CN111405890A - 包含芍药苷或芍药内酯苷的内因性老化预防或改善用组合物 - Google Patents
包含芍药苷或芍药内酯苷的内因性老化预防或改善用组合物 Download PDFInfo
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- CN111405890A CN111405890A CN201880076602.1A CN201880076602A CN111405890A CN 111405890 A CN111405890 A CN 111405890A CN 201880076602 A CN201880076602 A CN 201880076602A CN 111405890 A CN111405890 A CN 111405890A
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- Prior art keywords
- paeoniflorin
- albiflorin
- composition
- salt
- solvate
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Abstract
本说明书公开一种内因性老化预防或改善用组合物,其包含:芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的任一种作为有效成分。与由作为外因性老化的一种的UV引起的光老化(photoaging)不同,内因性老化是随着年龄增长出现的自然现象中的一个,本发明的芍药苷或者芍药内酯苷对于要延缓岁月流逝来保持美丽的对象是有用的。由此,本发明的芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物具有能够以化妆品或者健康功能食品等各种形式活用的优势。
Description
技术领域
本说明书公开一种内因性老化预防或改善用组合物。
背景技术
老化分为内因性老化和外因性老化。虽然历来所述两种老化没有在分子的机制水平上明确划分研究,但是确认到室内劳动者(indoor laborer)和室外劳动者(outdoorlaborer)的皮肤状态,尤其是老化引起的皱纹形态或变色等状态不同,开始了明确区分并分析内因性老化和外因性老化。内因性老化也被称为生理性老化,与随着年龄增长的正常性老化相关。相反,外因性老化是通常环境引起的老化,更详细地,这样的老化是由于暴露于太阳、光或者其它不同放射线而产生的光-老化现象的一种。室内劳动者相比于外因性老化,皮肤老化主要由于内因性老化而进行。
由于内因性老化而产生的皮肤变化是包含内生因子的遗传编码的序列的结果,这种内因性老化使皮肤细胞的再生渐减。由此,呈现出皮下脂肪组织的减少之类的临床性损伤的外观以及微细线和小皱纹的外观。另外,伴随着弹性纤维的数量和厚度增加、软组织纤维从弹性组织膜丧失以及从这样的弹性组织细胞产生大型不规则成纤维细胞之类的组织病理学变化。
与此相比,外因性老化呈现出皱纹增厚且下垂的皮肤之类的临床性损伤的外观,并伴随着皮肤上方的弹性物质的过度积累和胶原纤维的变质之类的组织病理学变化。
因此,具有需要区分并预防或改善内因性老化和外因性老化的必要性。作为一例,要防止UV的紫外线阻断剂通过针对太阳光的保护使得能够针对光-老化而保护、预防皮肤,从而呈现出预防或改善外因性老化的效果,但是无法呈现出预防或改善内因性老化的效果。
对此,本发明人等在针对能够本质上预防或改善内因性老化的方法进行的摸索中,确认到芍药苷或芍药内酯苷具有对内因性老化的预防或改善效果,并完成了本发明。
[现有技术文献]
[专利文献]
(专利文献1)韩国公开专利公报第10-2008-0076999号
[非专利文献]
(非专利文献1)Helfrich,Yolanda Rosi,Dana L.Sachs,and John J.Voorhees."Overview of skin aging and photoaging."Dermatology Nursing 20.3(2008):177。
发明内容
