CN1294896C - 干燥引起皮肤损伤的抑制剂或修复剂及其评价方法 - Google Patents

干燥引起皮肤损伤的抑制剂或修复剂及其评价方法 Download PDF

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CN1294896C
CN1294896C CNB018216110A CN01821611A CN1294896C CN 1294896 C CN1294896 C CN 1294896C CN B018216110 A CNB018216110 A CN B018216110A CN 01821611 A CN01821611 A CN 01821611A CN 1294896 C CN1294896 C CN 1294896C
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片桐千华
平尾哲二
藤田宏志
古贺信义
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Abstract

本发明提供一种皮肤外用剂，其中含有能够防止培养的人角化细胞暴露于气相引起的丝聚蛋白基因表达降低的物质，例如甜菜碱、多元醇、生药类或具有抗氧化作用的物质作为有效成分。

Description

干燥引起皮肤损伤的抑制剂或修复剂及其评价方法
技术领域
本发明涉及用于抑制或修复干燥引起的皮肤损伤(或者皮肤皲裂)的化妆品或皮肤科用制剂，以及这些制剂中含有的物质的评价方法。
背景技术
天然保湿因子(NMF)对于保持角质层的水分发挥着重要作用(Blank I.H.J.I.Dermatol.，18，433(1952)；Blank I.H.J.I.Dermatol.，21，259(1953))。有报道指出作为NMF主要成分的氨基酸通过来源于角质透明蛋白颗粒的丝聚蛋白的分解产生(ScottI.R.等，Biochem Biophys.Acta.，719，110-117(1982)；Horii I.等，J.Dermatol.，10，25-33(1983))。丝聚蛋白是317个氨基酸构成的蛋白质。明确作为NMF主要成分的氨基酸来源于丝聚蛋白以来，开始不断研究呈现干燥肌肤的病理与丝聚蛋白之间的相关性。近年来，已经逐步明确在老年性干皮病、特应性疾病等的干燥肌肤中，角质层中的氨基酸减少(Horii I.等，Br.J.Dermatol.，121，587-592(1989)；Tanaka M.等，Br.J.Dermatol.，139，618-621(1998))，而且丝聚蛋白的表达减少(Tezuka T.等，Dermatology，188，21-24(1994)；Seguchi T.等，Arch.Dermatol.Res.288，442-446(1996))。另外，由于环境干燥出现皮肤皲裂等皮肤问题也是众所周知的。
也许是基于这种情况，在FR2777185-A1中提出了一种处理皱纹用的组合物，其中将刺激丝聚蛋白合成的物质与其它活性物质组合，所述丝聚蛋白能够有利作用于保水能力的调节。但是，没有记载刺激丝聚蛋白合成的物质具体是何种物质。另外，在特开2000-26272号公报中记载了下述主旨，即，来源于白羽扇豆〔Lupinus albus〕种子粉末的蛋白质分解处理物具有增加人角化细胞的丝聚蛋白的mRNA、增加角质层厚度的作用。而且，在WO99/47117中记载了含有维生素B3化合物的组合物作为保湿剂发挥作用，而且能够增加选自丝聚蛋白、角蛋白和内披蛋白(インボクリン)的皮肤蛋白质的水平，提高角质层吸附或吸收水分的能力。
发明公开
如上所述，以前提出了提高丝聚蛋白产量、增加角质层厚度的物质，或者提高角质层吸收水分的能力的物质。但是，从参与丝聚蛋白的产生，并维持健康皮肤状态这样一种更广泛的观点来看，大概依然需要提供确认了有效性的物质或化合物。
本发明人对于人角化细胞中与干燥以及角质层水分量有关的因子进行了研究，结果发现丝聚蛋白的水平以及该基因的表达会由于干燥而降低。
而且，发现某种固定培养的人角化细胞暴露于气相时，丝聚蛋白基因的表达量显著降低，这种现象与上述干燥引起的皮肤损伤具有相关性。进而发现在使用该培养人角化细胞的培养体系中，能够显著抑制暴露于气相引起的丝聚蛋白基因表达量降低的物质，也能够抑制或修复上述干燥引起的皮肤损伤。
本发明就是基于上述发现完成的。
因此，按照本发明，提供一种皮肤外用剂，其中含有对于抑制人皮肤角质层的屏障功能降低来说足够量的能够显著抑制培养的人角化细胞暴露于气相引起的丝聚蛋白基因表达能力降低的物质，以及在化妆品和/或皮肤科制剂中允许使用的基质或添加剂。
按照本发明的优选方式，提供一种皮肤外用剂，其中上述能够显著抑制丝聚蛋白基因表达能力降低的物质是选自甜菜碱化合物及其衍生物、多元醇及其衍生物、生药、以及具有抗氧化作用的物质中的1种或2种以上。
另外，本发明还涉及能够显著抑制培养的人角化细胞暴露于气相引起的丝聚蛋白基因表达能力降低的物质在制备能够抑制人皮肤角质层的屏障功能和保湿功能降低的皮肤外用剂中的用途。
此外，本发明还涉及抑制或修复干燥引起的皮肤损伤的方法，其中包括将含有选自甜菜碱化合物及其衍生物、多元醇及其衍生物、生药、以及具有抗氧化作用的物质中的1种或2种以上的组合物涂敷在人皮肤上的步骤。
另外，按照本发明的另一种方式，提供用于评价化合物等是否能够防止干燥引起皮肤损伤的方法。该评价方法的特征在于，
(A)准备培养的人角化细胞，
(B)在被测物的存在下将该培养的人角化细胞暴露于气相后，检测该角化细胞中丝聚蛋白基因的表达能力，然后
(C)将检测出的丝聚蛋白基因的表达能力与对照相比较，以表达能力的大小作为抑制这种皮肤损伤的能力的指标。
附图说明
图1是表示培养的人角化细胞由于干燥(暴露于气相)引起丝聚蛋白水平相对经时变化的图。用试行n＝4～5的平均±SEM值表示。另外，**表示p＜0.01。
图2是表示培养的人角化细胞由于干燥(暴露于气相)引起丝聚蛋白基因表达水平经时变化的图。用试行n＝4～6的平均±SEM值表示。另外，**表示p＜0.01，*表示p＜0.05。
图3是表示甘油抑制培养的人角化细胞由于干燥(暴露于气相)引起丝聚蛋白水平降低的效果的图。成对的条形图中右侧表示在10％甘油存在下的培养例(左侧为对照)。用试行n＝3～6的平均±SEM值表示。另外，**表示p＜0.01，*表示p＜0.05。
图4是表示甘油和三甲基甘氨酸对培养的人角化细胞由于干燥引起丝聚蛋白基因表达降低的效果的图。用试行n＝3的平均±SEM值表示。另外，**表示p＜0.01。
图5是除了使用生药作为药物以外，具有与图4相同含义的图。另外，各药物浓度为干燥残留物浓度0.0025％。另外，n＝3，*表示p＜0.05，**表示p＜0.01，***表示p＜0.001。
图6是除了分别以1mM的浓度使用抗坏血酸和谷胱甘肽作为药物以外，具有与图4相同含义的图。另外，***表示p＜0.001，**表示p＜0.01。
图7是除了使用亚牛磺酸作为药物以外，具有与图4相同含义的图。*表示p＜0.05。
发明的最佳实施方式
本发明中所说的“能够显著抑制培养的人角化细胞暴露于气相引起的丝聚蛋白基因表达能力降低”是指，采用下述评价方法进行评价时，与对照(不含被测物质)体系中上述表达能力降低相比，在含有被测物质的体系中能够在统计学上显著抑制上述表达能力的降低。
另外，本发明中所说的“皮肤损伤”是指皮肤皲裂或皮肤上形成小皱纹、皮肤的柔软性降低等认为在健康皮肤上不会出现的各种形式的变化、皮肤问题。
在本发明中，只要是能够显著抑制上述表达能力降低的物质，均包括在本发明的外用剂、用途和方法的有效成分中。但是，作为这种有效成分的具体实例，可以例举甜菜碱化合物及其衍生物、多元醇及其衍生物、生药、以及具有抗氧化作用的物质。
“甜菜碱化合物及其衍生物”只要是符合本发明目的的物质，可以是甜菜碱(也称为甘氨酸甜菜碱)及其衍生物、以及相应的磺基甜菜碱(甜菜碱的羧基替换成磺基)的两性离子化合物中包含的任意一种化合物。作为这种衍生物的代表性物质，可以例举甘氨酸甜菜碱的1至3个N-甲基用其它可以带有支链的饱和或不饱和烃链或者下式(CnH2nCONH(CH2)m -)(式中，m和n独立地为1～30的整数)表示的用酰胺键中断的该烃链代替，或者改变季铵基与羧基或磺基之间的烃链长度(例如碳原子数2～6)，或者具有多个甜菜碱残基作为侧基的聚合物。另外，这些物质也可以是环状化合物。对此没有限定，作为这种衍生物的具体实例，除上述物质以外，还可以例举γ-丁内铵盐、癸基甜菜碱、月桂基甜菜碱、肉豆蔻基甜菜碱、十六烷基甜菜碱、硬脂基甜菜碱、二十二烷基甜菜碱、月桂酰氨基丙基甜菜碱、油酰氨基丙基甜菜碱、棕榈酰氨基丙基甜菜碱、月桂基磺基甜菜碱、可可磺基甜菜碱、聚(甲基丙烯酰氧基乙基甜菜碱)、聚(甲基丙烯酰氧基乙基甜菜碱-共-甲基丙烯酸2-羟乙酯)等。优选甘氨酸甜菜碱、磺基甜菜碱、聚(甲基丙烯酰氧基乙基甜菜碱)、聚(甲基丙烯酰氧基乙基甜菜碱-共-甲基丙烯酸2-羟乙酯)。
“多元醇及其衍生物”可以例举1分子中具有2个以上羟基的化合物及其衍生物，例如氧化乙烯加成物等。作为所述多元醇的具体实例，例如甘油、1，3-丙二醇、2-甲基-1，3-丙二醇、1，4-丁二醇、1，5-戊二醇、二甘油、赤藓醇、葡糖酸、1，2，6-己三醇、肌醇、乳糖醇、麦芽糖醇、甘露糖醇、木糖醇等。特别优选组合使用甘油和以木糖醇为首的糖醇。
“生药”是指作为药品或者民间药或其原料，对来源于植物的素材进行干燥、切断、粉碎或提取等操作得到的物质，只要遵从本发明的目的，不问植物的科或属。对此没有限定，具体而言作为生药，可以例举菊科(Compositae)的酒神菊属(Baccharis)植物，特别是来源于Baccharis genistelloids的生药carqueja(南美)，Achyrocline属植物，特别是来源于Achyrocline satureoides的生药macelamista(南美)，以及蓍草属(Achillea)植物，特别是来源于千叶蕃(Achillea millefolium L.)的生药千叶蕃；唇形科(Labiatae)的百里香属(Thymus)植物，特别是来源于百里香(Thymusserphyllum Linne subsp.serphyllum)的生药百里香提取物，牛至属(Origanum)植物，特别是来源于马郁兰(Origanum majorana L.)的生药マジヨラム提取物，黄芩属(Scutellaria)植物，特别是来源于黄芩(Scutellaria baicalensis Georgi)的生药黄芩，以及熏衣草属(Lavandula)植物，特别是来源于熏衣草(Lavandulaofficinalls)的生药熏衣草油；蔷薇科(Rosaceae)的蔷薇属(Rosa)植物，特别是来源于Rosa roxburghii的生药イザヨウバラ果实，以及李属(Prunus)植物，特别是来源于サトザクラ(Prunus lannesiana(Corr.)Wilson var.Spciosa(Koidz)Makino)的生药サクラリ-フ提取物；金镂梅科(Hamamelidaceae)的金缕梅属(Hamamelis)植物，特别是来源于北美金镂梅(Hamamelis virginiana L.)的生药金镂梅；鹿蹄草科(Pyrolaceae)的鹿蹄草属(Pyrola)植物，特别是来源于鹿蹄草(Pyrola japonicus Klenze)的生药鹿蹄草；以及豆科(Leguminosae)的Eysenhardtia属植物，特别是来源于Eysenhardtia polistachya的生药palo azul(南美)等。虽然对此没有限定，但是优选的生药为生药palo azul、生药macelamista和生药carqueja。
“具有抗氧化作用的物质”只要对皮肤没有不良影响，并能够实现本发明目的，可以是任何一种化合物或物质(混合物、组合物等)。基于不会对皮肤产生不良影响的观点，作为具体的物质，可以例举包括在化妆品领域已经作为抗氧化剂使用或者提议作为抗氧化剂使用的物质的化合物或物质。
作为这种化合物，没有限定，可以例举抗坏血酸及其盐或衍生物。作为盐或衍生物，例如抗坏血酸镁、抗坏血酸钠等，抗坏血酸烷基酯、抗坏血酸磷酸酯、抗坏血酸硫酸酯、抗坏血酸糖苷等抗坏血酸衍生物。更具体地说，作为抗坏血酸烷基酯，例如棕榈酸抗坏血酸酯、异棕榈酸抗坏血酸酯、二棕榈酸抗坏血酸酯、二异棕榈酸抗坏血酸酯、硬脂酸抗坏血酸酯、异硬脂酸抗坏血酸酯、二硬脂酸抗坏血酸酯、肉豆蔻酸抗坏血酸酯、异肉豆蔻酸抗坏血酸酯、二肉豆蔻酸抗坏血酸酯、二异肉豆蔻酸抗坏血酸酯、2-乙基己酸抗坏血酸酯、二(2-乙基己酸)抗坏血酸酯、油酸抗坏血酸酯、二油酸抗坏血酸酯等，作为其它衍生物，例如抗坏血酸多肽、磷酸抗坏血酸镁、甲基甲硅烷醇抗坏血酸酯、磷酸抗坏血酸生育酚钾等。
而且，关于生育酚及其衍生物，作为该衍生物没有限定，可以例举醋酸生育酚、亚油酸生育酚、烟酸生育酚、琥珀酸生育酚等生育酚酯，以及トコフエレス-5、トコフエレス-10、トコフエレス-12等生育酚的氧化乙烯加成物。另外，还可以例举含有含硫氨基酸的化合物(包括含硫氨基酸本身)及其中间代谢物，例如乙酰基半胱氨酸、蛋氨酸、半胱氨酸、高半胱氨酸、谷胱甘肽、亚牛磺酸、半胱亚磺酸、磺基丙氨酸、硫代半胱氨酸、牛磺酸、黎豆氨酸、胱硫醚、S-烯丙基半胱氨酸、蘑菇香精、乙硫氨酸等。
其中，亚牛磺酸在包括人在内的多种哺乳动物的主要脏器，例如心脏、脑、肝脏等中含有。另外，也没有报道对皮肤的刺激、搔痒、斑疹等副作用，是安全性非常优良的氨基乙基化合物。另外，亚牛磺酸通常可以由半胱氨酸等能够获得的硫化合物按照公知的方法制备后使用，也可以使用市售品。因此，本发明人等更多地规划了亚牛磺酸的使用。
按照本发明，上述有效成分可以将以上作为优选物质例举的生药与其它有效成分组合使用，更优选将作为生药的palo azul与甘油以及碳原子数4～6的糖醇中任意一种组合使用，将作为生药的palo azul与甘油以及谷胱甘肽或亚牛磺酸组合使用，将作为生药的生药palo azul与甘油以及抗坏血酸组合使用，或者将作为生药的生药palo azul与甘油以及甜菜碱化合物或其衍生物组合使用。另一方面，甘油以及碳原子数4～6的糖醇中任意一种与以上作为具体物质例举的生药，特别是生药carqueja(南美)、生药macelamista(南美)和/或生药palo azul(南美)的组合也是组合使用有效成分时优选的方式。
另外，以上药物的配制可以按照其自身公知的方法，例如“广川药用植物大事典，木岛正夫等编辑，昭和55年，株式会社广川书店发行”记载的方法进行。
本发明的外用剂中，除上述有效成分以外，也可以含有化妆品和/或皮肤科用制剂中常用的基质或添加剂，或者其它有效成分。
本发明的外用剂中，作为有效成分的甜菜碱化合物、多元醇类或具有抗氧化作用的物质相对于外用剂的总重量可以是0.0001～20重量％，优选0.01～1.0重量％。另外，生药由于有效成分含量根据其剂型发生改变，因此不能限定，但相对于制剂总量可以是0.0001～20重量％(按干燥物换算，约5×10-7～2×10-1重量％)，优选0.01～1.0重量％(按干燥物换算，约5×10-5～5×10-3重量％)。不管哪种有效成分，对于其特有的使用方式，只要以按照下述试验方法或评价方法得到的结果为基础，进一步考察志愿者试验性地实际使用的结果等，皮肤科领域的专家能够容易地确定上述有效成分发挥效力的最适用量。
本发明的外用剂作为化妆品、药品、保健品适用于皮肤，因此其剂型也可以采取水溶液系、可溶化系、乳化系、粉末系、凝胶系、软膏系、霜剂、水-油双相系、水-油-粉末三相系等广泛的形态。也就是说，如果是基础化妆品，适用于洗面产品、化妆水、乳液、面霜、凝胶、精华素(美容液)、美容涂敷剂(pack)、面膜等形态，在上述多种剂型中可以广泛适用。作为彩妆化妆品，可以广泛适用于粉底等形态。而且，如果是药品或保健品，可以广泛适用于各种软膏等形态。而且，本发明皮肤外用剂可以采取的形态并不受这些剂型和形态的限制。
