CN103282041A - 富含多酚的玛卡地上部分的提取物和包括其的组合物 - Google Patents
富含多酚的玛卡地上部分的提取物和包括其的组合物 Download PDFInfo
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- CN103282041A CN103282041A CN2011800623308A CN201180062330A CN103282041A CN 103282041 A CN103282041 A CN 103282041A CN 2011800623308 A CN2011800623308 A CN 2011800623308A CN 201180062330 A CN201180062330 A CN 201180062330A CN 103282041 A CN103282041 A CN 103282041A
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Abstract
本发明涉及富含多酚的玛卡地上部分的提取物,并且还涉及包含这种提取物和(如果适宜的话)合适的赋形剂的组合物。本发明还涉及富含多酚的玛卡地上部分的提取物的提取方法,并且还涉及能够通过所述方法获得的提取物。本发明还涉及所述组合物或者所述提取物在预防或治疗皮肤、粘膜或皮肤附属器的疾病或病理状况中的用途和/或在预防和/或治疗血管疾病中的用途。最后,本发明涉及用于皮肤、皮肤附属器或粘膜的美容护理方法,其目的在于改善皮肤、皮肤附属器或粘膜的状况或外观,所述方法包含施用所述组合物或者所述提取物。
Description
技术领域
本发明涉及富含多酚(并且更特别的是富含黄酮)的玛卡(迈因葶苈Lepidiummeyenii)地上部分的提取物(有利的是玛卡叶的提取物),和包含所述提取物的组合物。有利地,所述组合物是化妆品组合物、药物组合物、皮肤病学组合物或营养品组合物。
本发明还涉及富含多酚(并且更特别的是富含黄酮)的玛卡地上部分的提取物的提取方法,并且还涉及适合于通过所述方法获得的提取物。
本发明还涉及所述组合物或者所述提取物用于预防或治疗皮肤、粘膜或皮肤附属器(phanère)的疾病或病理状况的用途,用于预防或治疗血管疾病、炎症反应或病理状况的用途,用于预防或治疗脂肪组织调节或用于预防或治疗真皮组织改变的用途。最后,本发明涉及用于皮肤、皮肤附属器或粘膜的美容护理方法,其目的在于改善皮肤、皮肤附属器或粘膜的状况或外观,所述方法包含施用所述组合物或者所述提取物。
背景技术
玛卡植物(迈因葶苈Lepidium meyenii)
植物学和农艺学方面
玛卡(玛卡独行菜Lepidium meyenii Walp)是芸薹科Brassicaceae(十字花科Cruciferae)家族中的一员并且是一种12至20cm高的小型草本植物。其地下部分的尺寸为2至5cm。它包含覆盖有增大的肉质下胚轴的下部的主根。当干燥时,整体与小萝卜的形状相似。取决于栽培品种,下胚轴显示出从紫色到浅黄色的一系列颜色。
羽状的叶子形成莲座丛并且从其中心复生。小型花朵为自花授粉。果实为具有两个瓣膜的小型长角果(4至5mm),每个瓣膜包含一枚种子。
种子和地上部分的化学化合物
文献没有报导任何有关玛卡植物的这些部位的化学数据。应当注意的是,在美国生长的数个独行菜物种的种子含有显著量的脂肪(16至31%)。
生物学属性
关于玛卡的药理学属性的公开研究是非常少见的。
通过在大鼠上进行的药理学研究证实了玛卡的块茎对生殖力的影响的声誉。这项研究揭示了可能由于增加的囊状滤泡的发育而使生殖力增加。报导该信息的一般性文章引用难以获得的数据,包括于1961年提交的秘鲁论文(thèsispéruvienne)。
用途
现有技术中已经使用过在地下生长的玛卡的块茎或玛卡的下胚轴或根。
特别地,玛卡的块茎(类似于在食品中经常使用的谷物)的营养价值使其成为秘鲁高原上的人们主要选择的食品。其被新鲜食用(以发酵饮料的形式,在灰下烹调)、烹调食用(以果酱或蛋糕形式)或者干燥食用(以粥或菜泥的形式与水或牛奶混合并烹调)。
出于医学目的玛卡的块茎已经被广泛使用了几百年,以增加动物和人类的生殖力。据说以这种方式,西班牙征服者使用玛卡已经增加了他们的家畜的低繁殖。
Kallawaya(巡回安第斯治疗师)为在末次月经周期后的三或四天寻求受孕的未育妇女开出了一种切成薄片的新鲜块茎的煎剂。
所述块茎也被新鲜使用、烹煮和缩减为腹部药糊中的菜泥以诱导月经。
目前,由于归因于此的兴奋和催情属性,玛卡越来越受欢迎。玛卡块茎(不适当地由于前景良好的潜力市场)与人参(Panax ginseng)相关,故名为秘鲁人参。所述块茎的催情能力似乎是由于前列腺素和甾醇的存在。
块茎的其它用途包括其在呼吸系统疾病(结核)、慢性疲劳、记忆障碍、更年期症状的情况下的益处,作为对于风湿侵袭的疗法,或者用于润肠通便的功效。然而,这些适应症均未通过科学研究实现具体化。
此外,玛卡地上部分通常被认为是废弃的,并因此从未被用于或升级用于化妆品、皮肤病学、药物或营养品目的。
发明内容
发明描述
本发明人发现:玛卡(迈因葶苈Lepidium meyenii)地上部分的提取物,特别是叶、茎、花或种子的提取物,并且有利的是叶的提取物,具有迄今为止从未描述过的化妆品、皮肤病学或药学特性。
特别地,由于其特殊的性质,玛卡地上部分的提取物首次被这样使用,特别地,其目的在于增强皮肤坚实性或紧张性,或者作为抗老化剂。
本发明涉及富含多酚的玛卡地上部分的提取物,典型地其含有以没食子酸当量表示的相对于干燥提取物重量至少1重量%的多酚。
有利地,所述玛卡地上部分的提取物含有以没食子酸当量表示的相对于干燥提取物总重量的至少3重量%,有利地至少5重量%的多酚。
