CN107519163B - 大花红景天素的医药用途 - Google Patents
大花红景天素的医药用途 Download PDFInfo
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- CN107519163B CN107519163B CN201610458230.1A CN201610458230A CN107519163B CN 107519163 B CN107519163 B CN 107519163B CN 201610458230 A CN201610458230 A CN 201610458230A CN 107519163 B CN107519163 B CN 107519163B
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- rhodiola crenulata
- tyrosinase
- rhodiola
- dopa
- crenulata
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- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
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- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Landscapes
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Abstract
本发明涉及医药领域，特别是涉及一种大花红景天素的医药用途。本发明的大花红景天素可用于制备抑制酪氨酸酶活性的药物、保健品和化妆品。
Description
技术领域
本发明涉及医药领域，特别是涉及一种黄酮类化合物的用途及其相关产品。
背景技术
色素沉着是由于黑色素过度积累导致的。临床主要表现为雀斑、褐斑甚至黑色素瘤等皮肤问题和疾病。
目前一般认为黑色素合成途径是：酪氨酸在酪氨酸酶作用下生成多巴，多巴在酪氨酸酶作用下生成多巴醌，多巴醌形成多巴色素，多巴色素形成二羟基吲哚，二羟基吲哚氧化成酮式吲哚，最后酮式吲哚聚合成真黑素。在这条反应途径中，多巴醌还可以经谷胱甘肽酶或半胱氨酸酶催化生成褐黑素，真黑素与褐黑素组成了黑色素，其中真黑素是皮肤色素的主要组成部分，褐黑素在皮肤中的功效暂不清楚。
目前治疗色素沉着的西药主要为氢醌及其衍生物化合物。其安全窗较小，长期使用会在体内大量积蓄，引起皮肤毒性、致癌性、遗传毒性等毒副作用。曲酸和熊果酸等多酚类化合物的使用量也有非常严格的要求，过大剂量也会引起致癌，致畸等毒副作用。
大花红景天素(rhodiolinin)是一种黄酮类化合物，存在于多种植物中，具有抗氧化，抗病毒的作用。
发明内容
本发明的目的旨在提供一种大花红景天素的新用途。
具体地说，本发明的第一方面是提供了大花红景天素作为唯一的活性成分在制备抑制酪氨酸酶活性的药物或化妆品中的应用。
本发明各个方面的细节将在随后的章节中得以详尽描述。通过下文以及权利要求的描述，本发明的特点、目的和优势将更为明显。
附图说明
图1为大花红景天素在薄层板上抑制黑色素生成形成的白色斑点的作用效果图；
图2为用B16黑色素瘤细胞模型筛选法检测大花红景天素抑制酪氨酸酶生成黑色素的能力；
图3为用以多巴为底物的分光光度法检测大花红景天素抑制酪氨酸酶生成黑色素的能力。
具体实施方式
本发明的问世是基于这样一个意外发现：黄酮类化合物大花红景天素在体内/体外均具有良好的抑制酪氨酸酶活性的作用。因此，大花红景天素有望开发成为一种抑制酪氨酸酶活性的药物或化妆品。
如本发明所用，本发明的化合物大花红景天素，其分子式：C25H20O10，分子量：480.11，其结构式如下：
如本领域的普通技术人员所知，本发明的化合物大花红景天素可通过商业途径购买获得，亦可用本领域的常规方法从景天科植物大花红景天(学名：Rhodiola crenulata(HK.f.et.Thoms)H.Ohba)等中提取获得。其纯度均符合药用标准。
本发明的大花红景天素可以单独使用或以药物组合物的形式使用。药物组合物包括作为活性成分的本发明的大花红景天素及可药用载体。较佳地，本发明的药物组合物含有0.1～99.9％重量百分比的作为活性成分的本发明的大花红景天素。“可药用载体”不会破坏本发明的大花红景天素的药学活性，同时其有效用量，即能发挥药物载体作用时的用量对人体无毒。