上述基质成分可以根据这些剂型和形态进行选择，而且作为基质成分或添加剂，可以例举水、低级烷醇、液体油脂、固体油脂、蜡类、酯油、烃油、硅氧烷树脂、硅氧烷、阴离子表面活性剂、阴离子表面活性剂、阳离子表面活性剂、两性表面活性剂、非离子表面活性剂、低级烷醇、甾醇类、水溶性高分子、金属离子多价螯合剂、中和剂、pH调节剂、抗菌剂、香料、色素等。
以上所述的外用剂可以通过直接给志愿者适用确认功效，也可以在此之前，按照作为本发明另一种方式的评价物质是否能够抑制干燥引起皮肤损伤的方法进行确认。
所述评价方法中使用的人角化细胞，只要通过在被测物质存在下和不存在下分别进行培养，能够显著识别丝聚蛋白的量和基因表达量的变化，可以是任何细胞。但是，优选使用由来源于人表皮的正常细胞以及作为供养层(支持细胞)的来源于小鼠的3T3细胞(ATCC CRL-1658)构成的培养细胞系。这些细胞系例如可以按照Rheinwald等，Cell 6，331-344(1975)记载的方法进行制作，即用适当的培养皿培养3T3细胞，用丝裂霉素C进行处理，形成支持细胞层后，在该层上接种人正常角化细胞，例如在95％空气-5％二氧化碳环境中，在37℃下培养至铺满。
通常，在被测物质不存在的条件下进行培养的***(对照)优选与在被测物质存在的条件下培养的***(试验***)平行地进行处理。也可以预先在被测物质不存在的各种条件下进行培养，然后得到暴露于气相后丝聚蛋白的量和丝聚蛋白基因的表达量的值，以这些值作为对照。
另外，优选在培养的人角化细胞达到铺满后将被测物质添加到试验***中，直接进行短时间(例如30分钟)温育的方式。
这样培养的人角化细胞的气相暴露优选在除去培养基后，在例如95％空气-5％二氧化碳环境中，37℃下温育进行。这种气相暴露通常可以在约6小时内结束。
这样进行了气相暴露的培养人角化细胞按照丝聚蛋白量或丝聚蛋白基因表达量本身公知的测定方法，能够评价人角化细胞由于气相暴露受到损伤的程度或者被测物对该损伤的效力。这种评价方法对于筛选能够防止皮肤损伤的更有效物质有用，所述皮肤损伤是干燥引起的伴有体内人角化细胞的丝聚蛋白降低的皮肤损伤。
以下结合具体实例进一步说明本发明，但是并不要用这些实例限制本发明。在说明中使用的百分比只要没有特别的说明，均为重量标准。
丝聚蛋白基因表达量的测定试验：
(1)培养细胞
使用来源于人表皮的正常角化细胞以及来源于小鼠的3T3细胞。
(2)培养细胞用培养基
培养基在DMEM-Ham’s F12(3∶1)中含有氢化可的松、霍乱肠毒素、上皮增殖因子、胰岛素和10％FBS。
(3)培养
按照Rheinwald等，Cell 6，331-344(1975)记载的方法培养。
其概要如下所述。用丝裂霉素C处理3T3细胞，作为供养层(支持细胞)使用。将人正常角化细胞1×105个细胞接种在丝裂霉素C处理后的3T3细胞上，在95％空气-5％二氧化碳环境中，37℃下培养至铺满。除去培养上清液，进行气相暴露。另外，各被测物在进行气相暴露30分钟前添加，在37℃下进行培养。以未添加被测物的作为对照。气相暴露在37℃下进行0～6小时。
(4)丝聚蛋白量的测定
在上述培养***中，添加各被测物后，由气相暴露一定时间的细胞提取蛋白质。按照常规方法，通过Western印迹定量丝聚蛋白或丝聚蛋白前体(前丝聚蛋白)。其概要如下所述。对于提取的蛋白质用SDS-PAGE进行电泳后，复制到PDVF膜上，使用对丝聚蛋白特异的小鼠单克隆抗体(抗人丝聚蛋白单克隆抗体，anti-HUMAN Filaggrin MAb)作为一次抗体进行抗原-抗体反应。然后，使用通过辣根过氧化物酶(Horseradish peroxidase)或碱性磷酸酶(Alkalinephosphatase)标记的抗体作为二次抗体进行抗原-抗体反应。反应后，通过使用与标记酶对应的色原基质进行酶反应的显色法或者化学显色法进行测定。谱带的定量使用NIH图像(解析程序)进行。
(5)丝聚蛋白基因表达量的测定
在上述培养***中添加各被测物后，采用AGPC法由气相暴露一定时间的细胞提取RNA。对于这些RNA，如下所述进行RT-PCR。以McKinley-Grant L.J.等，Proc.Natl.Acad.Sci.U.S.A.，86，4848-4852(1989)报道的丝聚蛋白的碱基序列为基础，制作对丝聚蛋白特异的引物。RT-PCR是将mRNA用反转录酶一次转变成cDNA，以其作为模板，使用上述引物进行聚合酶反应(公知的反应)，测定丝聚蛋白的mRNA。PCR产物用琼脂糖凝胶进行电泳，将电泳后的凝胶浸渍于溴乙锭溶液中后，测定DNA。DNA谱带的定量使用NIH图像(解析程序)进行。补正使用甘油醛-3-磷酸脱氢酶(G3PDH)进行。
(6)结果
(6-1)将人角化细胞暴露于气相时丝聚蛋白量的经时变化如图1所示。根据图可以得知，人角化细胞的丝聚蛋白由于干燥显著降低。
(6-2)通过上述气相暴露，人角化细胞的丝聚蛋白基因表达量的经时变化如图2所示。根据图可以得知，人角化细胞的丝聚蛋白基因表达由于干燥显著降低。另外，其降低在比较短的时间内出现。
(6-3)通过有无向培养***添加该样品(10％甘油)得到的丝聚蛋白量评价对于人角化细胞由于暴露于气相(干燥刺激)对丝聚蛋白量的损伤的抑制作用。结果如图3所示。
(6-4)通过有无向培养***添加该样品(甘油和三甲基甘氨酸)得到的丝聚蛋白基因表达量评价对于人角化细胞由于暴露于气相(干燥刺激)使丝聚蛋白基因表达降低的损伤的抑制作用。结果如图4所示。
(6-5)通过有无向培养***添加生药提取物得到的丝聚蛋白基因表达量评价对于人角化细胞由于干燥使丝聚蛋白基因表达降低的损伤的抑制作用。结果如图5所示。
(6-6)通过有无向培养***添加抗坏血酸和谷胱甘肽得到的丝聚蛋白基因表达量评价对于人角化细胞由于干燥使丝聚蛋白基因表达降低的损伤的抑制作用。结果如图6所示。
(6-7)对于人角化细胞由于干燥使丝聚蛋白基因表达降低的损伤的抑制作用，即，有无向培养***添加亚牛磺酸得到的丝聚蛋白基因表达量的变化如图7所示。同时也显示出浓度依赖性。
(6-8)对于培养的人角化细胞由于干燥引起丝聚蛋白基因表达降低有效的其它有效成分以及有效成分组合的效力如下述表1和表2所示。表中，以干燥前的基因表达为100％，以干燥后的基因表达为0％，用添加药物产生的基因表达降低抑制率表示。表1中，有效成分以提取物浓度0.5％添加。另外，在表2中，使用其中所示的有效成分和浓度(重量％)的组合物进行试验。
                表1
  生药   恢复率(％)
  千叶蕃   41.9
  マジヨラム   30.8
  百里香提取物   19.9
  鹿蹄草   13.0
  熏衣草   8.6
  金镂梅   37.4
  黄芩水   65.0
  サクラリ-フ   30.8
  イザヨイバラ果实   53.1
                               表2
  被测物质   丝聚蛋白基因表达相对值(％)
平均 标准误差   恢复率(％)
  未处理   100   6
  仅干燥刺激   47   4
  0.025％palo azul提取物   60   6   24.5
  0.15％甘油   51   13   7.5
  0.30％甘油   79   7   60.4
  0.15％木糖醇   50   23   5.7
  0.30％木糖醇   67   16   37.7
  0.15％甘油+0.15％木糖醇   78   14   58.5
  0.025％palo azul提取物+0.15％甘油+0.15％木糖醇 94 5 88.7
另外，上述恢复率(％)表示通过添加各种被测物质，恢复到未给予干燥刺激的未处理组中丝聚蛋白基因表达水平的何种程度。
由这些图和表可以确认，本发明的制剂能够显著抑制人角化细胞由于干燥导致的角质层水分量降低，显著抑制以保持角质层水分所必需的氨基酸作为原料的丝聚蛋白量和基因表达的降低。
以下，列出本发明制剂的配方例。均可以按照常规方法配制。另外，制剂中各成分的含量只要没有特别的说明，均表示重量％。
配方例1(面霜)
二十二烷醇                                                  1.0
硬脂醇                                                      2.0
角鲨烷                                                      10.0
四辛酸季戊四醇酯                                            5.0
羊毛脂                                                      5.0
对羟基苯甲酸酯                                              0.3
聚氧乙烯二十二烷醇                                          1.0
甘油                                                        10.0
生药提取物(生药carqueja)                                    0.2
乙酰基透明质酸钠                                            0.1
蒸馏水                                                      余量
配方例2(面霜)
角鲨烷                                                      10.0
肉豆蔻酸异丙酯                                              20.0
十甲基环戊烷己烷                                            35.0
烷基改性羧基乙烯基聚合物                                    0.05
脱水山梨醇单油酸酯                                          5.0
一缩二丙二醇                                                3.0
生药提取物(生药macelamista)                                 1.0
蒸馏水                                                      余量
配方例3(面霜)
液体石蜡                                                    10.0
八甲基环四硅氧烷                                            5.0
1，3-丁二醇                                                 10.0
甘油                                                      3.0
抗坏血酸衍生物                                            3.0
三甲基甘氨酸                                              0.5
羧基乙烯基聚合物                                          0.15
黄原胶                                                    0.25
硬脂酸                                                    1.5
鲸蜡醇                                                    0.5
聚氧乙烯(10)单油酸酯                                      1.0
硬脂酸单甘油酯                                            1.0
乙醇                                                      3.0
香料                                                      适量
蒸馏水                                                    余量
配方例4(面霜)
鲸蜡硬脂醇(セトステアリルアルコ-ル)                       3.5
角鲨烷                                                    20.0
蜂蜡                                                      3.0
羊毛脂                                                    5.0
对羟基苯甲酸酯                                            0.3
聚氧乙烯(20)脱水山梨醇单棕榈酸酯                          2.0
硬脂酸单甘油酯                                            2.0
生药提取液(生药palo azul)                                 2.0
维生素A                                                   2.0
香料                                                      适量
蒸馏水                                                    余量
配方例5(面霜)
滑石                                                      3.0
二氧化钛                                                  5.0
红氧化铁                                                  0.5
黄氧化铁                                                  1.4
黑氧化铁                                                  1.0
单硬脂酸聚氧乙烯脱水山梨醇                                 0.9
三乙醇胺                                                   1.0
丙二醇                                                     5.0
生药提取物(或者三甲基甘氨酸或新海藻糖)                     1.0