术语富含多酚的玛卡地上部分的提取物是指通过用于浓缩在玛卡地上部分中潜在存在的多酚的方法(典型地使用Folin-Ciocalteu分析法)获得的提取物,以使得所述提取物含有以没食子酸当量表示的相对于干燥提取物总重量至少1重量%,优选至少3重量%并且更有利地至少5重量%的多酚。
根据本发明的一个有利的可选的实施方案,所述提取物含有以没食子酸当量表示的相对于所获得的干燥提取物1重量%至30重量%的多酚,有利地3重量%至20重量%的多酚,更有利地5重量%至10重量%的多酚。
根据本发明的提取物中的干燥提取物的含量相对于提取物总重量从0.01到90重量%变化,有利地从0.5到50重量%,更有利地从0.5到15重量%,甚至更有利地从0.5到5重量%。
特别有利地,根据本发明,所述多酚是黄酮,如黄酮醇。
根据本发明的一个特别的特征,典型地通过氯化铝分析法,根据本发明的提取物含有以芦丁当量表示的相对于干燥提取物总重量至少0.2重量%,有利地至少0.5重量%的黄酮。
有利地,所述玛卡地上部分的提取物含有以芦丁当量表示的相对于干燥提取物总重量至少1重量%,有利地至少2重量%,特别地介于1和5重量%之间,非常特别地介于2至4重量%之间的黄酮。
典型地,根据本发明的提取物的黄酮是黄酮醇,有利地选自槲皮素、山奈酚、其衍生物如其糖基化衍生物,及其混合物。
在本发明的一个特别的实施方案中,所述黄酮含有槲皮素和山奈酚、其衍生物如其糖基化衍生物,或其混合物,有利地其以芦丁当量表示的相对于黄酮总重量的浓度为至少30重量%、典型地至少50重量%、特别地至少70重量%,有利地至少80重量%,更有利地至少90重量%。
根据本发明的一个有利的可选的实施方案,典型地通过HPLC分析法,所述提取物还含有0重量%至70重量%。有利地10至60重量%,更有利地20至50重量%,更有利地30至40重量%的糖,%表示为相对于干燥提取物总重量的重量。
此外,根据本发明的提取物有利地含有0至50重量%、更有利地0至20重量%、甚至更有利地0至10重量%的脂肪,%表示为相对于干燥提取物总重量的重量。
此外,典型地通过Bradford分析法,根据本发明的提取物有利地含有0至60重量%、更有利地0.5至30重量%、甚至更有利地0.5至10重量%的蛋白质,%表示为相对于干燥提取物总重量的重量。
在本发明的范围内,玛卡地上部分选自叶、茎、花、种子、或其混合物。
因此,在地下生长的玛卡块茎、玛卡下胚轴和玛卡根不包括在根据本发明的玛卡地上部分中。
特别有利地,所述地上部分是玛卡叶。
有利地,通过新鲜或干燥的玛卡地上部分在溶剂中的固-液提取获得该提取物,所述溶剂选自水、醇如乙醇、甘油、二醇如丙二醇,及其混合物如二元混合物,水相对于其他溶剂的比例介于0%和100%之间,更有利地水相对于其他溶剂的比例介于0%和90%之间。
通常,使用二元溶剂混合物如水和选自乙醇、甘油或丙二醇的一种溶剂。
在一个特别的实施方案中,提取溶剂是水-醇溶剂,如水-乙醇混合物,水-甘油和/或水-二醇,如水-丙二醇混合物,有利地乙醇、甘油和/或乙二醇在水中的比例介于30和90%之间。
更特别地,在新鲜或干燥的玛卡地上部分的固-液提取的范围内,将介于0.1和50重量%之间(以干燥物质当量计)的合意的植物部分被引入到提取溶剂中,优选介于1和10重量%之间,典型地为5重量%(%表示为相对于所使用的总重量的干燥物质的重量)。玛卡的干燥部分可以是叶、茎、花、种子(单独或联合)并且优选叶。
特别地,在乙醇的存在下,选择乙醇在水中的比例介于0和100%之间,优选介于10和80%之间,并且有利地介于70和90%之间(%表示为相对于水+乙醇总重量的乙醇的重量)。
特别地,在甘油的存在下,甘油在水中的比例介于0和100%之间,优选介于30和80%之间,并且有利地为50%(%表示为相对于水+甘油总重量的甘油的重量)。
特别地,在二醇并且更加特别为丙二醇的存在下,选择丙二醇在水中的比例介于0和100%之间,优选介于10和80%之间,并且有利地为80%(%表示为相对于水+丙二醇总重量的丙二醇的重量)。
有利地,提取温度介于4℃和100℃之间,并且优选介于10℃和60℃之间,并且更特别地介于15℃和30℃之间。
有利地,提取时间从30分钟至4小时变化,并且优选从30分钟至2小时,并且更有利地为大约1小时。
在提取之后,有利地例如通过过滤、沉降或离心从液相中分离出残留的干燥物质。使用具有合适孔隙度的过滤器可以过滤所获得的液相,以获得澄清的溶液。
在这些第一分离步骤之后,例如通过超滤和/或纳米过滤可以跟随纯化步骤,以浓缩对于其它分子的损坏具有潜在能力的分子。
所获得的提取物可以是液体形式,但也可以使用本领域技术人员已知的方法干燥,如喷雾干燥或者含有或不含基质如麦芽糖糊精的冷冻干燥。
本发明还涉及一种制备玛卡地上部分(有利地为玛卡的叶)的提取物的方法,其包含至少一个玛卡地上部分在溶剂中的固-液提取的步骤,所述溶剂选自水、醇如乙醇、甘油、二醇如丙二醇,及其混合物。
典型地,所述方法包含以下连续步骤:
(a)玛卡地上部分并且有利地为叶在合适的溶剂中的分散和提取,所述溶剂有利地为水性溶剂和/或醇溶剂和/或含甘油溶剂和/或二醇溶剂,
(b)在步骤(a)之后获得的提取物的离心和/或过滤;
(c)如果适用的话,在步骤(b)之后获得的提取物的超滤和/或渗滤和/或纳米过滤;然后
(d)玛卡地上部分的提取物的回收;和
(e)任选地,步骤(d)中获得的提取物在基质上或不在基质上的干燥。
在步骤(a)的过程中,有利地以下列比例使用地上部分(特别是叶):0.1和50%之间的叶的干燥物质,并且优选5和20%之间,典型地为5%,百分比表示为相对于所使用的总重量(地上部分+溶剂)的干燥物质的重量。
有利地,在搅拌下进行步骤(a)中的提取。不添加酶。
在步骤(a)的过程中,有利地单独或者与水混合使用下列溶剂:乙醇、甘油或丙二醇,这些溶剂在水中的比例有利地介于30和90%之间并且更有利地介于50和80%之间(%表示为相对于溶剂+水总重量的溶剂的重量)。
