JP4693963B2 - Estrogen-like agent, collagen production promoter, and fibroblast proliferating agent - Google Patents

Estrogen-like agent, collagen production promoter, and fibroblast proliferating agent Download PDF

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JP4693963B2
JP4693963B2 JP2000210936A JP2000210936A JP4693963B2 JP 4693963 B2 JP4693963 B2 JP 4693963B2 JP 2000210936 A JP2000210936 A JP 2000210936A JP 2000210936 A JP2000210936 A JP 2000210936A JP 4693963 B2 JP4693963 B2 JP 4693963B2
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agent
skin
estrogen
collagen production
lotus
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JP2002029980A (en
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善仁 川嶋
直子 岸田
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Maruzen Pharmaceutical Co Ltd
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Maruzen Pharmaceutical Co Ltd
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Description

【0001】
【発明の属する技術分野】
本発明はエストロゲン様作用剤及びコラーゲン産生促進剤、線維芽細胞増殖作用剤、美容用食品並びに皮膚化粧料に関する。具体的には、女性ホルモンの一種であるエストロゲンと同様の作用を有する新規なエストロゲン様作用剤、皮膚を構成するコラーゲンの産生を促進するコラーゲン産生促進剤、人の皮膚にある線維芽細胞を活発化させる線維芽細胞増殖作用剤並びにこれらの薬剤を使用した美容用食品及び皮膚化粧料に関する。
【0002】
【従来の技術】
加齢に伴う皮膚老化の一因は、女性ホルモンの一種であるエストロゲンの分泌が減退することである。そこで、エストロゲンの分泌が衰える更年期以後の女性に対して、エストロゲンと同様の作用をする物質を経皮的または経口的に投与することが行われている。そのためのエストロゲン様作用剤として、従来から、ステロイド系エストロゲン、非ステロイド系エストロゲン、フラボン系化合物等が使用されてきた。
【0003】
ここにおいて、皮膚の表皮及び真皮は、表皮細胞、線維芽細胞及びこれらの細胞の外にあって皮膚構造を支持するコラーゲン等の細胞外マトリックスにより構成されている。
【0004】
若い皮膚においては、線維芽細胞の増殖は活発であり、線維芽細胞やコラーゲン等の皮膚構成組織の相互作用が恒常性を保つことにより水分保持、柔軟性、弾力性等が確保され、肌は外見的にも張りや艶があってみずみずしい状態に維持される。
【0005】
ところが、紫外線の照射、空気の著しい乾燥、過度の皮膚洗浄等、ある種の外的因子の影響があったり、加齢が進んだりすると、線維芽細胞の増殖が遅くなり、コラーゲンの産生量も減少する。その結果、皮膚はその保湿機能や弾力性が低下し、角質は異常剥離を始め、肌は張りや艶を失い、荒れ、シワ等の老化症状を呈するようになる。
【0006】
このような皮膚の老化を防止・改善するために最も普通に行われているのは、天然保湿因子(NMF)である糖、アミノ酸、有機酸、ピロリドンカルボン酸塩、コラーゲン、ヒアルロン酸等のムコ多糖類、グリセリン、1,3−ブチレングリコール等の保湿作用のある物質を塗布して皮膚の保湿性を高めることである。しかしながら、保湿剤は表皮の角質の状態を改善することは期待できない。また、皮膚からの水分蒸発を遅くするものであるから概して使用感が悪く、長期間使用すると皮膚障害を起こすことさえある。
【0007】
従って、皮膚の老化を効果的に防止し、張りや艶を失わせないためには、従来の保湿剤では不十分であり、線維芽細胞の賦活化作用やコラーゲン等の産生促進作用を有する薬剤を使用するのが好ましい。
【0008】
