CN104302271A - 包含氨基肽混合物的保湿组合物 - Google Patents
包含氨基肽混合物的保湿组合物 Download PDFInfo
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- CN104302271A CN104302271A CN201280061206.4A CN201280061206A CN104302271A CN 104302271 A CN104302271 A CN 104302271A CN 201280061206 A CN201280061206 A CN 201280061206A CN 104302271 A CN104302271 A CN 104302271A
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- skin care
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- care compositions
- skin
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Abstract
本发明涉及包含氨基肽混合物的皮肤保湿组合物，该氨基肽混合物包含水溶性氨基酸或官能化氨基酸；具有150至410的分子量的水溶性二肽；具有225至600的分子量的水溶性三肽或包含肽键的水溶性维生素或两者；和化妆品可接受的载体。该组合物补充皮肤天然保湿因子并提供优异的感官益处。该组合物在施加过程中和在施加后不会令人不快地粘稠。
Description
发明领域
本发明涉及包含氨基肽混合物的保湿组合物。本发明更特别涉及补充皮肤的天然保湿因子（natural moisturization factor）、同时令人惊讶地提供优异的感官益处的保湿组合物。本发明的组合物不粘稠或粘滞（draggy），具有适合渗透角质层的各种区段的组分并且不会在施加过程中和在施加后令人不快地变粘。
发明背景
皮肤的天然保湿因子(NMF)含有“负责”保持皮肤健康和确保表皮结构完好以使皮肤保湿的组分。NMF存在于角质层（表皮的最外层）顶层中的角质细胞（corneocyte）内。NMF是丝聚蛋白（filaggrin）的蛋白水解产物，其有助于构成角质细胞的角蛋白中间丝的自组装。角质层上层中的NMF的耗损（通常与皮肤清洗相关联）会引发皮肤干燥状况，尤其是在冬季。在另一些情况中，当产生丝聚蛋白的基因突变时，人皮肤中的NMF水平显著降低，造成严重的皮肤干燥和甚至皮肤病，如特应性皮炎和寻常型鱼鳞癣。
无论与NMF减少相关的成因如何，设计成模拟NMF的组合物的局部施加是困难的，因为此类组合物在施加时粘稠并且不适合消费者使用。实际上，此类已知组合物造成令人不快的粘性层，其为需要皮肤保湿的消费者提供极少的感官益处。
鉴于上述情况，越来越有兴趣开发输送以模拟身体NMF的方式润湿皮肤的组分的组合物。此外，希望开发此类组合物以使其不含高粘度和令人不快的粘着特性，尤其是在施加过程中和在施加后。本发明因此涉及包含氨基肽混合物的保湿组合物。该组合物模拟和补充皮肤的NMF，同时令人惊讶地提供优异的感官益处。本发明的组合物不粘稠或粘滞，具有适合渗透角质层的各种区段的组分并且不会在施加过程中和在施加后令人不快地变粘（即粘着）。
附加信息
已经公开了制造局部护肤组合物的努力。在DE 4127790A中，描述了具有寡肽和金属络合物的护肤化妆品。
已经公开了制造局部组合物的另一些努力。在美国专利No. 7,659,233中，描述了具有有机硅和二羟基丙基三烷基铵盐的个人护理组合物。
上述附加信息无一描述了如本发明中所述的含有氨基肽混合物的组合物。
已经公开了制造局部组合物的另一些努力。在美国专利申请No. 2004/0247631中，描述了用于皮肤保湿的组合物。
发明概述
第一方面，本发明涉及用于皮肤保湿的组合物，所述组合物包含：
a) 氨基肽混合物，其包含：
i. 水溶性氨基酸或官能化氨基酸；
ii. 具有150至410的分子量的水溶性二肽；
iii. 具有225至600的分子量的水溶性三肽、包含肽键的水溶性维生素或维生素衍生物或两者；和
b) 化妆品可接受的载体
其中氨基酸和水溶性二肽一起构成氨基肽混合物总重量的50至99重量%。
第二方面，本发明涉及通过施加模拟皮肤NMF的组分而润湿皮肤的方法，所述方法包括使皮肤与本发明的第一方面的组合物接触的步骤。