本发明还涉及一种组合物,其包含作为活性化合物的玛卡地上部分的提取物,任选地与合适的赋形剂组合。
有利地,所述组合物是化妆品组合物、药物组合物、皮肤病学组合物或营养品组合物。
所述组合物优选被配制成用于外用局部施用或口服施用。
根据本发明的一个有利的可选的实施方案,所述组合物含有0.001至10重量%,典型地为0.01至5重量%,有利地介于1和5重量%之间的提取物,其表示为干燥提取物的百分比。
根据本发明的另一个方面,所述组合物进一步包含除玛卡地上部分的提取物以外的至少一种其它的活性化合物。
这种其它的化合物可以选自下文中所列出的所有化合物及其功能等价物。
特别地,这种其它的化合物可以选自在皮肤病学、药物或化妆品中经常使用的和本领域技术人员已知的活性化合物,如润肤剂、保湿剂、角质调节剂、角质软化剂、皮肤屏障愈合和/或重塑剂、PPAR、RXR或LXR激动剂、皮脂分泌调节剂、抗刺激和/或抗炎和/或舒缓剂、抗氧化剂、抗老化剂、脱色或减色剂、着色剂、脂解剂或脂肪生成抑制剂或抗脂肪剂或减肥剂、矿物或有机滤光剂和遮光剂(色素或超细)、抗真菌化合物、防腐剂、抗细菌剂、益生元和益生菌、抗生素、免疫调节剂。
更特别地,适合于组合使用的皮肤屏障愈合和/或重塑剂有利地为泛醇(维生素B5)、阿拉伯半乳聚糖、氧化锌、神经酰胺、胆固醇、角鲨烷和磷脂。
适合于组合使用的皮脂分泌调节剂有利地选自5-α还原酶抑制剂。锌(和锌衍生物如其葡糖酸盐、水杨酸盐和焦谷氨酸盐)和螺内酯也具有皮脂分泌抑制活性。作用于皮脂质量的脂质来源的其它皮脂分泌调节剂(如亚油酸)是感兴趣的。
抗炎和/或抗刺激和/或舒缓剂可以是阿拉伯半乳聚糖。
适合于组合使用的防晒活性化合物有利地为UVB和/或UVA滤光剂或遮光剂;如本领域技术人员已知的矿物和/或有机遮光剂或滤光剂,本领域技术人员根据寻求保护的程度来调整其选择和浓度。
适合于组合使用的防腐剂是例如在化妆品和保健食品中通常使用的那些,具有抗细菌活性的分子(伪防腐剂)如辛酸衍生物例如辛酰基甘氨酸和辛酸甘油酯;己二醇、乙酰丙酸钠以及锌和铜的衍生物(葡糖酸盐和PCA)。
推荐与根据本发明的提取物组合使用的活性化合物包括植物提取物,特别是:
-植物油如大豆油和/或菜籽油、鳄梨油(WO2004/012496、WO2004/012752、WO2004/016106、WO2007/057439)、羽扇豆油,有利地为甜白羽扇豆油(WO98/47479),或者这些油的混合物;
-植物或动物油的油性蒸馏物(oléodistillat)或浓缩物,特别地为向日葵,更有利地为亚油酸向日葵浓缩物,如由法国科延公司(Laboratoires Expanscience)销售的浓缩为不皂化物的向日葵油(参见国际申请WO01/21150),浓缩为不皂化物的油如鳄梨油、菜籽油、玉米油或棕榈油,特别地应用其保湿和/或润肤、皮肤屏障愈合和/或重塑、抗炎和/或抗刺激和/或舒缓的活性;
-适合于通过在国际申请WO01/21605中描述的方法获得的植物或植物油的不皂化物,有利地为鳄梨呋喃鳄梨和/或大豆不皂化物,更特别地为呋喃型鳄梨不皂化物和大豆不皂化物的混合物,有利地以各自的大约1:3-2:3的比例(如);大豆不皂化物(如根据国际申请WO01/51596中描述的方法获得);甾醇不皂化物(典型地为不皂化物,其中甾醇、甲基甾醇和三萜醇相对于不皂化物总重量的含量介于20和95重量%之间,优选45-65重量%);植物甾醇、甾醇酯和维生素衍生物,特别地应用其皮肤屏障愈合和/或重塑、抗老化、抗炎的活性;
-植物肽或氨基酸复合物,特别地为鳄梨肽(如国际申请WO2005/105123中描述的那些),羽扇豆肽(如根据在申请WO2005/102259中描述的方法获得的那些),藜麦肽(如国际申请WO2008/080974中描述的那些),玛卡肽如国际申请WO2004/112742中描述的那些),任选发酵的大豆肽,大米肽(如国际申请WO2008/009709中描述的那些),特别地应用其保湿和/或润肤(鳄梨)、角质调节(羽扇豆、藜麦)、皮肤屏障愈合和/或重塑(玛卡、藜麦、大豆)、抗炎和/或抗刺激和/或舒缓(羽扇豆、藜麦)、抗氧化(鳄梨)、抗老化(羽扇豆、玛卡)、着色(大米)的活性;
-植物糖,特别地为鳄梨糖(如申请WO2005/115421中描述的那些),特别地应用其角质调节、皮肤屏障愈合和/或重塑、抗炎和/或抗刺激和/或舒缓的活性;
-富含多酚的提取物,并且更特别地为鳄梨果实提取物(如申请FR 1 061 047中描述的那种)和白花菜Gynandropsis gynandra地上部分的提取物(FR1061051);
-羽扇豆醇(FR 2 822 821、FR 2 857 596),特别地应用其促进愈合,
-羽扇豆总提取物(如国际申请WO2005/102259中描述的那些),特别地适合于治疗刺激;
-大穗金合欢Acacia macrostachya种子提取物(FR 0958525),华中五味子Schizandra sphenanthera种子提取物(FR 0955343和0955344 FR)和豇豆Vignaunguiculata种子提取物(FR 0958529)。
推荐与根据本发明的提取物组合使用的活性化合物包括噁唑啉类,特别地为选自下列的那些:2-十一烷基-4-羟甲基-4-甲基-1,3-噁唑啉、2-十一烷基-4,4-二甲基-1,3-噁唑啉、(E)-4,4-二甲基-2-十七碳-8-烯基-1,3-噁唑啉、4-羟甲基-4-甲基-2-十七烷基-1,3-噁唑啉、(E)-4-羟甲基-4-甲基-2-十七碳-8-烯基-1,3-噁唑啉、2-十一烷基-4-乙基-4-羟甲基-1,3-噁唑啉、优选2-十一烷基-4,4-二甲基-1,3-噁唑啉(OX-100或WO2004050052、WO2004050079和WO2004112741)。它们特别地应用其抗炎和/或抗刺激和/或舒缓、抗氧化、脱色、免疫调节的活性。