所述可药用载体包括但不限于：软磷脂、硬脂酸铝、氧化铝、离子交换材料、自乳化药物传递系统、吐温或其他表面活化剂、血清蛋白、缓冲物质如磷酸盐、氨基乙酸、山梨酸、水、盐、电解质如硫酸盐精蛋白、磷酸氢二钠、磷酸氢钾、氯化钠、锌盐、硅酸镁、饱和脂肪酸部分甘油酯混合物等。
其他常用的药物辅料如粘合剂(如微晶纤维素)、填充剂(如淀粉、葡萄糖、无水乳糖和乳糖珠粒)、崩解剂(如交联PVP、交联羧甲基淀粉钠、交联羧甲基纤维素钠、低取代羟丙基纤维素)、润滑剂(如硬脂酸镁)以及吸收促进剂、吸附载体、香味剂、甜味剂、赋形剂、稀释剂、润湿剂等。
本发明的大花红景天素以及其药物组合物可按本领域常规方法制备并可以通过肠道或非肠道或局部途径给药。口服制剂包括胶囊剂、片剂、口服液、颗粒剂、丸剂、散剂、丹剂、膏剂等；非肠道给药制剂包括注射液等；局部给药制剂包括霜剂、贴剂、软膏剂、喷雾剂等。优选为口服制剂。
本发明的大花红景天素以及其药物组合物的给药途径可以为口服、舌下、经皮、经肌肉或皮下、皮肤粘膜、静脉、尿道、阴道等。
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法，通常按照常规条件或按照制造厂商所建议的条件。除非另外说明，否则所有的百分数、比率、比例、或份数按重量计。
除非另行定义，文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外，任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
本发明提到的上述特征，或实施例提到的特征可以任意组合。本专利说明书所揭示的所有特征可与任何组合物形式并用，说明书中所揭示的各个特征，可以任何可提供相同、均等或相似目的的替代性特征取代。因此除有特别说明，所揭示的特征仅为均等或相似特征的一般性例子。
实施例子1检测大花红景天素在薄层板上抑制抑制酪氨酸酶生成黑色素的能力
1.实验材料
1.1仪器与试药
硅胶铝板薄层预制板(Merck-F254，10cm×20cm，Düren，Germany)。恒温水浴锅(SC-15，上海比朗仪器有限公司，上海)；AST4薄层色谱仪系统(薄层色谱自动点样仪，薄层色谱数码成像仪，薄层色谱板加热器，薄层色谱扫描仪，薄层色谱自动侵入衍生化装置)购自CAMAG公司，瑞士。大花红景天素购自上海中药标准化研究中心，并经HPLC检测纯度均在98％以上。酪氨酸酶(T3824-50 KU，SLBG4386V)，L-DOPA(100g，V900425)，曲酸(5g，K3125)均购自SIGMA公司，美国。
1.2样品溶液配制
取大花红景天素和曲酸适量，分别称定，加甲醇溶解配制成10mM的储备液，根据实验需要分别稀释成浓度范围为1～10mM的不同浓度的稀释液，0～4℃低温保存。
2.实验方法
将2μL供试品溶液点于Merck F254铝底硅胶预制薄层板上，挥干溶剂后，采用浸渍法，应用薄层色谱自动浸入衍生化装置将供试品板浸入酪氨酸酶溶液中1s，取出，拭去多余溶剂；再将该薄层板浸入底物L-DOPA溶液中1s，取出后置于25℃的密闭恒温水槽中反应15min，具有抑制酪氨酸酶活性的样品在薄层板的黑色背景下表现为白色斑点，以荧光模式，580nm为检测波长，对白色斑点进行扫描。实验结果见图1和表1。
表1大花红景天素在薄层板上抑制黑色素生成形成的白色斑点扫描数据表
实施例子2用B16黑色素瘤细胞模型筛选法检测大花红景天素抑制酪氨酸酶生成黑色素的能力
1实验材料
1.1仪器与试药
倒置荧光显微镜(CKX41，OLYMPUS，日本)，CO2恒温细胞培养箱(BB150，THERMO，美国)，超净工作台(1388，THERMO，美国)。恒温水浴锅(SC-15，上海比朗仪器有限公司，上海)；酶标仪(BOX-998，Winooski，美国)。酪氨酸酶(T3824-50 KU，SLBG4386V)，L-DOPA(100g，V900425)，Vc(100g，A7506)，曲酸(5g，K3125)均购自SIGMA公司，美国。B16小鼠黑色素瘤细胞，由上海科学院细胞库提供。大花红景天素购自上海中药标准化研究中心，并经HPLC检测纯度均在98％以上。DMEM培养基(500mL，1638605)，0.25％Trypsin-EDTA(500mL，1584897)，澳洲胎牛血清(500mL，20012-027)，FBS(500mL，10099-141)，RPMI1640培养基(500mL，11875-093)，Penicillin-Streptomycin，Liquid(100mL，15140-122)均购自THERMO FISHERSCIENTIFIC公司，美国；Theophylline(P08250，DAMAS-BETA，中国)。
