CN115024997B - 具有抗皮肤衰老功效的化妆品组合物 - Google Patents
具有抗皮肤衰老功效的化妆品组合物 Download PDFInfo
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- CN115024997B CN115024997B CN202210571114.6A CN202210571114A CN115024997B CN 115024997 B CN115024997 B CN 115024997B CN 202210571114 A CN202210571114 A CN 202210571114A CN 115024997 B CN115024997 B CN 115024997B
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- cosmetic composition
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- carnosine
- collagen
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Abstract
本发明涉及一种具有抗皮肤衰老功效的化妆品组合物,所述化妆品组合物采用水作为主溶剂,所述化妆品组合物还包括肌肽酯类衍生物、视黄醇棕榈酸酯、透明质酸钠、保湿剂和乳化剂。
Description
技术领域
本发明涉及化妆品技术领域,尤其涉及一种具有抗皮肤衰老功效的化妆品组合物。
背景技术
人的皮肤是一种延伸覆盖整个身体的复杂的器官,皮肤通常由两个主要的组织层组成,即最外层的表皮,以及由在上的乳头层和在下的网状层组成的真皮。表皮主要由角质形成细胞组成,真皮为表皮提供实体支持,因此真皮可视为表皮的滋养层。真皮主要由成纤维细胞组成,真皮还包含血管和神经纤维,真皮的无细胞部分(即在细胞之间的区域)称为细胞外基质。皮肤的细胞外基质由多种细胞外组分组成,包括蛋白(特别是胶原蛋白纤维和弹性蛋白)、糖胺聚糖、蛋白聚糖和多种糖蛋白,细胞外组分由真皮成纤维细胞合成。
细胞外基质组分的机能障碍和变化可能干扰组织完整性和细胞表现,因此,皮肤的细胞外基质组分的功能障碍和变化可能导致皮肤衰老、皮肤萎缩、皮肤受损或任意其他与细胞外基质组分的变化相关的皮肤的病况、紊乱和疾病。因此出于抗衰老的目的,存在对于维持或提高细胞外基质组分的活性水平的化妆品组合物的需要。
术语说明
本发明中所记载的“包含”、“含有”、“具有”和“包括”应该理解为开放式的,除非上下文另外指明。
本发明中记载的“皮肤衰老”是指皮肤对机体的防护能力和调节能力减退,不能适应内外环境的变化,出现颜色、形态等外观整体状况的改变,常表现为皮肤弹性减少或消失、皮肤松弛、皱纹增多、皮肤干燥、变薄、易脱屑、瘙痒、面色晦暗、没有光泽并伴随色斑及疣状物。
本发明中记载的“抗皮肤衰老”是指抑制和改善内在性衰老。皮肤衰老根据其原因分为内在性衰老和外性在衰老,内在性衰老是与环境变化无关的皮肤结构和皮肤的生理学功能随人变老而恶化过程,外在性衰老是由连续暴露于外部环境(如阳光和空气污染物)引起的。内在性衰老的特征包括:随着内在性皮肤衰老进展,皮肤变干,形成细纹和皱纹,并且随着年龄变得更明显和更深,此外,由于表皮和真皮的结构和功能变化,皮肤失去其弹性,并且看起来是下垂的;随着年龄真皮变得更薄,并且形成充分可见的皮肤褶皱;估计对于成人每年胶原蛋白减少的总量约为1%;剩余的胶原蛋白纤维逐渐变得更厚,而胶原蛋白纤维的交联增加,使其溶解性、弹性等降低;弹性蛋白纤维变得更厚,并且其交联也增加;真皮中的成纤维细胞的增殖活性随时间降低,衰老的成纤维细胞合成新的胶原蛋白、弹性蛋白、透明质酸和细胞外基质的其他组分的能力也降低。