一方、ハスは古来よりその実は食されてあるいは漢方薬として使用されており、その安全性は確立されている。このハスを用いたものとして、例えば、特開昭62−51606号公報に、日焼け後のほてり、カミソリまけや肌荒れ等に作用するとして、スイレン科植物から水や低級アルコールなどの溶媒を用いて抽出された抽出物が開示されている。また、ハスの種子の胚芽を用いたものとしては、特開昭63−66126号公報に、水や水混和性の有機溶媒などを用いて抽出された抽出物が血圧降下作用を有するとして、さらには、特開昭64−90129号公報に、同じくハスの胚芽から水や低級アルコールなどの溶媒を用いて抽出された抽出物が、高血圧症などの循環器疾患や気管支喘息などの呼吸器疾患、不眠症などの中枢神経疾患などに作用を有するとして、それぞれ開示されている。
【0009】
しかしながら、ハス(種子)の胚芽については上記作用・効果が知られているだけであり、皮膚の老化防止作用等については、知られていなかった。
【0010】
【発明が解決しようとする課題】
そこで、本発明者らは、皮膚の老化を効果的に防止し、張りや艶を維持するものとして、従来の保湿剤になり変わる新たな薬剤を求めるべく、鋭意努力したところ、ハス胚芽の抽出物中に、エストロゲン作用やコラーゲン産生の促進作用並びに線維芽細胞増殖作用があることを見い出し、本発明を完成させるに至った。
【0011】
【課題を解決するための手段】
本発明に係るエストロゲン様作用剤及びコラーゲン産生促進剤並びに線維芽細胞増殖作用剤は、それぞれハス胚芽抽出物からなることを特徴としている。本発明においては、すいれん科ハス属のハス(Nelumbo nucifera Gaertn.)の種子中にある胚(胚芽)が用いられる。胚芽は、通常緑色で棒状をしており、採取した種子から取り出し、直ちに乾燥したものが好適に用いられる。
【0012】
ハス胚芽抽出物は、この胚芽を、水やメタノール、エタノール、イソプロパノールなどの各種脂肪族低級アルコール、1,3−ブチレングリコール、エチレングリコール、グリセリンなどの親水性有機溶媒、これら親水性有機溶媒の混合物及びこれらの親水性有機溶媒と水との混液などの各種水系溶媒を用いて抽出することにより得られるものである。
【0013】
抽出に際しては得られた胚芽をそのまま用いることもできるが、抽出効率を高めるため、粉砕して用いるのが好ましい。また、ヘキサンなどの非水系溶媒(非極性溶媒)を用いて予め脱脂処理しておくと、不純物含量が少なくなり、より効果の高い抽出物が得られる。
【0014】
抽出は、室温ないし加熱下において、抽出溶媒に応じて任意の装置を用いて行うことができる。例えば、抽出溶媒を満たした処理槽に粉砕したハス胚芽を投入し、ときどき撹拌しながら可溶性成分を溶出させる。その後、ろ過して抽出残渣を除去し、抽出液を得ることができる。このとき用いる溶媒量は、概ねハス胚芽に対して重量比で、1:5〜1:20となるように用いるのがよい。
【0015】
こうして得られた抽出物(液)は、そのままエストロゲン様作用剤として、またはコラーゲン産生促進剤として、あるいは線維芽細胞増殖作用剤として用いることも出来るが、抽出液を濃縮した濃縮液やさらに濃縮したエキス状物あるいは、抽出溶媒等を留去した乾燥物として提供することもできる。
【0016】
また、ハス胚芽の抽出物は特有のにおいと味を有するので、生理活性を低下させない程度に脱臭や脱色等を目的として精製を行うのが好ましい。もちろん、その使用目的等に応じて、例えば本発明に係る美容用食品や皮膚化粧料に含有させる場合には、大量に使用するものではないため、そのまま使用しても実用上差し支えない。
【0017】
さらに本発明のエストロゲン様作用剤やコラーゲン産生促進剤並びに線維芽細胞増殖作用剤には、必要に応じて上記抽出物に、保存やその取り扱いを容易にすべく、ショ糖や乳糖などの各種糖類、たんぱく質やデンプンなどの賦形剤、その他の任意の助剤を用いることにしてもよい。また、適宜、製剤化して提供することも可能であって、例えば、粉末状、顆粒状、錠剤状など任意の剤形として提供することも可能なものである。
【0018】
これらのエストロゲン様作用剤やコラーゲン産生促進剤並びに線維芽細胞増殖作用剤は、任意の食品に添加することにより、あるいはこれらを主成分とした栄養補助食品などの美容用食品として、経口的に活用することができる。添加可能な食品には、例えば、各種の清涼飲料水や果汁飲料、和洋菓子、乳製品その他の畜産加工品、果実加工品、野菜加工品、穀物の加工品、水産加工品、調味料、ビタミンなどを主成分としたいわゆる各種の健康食品などの多くの飲食品が挙げられる。また、栄養補助食品としても、例えば、液剤の形態のものや錠剤などの形態のものとして提供することもできる。この場合の添加率は、添加対象である美容用食品の一般的な摂取量を考慮して、液状、固形状など抽出物の形態によっても異なるが、概ね通常成人1日当たりのハス胚芽抽出物摂取量として約1〜1000mg、原料であるハス胚芽乾燥物に換算して、概ね4〜1200mgになるように添加するのが適当である。