硬脂酸                                                     2.2
异十六烷醇                                                 7.0
硬脂酸单甘油酯                                             2.0
羊毛脂                                                     2.0
石蜡                                                       8.0
对羟基苯甲酸酯                                             适量
香料                                                       适量
配方例6(面霜)
液体石蜡                                                   5.0
凡士林                                                     2.0
聚甲基硅氧烷                                               1.0
硬脂醇                                                     2.0
二十二烷醇                                                 2.0
硬化油                                                     1.0
角鲨烷                                                     5.0
硬脂酸                                                     2.0
2-乙基己酸十六烷基酯                                       4.0
自身乳化型单硬脂酸甘油酯                                   2.0
4-叔-4’-甲氧基苯甲酰基甲烷                                0.1
澳洲坚果油(マカデミアナツツ油)                             1.0
偏磷酸钠                                                   0.02
胎盘提取物                                                 1.0
对羟基苯甲酸酯                                             适量
色素                                                       适量
甘油                                                       5.0
一缩二丙二醇                                               5.0
1，3-丁二醇                                                3.0
植物提取液(生药palo azul)                                  1.0
植物提取液(植物イザヨウバラ果实)                           0.5
蒸馏水                                                     余量
配方例7(面霜)
聚甲基硅氧烷                                               2.0
十甲基环戊硅氧烷                                           10.0
聚氧乙烯·聚甲基硅氧烷共聚物                               3.0
二甲基二硬脂基铵锂锰脱                                     3.0
政府规定改性醇                                             2.0
甘油                                                       5.0
一缩二丙二醇                                               3.0
聚乙二醇                                                   1.0
偏磷酸钠                                                   0.05
植物提取液(生药palo azul)                                  2.0
植物提取液(生药サクラリ-フ提取物)                          1.0
对羟基苯甲酸酯                                             适量
乙二胺四乙酸三钠                                           0.05
色素                                                       适量
香料                                                       适量
蒸馏水                                                     余量
配方例8(面霜)
聚甲基硅氧烷                                               5.0
十甲基环戊硅氧烷                                           10.0
聚氧乙烯·聚甲基硅氧烷共聚物                               0.5
聚(氧乙烯·氧丙烯)聚甲基硅氧烷共聚物                       0.5
球状聚丙烯酸烷基酯                                         2.0
甘油                                                       5.0
植物提取液(生药palo azul)                                  0.05
植物提取液(生药黄芩水SE)                                   2.0
1，3-丁二醇                                                5.0
氯化钠                                                      2.0
偏磷酸钠                                                    0.05
苯氧基乙醇                                                  适量
乙二胺四乙酸三钠                                            0.05
色素                                                        适量
香料                                                        适量
蒸馏水                                                      余量
配方例9(面霜)
聚甲基硅氧烷                                                5.0
十甲基环戊硅氧烷                                            15.0
二十二烷醇                                                  1.0
鲨肝醇                                                      1.0
白蜡                                                        2.0
三(2-乙基己酸)甘油酯                                        2.0
辛酸十六烷基酯                                              2.0
甘油                                                        4.0
植物提取液(生药palo azul)                                   0.1
植物提取液(生药金镂梅)                                      0.2
一缩二丙二醇                                                6.0
乙二胺四乙酸三钠                                            0.05
对羟基苯甲酸酯                                              适量
香料                                                        适量
蒸馏水                                                      余量
配方例10(面霜)
凡士林                                                      1.0
聚甲基硅氧烷                                                2.0
角鲨烷                                                      2.0
甘油                                                        5.0
一缩二丙二醇                                                3.0
1，3-丁二醇                                                 3.0
聚乙二醇                                                      2.0
植物提取液(生药palo azul)                                     2.0
植物提取液(生药黄芩水SE)                                      1.0
氢氧化钾                                                      0.25
偏磷酸钠                                                      0.05
色素                                                          适量
对羟基苯甲酸酯                                                适量
黄原胶                                                        0.1
丙烯酸·甲基丙烯酸烷基酯共聚物                                0.1
羧基乙烯基聚合物                                              0.5
蒸馏水                                                        余量
配方例11(面霜)
液体石蜡                                                      8.0
凡士林                                                        2.0
聚甲基硅氧烷                                                  2.0
硬脂醇                                                        2.0
二十二烷醇                                                    2.0
四辛酸季戊四醇酯                                              3.0
异硬脂酸聚氧乙烯甘油酯                                        2.0
单硬脂酸聚氧乙烯甘油酯                                        2.0
亲油型单硬脂酸甘油酯                                          2.0
4-叔丁基-4’-甲氧基苯甲酰基甲烷                               0.05
对甲氧基桂皮酸2-乙基己酯                                      0.5
羟乙基纤维素                                                  0.5
羧基乙烯基聚合物                                              0.04
乙二胺四乙酸三钠                                              0.05
植物提取液(生药palo azul)                                     1.0
植物提取液(生药熏衣草油)                                      1.0
甘油                                                          5.0
一缩二丙二醇                                                  5.0
香料                                                          适量
对羟基苯甲酸酯                                                适量
蒸馏水                                                        余量
配方例12(面霜)
凡士林                                                        2.0