在一方面,本发明的目的是提供一种内因性老化预防或改善用组合物,其包括:芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上作为有效成分。
为了实现所述课题,在一方面,本发明提供一种内因性老化预防或改善用组合物,其包含:芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上作为有效成分。
在一方面,本发明提供一种内因性老化预防或改善方法,其包括将芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上给予需要其的对象的步骤。
在一方面,本发明提供一种芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上的用途,用于制备用于内因性老化预防或改善的组合物。
在一方面,本发明可以提供用于内因性老化的芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上。
另外,在一方面,本发明提供所述组合物为化妆品组合物的内因性老化预防或改善用组合物。
另外,在一方面,本发明提供所述组合物为健康功能食品组合物的内因性老化预防或改善用组合物。
在一方面,本发明的芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物预防或改善内因性老化。与由作为外因性老化的一种的UV引起的光老化(photoaging)不同,内因性老化是随着年龄增长出现的自然现象中的一个,本发明的芍药苷或者芍药内酯苷对于要延缓岁月流逝来保持美丽的对象是有用的。由此,本发明的芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物具有能够以化妆品或者健康功能食品等各种形式活用的优势。
附图说明
图1是示出将TNF-α作为刺激源而确认基于芍药苷或芍药内酯苷的MMP-1抑制效果的结果的图。
图2是示出将TNF-α作为刺激源而确认基于芍药苷或芍药内酯苷的组合的MMP-1抑制效果的结果的图。
图3是示出将UV作为刺激源而确认基于芍药苷或芍药内酯苷的组合的MMP-1抑制效果的结果的图。
具体实施方式
在一方面,本发明提供一种内因性老化预防或改善用组合物,包含:芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上作为有效成分。
以下,进行详细说明。
在本说明书中,“芍药苷(paeoniflorin)”是分子式C23H28O11的分子量480的物质,由下面化学式1表示。
[化学式1]
在本说明书中,“芍药内酯苷(albiflorin)”是分子式C23H28O11的分子量480的物质,由下面化学式2表示。
[化学式2]
在本说明书中,“药学上可接受”指的是,以通常的服用量利用时,避免相当的毒性效果,从而可以获得可以对动物,更具体地对人体使用的政府或者与其等同的管制机构的批准或获得批准,或者罗列于药典或认定为其它普通药典。
在本说明书中,“盐”、尤其是“药学上可接受的盐”是对于个体比较非毒性且无害的具有有效作用的浓度,是将起因于芍药苷或芍药内酯苷的盐的副作用不会降低芍药苷或芍药内酯苷的有利功效的任意的所有有机或无机附加盐全部包括,将可存在于由芍药苷或芍药内酯苷表示的化合物的酸性或碱性基(group)的盐全部包括。有由药学上允许的游离酸(free acid)形成的酸附加盐或者由碱形成的金属盐。
作为所述游离酸,可以使用无机酸和有机酸,作为无机酸,可以使用盐酸、氢溴酸、溴酸、硫酸、盐酸、硫酸、亚硫酸、硝酸或磷酸,作为有机酸,可以使用乙酸、丙酸、己酸、环戊烷丙酸、乙醇酸、丙酮酸、乳酸、丙二酸、琥珀酸、苹果酸、马来酸、富马酸、酒石酸、柠檬酸、苯甲酸、3-(4-羟基苯甲酰基)苯甲酸、肉桂酸、扁桃酸、甲磺酸、乙磺酸、2-乙二磺酸、2-羟乙磺酸、苯磺酸、4-氯苯磺酸、2-萘磺酸、4-甲苯磺酸、樟脑磺酸、4-甲基双环[2,2,2]-辛-2-烯-1-羧酸、葡庚糖酸、3-苯基丙酸、三甲基乙酸、叔-7丁基乙酸、月桂基硫酸、葡萄糖酸、谷氨酸、羟基萘甲酸、水杨酸、硬脂酸、粘康酸、腐殖质或柠檬酸等。作为所述金属盐,有碱金属盐或碱土金属盐,钠、钾或钙盐是有用的。
