CN103338741B - 促进黑色素的局部组合物 - Google Patents
促进黑色素的局部组合物 Download PDFInfo
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- CN103338741B CN103338741B CN201180066218.1A CN201180066218A CN103338741B CN 103338741 B CN103338741 B CN 103338741B CN 201180066218 A CN201180066218 A CN 201180066218A CN 103338741 B CN103338741 B CN 103338741B
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- curcumin
- dopamine precursor
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Abstract
本发明提供了应用于皮肤的免晒美黑组合物，其包含有效量的至少一种多巴胺前体、有效量的姜黄素和皮肤病学可接受的载体。本发明公开了制备所述组合物的方法。当应用于皮肤时，该组合物可用来黑化皮肤。
Description
发明领域
本发明涉及皮肤变黑(免晒美黑(sunless tanning))的组合物和方法，其基于多巴胺前体和姜黄素。本发明提供了一种制备该组合物的方法。
发明背景
黑化皮肤是一种常见的个人外观所需的美学元素。黑化的外观往往看起来健康、年轻而且通常更具魅力。
天然的黑化过程是由暴露于阳光，特别是紫外线触发的，发生于皮肤表达黑色素时。黑色素由于其光化学特性具有光保护功能。它吸收有害的紫外线并将能量转化为热量。这防止了与恶性黑色素瘤和其他皮肤癌相关的间接DNA损伤的发生。
造成黑化的紫外线频率常被分为UVA和UVB范围。UVA引起黑素细胞的预成黑色素释放以结合氧(氧化)，而这又产生了皮肤的实际黑色。UVB诱导增加黑色素的生成。暴露于UVB约2天后会产生黑化。UVA，特别是UVB，能引起活性氧簇的形成，其反过来直接地和通过各种生化途径损伤DNA。紫外线辐射的有害影响是为大家所熟知的，而且世界范围内与任何其他的致癌物比，紫外线辐射与更多的癌症相关联。Nyugen et al.,Nonmelanoma skincancer,Curr Treat Opt Oncol3:193-203(2002).
晒黑床已经被用来模拟阳光效应。晒黑床使用若干具有磷光体混合物的荧光灯，该磷光体混合物设计以发射紫外线，该紫外线在有效引起黑化的光谱内。大多数晒黑床主要发射UVA辐射。
为了避免与阳光或晒黑床相关的紫外线辐射的危险，已经开发出产品在无紫外线下提供晒黑外表。因此，免晒美黑产品，包括自动黑化剂(self-tanner)和美黑喷雾(spraytans)已经被开发出来以提供黑化的外观。
大多数可得的免晒美黑产品是含二羟基丙酮(DHA)为活性成分的洗剂和喷雾。DHA与作为皮肤表面的角蛋白死层的一部分的氨基酸基团发生化学反应。各种氨基酸与DHA发生不同的反应，生成从黄色到褐色不同色调的颜色。所得色素称为蛋白黑素。这些与黑色素的颜色类似。由使用基于DHA产品产生的人工美黑着色，其颜色和均匀度可根据使用者的角蛋白层特点而变化。在一些人工美黑产品中，除DHA外还使用了赤藓酮糖。赤藓酮糖与DHA在皮肤表面以相同方式作用，但是提供了不同的颜色范围。胡桃醌和指甲花醌也被用作古铜色剂。
其它用于产生免晒美黑的试剂包括皮肤表面着色剂，如合成染料、天然着色剂和氧化铁。这些化妆方法并未提供满意的、表现自然的、持久的黑化。此外，着色剂可被洗掉或引起织物染色。
主要有两种类型与皮肤呈色相关的黑色素：真黑素和褐黑素。真黑素提供黑色或褐色的皮肤呈色，而褐黑素提供淡粉红色皮肤和红色头发的呈色。