本文所用的“皮肤”意在包括面部、颈部、胸、背、手臂（包括腋下）、手、腿、臀部和头皮上的皮肤。本文所用的“水溶性”是指至少0.5克材料溶解在100毫升25℃水中。本文所用的“包含”意在包括“基本由…构成”和“由…构成”。为避免疑问，本发明的氨基肽混合物可以基本由氨基酸、二肽和三肽构成或由氨基酸、二肽和三肽构成。如果例如没有明确提到，本文中指定的所有范围意在包括归入其中的所有范围。
优选实施方案详述
对可用于本发明的氨基酸或官能化氨基酸的仅有限制在于，其可用在局部组合物中并且是水溶性的。通常，氨基酸具有-4.5至0；优选-4.5至-1；最优选-4.5至-2的在正辛醇-水中的分配系数（规定为log kp）（如Journal
of Chromatography, 216 (198 I) 79-92 Elsevier Scientific Publishing
Company, Amsterdam - Printed in The Netherlands CHROM. 14,027中所述）。
其优选具有70至225的分子量。适用于本发明的氨基酸或官能化氨基酸的示例性但非限制性实例包括谷氨酰胺、天冬酰胺、甘氨酸、谷氨酸、苏氨酸、赖氨酸、丙氨酸、丝氨酸、羟基脯氨酸、N-乙酰基-L-酪氨酸、N-乙酰基-L-羟基脯氨酸、N-乙酰基-L-半胱氨酸、L-鸟氨酸（ornitine）一氯化物或其混合物。
关于适用的水溶性二肽，优选包括甘氨酰-L-谷氨酸盐、甘氨酰-L-酪氨酸、L-丙氨酰-L-谷氨酰胺、甘氨酰甘氨酸、赖氨酰赖氨酸、甘氨酰丙氨酸、甘氨酰赖氨酸、甘氨酰组氨酸或其混合物。
水溶性并适用于本发明的三肽包括L-谷胱甘肽、γ-L-谷氨酰-L-半胱氨酰-甘氨酸)、S-甲基谷胱甘肽、甘氨酰-脯氨酰-谷氨酸、赖氨酰-酪氨酰-赖氨酸、赖氨酰-酪氨酰-赖氨酸、甘氨酰-甘氨酰-组氨酸、赖氨酰-赖氨酰-赖氨酸或其混合物。可用于本发明的包含肽键的水溶性维生素包括例如D-L-泛醇。适用的水溶性维生素衍生物的实例包括泛酰巯基乙胺-S-磺酸钙。
在一个优选实施方案中，氨基酸和二肽在该氨基肽混合物中的总重量为50至80%，最优选地，氨基酸和二肽占该氨基肽混合物中氨基酸、二肽和三肽的总重量的60至75重量%。
最好地，氨基酸构成该氨基肽混合物中氨基酸、二肽和三肽的总重量的5至50重量%；最任选，10至30重量%。
通常，氨基肽混合物构成该组合物总重量的0.5至35重量%，优选2至20重量%，最优选6至12重量%。
在一个尤其优选的实施方案中，本发明中所用的氨基肽混合物具有-75至15℃，最优选-48至12℃，任选-40至5℃的玻璃化转变温度，包括归入其中的所有范围。在最佳实施方案中，当氨基肽混合物的水浓度为9至16%时，氨基肽混合物的玻璃化转变温度为-17至2℃。
本发明的组合物通常包括化妆品可接受的载体组分。水是最优选的附加载体。水的量可以为该组合物总重量的1至99重量%，优选5至90重量%，最优选35至80重量%，最好40至75重量%，包括归入其中的所有范围。本发明的组合物通常是水和油乳状液，最优选是水包油种类。但油包水乳状液，尤其是通常被归类为油包水和高内相乳状液的那些也是一个选择。在共有美国专利申请公开Nos.
2008/0311058和2009/0247445中描述了适用于携带本发明的珠粒的高内相乳状液的示例性实例，它们的公开内容经此引用并入本文。
适用于本发明的其它化妆品可接受的载体可包括矿物油、有机硅油、合成或天然酯和醇。这些材料的量可以为该组合物的0.1至50重量%，优选0.1至30重量%，最优选1至20重量%，包括归入其中的所有范围。
有机硅油可分成挥发性和非挥发性种类。本文所用的术语“挥发性”是指在环境温度下具有可测得的蒸气压的那些材料。挥发性有机硅油优选选自含有3至9，优选4至5个硅原子的环状或线性聚二甲基硅氧烷。
线性挥发性有机硅材料通常具有在25℃下小于5厘沲的粘度，而环状材料通常具有小于10厘沲的粘度。
可用作载体材料的非挥发性有机硅油包括聚烷基硅氧烷、聚烷基芳基硅氧烷和聚醚硅氧烷共聚物。此处可用的基本非挥发性聚烷基硅氧烷包括例如在25℃下的粘度为5至100,000厘沲的聚二甲基硅氧烷（如二甲硅油）。
通常优选的有机硅源是环五硅氧烷和聚二甲基硅氧烷醇溶液。
合适的酯包括：
(1) 具有10至20个碳原子的脂肪酸的烯基或烷基酯，如棕榈酸异丙酯、异硬脂酸异丙酯、异壬酸异壬酯、肉豆蔻酸油基酯、肉豆蔻酸异丙酯、硬脂酸油基酯和油酸油基酯；