在本说明书中,“异构体”不仅尤其包括光学异构体(optical isomers)(例如,基本上纯的对映异构体(essentially pure enantiomers)、基本上纯的非对映异构体(essentially pure diastereomers)或者它们的混合物),而且包括构象异构体(conformation isomers)(即仅一个以上的化学键的其角度不同的异构体)、位置异构体(position isomers)(尤其,互变异构体(tautomers))或几何异构体(geometric isomers)(例如,顺反异构体)。
所述“基本上纯的(essentially pure)”指的是,例如在与对映异构体或非对映异构体相关使用的情况下,可以将对映异构体或非对映异构体作为示例举出的具体化合物以约90%以上存在,优选地约95%以上,更优选地约97%以上或者约98%以上,还更优选地约99%以上,更加还更优选地约99.5%以上(w/w)。
在本说明书中,“水合物(hydrate)”指的是结合有水的化合物,是包括在水和化合物之间没有化学结合力的内含化合物的广范围概念。
在本说明书中,“溶剂化物”指的是形成于溶质的分子或离子和溶剂的分子或离子之间的高阶化合物。
在此,所述芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物可以购买市售的物质而使用,或者可以从芍药或牡丹等属于牡丹科的植物的提取物或分离物通过公知的方法分离和提纯而使用。但是,虽然在芍药或牡丹等属于牡丹科的植物的提取物或分离物等中包含有芍药苷或其盐、异构体、水合物或溶剂化物或者芍药内酯苷或其盐、异构体、水合物或溶剂化物,但是两种物质的组成和含量不同,经过从所述提取物或分离物提纯及分离的额外过程而获得的化合物即芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上相当于本发明的有效成分。
在一实施例中,为了得到基于有效成分的组合的协同效果,可以将所述芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物全部作为有效成分。作为一例,相对于100重量份的芍药苷或其盐、异构体、水合物或溶剂化物,芍药内酯苷或其盐、异构体、水合物或溶剂化物可以为1以上、2以上、3以上、4以上、5以上、6以上、7以上、8以上、9以上、10以上、11以下、12以下、13以下、14以下、15以下、16以下、17以下、18以下、19以下、20以下、21以下、22以下、23以下、24以下、25以下、26以下、27以下、28以下、29以下、30以下重量份,优选地可以为1至30重量份,更优选地可以为5至15重量份,但是不限于此。
在本说明书中,“内因性老化”也称为生理学老化,与随着年龄增长的正常老化相关,是遗传编码的序列的结果。相反,外因性老化是由于通常环境的老化,更详细地,这样的老化是由于暴露于太阳、光或者其它不同放射线而产生的光-老化现象的一种。
所述内因性老化使皮肤细胞的再生渐减,由此呈现出皮下脂肪组织减少之类的临床性损伤外观以及微细线和小皱纹的外观。另外,伴随着弹性纤维的数量和厚度增加、软组织纤维从弹性组织膜丧失以及从这样的弹性组织细胞产生大型不规则成纤维细胞之类的组织病理学变化。
作为一实施例,可以是由于内因性炎症、尤其是基于TNF-α的内因性炎症的老化。另外,本发明的内因性老化作为炎症因子除TNF-α之外,包括由于生物体内TNF-α增加而可能发生的所有内因性老化。即,作为一实施例,本发明的内因性老化可以是TNF-α引起的老化。
在本说明书中,“预防”指的是通过组合物的给予抑制内因性老化或者延迟内因性老化的发生的所有行为。
在本说明书中,“改善”指的是通过组合物的给予,使由于内因性老化的皱纹数量减少或者皮肤表面更有弹性,从而使得皮肤看起来更年轻的所有行为。
内因性老化和外因性老化的预防或改善的接近方法不同,作为一实施例,本发明的内因性老化预防或改善包括通过MMP-1抑制的方法,但不限于此。