聚甲基硅氧烷                                                  2.0
二十二烷醇                                                    0.5
鲨肝醇                                                        0.5
霍霍巴油                                                      3.0
角鲨烷                                                        2.0
四辛酸季戊四醇酯                                              1.0
聚氧乙烯硬化蓖麻油                                            0.5
政府规定改性醇                                                5.0
植物提取液(生药palo azul)                                     1.5
植物提取液(生药鹿蹄草)                                        0.5
甘油                                                          5.0
1，3-丁二醇                                                   5.0
聚乙二醇                                                      2.0
氢氧化钾                                                      0.09
对羟基苯甲酸酯                                                适量
乙二胺四乙酸三钠                                              0.05
色素                                                          适量
黄原胶                                                        0.05
偏磷酸钠                                                      0.05
羧基乙烯基聚合物                                              0.25
蒸馏水                                                        余量
配方例13(面霜)
液体石蜡                                                      10.0
聚甲基硅氧烷                                                  5.0
角鲨烷                                                        5.0
四(2-乙基己酸)季戊四醇酯                                      5.0
植物提取液(生药palo azul)                                       0.05
植物提取液(生药百里香提取物)                                    2.0
1，3-丁二醇                                                     5.0
赤藓醇                                                          5.0
聚乙二醇                                                        5.0
氢氧化钾                                                        0.1
偏磷酸钠                                                        0.05
对羟基苯甲酸酯                                                  适量
苯氧基乙醇                                                      适量
羟丙基甲基纤维素                                                0.2
聚乙烯醇                                                        0.2
羧基乙烯基聚合物                                                0.1
丙烯酸·甲基丙烯酸烷基酯共聚物                                  0.1
色素                                                            适量
香料                                                            适量
蒸馏水                                                          余量
配方例14(面霜)
液体石蜡                                                        5.0
凡士林                                                          5.0
地蜡                                                            2.0
角鲨烷                                                          15.0
蜂蜡                                                            0.5
二异硬脂酸聚甘油酯                                              5.0
植物提取液(生药palo azul)                                       0.05
植物提取液(生药マジヨラム提取物)                                1.0
聚乙烯粉末                                                      适量
丙二醇                                                          适量
谷氨酸钠                                                        适量
丝氨酸                                                          适量
甘氨酸                                                          适量
尿囊素                                                          适量
香料                                                      适量
氯化钠                                                    适量
蒸馏水                                                    余量
配方例15(面霜)
烯烃低聚物                                                8.0
凡士林                                                    5.0
地蜡                                                      4.0
角鲨烷                                                    18.0
蜂蜡                                                      1.0
二异硬脂酸聚甘油酯                                        5.0
丝氨酸                                                    适量
偏磷酸钠                                                  0.05
植物提取液(生药palo azul)                                 0.5
植物提取液(生药千叶蕃)                                    1.0
甘油                                                      2.0
1，3-丁二醇                                               5.0
氯化钠                                                    适量
聚乙烯粉末                                                0.1
对羟基苯甲酸酯                                            适量
香料                                                      适量
色素                                                      适量
蒸馏水                                                    余量
配方例16(面霜)
烯烃低聚物                                                6.0
十甲基环戊烷硅氧烷                                        18.0
聚氧乙烯·聚甲基硅氧烷共聚物                              2.0
聚甲基苯基硅氧烷                                          1.0
硬脂醇                                                    0.5
二十二烷醇                                                1.3
澳洲坚果油脂肪酸植物甾醇酯                                0.3
N-硬脂酰基-L-谷氨酸钠                                          0.9
二甲基二硬脂基铵锂蒙脱石                                       0.8
甘油                                                           4.0
植物提取液(生药palo azul)                                      5.0
1，3-丁二醇                                                    5.0
氯化钠                                                         0.05
对羟基苯甲酸酯                                                 适量
苯氧基乙醇                                                     适量
色素                                                           适量
香料                                                           适量
蒸馏水                                                         余量
配方例17(乳液)
聚甲基硅氧烷                                                   2.0
十甲基环戊烷硅氧烷                                             2.0
角鲨烷                                                         2.0
政府规定改性醇                                                 5.0
甘油                                                           5.0
1，3-丁二醇                                                    5.0
聚氧乙烯甲基葡糖苷                                             5.0
植物提取液(生药palo azul)                                      0.02
氢氧化钾                                                       0.1
偏磷酸钠                                                       0.05
对羟基苯甲酸酯                                                 适量
色素                                                           适量
羧基乙烯基聚合物                                               0.15
丙烯酸·甲基丙烯酸烷基酯共聚物                                 0.1
蒸馏水                                                         余量
配方例18(乳液)
聚甲基硅氧烷                                                   2.0