本发明中记载的“抗皮肤衰老”具体指预防性和/或治疗性调节皮肤状况,包括延缓、减少、最少化和/或防止皮肤中可见的和/或可触摸的不连续性(皮肤中可以通过视觉上或通过触摸检测到的纹理不规则),包括皮肤衰老体征,改善皮肤外观和/或触感。
本发明中记载的“化妆品组合物”和“化妆品产品”可互换使用,涉及可以用于化妆目的或卫生目的或作为递送一种或多种化妆品和/或药物物质、产品和/或成分的基质的制剂。“化妆品组合物”包括但不限于个人护理产品、皮肤产品、皮肤乳膏、皮肤凝胶、皮肤软膏、皮肤洗液、皮肤贴片、皮肤面膜等。
本发明中所记载的“水”指去离子水。
本发明中所记载的“肌肽”指β-丙氨酰-组氨酸和所有相关的化合物,如鹅肌肽(β-丙氨酰-1-甲基-组氨酸),高肌肽(γ-氨基-丁酰-组氨酸),D-肌肽,L-肌肽,及其盐。
发明内容
本发明提供一种具有抗皮肤衰老功效的化妆品组合物,该化妆品组合物可以施用到皮肤上,通过刺激人中的细胞外基质组分,例如胶原蛋白、弹性蛋白和透明质酸,而改善衰老皮肤的外观,达到抗皮肤衰老功效。
本发明提供的一种具有抗皮肤衰老功效的化妆品组合物,所述化妆品组合物采用水作为主溶剂,所述化妆品组合物还包括:
(a)肌肽酯类衍生物;
(b)视黄醇棕榈酸酯;
(c)透明质酸钠;
(d)保湿剂;
(e)乳化剂。
本发明提供的化妆品组合物可促进成细胞外基质中胶原蛋白I、III、IV、VII、XVII、弹性蛋白、层粘连蛋白等的合成,减少金属基质蛋白酶MMP-1的表达,促进透明质酸生成,强化表皮、真皮以及真皮-表皮连接处的结构完整和功能性,改善皮肤弹性,减少皱纹,同时具有提升皮肤屏障,减少经皮水分流失的作用,从而提供显著的抗衰老、尤其是抗皱纹形成功效。
本发明提供的化妆品组合物中不添加EDTA盐、多磷酸钠、偏磷酸钠、葡萄糖酸等螯合剂。
所述组分(a)的肌肽酯类衍生物,与肌肽在结构和生物学特性上是不同的。肌肽的化学结构提供如下:
(式I)肌肽(β-丙氨酰-组氨酸);
而组分(a)的肌肽酯类衍生物的化学结构提供如下:
(式II)肌肽酯类衍生物
其中R是含碳侧链,所述含碳侧链是饱和的直链或饱和的支链,并且不包含杂原子(例如硫原子、氧原子、氮原子、磷原子、卤素原子等),并且含碳侧链的碳原子的个数为不大于8并且不小于4。所述组分(a)的肌肽酯类衍生物不是天然存在的,是通过使肌肽的羧基成酯所合成的肌肽酯类衍生物。所述组分(a)的含量为约0.02-0.15%重量,基于所述化妆品组合物的总重量。需要说明的是,所述肌肽酯类衍生物可以包括几种包含不同含碳侧链R的肌肽酯类衍生物组成。
所述组分(b)中的视黄醇棕榈酸酯可商购获得,所述组分(b)的含量为约0.04-0.15%重量,基于所述化妆品组合物的总重量。
所述组分(c)中,透明质酸钠包括大分子量透明质酸钠(1800-2200KDa)、中分子量透明质酸钠(1000-1800KDa)、小分子量透明质酸钠(10-1000KDa)、水解透明质酸钠(1-10KDa)、乙酰化透明质酸钠中的一种或多种。透明质酸钠可以通过本领域已知的方法制备,例如通过发酵法由植物性来源培养基(蛋白胨、葡萄糖等)制得透明质酸钠。透明质酸钠也可以商购获得。所述组分(c)的含量为约0.01-0.15%重量,基于所述化妆品组合物的总重量。