黑色素是通过酪氨酸酶(由皮肤黑素细胞形成)由酪氨酸生成的。酪氨酸酶将酪氨酸转变为二羟基苯丙氨酸(左旋多巴(l-dopa))，然后转变为多巴醌。多巴醌然后转变为真黑素或褐黑素。
刺激皮肤黑色素生成的产品已被提议。例如，黑色素前体如酪氨酸和催化黑色素形成必需的酪氨酸酶的使用，已被提议。例如，美国专利4,515,773(Herlihy)涉及黑化人类表皮的组合物。该组合物含10nM至1M浓度的前体，如酪氨酸、苯丙氨酸和儿茶酚衍生物，其与酪氨酸酶一起分布在整个基质中。
美国专利5,061,480(Marchese et al.)，涉及皮肤黑化组合物，公开了含酪氨酸活性成分的组合物，其中酪氨酸活性成分与非离子型表面活性剂(例如，聚氧乙烯醚和聚氧乙烯脱水山梨糖醇脂肪酸酯如BRIJ、TWEEN或ARLACEL协同作用以增加对皮肤的穿透率。该申请公开了加入核黄素或三磷酸腺苷以加速生成皮肤黑化色素的氧化过程。其教导了酪氨酸或其衍生物以0.2至0.5重量%存在。
然而，这些产品并未有效的提供有意义的免晒黑色素产品且未取得商业上的成功。
美国专利公开2005/0175556(Gupta)，其内容在此引入作为参考，涉及基于通过酪氨酸酶增强黑色素合成的皮肤变黑组合物。Gupa公开了局部皮肤变黑组合物，其包含(i)至少一种酪氨酸底物，(ii)至少一种酪氨酸活化剂，及任选地，一种药物载体。所有的实施例教导Mucuna prurience提取物或二羟苯丙氨酸(D-和L-多巴)作为酪氨酸酶底物。ATP铜和谷胱甘肽铜被教导作为酪氨酸活化剂。
然而工业上仍然需要有效且无需通过合成化合物或金属活化的免晒美黑组合物。理想地，免晒美黑化合物将使用以天然植物为基础的化合物作为酪氨酸活化剂来配制。
发明内容
本发明提供免晒美黑组合物，其包含多巴胺前体和姜黄素的协同组合。
在一个实施方案中，提供了一种施用于皮肤的免晒美黑洗剂，其包含有效量的至少一种多巴胺前体、有效量的姜黄素，和皮肤病学可接受的载体。
多巴胺前体选自酪氨酸、N-乙酰基酪氨酸和苯丙氨酸，其含量为约1至约30重量%。在优选实施方案中，多巴胺前体含量约5至约20重量%，最优选的约10至约15重量%。
姜黄素含量约0.05至约10重量%。在优选实施方案中，姜黄素含量约1.0至约5重量%，最优选的约2.0重量%。
皮肤病学可接受的载体可包含任何透明质酸钠、磷脂酰胆碱、棕榈酸异丙酯、鲸蜡硬脂醇、单硬脂酸甘油酯、乳木果油(shae butter)、角鲨烷、硅酮和二甲基乙醇胺。该组合物的pH范围为约2.5至约6.0。在优选实施方案中，该组合物的pH范围为约3.0至约5.5，最优选的，约3.8至5.0。
在一些实施方案中，该组合物可能还含有约0.5至约10.0重量%的异硫氰酸苯酯。在优选实施方案中，异硫氰酸苯酯的含量为约1.0至约8.0重量%，最优选的约2.0至5.0重量%。
在另一实施方案中，该组合物可能包含以下的任一种：α-羟基酸、咖啡因、维生素D3、槲皮素(quercertin)、莱菔硫烷(sulforaphane)，以及天冬氨酸镁、葡萄糖酸锌和葡萄糖酸铜的混合物。
在另一个实施方案中，本发明提供了免晒美黑组合物，其包含约10至15重量%的多巴胺前体、约1至约3重量%的姜黄素及约4至约6重量%的异硫氰酸苯酯，余量为皮肤病学可接受的载体，其中所述的多巴胺前体选自酪氨酸、N-乙酰基酪氨酸、苯丙氨酸及其混合物。
此外，本发明提供了制备免晒美黑组合物的方法，该组合物包含水相、油相、含水DMAE混合物、多巴胺前体、姜黄素和防腐剂。该组合物的制备过程为：将水相加入到油相中；混合水相和油相；冷却至38-40℃；在约38℃加入DMAE混合物；在约35℃向生成的混合物中加入多巴胺前体和姜黄素；混匀。然后，加入防腐剂，组合物加水足量至100%。
在另一个实施方案中，提供了变黑皮肤的方法。该方法包括给皮肤使用有效量的至少一种多巴胺前体和姜黄素，其中姜黄素与所述的多巴胺前体协同作用以向上调节黑色素的生成。在这个实施方案中，多巴胺前体含量可为约10至约15重量%而姜黄素约1.0至约5重量%。
发明详述