【0019】
また、ハス胚芽抽出物の作用を最も効果的に発揮させるためには、各種の皮膚化粧料に配合することである。配合対象として適当な皮膚化粧料は、例えば、軟膏、クリーム、乳液、ローション、パック、入浴剤等であり、この場合の配合量として、ハス胚芽抽出物として概ね0.01〜10重量%、原料であるハス胚芽乾燥物換算として、概ね0.04〜40%になるように添加するのが適当である。
【0020】
なお、本発明に係る美容用食品や皮膚化粧料には、これらのエストロゲン様作用,コラーゲン産生促進作用あるいは線維芽細胞増殖作用のいずれかを妨げない限り、これらの美容用食品や皮膚化粧料の製造に通常用いられる各種の原材料を用いることができるのは言うまでもない。
【0021】
【実施例】
次に、本発明の実施例であるエストロゲン様作用剤やコラーゲン産生促進剤並びに線維芽細胞増殖作用剤並びに本発明の製剤例である美容用食品及び皮膚化粧料を示し、さらに本発明について詳細に説明する。
【0022】
(実施例1)
ハス胚芽の粗砕物300gを表1に示す抽出溶媒2000mlにそれぞれ投入し、ゆるく撹拌しながら70℃で3時間抽出した。その後、ろ過して得たろ液を40℃で減圧下に濃縮した後、さらに減圧乾燥機で乾燥して、粉末状のハス胚芽抽出物であるエストロゲン様作用剤、コラーゲン産生促進作用剤、線維芽細胞増殖作用剤を得た。その収量を表1に示す。
【0023】
【表1】

Figure 0004693963
【0024】
(実施例2)
ハス胚芽の粗砕物300gを、1,3−ブチレングリコールと水の混液(容量比1:1)2000mlに投入し、撹拌しながら80℃で3時間抽出した。その後、ろ過して液体状のハス胚芽抽出物であるエストロゲン様作用剤、コラーゲン産生促進作用剤、線維芽細胞増殖作用剤、1440mlを得た。このものの固形分濃度は、4.0重量%であった。なお、固形分濃度は、当該抽出物の少量を取り、蒸発乾固させて求めた(以下同様)。
【0025】
(実施例3)
抽出溶媒をグリセリンと水の混液(容量比1:1)を用いた他は、実施例2と同様にして、液体状のハス胚芽抽出物1540mlを得た。このものの固形分濃度は、3.5重量%であった。
【0026】
(実施例4)
抽出溶媒をプロピレングリコールと水の混液(容量比1:1)2000mlを用いた他は、実施例2と同様にして、液体状のハス胚芽抽出物1540mlを得た。このものの固形分濃度は、3.3重量%であった。
【0027】
次に、上記実施例1ないし実施例4で得た各種エストロゲン様作用剤、コラーゲン産生促進作用剤、線維芽細胞増殖作用剤を用いて、本発明に係る皮膚化粧料及び美容用食品を各種作製した。
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る皮膚化粧料である乳液を作製した。
【0028】
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る皮膚化粧料である乳液を作製した。
【0029】
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る皮膚化粧料である化粧水を作製した。
【0030】
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る皮膚化粧料であるW/O型のクリームを作製した。
【0031】
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る皮膚化粧料であるパックを作製した。
【0032】
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る美容用食品である錠剤状の健康・栄養補助食品を製造した。
【0033】
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る美容用食品である顆粒状の健康・栄養補助食品を製造した。
【0034】
Figure 0004693963
上記成分分量を取り、常法に従ってゼラチンカプセル化し、本発明に係る美容用食品であるカプセル状の健康・栄養補助食品を製造した。
【0035】
Figure 0004693963
上記成分分量を取り、撹拌溶解して、本発明に係る美容用食品である清涼飲料水状の健康・栄養補助食品を製造した。
【0036】
Figure 0004693963
上記成分分量を取り、常法に従って本発明に係る美容用食品であるキャンディ状の健康・栄養補助食品を製造した。
【0037】
(効果試験)
〔エストロゲン様作用〕
上記実施例1〜4で得た各種ハス胚芽抽出物について、エストロゲン依存性細胞の増殖に対する影響を調べるThomasらの方法(In Vitro Cell. Dev. Biol. 28A,595−602,1992)に従って、エストロゲン様作用を調べた。その結果を表2に示す。なお、水を用いたコントロール値を100として示す。
