JP2021116276A - Skin aging inhibitor - Google Patents
Skin aging inhibitor Download PDFInfo
- Publication number
- JP2021116276A JP2021116276A JP2020012419A JP2020012419A JP2021116276A JP 2021116276 A JP2021116276 A JP 2021116276A JP 2020012419 A JP2020012419 A JP 2020012419A JP 2020012419 A JP2020012419 A JP 2020012419A JP 2021116276 A JP2021116276 A JP 2021116276A
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- JP
- Japan
- Prior art keywords
- extract
- acid
- skin aging
- prevention
- expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Abstract
Description
本発明は、LncRNA発現促進剤、同発現促進剤からなる皮膚老化抑制剤、同皮膚老化抑制剤を含む皮膚老化抑制用組成物等に関する。 The present invention relates to an LncRNA expression promoter, a skin aging inhibitor composed of the expression promoter, a skin aging inhibitor composition containing the skin aging inhibitor, and the like.
生物を構成する細胞は加齢により老化する。細胞は、生体反応を担っており、生命活動を担う組織・器官を形成・維持しており、細胞の老化は個体の老化にも繋がる。
また、老化した細胞は周囲の細胞に対しても老化細胞様の反応を惹起させる因子を放出し、組織・器官の老化を加速させる。このため、老化細胞を取り除くと個体や組織の老化を遅らすことができ、既に生じた老化症状を改善できることが示唆されている(例えば、非特許文献1参照)。
The cells that make up an organism age with age. Cells are responsible for biological reactions and form and maintain tissues and organs responsible for vital activities, and cell aging also leads to individual aging.
In addition, aged cells release factors that induce an aged cell-like reaction to surrounding cells, accelerating the aging of tissues and organs. Therefore, it has been suggested that removing aging cells can delay the aging of individuals and tissues and improve the aging symptoms that have already occurred (see, for example, Non-Patent Document 1).
したがって、老化細胞は抗老化のターゲットとして期待されている(例えば、非特許文献2参照)。しかしながら、非侵襲的に老化細胞を取り除くことは実施が難しいという課題があった。 Therefore, senescent cells are expected as a target for anti-aging (see, for example, Non-Patent Document 2). However, there is a problem that it is difficult to remove senescent cells non-invasively.
一方、近年、細胞老化をコントロールする生体成分として、タンパク質をコードしていないRNAであるノンコーディングRNA(ncRNA)が報告されている(例えば、非特許文献3参照)。このncRNAの中には塩基数200以上のRNAである長鎖ncRNA(LncRNA)が知られており、LncRNAは8200種ほど存在すると推測されている(例えば、非特許文献4参照)。LncRNAに関して、近年、若齢および老齢ドナーから皮膚を採取し、発現量が比較され、いくつかのLncRNAの量が加齢により変化していることが報告されている(例えば、非特許文献5参照)。 On the other hand, in recent years, non-coding RNA (ncRNA), which is an RNA that does not encode a protein, has been reported as a biological component that controls cell senescence (see, for example, Non-Patent Document 3). Among these ncRNAs, long-chain ncRNAs (LncRNAs), which are RNAs having 200 or more bases, are known, and it is estimated that there are about 8200 types of LncRNAs (see, for example, Non-Patent Document 4). Regarding LncRNA, in recent years, skin samples have been collected from young and old donors, their expression levels have been compared, and it has been reported that the levels of some LncRNAs change with age (see, for example, Non-Patent Document 5). ).
加齢により発現が増加するNESPAS、FLJ46906、HOTAIRのLncRNAと、加齢により発現が減少するSNHG5、LOC100292680(別名「LINC00942」であり、これらは同一のLncRNAを示す)、IPWのLncRNAが、特に細胞老化の抑制効果を判断するのに有力な指標であり、該LncRNAを指標として皮膚老化を抑制する効果を判断できることが報告されている(例えば、特許文献1および2参照)。 NESPAS, FLJ46906, and HOTAIR LncRNAs whose expression increases with age, and SNHG5, LOC100292680 (also known as "LINC00942", which indicate the same LncRNA) whose expression decreases with age, IPW LncRNAs, especially cells. It is a powerful index for determining the effect of suppressing aging, and it has been reported that the effect of suppressing skin aging can be determined using the LncRNA as an index (see, for example, Patent Documents 1 and 2).
他方、シソ目植物に含まれるカルノシン酸、ロスマノールおよびイソロスマノール等のロスマノールおよびその類縁体は抗酸化作用を有することが知られているが、抗老化等の作用については知られていない。 On the other hand, rosmanols such as carnosic acid, rosmanol and isorosmanol and their analogs contained in Lamiales plants are known to have an antioxidant effect, but their effects such as anti-aging are not known.
抗老化の化粧料等への要望は高く、新たな皮膚老化抑制素材が求められている。このような要望に対応するため、本発明はなされたものであり、本発明は、新たな皮膚老化抑制素材を提供することを課題とする。 There is a high demand for anti-aging cosmetics and the like, and new skin aging-suppressing materials are required. In order to meet such a demand, the present invention has been made, and it is an object of the present invention to provide a new skin aging inhibitory material.
本発明者らは、新たな皮膚老化抑制素材を求めて各種素材について検討を行ったところ、シソ目植物に含まれるカルノシン酸、ロスマノール、イソロスマノール等のロスマノールおよびその類縁体、その他にガルス酸等の芳香族ヒドロキシ酸といった化合物がLncRNAであるLINC00942の発現を促進(または亢進)する効果を有し、皮膚老化抑制素材として有効であることを見出し、本発明を完成した。
すなわち、本発明の要旨は以下に関する。
The present inventors investigated various materials in search of a new skin aging inhibitory material, and found that rosmanols such as carnosic acid, rosmanol, and isolosmanol contained in Lamiales plants and their analogs, and other galsic acids. We have found that compounds such as aromatic hydroxy acids such as LncRNA have an effect of promoting (or enhancing) the expression of LINC00942, which is an LncRNA, and are effective as a skin aging inhibitory material, and completed the present invention.
That is, the gist of the present invention relates to the following.
[1] ロスマノールおよびその類縁体、並びに芳香族ヒドロキシ酸から選ばれる1種または2種以上からなる、LINC00942の発現促進剤。
[2] ロスマノールおよびその類縁体が、下記式(I)で表される化合物である、[1]に記載の発現促進剤。
[1] An expression promoter of LINC00942, which comprises one or more selected from rosmanol and its analogs, and aromatic hydroxy acids.
[2] The expression-promoting agent according to [1], wherein Rosmanol and its analogs are compounds represented by the following formula (I).
(式中、
R1およびR2は、それぞれ独立に、水素、酸素、ヒドロキシ、または炭素数1〜6のアルキルオキシであり、
R3は、カルボキシ、もしくは炭素数1〜6のアルコキシカルボニルであるか、またはR4またはR5と一緒になって-CO-O-であり、
R4およびR5は、それぞれ独立に、水素、酸素、ヒドロキシ、もしくは炭素数1〜6のアルキルオキシであり、
環に結合する水素は、それぞれ独立に、酸素、炭素数1〜6のアルキル、炭素数2〜6のアルケニルもしくはアルキニル、または炭素数1〜6のアルキルオキシで置換されてもよい。)
[3] ロスマノールおよびその類縁体が、カルノシン酸、ロスマノールおよびイソロスマノールから選ばれる1種または2種以上である、[1]または[2]に記載の発現促進剤。
[4] 芳香族ヒドロキシ酸が、トリヒドロキシ安息香酸である、[1]〜[3]のいずれかに記載の発現促進剤。
[5] 芳香族ヒドロキシ酸が、ガルス酸である、[1]〜[4]のいずれかに記載の発現促進剤。
[6] ロスマノールおよびその類縁体から選ばれる1種または2種以上、並びに芳香族ヒドロキシ酸から選ばれる1種または2種以上の組合せからなる、LINC00942の発現促進剤。
[7] [1]〜[6]のいずれかに記載の発現促進剤からなる、皮膚老化抑制剤。
[8] [7]に記載の皮膚老化抑制剤を含む、皮膚老化抑制用組成物。
[9] 皮膚老化抑制が、肌弾力性低下防止、しわ防止、たるみ防止、シミ形成防止、くすみ防止および毛穴拡大防止から選ばれる1種または2種以上である、[8]に記載の組成物。
[10] 医薬部外品を含む化粧料である、[8]または[9]に記載の組成物。
[11] シソ抽出物、ラベンダー抽出物、セージ抽出物、ローズマリー抽出物、およびクマツヅラ抽出物のいずれか1種または2種以上からなる、LINC00942の発現促進剤。
[12] [11]に記載の発現促進剤からなる、皮膚老化抑制剤。
[13] [12]に記載の皮膚老化抑制剤を含む、皮膚老化抑制用組成物。
[14] 皮膚老化抑制が、肌弾力性低下防止、しわ防止、たるみ防止、シミ形成防止、くすみ防止および毛穴拡大防止から選ばれる1種または2種以上である、[13]に記載の組成物。
[15] 医薬部外品を含む化粧料である、[13]または[14]に記載の組成物。
(During the ceremony,
R 1 and R 2 are independently hydrogen, oxygen, hydroxy, or alkyloxy with 1 to 6 carbon atoms, respectively.
R 3 is a carboxy, or an alkoxycarbonyl with 1 to 6 carbon atoms, or is -CO-O- with R 4 or R 5.
R 4 and R 5 are independently hydrogen, oxygen, hydroxy, or alkyloxy with 1 to 6 carbon atoms, respectively.