(2) 醚酯，如乙氧基化脂肪醇的脂肪酸酯；
(3) 多元醇酯，如乙二醇单-和二-脂肪酸酯、二乙二醇单-和二-脂肪酸酯、聚乙二醇(200-6000)单-和二-脂肪酸酯、丙二醇单-和二-脂肪酸酯、聚丙二醇2000单油酸酯、聚丙二醇2000单硬脂酸酯、乙氧基化丙二醇单硬脂酸酯、单-和二-脂肪酸甘油酯、聚甘油聚脂肪酸酯、乙氧基化单硬脂酸甘油酯、1,3-丁二醇单硬脂酸酯、1,3-丁二醇二硬脂酸酯、聚氧乙烯多元醇脂肪酸酯、山梨糖醇酐脂肪酸酯和聚氧乙烯山梨糖醇酐脂肪酸酯；
(4) 蜡酯，如蜂蜡、鲸蜡、肉豆蔻醇肉豆蔻酸酯、醇硬脂酸硬脂基酯；和
(5) 甾醇酯，其中大豆甾醇酯和胆甾醇脂肪酸酯是其实例。
在本发明的皮肤保湿组合物中可存在乳化剂。乳化剂的总浓度可以为该组合物的0.1至40重量%，优选1至20重量%，最优选1至5重量%，包括归入其中的所有范围。该乳化剂可选自阴离子型、非离子型、阳离子型和两性活性剂。特别优选的非离子型活性剂是具有与每摩尔疏水物大约2至大约100摩尔环氧乙烷或环氧丙烷缩合的C10-C20脂肪醇或酸疏水物；与2至20摩尔环氧烷缩合的C2-C10烷基酚；乙二醇的单-和二-脂肪酸酯；脂肪酸甘油单酯；山梨糖醇酐单-和二-C8-C20-脂肪酸；和聚氧乙烯山梨糖醇酐及其组合的那些。烷基聚糖苷和糖脂肪酰胺（例如甲基葡糖酰胺）也是合适的非离子型乳化剂。
优选的阴离子型乳化剂包括烷基醚硫酸盐和磺酸盐、烷基硫酸盐和磺酸盐、烷基苯磺酸盐、烷基和二烷基磺基丁二酸盐、C8-C20酰基羟乙基磺酸盐、C8-C20烷基醚磷酸盐、烷基醚羧酸盐及其组合。
可用的阳离子型乳化剂包括例如棕榈酰氨基丙基三甲基氯化铵、二硬脂基二甲基氯化铵及其混合物。可用的两性乳化剂包括椰油酰氨基丙基甜菜碱、C12-C20三烷基甜菜碱、月桂酰两性基乙酸钠和月桂酰二两性基乙酸钠或其混合物。
可用于本发明的另一些乳化剂包括氨基酸衍生的两亲化合物，如二月桂酰氨基glytamide赖氨酸钠（也以商品名Pellicer™ L-30为人所知）、具有含8至14个碳原子的酰基的N-酰基精氨酸甲基酯盐酸盐和含有8至14个碳原子的精氨酸、组氨酸、赖氨酸、天冬氨酸或谷氨酸的N-烷基酰胺和酯衍生物。
其它通常优选的乳化剂包括硬脂酸甘油酯、乙二醇硬脂酸酯、硬脂酰胺AMP、PEG-100硬脂酸酯、鲸蜡醇以及乳化/增稠添加剂，如丙烯酸羟乙酯/丙烯酰二甲基牛磺酸钠共聚物/角鲨烷及其混合物。
防腐剂可合意地并入本发明的皮肤保湿组合物中以防止可能有害的微生物的生长。适用于本发明的组合物的传统防腐剂是对羟基苯甲酸的烷基酯。更最近开始使用的其它防腐剂包括乙内酰脲衍生物、丙酸盐和各种季铵化合物。化妆品化学家熟悉适当的防腐剂并照常选择它们以满足防腐剂挑战试验和提供产品稳定性。特别优选的防腐剂是碘代丙炔基丁基氨基甲酸酯（iodopropynyl butyl carbamate）、苯氧基乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、咪唑烷基脲、去氢乙酸钠和苄醇。应根据该组合物的用途和防腐剂与该乳状液中的其它成分之间的可能的不相容性选择防腐剂。防腐剂优选以该组合物的0.01重量%至2重量%的量使用，包括归入其中的所有范围。
在本发明的组合物中可任选包括增稠剂。特别可用的是多糖。实例包括淀粉、β-葡聚糖、天然/合成树胶和纤维素。淀粉的代表是化学改性淀粉，如羟丙基淀粉磷酸钠和辛烯基琥珀酸淀粉铝。木薯淀粉通常优选。合适的树胶包括黄原胶、菌核、果胶、刺梧桐树胶、阿拉伯树胶、琼脂、瓜尔胶、角叉菜胶、藻酸盐及其组合。合适的纤维素包括羟丙基纤维素、羟丙基甲基纤维素、乙基纤维素和羧甲基纤维素钠。合成聚合物是另一类有效增稠剂。这一类包括交联聚丙烯酸酯，如Carbomers，聚丙烯酰胺，如Sepigel® 305，和牛磺酸酯共聚物，如Simulgel
EG®和Aristoflex® AVC，所述共聚物通过各自的INCI命名法识别为丙烯酸钠/丙烯酰二甲基牛磺酸钠和丙烯酰二甲基牛磺酸盐/乙烯基吡咯烷酮共聚物。适用于增稠的另一优选合成聚合物是由Seppic商业供应并以Simulgel INS100为名出售的丙烯酸酯基聚合物。
当使用时，增稠剂的量可以为该组合物的0.001至5重量%，优选0.1至2重量%，最优选0.2至0.5重量%，包括归入其中的所有范围。