【0038】
【表2】
Figure 0004693963
【0039】
〔コラーゲン産生促進作用〕
上記実施例1〜4で得た各抽出物について、Websterらの方法(Anal.Biochem.,Vol96,220,1979)に従って、各抽出物を添加した培地で培養した線維芽細胞によって産生されたコラーゲン量を測定した。一方、各抽出物を添加しない培地で産生された放射活性を測定し、このコラーゲン量を100とした場合のコラーゲン産生量割合を求めた。以下に具体的な試験方法を示し、その結果を表3に示す。
試験法:ヒトの線維芽細胞をプレートに播種し、37℃、5%二酸化炭素下、2種類の試料添加培地(試料濃度:200ppm及び50ppm)で数日間培養した後、β−アミノプロピオニトリルと[3H]−プロリンとを添加し、更に24時間培養した。当該培養液全体にペプシン/酢酸溶液を加えて4℃下で16時間消化し、次いでこの消化液にキャリアーを加えて、0.7M食塩水で沈殿させ、さらに中性条件下で再溶解させて、4.2M食塩水で再沈殿させた。得られた沈殿物を20v/v%エタノールで洗浄した後、その沈殿物の放射活性を測定した。
【0040】
【表3】
Figure 0004693963
【0041】
〔線維芽細胞増殖作用〕
上記実施例1〜4で得た各種ハス胚芽抽出物について、多田らによるMTT法(J.Immunol.Medhods.93,157,1986)に従い、ヒト正常新生児皮膚線維芽細胞(NBIRGB)を用いて線維芽細胞増殖作用を測定した。その結果を表4に示す。なお、水を用いたコントロール値を100として示す。
【0042】
【表4】
Figure 0004693963
(評価結果)
表2ないし表4に示すように、水やエタノール、イソプロパノールと水の混液、1,3−ブチレングリコールと水の混液など各種水系溶媒を用いたハス胚芽抽出物には、それぞれ良好なエストロゲン様作用、コラーゲン産生促進作用並びに線維芽細胞増殖作用が認められた。
【0043】
〔肌荒れ改善効果〕
次に上記製剤例1に示す乳液について、下記の評価試験を行った。なお、比較例として、ハス胚芽抽出物を含まない乳液を作製し、これを用いた。
・被験者:22〜43歳の健常な多数の女性の中から、下記評価基準に従って評点1又は2に該当する肌荒れと判断された者20名を被験者として選定した。
・塗布試験:各被験者に、顔の右半分製剤例1に示す乳液を、左半分には比較例である乳液を、朝夕各1回、その適量を30日間塗布してもらった。
・評価:塗布試験終了後、シルフロ(Flexicl Developments Ltd 製)によるレプリカ法を用いて、顔のレプリカを取り、倍率50倍の光学顕微鏡で皮紋の状態及び角質剥離状態を観察し、下記の評価基準に従って肌の状態を判定した。その判定結果を表5に示す。
【0044】
Figure 0004693963
【0045】
【表5】
Figure 0004693963
【0046】
表5に示すように、本発明の製剤例である乳液を塗布した領域においては、比較例である乳液を塗布した場合に比べ、顕著に肌荒れが改善されたことが分かる。
【0047】
【発明の効果】
本発明によれば、安全性が高く、エストロゲンと同様の作用を有する新規なエストロゲン様作用剤、皮膚を構成するコラーゲンの産生を促進するコラーゲン産生促進剤、人の皮膚にある線維芽細胞を活発化させる線維芽細胞増殖作用剤を提供できる。これらを美容用食品や皮膚化粧料に適用することにより、皮膚の老化を効果的に防止し、張りや艶の維持に大きく貢献できる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an estrogen-like agent, a collagen production promoter, a fibroblast proliferation agent, a cosmetic food, and a skin cosmetic. Specifically, a novel estrogen-like agent having the same action as estrogen, a female hormone, a collagen production promoter that promotes the production of collagen that constitutes the skin, and active fibroblasts in human skin The present invention relates to a fibroblast proliferating agent to be activated, and a cosmetic food and skin cosmetic using these agents.