所述组分(d)中,所述保湿剂占所述化妆品组合物重量约0.01%-约50%、更优选约0.1%-约30%,所述保湿剂是帮助保持皮肤中的含水水平的成分。所述保湿剂可以选自由下述组成的组:多元醇,水溶性烷氧基化非离子聚合物和它们的混合物。另外的湿润剂包括但不限于乙酰基精氨酸,海藻提取物,库拉索芦荟(aloebarbadensis)叶提取物,甲基葡糖醇聚醚-10,甲基葡糖醇聚醚-20,甘油聚醚-7,甘油聚醚-26,甘油葡糖苷,蔗糖,海藻糖,鼠李糖,甘露糖,棉子糖,甜菜碱,赤藓醇,木糖醇,甘油聚醚-5乳酸酯,聚谷氨酸钠,水解小核菌胶,出芽短梗酶多糖,银耳多糖,酸豆籽多糖,天然的保湿因子,和/或尿素。
所述组分(e)中,所述乳化剂占所述化妆品组合物重量约0.01%-约20%、更优选约0.1%-约10%,所述乳化剂用于保持或增强所述化妆品组合物的物理和化学稳定性。所述乳化剂包括宽泛种类的非离子、阳离子、阴离子、两性离子和两性表面活性剂,可用于所述化妆品组合物的亲水性表面活性剂(阳离子、阴离子、两性离子、两性的)可以包含单种表面活性剂或适当的表面活性剂的任意组合。所选的确定的一种表面活性剂(或多种表面活性剂)将取决于所述化妆品组合物的pH和存在的其他组分。其中,有用的非离子表面活性剂优选的是选自由下述组成的组的那些:硬脂醇聚醚-21,鲸蜡硬脂醇聚醚-20,鲸蜡硬脂醇聚醚-12,硬脂醇聚醚-100,PEG-100硬脂酸酯,PEG-40氢化蓖麻油,PPG-26丁醇聚醚-26,和它们的混合物;有用的阳离子表面活性剂是选自下述的那些:山嵛酰胺丙基PG二甲基氯化铵,二月桂基二甲基氯化铵,二硬脂基二甲基氯化铵,二肉豆蔻基二甲基氯化铵,二棕榈基二甲基氯化铵,和它们的混合物;优选的用于所述化妆品组合物的阴离子表面活性剂包括烷酰基羟乙基磺酸酯,以及烷基和烷基醚硫酸酯。优选的用于所述化妆品组合物的两性表面活性剂包括椰油酰两性乙酸酯,椰油酰两性二乙酸酯,两性月桂乙酸酯,月桂基两性二乙酸酯和它们的混合物。
除了上述组分外,所述化妆品组合物还可任选地包含护肤化妆品中常用的成分,其实例包括但不限于活性成分、辅料等。所述活性成分的实例包括但不限于皮肤调理剂,所述辅料的实例包括但不限于抗氧化剂、防腐剂、增稠剂、香料。
所述皮肤调理剂可以包括,但不限于,胍,尿素,羟基乙酸,羟乙酸盐(例如,铵和季烷基铵),水杨酸,乳酸,乳酸盐(例如,铵和季烷基铵),以其多种形式中的任一种形式的芦荟(例如,芦荟胶),多元醇,诸如山梨醇、甘露醇、木糖醇、赤藓醇、己三醇、丁三醇、丙二醇、丁二醇、己二醇等,聚乙二醇,丙氧基化甘油,糖(例如,蜜二糖),淀粉,糖和淀粉衍生物(例如,烷氧基化葡萄糖,果糖,葡糖胺),糖的C1-C30单酯和多酯和相关物质,透明质酸,乳酰胺单乙醇胺,乙酰胺单乙醇胺,泛醇,右旋泛醇,尿囊素,和它们的混合物。皮肤调理剂还可以包括脂肪酸,脂肪酸酯,脂质,神经酰胺,胆固醇,胆固醇酯,蜂蜡,矿脂,和矿物油。所述皮肤调理剂在所述化妆品组合物中的含量是本领域已知的,例如,其通常占所述化妆品组合物总重量的0.01-10%。
所述抗氧化剂可以包括,但不限于,抗坏血酸(维生素C)及其盐,脂肪酸的抗坏血酸基酯,和其他抗坏血酸衍生物,生育酚(维生素E),生育酚山梨酸酯,生育酚乙酸酯,生育酚的其他酯类,β-胡萝卜素,丁酸化羟基苯甲酸及其盐,过氧化物(包括过氧化氢),过硼酸盐,巯乙酸酯,过硫酸盐,没食子酸及其烷基酯,尿酸及其盐和烷基酯,胺,去甲二氢愈创木酸,生物类黄酮,巯基化合物,二羟基延胡索酸及其盐,赖氨酸吡酮酸盐,精氨酸吡酮酸盐,氨基酸,水飞蓟素,赖氨酸,1-甲硫氨酸,脯氨酸,超氧化物歧化酶,山梨酸及其盐,硫辛酸,橄榄提取物,茶提取物,白藜芦醇,多酚或包含多酚的植物提取物,类胡萝卜素,姜黄素化合物,辅酶Q10,OCTA(L-2-氧代-4-噻唑烷羧酸),硒,肌酸,谷胱甘肽,N-乙酰基半胱氨酸,N-乙酰基半胱氨酸酯,二甲基甲氧基色原烷醇,硫辛酸,黑色素。优选的抗氧化剂选自对羟基苯乙酮。优选的,所述抗氧化剂占所述化妆品组合物总重量的0.01-2%。