The hydrogen bonded to the ring may be independently substituted with oxygen, an alkyl having 1 to 6 carbon atoms, an alkenyl or alkynyl having 2 to 6 carbon atoms, or an alkyloxy having 1 to 6 carbon atoms. )
[3] The expression-promoting agent according to [1] or [2], wherein the rosmanol and its analogs are one or more selected from carnosic acid, rosmanol and isorosmanol.
[4] The expression promoter according to any one of [1] to [3], wherein the aromatic hydroxy acid is trihydroxybenzoic acid.
[5] The expression promoter according to any one of [1] to [4], wherein the aromatic hydroxy acid is a gals acid.
[6] An expression promoter of LINC00942, which comprises one or more selected from Rosmanol and its analogs, and one or a combination of one or more selected from aromatic hydroxy acids.
[7] A skin aging inhibitor comprising the expression-promoting agent according to any one of [1] to [6].
[8] A composition for suppressing skin aging, which comprises the skin aging inhibitor according to [7].
[9] The composition according to [8], wherein the skin aging suppression is one or more selected from skin elasticity reduction prevention, wrinkle prevention, sagging prevention, stain formation prevention, dullness prevention and pore expansion prevention. ..
[10] The composition according to [8] or [9], which is a cosmetic containing a quasi-drug.
[11] An expression promoter of LINC00942, which comprises any one or more of perilla extract, lavender extract, sage extract, rosemary extract, and verbena extract.
[12] A skin aging inhibitor comprising the expression-promoting agent according to [11].
[13] A composition for suppressing skin aging, which comprises the skin aging inhibitor according to [12].
[14] The composition according to [13], wherein the skin aging suppression is one or more selected from skin elasticity reduction prevention, wrinkle prevention, sagging prevention, stain formation prevention, dullness prevention and pore expansion prevention. ..
[15] The composition according to [13] or [14], which is a cosmetic containing a quasi drug.
本発明によれば、LINC00942の発現を促進する効果を有する、新たな皮膚老化抑制素材を提供することができる。 According to the present invention, it is possible to provide a new skin aging inhibitory material having an effect of promoting the expression of LINC00942.
以下、本発明について説明する。
<LINC00942の発現促進剤>
本発明の一態様は、ロスマノールおよびその類縁体、シソ目植物抽出物および芳香族ヒドロキシ酸から選ばれる1種または2種以上からなる、LINC00942の発現促進剤(以下、「本発明の発現促進剤」ということがある)に関する。
Hereinafter, the present invention will be described.
<Expression promoter of LINC00942>
One aspect of the present invention is an expression promoter of LINC00942, which comprises one or more selected from Rosmanol and its analogs, Lamiales plant extracts and aromatic hydroxy acids (hereinafter, "expression promoter of the present invention"). ”).
本発明者らは、新たな皮膚老化抑制素材を求めて各種素材について検討を行ったところ、ロスマノールおよびその類縁体、芳香族ヒドロキシ酸が、皮膚老化抑制作用を有することを知見した。また、ロスマノールおよびその類縁体、シソ目植物抽出物および芳香族ヒドロキシ酸が、LINC00942の発現促進作用を有することを知見した。このようにして、本発明のLINC00942の発現促進剤は、見出されたものである。
本発明の発現促進剤としては、具体的には、以下の化合物が挙げられる。
The present inventors investigated various materials in search of a new skin aging inhibitory material, and found that Rosmanol and its analogs, aromatic hydroxy acids, have a skin aging inhibitory effect. It was also found that Rosmanol and its analogs, Lamiales plant extract and aromatic hydroxy acids have an expression-promoting effect on LINC00942. In this way, the expression promoter of LINC00942 of the present invention has been found.
Specific examples of the expression promoter of the present invention include the following compounds.
≪ロスマノールおよびその類縁体≫
本発明の発現促進剤として用いられるロスマノールおよびその類縁体は、LINC00942の発現促進作用を有するものであれば、限定されない。ロスマノールおよびその類縁体は、シソ、ラベンダー、セージ、ローズマリー、クマツヅラ等のシソ目(Lamiales)植物等に含まれる、ロスマノールおよびロスマノール類縁化合物である。ロスマノールおよびその類縁体の由来は、限定されない。ロスマノールおよびその類縁体は、1種または2種以上の組合せをLINC00942の発現促進剤として使用できる。
≪Rosmanol and its analogs≫
Rosmanol and its analogs used as the expression-promoting agent of the present invention are not limited as long as they have the expression-promoting action of LINC00942. Rosmanol and its analogs are Rosmanol and Rosmanol analogs contained in Lamiales plants such as perilla, lavender, sage, rosemary, and verbena. The origin of Rosmanol and its analogs is not limited. Rosmanol and its analogs can be used alone or in combination of two or more as an expression promoter for LINC00942.
ロスマノールおよびその類縁体としては、例えば、下記式(I)で表される化合物が挙げられる。 Examples of Rosmanol and its analogs include compounds represented by the following formula (I).
式中、R1およびR2は、それぞれ独立に、水素、酸素、ヒドロキシ、または炭素数1〜6(好ましくは炭素数1〜3、より好ましくは炭素数1〜2)のアルキルオキシである。ただし、R1またはR2が酸素のときは、二重結合で環に結合する。R1およびR2は、好ましくはヒドロキシ、またはアルキルオキシである。
炭素数1〜6のアルキルオキシとしては、例えば、メトキシ、エトキシ、n-プロポキシ、イソプロポキシ、n-ブトキシ、イソブトキシ、sec-ブトキシ、tert-ブトキシ、n-ペントキシ、n-ヘキソキシ等が挙げられる。
In the formula, R 1 and R 2 are independently hydrogen, oxygen, hydroxy, or alkyloxy having 1 to 6 carbon atoms (preferably 1 to 3 carbon atoms, more preferably 1 to 2 carbon atoms). However, when R 1 or R 2 is oxygen, it is bonded to the ring by a double bond. R 1 and R 2 are preferably hydroxy or alkyloxy.
Examples of alkyloxy having 1 to 6 carbon atoms include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexoxy and the like.
R3は、カルボキシ、もしくは炭素数1〜6(好ましくは炭素数1〜3、より好ましくは炭素数1〜2)のアルコキシカルボニルであるか、またはR4またはR5と一緒になって-CO-O-である。R3は、好ましくはカルボキシ、またはR4またはR5と一緒になって-CO-O-である。R3が、R4またはR5と一緒になって-CO-O-である場合、R3と結合しないR4またはR5は、好ましくは水素以外である。
炭素数1〜6のアルコキシカルボニルとしては、例えば、メトキシカルボニル、エトキシカルボニル、n-プロポキシカルボニル、イソプロポキシカルボニル、n-ブトキシカルボニル、イソブトキシカルボニル、sec-ブトキシカルボニル、tert-ブトキシカルボニル、n-ペントキシカルボニル、n-ヘキソキシカルボニル等が挙げられる。
R 3 is a carboxy, or alkoxycarbonyl with 1 to 6 carbons (preferably 1-3 carbons, more preferably 1-2 carbons), or with R 4 or R 5 -CO. -O-. R 3 is preferably -CO-O- with carboxy, or R 4 or R 5. R 3 is, if taken together with R 4 or R 5 is -CO-O-, R 4 or R 5 is not bonded to R 3 is preferably other than hydrogen.
Examples of the alkoxycarbonyl having 1 to 6 carbon atoms include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, and n-pen. Examples thereof include toxicarbonyl, n-hexoxycarbonyl and the like.
R4およびR5は、それぞれ独立に、水素、酸素、ヒドロキシ、もしくは炭素数1〜6(好ましくは炭素数1〜3、より好ましくは炭素数1〜2)のアルキルオキシである。アルキルオキシの具体例としては、上記と同様である。R4およびR5は、好ましくは、水素、ヒドロキシ、またはアルキルオキシである。 R 4 and R 5 are independently hydrogen, oxygen, hydroxy, or alkyloxy having 1 to 6 carbon atoms (preferably 1 to 3 carbon atoms, more preferably 1 to 2 carbon atoms). Specific examples of alkyloxy are the same as described above. R 4 and R 5 are preferably hydrogen, hydroxy, or alkyloxy.
環に結合する水素は、それぞれ独立に、酸素、炭素数1〜6の直鎖状、分岐鎖状、もしくは環状アルキル、炭素数2〜6の直鎖状、分岐鎖状のアルケニルもしくはアルキニル、または炭素数1〜6のアルキルオキシで置換されてもよい。
アルキルとしては、例えば、メチル、エチル、n-プロピル、イソプロピル、n-ブチル、イソブチル、sec-ブチル、tert-ブチル、n-ペンチル、n-ヘキシル、シクロプロピル、シクロブチル、シクロペンチルおよびシクロヘキシル等が挙げられる。
アルケニルは、前記アルキルのいずれか1カ所以上に炭素・炭素二重結合を有する炭素数2〜6の直鎖状、または分岐鎖状のアルケニルである。例えば、ビニル、1−プロペニル、アリル、1−ブテニル、2−ブテニル、3−ブテニル、1−ペンテニル、2−ペンテニル、3−ペンテニル、4−ペンテニル、1−ヘキセニル、2−ヘキセニル、3−ヘキセニル、4−ヘキセニル、5−ヘキセニル等が挙げられる。
アルキニルは、前記アルキルのいずれか1カ所以上に炭素・炭素三重結合を有する炭素数2〜6の直鎖状、または分岐鎖状のアルキニルである。例えば、エチニル、1−プロピニル、プロパルギル、1−ブチニル、2−ブチニル、3−ブチニル、1−ペンチニル、2−ペンチニル、3−ペンチニル、4−ペンチニル、1−ヘキシニル等である。
アルキルオキシの具体例としては、上記と同様である。
The hydrogens attached to the rings are independently oxygen, linear, branched or cyclic alkyl with 1 to 6 carbon atoms, linear or branched chain alkynyl or alkynyl with 2 to 6 carbon atoms, or It may be replaced with an alkyloxy having 1 to 6 carbon atoms.
