CN1720019A - 黑素细胞的树突伸长抑制剂以及含有该抑制剂的皮肤外用剂 - Google Patents
黑素细胞的树突伸长抑制剂以及含有该抑制剂的皮肤外用剂 Download PDFInfo
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- CN1720019A CN1720019A CNA2003801048101A CN200380104810A CN1720019A CN 1720019 A CN1720019 A CN 1720019A CN A2003801048101 A CNA2003801048101 A CN A2003801048101A CN 200380104810 A CN200380104810 A CN 200380104810A CN 1720019 A CN1720019 A CN 1720019A
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- melanocyte
- inhibitor
- dendron
- chemical compound
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/70—Biological properties of the composition as a whole
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及含有下述通式(1)所示的化合物和/或其盐的黑素细胞树突伸长抑制剂以及以其为有效成分的皮肤外用剂其中，式中R1、R2、R3分别独立表示碳原子数1～4的烷基或氢原子。
Description
技术领域
本发明涉及黑素细胞树突伸长抑制剂以及以该抑制剂作为有效成分的皮肤外用剂。
背景技术
保持肌肤洁白美丽，这是大多数女性的愿望，因此开发出很多美白化妆品。例如含有抗坏血酸及其衍生物、曲酸及其衍生物、凝血酸及其衍生物、氢醌苷等的化妆品。但是，它们大多数的作用机理是抑制酪氨酸酶，从而抑制黑素的生物合成，而对黑素本身的效果则有限。也就是说，在以这些成分为有效成分的美白化妆品中，即使对起因于黑素生成异常亢进的色斑、雀斑、肤色深等症状有效，但对于与黑素生成量不大相关的色素异常也只能说是单一的效果。换言之，由于存在用酪氨酸酶抑制剂没有效或者有效性低的色素异常症，所以人们希望开发出可以改善这样的色素异常症的方法。
另一方面，与黑素生成量不大有关系的色素异常例如有来自黑素细胞树突的黑素颗粒移动亢进导致的色素异常。对于这样的色素异常，人们考虑抑制黑素细胞在使黑素颗粒移动时，树突的伸长。但这样机理的美白剂尚不为人所知太多。也就是说，需要开发这样机理的美白剂。
麦冬(麦門冬)是汉方生药，在生津方面得到广泛应用(日本特开2000-103718)。并且已知在化妆品等皮肤外用剂领域，含有麦冬作为具有保湿性的有效成分(日本特开平11-29968)、作为黑素生成抑制剂(日本特开平08-133949)、作为脂质分解剂(日本特开2000-103718)，但所述麦冬中含有的成分甲基麦冬二氢高异黄酮B(methylophiopogonanoneB；2，3-二氢-3-[(4-甲氧基苯基)甲基]-5，7-二羟基-6，8-二甲基-4H-1-苯并吡喃-4-酮；以下称为“化合物1”)等下述通式(1)所示的化合物和/或其盐可抑制黑素细胞树突的伸长，以及通过该作用，对通常的作用机理为酪氨酸酶抑制作用的黑素生成抑制剂无效或不太奏效的色素异常症的改善有效，这完全未被人所知。
另外，已知麦冬等中含有甲基麦冬二氢高异黄酮B等通式(1)所示的化合物和/或其盐(Watanabe Yoshiaki等.，Chemical&Pharmaceutical Bulltin，(1985)，33(12)，5358-5363)，其分离方法也是已知的。
发明内容
本发明基于上述状况而进行，其目的在于提供一种成分，该成分抑制黑素细胞树突的伸长，并通过该作用，对色素异常症的改善有效，其中所述色素异常症是对通常的作用机理为酪氨酸酶抑制作用的黑素生成抑制剂无效或者不太奏效的病症。