酪氨酸(Tyr)是一种由氨基酸苯丙氨酸(Phe)合成的非必需氨基酸。已发现许多高蛋白食物产品如豆制品、鸡肉、火鸡、鱼、花生、杏仁、酪梨、牛奶、乳酪、酸乳酪、茅屋芝士、利马豆、南瓜子和芝麻中都含有它。Phe至Tyr的转变由苯丙氨酸羟化酶，一种单加氧酶催化进行。该酶催化反应引起羟基基团加到苯丙氨酸6碳芳环的末端，从而使其变成酪氨酸。尽管酪氨酸是疏水性的，但很明显它比苯丙氨酸更可溶解。
酪氨酸吸收紫外线辐射并促成蛋白质的吸收光谱。酪氨酸也是若干重要神经递质的构件，如多巴胺(多巴)，并有助于生成黑色素。共有两种类型的黑色素：褐黑素(黄色、红色)和真黑素(黑色、棕色)。
黑色素生成的生物合成途径如下所示。
真黑素和褐黑素生物合成途径的前两步均由酪氨酸酶催化。酪氨酸酶是铜基酶，其催化酚类(如酪氨酸)的氧化，反过来这些酚类的氧化生成黑色素和其他色素。酪氨酸酶活性位点的两个铜原子与分子氧相互作用形成高度活性的化学中间体，该化学中间体然后氧化底物。酪氨酸酶也介导5,6-二羟基吲哚氧化成吲哚-5,6-醌。尽管酪氨酸酶在Tyr转变成多巴的过程起着一定的作用，但近来显示从酪氨酸形成多巴主要通过非酶途径进行。见Hearing et al.,From Melanocytes to melanoma:the progression tomalignancy2006Humana Press Inc.,NJ at p.581.
多巴醌可通过两种途径与半胱氨酸结合以生成苯并噻嗪和褐黑素：
多巴醌+半胱氨酸→5-S-半胱氨酰多巴→苯并噻嗪中间体→褐黑素
多巴醌+半胱氨酸→2-S-半胱氨酰多巴→苯并噻嗪中间体→褐黑素
或者，多巴胺能够转变成无色多巴色素(leucodopachrome)并按照另外两种途径生成真黑素：
多巴醌→无色多巴色素→多巴色素→5,6-二羟基吲哚-2-羧酸→醌→真黑素
多巴醌→无色多巴色素→多巴色素→5,6-二羟基吲哚→醌→真黑素
本发明意识到苯丙氨酸和酪氨酸在黑色素生成中的作用，并提供了包含多巴胺前体与姜黄素组合的组合物以促进人体皮肤黑色素的生成。本发明的组合物可能被用来提供皮肤着色而无太阳的有害影响。本发明的组合物可通过在皮肤病学可接受的载体中将多巴胺前体与姜黄素结合制备。
根据本发明，术语“皮肤”指的是皮肤的表皮层和真皮层。此处所用的术语“皮肤”是广义上的，意味着面部、身体和脖颈的皮肤。
适用于本发明的目的，术语“多巴胺前体”指的是苯丙氨酸、酪氨酸和/或N-乙酰基酪氨酸。
如文中所讨论的，苯丙氨酸是酪氨酸的前体。N-乙酰基酪氨酸是L-酪氨酸的乙酰化衍生物。普通的L-酪氨酸更不稳定而且也不易溶于水，这可能导致生物利用度降低。乙酰化增强了氨基酸的溶解性和稳定性，并因此是水基制剂所需的，而且也使得可穿透皮肤从而可与蛋白质相互作用。
多巴胺前体与姜黄素结合使用。姜黄素是流行的印度香料姜黄的主要类姜黄色素，其为姜科(Zingiberaceae)的一员。姜黄素起着自由基清除剂和抗氧化剂的作用，抑制脂质过氧化和氧化性DNA损伤。类姜黄色素诱导谷胱甘肽S-转移酶并且是细胞色素P450的有效抑制剂。
本发明中通过将姜黄素溶解在油包水乳液中增强其效果，认为该方法能增加其生物利用度。
不希望被任何理论束缚，据信本发明的制剂中姜黄素模拟通常与暴露于UV辐射相关的应激条件，刺激黑素细胞生成黑色素。多巴胺前体和姜黄素的协同组合上调黑色素的生成以提供美黑效果。而且，不像DHA，该化合物不与水反应，因此能够与角质层的内层和外层和活皮肤组织作用。
应当指出，通过使用不同比例的成分和/或包括增稠剂如树胶(gum)或其他形式的亲水胶体，这些成分可被配制成洗剂、乳膏剂或凝胶剂或喷雾剂。优选实施方案是洗剂。另一个可能的实施方案是可以细微喷雾喷洒到皮肤上的溶液。此处的洗剂、乳膏剂、凝胶剂和溶液指的是皮肤或皮肤病学可接受的载体，而且可通过本领域的普通技术人员熟知的传统技术配制得到。此处所用的术语“免晒美黑组合物”应当指施加于人皮肤的完整的产品，包括如此处所述的多巴胺前体、姜黄素、载体和任何佐剂、增稠剂、赋形剂等。