所述防腐剂的实例包括但不限于羟苯甲酯、羟苯丙酯、苯氧乙醇、苯甲醇、苯乙醇、双(羟甲基)咪唑烷基脲、山梨酸钾、苯甲酸钠、氯苯甘醚、脱氢乙酸钠、辛酰羟肟酸、1,2-己二醇、1,2-戊二醇、对羟基苯乙酮、辛甘醇、甘油辛酸酯、十一碳烯酸甘油酯、山梨坦辛酸酯、乙基己基甘油、牡丹根提取物等中的一种或多种。所述防腐剂在所述化妆品组合物中的含量是本领域已知的,例如,其通常占所述化妆品组合物总重量的0.01-2%。
所述增稠剂包括常用作局部应用的赋形剂或载体以增加制剂的粘度的那些试剂。增稠剂还可以用于提高制剂和产品的稳定性。更具体地,这样的实例包括但不限于,丙烯酰胺共聚物,琼脂糖,支链淀粉,膨润土,藻酸钙,羧甲基纤维素钙,卡波姆,羧甲基壳多糖,纤维素胶,糊精,明胶,氢化牛脂,羟乙基-纤维素,羟丙基纤维素,羟丙基淀粉,藻酸镁,甲基纤维素,微晶纤维素,果胶,各种聚乙二醇,聚丙烯酸,聚甲基丙烯酸,聚乙烯醇,各种聚丙二醇,丙烯酸钠共聚物,角叉菜胶钠,黄原胶,和/或酵母β-葡聚糖。宽泛种类的多糖可作为增稠剂用于所述化妆品组合物。本发明优选的化妆品组合物包含选自下述的增稠剂:羧酸聚合物、交联的聚丙烯酸聚合物、聚丙烯酰胺聚合物和它们的混合物,更优选地选用丙烯酸酯/C10-30丙烯酸烷基酯交联聚合物。优选的,所述增稠剂占所述化妆品组合物总重量的0.01-2%。
本发明提供的具有抗皮肤衰老功效的化妆品组合物可以通过本领域已知的任何合适的方法制备。例如,使用化妆品领域中常用的溶解槽、乳化锅、分散器、输送泵等设备制备。例如,制备时先将水溶性物质投入水相溶解釜,将油溶性物质投入油相溶解釜,将两个釜的温度加热至合适温度,其中对于易结块的原料可先用分散器将其预分散,待溶解完成后将油相和水相输送至乳化锅中进行均质乳化,乳化完成后将料体温度降至常温,加入任选的抗氧化剂、防腐剂等,并视需要调节产物的pH,相关检测指标都合格后方可灌装出货。所述制备方法可根据剂型要求进行删减或调整。根据需要,可将所述化妆品组合物制成膏、霜、乳液、精华液等各种剂型。
所述化妆品组合物可以填装到适当的包装(容器)中,诸如,例如,管,泵,真空泵,罐,瓶,气雾剂容器或其他容器中,这取决于用途。所述化妆品组合物通常在这些容器中商品化。所述化妆品组合物还可以提供良好的美观,并且可以是美容上精致的。
下面结合具体实施例进行说明。
具体实施方式
以下结合实施例,对本发明进行进一步详细说明。但是,应当理解为,这些实施例、对比例仅仅是用于具体地说明本发明,而不应理解为用于以任何形式限制本发明所附权利要求书的范围。
本发明提供的具有抗皮肤衰老功效的化妆品组合物可以适用于局部施用到人的皮肤、衰老的皮肤、受损的皮肤、美容和/或皮肤病学程序后的皮肤、萎缩的皮肤、受伤的皮肤,具有改善人皮肤中的可见的衰老体征、改善其他皮肤纹理缺陷、减小眼袋、减轻黑眼圈以及减轻萎缩的皮肤的有益效果。本发明提供的化妆品组合物特别适用于皮肤复新或改善衰老皮肤的外观,所述化妆品组合物还可以用于保持健康的皮肤。本发明提供的化妆品组合物可以一天至少一次或多次施用给受试者,并且可以持续施用较长时间,例如不少于30天。
本发明提供的具有抗皮肤衰老功效的化妆品组合物包含肌肽酯类衍生物,所述肌肽酯类衍生物用于刺激一种或多种细胞外基质组分(例如,胶原蛋白I,胶原蛋白III,胶原蛋白V,胶原蛋白VI,胶原蛋白VII,胶原蛋白XVI,弹性蛋白,层粘连蛋白,透明质酸,原纤维蛋白,硫酸乙酰肝素蛋白聚糖2,和/或它们的任意组合)形成的组合物。所述肌肽酯类衍生物与肌肽在结构和生物学特性上是不同的,并且提供显著不同的物理化学特性(例如,分子量、扩散性、水溶性、亲脂性、辛醇-水分配系数、氢键形成等)、化学特性(例如,与化学反应剂的化学反应性、化学稳定性、自发水解、被肌肽酶的转化等)、代谢稳定性(蛋白水解和/或酶降解)和生物学特性(例如,刺激细胞外基质组分,包括但不限于,胶原蛋白I和III;是否与不同的酶动力学、针对细胞表面或细胞核受体的不同亲和力和/或增加的通过细胞膜或其他生理屏障的扩散性相关)。