1.2样品溶液配制
取大花红景天素和曲酸适量，分别称定，加DMSO溶解配制成100mM的储备液，根据实验需要分别稀释成浓度范围为1～100mM的不同浓度的稀释液，0～4℃低温保存。
2.B16小鼠黑色素瘤细胞的培养
B16小鼠黑色素瘤细胞生长在含10％的胎牛血清、100U/mL青霉素、100U/mL链霉素的完全RPMI 1640培养基中。在37℃，5％CO2条件下培养下，细胞贴壁培养到对数期后，0.25％胰蛋白酶消化，以每瓶约106个细胞传代至100cm2的培养皿中，每3天传代一次。
3.B16小鼠黑色素瘤细胞增殖活性测定(CCK-8法)
取对数生长期细胞常规消化，用完全RPMI1640培养基调整细胞为5×104的细胞悬液，将细胞接种于96孔细胞培养板中，每孔199μL。在37℃，5％CO2条件下培养，加入1μL待测样品作用3天后，弃上清并用PBS洗涤两编，每孔添加100μL含10％CCK-8的培养基溶液后，在培养箱中反应1h，于酶标仪上450nm波长下测定吸光度。
4.B16小鼠黑色素瘤细胞酪氨酸酶活性实验
常规消化下的细胞用含1％茶碱的DMEM完全培养液将小鼠B16黑色素瘤细胞的密度调为5×104个/mL，每孔199μL接种于96孔细胞培养板中，加入1μL待测样品作用3天后，弃上清并用PBS洗涤两编，每孔添加80μL含1％TritonX-100的PBS溶液后，冰水浴中超声30s破碎，每孔加入4mM L-DOPA 50μL，37℃水浴孵育60min，分别取100μL移至96孔细胞培养板中，于酶标仪检测475nm波长下的吸光度值，计算细胞内酪氨酸酶活性抑制率[2]。实验结果见图2和表2(以下检测浓度都控制在没有细胞毒性范围内)。
酪氨酸酶抑制率计算使用以下公式：
表2用B16黑色素瘤细胞模型筛选法检测大花红景天素抑制酪氨酸酶生成黑色素的抑制率
实施例子3用以多巴为底物的分光光度法检测大花红景天素抑制酪氨酸酶生成黑色素的能力
1.实验材料
1.1仪器与试药
恒温水浴锅(SC-15，上海比朗仪器有限公司，上海)；酶标仪(BOX-998，Winooski，美国)。大花红景天素购自上海中药标准化研究中心，并经HPLC检测纯度均在98％以上。L-DOPA(100g，V900425)，曲酸(5g，K3125)均购自SIGMA公司，美国。
1.2样品配制同
2多巴为底物的分光光度法
目前常用的分光光度法多采用L-DOPA和酪氨酸酶为反应体系。操作方法就是最终体积3mL(包括1.5mM L-DOPA，0.1mM PBS pH＝6.5，酪氨酸酶12.4U/mL)。加入酶后触发反应，在30℃密闭水浴锅反应20min，最后移至96孔板中在475nm波长下检测[3]，实验结果见图3和表3。
酪氨酸酶抑制率计算使用以下公式：
表3用以多巴为底物的分光光度法检测大花红景天素抑制酪氨酸酶生成黑色素的抑制率
本发明所涉及的多个方面已做如上阐述。然而，应理解的是，在不偏离本发明精神之前提下，本领域专业人员可对其进行等同改变和修饰，所述改变和修饰同样落入本申请所附权利要求的覆盖范围。
Claims (1)
1.大花红景天素作为唯一的活性成分在制备抑制酪氨酸酶活性的药物或化妆品中的应用。
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| WO2015160030A1 (ko) * | 2014-04-15 | 2015-10-22 | 한국콜마주식회사 | 피부 미백 활성을 갖는 마키아신 및 이의 용도 |
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| CN104257545A (zh) * | 2014-09-18 | 2015-01-07 | 北京工商大学 | 一种红景天发酵原浆化妆品及其制备方法 |
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