二十二烷醇                                                     0.5
鲨肝醇                                               0.5
硬化油                                               3.0
角鲨烷                                               6.0
四(2-乙基己酸)季戊四醇酯                             2.0
异硬脂酸聚氧乙烯甘油酯                               1.5
单硬脂酸聚氧乙烯甘油酯                               1.5
甘油                                                 5.0
1，3-丁二醇                                          5.0
赤藓醇                                               3.0
植物提取液(生药palo azul)                            0.05
氢氧化钾                                             0.05
偏磷酸钠                                             0.03
苯氧基乙醇                                           适量
羧基乙烯基聚合物                                     0.12
蒸馏水                                               余量
配方例19(乳液)
液体石蜡                                             8.0
凡士林                                               3.0
十甲基环戊硅氧烷                                     1.0
二十二烷醇                                           2.0
霍霍巴油                                             1.0
硬脂酸                                               1.0
二十二烷酸                                           0.5
四(2-乙基己酸)季戊四醇酯                             3.0
 2-乙基己酸十六烷基酯                                3.0
自身乳化型单硬脂酸甘油酯                             1.5
对甲氧基桂皮酸2-乙基己酯                             0.1
甘油                                                 8.0
植物提取液(生药palo azul)                            5.0
一缩二丙二醇                                         5.0
聚乙二醇                                             5.0
氢氧化钾                                     0.1
偏磷酸钠                                     0.05
乙二胺四乙酸三钠                             0.05
对羟基苯甲酸酯                               适量
色素                                         适量
香料                                         适量
蒸馏水                                       余量
配方例20(乳液)
十甲基环戊烷硅氧烷                           15.0
聚氧乙烯·聚甲基硅氧烷共聚物                 3.0
澳洲坚果油                                   1.0
角鲨烷                                       2.0
羟基硬脂酸胆甾醇酯                           0.2
2-乙基己酸十六烷基酯                         2.0
氯化二硬脂基二甲基铵                         0.3
甘油                                         8.0
1，3-丁二醇                                  5.0
植物提取液(生药palo azul)                    3.0
麦芽糖醇液                                   2.0
乙二胺四乙酸三钠                             0.05
硅酸铝镁                                     0.3
对羟基苯甲酸酯                               适量
色素                                         适量
离子交换水                                   余量
配方例21(乳液)
角鲨烷                                       0.2
羟基硬脂酸胆甾醇酯                           0.1
三(2-乙基己酸)甘油酯                         0.4
聚氧乙烯硬化蓖麻油                           0.4
二异硬脂酸聚甘油酯                           0.3
改性醇                                       5.0
甘油                                         2.0
植物提取液(生药palo azul)                    1.0
一缩二丙二醇                                 5.0
聚乙二醇                                     2.0
氢氧化钾                                     0.6
乙二胺四乙酸三钠                             0.05
黄原胶                                       0.2
羟乙基纤维素                                 0.03
羧基乙烯基聚合物                             0.3
香料                                         适量
对羟基苯甲酸酯                               适量
蒸馏水                                       余量
配方例22(乳液)
凡士林                                       5.0
二十二烷醇                                   0.5
硬化油                                       1.5
霍霍巴油                                     2.5
角鲨烷                                       4.0
四辛酸季戊四醇酯                             3.0
聚氧乙烯硬化蓖麻油                           0.5
甘油                                         5.0
1，3-丁二醇                                  5.0
聚乙二醇                                     2.0
植物提取液(生药palo azul)                    1.0
氢氧化钾                                     0.07
羧基乙烯基聚合物                             0.2
对羟基苯甲酸酯                               适量
色素                                         适量
蒸馏水                                       余量
配方例23(乳液)
凡士林                                        2.0
聚甲基硅氧烷                                  2.0
二十二烷醇                                    0.3
鲨肝醇                                        0.3
羟基硬脂酸胆甾醇酯                            0.1
4-叔丁基-4’-甲氧基苯甲酰基甲烷               0.1
改性醇                                        3.0
甘油                                          8.0
植物提取液(生药palo azul)                     1.0
1，3-丁二醇                                   4.0
聚乙二醇                                      3.0
椰子油脂肪酸水解胶原钾液                      0.2
氢氧化钾                                      0.08
乙二胺四乙酸三钠                              0.05
黄原胶                                        0.05
羧基乙烯基聚合物                              0.22
色素                                          适量
对羟基苯甲酸酯                                适量
香料                                          适量
蒸馏水                                        余量
配方例24(乳液)
凡士林                                        0.7
聚甲基硅氧烷                                  0.3
二十二烷醇                                    0.7
角鲨烷                                        2.0
2-乙基己酸十六烷基酯                          0.5
N-硬脂酰基-L-谷氨酸钠                         0.3
改性醇                                        3.0
甘油                                          4.0
一缩二丙二醇                                  6.0
1，3-丁二醇                                  4.0
植物提取液(生药palo azul)                    1.0
氢氧化钾                                     0.07
偏磷酸钠                                     0.01
黄原胶                                       0.02
羧基乙烯基聚合物                             0.14
色素                                         适量
对羟基苯甲酸酯                               适量
香料                                         适量
蒸馏水                                       余量
配方例25(化妆水)
1，3-丁二醇                                  6.0
甘油                                         4.0
油醇                                         0.1
POE(20)脱水山梨醇单月桂酸酯                  0.5
POE(15)月桂醇醚                              0.5
植物提取液(生药palo azul)                    1.0
植物提取液(生药金镂梅)                       0.5
乙醇                                         10.0
香料                                         适量
色素                                         适量
蒸馏水                                       余量
配方例26(化妆水)
山梨醇                                       4.0
一缩二丙二醇                                 6.0
PEG 1500                                     5.0
POE(20)油醇醚                                0.5
甲基纤维素                                   0.2
クインズシ-ド提取物                          0.1
植物提取液(生药palo azul)                    0.5