本发明中,肌肽酯类衍生物的化学结构提供如下:
(式II)肌肽酯类衍生物
其中R是含碳侧链,所述含碳侧链是饱和的直链或饱和的支链,并且不包含杂原子(例如硫原子、氧原子、氮原子、磷原子、卤素原子等),并且含碳侧链的碳原子的个数为不大于8且不小于4。所述肌肽酯类衍生物是以三甲基氯硅烷为起始原料,与一元醇类化合物反应生成相应的三甲基硅醚化合物和一分子的氯化氢;肌肽的羧基与三甲基硅醚化合物反应温和地得到所述肌肽酯类衍生物和三甲基硅醇,合成路线如下:
在下述实施例中,所述肌肽酯类衍生物的合成方法包括如下步骤:
步骤一,在100mL的反应瓶中加入10mL的一元醇类化合物,于室温下在搅拌状态下滴加10mmol的三甲基氯硅烷;
步骤二,再向反应瓶中加入5mmol的肌肽,室温下搅拌1h后加热至60℃反应8-12h,TLC检测反应进程;
步骤三,反应完毕后冷却至室温,再向反应瓶中加入20mL的乙酸乙酯,超声0.5h后倾出溶剂,重复3次后减压浓缩回收溶剂得无色透明油状的所述肌肽酯类化合物纯品。
意外发现,一元醇类化合物的碳链长度对合成所述肌肽酯类化合物的收率有影响,当一元醇类化合物的碳原子的个数不大于8时,一元醇类化合物和三甲基氯硅烷的反应活性最好,此时收率为80-95%;当一元醇类化合物的碳原子的个数大于8时,此时收率不大于56.8%,这无疑会提高成本。
意外发现,所述肌肽酯类衍生物的含碳侧链R的碳链长度对于刺激一种或多种细胞外基质组分形成的组合物的效果有影响,当含碳侧链R的碳原子的个数小于4时,碳链很短,所述肌肽酯类衍生物对细胞外基质组分的有效刺激不足,这使得包含所述肌肽酯类衍生物的化妆品组合物的抗皮肤衰老功效较弱。另外,含碳侧链R的结构对所述肌肽酯类衍生物的活性也有影响,碳原子个数相同时,包含支链型的含碳侧链的所述肌肽酯类衍生物的活性高于包含直链型的含碳侧链的所述肌肽酯类衍生物。
因此出于成本和提高活性的观点出发,所述肌肽酯类衍生物的含碳侧链的碳原子的个数为不大于8并且不小于5,优选的,所述含碳侧链为饱和支链型。
所述肌肽酯类衍生物提供更高的通过人体皮肤的渗透性,因此提供比肌肽更高的功效;所述肌肽酯类衍生物比肌肽更耐受降解(即更高的代谢稳定性)因此提供比肌肽更长久更持续的功效;所述肌肽酯类衍生物提供新颖的出乎意料的生物学特性,从而差异性地且更有效地刺激细胞外基质组分的形成。
化妆品组合物中所述肌肽酯类衍生物足以有效地用于刺激胶原蛋白I、胶原蛋白III、胶原蛋白V、胶原蛋白VI、胶原蛋白VII、胶原蛋白XVI、弹性蛋白、层粘连蛋白、透明质酸合成酶2、原纤维蛋白1、硫酸乙酰肝素蛋白聚糖和/或透明质酸(或它们的组合)的形成,即所述肌肽酯类衍生物刺激主要与皮肤衰老相关的细胞外基质组分中的一种或多种(例如,胶原蛋白I,胶原蛋白III,胶原蛋白V,弹性蛋白,透明质酸,和/或它们的任意的组合)的形成。因此所述化妆品组合物可以特别用于抗皮肤衰老。
此外,本领域未理解和更是出乎意料地,所述肌肽酯类衍生物刺激比胶原蛋白I显著更多的胶原蛋白III的形成,并且所述肌肽酯类衍生物以协同方式刺激透明质酸的形成。所述肌肽酯类衍生物、所述视黄醇棕榈酸酯和所述透明质酸钠组成的的组合比单独的活性成分中的任一种或两种更大的程度刺激皮肤中细胞外基质组分的形成。即,所述化妆品组合物的组分产生协同性结果。