在本发明中可以使用传统保湿剂。这些通常是多元醇类型的材料。典型的多元醇包括甘油（即，glycerine或glycerin）、丙二醇、二丙二醇、聚丙二醇、聚乙二醇、山梨糖醇、羟丙基山梨糖醇、己二醇、1,3-丁二醇、异戊二醇、1,2,6-己三醇、乙氧基化甘油、丙氧基化甘油及其混合物。最优选的是甘油、丙二醇或其混合物。所用保湿剂的量可以为该组合物的0.5至20重量%，优选1至15重量%。
在本发明的组合物中可任选包括香料、着色剂、固定剂（fixatives）和磨料。这些物质各自可以为0.05至5重量%，优选0.1至3重量%。
关于适用于此的包含活性剂的其它组分，，其可包括乳浊剂，如TiO2和ZnO，和着色剂，如氧化铁红、氧化铁黄和氧化铁黑。此类乳浊剂和着色剂通常具有50至1200纳米，优选50至350纳米的粒度。
为了进一步增强皮肤保湿，在本发明的组合物中可任选使用被归类为阳离子铵化合物的活性剂。此类化合物包括单取代糖的羟丙基三(C1-C3烷基)铵盐（salts of hydroxypropyltri (C1-C3
alkyl) ammonium mono-substituted-saccharide）、单取代多元醇的羟丙基三(C1-C3烷基)铵盐（salts of hydroxypropyltri (C1-C3
alkyl) ammonium mono-substituted polyols）、二羟丙基三(C1-C3烷基)铵盐、二羟丙基二(C1-C3烷基)单(羟乙基)铵盐、瓜尔胶羟丙基三甲基铵盐、2,3-二羟丙基三(C1-C3烷基或羟基烷基)铵盐或其混合物。在最优选的实施方案中和在需要时，用于本发明的阳离子铵化合物是季铵化合物1,2-二羟丙基三甲基氯化铵（quaternary
ammonium compound 1,2-dihydroxypropyltrimonium chloride）。如果使用，此类化合物通常占该组合物的0.01至30重量%，优选0.1至15重量%。
当使用阳离子铵化合物时，与其一起使用的优选的附加活性剂是保湿剂，如取代脲，如羟甲基脲、羟乙基脲、羟丙基脲；双(羟甲基)脲；双(羟乙基)脲；双(羟丙基)脲；Ν,Ν'-二羟甲基脲；N,N'-二羟乙基脲；N,N'-二羟丙基脲；N,N,N'-三羟乙基脲；四(羟甲基)脲；四(羟乙基)脲；四(羟丙基)脲；N-甲基-N’-羟乙基脲；N-乙基-N,N-N’-羟乙基脲；N-羟丙基-N’-羟乙基脲和N,N’-二甲基-N-羟乙基脲或其混合物。在出现术语羟丙基时，意思是3-羟基-正丙基、2-羟基-正丙基、3-羟基-异丙基或2-羟基-异丙基的通用名。最优选的是羟乙基脲。后者可以以50%水性液形式以商标Hydrovance获自National Starch & Chemical Division of ICI。
当使用时，取代脲在本发明的组合物中的量为该组合物总重量的0.01至20%，优选0.5至15%，最优选2至10%，包括归入其中的所有范围。
当使用阳离子铵化合物和取代脲时，在最尤其优选的实施方案中，使用占该组合物总重量的至少1至15%的在颗粒外（external to the particle）的甘油，包括归入其中的所有范围。
本发明的组合物可包括维生素作为所需活性剂。示例性维生素是维生素A（视黄醇）以及视黄醇酯，如棕榈酸视黄醇酯和丙酸视黄醇酯，维生素B2、维生素B3（烟酰胺）、维生素B6、维生素C、维生素E、叶酸和生物素。也可以使用维生素衍生物。例如，维生素C衍生物包括四异棕榈酸抗坏血酸酯、磷酸抗坏血酸酯镁和抗坏血酸基糖苷。维生素E的衍生物包括生育酚乙酸酯、生育酚棕榈酸酯和生育酚亚油酸酯。当存在于本发明的组合物中时，维生素总量可以为该组合物的0.001至10重量%，优选0.01%至1重量%，最好0.1至0.5重量%。
十八碳烯二酸、壬二酸、泛醌、二羟基丙酮（DHA）及其混合物也可以用作本发明的组合物中的活性剂。此类化合物在使用时，通常占该组合物的0.2至4.5重量%，优选0.5至3重量%，包括归入其中的所有范围。
适用于本发明的其它任选活性剂包括白藜芦醇、间苯二酚，如4-乙基间苯二酚、4-己基间苯二酚、4-苯基乙基间苯二酚、二甲氧基甲苯酰基丙基间苯二酚、4-环戊基间苯二酚、4-环己基间苯二酚、α-和/或β-羟基酸、岩芹酸、共轭亚油酸、十八烷酸、苯基乙基间苯二酚（来自Symrise的Symwhite 377）、undecylenol苯基丙氨酸（来自Seppic的Seppi White）、它们的混合物等。此类活性剂在使用时，一起构成该组合物的0.001至12重量%。