植物提取液(生药黄芩水SE)                    0.1
乙醇                                        10.0
香料                                        适量
色素                                        适量
蒸馏水                                      余量
配方例27(化妆水)
1，3-丁二醇                                 6.0
甘油                                        3.0
PEG 4000                                    3.0
橄榄油                                      0.5
POE(20)脱水山梨醇单硬脂酸酯                 1.5
POE(5)油醇醚                                0.3
乙醇                                        10.0
植物提取液(生药palo azul)                   0.3
植物提取液(生药マジヨラム提取物)            1.5
香料                                        适量
色素                                        适量
蒸馏水                                      余量
配方例28(化妆水)
一缩二丙二醇                                1.0
山梨醇                                      1.0
POE(20)油醇醚                               1.0
苯酚磺酸锌                                  0.2
枸橼酸                                      0.1
乙醇                                        15.0
植物提取液(生药palo azul)                   0.3
植物提取液(生药イザヨイバラ果实)            1.5
香料                                        适量
色素                                        适量
蒸馏水                                      余量
配方例29(化妆水)
1，3-丁二醇                                     6.0
一缩二丙二醇                                    6.0
PEG 400                                         6.0
POE(20)脱水山梨醇单月桂酸酯                     1.0
聚氧乙烯聚氧丙烯嵌段共聚物                      1.5
乙醇                                            15.0
植物提取液(生药黄芩水SE)                        1.0
植物提取液(生药イザヨイバラ果实)                0.5
香料                                            适量
色素                                            适量
蒸馏水                                          余量
配方例30(面霜)
二十二烷醇                                      1.0
硬脂醇                                          2.0
角鲨烷                                          10.0
四辛酸季戊四醇酯                                5.0
羊毛脂                                          5.0
对羟基苯甲酸酯                                  0.3
聚氧乙烯二十二烷醇                              1.0
甘油                                            10.0
亚牛磺酸                                        0.1
乙酰基透明质酸钠                                0.1
蒸馏水                                          余量
配方例31(乳液)
角鲨烷                                          10.0
肉豆蔻酸异丙酯                                  20.0
十甲基环戊烷己烷                                35.0
烷基改性羧基乙烯基聚合物                        0.05
脱水山梨醇单油酸酯                                  5.0
一缩二丙二醇                                        3.0
谷胱甘肽                                            1.0
蒸馏水                                              余量
配方例32(乳液)
液体石蜡                                            10.0
八甲基环四硅氧烷                                    5.0
1，3-丁二醇                                         10.0
甘油                                                3.0
抗坏血酸衍生物                                      3.0
谷胱甘肽                                            0.1
羧基乙烯基聚合物                                    0.15
黄原胶                                              0.25
硬脂酸                                              1.5
鲸蜡醇                                              0.5
聚氧乙烯(10)单油酸酯                                1.0
硬脂酸单甘油酯                                      1.0
乙醇                                                3.0
香料                                                适量
蒸馏水                                              余量
配方例33(面霜)
鲸蜡硬脂醇                                          3.5
角鲨烷                                              20.0
蜂蜡                                                3.0
羊毛脂                                              5.0
对羟基苯甲酸酯                                      0.3
聚氧乙烯(20)脱水山梨醇单棕榈酸酯                    2.0
硬脂酸单甘油酯                                      2.0
亚牛磺酸                                            0.1
维生素A                                             2.0
香料                                                适量
蒸馏水                                              余量
配方例34(粉底)
滑石                                                3.0
二氧化钛                                            5.0
红氧化铁                                            0.5
黄氧化铁                                            1.4
黑氧化铁                                            1.0
单硬脂酸聚氧乙烯脱水山梨醇酯                        0.9
三乙醇胺                                            1.0
丙二醇                                              5.0
亚牛磺酸                                            1.0
硬脂酸                                              2.2
异十六烷醇                                          7.0
硬脂酸单甘油酯                                      2.0
羊毛脂                                              2.0
石蜡                                                8.0
对羟基苯甲酸酯                                      适量
香料                                                适量
配方例35(面霜)
液体石蜡                                            3
凡士林                                              1
聚甲基硅氧烷                                        1
硬脂醇                                              1.8
二十二烷醇                                          1.6
甘油                                                8
一缩二丙二醇                                        5
澳洲坚果油                                          2
硬化油                                              3
角鲨烷                                              6
木糖醇                                                    3
硬脂酸                                                    2
羟基硬脂酸胆甾醇酯                                        0.5
2-乙基己酸十六烷基酯                                      4
自身乳化型单硬脂酸甘油酯                                  3
氢氧化钾                                                  0.15
偏磷酸钠                                                  0.05
三甲基甘氨酸                                              2
DL-α-生育酚2-L-抗坏血酸磷酸二酯钾                        1
醋酸DL-α-生育酚                                          0.1
Palo azul提取液(生药palo azul)                            0.05
甜茶提取物                                                0.1
对羟基苯甲酸酯                                            适量
乙二胺四乙酸三钠                                          0.05
4-叔丁基-4’-甲氧基二苯甲酰基甲烷                         0.05
二对甲氧基桂皮酸一(2-乙基己酸)甘油酯                      0.05
红氧化铁                                                  适量
黄氧化铁                                                  适量
羧基乙烯基聚合物                                          0.05
蒸馏水                                                    余量
配方例36(面霜)
液体石蜡                                                  8
凡士林                                                    3
聚甲基硅氧烷                                              2
硬脂醇                                                    3