Examples of the alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. ..
The alkenyl is a linear or branched alkenyl having 2 to 6 carbon atoms and having a carbon-carbon double bond at one or more of the above alkyls. For example, vinyl, 1-propenyl, allyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, Examples thereof include 4-hexenyl, 5-hexenyl and the like.
The alkynyl is a linear or branched alkynyl having 2 to 6 carbon atoms and having a carbon-carbon triple bond at one or more of the alkyl. For example, ethynyl, 1-propynyl, propargyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl and the like.
Specific examples of alkyloxy are the same as described above.
ロスマノールおよびその類縁体は、限定されないが、好ましくはカルノシン酸、ロスマノール、イソロスマノール、11,12-ジ-O-メチルイソロスマノール、12-O-カルノシン酸、ロスマノール-9-エチルエーテル、エピロスマノール、7-メチル-エピロスマノールであり、より好ましくはカルノシン酸、ロスマノールまたはイソロスマノールである。 Rosmanol and its analogs are preferably, but not limited to, carnosic acid, rosmanol, isolosmanol, 11,12-di-O-methylisorosmanol, 12-O-carnosic acid, rosmanol-9-ethyl ether, epirus. Manol, 7-methyl-epirosmanol, more preferably carnosic acid, rosmanol or isorosmanol.
ロスマノールおよびその類縁体は、常法に基づいて製造、クロマトグラフィー等を用いて分離精製されたものを用いることができ、市販されたものを用いることもできる。 As Rosmanol and its analogs, those which have been separated and purified by production, chromatography or the like based on a conventional method can be used, and commercially available ones can also be used.
≪シソ目植物抽出物≫
本発明の発現促進剤として用いられるシソ目植物抽出物は、LINC00942の発現促進作用を有するものであれば、限定されない。シソ目植物抽出物は、シソ目の果実、および/または葉、および/または茎、および/または根を、水、および/または有機溶媒で抽出することで得ることができる。
使用可能な有機溶媒として、メタノール、エタノール等の脂肪族アルコール、アセトン等の脂肪族ケトン、ジオキサン、エチルエーテル等の脂肪族エーテル、塩化メチレン、クロロホルム等のハロゲン化炭化水素、酢酸エチル、酢酸ブチル、酢酸イソブチル等の脂肪酸エステル、ヘキサン、ベンゼン等の炭化水素類、およびこれらの溶媒の2種以上の混合物が例示できる。
≪Lamiales plant extract≫
The Lamiales plant extract used as the expression-promoting agent of the present invention is not limited as long as it has the expression-promoting action of LINC00942. Lamiales plant extracts can be obtained by extracting Lamiales fruits and / or leaves and / or stems and / or roots with water and / or organic solvents.
As usable organic solvents, aliphatic alcohols such as methanol and ethanol, aliphatic ketones such as acetone, aliphatic ethers such as dioxane and ethyl ether, halogenated hydrocarbons such as methylene chloride and chloroform, ethyl acetate and butyl acetate, Examples thereof include fatty acid esters such as isobutyl acetate, hydrocarbons such as hexane and benzene, and mixtures of two or more of these solvents.
≪芳香族ヒドロキシ酸≫
本発明の発現促進剤として用いられる芳香族ヒドロキシ酸は、LINC00942の発現促進作用を有するものであれば、限定されない。芳香族ヒドロキシ酸としては特に限定されないが、例えば、モノヒドロキシ安息香酸誘導体としてサリチル酸、クレオソート酸(ホモサリチル酸、ヒドロキシ(メチル)安息香酸)、バニリン酸、シリング酸、ジヒドロキシ安息香酸誘導体としてピロカテク酸、レソルシル酸、プロトカテク酸、ゲンチジン酸、オルセリン酸、トリヒドロキシ安息香酸誘導体として、ガルス酸、フェニル酢酸誘導体として、マンデル酸、ベンジル酸、アトロラクチン酸、ケイヒ酸・ヒドロケイヒ酸誘導体として、メリロト酸、フロレト酸、クマル酸、ウンベル酸、コーヒー酸、フェルラ酸、シナピン酸等が挙げられ、これらの異性体であってもよい。芳香族ヒドロキシ酸として、好ましくはトリヒドロキシ安息香酸誘導体であり、より好ましくはガルス酸である。芳香族ヒドロキシ酸は、1種または2種以上の組合せをLINC00942の発現促進剤として使用できる。
≪Aromatic hydroxy acids≫
The aromatic hydroxy acid used as the expression-promoting agent of the present invention is not limited as long as it has an expression-promoting action of LINC00942. The aromatic hydroxy acid is not particularly limited. Resolcilic acid, protocatechuic acid, gentidic acid, orseric acid, trihydroxybenzoic acid derivatives, gals acid, phenylacetic acid derivatives, mandelic acid, benzylic acid, atrolactic acid, silicic acid / hydrosilicic acid derivatives, melilothic acid, floretic acid , Kumaric acid, Umberic acid, coffee acid, ferulic acid, synapic acid and the like, and may be isomers of these. The aromatic hydroxy acid is preferably a trihydroxybenzoic acid derivative, more preferably galsic acid. Aromatic hydroxy acids can be used alone or in combination of two or more as an expression promoter for LINC00942.
ガルス酸は、別名、没食子酸ともいい、月見草抽出物や赤ワイン抽出物、メリッサ葉抽出物等に含まれる化合物である。本発明に用いるガルス酸の由来は、限定されない。
上記化合物は、常法に基づいて製造、分離精製されたものを用いることができ、市販されたものを用いることもできる。
Gallic acid, also known as gallic acid, is a compound contained in evening primrose extract, red wine extract, Melissa leaf extract and the like. The origin of the gallic acid used in the present invention is not limited.
As the above compound, a compound produced, separated and purified based on a conventional method can be used, and a commercially available compound can also be used.
本発明の別の一態様としては、ロスマノールおよびその類縁体から選ばれる1種または2種以上、並びに芳香族ヒドロキシ酸から選ばれる1種または2種以上の組合せからなる、LINC00942の発現促進剤が挙げられる。 Another aspect of the present invention is an expression promoter of LINC00942, which comprises one or more selected from Rosmanol and its analogs, and one or more combinations selected from aromatic hydroxy acids. Can be mentioned.
LINC00942の発現促進作用は、例えば、特開2015-130857号公報に記載の方法に基づいて、確認できる。 The expression-promoting action of LINC00942 can be confirmed, for example, based on the method described in JP-A-2015-130857.
<皮膚老化抑制剤>
本発明のさらなる一態様は、本発明の発現促進剤からなる、皮膚老化抑制剤(以下、「本発明の皮膚老化抑制剤」ということがある)に関する。
本発明の皮膚老化抑制剤は、LINC00942の発現促進作用を有し、肌弾力性改善効果、しわ防止効果、たるみ防止効果、シミ形成防止効果、くすみ防止効果、毛穴拡大防止効果から選択される1種以上の効果を奏し、後述するように化粧料、医薬部外品、食品、医薬品等に配合されることで、アンチエイジング効果を奏する。
<Skin aging inhibitor>
A further aspect of the present invention relates to a skin aging inhibitor (hereinafter, may be referred to as "the skin aging inhibitor of the present invention"), which comprises the expression promoter of the present invention.
The skin aging inhibitor of the present invention has an expression promoting effect of LINC00942 and is selected from the skin elasticity improving effect, the wrinkle preventing effect, the sagging preventing effect, the stain formation preventing effect, the dullness preventing effect, and the pore enlargement preventing effect1 It has more than a seed effect, and when it is added to cosmetics, quasi-drugs, foods, pharmaceuticals, etc. as described later, it has an anti-aging effect.
<皮膚老化抑制用組成物>
本発明のさらなる一態様は、本発明の皮膚老化抑制剤を含む、皮膚老化抑制用組成物(以下、「本発明の組成物」ということがある)に関する。
本発明の皮膚老化抑制用組成物は、本発明の皮膚老化抑制剤を含み、その効果を妨げない限り、さらに化粧料、医薬部外品、食品、医薬品等に使用される成分を含有し、皮膚老化抑制用に用いることができる組成物である。
本発明の皮膚老化抑制用組成物は、化粧料、医薬部外品、食品、医薬品等として適用され、化粧料、医薬部外品、医薬品の場合には肌に組成物を塗布することで皮膚老化抑制用組成物の摂取を行い、食品の場合には、経口により摂取する。
<Composition for suppressing skin aging>
A further aspect of the present invention relates to a skin aging inhibitory composition (hereinafter, may be referred to as "the composition of the present invention") containing the skin aging inhibitor of the present invention.
The composition for suppressing skin aging of the present invention contains the skin aging inhibitor of the present invention, and further contains ingredients used in cosmetics, quasi-drugs, foods, pharmaceuticals, etc. as long as the effects are not impaired. It is a composition that can be used for suppressing skin aging.