所有这些组合均包含除了玛卡地上部分的提取物以外的至少一种其它的活性化合物,并且可以包含两种、三种、四种或多种如上所述的活性化合物。
根据本发明的组合物可以被配制成适合于局部施用、口服、直肠、阴道、鼻、耳或支气管施用,以及用于肠胃外施用的各种制剂形式。
有利地,根据本发明的组合物被配制成适合于局部施用的各种制剂形式,更特别地在皮肤和/或皮肤附属器和/或粘膜上应用。
根据第一个可选的实施方案,所述各种制剂适合于局部施用并且特别地包括霜剂、乳剂、乳、软膏剂、洗剂、油、水性或水-醇性或二醇性溶液剂、粉剂、贴剂、喷雾剂、香波、清漆或用于外部应用的任何其它产品。
根据第二个可选的实施方案,所述各种制剂适合于口服施用;玛卡地上部分的提取物适合于或者在膳食补充剂中或者在营养品组合物中使用。所述膳食补充剂可以是玛卡地上部分的提取物本身的形式或者是在本发明的范围之内的硬质或软质的明胶或植物胶囊的形式。在这种情况下,所述膳食补充剂可以含有10至100重量%的玛卡地上部分。
根据标准可以确定施用的最佳方式、剂量和根据本发明的化合物和组合物的药物形式,所述标准通常被考虑在内用于确定药物治疗,特别是适合于患者或动物的皮肤病治疗、美容治疗或兽医治疗,该标准例如患者或动物的年龄或体重、健康状况的严重程度、治疗的耐受性、所观察到的副作用、皮肤类型。根据寻求的施用方式,根据本发明的组合物和/或活性化合物可以进一步包含至少一种药学上可接受的赋形剂,特别地为皮肤病学上可接受的赋形剂或化妆品学上可接受的赋形剂。根据第一个可选的实施方案,使用适用于外用局部施用的赋形剂。根据本发明的组合物可以进一步包含至少一种本领域技术人员已知的药物或化妆品佐剂,其选自增稠剂、防腐剂、芳香剂、着色剂,化学或矿物过滤剂、保湿剂、泉水等。
特别地,具有所述规格的包含玛卡地上部分的提取物的组合物旨在用于化妆品、药物、皮肤病学或营养品用途。
在化妆品、药物或皮肤病学用途范围之内,有利地,所述组合物将被配制成适合于局部施用的制剂形式。
在出于营养品或化妆品目的(“化妆品-食品”)的用途范围之内,有利地,所述组合物将被配制成适合于口服施用的制剂形式。
本发明还涉及玛卡地上部分的提取物在制备化妆品组合物、药物组合物、皮肤病学组合物或营养品组合物中的用途。
有利地,根据本发明的组合物或提取物用于预防和/或治疗皮肤和/或粘膜和/或皮肤附属器的疾病或病理状况。
特别有利地,根据本发明的提取物或组合物用于化妆品应用,有利地通过局部途径,特别地用于皮肤和/或粘膜和/或皮肤附属器如头发的护理或卫生,或者用于预防和/或治疗皮肤和/或粘膜和/或皮肤附属器如头发的疾病。
有利地,根据本发明的组合物或提取物也可以用于预防和/或治疗血管疾病。
特别地,根据本发明的组合物或提取物用于强化血管、血管壁和紧张性和/或用于对血液循环刺激起作用,和/或用于对血管内皮细胞起作用,因此有助于针对水肿腿、眼袋、橘皮组织、皮肤松弛的排水效果。
血管紧张性的强化促进了血管收缩和血管壁内稳态的维持。
有利地,根据本发明的组合物或提取物也可以用于预防和/或治疗真皮组织改变。
真皮组织改变的实例包括真皮基质失衡如皱纹、愈合问题、皮肤的坚实性或弹性。
这样,根据本发明的组合物或提取物还有利地用于防止老化,特别是内因性老化或光致性老化和妊娠纹皮肤。
有利地,根据本发明的组合物或提取物也可以用于预防和/或治疗脂肪组织调节,并且更特别地用于对抗脂肪组织的积累和含有橘皮组织的皮肤。
特别地,根据本发明的组合物或提取物旨在预防和/或治疗过敏性、炎症性、刺激性的反应或病理状况,或者未成熟的、正常的或成熟/老化的皮肤、皮肤附属器(头发和指甲)和/或粘膜(牙龈、牙周、生殖器粘膜)的屏障或内稳态的疾病。
术语皮肤、皮肤附属器和/或粘膜的屏障的疾病是指涉及表皮外层的疾病。
术语皮肤、皮肤附属器和/或粘膜的内稳态的疾病是指由细胞的再生和平衡过程导致的疾病如牛皮癣、尿布疹、特异性皮炎、皮肤干燥(干燥症)、脱水性皮肤和光敏性皮肤。
有利地,根据本发明的组合物或提取物可以用于预防和/或治疗反应、疾病或病理状况:
-皮肤的反应、疾病或病理状况,如痤疮、酒渣鼻或斑点、牛皮癣、尿布疹、特异性皮炎、湿疹、接触性皮炎、刺激性皮炎、过敏性皮炎、脂溢性皮炎(乳痂)、敏感性皮肤、反应性皮肤、干燥性皮肤(干燥症)、脱水性皮肤、皮肤潮红、皮肤红斑、光敏性皮肤、色素性皮肤(黄褐斑、炎症后色素沉着等)、脱色性皮肤(白癜风)、褥疮、皲裂、叮咬、裂性皮肤(特别是在乳房上)、晒斑、由于各种辐射的炎症、通过化学、物理(例如孕妇妊娠)、细菌、真菌或病毒、寄生虫(虱、疥疮、癣、尘螨、皮肤癣菌)、放射性试剂或者由于天然(抗微生物肽)或获得性(细胞、体液、细胞因子)免疫缺陷的刺激,和/或
-粘膜的反应、疾病或病理状况,如牙龈和牙周上容易呈现的牙龈炎(新生儿中的敏感性牙龈、卫生问题、由于吸烟或其它原因)、牙周状况、或者生殖器粘膜上容易呈现的外部或内部的男性或女性生殖道的刺激,和/或
-皮肤附属器的反应、疾病或病理状况如未成熟的、正常的或成熟的指甲(脆性的、软的指甲等)和头发(脱发、头皮屑、多毛症、脂溢性皮炎、毛囊炎),特别地出现头皮疾病如雄激素性、急性、局部性、瘢痕性、先天性、新生儿枕部、或由于化疗/放疗的斑秃性(或脱发),或者休止期脱发、生长期脱发、头发营养不良、拔毛症、体癣或者油腻或干燥的头皮屑。
本发明还涉及一种用于皮肤、皮肤附属器或粘膜的美容护理方法,其目的在于改善皮肤、皮肤附属器或粘膜的状况和/或其外观,所述方法包含施用根据本发明的化妆品组合物或提取物。
在根据本发明的美容方法的一个实施方案中,根据本发明的组合物或提取物用于增强皮肤的坚实性、弹性或紧张性,或者用于预防皮肤的坚实性或紧张性或弹性的缺乏,或者用于合成和/或保护细胞外基质,或者用于预防和/或治疗真皮组织改变。