[0002]
[Prior art]
One cause of skin aging associated with aging is a decrease in the secretion of estrogen, a female hormone. Therefore, a substance having the same action as estrogen is transdermally or orally administered to women after menopause, whose estrogen secretion declines. For this purpose, steroidal estrogens, nonsteroidal estrogens, flavone compounds and the like have been used as estrogen-like agents.
[0003]
Here, the epidermis and dermis of the skin are composed of epidermal cells, fibroblasts, and an extracellular matrix such as collagen that is outside these cells and supports the skin structure.
[0004]
In young skin, the proliferation of fibroblasts is active, and moisture retention, flexibility, elasticity, etc. are secured by maintaining the homeostasis of the interaction of skin constituents such as fibroblasts and collagen. It is maintained in a fresh state with its tension and gloss.
[0005]
However, when there is an influence of certain external factors such as ultraviolet irradiation, drastic air drying, excessive skin washing, etc., or when aging progresses, the growth of fibroblasts slows down and the amount of collagen produced also increases. Decrease. As a result, the skin retains its moisturizing function and elasticity, the keratin begins to exfoliate abnormally, the skin loses tension and gloss, and exhibits aging symptoms such as roughness and wrinkles.
[0006]
In order to prevent and improve such skin aging, the most commonly used is a natural moisturizing factor (NMF) such as sugar, amino acid, organic acid, pyrrolidone carboxylate, collagen, hyaluronic acid, etc. It is to apply a substance having a moisturizing action such as polysaccharides, glycerin, 1,3-butylene glycol to enhance the moisturizing property of the skin. However, humectants cannot be expected to improve the keratinous state of the epidermis. In addition, since it slows the evaporation of moisture from the skin, the feeling of use is generally poor, and skin damage may occur even if it is used for a long time.
[0007]
Therefore, in order to effectively prevent skin aging and not lose tension and gloss, conventional moisturizers are insufficient, and have a fibroblast activation effect and a collagen production promotion effect. Is preferably used.
[0008]
On the other hand, lotus has been eaten or used as a traditional Chinese medicine since ancient times, and its safety has been established. As an example of using this lotus, for example, in JP-A-62-51606, it is extracted from a water lily family using a solvent such as water or a lower alcohol as acting on hot flashes after sunburn, razor baldness and rough skin. The extracted extract is disclosed. Further, as an example of using a lotus seed germ, JP-A-63-66126 states that an extract extracted with water or a water-miscible organic solvent has a blood pressure lowering effect. In Japanese Patent Application Laid-Open No. 64-90129, an extract extracted from a lotus germ using a solvent such as water or a lower alcohol is used for circulatory diseases such as hypertension and respiratory diseases such as bronchial asthma, Each is disclosed as having an effect on central nervous system diseases such as insomnia.
[0009]
However, the above-mentioned action / effect is only known for the lotus (seed) germ, and the anti-aging action of the skin has not been known.
[0010]
[Problems to be solved by the invention]
Therefore, the present inventors have made an utmost effort to find a new drug that can be used as a conventional moisturizing agent to effectively prevent skin aging and maintain tension and gloss. The present invention has been found to have estrogen action, collagen production promoting action, and fibroblast proliferation action, and has completed the present invention.
[0011]
[Means for Solving the Problems]
The estrogen-like agent, collagen production promoter and fibroblast proliferation agent according to the present invention are each characterized by comprising a lotus germ extract. In the present invention, an embryo (embryo) in the seed of a lotus (Nelumbo nucifera Gaertn.) Is used. Embryos are usually green and stick-shaped, and those that are taken out from the collected seeds and dried immediately are preferably used.