基于所述肌肽酯类衍生物在所述化妆品组合物中的溶解度和成本占比,优选的,所述肌肽酯类衍生物占所述化妆品组合物重量约0.02%-约0.15%。所述化妆品组合物中使用所述肌肽酯类衍生物的另外的优点还包括:所述肌肽酯类衍生物具有较少的副作用、不是免疫原性的或免疫原性较低而不会引起引起变态反应、并且局部应用后的降解产物无毒或无害。所述肌肽酯类衍生物属于二肽,能更好地吸收和透过皮肤。
尽管现有技术中公开了肌肽的抗衰老特性,但是之前没有描述所述肌肽酯类衍生物的特性,并且其特性是令人惊讶和出乎意料的。肌肽的抗衰老特性可以归因于肌肽的抗氧化特性、抗糖化作用,以及由作为肌肽的组分的组氨酸的组胺合成,和/或通过β-丙氨酸对胶原蛋白I合成的刺激,β-丙氨酸是肌肽的另一种组分。但没有记载肌肽以高于胶原蛋白I的水平诱导胶原蛋白III的形成,或者刺激已经被记载随着皮肤衰老显著改变的所有细胞外基质组分的形成,所述所有细胞外基质组分即胶原蛋白I,胶原蛋白III,胶原蛋白V,弹性蛋白和透明质酸。
意外发现,由于本发明提供的化妆品组合物采用水为主溶剂,若化妆品组合物中添加其它具有抗衰老活性和/或美容活性的植物提取物(包含中药提取物或者草药提取物)和/或动物提取物和/或组织培养产物,存在发生肌肽水解生成β-丙氨酸和L-组氨酸的情况,而肌肽酯类衍生物通过对肌肽的羧基修饰成酯,改变了肌肽的结构,增加了肽键附近的空间位阻,从而极大地提高了化妆品组合物的稳定性,即本发明提供的化妆品组合物可以通过添加其它植物提取物和/或动物提取物和/或组织培养产物来配合所述肌肽酯类衍生物,进一步提升抗衰老活性和/或美容活性。并且所述肌肽酯类衍生物具有更高的水溶性,可以通过增加化妆品组合物中所述肌肽酯类衍生物的含量来进一步提升抗衰老功效。
本发明中所记载的胶原蛋白包括胶原蛋白I,胶原蛋白II,胶原蛋白III,胶原蛋白IV和胶原蛋白V,在人皮肤中,胶原蛋白I和胶原蛋白III是主要的胶原蛋白类型。胶原蛋白和细胞外基质的其他组分(包括,但不限于,弹性蛋白和透明质酸)的含量和结构上的变化是衰老的人皮肤的特征。弹性蛋白是为皮肤提供包括弹性和拉伸强度。透明质酸(还称为透明质烷)是一种阴离子、非硫酸化的糖胺聚糖,其分子量通常达到数百万,是皮肤的细胞外基质的主要组分,透明质酸显著有助于真皮中的细胞增殖和迁移,另外通过透明质酸的得水性有助于皮肤的水合。
本发明提供的化妆品组合物包含所述肌肽酯类衍生物、视黄醇棕榈酸酯和透明质酸钠,这些组分的包含浓度足以表现出改善皮肤衰老。肌肽酯类衍生物、视黄醇棕榈酸酯和透明质酸钠的组合能有效实现刺激胶原蛋白I、胶原蛋白III、胶原蛋白V、弹性蛋白和透明质酸。
本发明还提供使用所述化妆品组合物来改善人皮肤的状态和外观并且减少皮肤衰老体征的方法。
本发明还提供使用所述化妆品组合物来来保持健康皮肤和/或防止皮肤衰老的方法。
本发明提供的化妆品组合物可以用在人中。所述化妆品组合物还可以用于哺乳动物。
[实施例]
实施例1-3提供的化妆品组合物的具体组分参数如表1所示。
对比例1-5提供的化妆品组合物的具体组分参数如表2所示。
表1
表2
表1和表2中的组分的含量是基于组合物的总重量。实施例1-3、对比例1-5提供的化妆品组合物均为透明的液体。
实施例1-3提供的化妆品组合物的制备方法包括:混合B相组分,高速剪切直至制备成透明外观,备用;混合A相组分,将混合的B相组分加入混合的A相组分中,搅拌均匀直至混合均匀,出料得到所述化妆品组合物。这和对比例1-5提供的化妆品组合物的制备方法相类似。
为了方便叙述,将实施例1提供的化妆品组合物中含有的肌肽酯类衍生物的含碳侧链标记为R1,将实施例2提供的化妆品组合物中含有的肌肽酯类衍生物的含碳侧链标记为R2,将实施例3、对比例1-3提供的化妆品组合物中含有的肌肽酯类衍生物的含碳侧链标记为R3,将对比例4提供的化妆品组合物中含有的肌肽酯类衍生物的含碳侧链标记为R4,将对比例5提供的化妆品组合物中含有的肌肽酯类衍生物的含碳侧链标记为R5。