本发明的局部(topical)组合物可包含的附加成分常见于皮肤护理组合物和化妆品，例如染色剂、润肤剂、皮肤调节剂、乳化剂、保湿剂、防腐剂、抗氧化剂、香料、螯合剂等，条件是他们与该组合物的其它成分具有物理和化学相容性。
防腐剂包括但不限于，C1-C3烷基对羟基苯甲酸酯、山梨酸和苯氧基乙醇，典型地含量范围从约0.1重量%至约2.0重量%，基于总组合物的重量。优选的防腐剂是ISP’sOptiphenTMPlus，一种液体防腐制剂，其特征在于苯氧基乙醇、山梨酸和柔润基质的混合物。
润肤剂，典型地占总组合物的量的范围约0.01%至5%，包括但不限于，烃、脂肪酯、脂肪醇、矿物油、聚醚硅氧烷共聚物及它们的混合物。优选实施方案是角鲨烷、乳木果油和棕榈酸异丙酯。
保湿剂，典型地占总组合物的量的范围约0.1重量%至约5重量%，包括但不限于，多元醇如甘油、聚亚烷基二醇(例如，丁二醇、丙二醇、一缩二丙二醇、聚丙二醇和聚乙二醇)及其衍生物、亚烷基多元醇及其衍生物、山梨醇、羟基山梨醇、己二醇、(一缩)1,3-二丁二醇(1,3-dibutylene glycol)、1,2,6-己三醇，乙氧基化甘油、丙氧基化甘油和它们的混合物。优选的保湿剂是乳木果油。
乳化剂，典型地占该组合物的量的范围约0.5重量%至约10重量%，包括但不限于硬脂酸、鲸蜡醇、硬脂醇、硬脂醇聚醚2、硬脂醇聚醚20、丙烯酸酯/C10-30烷基丙烯酸酯交联聚合物、硅酮、二甲基乙醇胺(DMAE)、磷脂酰胆碱(PPC)和它们的混合物。优选的乳化剂是透明质酸钠、
(Amerchol公司销售的75%鲸蜡硬脂醇和25%乙氧基化鲸蜡硬脂醇的混合物)、Arlacel165(Croda Inc.销售的硬脂酸甘油酯和PEG-100硬脂酸酯)、硅酮(DowCorning200Fluid,350CST)、DMAE和Phosphlipon90G(Phospholipid GmbH出售的含10%脂肪酸的磷脂酰胆碱)。
螯合剂，典型地含量范围约0.01重量%至约2重量%，包括但不限于乙二胺四乙酸(EDTA)及其衍生物和盐、二羟乙基甘氨酸、酒石酸和它们的混合物。
抗氧化剂，占该组合物的量的典型范围约0.02重量%至约5重量%，包括但不限于丁基羟基甲苯(BHT)；维生素C和/或维生素C衍生物，如抗坏血酸的脂肪酸酯，尤其是抗坏血酸棕榈酸酯；丁基羟基茴香醚(BHA)；苯基-α-萘基胺；氢醌；没食子酸丙酯；去甲二氢愈创木酸；维生素E和/或维生素E衍生物，包括生育三烯酚和/或生育三烯酚衍生物；泛酸钙；绿茶提取物；混合多酚；和其任何的混合物。尤其优选的抗氧化剂是那些能够给皮肤提供额外益处的抗氧化剂，如绿茶提取物槲皮素。
缓冲剂在很多组合物中使用。本发明组合物的优选缓冲剂为酸性介质。缓冲剂的优选用量为使组合物的pH范围为约2.5至约6.0，更优选地从约3.0至约5.5，最优选地从约3.8至约5.0的量。典型地缓冲剂是常见于化妆品的化学和物理学稳定的试剂，且可包括也为辅助成分的化合物，如柠檬酸、苹果酸和羟乙酸缓冲剂。优选的缓冲剂为羟乙酸。
本发明的一些优选实施方案除多巴胺前体和姜黄素外含有至少一种其它辅助成分，其典型地占组合物的约0.05重量%至约10重量%范围。辅助成分包括但不限于以下的一种或多种：异硫氰酸酯(isothiocyanates)、咖啡因、维生素D3、硫辛酸；α-羟基酸如羟乙酸或乳酸；抗坏血酸及其衍生物，特别是抗坏血酸的脂肪酸酯；或生育三烯酚和生育三烯酚衍生物和富含生育三烯酚或生育三烯酚衍生物的维生素E组合物。优选的辅剂是羟乙酸、咖啡因和含有天冬氨酸镁、葡萄糖酸锌和葡萄糖酸铜的Seppic公司的SepitonicTMM3。
尤其优选的辅助成分是异硫氰酸酯。异硫氰酸酯是含硫的化合物。从植物获取的许多天然的异硫氰酸酯是由芥子油的酶转化生成的。在一个优选实施方案中，本发明使用绿芥末(wasabi mustard)或其提取物，例如从绿芥末获得的异硫氰酸甲硫基己酯。本发明的其它实施方案可能含有异硫氰酸苯酯。另一可能的实施方案可能包括莱菔硫烷，一种从十字花科蔬菜如花茎甘蓝中获得的异硫氰酸酯。异硫氰酸酯已显示抑制致癌作用和肿瘤发生，并且是癌症发展和增生的有用的化学预防剂。Talalay et al.,Sulforaphanemobilized cellular defenses that protect skin against damage by UV radiation,Proc Natl Acad Sci USA2007104(44):17500-17505。