可存在去角质促进剂。实例是α-羟基羧酸、β-羟基羧酸。术语“酸”意在不仅包括游离酸，还包括其盐和C1-C30烷基或芳基酯，和通过除去水生成的内酯以形成环状或线性内酯结构。代表性的酸是乙醇酸及其衍生物、乳酸和苹果酸。水杨酸是β-羟基羧酸的代表。当存在时，这些材料的量可以为该组合物的0.01至15重量%。
在本发明的组合物中可任选包括各种草本提取物。该提取物可以是水溶性的或水不溶性的，载在分别亲水或疏水的溶剂中。水和乙醇是优选的提取溶剂。示例性提取物包括获自绿茶、蓍草、洋甘菊、甘草、芦荟、葡萄籽、温州蜜柑（citrus
unshui）、柳树皮、鼠尾草、百里香和迷迭香的那些。可以使用大豆提取物，尤其是在希望包括视黄醇时。
也任选适用的包括如螯合剂（例如EDTA）、C8-22脂肪酸取代糖、硫辛酸、视黄氧基三甲基硅烷（retinoxytrimethylsilane）（可以以Silcare 1M-75商标获自Clariant
Corp.）、脱氢表雄甾酮（DHEA）及其组合之类的材料。神经酰胺（包括神经酰胺1、神经酰胺3、神经酰胺3B和神经酰胺6）以及拟神经酰胺也可用。通常需要封闭剂（Occlusives），如Oilwax LC。这些材料的量可以为该组合物的0.000001至10重量%，优选0.0001至1重量%。
在本发明的组合物中还可以包括防晒活性剂，并由包含如本文所述的疏水材料的颗粒携带。特别优选的是如苯基苯并咪唑磺酸（Ensulizole）、对甲氧基肉桂酸乙基己酯（可作为Parsol MCX®获得）、阿伏苯宗（可作为Parsol 1789®获得）和二苯甲酮-3（也称作Oxybenzone）之类的材料。可以使用无机防晒活性剂，如微细二氧化钛、氧化锌、聚乙烯和各种其它聚合物。 奥克立林（octocrylene）也适用。当存在时，防晒剂的量通常为0.1至30重量%，优选0.5至20重量%，最好0.75至10重量%。
可以使用传统缓冲剂/pH调节剂。这些包括常用的添加剂，如氢氧化钠、氢氧化钾、盐酸、柠檬酸和柠檬酸盐/柠檬酸缓冲剂。在一个尤其优选的实施方案中，本发明的组合物的pH为4至8，优选4.25至7.75，最优选6至7.5，包括归入其中的所有范围。本发明的组合物可以是固体棒或条。但是，用可以以ARES为名购自T.A. Instruments之类的供应商的应变控制平行板流变仪在环境温度和1s-1剪切速率下获取的本发明的组合物的粘度优选为1,000至120,000
cps，最优选5,000至80,000
cps。
各种各样的包装可用于储存和输递本发明的组合物。包装通常取决于个人护理最终用途的类型。例如，免洗型护肤液和霜、香波、调理剂和沐浴凝胶通常使用塑料容器，在分配端具有被封闭件覆盖的开口。典型封闭件是螺旋帽、非气溶胶泵和翻盖式铰链盖（flip-top hinged lid）。止汗剂、除臭剂和脱毛剂的包装可能涉及在分配端带有滚珠的容器。或者，这些类型的个人护理产品可以在带有伸缩机构（propel-repel mechanism）的容器中在棒状组合物制剂中提供，其中该棒在一个平台上朝分配口移动。由推进剂加压并具有喷嘴的金属罐充当止汗剂、剃须膏和其它个人护理产品的包装。皂条可具有由纤维素或塑料包装纸构成的包装或包装在硬纸盒里或甚至被收缩包装塑料膜包裹。
当局部施加本发明的组合物时，通常每平方厘米皮肤施加0.5至5毫克组合物。
提供下列实施例以利于理解本发明。这些实施例无意限制权利要求的范围。
实施例1
通过合并下列成分，制造下列实施例中的组合物。通过在中等剪切下、在大气压和环境温度条件下混合成分，制造组合物。
| 样品3 | 样品4 | 样品5 | 样品6 | |
| 成分 | 重量% | 重量% | 重量% | 重量% |
| N-乙酰基-L-羟基脯氨酸 | 2.22 | 2.5 | 2.5 | 2.5 |
| L-丙氨酰-L-谷氨酸盐 | 2.22 | 2.5 | 3.75 | 2.5 |
| 甘氨酰甘氨酸 | 2.22 | 2.5 | 2.5 | 3.75 |
| L-谷胱甘肽 | 3.33 | 2.5 | 1.25 | 1.25 |
| 水 | 余量 | 余量 | 余量 | 余量 |
其它实施例：
实施例2
皮肤保湿
按使用Corneometer（Courage+Khazaka, Germany, 型号CM
825, 与Bioengineering of the Skin:Water and the
Stratum Corneum, G. Borroni等人著, P.