具体的,R1-R5的结构如下所示:
对实施例1-3、对比例1-5提供的化妆品组合物进行如下测试。
[化妆品组合物对与衰老相关的蛋白表达的影响]
实验仪器:荧光定量PCR仪(Roche)、超净工作台(苏净)、二氧化碳培养箱(Binder)、酶标仪(BIO-TEK)、微量振荡器。
实验试剂与耗材:人原代成纤维细胞、6孔板、成纤维细胞培养液、RNA提取试剂盒、反转录试剂盒、Trizol裂解液等。
基于成纤维细胞的基因表达分析步骤如下:
(1)接种:以5E5/孔的接种密度,接种细胞至6孔板中,在37℃和5%CO2培养箱中孵育过夜;
(2)给药:待6孔板中细胞铺板率达到60%左右时,加入各化妆品组合物的受试物,每种组合物设6个复孔;
(3)收样:在37℃和5%CO2培养箱种24h后,弃掉培养液,每孔加入1mL Trizol,吹打裂解细胞后,收样;
(4)PCR检测:提取RNA,反转录至cDNA后,进行荧光定量PCR检测;
(5)进行统计分析,测试结果如表3所示。
表3
样品 | 胶原蛋白I | 胶原蛋白III | 胶原蛋白VI | 胶原蛋白VII | 弹性蛋白 | 层粘连蛋白 |
实施例1 | 19.04 | 9.75 | 11.02 | 8.02 | 18.75 | 5.61 |
实施例2 | 18.92 | 9.88 | 10.55 | 8.15 | 18.02 | 5.04 |
实施例3 | 22.02 | 10.22 | 11.23 | 8.72 | 19.88 | 5.92 |
对比例1 | 11.56 | 5.68 | 6.12 | 4.56 | 10.01 | 2.46 |
对比例2 | 12.05 | 6.12 | 6.44 | 5.29 | 10.84 | 2.54 |
对比例3 | 2.84 | 1.17 | 1.75 | 1.71 | 4.61 | 0.98 |
对比例4 | 15.43 | 9.02 | 10.28 | 7.54 | 15.64 | 3.84 |
对比例5 | 16.02 | 9.04 | 10.01 | 7.12 | 16.32 | 3.62 |
表3的结果表明,包含所述肌肽酯类衍生物、视黄醇棕榈酸酯和透明质酸钠的化妆品组合物(实施例1-3)均具有一定的抗皱功效。对比实施例3与对比例1-3的结果可以显然看出,所述肌肽酯类衍生物、视黄醇棕榈酸酯和透明质酸钠的组合非常显著地提高了各蛋白的基因表达水平,这充分表明了它们之间产生了协同增效作用。比实施例3与对比例4-5的结果可以显然看出,所述肌肽酯类衍生物的含碳侧链R的碳原子的个数大于8(对比例5)或者小于4(对比例4)时,化妆品组合物的抗皮肤衰老功效降低。
[临床检测1:抗衰老研究]
研究实施例3提供的化妆品组合物的保持健康的皮肤和皮肤复新效果。在六个月的时间期间,人受试者每天向他们的脸上涂抹所述化妆品组合物两次。他们被要求如同他们正常使用面部化妆品(例如,面部保湿剂)一样涂抹所述化妆品组合物。分别在开始使用该化妆品组合物的治疗之前(基线)和在1、2、3和6个月后进行安全性和有效性评价。评价包括由经过训练的研究者对眼周区域的细纹和粗皱纹、嘴周区域的细纹和粗皱纹、可触知的粗糙、有斑点的色素沉着过度、发红和毛细管扩张、皮肤毛孔和毛孔尺寸、肤色和使用视觉严重性评分的整体皮肤损伤对受试者面部进行评估。有效性评价还包括临床面部照相(在标准化条件下,包括受试者的位置和光照),使用PRIMOS-3D系统(GFMesstechnikGmbH)量化眼周皮肤区域的皮肤粗糙度和皱纹深度,以及在受试者在环境受控的房间保持坐位至少30分钟后用