本发明人鉴于上述状况，为了获得抑制黑素细胞树突的伸长，并通过该作用，对通常的作用机理为酪氨酸酶抑制作用的黑素生成抑制剂无效或者不太奏效的色素异常症的改善有效的成分，进行了深入的研究，结果发现麦冬中含有的通式(1)所示的化合物和/或其盐具有所述作用，从而完成了本发明。即，本发明涉及以下所示的技术。
(1)含有下述通式(1)所示化合物和/或其盐的黑素细胞的树突伸长抑制剂。
通式(1)
(其中，式中R1、R2、R3分别独立表示碳原子数1～4的烷基或氢原子)
(2)(1)中所述的黑素细胞树突伸长抑制剂，其特征在于：通式(1)所示的化合物为下式所示的甲基麦冬二氢高异黄酮B(methylophiopogonanone B)。
甲基麦冬二氢高异黄酮B(methylophiopogonanone B)
(3)黑素细胞树突伸长抑制剂用皮肤外用剂，其含有(1)或(2)中所述的黑素细胞树突伸长抑制剂作为有效成分。
(4)(3)中所述的黑素细胞树突伸长抑制剂用皮肤外用剂，其特征在于：可用于改善酪氨酸酶抑制剂效果不充分的色素异常症。
(5)(3)或(4)中所述的黑素细胞树突伸长抑制剂用皮肤外用剂，其特征在于该皮肤外用剂为化妆品。
实施发明的最佳方式
(1)本发明的黑素细胞树突伸长抑制剂
本发明的黑素细胞树突伸长抑制剂含有上述通式(1)所示化合物和/或其盐。
上述通式(1)中，R1、R2、R3分别独立表示烷基或氢原子。
烷基优选碳原子数1～4的烷基，例如甲基、乙基、丙基、1-甲基乙基、正丁基、1-甲基丙基、2-甲基丙基、1，1-二甲基乙基等。其中特别优选甲基。
通式(1)所表示的化合物可优选例举甲基麦冬二氢高异黄酮B(methylophiopogonanone B；化合物1)。
所述通式(1)所示的化合物可以直接使用，也可以与碱一起处理，成盐后使用。
只要是生理上可接受的盐均可使用，没有特别限定，例如优选钠盐、钾盐等碱金属盐；钙盐、镁盐等碱土金属盐；铵盐、三乙醇胺盐、三乙胺盐等有机胺盐类；赖氨酸盐、精氨酸盐等碱性氨基酸盐等。特别优选的是容易制备的碱金属盐。
本发明的皮肤外用剂中，可以单独含有上述通式(1)所示化合物和/或其盐，也可以将两种或以上组合含有。
所述通式(1)所示化合物和/或其盐可以是提纯的，也可以是含有有效量的通式(1)所示化合物和/或其盐的植物提取液或级分等。
这样的植物可以使用百合科(Liliaceae)的沿阶草属(Ophiopogon)植物，优选麦冬(Ophiopogon Japonicus Ker-Gawler)。用于提取通式(1)所示化合物和/或其盐的植物可以是整株植物，也可以是含有通式(1)所示化合物和/或其盐的植物的一部分，还可以是它们的加工品。例如可通过将百合科沿阶草属植物的块状根麦冬的提取物纯化分级得到。通式(1)所示的化合物和/或其盐的鉴定可通过X射线分析进行。
提取物特别优选由高极性溶剂提取的提取物。高极性溶剂优选例举二乙醚、异丙醚、四氢呋喃等醚类；二氯甲烷、氯仿等卤代烃类；乙酸乙酯、甲酸甲酯等酯类；丙酮或甲乙酮等酮类；乙腈等腈类；1，3-丁二醇、乙醇、异丙醇等醇类；水等。其中特别优选醇类。上述溶剂可以是1种，也可以是2种或以上的混合物。
提取通常相对于植物体或其一部分加入1～10倍重量的溶剂，如果在室温下则浸渍数日，如果是沸点附近的温度则浸渍数小时。提取后，可根据需要进行减压浓缩等除去溶剂。除去了溶剂的提取物用乙酸乙酯和水等进行液液萃取，或者以氯仿-甲醇等作为洗脱溶剂通过硅胶层析等进行纯化，由此可以分离出上述通式(1)所示的化合物。
相对于皮肤外用剂总量通式(1)所示化合物和/或其盐在本发明的皮肤外用剂中优选的含量为0.001～10重量％，进一步优选0.005～5重量％。过少，可能无法发挥黑素细胞树突伸长抑制效果；过多，其效果也有上限，可能阻碍配方的自由度。
(制备例)
将3kg麦冬(百合科沿阶草属麦冬的块状根)切碎，加入10L乙醇，加热回流3小时。冷却至室温后减压浓缩，向其中加入1L的乙酸乙酯和水，进行液液萃取，取乙酸乙酯相，减压浓缩。将残余物溶解于氯仿，进行硅胶柱层析，用洗脱溶剂氯仿∶甲醇＝100∶1→70∶30纯化，得到225mg化合物1。其结构由X射线分析确定。