所述芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物各自的给予量确定在本领域技术人员水平内,其一日给予容量可以是0.001以上、0.002以上、0.003以上、0.004以上、0.005以上、0.006以上、0.007以上、0.008以上、0.009以上、0.01以上、0.02以上、0.03以上、0.04以上、0.05以上、0.06以上、0.07以上、0.08以上、0.09以上、0.1以上、0.2以上、0.3以上、0.4以上、0.5以上、0.6以上、0.7以上、0.8以下、0.9以下、1以下、1.1以下、1.2以下、1.3以下、1.4以下、1.5以下、1.6以下、1.7以下、1.8以下、1.9以下、2以下、2.1以下、2.2以下、2.3以下、2.4以下、2.5以下、2.6以下、2.7以下、2.8以下、2.9以下、3以下、4以下、5以下、6以下、7以下、8以下、9以下、10以下mg/kg/日,不限于此,可以根据要给予的对象的年龄、健康状态、并发症等各种因素而不同。
另外,在一方面中,本发明提供一种内因性老化预防或改善用化妆品组合物,其包括:芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上作为有效成分。
在本说明书中,“化妆品组合物”是包括美化人体外貌的所有物品的概念,本发明的内因性老化预防或改善用化妆品组合物是指抑制作为根据生体节律的生理学现象的皮肤中的负面影响而美化人体外貌的物品的概念,但是不限于此。
所述化妆品组合物可以除了芍药苷或其盐、异构体、水合物或溶剂化;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物之外,还包括通常使用于化妆品组合物的抗氧化剂、稳定剂、增溶剂、维生素、色素、香料等之类通常辅助剂和载体。例如,在所述化妆品组合物中可以附加地还包括甘油、丁二醇、聚氧乙烯氢化蓖麻油、生育酚乙酸酯、柠檬酸、泛醇、角鲨烷、柠檬酸钠、尿囊素等辅助成分。此时,所述化妆品组合物内有效成分的含量(单位:重量%)相比于组合物整体重量可以为0.000001以上、0.000005以上、0.00001以上、0.00005以上、0.0001以上、0.0005以上、0.001以上、0.005以上、0.01以上、0.05以上、0.1以上、0.5以上、1以下、2以下、3以下、4以下、5以下、6以下、7以下、8以下、9以下、10以下,优选地可以为0.000001至10重量%,更优选地可以为0.000001至1重量%,最优选地可以为0.00001重量%,但是不限于此。作为一实施例,所述有效成分为芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上。由于所述化妆品组合物基本上涂抹于皮肤,因此可以参照本领域的化妆品组合物而制造为通常制造的任何制型。例如,可以制型化为溶液、悬浊液、乳浊液、膏、凝胶、霜、乳液、粉末、香皂、含有表面活性剂的洁面乳、油、粉末粉底、乳浊液粉底、蜡粉底和喷雾等,但是不限于此。更详细地,可以制造为柔软化妆水、营养化妆水、营养霜、按摩霜、精华液、眼霜、洁面乳、洁面泡沫、洁面水、面膜、喷雾或者粉末的制型。
在本发明的制型为膏、霜或凝胶的情况下,作为载体成分,可以包括动物油、植物油、蜡、石蜡、淀粉、黄芪胶、纤维素衍生物、聚乙二醇、硅酮、膨润土、二氧化硅、滑石粉、氧化锌等。
在本发明的制型为粉末或喷雾的情况下,作为载体成分,可以包括乳糖、滑石粉、二氧化硅、氢氧化铝、硅酸钙、聚酰胺粉末等,尤其在喷雾的情况下,可以附加地包括氯氟烃、丙烷/丁烷、二甲醚等推进剂。
在本发明的制型为溶液或乳浊液的情况下,作为载体成分,可以包括溶剂、增溶剂、乳化剂等,具体地,可以包括水、乙醇、异丙醇、碳酸乙酯、乙酸乙酯、苄醇、苯甲酸苄酯、丙二醇、1,3-丁二醇油、甘油脂族酯、聚乙二醇、脱水山梨醇的脂肪酸酯等
在本发明的制型为悬浊液的情况下,作为载体成分,可以包括:水、乙醇和丙二醇等液体稀释剂;乙氧基化异硬脂醇、聚氧乙烯山梨醇酯、聚氧乙烯山梨糖醇酯等悬浊剂;微晶纤维素、偏氢氧化铝、膨润土、琼脂、黄芪胶等。
在本发明的制型为含有表面活性剂的洁面乳的情况下,作为载体成分,可以包括脂肪醇硫酸盐、脂肪醇醚硫酸盐、磺基琥珀酸单酯、羟乙磺酸盐、咪唑啉鎓衍生物、牛磺酸甲酯、肌氨酸盐、脂肪酸酰胺醚硫酸盐、烷基氨基甜菜碱、脂肪醇、脂肪酸甘油酯、脂肪酸二乙醇酰胺、植物油、羊毛脂衍生物、乙氧基化甘油脂肪酸酯等。