The composition for suppressing skin aging of the present invention is applied as cosmetics, non-pharmaceutical products, foods, pharmaceuticals, etc., and in the case of cosmetics, non-pharmaceutical products, pharmaceuticals, the composition is applied to the skin to make the skin. Ingest the anti-aging composition, and in the case of food, ingest it orally.
本実施態様における、皮膚老化抑制用組成物中の皮膚老化抑制素材の含有量(配合量)は、限定されないが、通常0.00001質量%以上、好ましくは0.0001質量%以上、より好ましくは0.001質量%以上であり、通常80質量%以下、好ましくは30質量%以下、より好ましくは10質量%である。上記範囲とすることで、好適にアンチエイジング効果を奏する皮膚老化防止組成物とすることができる。
また、皮膚老化防止組成物に含有させる皮膚老化抑制剤の種類は、1種類のみでなく2種類以上であってもよい。
The content (blending amount) of the skin aging inhibitory material in the skin aging inhibitory composition in the present embodiment is not limited, but is usually 0.00001% by mass or more, preferably 0.0001% by mass or more, and more preferably 0.001% by mass or more. It is usually 80% by mass or less, preferably 30% by mass or less, and more preferably 10% by mass. Within the above range, a skin anti-aging composition that preferably exerts an anti-aging effect can be obtained.
Further, the type of the skin aging inhibitor contained in the skin aging prevention composition may be not only one type but also two or more types.
皮膚老化抑制用組成物は、化粧品、医薬部外品、食品、医薬品等に適用することが可能であり、それぞれの用途に応じて、適宜必要な成分を含有させることができる。皮膚老化抑制用組成物は、常法に基づいて、本発明の皮膚老化抑制剤および化粧品、医薬部外品、食品、医薬品等に使用される任意成分を配合し、製剤化することで製造することができる。 The composition for suppressing skin aging can be applied to cosmetics, quasi-drugs, foods, pharmaceuticals, etc., and can appropriately contain necessary components according to each use. The composition for suppressing skin aging is produced by blending and formulating the skin aging inhibitor of the present invention and any ingredient used in cosmetics, quasi-drugs, foods, pharmaceuticals, etc., based on a conventional method. be able to.
皮膚老化抑制用組成物は、特に化粧料に適用させることが好ましい。
化粧料に適用される場合、通常化粧料に使用される成分を広く配合することが可能であり、また、その剤形や用途についても、何ら限定されない。
The composition for suppressing skin aging is particularly preferably applied to cosmetics.
When applied to cosmetics, it is possible to widely blend ingredients normally used in cosmetics, and the dosage form and use thereof are not limited in any way.
以下、化粧料に適用される場合、化粧料中に含有させることができる成分について説明する。
本発明の皮膚老化抑制用組成物には、本発明の皮膚老化抑制剤以外に、さらに、同じまたは異なる機能を有する有効成分を配合してもよい。
有効成分としては、美白成分、しわ改善成分、抗炎症成分、動植物由来のエキス等が挙げられる。
Hereinafter, the ingredients that can be contained in the cosmetics when applied to the cosmetics will be described.
In addition to the skin aging inhibitor of the present invention, the skin aging inhibitory composition of the present invention may further contain an active ingredient having the same or different functions.
Examples of the active ingredient include a whitening ingredient, a wrinkle improving ingredient, an anti-inflammatory ingredient, an animal and plant-derived extract, and the like.
美白成分としては、一般的に化粧料に用いられているものであれば特に限定はない。例えば、4-n-ブチルレゾルシノール、アスコルビン酸グルコシド、3-О-エチルアスコルビン酸、トラネキサム酸、アルブチン、1-トリフェニルメチルピペリジン、1-トリフェニルメチルピロリジン、2-(トリフェニルメチルオキシ)エタノール、2-(トリフェニルメチルアミノ)エタノール、2-(トリフェニルメチルオキシ)エチルアミン、トリフェニルメチルアミン、トリフェニルメタノール、トリフェニルメタンおよびアミノジフェニルメタン、N-(p-トルイル)システイン酸、N-(p-メトキシベンゾイル)システイン酸等が挙げ
られる。さらにその他の美白成分として、N-ベンゾイル−セリン、N-(p-メチルベンゾイル)セリン、N-(p-エチルベンゾイル)セリン、N-(p-メトキシベンゾイル)セリン、N-(p-フルオロベンゾイル)セリン、N-(p-トリフルオロメチルベンゾイル)セリン、N-(2-ナフトイル)セリン、N-(4-フェニルベンゾイル)セリン、N-(p-メチルベンゾイル)セリン メチルエステル、N-(p-メチルベンゾイル)セリン エチルエステル、N-(2-ナフトイル)セリン メチルエステル、N-ベンゾイル-O-メチルセリン、N-(p-メチルベンゾイル)-O-メチルセリン、N-(p-メチルベンゾイル)-O-アセチルセリン、N-(2-ナフトイル)-O-メチルセリン、ナイアシンアミド、D-パントテニルアルコール等があげられる。
The whitening ingredient is not particularly limited as long as it is generally used in cosmetics. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-О-ethylascorbic acid, tranexamic acid, arbutine, 1-triphenylmethylpiperidin, 1-triphenylmethylpyrrolidin, 2- (triphenylmethyloxy) ethanol, 2- (Triphenylmethylamino) ethanol, 2- (triphenylmethyloxy) ethylamine, triphenylmethylamine, triphenylmethane, triphenylmethane and aminodiphenylmethane, N- (p-toluyl) cysteine acid, N- (p) -Methylbenzoyl) Cyctic acid and the like can be mentioned. Other whitening ingredients include N-benzoyl-serine, N- (p-methylbenzoyl) serine, N- (p-ethylbenzoyl) serine, N- (p-methoxybenzoyl) serine, N- (p-fluorobenzoyl). ) Serine, N- (p-trifluoromethylbenzoyl) serine, N- (2-naphthoyl) serine, N- (4-phenylbenzoyl) serine, N- (p-methylbenzoyl) serine methyl ester, N- (p) -Methylbenzoyl) serine ethyl ester, N- (2-naphthoyl) serine methyl ester, N-benzoyl-O-methylserine, N- (p-methylbenzoyl) -O-methylserine, N- (p-methylbenzoyl) -O -Acetylserine, N- (2-naphthoyl) -O-methylserine, niacinamide, D-pantothenyl alcohol and the like can be mentioned.
これらの美白成分は、既に市販されているものもあれば、合成により入手することもできる。例えば、3-О-エチルアスコルビン酸は、特開平8-134055号公報に記載の公知の方法で合成することができる。市販品(日本精化製「VCエチル」)もあるので、これらを入手して使用することが可能である。1-トリフェニルメチルピペリジン、1-トリフェニルメチルピロリジン、2-(トリフェニルメチルオキシ)エタノール、2-(トリフェニルメチルアミノ)エタノール、2-(トリフェニルメチルオキシ)エチルアミン、トリフェニルメチルアミン、トリフェニルメタノール、トリフェニルメタン、アミノジフェニルメタンは特許文献WO2010/074052号パンフレットに、N-(o-トルオイル)システイン酸、N-(m-トルオイル)システイン酸、N-(p-トルオイル)システイン酸、N-(p-メトキシベンゾイル)システイン酸、N-(4-フェニルベンゾイル)システイン酸、N-(p-トルオイル)ホモシステイン酸、はWO/2011/058730号パンフレットに、N-ベンゾイル−セリン、N-(p-メチルベンゾイル)セリン、N-(p-エチルベンゾイル)セリン、N-(p-メトキシベンゾイル)セリン、N-(p-フルオロベンゾイル)セリン、N-(p-トリフルオロメチルベンゾイル)セリン、N-(2-ナフトイル)セリン、N-(4-フェニルベンゾイル)セリン、N-(p-メチルベンゾイル)セリン メチルエステル、N-(p-メチルベンゾイル)セリン エチルエステル、N-(2-ナフトイル)セリン メチルエステル、N-ベンゾイル-O-メチルセリン、N-(p-メチルベンゾイル)-O-メチルセリン、N-(p-メチルベンゾイル)-O-アセチルセリン、N-(2-ナフトイル)-O-メチルセリン等はWO/2011/074643号パンフレットに、それぞれその合成方法が公開されているので、該開示に従い合成することができる。
化粧料における美白成分の含有量は、通常0.01〜30質量%であり、0.1〜10質量%が好ましく、1〜5質量%がより好ましい。
Some of these whitening ingredients are already on the market, and some can be obtained synthetically. For example, 3-О-ethylascorbic acid can be synthesized by a known method described in JP-A-8-134055. There are also commercially available products (Nippon Fine Chemical Co., Ltd. "VC Ethyl"), so it is possible to obtain and use these. 1-Triphenylmethylpiperidin, 1-triphenylmethylpyrrolidin, 2- (triphenylmethyloxy) ethanol, 2- (triphenylmethylamino) ethanol, 2- (triphenylmethyloxy) ethylamine, triphenylmethylamine, tri Phenylmethanol, triphenylmethane, aminodiphenylmethane are described in Patent Document WO2010 / 074052 pamphlet, N- (o-toluoil) esteric acid, N- (m-toluoil) esteric acid, N- (p-toluoil) esteric acid, N -(P-methoxybenzoyl) cysteine acid, N- (4-phenylbenzoyl) cysteine acid, N- (p-toluoil) homocysteine acid, in WO / 2011/058730 pamphlet, N-benzoyl-serine, N- (P-Methylbenzoyl) esterin, N- (p-ethylbenzoyl) serum, N- (p-methoxybenzoyl) esterin, N- (p-fluorobenzoyl) esterin, N- (p-trifluoromethylbenzoyl) serum, N- (2-naphthoyl) serine, N- (4-phenylbenzoyl) serine, N- (p-methylbenzoyl) serine methyl ester, N- (p-methylbenzoyl) serine ethyl ester, N- (2-naphthoyl) Serine Methyl Ester, N-Benzoyl-O-Methylserine, N- (p-Methylbenzoyl) -O-Methylserine, N- (p-Methylbenzoyl) -O-Acetylserine, N- (2-Naftyl) -O-Methylserine Et al. Are published in WO / 2011/074643 pamphlet, and their synthesis methods can be synthesized in accordance with the disclosure.