(2)本发明的皮肤外用剂
本发明的皮肤外用剂的特征在于：含有上述本发明的黑素细胞树突伸长抑制剂。本发明中所述皮肤外用剂是指适合皮肤外用的组合物的总称，可以例举包括医药部外品的化妆品、皮肤外用药、皮肤外用制品等。其中特别优选化妆品。这是由于，上述本发明的黑素细胞的树突伸长抑制剂具有优异的安全性，因此可以向化妆品那样连续、习惯性地使用，这样的使用方式可以充分地发挥美白作用。
化妆品的剂型并没有特别限定，由于本发明的树突伸长抑制剂具有极性极高的物性，因此不仅在乳膏或乳液等乳化剂型中使用，也可以在化妆水或精华液等溶液剂型中使用。
本发明的皮肤外用剂中，除上述黑素细胞树突伸长抑制剂以外，还可以含有通常的皮肤外用剂所使用的任何成分。所述任何成分例如有角鲨烷、液体石蜡、轻质液体石蜡、重质液体石蜡、微晶蜡、固体石蜡等烃类；二甲基硅油、フエメチコン、环甲基硅酮、アモジメチコン、聚醚改性硅氧烷等硅氧烷类；霍霍巴油、巴西棕榈蜡、木蜡、蜜蜡、鲸蜡、油酸辛基十二醇酯、肉豆蔻酸异丙酯、新戊二醇二异硬脂酸酯、苹果酸二异硬脂酸酯等的酯类；硬脂酸、月桂酸、肉豆蔻酸、棕榈酸、异硬脂酸、异棕榈酸、山萮酸、油酸等脂肪酸类；山萮醇、鲸蜡醇、油醇、十八烷醇等高级醇类；蓖麻油、椰子油、氢化椰子油、山茶油、小麦胚芽油、异硬脂酸甘油三酯、异辛酸甘油三酯、橄榄油等甘油三酯类；1，3-丁二醇、甘油、双甘油、双丙甘醇、聚乙二醇、1，2-戊二醇、1，2-己二醇、异戊二醇等多元醇类；
脱水山梨糖醇倍半油酸酯、脱水山梨糖醇单油酸酯、脱水山梨糖醇三油酸酯、脱水山梨糖醇倍半硬脂酸酯、脱水山梨糖醇单硬脂酸酯、聚氧乙烯脱水山梨糖醇单油酸酯、聚氧乙烯脱水山梨糖醇单硬脂酸酯、聚氧乙烯硬脂酸酯、聚氧乙烯油酸酯、聚氧乙烯甘油脂肪酸酯、聚氧乙烯烷基醚、聚氧乙烯硬化蓖麻油等非离子表面活性剂类；月桂基硬脂酸钠、聚氧乙烯烷基硫酸盐、磺基琥珀酸酯盐等阴离子表面活性剂类；烷基季铵盐等阳离子表面活性剂类；烷基甜菜碱等两性表面活性剂类；
结晶纤维素或交联型聚甲基硅氧烷、聚乙烯粉末、丙烯酸树脂粉体等有机粉体类；滑石粉、云母、绢云母、碳酸镁、碳酸钙、二氧化钛、氧化铁、深蓝、群青、云母钛、绢云母钛、二氧化硅等可进行表面处理的粉体类；
丙烯酸·甲基丙烯酸烷基酯共聚物和/或其盐、羧基乙烯基聚合物和/或其盐、黄原酸胶或羟丙基纤维素等增稠剂；
视黄醇、视黄酸、生育酚、核黄素、吡哆醇、抗坏血酸、抗坏血酸磷酸酯盐等维生素或者甘草酸盐、甘草亭、乌索酸、齐墩果醇酸等萜类；雌二醇、乙炔雌二醇、雌三醇等类固醇类等的有效成分；
苯氧基乙醇、对羟基苯甲酸酯类、洗必泰葡糖酸酯、苯扎氯铵等防腐剂；二甲基氨基苯甲酸酯类、肉桂酸酯类、二苯酮类等紫外吸收剂等。
当然，还可以含有与本发明的树突伸长抑制剂机理不同的美白剂、例如抗坏血酸及其衍生物、曲酸及其衍生物、凝血酸及其衍生物、氢醌苷等，含有上述物质时至少可以获得协同效果，因而优选。相对于皮肤外用剂总量与所述树突伸长抑制剂机理不同的美白剂的优选以总含量计为0.01～5重量％。
本发明的皮肤外用剂适应症优选为酪氨酸酶抑制剂的效果不充分的色素异常症。本说明书中，“酪氨酸酶抑制剂的效果不充分的色素异常症”是指使用酪氨酸酶抑制剂(例如熊果苷等)，通过实施例2所述的方法等进行试验时，70％或以上的专业评价人员判断为“色素异常未改善”的色素异常症。
本发明的皮肤外用剂可通过按照常规方法处理上述必须成分和任意成分来制备。
实施例
以下给出实施例，对本发明进行更详细的说明，当然本发明并不仅限于所述实施例。
<实施例1>
使用人黑素细胞，按照以下方法研究树突伸长抑制作用。
(试剂类)细胞、基础培养基、增殖添加剂均购自仓敷纺织(株)。
(细胞)正常人黑素细胞
(培养基)基础培养基(Medium 154S)中添加以下试剂。