另外,在一方面,本发明提供一种内因性老化预防或改善用健康功能食品组合物,其包括:芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上作为有效成分。
在本说明书中,“健康功能食品”指的是作为对食品利用物理、生化学、生物工学手段等而赋予附加价值以将相应食品的功能应用、体现于特定目的的食品群或具有食品组成的设计为针对生物体充分体现生物体防御节律调节、疾病防止和恢复等相关的体内调节功能的加工食品,应长期服用时对人体无害。
在所述健康功能食品中可以包括食品学可接受的食品辅助添加剂,可以还包括通常使用于健康功能食品制造的合适的载体、赋形剂和稀释剂。
在将所述健康功能食品组合物作为食品添加剂使用的情况下,可以将所述组合物直接添加或者与其它食品或食品成分一起使用,可以按照通常方法适当地使用。有效成分的混合量可以根据使用目的(预防、健康或者治疗性处置)适当地确定。一般地,所述食品组合物内有效成分的含量(单位:重量%)相比于组合物整体重量可以为0.000001以上、0.000005以上、0.00001以上、0.00005以上、0.0001以上、0.0005以上、0.001以上、0.005以上、0.01以上、0.05以上、0.1以上、0.5以上、1以下、2以下、3以下、4以下、5以下、6以下、7以下、8以下、9以下、10以下,优选地可以为0.000001至10重量%,更优选地可以为0.000001至1重量%,最优选地可以为0.00001重量%,但是不限于此。作为一实施例,所述有效成分为芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上。但是,在以健康和卫生为目的或者以健康调节为目的的长期摄取的情况下,可以是所述范围以下,由于从安全性层面没有任何问题,因此有效成分也可以以所述范围以上的量使用。
所述健康功能食品的重量没有特别限制。作为可以添加所述物质的健康功能食品的示例,存在含冰激凌类的乳产品、各种调料、饮料、茶、口服液、乙醇饮料和维生素复合剂等,将赋予附加价值以将通常含义上的相应食品的功能应用、体现于特定目的的食品群或具有食品组成的设计为针对生物体充分体现生物体防御节律调节、疾病防止和恢复等相关的体内调节功能的食品全部包括。
上述之外,本发明书中公开的健康功能食品组合物可以包括各种营养剂、维生素、电解质、风味剂、着色剂、果胶酸及其盐、海藻酸及其盐、有机酸、保护性胶体增稠剂、pH调节剂、稳定剂、防腐剂、甘油、乙醇、使用于碳酸饮料的碳酸化剂等。除此之外,本发明的食品组合物可以包括天然果汁、用于果汁饮料和蔬菜饮料的制造的果肉。这样的成分可以独立或组合使用。这样的添加剂的比例虽然不是很重要,但是通常在本发明的组合物的每100重量份中为0.01至0.1重量份的范围内选择。
考虑到本说明中的复杂性,省略重复的内容,在本说明书中没有不同地定义的用语具有在本发明所属技术领域中通常使用的含义。
以下,为了帮助理解本发明,举出实施例和比较例,进行详细说明。但是,下面的实施例和比较例仅是例示本发明的内容,本发明的范围不限制于下面实施例和比较例。为了向本技术领域中具有平均知识的人员更完整地说明本发明而提供本发明的实施例和比较例。
实施例1.基于芍药苷(paeoniflorin)或芍药内酯苷(albiflorin)的MMP-1抑制效果确认(刺激源:TNF-α)
将从ATCC公司获得的成纤维细胞分株于包含10%(v/v)FBS的培养基后,在37℃和5%CO2条件下培养24小时。之后将上述培养基更换为无血清培养基后,培养细胞6小时以上。然后,作为使内因性老化发生的内因性炎症因子,进行10ng/ml TNF-α处理,并以0.1ppm或1ppm进行芍药苷(Sigma Aldrich公司)处理后,培养48小时。经过48小时后,仅部分分离培养液,以该技术领域中通常使用的方式执行MMP-1ELISA。另一方面,对阴性对照组不进行芍药苷处理,对阳性对照组添加2μM ATRA(全反式维甲酸,All-trans retinoic acid)代替芍药苷。
接着,单独地部分分离剩余培养液,以该技术领域中通常使用的方式执行CCK8(细胞计数试剂盒-8,cell count kit-8)分析,从而测定细胞生存(cell viability),即细胞增殖率,利用上述测定值而校正通过执行上述MMP-1ELISA获得的结果值。