也可使用在我们的以下美国专利中公开另外的成分和方法：5,376,361、5,409,693、5,545,398、5,554,647、5,574,063、5,643,586、5,709,868、5,879,690、6,051,244、6,191,121、6,296,861、6,437,004、6,979,459、7,037,512、7,226,608、和7,438,896；以上专利此处引入作为参考。
通常在本发明方法的实践中，局部组合物在预定的间隔局部施加于皮肤区域，如身体和面部区域，一般随着每次连续的应用会发现颜色逐渐发展。迄今为止，基于临床研究，尚未发生不良副作用。
本发明的一项优势是深色是在表皮的色素层产生的，而不像DHA仅仅是使死细胞层着色，因此颜色不会随着天然脱落过程而很快丢失。本发明的还一项优势是组合物是基于水的。常用于免晒美黑组合物的更刺激的溶剂是不需要的。因此该组合物更安全、更稳定而且无基于DHA的产品常伴有的不良气味。
下面的实施例进一步描述和证明本发明范围内的实施方案。所列出实施例仅为说明而非限制本发明，因为在不脱离本发明的精神和范围的情况下可能有许多变化。
实施例
实施例I和实施例II为通过常规混合技术将以下成分组合制备得到的水包油型乳剂。
实施例/成分实施例I实施例II
重量百分数
第1相
水 补足至100 补足至100
透明质酸钠 0.50 0.50
羟乙酸 0.25 0.50
Phospholipon90-G 0.50 0.50
第2相
棕榈酸异丙酯 3.00 3.00
Promulgen-D 3.50 3.50
Arlacel165 3.50 3.50
乳木果油-未漂白的 0.50 --
角鲨烷-橄榄色 0.50 0.50
DC Fluid200,350CST0.500.50
第3部分
二甲基乙醇胺(DMAE) 1.00 1.00
水 2.00 2.00
第4部分
L-酪氨酸 10.00 --
N-乙酰基酪氨酸 -- 10.00
咖啡因 0.10 1.00
维生素D3 0.10 0.10
姜黄素98% 2.00 2.00
苯丙氨酸 5.00 5.00
异氰硫酸苯酯 2.00 5.00
槲皮素60% -- 2.00
莱菔硫烷(Sulforafames) 0.20 --
倍半萜 0.10 --
第5部分
Sepitonic M3 2.00 2.00
Optiphen Plus0.500.50
配制：在适合的容器内，第2相成分在搅拌下分散到第1相成分中。混合物冷却至38-40℃并加入第3相。当温度达到约35℃时，加入第4相成分。生成的混合物匀化约30分钟。混合物彻底混合，如有必要加入第5相。
形成的洗剂的pH约为3.8至5.0，显示出良好的物理和化学稳定性、深色形成特性，并且可用于局部施加到人体皮肤以提供免晒美黑。
在实施例I和II的制剂有效性的预试验中，发现两种制剂均可有效地诱导免晒美黑，其中实施例I的制剂每天一次应用约4周后生成明显的皮肤变黑结果，实施例II的制剂每天一次应用约3周后生成明显的皮肤变黑结果。因此本发明包括通过给皮肤使用有效量的至少一种多巴胺前体和姜黄素而美黑皮肤的方法，其中姜黄素与所述的多巴胺前体协同作用向上调节黑色素的生成。
上述描述的目的是教导本领域的普通技术人员如何实施本发明，而并非详述本发明所有明显的修改和变化，对于阅读说明书的技术人员本发明将变得很清楚。然而，所有这些明显的修改和变化均包括在本发明的范围内，如以下权利要求所定义的。权利要求的目的是覆盖要求保护的组分和可有效的达到预期目的的任何顺序的步骤，除非具体的上下文另有指明。