(试剂)增殖添加剂：牛脑垂体提取液(BPE)(培养基中的终浓度为0.4％v/v)、胎牛血清(FBS)(培养基中的终浓度为0.5％v/v)、重组人碱性成纤维细胞生长因子(rFGF-B)(培养基中的终浓度为3ng/ml)、氢化可的松(培养基中的终浓度为0.18μg/ml)、胰岛素(培养基中的终浓度为5μg/ml)、运铁蛋白(培养基中的终浓度为5μg/ml)、12-肉豆蔻13-乙酸-佛波醇酯(PMA)(培养基中的终浓度为10ng/ml)、肝素(培养基中的终浓度为3μg/ml)、PSA溶液(青霉素浓度50,000单位/ml、链霉素浓度50μg/ml、两性霉素B浓度12.5μg/ml的混合溶液。每500ml培养基添加1ml。)
(方法)
·将上述制备例中所得化合物1(甲基麦冬二氢高异黄酮B)用基础培养基稀释为浓度100μg/ml，制备样品溶液。对照为只有基础培养基的溶液。
·将正常人黑素细胞接种于48孔板中(3000细胞/孔、200μl培养基)，在37℃下培养。
·24小时后加入50μl样品溶液。
·添加样品24小时后观察对树突伸长的抑制。
(结果)
以树突的长度为结果，如表1所示。可知：对照中因生长因子的添加效果，树突伸长，但化合物1添加组中伸长被抑制。
表1
| 添加化合物 | 树突的长度(μm) |
| 化合物1 | 22±6 |
| 对照 | 140±29 |
<实施例2>
按照下述配方制备作为本发明的皮肤外用剂的化妆品。即，将(一)、(二)、(三)的成分分别加热到70℃，将(二)用(三)中和，边搅拌边慢慢加入(一)，乳化，用均化器进行均化，然后搅拌冷却，得到乳液。同时制备比较例1，其中将化合物1置换为角鲨烷，采用通常使用抑制黑素生成的化妆品而没有改善的因肤色深而烦恼的人，10名为一组，共采用20名，进行早晚共两次，连续使用30天的使用测试，研究肤色深度的改善程度。使用30天后，由专业评价人员打分评价改善程度，5分：显著改善，4分：明显改善，3分：改善，2分：稍有改善，1分：未改善。结果如表2所示。由此可知：作为本发明的皮肤外用剂的化妆品具有优异的美白效果。
(一)
角鲨烷 10重量份
脱水山梨糖醇倍半硬脂酸酯 2重量份
化合物1 0.005重量份
对羟基苯甲酸丁酯 0.1重量份
(二)
1，3-丁二醇 5重量份
黄原酸胶 0.1重量份
丙烯酸·甲基丙烯酸烷基酯(C10～C30) 0.4重量份
对羟基苯甲酸甲酯 0.1重量份
水 50重量份
(三)
氢氧化钾 0.2重量份
水 32.095重量份
表2
| 样品 | 得分5 | 得分4 | 得分3 | 得分2 | 得分1 |
| 实施例2 | 1 | 1 | 6 | 2 | |
| 比较例1 | 2 | 8 |
<实施例3>
与实施例2同样，改变化合物1的量，制备皮肤外用剂(化妆品)，仍使用上述10名专业评价人员进行同样的评价。可确认该皮肤外用剂也取得了同样的效果。
(一)
角鲨烷 10重量份
脱水山梨糖醇倍半硬脂酸酯 2重量份
化合物1 0.01重量份
对羟基苯甲酸丁酯 0.1重量份
(二)
1，3-丁二醇 5重量份
黄原酸胶 0.1重量份
丙烯酸·甲基丙烯酸烷基酯(C10～C30) 0.4重量份
对羟基苯甲酸甲酯 0.1重量份
水 50重量份
(三)
氢氧化钾 0.2重量份
水 32.09重量份
表3
| 样品 | 得分5 | 得分4 | 得分3 | 得分2 | 得分1 |
| 实施例3 | 1 | 4 | 3 | 2 |
<实施例4>
按照以下配方，与实施例2、3同样地制备皮肤外用剂(化妆品)，由同样的专业评价人员进行同样的评价。将化合物1置换为熊果苷，以此作为比较例2，进行同样的评价，。结果见表4。专业评价人员未证实酪氨酸酶抑制剂的美白效果，但这些专业评价人员证实了本发明的黑素细胞树突伸长抑制剂有效地发挥了作用。
(一)
角鲨烷 10重量份
脱水山梨糖醇倍半硬脂酸酯 2重量份
化合物1 1重量份
对羟基苯甲酸丁酯 0.1重量份
(二)
1，3-丁二醇 5重量份
黄原酸胶 0.1重量份
丙烯酸·甲基丙烯酸烷基酯(C10～C30) 0.4重量份
对羟基苯甲酸甲酯 0.1重量份
水 50重量份
(三)
氢氧化钾 0.2重量份
水 31.1重量份
表4
| 样品 | 得分5 | 得分4 | 得分3 | 得分2 | 得分1 |
| 实施例3 | 2 | 4 | 4 | ||