The content of the whitening component in the cosmetic is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass.
しわ改善成分としては、一般的に化粧料に用いられているものであれば特に限定はない。例えば、ビタミンAまたはその誘導体、三フッ化イソプロピルオキソプロピルアミノカルボニルピロリジンカルボニルメチルプロピルアミノカルボニルベンゾイルアミノ酢酸Na、ナイアシンアミド、シクロヘキシルグリセリン、レチノール、レチナール、レチノイン酸、トレチノイン、イソトレチノイン、レチノイン酸トコフェロール、パルミチン酸レチノール、酢酸レチノールやウルソール酸ベンジルエステル、ウルソール酸リン酸エステル、ベツリン酸ベンジルエステル、ベンジル酸リン酸エステル、N-(p-トルイル)システイン酸、N-(p-メトキシベンゾイル)システイン酸等が挙げられる。
化粧料におけるしわ改善成分の含有量は、通常0.01〜30質量%であり、0.1〜10質量%が好ましく、1〜5質量%がより好ましい。
The wrinkle improving ingredient is not particularly limited as long as it is generally used in cosmetics. For example, vitamin A or a derivative thereof, isopropyloxopropylaminocarbonylpyrrolidincarbonylmethylpropylaminocarbonylbenzoylaminoacetate Na trifluoride, niacinamide, cyclohexylglycerin, retinol, retinal, retinoic acid, tretinone, isotretinoin, tocopherol retinoate, palmitin. Retinol acid, retinol acetate, ulsoleic acid benzyl ester, ursoleic acid phosphate ester, bethuric acid benzyl ester, benzylic acid phosphate ester, N- (p-toluyl) cysteic acid, N- (p-methoxybenzoyl) cysteic acid, etc. Can be mentioned.
The content of the wrinkle improving component in the cosmetic is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass.
動植物由来のエキスとしては、一般的に医薬品、化粧料、食品等に用いられているものであれば特に限定はない。例えば、アケビエキス、アスナロエキス、アスパラガスエキス、アボガドエキス、アマチャエキス、アーモンドエキス、アルニカエキス、アロエエキス、アロニアエキス、アンズエキス、イザヨイバラエキス、イチョウエキス、インドキノエキス、ウイキョウエキス、ウドエキス、エイジツエキス、エゾウコギエキス、エンメイソウエキス、オウゴンエキス、オウバクエキス、オウレンエキス、オタネニンジンエキス、オトギリソウエキス、オドリコソウエキス、オレンジエキス、カキョクエキス、加水分解
コンキオリン液、加水分解シルク、カッコンエキス、カモミラエキス、カロットエキス、カワラヨモギエキス、カンゾウエキス、キウイエキス、キューカンバーエキス、グアバエキス、クジンエキス、クチナシエキス、クマザサエキス、クララエキス、クルミエキス、グレープフルーツエキス、黒米エキス、クローブエキス、クロレラエキス、クワエキス、ケイケットウエキス、ゲットウヨウエキス、ゲンチアナエキス、ゲンノショウコエキス、紅茶エキス、ゴボウエキス、コメエキス、コメ発酵エキス、コメヌカ発酵エキス、コメ胚芽油、コケモモエキス、サルビアエキス、サボンソウエキス、ササエキス、サンザシエキス、サンシャエキス、サンショウエキス、シイタケエキス、ジオウエキス、シコンエキス、シナノキエキス、シモツケソウエキス、シャクヤクエキス、ショウキョウエキス、ショウブ根エキス、シラカバ樹皮エキス、スギナエキス、スターフルーツエキス、ステビアエキス、ステビア発酵物、セイヨウキズタエキス、セイヨウサンザシエキス、セイヨウニワトコエキス、セイヨウノコギリソウエキス、セイヨウハッカエキス、ゼニアオイエキス、センキュウエキス、センニンコクエキス、センブリエキス、ソウハクヒエキス、ダイオウエキス、ダイズエキス、タイソウエキス、タイムエキス、タンポポエキス、茶エキス、チョウジエキス、チンピエキス、甜茶エキス、トウガラシエキス、トウキエキス、トウキンセンカエキス、トウニンエキス、トウヒエキス、トゲナシエキス、ドクダミエキス、トマトエキス、納豆エキス、ニンジンエキス、ニンニクエキス、ノバラエキス、ハイビスカスエキス、バクモンドウエキス、ハスエキス、パセリエキス、バーチエキス、ハトムギ種子エキス、ハマメリスエキス、ヒキオコシエキス、ヒノキエキス、ビワエキス、フキタンポポエキス、フキノトウエキス、ブクリョウエキス、ブッチャーブルームエキス、ブドウエキス、ブドウ種子エキス、ヘチマエキス、ベニバナエキス、ペパーミントエキス、ボダイジュエキス、ボタンエキス、ホップエキス、マジョラムエキス、マツエキス、マロニエエキス、ミズバショウエキス、ムクロジエキス、メリッサエキス、モズクエキス、モモエキス、モモ葉エキス、ヤグルマギクエキス、ユーカリエキス、ユキノシタエキス、ユズエキス、ユリエキス、ヨクイニンエキス、ヨモギエキス、緑茶エキス、ライムエキス、リンゴエキス、ルイボス茶エキス、レイシエキス、レタスエキス、レモンエキス、レンギョウエキス、レンゲソウエキス、ローズエキス、ローマカミツレエキス、ローヤルゼリーエキス、ワレモコウエキス等のエキスが好ましいものとして挙げられる。
化粧料中における動植物由来エキスの含有量は、通常0.01〜30質量%であり、0.1〜10質量%が好ましく、1〜5質量%がより好ましい。
The animal and plant-derived extracts are not particularly limited as long as they are generally used in pharmaceuticals, cosmetics, foods and the like. For example, akebi extract, asunaro extract, asparagus extract, avocado extract, amacha extract, almond extract, arnica extract, aloe extract, aronia extract, apricot extract, izayoi rose extract, ginkgo extract, indokino extract, uikyo extract, udo extract, agetsu extract. , Ezokogi extract, Enmeisou extract, Ogon extract, Oubaku extract, Ouren extract, Otaneninjin extract, Otogirisou extract, Odorikosou extract, Orange extract, Kakyoku extract, Hydrolyzed conchiolin solution, Hydrolyzed silk, Kakon extract, Chamomile extract, Carrot extract, Kawarayomogi extract, Kanzo extract, Kiwi extract, Cucumber extract, Guava extract, Kujin extract, Kuchinashi extract, Kumazasa extract, Clara extract, Walnut extract, Grapefruit extract, Black rice extract, Clove extract, Chlorella extract, Kuwa extract, Keiketto extract, Gettoyo extract , Gentiana extract, Gennoshoco extract, Tea extract, Gobo extract, Rice extract, Fermented rice extract, Fermented rice bran extract, Rice germ oil, Kokemomo extract, Salvia extract, Sabonsou extract, Sasa extract, Sanzashi extract, Sansha extract, Sansho extract, Shiitake Extract, Jio extract, Shikon extract, Shinanoki extract, Shimotsukesou extract, Shakuyaku extract, Shokyo extract, Shobu root extract, Shirakaba bark extract, Sugina extract, Star fruit extract, Stevia extract, Stevia fermented product, Seiyoukizuta extract, Seiyousanzashi extract, Seiyo Niwatoko extract, Seiyou nokogirisou extract, Seiyouhakka extract, Zeniaoi extract, Senkyu extract, Senninkoku extract, Senburi extract, Souhakuhi extract, Daiou extract, Soybean extract, Taisou extract, Thyme extract, Dandelion extract, Tea extract, Chouji extract, Chinpi extract, Jincha Extract, Togarashi extract, Touki extract, Tokinsenka extract, Tounin extract, Tohi extract, Togenashi extract, Dokudami extract, Tomato extract, Natto extract, Carrot extract, Garlic extract, Novara extract, Hibiscus extract, Bakumondou extract, Hass extract, Parsley extract, Birch Extract, Hatomugi seed extract, Hamamelis extract, Hikiokoshi extract, Hinoki extract, Biwa extract, Fukitanpopo extract, Fukinotueki Su, Bukuryo Extract, Butcher Bloom Extract, Grape Extract, Grape Seed Extract, Hechima Extract, Benibana Extract, Peppermint Extract, Bodaiju Extract, Button Extract, Hop Extract, Majorum Extract, Pine Extract, Maronie Extract, Mizubasho Extract, Mukuroji Extract, Melissa Extract , Mozuku extract, peach extract, peach leaf extract, yagurumagiku extract, eucalyptus extract, yukinoshita extract, yuzu extract, lily extract, yokuinin extract, yomogi extract, green tea extract, lime extract, apple extract, louis boss tea extract, reishi extract, lettuce extract, lemon extract , Renkyo extract, Rengesou extract, Rose extract, Roman chamomile extract, Royal jelly extract, Waremokou extract and the like are preferable.