Elsner等人编辑, CBC Press, 第18章, 1995中描述的吸附-解吸试验一致）测得的水润度（hydration）评估皮肤保湿。仪器读数通常为5至120单位不等，小数值(~6)是指甲的典型值，较高数值是干燥皮肤的典型值(~10-20)，中等数值是水润皮肤的典型值(~40)，大数值是刚施加水基湿润剂后皮肤的典型值（高于100）。
用0.1毫升表1中规定的组合物以及10%甘油溶液和去离子水作为对照物处理离体猪皮（面积1.5
cm x 1.5 cm）。取处理前的读数作为基线，并在相同位置以表中所示的时间间隔进行至少5次测量。
作为100%* (Ct-C0)/C0计算相对水润值，其中C0是处理前的读数，Ct是在处理后的时间t获取的读数。
发现在根据本发明制成的样品3的含氨基肽的组合物的情况中，在组合物施加到模型皮肤上10、30和60分钟后在给定皮肤面积上相对于初始水润值的水润变化最大。当仅使用水溶性氨基酸的组合时（样品1），皮肤水润度较低，在甘油的情况下观察到的皮肤水润度也较低。
表1
该表中的结果出乎意料地表明，当施加根据本发明制成的组合物时，获得优异的保湿结果。
实施例3
玻璃化转变温度
使用差式扫描量热计（DSC Q1000, TA Instruments）以10 K/min的加热速率从-80到+ 40℃测量玻璃化转变温度。使用TA instrument软件(TA Advantage)从热容曲线的中部测定玻璃化转变温度。对照甘油和含氨基酸的其它组合评估根据本发明的包含氨基肽混合物的组合物。下表2描述所评估的组合物的玻璃化转变温度。水浓度是指在获得玻璃化转变温度时该组合物的水浓度。通过将其储存在室温和大约33%的相对湿度下，从所含的组合物中蒸发水。
表2
| 水浓度(读数时在组合物中的%) | 样品3 | 样品2 | 样品4 | 样品5 | 甘油 |
| 40 | - | - | - | - | -108 |
| 23 | -50 | -67 | -68.26 | - | - |
| 19 | -33 | -50 | -56.42 | - | - |
| 15 | -16 | -37 | -44.58 | - | - |
| 10.3 | - | - | - | -36.4 | - |
| 10 | 3 | -21 | -29.77 | - | - |
| 9.6 | - | - | - | -11.5 | - |
| 8.7 | 14 | -9 | -25.92 | 2.4 | - |
| 0 | - | - | - | - | -83 |
表2中的数据表明，出乎意料地，根据本发明制成的组合物产生消费者喜爱的玻璃状膜，其产生优异的保水性。对样品6而言，观察到的玻璃化转变温度类似于样品5。在不符合本发明的样品中，观察到快速水蒸发（即差的保湿）。
实施例4
角质层的水润度
由在吸附-解吸周期过程中观察到的滞后性（hysteresis）评估角质层的水润度。角质层圆片（disc）（6毫米直径）在两面上都用0.06毫升氨基肽混合物、甘油或水处理，并干燥。然后将样品置于具有受控湿度的Dynamic
Water Sorption Analyzer中。在以小的步幅（Delta RH=10%）提高湿度时，对于各步，在平衡3小时后测量吸水（water uptake）。吸水是指水质量/角质层的干质量。
表3描绘用根据本发明的氨基肽混合物（样品3）、甘油处理的角质层和用去离子水处理的角质层在吸附和解吸时的吸水值。吸附和解吸时的吸水值之差显示在给定实验条件下的保湿度。
表3（样品3的结果）
| 相对湿度, % | 吸水, mg/g-吸附 | 吸水, mg/g-解吸 | 以mg/g计的吸水差异 |
| 20 | 26.97 | 39.63 | 12.66 |
| 30.8 | 48.98 | 57.79 | 8.81 |
| 40.8 | 73.75 | 105.12 | 31.37 |
| 50.7 | 103.47 | 146.84 | 43.37 |
| 61 | 144.74 | 208.42 | 63.68 |
| 71 | 206.93 | 264 | 57.07 |
表3中的数据出乎意料地显示在高相对湿度下的高吸水，意味着优异的保水和滋润结果。
表4
(甘油(10%)和水处理的结果，施加0.12毫升)
表4中的结果表明，令人惊讶地，根据本发明制成的组合物的保水性和滋润性明显更好。
实施例5
粘度测量
使用标准板-板几何（25毫米）在振荡变形状态（oscillatory
deformation regime）中（频率1 Rad/s，根据样品粘度，振幅为0.1至10%）在不同温度和水浓度下测量根据本发明的氨基肽混合物和氨基酸混合物的粘度。在这些条件下的动态粘度被定义为是损耗模量G”除以振荡变形频率。在低水浓度下的粘度的提高表明该配方在皮肤上粘着和缺乏吸引力。当组合物干燥且水浓度降至低于20%时，不符合本发明的组合物（样品2）导致在皮肤上形成粘性膜，而具有根据本发明的氨基肽混合物的组合物（样品3）的粘度产生较低和合意的粘度。这一性能出乎意料地产生较不粘稠和粘滞的组合物。