[0012]
The lotus germ extract is obtained by mixing the germ with various aliphatic lower alcohols such as water, methanol, ethanol and isopropanol, hydrophilic organic solvents such as 1,3-butylene glycol, ethylene glycol and glycerin, and mixtures of these hydrophilic organic solvents. And it is obtained by extracting using various aqueous solvents, such as a liquid mixture of these hydrophilic organic solvents and water.
[0013]
In the extraction, the obtained embryo can be used as it is, but it is preferably used after pulverization in order to increase the extraction efficiency. In addition, when a degreasing treatment is performed in advance using a non-aqueous solvent (non-polar solvent) such as hexane, the impurity content is reduced, and a more effective extract can be obtained.
[0014]
The extraction can be performed using an arbitrary apparatus depending on the extraction solvent at room temperature or under heating. For example, the ground lotus germ is introduced into a treatment tank filled with the extraction solvent, and the soluble components are eluted with occasional stirring. Then, it can filter and remove an extraction residue and can obtain an extract. The amount of the solvent used at this time is preferably about 1: 5 to 1:20 in a weight ratio with respect to the lotus germ.
[0015]
The extract (liquid) thus obtained can be used as it is as an estrogen-like agent, as a collagen production promoter, or as a fibroblast proliferation agent. However, the extract is concentrated or further concentrated. It can also be provided as an extract or a dried product obtained by distilling the extraction solvent and the like.
[0016]
Further, since the lotus germ extract has a unique smell and taste, it is preferably purified for the purpose of deodorization and decolorization to the extent that the physiological activity is not lowered. Of course, depending on the purpose of use, for example, when it is contained in the cosmetic food or skin cosmetic according to the present invention, since it is not used in large quantities, it can be used as it is.
[0017]
Further, the estrogen-like agent, collagen production promoter and fibroblast proliferation agent of the present invention include various sugars such as sucrose and lactose to facilitate storage and handling of the extract as necessary. Further, excipients such as protein and starch, and other optional auxiliaries may be used. Moreover, it can also be provided by formulating as appropriate, and for example, it can also be provided as an arbitrary dosage form such as powder, granule, tablet and the like.
[0018]
These estrogen-like agents, collagen production promoters and fibroblast proliferation agents can be used orally by adding them to any food or as cosmetic foods such as nutritional supplements based on these. can do. Examples of foods that can be added include various soft drinks and fruit juice drinks, Japanese and Western confectionery, dairy products and other livestock processed products, processed fruit products, processed vegetable products, processed cereal products, processed fishery products, seasonings, and vitamins. Many foods and drinks such as so-called various health foods mainly composed of these are listed. Moreover, also as a dietary supplement, it can also provide as a thing of the form of a liquid agent, a tablet, etc., for example. The addition rate in this case varies depending on the form of the extract such as liquid or solid, taking into account the general intake of cosmetic foods to be added, but generally intake of lotus germ extract per day for adults It is appropriate to add approximately 1 to 1000 mg as an amount, approximately 4 to 1200 mg in terms of the dried lotus germ as a raw material.
[0019]
Moreover, in order to exhibit the effect | action of a lotus germ extract most effectively, it is mix | blending with various skin cosmetics. Suitable skin cosmetics for blending are, for example, ointments, creams, emulsions, lotions, packs, bathing agents, and the like. In this case, the blending amount is approximately 0.01 to 10% by weight as a lotus germ extract. It is suitable to add so that it may become 0.04 to 40% in terms of dried lotus germ.
[0020]
The cosmetic foods and skin cosmetics according to the present invention do not interfere with any of these estrogen-like actions, collagen production promoting actions or fibroblast proliferation actions. It goes without saying that various raw materials usually used in production can be used.
[0021]
【Example】
Next, an estrogen-like agent, a collagen production promoter and a fibroblast proliferating agent that are examples of the present invention, and cosmetic foods and skin cosmetics that are formulation examples of the present invention will be shown, and the present invention will be described in detail. explain.
[0022]
Example 1
300 g of the lotus germ crushed material was put into 2000 ml of the extraction solvent shown in Table 1 and extracted at 70 ° C. for 3 hours with gentle stirring. Thereafter, the filtrate obtained by filtration is concentrated under reduced pressure at 40 ° C., and further dried by a vacuum dryer, and is then a powdered lotus germ extract estrogen-like agent, collagen production promoting agent, fibroblast A cell proliferation agent was obtained. The yield is shown in Table 1.