| 比较例2 | 3 | 7 |
产业实用性
本发明提供一种成分，该成分抑制黑素细胞树突的伸长，并通过该作用，对通常的机理为酪氨酸酶抑制作用的黑素生成抑制剂无效或者不太奏效的色素异常症的改善有效。
Claims (5)
1.一种黑素细胞树突伸长抑制剂，该抑制剂含有下述通式(1)所示的化合物和/或其盐
通式(1)
其中，式中R1、R2、R3分别独立表示碳原子数1～4的烷基或氢原子。
2.如权利要求1所述的黑素细胞树突伸长抑制剂，其特征在于：通式(1)所示的化合物为下式所表示的甲基麦冬二氢高异黄酮B：
甲基麦冬二氢高异黄酮B(methylophiopogonanone B)
3.黑素细胞树突伸长抑制剂用皮肤外用剂，其含有权利要求1或2所述的黑素细胞树突伸长抑制剂作为有效成分。
4.如权利要求3所述的黑素细胞树突伸长抑制用皮肤外用剂，其特征在于：可用于改善酪氨酸酶抑制剂的作用效果不充分的色素异常症。
5.权利要求3或4所述的黑素细胞树突伸长抑制的用皮肤外用剂，其特征在于该皮肤外用剂为化妆品。
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP349376/2002 | 2002-12-02 | ||
| JP2002349376 | 2002-12-02 |
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| Publication Number | Publication Date |
|---|---|
| CN1720019A true CN1720019A (zh) | 2006-01-11 |
| CN100352420C CN100352420C (zh) | 2007-12-05 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2003801048101A Expired - Fee Related CN100352420C (zh) | 2002-12-02 | 2003-11-28 | 黑素细胞的树突伸长抑制剂以及含有该抑制剂的皮肤外用剂 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7141601B2 (zh) |
| EP (1) | EP1570837B1 (zh) |
| JP (1) | JP4641419B2 (zh) |
| KR (1) | KR101156968B1 (zh) |
| CN (1) | CN100352420C (zh) |
| AU (1) | AU2003284490A1 (zh) |
| ES (1) | ES2438966T3 (zh) |
| WO (1) | WO2004050053A1 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591316A (zh) * | 2009-06-30 | 2009-12-02 | 沈阳药科大学 | 高异黄酮、二氢高异黄酮、高异黄烷类衍生物及其用途 |
| CN104257651A (zh) * | 2014-06-24 | 2015-01-07 | 上海中医药大学 | 麦冬黄烷酮f的医药用途 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4250071B2 (ja) * | 2003-12-15 | 2009-04-08 | 株式会社クラレ | 皮膚外用剤 |
| JP4989119B2 (ja) * | 2006-06-16 | 2012-08-01 | ポーラ化成工業株式会社 | ベシクル系に好適な皮膚外用剤 |
| WO2010027189A2 (ko) * | 2008-09-02 | 2010-03-11 | 가톨릭대학교 산학협력단 | 호모아이소플라베논 또는 이의 염의 신규한 용도 |