二十二烷醇                                                2
甘油                                                      5
一缩二丙二醇                                              4
木糖醇                                                    1
四(2-乙基己酸)季戊四醇酯                                  4
异硬脂酸聚氧乙烯甘油酯                                    2
单硬脂酸聚氧乙烯甘油酯                                1
亲油型单硬脂酸甘油酯                                  2
枸橼酸                                                0.05
枸橼酸钠                                              0.05
氢氧化钾                                              0.015
Palo azul提取液(生药palo azul)                        0.1
肝脏(カンゾウ)类黄酮                                  0.1
棕榈酸视黄醇(パルミチンレチノ-ル)(100                 0.25万单位)
醋酸DL-α-生育酚                                      0.1
对羟基苯甲酸酯                                        适量
苯氧基乙醇                                            适量
二丁基羟基甲苯                                        0.1
乙二胺四乙酸三钠                                      0.05
4-叔丁基-4’-甲氧基二苯甲酰基甲烷                     0.01
对甲氧基桂皮酸2-乙基己酯                              0.1
B-胡萝卜素                                            0.01
聚乙烯醇                                              0.5
羟乙基纤维素                                          0.5
羧基乙烯基聚合物                                      0.05
蒸馏水                                                余量
香料                                                  适量
配方例37(保湿面霜)
液体石蜡                                              10
聚甲基硅氧烷                                          2
甘油                                                  10
1，3-丁二醇                                           2
赤藓醇1
木糖醇                                                1.5
聚乙二醇1500                                          5
角鲨烷                                                15
四(2-乙基己酸)季戊四醇酯                            5
氢氧化钾                                            0.1
Palo azul提取液(生药palo azul)                      0.08
偏磷酸钠                                            0.05
醋酸生育酚                                          0.05
对羟基苯甲酸酯                                      适量
羟丙基甲基纤维素                                    0.3
聚乙烯醇                                            0.1
羧基乙烯基聚合物                                    0.2
丙烯酸·甲基丙烯酸烷基酯共聚物                      0.1
蒸馏水                                              余量
配方例38(面霜(不含油))
シクロメチコン                                      30
聚氧乙烯·聚甲基硅氧烷共聚物                        1.5
甘油                                                5
一缩二丙二醇                                        5
木糖醇                                              3
滑石                                                5
对羟基苯甲酸酯                                      适量
Palo azul提取液(生药palo azul)                      0.03
苯氧基乙醇                                          0.3
乙二胺四乙酸三钠                                    0.02
二甲基二硬脂基铵锂蒙脱石                            0.5
蒸馏水                                              余量
三甲基甲硅烷氧基硅酸                                0.5
球状硅酸酐                                          0.5
微粒二氧化钛(疏水化处理品30nm)                      7
球状聚乙烯粉末                                      2
聚(氧化乙烯·氧化丙烯)·聚甲基硅氧烷共聚            1物
配方例39(乳液)
液体石蜡                                                7
凡士林                                                  3
十甲基环戊硅氧烷                                        2
二十二烷醇                                              2
甘油                                                    5
一缩二丙二醇                                            7
聚乙二醇1500                                            2
木糖醇                                                  2
霍霍巴油                                                1
异硬脂酸                                                0.5
硬脂酸                                                  0.5
二十二烷酸                                              0.5
四(2-乙基己酸)季戊四醇酯                                3
2-乙基己酸十六烷基酯                                    3
单硬脂酸甘油酯                                          1
单硬脂酸聚氧乙烯甘油酯                                  1
氢氧化钾                                                0.1
六偏磷酸钠                                              0.05
甘草次酸十八烷基酯                                      0.05
L-精氨酸                                                0.1
蜂王浆提取物                                            0.1
醋酸生育酚                                              0.1
透明质酸钠                                              0.1
Palo azul提取液(生药palo azul)                          0.05
对羟基苯甲酸酯                                          适量
乙二胺四乙酸三钠                                        0.05
4-叔丁基-4’-甲氧基二苯甲酰基甲烷                       0.1
对甲氧基桂皮酸2-乙基己酯                                0.1
黄氧化铁                                                适量
羧基乙烯基聚合物                                        0.15
蒸馏水                                                  余量
香料                                                适量
配方例40(乳液)
聚甲基硅氧烷                                        2
二十二烷醇                                          1
鲨肝醇                                              0.5
甘油                                                5
1，3-丁二醇                                         7
木糖醇                                              2
赤藓醇                                              2
硬化油                                              3
角鲨烷                                              6
四(2-乙基己酸)季戊四醇酯                            2
异硬脂酸聚氧乙烯甘油酯                              1
单硬脂酸聚氧乙烯甘油酯                              1
Palo azul提取液(生药palo azul)                      0.1
氢氧化钾                                            适量
六偏磷酸钠                                          0.05
苯氧基乙醇                                          适量
羧基乙烯基聚合物                                    0.11
蒸馏水                                              余量
配方例41(皱纹护理用乳液)
十甲基环戊硅氧烷                                    15
三甲基甲硅烷氧基硅酸                                5
聚氧乙烯·聚甲基硅氧烷共聚物                        5
甘油                                                5
1，3-丁二醇                                         5
麦芽糖醇液                                          2
澳洲坚果油                                          2
角鲨烷                                              2
木糖醇                                              3
羟基硬脂酸胆甾醇酯                                    0.5
2-乙基己酸十六烷基酯                                  2
氯化二硬脂基二甲基铵                                  0.2
L-抗坏血酸硫酸酯二钠                                  0.1
DL-α-生育酚2-L-抗坏血酸磷酸二酯钾                    0.1
醋酸生育酚                                            0.05
鱼胶原                                                0.4
硫酸软骨素钠                                          0.01
透明质酸钠                                            0.1
Palo azul提取液(生药palo azul)                        0.1