Claims (19)
1.施用于皮肤的免晒美黑组合物，其包含：
协同黑色素上调组合，其由有效量的至少一种多巴胺前体和有效量的姜黄素组成，该多巴胺前体选自酪氨酸、N-乙酰基酪氨酸和苯丙氨酸；和
皮肤病学可接受的载体；
其中该多巴胺前体的含量为该美黑组合物的1重量％至30重量％；姜黄素的含量为该美黑组合物的0.05重量％至10重量％；以及
所述组合物还包含异硫氰酸苯酯，其中异硫氰酸苯酯的含量为该美黑组合物的0.5重量％至10.0重量％。
2.权利要求1的组合物，其中该多巴胺前体的含量为该美黑组合物的5重量％至20重量％。
3.权利要求2的组合物，其中该多巴胺前体的含量为该美黑组合物的10重量％至15重量％。
4.权利要求1的组合物，其中该多巴胺前体为N-乙酰基酪氨酸。
5.权利要求1的组合物，其中该多巴胺前体为N-乙酰基酪氨酸和苯丙氨酸的组合。
6.权利要求1的组合物，其中姜黄素的含量为该美黑组合物的1.0重量％至5重量％。
7.权利要求6的组合物，其中姜黄素的含量为该美黑组合物的2.0重量％。
8.权利要求1的组合物，其中异硫氰酸苯酯的含量为该美黑组合物的1.0重量％至8.0重量％。
9.权利要求8的组合物，其中异硫氰酸苯酯的含量为该美黑组合物的2.0重量％至5.0重量％。
10.权利要求1的组合物，其中皮肤病学可接受的载体包括一种或多种选自以下的试剂：透明质酸钠盐、磷脂酰胆碱、棕榈酸异丙酯、鲸蜡硬脂醇、单硬脂酸甘油酯、乳木果油、角鲨烷、硅酮和二甲基乙醇胺。
11.权利要求1的组合物，还包含一种或多种选自以下的试剂：α-羟基酸、咖啡因、维生素D3、槲皮素、莱菔硫烷，以及天冬氨酸镁、葡萄糖酸锌和葡萄糖酸铜的混合物。
12.权利要求1的组合物，其中该组合物的pH范围为2.5至6.0。
13.权利要求11的组合物，其中该组合物的pH范围为3.0至5.5。
14.权利要求13的组合物，其中该组合物的pH范围为3.8至5.0。
15.权利要求1的组合物，其中该组合物为洗剂。
16.免晒美黑组合物，其包含:
10重量％至15重量％的多巴胺前体；
1重量％至3重量％的姜黄素；和
4重量％至6重量％的异硫氰酸苯酯；
余量为水，其中所述的多巴胺前体选自酪氨酸、N-乙酰基酪氨酸、苯丙氨酸、和它们的混合物。
17.制备免晒美黑组合物的方法，该组合物包含水相、油相、含水二甲基乙醇胺混合物、多巴胺前体、姜黄素和防腐剂，该多巴胺前体选自酪氨酸、N-乙酰基酪氨酸和苯丙氨酸，其中该多巴胺前体的含量为该美黑组合物的1重量％至30重量％；姜黄素的含量为该美黑组合物的0.05重量％至10重量％；以及所述组合物还包含异硫氰酸苯酯，其中异硫氰酸苯酯的含量为该美黑组合物的0.5重量％至10.0重量％；
该方法包括以下步骤：
将水相加入油相；
将水相与油相混合；
冷却到38℃至40℃；
在38℃下加入二甲基乙醇胺混合物；
在35℃下，将多巴胺前体和姜黄素加入生成的混合物中；
匀化；
加入防腐剂；和
用水补足至100.00％。
18.美黑皮肤的方法，该方法包括向皮肤施用组合物，该组合物包含有效量的至少一种多巴胺前体和姜黄素，该多巴胺前体选自酪氨酸、N-乙酰基酪氨酸和苯丙氨酸，其中姜黄素与所述多巴胺前体协同作用以向上调节黑色素的生成，其中该多巴胺前体的含量为该美黑组合物的1重量％至30重量％；姜黄素的含量为该美黑组合物的0.05重量％至10重量％；以及所述组合物还包含异硫氰酸苯酯，其中异硫氰酸苯酯的含量为该美黑组合物的0.5重量％至10.0重量％。
19.权利要求18的方法，其中多巴胺前体存在的量为10重量％至15重量％而姜黄素存在的量为1.0重量％至5.0重量％。
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| US10434082B2 (en) | 2012-07-26 | 2019-10-08 | The William M. Yarbrough Foundation | Isothiocyanate functional compounds augmented with secondary antineoplastic medicaments and associated methods for treating neoplasms |