表5
表5中的结果出乎意料地揭示，包含根据本发明的氨基肽混合物的组合物在失水后不会变稠厚和粘着。
将根据本发明制成的组合物（包括样品7-11中描述的那些）局部施加到有经验的评审人员身上，他们都断定该组合物容易施加并在施加过程中和在施加后不粘着。所有评审人员进一步断定，此类组合物产生与优异保湿性一致的感官结果。
Claims (15)
1.护肤组合物，其包含
a) 氨基肽混合物，其包含：
i. 水溶性氨基酸或官能化氨基酸；
ii. 具有150至410的分子量的水溶性二肽；
iii. 具有225至600的分子量的水溶性三肽或包含肽键的水溶性维生素或两者；和
b) 化妆品可接受的载体
其中氨基酸和水溶性二肽一起构成所述氨基肽混合物总重量的50至99重量%。
2.根据权利要求1的护肤组合物，其中所述氨基酸或官能化氨基酸在正辛醇-水中具有-4.5至0的分配系数log kp。
3.根据权利要求1或权利要求2的护肤组合物，其中所述氨基酸或官能化氨基酸选自谷氨酰胺、天冬酰胺、甘氨酸、谷氨酸、苏氨酸、赖氨酸、丙氨酸、丝氨酸、羟基脯氨酸、N-乙酰基-L-酪氨酸、N-乙酰基-L-羟基脯氨酸、N-乙酰基-L-半胱氨酸、L-鸟氨酸一氯化物及其混合物。
4.根据权利要求1至3任一项的护肤组合物，其中所述二肽是甘氨酰-L-谷氨酰胺、甘氨酰-L-酪氨酸、L-丙氨酰-L-谷氨酰胺、甘氨酰甘氨酸、赖氨酰赖氨酸、甘氨酰丙氨酸、甘氨酰赖氨酸、甘氨酰组氨酸或其混合物。
5.根据权利要求1至4任一项的护肤组合物，其中所述包含肽键的水溶性维生素包含D-L-泛醇，且所述水溶性维生素衍生物包含泛酰巯基乙胺-S-磺酸钙。
6.根据权利要求1至5任一项的护肤组合物，其中所述三肽是L-谷胱甘肽、S-甲基谷胱甘肽、甘氨酰-脯氨酰-谷氨酸、赖氨酰-酪氨酰-赖氨酸、赖氨酰-酪氨酰-赖氨酸、甘氨酰-甘氨酰-组氨酸、赖氨酰-赖氨酰-赖氨酸或其混合物。
7.根据权利要求1至6任一项的护肤组合物，其中氨基酸和二肽在所述氨基肽混合物中的总重量为50至80%。
8.根据权利要求1至7任一项的护肤组合物，其中氨基酸占所述氨基肽混合物的5至50重量%。
9.根据权利要求1至8任一项的护肤组合物，其中所述氨基肽混合物具有-75至15℃，优选-48至12℃的玻璃化转变温度。
10.根据权利要求1至9任一项的护肤组合物，其中所述组合物进一步包含烟酰胺。
11.根据权利要求1至10任一项的护肤组合物，其中所述组合物进一步包含阳离子铵化合物、取代脲、甘油或其混合物。
12.根据权利要求1至11任一项的护肤组合物，其中所述组合物进一步包含防晒剂、间苯二酚或其混合物。
13.根据权利要求1至12任一项的护肤组合物，其中所述组合物能够补充皮肤天然保湿因子。
14.根据权利要求1至13任一项的护肤组合物，其中所述组合物进一步包含水、有机硅和乳化剂。
15.通过补充皮肤的天然保湿因子而润湿皮肤的方法，所述方法包括将权利要求1至14任一项的组合物局部施加到皮肤上的步骤。
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| CN110121332A (zh) * | 2016-12-21 | 2019-08-13 | 荷兰联合利华有限公司 | 具有包含烟酰胺和氨基酸的谷胱甘肽前体的个人护理组合物 |
| CN110325168A (zh) * | 2016-12-21 | 2019-10-11 | 荷兰联合利华有限公司 | 含有胱氨酸的个人护理组合物 |
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| US10456437B1 (en) * | 2018-05-22 | 2019-10-29 | Shulan Jiang | Antibacterial wet wipe for skin care |
| EA202092461A1 (ru) | 2018-05-23 | 2021-02-20 | Юнилевер Н.В. | Наноэмульсии и способ их получения |
| KR20210011964A (ko) | 2018-07-03 | 2021-02-02 | 더 프록터 앤드 갬블 캄파니 | 피부 병태를 치료하는 방법 |
| JP6644225B1 (ja) * | 2018-09-14 | 2020-02-12 | 株式会社ホーマーイオン研究所 | 化粧料 |
| CN110192552B (zh) * | 2019-06-17 | 2021-10-01 | 广东创晟控股集团有限公司 | 甘酪二肽条件培养基在间充质干细胞冻存和制备商品化冻存保护剂方面的应用 |