对羟基苯甲酸酯                                        适量
乙二胺四乙酸三钠                                      0.05
二对甲氧基桂皮酸一(2-乙基己酸)甘油酯                  0.05
硅酸铝镁                                              0.3
蒸馏水                                                余量
配方例42(乳液)
聚甲基硅氧烷                                          3
十甲基环戊硅氧烷                                      4
乙醇                                                  5
甘油                                                  6
1，3-丁二醇                                           5
聚氧乙烯甲基葡糖苷                                    3
向日葵油                                              1
角鲨烷                                                2
木糖醇                                                3
氢氧化钾                                              0.1
六偏磷酸钠                                            0.05
羟丙基-β-环糊精                                      0.1
甘草酸二钾                                            0.05
枇杷叶提取物                                          0.1
L-谷氨酸钠                                            0.05
茴香提取物                                            0.1
熏衣草油                                              0.1
Palo azul提取液(生药palo azul)                        0.05
对羟基苯甲酸酯                                        适量
二吗啉基哒嗪                                          0.1
红氧化铁                                              适量
黄氧化铁                                              适量
黄原胶                                                0.1
羧基乙烯基聚合物                                      0.1
丙烯酸·甲基丙烯酸烷基酯共聚物                        0.1
蒸馏水                                                余量
配方例43(乳液)
凡士林                                                5
二十二烷醇                                            0.4
鲨肝醇                                                0.4
甘油                                                  7
1，3-丁二醇                                           7
木糖醇                                                3
聚乙二醇20000                                         2
硬化油                                                2
霍霍巴油                                              2
角鲨烷                                                5
异硬脂酸                                              0.4
四(2-乙基己酸)季戊四醇酯                              2
聚氧乙烯硬化蓖麻油                                    0.5
月桂基二甲氨基乙酸甜菜碱                              0.4
氢氧化钾                                              适量
焦亚硫酸钠                                            0.01
六偏磷酸钠                                            0.05
甘草酸二钾                                            0.05
三甲基甘氨酸                                          3
熊果苷                                                    3
酵母提取物                                                0.1
醋酸生育酚                                                0.1
硫代牛磺酸                                                0.1
Palo azul提取液(生药palo azul)                            0.05
苦参提取物                                                0.1
苯氧基乙醇                                                适量
红氧化铁                                                  适量
クインズシ-ド提取物                                       0.1
羧基乙烯基聚合物                                          0.2
蒸馏水                                                    余量
配方例44(化妆水)
乙醇                                                      5
甘油                                                      2
1，3-丁二醇                                               5
聚氧乙烯聚氧丙烯癸基十四烷基醚                            0.2
六偏磷酸钠                                                0.03
三甲基甘氨酸                                              1
木糖醇                                                    3
聚天冬氨酸钠                                              0.1
DL-α-生育酚2-L-抗坏血酸磷酸二酯钾                        0.1
硫代牛磺酸                                                0.1
绿茶提取物                                                0.1
Palo azul提取液(生药palo azul)                            0.05
鸢尾根提取物                                              0.1
苯氧基乙醇                                                0.12
乙二胺羟乙基乙酸三钠(HEDTA)                               0.07
羧基乙烯基聚合物                                          0.09
蒸馏                                                      余量
香料                                                      适量
配方例45(化妆水)
甘油                                                     2
1，3-丁二醇                                              4
赤藓醇                                                   2
本糖醇                                                   3
Palo azul提取液(生药palo azul)                           0.2
聚氧乙烯甲基葡糖苷                                       1
聚氧乙烯硬化蓖麻油                                       0.5
枸橼酸                                                   0.02
枸橼酸钠                                                 0.08
苯氧基乙醇                                               0.25
N-椰子油脂肪酸酰基L-精氨酸乙酯·DL-吡咯                  0.1
烷酮甲酸
蒸馏水                                                   余量
配方例46(化妆水)
乙醇                                                     5
甘油                                                     0.1
一缩二丙二醇                                             2
1，3-丁二醇                                              6
木糖醇                                                   6
迷迭香油                                                 0.001
洋苏叶油                                                 0.001
枸橼酸                                                   0.02
枸橼酸钠                                                 0.08
六偏磷酸钠                                               0.03
羟丙基-β-环糊精                                         0.1
无患子提取物                                             0.1
玫瑰果提取物                                             0.1
百合提取物                                               0.1
黄柏提取物                                               0.1
トゲナシ提取物                                           0.1
树莓提取物                                                    0.1
熏衣草油                                                      0.1
桃仁提取物                                                    0.1
Palo azul提取液(生药palo azul)                                0.1
精氨酸钠                                                      0.001
蒸馏水                                                        余量
工业实用性
本发明的外用剂能够显著防止人角化细胞由于干燥引起的角质层水分量降低，同时能够抑制角质层的皮肤屏障功能降低。因此，本发明能够在化妆品或皮肤科制剂的制造业中利用。

Claims (4)

1、来源于Eysenhardtia polistachya的生药palo azul作为制备抑制或修复干燥引起的皮肤损伤的皮肤外用剂的成分的用途。
2、如权利要求1所述的用途，其中，所述成分是生药palo azul和甘油与赤藓醇、肌醇、乳糖醇、麦芽糖醇、甘露糖醇或木糖醇的组合。
3、如权利要求2所述的用途，成分是生药palo azul和甘油以及木糖醇的组合。
4、一种抑制或修复干燥引起的皮肤损伤的皮肤外用剂，其含有生药palo azul、甘油以及木糖醇。
CNB018216110A 2000-12-28 2001-12-28 干燥引起皮肤损伤的抑制剂或修复剂及其评价方法 Withdrawn - After Issue CN1294896C (zh)

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