The content of the animal and plant-derived extract in the cosmetic is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass.
抗炎症成分としては、クラリノン、グラブリジン、グリチルリチン酸、グリチルレチン酸、パントテニルアルコール、トラネキサム酸、ナイアシンアミド等が挙げられ、好ましくは、グリチルリチン酸およびその塩、グリチルレチン酸アルキルおよびその塩、並びに、グリチルレチン酸およびその塩である。
化粧料中における抗炎症成分の含有量は、通常0.01〜30質量%であり、0.1〜10質量%が好ましく、1〜5質量%がより好ましい。
Examples of the anti-inflammatory component include clarinone, glabridin, glycyrrhizinic acid, glycyrrhetinic acid, pantothenyl alcohol, tranexamic acid, niacinamide and the like, preferably glycyrrhizic acid and its salt, alkyl glycyrrhetinate and its salt, and glycyrrhetinic acid. And its salt.
The content of the anti-inflammatory component in the cosmetic is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass.
化粧料中に含有させることができるその他の成分を、以下に例示する。
油性成分としては、極性油、揮発性炭化水素油等が挙げられる。
極性油としては、合成エステル油として、ミリスチン酸イソプロピル、オクタン酸セチル、ミリスチン酸オクチルドデシル、パルミチン酸イソプロピル、ステアリン酸ブチル、ラウリン酸ヘキシル、ミリスチン酸ミリスチル、オレイン酸デシル、ジメチルオクタン酸ヘキシルデシル、乳酸セチル、乳酸ミリスチル、酢酸ラノリン、ステアリン酸イソセチル、イソステアリン酸イソセチル、12-ヒドロキシステアリル酸コレステリル、ジ-2-エチルヘキシル酸エチレングリコール、ジペンタエリスリトール脂肪酸エステル、モノイソステアリン酸N−アルキルグリコール、ジカプリン酸ネオペンチルグリコール、リンゴ酸ジイソステアリル、ジ-2-ヘプチルウンデカン酸グリセリン、トリ-2-エチルヘキシル酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、テトラ−2−エチルヘキシル酸ペンタンエリスリトール、トリ-2-エチルヘキシル酸グリセリン、トリイソス
テアリン酸トリメチロールプロパンを挙げることができる。
さらに、セチル2-エチルヘキサノエート、2-エチルヘキシルパルミテート、トリミリスチン酸グリセリン、トリ-2-ヘプチルウンデカン酸グリセライド、ヒマシ油脂肪酸メチルエステル、オレイン酸オイル、セトステアリルアルコール、アセトグリセライド、パルミチン酸2−ヘプチルウンデシル、アジピン酸ジイソブチル、N-ラウロイル-L-グルタミン酸-2-オクチルドデシルエステル、アジピン酸ジ-2-ヘプチルウンデシル、エチルラウレート、セバチン酸ジ-2-エチルヘキシル、ミリスチン酸2-ヘキシルデシル、パルミチン酸2−ヘキシルデシル、アジピン酸2-ヘキシルデシル、セバチン酸ジイソプロピル、コハク酸2-エチルヘキシル、酢酸エチル、酢酸ブチル、酢酸アミル、クエン酸トリエチル、オクチル メトキシシンナメート等も挙げられる。
また、天然油として、アボガド油、ツバキ油、タートル油、マカデミアナッツ油、トウモロコシ油、ミンク油、オリーブ油、ナタネ油、卵黄油、ゴマ油、パーシック油、小麦胚芽油、サザンカ油、ヒマシ油、アマニ油、サフラワー油、綿実油、エノ油、大豆油、落花生油、茶実油、カヤ油、コメヌカ油、シナギリ油、日本キリ油、ホホバ油、胚芽油、トリグリセリン、トリオクタン酸グリセリン、トリイソパルミチン酸グリセリン等が挙げられる。
Other ingredients that can be contained in cosmetics are illustrated below.
Examples of the oily component include polar oils and volatile hydrocarbon oils.
Polar oils include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctanoate, and lactic acid as synthetic ester oils. Cetyl, myristyl lactate, lanolin acetate, isosetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearyl, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl dicaprate Glycol, diisostearyl malate, glycerin di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentanerythritol tetra-2-ethylhexylate, glycerin tri-2-ethylhexylate , Trimethylol propane triisostearate can be mentioned.
In addition, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glycerin trimyristate, glyceride tri-2-heptyl undecanoate, methyl ester of castor oil fatty acid, oleic acid oil, cetostearyl alcohol, acetoglyceride, palmitic acid 2 −Heptylundecyl, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyllaurate, di-2-ethylhexyl sebatate, 2-hexyl myristate Examples thereof include decyl, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebatate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, and octyl methoxycinnamate.
Also, as natural oils, avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, southern ka oil, castor oil, flaxseed oil, Saflower oil, cotton seed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnamon oil, Japanese millet oil, jojoba oil, germ oil, triglycerin, glycerin trioctanoate, glycerin triisopalmitate And so on.
揮発性炭化水素油としては、イソドデカン、イソヘキサデカン等が挙げられる。 Examples of the volatile hydrocarbon oil include isododecane and isohexadecane.
界面活性剤としては、脂肪酸セッケン(ラウリン酸ナトリウム、パルミチン酸ナトリウム等)、ラウリル硫酸カリウム、アルキル硫酸トリエタノールアミンエーテル等のアニオン界面活性剤類、塩化ステアリルトリメチルアンモニウム、塩化ベンザルコニウム、ラウリルアミンオキサイド等のカチオン界面活性剤類、ベタイン系界面活性剤(アルキルベタイン、アミドベタイン、スルホベタイン等)、イミダゾリン系両性界面活性剤(2-ココイル-2-イミダゾリニウムヒドロキサイド-1-カルボキシエチロキシ2ナトリウム塩等)、アシルメチルタウリン等の両性界面活性剤類、ソルビタン脂肪酸エステル類(ソルビタンモノステアレート、セスキオレイン酸ソルビタン等)、グリセリン脂肪酸類(モノステアリン酸グリセリン等)、プロピレングリコール脂肪酸エステル類(モノステアリン酸プロピレングリコール等)、硬化ヒマシ油誘導体、グリセリンアルキルエーテル、POEソルビタン脂肪酸エステル類(POEソルビタンモノオレエート、モノステアリン酸ポリオキシエチレンソルビタン等)、POEソルビット脂肪酸エステル類(POE-ソルビットモノラウレート等)、POEグリセリン脂肪酸エステル類(POE-グリセリンモノイソステアレート等)、POE脂肪酸エステル類(ポリエチレングリコールモノオレート、POEジステアレート等)、POEアルキルエーテル類(POE2-オクチルドデシルエーテル等)、POEアルキルフェニルエーテル類(POEノニルフェニルエーテル等)、プルロニック型類、POE・POPアルキルエーテル類(POE・POP2-デシルテトラデシルエーテル等)、テトロニック類、POEヒマシ油・硬化ヒマシ油誘導体(POEヒマシ油、POE硬化ヒマシ油等)、ショ糖脂肪酸エステル、アルキルグルコシド等の非イオン界面活性剤類、等が挙げられる。 Examples of the surfactant include anionic surfactants such as fatty acid sucrose (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine alkyl sulfate ether, stearyltrimethylammonium chloride, benzalconium chloride, laurylamine oxide. Cationic surfactants such as, betaine-based surfactants (alkylbetaine, amide betaine, sulfobetaine, etc.), imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy 2) (Sodium salt, etc.), amphoteric surfactants such as acylmethyltaurine, sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glycerin monostearate, etc.), propylene glycol fatty acid esters (such as glycerin monostearate) Protin glycol monostearate, etc.), hardened castor oil derivative, glycerin alkyl ether, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbit fatty acid esters (POE-Solbit monolaure, etc.) Rate, etc.), POE glycerin fatty acid esters (POE-glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkyl Phenyl ethers (POE nonylphenyl ethers, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ethers, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, etc.) POE-hardened castor oil, etc.), non-ionic surfactants such as sucrose fatty acid ester, alkyl glucoside, etc., and the like.
多価アルコールとしては、ポリエチレングリコール、グリセリン、1,3-ブチレングリコール、エリスリトール、ソルビトール、キシリトール、マルチトール、プロピレングリコール、ジプロピレングリコール、ジグリセリン、イソプレングリコール、1,2-ペンタンジオール、2,4-ヘキシレングリコール、1,2-ヘキサンジオール、1,2-オクタンジオール等が挙げられる。 Polyhydric alcohols include polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, martitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4. -Hexylene glycol, 1,2-hexanediol, 1,2-octanediol and the like can be mentioned.