| US10434081B2 (en) | 2012-07-26 | 2019-10-08 | The William M. Yarbrough Foundation | Inhibitors of macrophage migration inhibitory factor |
| US10335387B2 (en) | 2012-07-26 | 2019-07-02 | The William M. Yarbrough Foundation | Method for treating infectious diseases with isothiocyanate functional compounds |
| US10441561B2 (en) | 2012-07-26 | 2019-10-15 | The William M. Yanbrough Foundation | Method for treating benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer |
| US20140234433A1 (en) * | 2013-02-15 | 2014-08-21 | Nicholas V. Perricone | Topical Composition for Stimulating Epidermis and Dermis Layers of the Skin |
| US9289374B2 (en) * | 2014-04-23 | 2016-03-22 | Lifevantage Corporation | Topical compositions and methods for reducing oxidative stress |
| US9969928B2 (en) * | 2014-07-02 | 2018-05-15 | Multi-Chem Group, Llc | Surfactant formulations and associated methods for reduced and delayed adsorption of the surfactant |
| FR3032351B1 (fr) * | 2015-02-05 | 2018-03-23 | Gelyma | Utilisation d'au moins un extrait de macralgue pour augmenter la synthese de melanine dans les melanocytes |
| CN111732951B (zh) * | 2020-07-06 | 2022-05-20 | 山西大学 | 一种氮掺杂绿色荧光碳量子点及其制备方法和应用 |
| US20230248849A1 (en) * | 2020-07-27 | 2023-08-10 | Board Of Regents, The University Of Texas System | Contrast agents for detection of enzyme activities based on melanin synthesis |
| CN112472818B (zh) * | 2020-11-16 | 2022-05-03 | 安徽农业大学 | 一种通过修饰天然黑色素作为载体的纳米材料及其制备方法和应用 |
| CN114159351B (zh) * | 2021-12-16 | 2023-08-04 | 四川大学 | 一种具有紫外防护功能的人造黑色素染发剂及其制备方法 |
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