| DE102011004335A1 (de) | 2011-02-17 | 2012-08-23 | Thomas Grammel | Verfahren zur Herstellung eines Vakzins |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05345718A (ja) * | 1992-02-03 | 1993-12-27 | Nippon Shinyaku Co Ltd | 美白化粧料組成物 |
| JPH08133949A (ja) * | 1994-11-07 | 1996-05-28 | Shiseido Co Ltd | 皮膚外用剤 |
| JPH08208451A (ja) | 1995-02-03 | 1996-08-13 | Kao Corp | 植物生薬抽出物配合美白剤 |
| JP3389071B2 (ja) | 1997-09-04 | 2003-03-24 | 花王株式会社 | 化粧料 |
| JPH10287544A (ja) * | 1997-04-11 | 1998-10-27 | Yakult Honsha Co Ltd | 色素沈着防止剤並びに皮膚化粧料および皮膚外用剤 |
| US8039026B1 (en) * | 1997-07-28 | 2011-10-18 | Johnson & Johnson Consumer Companies, Inc | Methods for treating skin pigmentation |
| FR2767059B1 (fr) * | 1997-08-11 | 2000-03-24 | Lvmh Rech | Utilisation d'extraits de polygonatum pour stimuler la synthese de l'elastine cutanee |
| JP2000013718A (ja) | 1998-06-18 | 2000-01-14 | Olympus Optical Co Ltd | 画像印刷装置 |
| US6750229B2 (en) * | 1998-07-06 | 2004-06-15 | Johnson & Johnson Consumer Companies, Inc. | Methods for treating skin pigmentation |
| JP2000103718A (ja) | 1998-09-28 | 2000-04-11 | Pola Chem Ind Inc | 生体活動改善用の組成物 |
| JP4290841B2 (ja) * | 2000-01-24 | 2009-07-08 | ポーラ化成工業株式会社 | メラノサイトのデンドライトの伸長抑制剤及びそれを含有する化粧料 |
| JP2001199866A (ja) * | 2000-01-24 | 2001-07-24 | Pola Chem Ind Inc | メラノサイトのデンドライトの伸長抑制剤及びそれを含有する化粧料 |
| WO2001056580A1 (en) * | 2000-02-01 | 2001-08-09 | Rutgers, The State University | Compositions of polygonum odoratum for prevention and treatment of disease |
| JP4992164B2 (ja) * | 2000-04-19 | 2012-08-08 | 日油株式会社 | 化粧料組成物 |
| JP2001335485A (ja) * | 2000-05-31 | 2001-12-04 | Pola Chem Ind Inc | メラノサイトのデンドライトの伸長抑制剤及びそれを含有する化粧料 |
| JP2002154920A (ja) * | 2000-11-14 | 2002-05-28 | Pola Chem Ind Inc | メラノサイトのデンドライトの伸長抑制剤及びそれを含有する化粧料 |
