)的甲基水杨醇。
15.权利要求1-14中任一项所述的局部防晒组合物、其中该组合物包括浓度为1%-9%(w/w)的阿莰舒。
16.权利要求1-15中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.5%-7%(w/w)的奥克立林。
17.如权利要求1-16中任一项所述的局部防晒组合物、其中该组合物包括一种可抑制皮肤黑素生成的化合物。
18.如权利要求1-17中任一项所述的局部防晒组合物、其中该组合物包括一种可通过抑制酪氨酸酶活性来抑制皮肤黑素生成的化合物。
19.如权利要求1-17中任一项所述的局部防晒组合物、其中该组合物包括一种可通过抑制黑素体转移来抑制皮肤黑素生成的化合物。
20.如权利要求1-19中任一项所述的局部防晒组合物、其中该组合物包括一种可抑制黑素生成、且选自以下成分的化合物:L-抗坏血酸-2-磷酸镁、来自甘草根和乌拉甘草的、含光甘草定的甘草提取物、N-十一碳烯酰基苯丙氨酸、1-甲基乙内酰脲-2-酰亚胺、苯乙基间苯二酚、反式-4-氨基甲基环己烷羧酸、乳酸、甘氨酸锌、葡萄糖酸、二硫代辛二醇、葡糖胺、N-乙酰基-D-葡糖胺、寡肽-34、曲酸、4-羟基苯基-α-D-吡喃葡萄糖苷、红藻萃取液、乙醇酸、烟酰胺及其衍生物、羟基均二苯乙烯及其衍生物、芦荟素、羟基醌及其衍生物、烟酰胺、掌叶树萃取液、类黄酮衍生物如5,7,3-三羟基-3,6,4-三甲氧基黄酮和抑制PAR-2通路的大豆提取物。
21.如权利要求1-20中任一项所述的局部防晒组合物、其中该组合物包括至少一种可抑制黑素生成、且选自以下成分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁;其中、本组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
22.如权利要求1-21中任一项所述的局部防晒组合物、其中该组合物包括至少两种可抑制黑素生成、且选自以下成分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁;其中、本组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
23.如权利要求1-22中任一项所述的局部防晒组合物、其中该组合物包括至少三种可抑制黑素生成、且选自以下成分的化合物:1-甲基乙内酰脲-2-酰亚胺、烟酰胺、苯乙基间苯二酚、N-十一碳烯酰基苯丙氨酸、N-乙酰基-D-葡糖胺和L-抗坏血酸-2-磷酸镁;其中、本组合物按浓度计包括:约0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺、约0.5%-10%(w/w)的烟酰胺、约0.05%-7%(w/w)的苯乙基间苯二酚、约0.1%-10%(w/w)的N-十一碳烯酰基苯丙氨酸、约0.5%-6%(w/w)的N-乙酰基-D-葡糖胺和约0.1%-12%(w/w)的L-抗坏血酸-2-磷酸镁。
24.如权利要求17-23中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.05%-7%(w/w)的苯乙基间苯二酚。
25.如权利要求17-24中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.05%-5%(w/w)的1-甲基乙内酰脲-2-酰亚胺。
26.如权利要求17-25中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.5%-10%(w/w)的烟酰胺。
27.如权利要求1-26中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.25%-10%(w/w)的甘油。
28.如权利要求1-27中任一项所述的局部防晒组合物、其中该组合物包括浓度为0.25%-10%(w/w)的泛醇。
29.如权利要求1-28中任一项所述的局部防晒组合物、其中该组合物用于皮肤时可减少或抑制功能性着色及色素过度沉着。
30.如权利要求1-28中任一项所述的局部防晒组合物、其中该组合物用于皮肤时可减少或抑制诱发红斑。
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