在根据本发明的美容方法的另一个实施方案中,根据本发明的组合物或提取物用作皮肤、皮肤附属器或粘膜(特别地对抗内在性或外在性老化)的抗老化剂,即用作抗光老化剂或抗紫外线剂,或者用作对抗脂肪组织的积累和含有橘皮组织的皮肤的试剂。
在根据本发明的美容方法的另一个实施方案中,所提及的皮肤和/或皮肤附属器和/或粘膜有利地为呈现出循环或血管紧张性疾病的那些。
具体实施方式
实施例1
在环境温度下,将5%的干燥并磨碎的玛卡多叶茎在搅拌下悬浮于10/90w/w的乙醇/水混合物中共1小时。通过过滤、沉降或离心从液相中分离出残留的干燥物质,并且使用具有合适孔隙度的过滤器可以过滤所获得的液相,以获得澄清的溶液。所获得的提取物具有以下特征:
-干燥提取物:1.8%
-总糖(HPLC):32%/干燥物
-总多酚(Folin-Ciocalteu):5.7%/干燥物
-总黄酮(AlCl3):1.7%
该提取物具有“管内(in tubo)”抗自由基、抗DPPH活性,其中半数抑制浓度(IC50)得到测定,并且其为0.29mg的干燥提取物,代表反应介质中20μg的多酚。
实施例2
在环境温度下,将5%的干燥并磨碎的玛卡多叶茎在搅拌下悬浮于50/50w/w的甘油/水混合物中共1小时。通过过滤、沉降或离心从液相中分离出残留的干燥物质,并且使用具有合适孔隙度的过滤器可以过滤所获得的液相,以获得澄清的溶液。所获得的提取物具有以下特征:
-干燥提取物:1.8%
-总糖(HPLC):37%/干燥物
-总多酚(Folin-Ciocalteu):6.4%/干燥物
-总黄酮(AlCl3):2.2%
该提取物具有“管内(in tubo)”抗自由基、抗DPPH活性,其中半数抑制浓度(IC50)得到测定,并且其为0.26mg的干燥提取物,代表反应介质中16.5μg的多酚。
实施例3
在环境温度下,将5%的干燥并磨碎的玛卡多叶茎在搅拌下悬浮于80/20w/w的丙二醇/水混合物中共1小时。通过过滤、沉降或离心从液相中分离出残留的干燥物质,并且使用具有合适孔隙度的过滤器可以过滤所获得的液相,以获得澄清的溶液。所获得的提取物具有以下特征:
-干燥提取物:1.1%
-总糖(HPLC):40%/干燥物
-总多酚(Folin-Ciocalteu):7.6%/干燥物
-总黄酮(AlCl3):3.6%
该提取物具有“管内(in tubo)”抗自由基、抗DPPH活性,其中半数抑制浓度(IC50)得到测定,并且其为0.28mg的干燥提取物,代表反应介质中22.5μg的多酚。
实施例4:用于局部应用的组合物
本发明人在下文中描述了多种用于局部应用的组合物。玛卡地上部分(PAMaca)的提取物可以被并入各种化妆品中,如洁肤水、水包油乳液、油包水乳液、油、乳、洗剂、香波、发泡产品和喷雾剂,其组成如下所述。百分比表示相对于组合物总重量的产品重量。
用于敏感性皮肤的洁肤水
商品名或INCI名称 | % |
辛酰甘氨酸 | 0至1% |
氢氧化钠 | 0至1% |
隐蔽剂 | 0至1% |
丁二醇 | 1至5% |
β胡萝卜 | 0至2% |
玛卡叶提取物 | 0.01至10% |
防腐剂 | 0至1% |
PEG-32 | 1至5% |
PEG-7棕榈椰油酸酯 | 1至5% |
葡萄糖酸锌 | 0至1% |
柠檬酸 | 0至1% |
纯净水 | 适量至100% |
香水 | 0至1% |
泊洛沙姆184 | 1至5% |
抗老化乳液
商品名或INCI名称 | % |
液体异构烷烃 | 5至20% |
硬脂酸异鲸蜡酯 | 5至20% |
AL-MG羟基硬脂酸酯 | 5至20% |
ABIL WE09 | 1至5% |
甘油 | 1至5% |
凡士林油 | 1至5% |
微粒化的氧化锌 | 1至5% |
丁二醇 | 1至5% |
视黄醇 | 0至1% |
维生素C | 0至5% |
玛卡叶提取物 | 0.01至10% |
异壬酸异壬酯 | 1至5% |
蜂蜡 | 1至5% |
酒石酸钠 | 1至5% |
氯化钠 | 0至5% |
甘氨酸 | 1至5% |
防腐剂 | 0至1% |
胆固醇 | 0至1% |
植物鞘氨醇 | 0至1% |
酒石酸 | 0至1% |
纯净水 | 适量至100% |
重塑乳液
原料/商品名或INCI名称 | % |
氢化聚癸烯 | 5至20% |
月桂基葡糖苷-硬脂酸甘油酯 | 1至5% |
碳酸二辛酯 | 1至5% |
甘油 | 5至20% |
卡波普 | 0至1% |
黄原胶 | 0至1% |
积雪草酸 | 0至1% |
维生素B5 | 0至5% |
玛卡叶提取物 | 0.01至10% |
氢氧化钠 | 0至1% |
防腐剂 | 0至1% |
柠檬酸 | 0至1% |
纯净水 | 适量至100% |
用于干燥性、特异性皮肤的乳
原料/商品名或INCI名称 | % |
甜杏仁油 | 1至5% |
玉米油 | 1至5% |
硬脂酸 | 1至5% |
C16C18鲸蜡醇 | 0至1% |
消泡剂70414 | 0至1% |
月桂酸11OE | 1至5% |
PEG300单月桂酸酯 | 0至1% |
单油酸甘油酯 | 0至1% |
单硬脂酸甘油酯 | 1至5% |
维生素B12 | 0至5% |
玛卡叶提取物 | 0.1至10% |
防腐剂 | 0至1% |
柠檬酸 | 0至1% |
柠檬酸三钠 | 0至1% |
纯净水 | 适量至100% |
香水 | 0至1% |
花生油 | 1至5% |
氢化棕榈仁油 | 1至5% |
舒缓喷雾剂
原料/商品名或INCI名称 | % |
纯净水 | 适量至100% |
三月桂醇聚醚-4磷酸酯 | 1至5% |
碳酸二辛酯 | 1至5% |
丁二醇 | 1至5% |
赤藓醇酯 | 1至5% |
流体凡士林油 | 1至5% |
乳木果黄油 | 0至1% |
植物油 | 0至1% |
防腐剂 | 0至1% |
番茄红素 | 0至5% |