使用MPA580装置(Courage&Khazaka)测量上面颊区域的皮肤弹性。进行红斑(发红)、水肿(肿胀)、干燥和起皮(脱皮)的评估来确定该化妆品组合物的安全性。为了这一目的,研究者使用下述5点评级:0=无,1=轻度,2=中度,3=显著的,4=严重的。此外,在整个研究持续过程中记录不良事件。
下述结果是在包括具有至少中度的面部皱纹体征的I-III型皮肤的女性的研究中获得的,具体为20名受试者。1个月后,35%的受试者眼周皱纹改善,3个月后71%的受试者,和6个月后88%的受试者眼周皱纹改善。1个月后,30%的受试者嘴周皱纹改善,3个月后47%的受试者(2.2±0.5;n=17),和6个月后71%的受试者嘴周皱纹改善。该产品是充分耐受性的。
研究清楚地证明实施例3提供的化妆品组合物使衰老的皮肤复新化妆品组合物在所有的受试者中还是充分耐受的,并且没有引起任何不良事件。
[临床检测1:皮肤萎缩研究]
在具有皮肤萎缩的人中研究实施例3提供的化妆品组合物,所述皮肤萎缩由于长期的局部使用皮质类固醇导致,或者在妇女中绝经后引起。受试者被要求每天向受影响的皮肤区域涂抹所述化妆品组合物一至六次,持续至少四周。该涉及不同临床病例试验的该研究证明,所述化妆品组合物减轻皮肤萎缩的严重性,并且帮助恢复正常的皮肤屏障。所述组合物也是充分耐受的。
以上所述实施例的各技术特征可以进行任意的组合,为使描述简洁,未对上述实施例中的各个技术特征所有可能的组合都进行描述,然而,只要这些技术特征的组合不存在矛盾,都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式,其描述较为具体和详细,但并不能因此而理解为对发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。因此,本发明专利的保护范围应以所附权利要求为准。
Claims (10)
1.一种具有抗皮肤衰老功效的化妆品组合物,其特征在于:
所述化妆品组合物采用水作为主溶剂,所述化妆品组合物还包括肌肽酯类衍生物、视黄醇棕榈酸酯、透明质酸钠、保湿剂和乳化剂;
所述肌肽酯类衍生物的化学结构为:
其中R是含碳侧链,所述含碳侧链是饱和的直链或饱和的支链,所述含碳侧链的碳原子的个数为不大于8并且不小于4。
2.根据权利要求1所述的化妆品组合物,其特征在于:基于所述化妆品组合物的总重量,所述肌肽酯类衍生物的含量为0.02-0.15wt%。
3.根据权利要求1所述的化妆品组合物,其特征在于:基于所述化妆品组合物的总重量,所述视黄醇棕榈酸酯的含量为0.04-0.15wt%。
4.根据权利要求1所述的化妆品组合物,其特征在于:基于所述化妆品组合物的总重量,所述透明质酸钠的含量为0.01-0.15wt%。
5.根据权利要求1所述的化妆品组合物,其特征在于:所述保湿剂包括二丙二醇、甘油聚醚-26、聚乙二醇-8、丁二醇、甜菜碱和1,3丙二醇。
6.根据权利要求1所述的化妆品组合物,其特征在于:所述乳化剂包括PEG-40氢化蓖麻油和PPG-26丁醇聚醚-26。
7.根据权利要求1所述的化妆品组合物,其特征在于:所述化妆品组合物还包括抗氧化剂、增稠剂和防腐剂。
8.根据权利要求7所述的化妆品组合物,其特征在于:所述抗氧化剂包括对羟基苯乙酮。
9.根据权利要求7所述的化妆品组合物,其特征在于:所述增稠剂包括丙烯酸(酯)类/C10-30烷醇丙烯酸酯交联聚合物。
10.根据权利要求7所述的化妆品组合物,其特征在于:所述防腐剂包括1,2己二醇。
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