另一方面,除代替进行0.1ppm或1ppm芍药苷处理,进行0.1ppm或1ppm芍药内酯苷(Wako chemical公司)处理之外,通过与确认进行所述芍药苷处理而确认的MMP-1抑制效果相同的方式,确认基于芍药内酯苷的MMP-1抑制效果。
图1中示出根据上述实验的MMP-1值,表1中示出以阴性对照组为基准将上述图1的MMP-1值换算为MMP-1抑制率(%)的值。
[表1]
如上述表1和图1所示,在以进行了TNF-α处理的阴性对照组的值为100,作为阳性对照组的ATRA、实验组分别进行芍药苷或芍药内酯苷处理的情况下,确认到相比于阳性对照组,在作为实验组的芍药苷或芍药内酯苷中MMP-1具有约40左右的值。即,确认到基于芍药苷或芍药内酯苷的MMP-1抑制率为约60%左右。这表示芍药苷或芍药内酯苷具有优异的内因性老化预防或改善效果。
实施例2.基于芍药苷(paeoniflorin)和芍药内酯苷(albiflorin)组合的MMP-1抑制效果确认(刺激源:TNF-α)
除代替进行0.1ppm或1ppm芍药苷处理,分别以0.1+0.01ppm或0.1+0.01ppm进行10:1比例混合的芍药苷和芍药内酯苷组合(P+A)处理之外,通过与上述实施例1-1相同的方式确认基于芍药苷和芍药内酯苷组合的MMP-1抑制效果。
图2中示出根据上述实验的MMP-1值,表2中示出以阴性对照组为基准将上述图2的MMP-1值换算为MMP-1抑制率(%)的值。
[表2]
如表2和图2所示,在将芍药苷和芍药内酯苷适当混合而进行处理的情况下,确认到MMP-1抑制率为平均70%以上,具体地分别为70.02%和76.67%。是与从在上述实施例1中确认的芍药苷和芍药内酯苷分别获得的MMP-1抑制率相比显著的值。由此,上述实验结果表示芍药苷和芍药内酯苷组合具有显著的内因性老化预防或改善效果。
比较例1.基于芍药苷(paeoniflorin)或芍药内酯苷(albiflorin)的MMP-1抑制效果确认(刺激源:UV)
将从ATCC公司获得的成纤维细胞分株于包含10%(v/v)FBS的培养基后,在37℃和5%CO2条件下培养24小时。之后将上述培养基更换为无血清培养基后,培养细胞6小时以上。然后,作为使外因性老化发生的外因性炎症因子,以30mJ/cm2进行UVB处理,并以0.1ppm或1ppm进行芍药苷(Sigma Aldrich公司)处理后,培养48小时。经过48小时后,仅部分分离培养液,以该技术领域中通常使用的方式执行MMP-1ELISA。另一方面,对阴性对照组不进行芍药苷处理,对阳性对照组添加2μM ATRA(全反式维甲酸,All-trans retinoic acid)代替芍药苷。
接着,单独地部分分离剩余培养液,以该技术领域中通常使用的方式执行CCK8(细胞计数试剂盒-8,cell count kit-8)分析,从而测定细胞生存(cell viability),即细胞增殖率,利用上述测定值而校正通过执行上述MMP-1ELISA获得的结果值。
另一方面,除代替进行0.1ppm或1ppm芍药苷处理,进行0.1ppm或1ppm芍药内酯苷(Wako chemical公司)处理之外,通过与确认进行所述芍药苷处理而确认的MMP-1抑制效果相同的方式,确认基于芍药内酯苷的MMP-1抑制效果。
图3中示出根据上述实验的MMP-1值,表3中示出以阴性对照组为基准将上述图3的MMP-1值换算为MMP-1抑制率(%)的值。
[表3]
如上述表1和图1所示,在以进行了UBV处理的阴性对照组的值为100,作为阳性对照组的ATRA、作为实验组的芍药苷或芍药内酯苷分别进行处理的情况下,确认到相比于阳性对照组,在作为实验组的芍药苷或芍药内酯苷中MMP-1反而增加。相比于阴性对照组,MMP-1增加到最大22.03%程度。上述的结果表示芍药苷或芍药内酯苷对作为外因性老化的一种的光老化没有效果,同时启示是对内因性老化具有更特异效果的物质。
下面说明本发明的一实施例的组合物的制型例。也可以应用为其它各种制型,这不是为了限制本发明,是为了具体说明本发明。
制剂例1:化妆品制剂的制造
1-1.制造柔软化妆水
将0.1重量%的芍药苷或芍药内酯苷、5.2重量%的1,3-丁二醇、1.5重量%的油醇、3.2重量%的乙醇、3.2重量%的聚山梨酯20、2.0重量%的二苯甲酮-9、1.0重量%的羧乙烯基聚合物、3.5重量%的甘油、微量的香、微量的防腐剂和余量的纯净水混合而通过通常的方法制造柔软化妆水。