玛卡叶提取物 | 0.01至10% |
氢氧化钠 | 0至1% |
香水 | 0至1% |
黄原胶 | 0至1% |
卡波普 | 0至1% |
隐蔽剂 | 0至1% |
柠檬酸 | 0至1% |
去屑香波
原料/商品名或INCI名称 | % |
纯净水 | 适量至100% |
月桂酰两性基乙酸酯 | 5至20% |
可可葡糖苷 | 5至20% |
PEG6000二硬脂酸酯 | 1至5% |
防腐剂 | 0至2% |
维生素F | 0至5% |
吡罗克酮乙醇胺盐 | 0至2% |
玛卡叶提取物 | 0.01至10% |
吡啶硫酮锌 | 0至1% |
PH调节剂 | 0至1% |
隐蔽剂 | 0至1% |
香水 | 0至1% |
实施例5:用于口服施用的组合物
玛卡叶的提取物被引入口服组合物中,在组合物中适合于每天施用50mg至200mg玛卡叶的提取物。
1/软胶囊形式的抗妊娠纹组合物
采用每天4至6枚500mg的胶囊的方式施用该组合物。
2/防脱发片剂
采用每天5至8枚药片的方式施用该组合物。
3/纤体药筒实例
每天两次施用该组合物。
实施例6:生物学活性
1、血管壁的强化
a.对内皮细胞的活性
通过PCR分析筛选来研究玛卡叶的提取物对真皮内皮细胞的作用。
内皮细胞是血管壁的构成细胞,因此在维持血管平衡中发挥重大作用并调节血管和周围组织(真皮)之间的相互作用。
-材料和方法:
用0.005%和0.01%(活性物质的w/v)玛卡(MC)叶的提取物处理人类微血管内皮细胞24小时。
孵育后,通过使用PCR分析的实时定量RT-PCR分析各种标记物的基因表达。
-结果和结论:
内皮细胞上的筛选结果表明玛卡叶的提取物(表1):
-刺激参与强化血管的分子的基因表达:血管生成素1(血管建立和稳定中的作用),丝氨酸蛋白酶抑制剂1(抗蛋白酶),钙粘蛋白5,原纤蛋白1,整联蛋白αV(参与血管稳定的细胞/细胞或细胞/基质粘附分子),αSMA或α平滑肌肌动蛋白和肌钙蛋白1(强化血管/弹性);
-刺激参与血管紧张性的分子的基因表达:钙调素(血管通透性控制),内皮素1和ECE1或内皮素转换酶1(血管收缩);
-刺激防御分子的基因表达:血红素氧合酶1(通过防止游离的血红素参与助氧化反应的保护作用)和硫氧还蛋白(对蛋白质氧化损伤的修复);和
-抑制参与炎症的分子的基因表达:CSF1或巨噬细胞集落刺激因子1(巨噬细胞的生产/分化/功能控制)和E-选择素(粘附分子,在炎性细胞募集中的作用)。
这些效果表明了血管紧张性的刺激活性和血管强化活性。
表1:PCR分析对内皮细胞的活性筛选
2、真皮基质的保护和强化
a.对真皮基质标记物的活性
通过分析各种标记物的基因表达,在真皮成纤维细胞中测试玛卡叶的提取物对真皮基质的活性:
-I型胶原蛋白(真皮细胞外基质的主要组成)负责皮肤坚实性和抵抗力;
-弹性蛋白,负责皮肤的弹性;
-MMP1(1型基质金属蛋白酶),负责I型和III型胶原蛋白的降解;
-皮连蛋白,其参与组装胶原蛋白纤维并且对于维持真皮细胞外基质的结构和组织韧性很重要;
-核心蛋白聚糖,其与胶原蛋白纤维结合,以防止MMP1的裂解;
-纤连蛋白:参与真皮细胞外基质的结构的高分子量糖蛋白;
-透明质酸合成酶2:参与形成透明质酸(一种对于皮肤的滋润和密度重要的吸湿性分子)的酶。
-材料和方法:
用0.002%和0.005%(活性物质的w/v)玛卡(MC)叶的提取物或者采用5ng/mlTGFβ1(参考物)处理正常人类真皮成纤维细胞24小时。
在孵育结束时,通过实时RT-PCR分析各种真皮基质标记物的基因表达。
通过单因素方差分析,然后通过Dunnett检验,对结果进行统计学分析。
-结果和结论:
如表2所示,玛卡叶的提取物显著增加了胶原蛋白I、弹性蛋白、皮连蛋白、核心蛋白聚糖、纤连蛋白和透明质酸合成酶2的基因表达。
此外,玛卡叶的提取物显著抑制了MMP1的基因表达。
这些结果表明真皮细胞外基质的强化。
表2:成纤维细胞中真皮基质标记物的基因表达(相对数量)
nd:未测定
b.对老化的成纤维细胞中真皮基质标记物的活性
通过分析双链蛋白聚糖的基因表达,在通过H2O2处理早老化的真皮成纤维细胞中测试玛卡叶的提取物的作用。
双链蛋白聚糖是一种影响胶原蛋白成纤维作用的小型蛋白聚糖。
-材料和方法:
用600μM H2O2将正常人类真皮成纤维细胞早老化。
然后在0.005%和0.01%(活性物质的w/v)玛卡(MC)叶的提取物或10ng/mlTGFβ提取物(参考物)的存在下孵育成纤维细胞72小时。
孵育后,通过实时定量RT-PCR分析双链蛋白聚糖的基因表达。
-结果和结论:
用H2O2处理诱导的成纤维细胞老化抑制了双链蛋白聚糖的表达;玛卡叶的提取物有可能恢复该表达(表3)。
玛卡叶的提取物在老化条件下保护真皮基质。
表3:用H2O2老化的真皮成纤维细胞中双链蛋白聚糖的基因表达
c.弹性蛋白酶生产的抑制
在各种刺激(炎症、UV辐射等)的影响下,人类中性粒细胞释放氧合物质和酶如弹性蛋白酶。
过量的弹性蛋白酶可以降解皮肤的基质蛋白,如弹性蛋白、蛋白聚糖、胶原蛋白、核心蛋白聚糖等。
通过人类中性粒细胞评价玛卡叶的提取物对弹性蛋白酶释放的作用。
-材料和方法:
用0.005%和0.01%(活性物质的w/v)玛卡(MC)叶的提取物或者用10μg/ml乳香脂酸(参考物)处理人类中性粒细胞15分钟并用1μM钙离子载体A23187刺激10分钟。
用分光光度法,通过测定弹性蛋白酶的活性来评价弹性蛋白酶的释放。
使用学生t检验对结果进行统计学分析。
-结果和结论:
通过中性粒细胞可知玛卡叶的提取物显著抑制了弹性蛋白酶的释放(表4)。
这些结果表明了对于真皮基质的保护作用。
表4:通过中性粒细胞的弹性蛋白酶的释放
3、抗炎和抗氧化防御
a.防止脂质过氧化的保护
-材料和方法:
在0.005%和0.01%(活性物质的w/v)玛卡(MC)叶的提取物或100μM BHT(参考物)的存在下以及在C11-氟荧光探头(特异用于脂质过氧化)的存在下,将Jurkat细胞系预孵育45分钟。
然后采用UVA+B辐射细胞并在MC或BHT的存在下孵育30分钟。
在孵育结束时,通过借助于荧光强度(与氧化成反比)的流式细胞分析法来评价脂质过氧化物的数量。
使用学生t检验对结果进行统计学分析。
-结果和结论:
玛卡叶的提取物显著保护了细胞对抗由UV辐射诱导的脂质过氧化(表5)。
表5:UV诱导的脂质过氧化
b.PMA诱导的炎症的抑制
-材料和方法:
采用或不采用(对照)0.005%和0.01%(活性物质的w/v)玛卡(MC)叶的提取物或参考用抗炎分子(10-7M地塞米松;10-6M吲哚美辛)将人类角质形成细胞(NCTC-2544系)预孵育24小时。然后同样在MC或参考物的存在下,用0.1μg/mlPMA(佛波醇肉豆蔻酸乙酸酯)将细胞处理24小时。
处理后,通过ELISA测定培养上清液中分泌的IL8(白介素8)和PGE2(前列腺素E2)的数量。
使用学生t检验对结果进行统计学分析。
-结果和结论:
玛卡叶的提取物强烈并显著抑制了通过角质形成细胞中的PMA刺激的炎性介质IL8和PGE2的生产(表6)。这些结果表明了玛卡叶的提取物的抗炎活性。
表6:通过角质形成细胞的IL8与PGE2的生产
c.痤疮丙酸杆菌P.Acnes诱导的炎症的抑制
在由痤疮丙酸杆菌Propionibacterium Acnes侵占的角质形成细胞上研究玛卡叶的提取物对于由这种细菌诱导的炎症的保护作用。
-材料和方法:
在0.008%和0.031%(活性物质的w/v)玛卡(MC)叶的提取物或参考用抑制剂:尼克酰胺的存在下,将人类角质形成细胞(HaCaT系)预孵育48小时。
然后,通过用痤疮丙酸杆菌(ATCC6919株)的细菌悬浮液孵育18小时来刺激角质形成细胞。
在孵育结束时,使用ELISA技术,在培养上清液中测定由角质形成细胞产生的IL-8的数量。
使用学生t检验对结果进行统计学分析:ns p>0.05(不显著);*p<0.05;**p<0.01;***p<0.001。
-结果和结论:
图1表示预孵育18小时,根据以%计的活性物质的浓度的用痤疮丙酸杆菌刺激的角质形成细胞的IL-8的生产(以pg/ml计)。
玛卡叶的提取物显著抑制了角质形成细胞上痤疮丙酸杆菌诱导的IL8生产(图1)。
因此,玛卡叶的提取物调节了痤疮丙酸杆菌诱导的炎症。
4、脂肪细胞中的脂肪合成抑制
-材料和方法:
在0.005%和0.01%(活性物质的w/v)玛卡(MC)叶的提取物或参考物(20μM浅蓝菌素)的存在下,将正常的人类脂肪细胞孵育1小时。在孵育之后,加入放射性标记物[14C]-乙酸盐并将样品孵育过夜。
孵育结束时,提取脂质并通过液体闪烁法测量引入的放射活性(对应于脂肪生成)。
使用学生t检验对结果进行统计学分析。
-结果和结论:
玛卡叶的提取物显著抑制了通过脂肪细胞的脂质新合成(表7)。
这样,该提取物因此具有纤体作用。
表7:脂肪细胞中脂肪生成的评价
Claims (15)
1.一种玛卡地上部分的提取物,其含有以没食子酸当量表示的相对于干燥提取物重量至少1重量%,有利地至少3重量%,更有利地至少5重量%的多酚,所述多酚有利地为黄酮,典型地所述提取物具有以芦丁当量表示的相对于干燥提取物总重量0.2%以上,有利地0.5%以上,更有利地1%以上,甚至更有利地2%以上的黄酮含量。
2.根据权利要求1所述的提取物,其特征在于所述黄酮含有槲皮素、山奈酚、其衍生物或其混合物,有利地其以没食子酸当量表示的相对于所述黄酮总重量的浓度为至少30重量%、典型地至少50重量%。
3.根据权利要求1或2所述的提取物,其特征在于所述地上部分是玛卡叶。
4.根据上述权利要求中任一项所述的提取物,其特征在于通过玛卡地上部分在溶剂中的固-液提取获得所述提取物,所述溶剂选自水、醇、甘油、二醇或其混合物。
5.根据权利要求4所述的提取物,其特征在于通过玛卡地上部分在溶剂中的固-液提取获得所述提取物,所述溶剂选自水-醇溶剂,水-甘油溶剂和/或水-二醇溶剂或其混合物,有利地为二元混合物,并且优选醇、甘油和/或二醇在水中的比例介于30和90%之间。
6.一种组合物,其包含作为活性化合物的根据上述权利要求中任一项所述的提取物和有利地合适的赋形剂,其特征在于所述组合物由化妆品组合物、药物组合物、皮肤病学组合物或营养品组合物组成。
7.根据权利要求6所述的组合物,其进一步包含除玛卡地上部分的提取物以外的至少一种其它的活性化合物,所述活性化合物特别地选自润肤剂、保湿剂、角质调节剂、角质软化剂、皮肤屏障愈合和/或重塑剂、PPAR、RXR或LXR激动剂、皮脂分泌调节剂,抗刺激和/或抗炎和/或舒缓剂、抗氧化剂、抗老化剂、脱色或减色剂、着色剂、脂解剂或脂肪生成抑制剂或抗脂肪剂或减肥剂、矿物或有机滤光剂和遮光剂、抗真菌化合物、防腐剂、抗细菌剂、益生元和益生菌、抗生素和免疫调节剂。
8.根据权利要求7所述的组合物,其特征在于所述其它的活性化合物选自:
-皮肤屏障愈合和/或重塑剂,优选泛醇、阿拉伯半乳聚糖和氧化锌,
-皮脂分泌调节剂,优选5-α还原酶抑制剂、锌衍生物、螺内酯和亚油酸,
-抗炎和/或抗刺激和/或舒缓剂,优选阿拉伯半乳聚糖,
-减色或脱色剂,优选N-十一碳烯酰基-L-苯丙氨酸,
-矿物和/或有机遮光剂或滤光剂,优选UVB和/或UVA滤光剂或遮光剂,和
-防腐剂,优选辛酰基甘氨酸,辛酸甘油酯,己二醇,乙酰丙酸钠,锌和铜的衍生物。
9.根据权利要求6至8中任一项所述的组合物,其进一步包含至少一种其它的活性物质,所述其它的活性物质选自:
-植物油,优选大豆油、菜籽油、鳄梨油、羽扇豆油并且有利地为甜白羽扇豆油,或者这些油的混合物,
-植物或动物油的油性蒸馏物或浓缩物,优选向日葵油、鳄梨油、菜籽油、玉米油和棕榈油,有利地被浓缩为不皂化物,