増粘剤としては、グアガム、クインスシード、カラギーナン、ガラクタン、アラビアガム、ペクチン、マンナン、デンプン、キサンタンガム、カードラン、メチルセルロース、ヒドロキシエチルセルロース、カルボキシメチルセルロース、メチルヒドロキシプロピルセルロース、コンドロイチン硫酸、デルマタン硫酸、グリコーゲン、ヘパラン硫酸、ヒアルロン酸、ヒアルロン酸ナトリウム、トラガントガム、ケラタン硫酸、コンドロイチン、
ムコイチン硫酸、ヒドロキシエチルグアガム、カルボキシメチルグアガム、デキストラン、ケラト硫酸、ローカストビーンガム、サクシノグルカン、カロニン酸,キチン、キトサン、カルボキシメチルキチン、寒天、ポリビニルアルコール、ポリビニルピロリドン、カルボキシビニルポリマー、アルキル変性カルボキシビニルポリマー、ポリアクリル酸ナトリウム、ポリエチレングリコール、ベントナイト等が挙げられる。
Thickeners include guagam, quince seed, carrageenan, galactan, arabic gum, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatane sulfate, glycogen, Heparan Sulfate, Hyaluronic Acid, Sodium Hyaluronate, Tragant Gum, Keratan Sulfate, Chondroitin,
Mucoitin sulfate, hydroxyethyl guagam, carboxymethyl guagam, dextran, keratosulfate, locust bean gum, succinoglucan, caronic acid, chitin, chitosan, carboxymethyl chitin, agar, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl-modified carboxy Examples thereof include vinyl polymers, sodium polyacrylate, polyethylene glycol, bentonite and the like.
粉体類としては、表面を処理されていてもよい、マイカ、タルク、カオリン、合成雲母、炭酸カルシウム、炭酸マグネシウム、無水ケイ酸(シリカ)、酸化アルミニウム、硫酸バリウム等の粉体類、表面を処理されていてもよい、ベンガラ、黄酸化鉄、黒酸化鉄、酸化コバルト、群青、紺青、酸化チタン、酸化亜鉛の無機顔料類、表面を処理されていてもよい、雲母チタン、魚燐箔、オキシ塩化ビスマス等のパール剤類、レーキ化されていてもよい赤色202号、赤色228号、赤色226号、黄色4号、青色404号、黄色5号、赤色505号、赤色230号、赤色223号、橙色201号、赤色213号、黄色204号、黄色203号、青色1号、緑色201号、紫色201号、赤色204号等の有機色素類、ポリエチレン末、ポリメタクリル酸メチル、ナイロン粉末、オルガノポリシロキサンエラストマー等の有機粉体類等が挙げられる。 As the powders, the surface may be treated, such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic acid anhydride (silica), aluminum oxide, barium sulfate, etc., and the surface. May be treated, red iron oxide, black iron oxide, cobalt oxide, ultramarine, dark blue, titanium oxide, zinc oxide inorganic pigments, surface may be treated, mica titanium, fish phosphorus foil, Pearl agents such as bismuth oxychloride, red 202, red 228, red 226, yellow 4, blue 404, yellow 5, red 505, red 230, red 223, which may be raked. Organic pigments such as No. 201, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204, Polyethylene powder, Polymethyl methacrylate, Nylon powder, Examples thereof include organic powders such as organopolysiloxane elastomer.
紫外線吸収剤としては、パラアミノ安息香酸系紫外線吸収剤、アントラニル酸系紫外線吸収剤、サリチル酸系紫外線吸収剤、桂皮酸系紫外線吸収剤、ベンゾフェノン系紫外線吸収剤、糖系紫外線吸収剤、2-(2’-ヒドロキシ-5'-t-オクチルフェニル)ベンゾトリアゾール、4-メトキシ-4'-t-ブチルジベンゾイルメタン等の紫外線吸収剤類等が挙げられる。 Examples of UV absorbers include para-aminobenzoic acid-based UV absorbers, anthranilic acid-based UV absorbers, salicylic acid-based UV absorbers, cinnamic acid-based UV absorbers, benzophenone-based UV absorbers, sugar-based UV absorbers, 2- (2). Examples thereof include ultraviolet absorbers such as'-hydroxy-5'-t-octylphenyl) benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane.
化粧料中には、その他に、水、エタノール、香料、防腐剤、pH調整剤、着色料などを含有させることができる。 In addition, water, ethanol, fragrances, preservatives, pH adjusters, colorants and the like can be contained in the cosmetics.
また、化粧料として適用される場合の剤型は、通常知られているローション剤形、乳液剤形、エッセンス剤形、クリーム剤形、粉体含有剤形等の何れをも取ることができる。 In addition, the dosage form when applied as a cosmetic can be any of commonly known lotion dosage forms, emulsion dosage forms, essence dosage forms, cream dosage forms, powder-containing dosage forms and the like.
以下、実施例によって本発明を具体的に説明するが、これらは本発明の例示であり、本発明の範囲はこれらに限定されるものではない。 Hereinafter, the present invention will be specifically described with reference to Examples, but these are examples of the present invention, and the scope of the present invention is not limited thereto.
<材料>
評価に使用した植物抽出物は、市販の植物エキスを用いた。すなわち、シソエキス(アミノアップ社)、ラベンダーエキス(丸善製薬社)、セージエキス(一丸ファルコス社)、ローズマリーエキス(香栄興業社)、クマツヅラエキス(セティ社)、ソウハクヒエキス(丸善製薬社)、チョウジエキス(一丸ファルコス社)、ニンジンエキス(丸善製薬社)、ブクリョウエキス(一丸ファルコス社)、ライムエキス(丸善製薬社)を用いた。
評価に使用した化合物は、市販の化合物を用いた。すなわち、ロスマノール(rosmanol)(PhytoLab社)、イソロスマノール(isorosmanol)(Sigma-Aldrich社)、カルノシン酸(carnosic acid)(東京化成株式会社社)、ガルス酸(gallic acid)(Supelco社)を用いた。
<Material>
As the plant extract used for the evaluation, a commercially available plant extract was used. That is, Shiso extract (Amino Up), Lavender extract (Maruzen Pharmaceuticals), Sage extract (Ichimaru Falcos), Rosemary extract (Koei Kogyo), Kumatsuzura extract (Seti), Souhakuhi extract (Maruzen Pharmaceuticals), Chouji extract (Ichimaru Falcos), carrot extract (Maruzen Pharmaceuticals), Bukuryo extract (Ichimaru Falcos), and lime extract (Maruzen Pharmaceuticals) were used.
As the compound used for the evaluation, a commercially available compound was used. That is, rosmanol (PhytoLab), isorosmanol (Sigma-Aldrich), carnosic acid (Tokyo Kasei Co., Ltd.), gallic acid (Supelco) are used. board.
<実施例1>シソ目植物エキスによるLINC00942発現促進作用確認試験
老化した細胞として68歳白人由来の真皮線維芽細胞を用いた。
10%FBS含有DMEM培地で継代培養した線維芽細胞を、96ウェルプレートに7000個/ウェルになる様に播種し、37℃、5% CO2環境下で24時間培養した。その後、各植物エキスを表1に示した各濃度(v/v%)含む培地に交換し、さらに24時間培養した。また、溶媒対照として各植物エキスの溶媒を評価エキスと同濃度(v/v%)含む培地で同様に培養した。
培養終了時に、FastLane Cell SYBR Green Kit(キアゲン社 216213)とLINC00942特異的プライマー(キアゲン社 Hs_LINC00942_1_SG)を用いた定量的リアルタイムPCR法により、L
INC00942の発現量を解析し、溶媒対照での発現量を1とした場合の相対値を求めた。各群3ウェルずつ、n=3にて実施した。結果をもとに、溶媒対照群に対するDunnett検定を行い、溶媒対照群と比較して有意に大きい値であるかどうかを評価した。
結果を表1に示す。表1の植物名にて、シソエキスをシソ、ラベンダーエキスをラベンダー、セージエキスをセージ、ローズマリーエキスをローズマリー、クマツヅラエキスをクマツヅラ、ソウハクヒエキスをソウハクヒ、チョウジエキスをチョウジ、ニンジンエキスをニンジン、ブクリョウエキスをブクリョウ、ライムエキスをライムと示した。
<Example 1> Confirmation test of LINC00942 expression promoting action by Lamiales plant extract As aged cells, dermal fibroblasts derived from 68-year-old Caucasian were used.
Fibroblasts subcultured in DMEM medium containing 10% FBS were seeded in a 96-well plate at a rate of 7,000 cells / well, and cultured for 24 hours in a 37 ° C., 5% CO 2 environment. Then, each plant extract was replaced with a medium containing each concentration (v / v%) shown in Table 1, and further cultured for 24 hours. In addition, as a solvent control, the solvent of each plant extract was similarly cultured in a medium containing the same concentration (v / v%) as that of the evaluation extract.
At the end of culturing, L
The expression level of INC00942 was analyzed, and the relative value was obtained when the expression level on the solvent control was 1. Three wells in each group were performed at n = 3. Based on the results, Dunnett's test was performed on the solvent control group, and it was evaluated whether the value was significantly larger than that on the solvent control group.
The results are shown in Table 1. Under the plant names in Table 1, perilla extract is perilla, lavender extract is lavender, sage extract is sage, rosemary extract is rosemary, kumatsuzura extract is kumatsuzura, sohakuhi extract is souhakuhi, chouji extract is chouji, carrot extract is carrot, bukuryo. The extract was shown as Bukuryo and the lime extract was shown as lime.
表1のEtOHはエタノール、BGは1,3-ブチレングリコールを示す。*はp<0.05、**はp<0.01、NSは有意差なしを示す。 In Table 1, EtOH indicates ethanol and BG indicates 1,3-butylene glycol. * Indicates p <0.05, ** indicates p <0.01, and NS indicates no significant difference.
上記結果のとおり、シソ目植物抽出物である、シソエキス、ラベンダーエキス、セージエキス、ローズマリーエキス、クマツヅラエキスに優れたLINC00942発現促進作用が認められた。 As shown in the above results, the excellent LINC00942 expression promoting action was observed in the Lamiales plant extract, which is a perilla extract, a lavender extract, a sage extract, a rosemary extract, and a bear vine extract.