| JP2002179516A (ja) * | 2000-12-13 | 2002-06-26 | Pola Chem Ind Inc | 美白用組成物 |
| JP4953216B2 (ja) * | 2000-12-13 | 2012-06-13 | ポーラ化成工業株式会社 | 美白用の組成物 |
| JP3709363B2 (ja) * | 2001-10-09 | 2005-10-26 | ポーラ化成工業株式会社 | メラノサイトのデンドライトの伸長抑制剤及びそれを含有する化粧料 |
-
2003
- 2003-11-28 EP EP03775959.4A patent/EP1570837B1/en not_active Expired - Lifetime
- 2003-11-28 KR KR1020057009913A patent/KR101156968B1/ko not_active IP Right Cessation
- 2003-11-28 US US10/536,675 patent/US7141601B2/en not_active Expired - Fee Related
- 2003-11-28 ES ES03775959.4T patent/ES2438966T3/es not_active Expired - Lifetime
- 2003-11-28 AU AU2003284490A patent/AU2003284490A1/en not_active Abandoned
- 2003-11-28 WO PCT/JP2003/015266 patent/WO2004050053A1/ja active Application Filing
- 2003-11-28 CN CNB2003801048101A patent/CN100352420C/zh not_active Expired - Fee Related
- 2003-11-28 JP JP2004556861A patent/JP4641419B2/ja not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591316A (zh) * | 2009-06-30 | 2009-12-02 | 沈阳药科大学 | 高异黄酮、二氢高异黄酮、高异黄烷类衍生物及其用途 |
| CN101591316B (zh) * | 2009-06-30 | 2014-05-21 | 沈阳药科大学 | 高异黄酮、二氢高异黄酮、高异黄烷类衍生物及其用途 |
| CN104257651A (zh) * | 2014-06-24 | 2015-01-07 | 上海中医药大学 | 麦冬黄烷酮f的医药用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| US7141601B2 (en) | 2006-11-28 |
| ES2438966T3 (es) | 2014-01-21 |
| KR20050084088A (ko) | 2005-08-26 |
| EP1570837A1 (en) | 2005-09-07 |
| EP1570837B1 (en) | 2013-09-11 |
| CN100352420C (zh) | 2007-12-05 |
| US20050288361A1 (en) | 2005-12-29 |
| KR101156968B1 (ko) | 2012-06-20 |
| JP4641419B2 (ja) | 2011-03-02 |
| EP1570837A4 (en) | 2009-02-25 |
| JPWO2004050053A1 (ja) | 2006-03-30 |
| AU2003284490A1 (en) | 2004-06-23 |
| WO2004050053A1 (ja) | 2004-06-17 |
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