| US10959933B1 (en) | 2020-06-01 | 2021-03-30 | The Procter & Gamble Company | Low pH skin care composition and methods of using the same |
| EP4157206A1 (en) | 2020-06-01 | 2023-04-05 | The Procter & Gamble Company | Method of improving penetration of a vitamin b3 compound into skin |
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- 2012-11-19 CA CA2854700A patent/CA2854700A1/en not_active Abandoned
- 2012-11-19 EA EA201491212A patent/EA201491212A1/ru unknown
- 2012-11-19 EP EP12787740.5A patent/EP2793828B1/en not_active Not-in-force
- 2012-11-19 CN CN201280061206.4A patent/CN104302271A/zh active Pending
- 2012-11-19 JP JP2014547800A patent/JP6360437B2/ja not_active Expired - Fee Related
- 2012-11-19 WO PCT/EP2012/072972 patent/WO2013092050A2/en active Application Filing
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| CN110121332A (zh) * | 2016-12-21 | 2019-08-13 | 荷兰联合利华有限公司 | 具有包含烟酰胺和氨基酸的谷胱甘肽前体的个人护理组合物 |
| CN110325168A (zh) * | 2016-12-21 | 2019-10-11 | 荷兰联合利华有限公司 | 含有胱氨酸的个人护理组合物 |
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| CN110325168B (zh) * | 2016-12-21 | 2022-10-21 | 联合利华知识产权控股有限公司 | 含有胱氨酸的个人护理组合物 |
| CN110121332B (zh) * | 2016-12-21 | 2022-11-08 | 联合利华知识产权控股有限公司 | 具有包含烟酰胺和氨基酸的谷胱甘肽前体的个人护理组合物 |
| US11666519B2 (en) | 2016-12-21 | 2023-06-06 | Conopco, Inc. | Personal care compositions with cystine |
| CN107400160A (zh) * | 2017-08-07 | 2017-11-28 | 温州千瑞生物科技有限公司 | 抗松弛、紧致的肽以及包含其的化妆品 |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2014007655A (es) | 2014-12-05 |
| WO2013092050A3 (en) | 2013-08-15 |
| MX347811B (es) | 2017-05-15 |
| US8815800B2 (en) | 2014-08-26 |
| BR112014012753A8 (pt) | 2017-06-20 |
| EA201491212A1 (ru) | 2014-09-30 |
| WO2013092050A2 (en) | 2013-06-27 |
| US20130157957A1 (en) | 2013-06-20 |
| CA2854700A1 (en) | 2013-06-27 |
| ZA201403381B (en) | 2016-02-24 |
| EP2793828B1 (en) | 2016-08-24 |
| EP2793828A2 (en) | 2014-10-29 |
| JP6360437B2 (ja) | 2018-07-18 |
| BR112014012753A2 (pt) | 2017-06-13 |
| JP2015500847A (ja) | 2015-01-08 |
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