<実施例2>ロスマノールおよびその類縁体によるLINC00942発現促進作用確認試験
シソ目植物に含まれる各種化合物について、LINC00942の発現促進作用を評価した。
老化した細胞として68歳白人由来の真皮線維芽細胞を用いた。
10%FBS含有DMEM培地で継代培養した線維芽細胞を、96ウェルプレートに7000個/ウェルになる様に播種し、37℃、5% CO2環境下で24時間培養した。その後、DMSOに溶解した評価化合物(表2)を終濃度0.0005%(w/v)含む培地に交換し、さらに24時間培養した。また、溶媒対照としてDMSOを0.1%(v/v%)含む培地で同様に培養した。
培養終了時に、FastLane Cell SYBR Green Kit(キアゲン社 216213)とLINC00942特異的プライマー(キアゲン社 Hs_LINC00942_1_SG)を用いた定量的リアルタイムPCR法により、LINC00942の発現量を解析し、溶媒対照での発現量を1とした場合の相対値を求めた。各群3ウェルずつ、n=3にて実施した。結果をもとに、溶媒対照群に対するDunnett検定を行い、溶媒対照群と比較して有意に大きい値であるかどうかを評価した。
結果を表2に示す。
<Example 2> LINC00942 expression-promoting action confirmation test by Rosmanol and its analogs The expression-promoting action of LINC00942 was evaluated for various compounds contained in Lamiales plants.
As the aged cells, dermal fibroblasts derived from 68-year-old Caucasian were used.
Fibroblasts subcultured in DMEM medium containing 10% FBS were seeded in a 96-well plate at a rate of 7,000 cells / well, and cultured for 24 hours in a 37 ° C., 5% CO 2 environment. Then, the evaluation compound (Table 2) dissolved in DMSO was replaced with a medium containing a final concentration of 0.0005% (w / v), and the cells were further cultured for 24 hours. In addition, DMSO was similarly cultured in a medium containing 0.1% (v / v%) as a solvent control.
At the end of culture, the expression level of LINC00942 was analyzed by a quantitative real-time PCR method using FastLane Cell SYBR Green Kit (Qiagen 216213) and LINC00942 specific primer (Qiagen Hs_LINC00942_1_SG), and the expression level on a solvent control was 1 The relative value was calculated. Three wells in each group were performed at n = 3. Based on the results, Dunnett's test was performed on the solvent control group, and it was evaluated whether the value was significantly larger than that on the solvent control group.
The results are shown in Table 2.
表2のDMSOはジメチルスルホキシドを示す。*はp<0.05、**は p<0.01を示す。 The DMSO in Table 2 shows dimethyl sulfoxide. * Indicates p <0.05, ** indicates p <0.01.
上記結果のとおり、シソ目植物に含まれるロスマノールおよびその類縁体である、ロスマノール、イソロスマノールおよびカルノシン酸に優れたLINC00942の発現促進作用が認められた。 As shown in the above results, the expression promoting action of LINC00942, which is excellent in rosmanol contained in Lamiales and its analogs, rosmanol, isorosmanol and carnosic acid, was observed.
<実施例3>ガルス酸によるLINC00942の発現促進作用とロスマノールとの相乗効果確認試験
上記シソ目植物含有化合物以外にも同様の作用を有する植物含有化合物があるか評価した結果、ガルス酸にLINC00942発現促進作用が認められた。また、ロスマノールとガルス酸との相乗について評価した。
老化した細胞として68歳白人由来の真皮線維芽細胞を用いた。
10%FBS含有DMEM培地で継代培養した線維芽細胞を、96ウェルプレートに7000個/ウェルになる様に播種し、37℃、5% CO2環境下で24時間培養した。その後、DMSOに溶解したロスマノールあるいはガルス酸を終濃度0.0005%(w/v)含む培地に交換し、さらに24時間培養した。または、ロスマノールとガルス酸の両方を各々終濃度0.0005%(w/v)含む培地に交換し、さらに24時間培養した。また、溶媒対照としてDMSOを0.1%(v/v%)含む培地で同様に培養した。
培養終了時に、FastLane Cell SYBR Green Kit(キアゲン社 216213)とLINC00942特異的プライマー(キアゲン社 Hs_LINC00942_1_SG)を用いた定量的リアルタイムPCR法により、LINC00942の発現量を解析し、溶媒対照での発現量を1とした場合の相対値を求めた。各群3ウェルずつ、n=3にて実施した。結果をもとに、溶媒対照群に対するDunnett検定を行い、溶媒対照群と比較して有意に大きい値であるかどうかを評価した。
結果を表3に示す。
<Example 3> Test for confirming synergistic effect between LINC00942 expression promoting action by gals acid and rosmanol As a result of evaluating whether there is a plant-containing compound having the same action other than the above Lamiales plant-containing compound, LINC00942 expression was expressed in gals acid. A promoting effect was observed. We also evaluated the synergies between rosmanol and gals acid.
As the aged cells, dermal fibroblasts derived from 68-year-old Caucasian were used.
Fibroblasts subcultured in DMEM medium containing 10% FBS were seeded in a 96-well plate at a rate of 7,000 cells / well, and cultured for 24 hours in a 37 ° C., 5% CO 2 environment. Then, rosmanol or gals acid dissolved in DMSO was replaced with a medium containing a final concentration of 0.0005% (w / v), and the cells were further cultured for 24 hours. Alternatively, both rosmanol and gals acid were replaced with a medium containing 0.0005% (w / v) of each final concentration, and the cells were further cultured for 24 hours. In addition, DMSO was similarly cultured in a medium containing 0.1% (v / v%) as a solvent control.
At the end of culture, the expression level of LINC00942 was analyzed by a quantitative real-time PCR method using FastLane Cell SYBR Green Kit (Qiagen 216213) and LINC00942 specific primer (Qiagen Hs_LINC00942_1_SG), and the expression level on a solvent control was 1 The relative value was calculated. Three wells in each group were performed at n = 3. Based on the results, Dunnett's test was performed on the solvent control group, and it was evaluated whether the value was significantly larger than that on the solvent control group.
The results are shown in Table 3.
表3のDMSOはジメチルスルホキシドを示す。***はp<0.001を示す。 The DMSO in Table 3 shows dimethyl sulfoxide. *** indicates p <0.001.
上記結果のとおり、ガルス酸にLINC00942の発現促進作用が認められた。更に、ロスマ
ノールとガルス酸を両方添加した場合のLINC00942の相対値は、ロスマノールおよびガルス酸単独添加時のLINC00942の相対値を合計した値(3.63)よりも明らかに高いことが確認された。以上のことから、ロスマノールとガルス酸両方を添加した場合には、それぞれを単独に添加した場合と比較して相乗的な効果があることが確認された。
As shown in the above results, gallic acid was found to have an expression-promoting effect on LINC00942. Furthermore, it was confirmed that the relative value of LINC00942 when both rosmanol and gals acid were added was clearly higher than the total value (3.63) of LINC00942 when both rosmanol and gals acid were added. From the above, it was confirmed that when both rosmanol and gals acid were added, there was a synergistic effect as compared with the case where each was added alone.
<被験物質の抗老化効果>
特開2015-130857号公報の実施例等に記載されるとおり、LINC00942の発現促進作用と皮膚老化抑制作用との相関が示されている。
したがって、シソ目植物抽出物、ロスマノールおよびその類縁体、およびガルス酸は、皮膚老化抑制効果を示すものと判断できる。
<Anti-aging effect of test substance>
As described in Examples of JP-A-2015-130857, the correlation between the expression-promoting action of LINC00942 and the skin aging-suppressing action has been shown.
Therefore, it can be judged that the Lamiales plant extract, Rosmanol and its analogs, and galsic acid show an inhibitory effect on skin aging.
本発明は、化粧品、医薬部外品、食品、医薬品等に応用できる。 The present invention can be applied to cosmetics, quasi-drugs, foods, pharmaceuticals and the like.
Claims (15)
R1およびR2は、それぞれ独立に、水素、酸素、ヒドロキシ、または炭素数1〜6のアルキルオキシであり、
R3は、カルボキシ、もしくは炭素数1〜6のアルコキシカルボニルであるか、またはR4またはR5と一緒になって-CO-O-であり、
R4およびR5は、それぞれ独立に、水素、酸素、ヒドロキシ、もしくは炭素数1〜6のアルキルオキシであり、
環に結合する水素は、それぞれ独立に、酸素、炭素数1〜6のアルキル、炭素数2〜6のアルケニルもしくはアルキニル、または炭素数1〜6のアルキルオキシで置換されてもよい。) The expression-promoting agent according to claim 1, wherein Rosmanol and an analog thereof are compounds represented by the following formula (I).
R 1 and R 2 are independently hydrogen, oxygen, hydroxy, or alkyloxy with 1 to 6 carbon atoms, respectively.
R 3 is a carboxy, or an alkoxycarbonyl with 1 to 6 carbon atoms, or is -CO-O- with R 4 or R 5.
R 4 and R 5 are independently hydrogen, oxygen, hydroxy, or alkyloxy with 1 to 6 carbon atoms, respectively.
The hydrogen bonded to the ring may be independently substituted with oxygen, an alkyl having 1 to 6 carbon atoms, an alkenyl or alkynyl having 2 to 6 carbon atoms, or an alkyloxy having 1 to 6 carbon atoms. )
。 The composition according to claim 8, wherein the skin aging suppression is one or more selected from skin elasticity reduction prevention, wrinkle prevention, sagging prevention, stain formation prevention, dullness prevention and pore expansion prevention.
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