1-2.制造乳液
将0.1重量%的芍药苷或芍药内酯苷、5.1重量%的甘油、4.2重量%的丙二醇、3.0重量%的生育酚乙酸酯、4.6重量%的液体石蜡、1.0重量%的三乙醇胺、3.1重量%的角鲨烷、2.5重量%的澳洲坚果油、1.6重量%的聚山梨酯60、1.6重量%的脱水山梨醇倍半油酸酯、0.6重量%的对羟基苯甲酸丙酯、1.5重量%的羧乙烯基聚合物、微量的香、微量的防腐剂和余量的纯净水混合而通过通常的方法制造乳液。
1-3.制造营养霜
将0.5重量%的芍药苷或芍药内酯苷、4.0重量%的甘油、3.5重量%的凡士林、2.1重量%的三乙醇胺、5.3重量%的液体石蜡、3.0重量%的角鲨烷、2.6重量%的蜂蜡、5.4重量%的生育酚乙酸酯、3.2重量%的聚山梨酯60、1.0重量%的羧乙烯基聚合物、3.1重量%的脱水山梨醇倍半油酸酯、微量的香、微量的防腐剂和余量的纯净水混合而通过通常的方法制造营养霜。
1-4.制造按摩霜
将0.5重量%的芍药苷或芍药内酯苷、4.0重量%的甘油、3.5重量%的凡士林、0.5重量%的三乙醇胺、24.0重量%的液体石蜡、3.0重量%的角鲨烷、2.1重量%的蜂蜡、0.1重量%的生育酚乙酸酯、2.4重量%的聚山梨酯60、1.0重量%的羧乙烯基聚合物、2.3重量%的脱水山梨醇倍半油酸酯、微量的香、微量的防腐剂和余量的纯净水混合而通过通常的方法制造按摩霜。
1-5.制造清洗用沐浴乳
将1g芍药苷或芍药内酯苷、18g阴离子表面活性剂、5g非离子表面活性剂、7g甘油、3g氯化钠、1.5g天然橄榄液体肥皂、1g香料和100g水混合而通过通常的方法制造清洗用沐浴乳。
制剂例2:食品制剂的制造
2-1.制造健康食品
将100mg芍药苷或芍药内酯苷、适量的维生素混合物、70g乙酸维生素A、1.0mg维生素E、0.13mg维生素B1、0.15mg维生素B2、0.5mg维生素B6、0.2g维生素B12、10mg维生素C、10g生物素、1.7mg烟酰胺、50g叶酸、0.5mg泛酸钙、适量的矿物质混合物、1.75mg硫酸亚铁、0.82mg氧化锌、25.3mg碳酸镁、15mg磷酸一钾、55mg磷酸二钙、90mg柠檬酸钾、100mg碳酸钙和24.8mg氯化镁混合后,制造颗粒,并按照通常的方法制备健康食品。
此时,上述维生素和矿物质混合物的组成比是将比较适合于健康食品的成分以优选的实施例混合组成,但是将其配比任意变形实施也无妨。
2-2.制造健康饮料
按照通常的健康饮料制造方法,将100mg芍药苷或芍药内酯苷、15g维生素C、100g维生素E(粉末)、19.75g乳酸铁、3.5g氧化锌、3.5g烟酰胺、0.2g维生素A、0.25g维生素B1、0.3g维生素B2和定量的水混合后,在85℃下搅拌加热约1小时后,过滤制备的溶液,获取于灭菌的2L容器,密封灭菌后,冷藏保管,从而制造健康饮料。
此时,上述组成比是将比较适合于喜好饮料的成分以优选的实施例混合组成,但是根据需求阶层或需求国家、使用用途等地域性、民族性喜好,将其配比任意变形实施也无妨。
Claims (7)
1.一种内因性老化预防或改善用组合物,包含:芍药苷或其盐、异构体、水合物或溶剂化物;以及芍药内酯苷或其盐、异构体、水合物或溶剂化物中的一种以上作为有效成分。
2.根据权利要求1所述的内因性老化预防或改善用组合物,其中,
相对于100重量份的所述芍药苷或其盐、异构体、水合物或溶剂化物,所述芍药内酯苷或其盐、异构体、水合物或溶剂化物为1至30重量份。
3.根据权利要求1或2所述的内因性老化预防或改善用组合物,其中,
所述内因性老化为内因性炎症引起的老化。
4.根据权利要求1或2所述的内因性老化预防或改善用组合物,其中,
所述内因性老化为TNF-α引起的老化。
5.根据权利要求1或2所述的内因性老化预防或改善用组合物,其中,
所述内因性老化预防或改善是通过抑制MMP-1实现。
6.根据权利要求1或2所述的内因性老化预防或改善用组合物,其中,
所述组合物是化妆品组合物。
7.根据权利要求1或2所述的内因性老化预防或改善用组合物,其中,
所述组合物是健康功能食品组合物。
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