-植物或植物油的不皂化物,优选鳄梨不皂化物、大豆不皂化物、或其混合物,有利地为鳄梨呋喃,并且特别地为呋喃型鳄梨不皂化物和大豆不皂化物以各自的大约1:3-2:3的比例的混合物,甾醇不皂化物、植物甾醇、甾醇酯和维生素衍生物,
-植物肽或氨基酸复合物,优选鳄梨肽、羽扇豆肽、藜麦肽、玛卡肽,任选发酵的大豆肽、大米肽,
-植物糖,优选鳄梨糖,
-鳄梨油酸丁酯,
-富含多酚的提取物,优选鳄梨提取物和白花菜Gynandropsis gynandra地上部分的提取物,
-羽扇豆醇,
-羽扇豆总提取物,
-古布阿苏黄油,
-大穗金合欢Acacia macrostachya种子提取物、华中五味子Schizandrasphenanthera种子提取物和豇豆Vigna unguiculata种子提取物,
-噁唑啉类,优选2-十一烷基-4-羟甲基-4-甲基-1,3-噁唑啉、2-十一烷基-4,4-二甲基-1,3-噁唑啉、(E)-4,4-二甲基-2-十七碳-8-烯基-1,3-噁唑啉、4-羟甲基-4-甲基-2-十七烷基-1,3-噁唑啉、(E)-4-羟甲基-4-甲基-2-十七碳-8-烯基-1,3-噁唑啉、2-十一烷基-4-乙基-4-羟甲基-1,3-噁唑啉和2-十一烷基-4,4-二甲基-1,3-噁唑啉,
以及其混合物。
10.根据权利要求6至9中任一项所述的组合物,其特征在于所述组合物被配制成用于局部或口服施用。
11.根据权利要求6至10中任一项所述的组合物或如权利要求1至5中任一项所定义的提取物用于预防和/或治疗皮肤和/或粘膜和/或皮肤附属器的疾病或病理状况的用途。
12.根据权利要求6至10中任一项所述的组合物或如权利要求1至5中任一项所定义的提取物用于预防和/或治疗血管性疾病,并且更特别地用于强化血管壁和紧张性的用途。
13.根据权利要求6至10中任一项所述的组合物或如权利要求1至5中任一项所定义的提取物用于预防和/或治疗过敏性、炎症性、刺激性的反应或病理状况,或者未成熟的、正常的或成熟/老化的皮肤、皮肤附属器和/或粘膜的屏障或内稳态疾病的用途。
14.根据权利要求6至10中任一项所述的组合物或如权利要求1至5中任一项所定义的提取物用于预防和/或治疗脂肪组织改变,并且更特别地用于治疗脂肪组织调节的用途。
15.一种用于皮肤和/或皮肤附属器和/或粘膜的美容护理方法,其目的在于改善皮肤和/或皮肤附属器和/或粘膜的状况和/或其外观,有利地其目的在于增强皮肤的坚实性、弹性或紧张性,或者用于对抗脂肪组织的积累和含有橘皮组织的皮肤,或者用于预防和/或治疗真皮组织改变,或者用于预防和/或治疗血液循环疾病并增加血管紧张性,或者用于预防和/或治疗老化,所述方法包含施用根据权利要求6至10中任一项所定义的化妆品组合物或根据权利要求1至5中任一项所定义的提取物。
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FR1061047A FR2969495B1 (fr) | 2010-12-22 | 2010-12-22 | Extrait de parties aeriennes de maca riche en polyphenols et composition le comprenant |
PCT/EP2011/073834 WO2012085226A1 (fr) | 2010-12-22 | 2011-12-22 | Extrait de parties aeriennes de maca riche en polyphenols et composition le comprenant |
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CN106266453A (zh) * | 2016-08-31 | 2017-01-04 | 郑向东 | 一种皮肤外用组合物及其应用 |
CN107417471A (zh) * | 2017-09-06 | 2017-12-01 | 汪建利 | 肥料省一半、作物不减产的土壤肥力激活剂及其制备方法 |
CN111083923A (zh) * | 2018-08-20 | 2020-04-28 | 安帝芭株式会社 | 舒缓霜以及其制造方法 |
CN116322729A (zh) * | 2020-07-24 | 2023-06-23 | 科学发展实验室 | 富含多糖的肋果木棉花提取物 |
CN115477604A (zh) * | 2021-05-31 | 2022-12-16 | 高雄医学大学 | 马卡萃取物及其用途 |
CN114409544A (zh) * | 2022-01-30 | 2022-04-29 | 西安交通大学 | 具有血管舒张活性的苯丙素及其提取方法和应用 |
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CA2822182A1 (fr) | 2012-06-28 |
KR20140012964A (ko) | 2014-02-04 |
WO2012085226A1 (fr) | 2012-06-28 |
US20130177513A1 (en) | 2013-07-11 |
EP2654765A1 (fr) | 2013-10-30 |
US20200085897A1 (en) | 2020-03-19 |
FR2969495B1 (fr) | 2013-10-11 |
EP2654765B1 (fr) | 2019-03-13 |
BR112013015976A2 (pt) | 2018-11-06 |
FR2969495A1 (fr) | 2012-06-29 |
ES2727832T3 (es) | 2019-10-21 |
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