[0023]
[Table 1]
Figure 0004693963
[0024]
(Example 2)
300 g of the crude lotus germ was put into 2000 ml of a mixture of 1,3-butylene glycol and water (volume ratio 1: 1), and extracted at 80 ° C. for 3 hours with stirring. Thereafter, filtration was performed to obtain 1440 ml of an estrogen-like agent, collagen production promoting agent, fibroblast proliferation agent, which is a liquid lotus germ extract. The solid content concentration of this product was 4.0% by weight. The solid content concentration was determined by taking a small amount of the extract and evaporating to dryness (the same applies hereinafter).
[0025]
(Example 3)
A liquid lotus germ extract 1540 ml was obtained in the same manner as in Example 2 except that a mixture of glycerin and water (volume ratio 1: 1) was used as the extraction solvent. The solid content concentration of this product was 3.5% by weight.
[0026]
Example 4
A liquid lotus germ extract 1540 ml was obtained in the same manner as in Example 2 except that 2000 ml of a mixture of propylene glycol and water (volume ratio 1: 1) was used as the extraction solvent. The solid concentration of this product was 3.3% by weight.
[0027]
Next, using the various estrogen-like agents, collagen production promoting agents, and fibroblast proliferation agents obtained in Examples 1 to 4 above, various skin cosmetics and cosmetic foods according to the present invention are prepared. did.
Figure 0004693963
The amount of the above components was taken, and an emulsion that was a skin cosmetic according to the present invention was prepared according to a conventional method.
[0028]
Figure 0004693963
The amount of the above components was taken, and an emulsion that was a skin cosmetic according to the present invention was prepared according to a conventional method.
[0029]
Figure 0004693963
The amount of the above components was taken, and a skin lotion that was a skin cosmetic according to the present invention was prepared according to a conventional method.
[0030]
Figure 0004693963
The amount of the above components was taken, and a W / O type cream, which is a skin cosmetic according to the present invention, was prepared according to a conventional method.
[0031]
Figure 0004693963
The amount of the above components was taken, and a pack which is a skin cosmetic according to the present invention was prepared according to a conventional method.
[0032]
Figure 0004693963
The amount of the above components was taken, and a tablet-like health / nutritional supplement, which is a cosmetic food according to the present invention, was produced according to a conventional method.
[0033]
Figure 0004693963
The amount of the above ingredients was taken, and a granular health / nutritional supplement which is a cosmetic food according to the present invention was produced according to a conventional method.
[0034]
Figure 0004693963
The above component amounts were taken and gelatin-encapsulated according to a conventional method to produce a capsule-like health / nutritional supplement which is a cosmetic food according to the present invention.
[0035]
Figure 0004693963
The amount of the above components was taken and dissolved by stirring to produce a soft drink-like health / nutritional supplement that is a beauty food according to the present invention.
[0036]
Figure 0004693963
The amount of the above ingredients was taken, and a candy-like health / nutritional supplement, which is a cosmetic food according to the present invention, was produced according to a conventional method.
[0037]
(Effectiveness test)
[Estrogen-like action]
According to the method of Thomas et al. (In Vitro Cell. Dev. Biol. 28A, 595-602, 1992) for examining the effect of various lotus germ extracts obtained in Examples 1 to 4 on the proliferation of estrogen-dependent cells. The action was examined. The results are shown in Table 2. In addition, the control value using water is shown as 100.
[0038]
[Table 2]
Figure 0004693963
[0039]
[Promoting collagen production]
For each extract obtained in Examples 1-4 above, collagen produced by fibroblasts cultured in a medium supplemented with each extract according to the method of Webster et al. (Anal. Biochem., Vol 96, 220, 1979). The amount was measured. On the other hand, the radioactivity produced in the medium without the addition of each extract was measured, and the collagen production rate when this collagen content was taken as 100 was determined. Specific test methods are shown below, and the results are shown in Table 3.
Test method: Human fibroblasts are seeded on a plate, cultured at 37 ° C. and 5% carbon dioxide in two types of sample-added media (sample concentrations: 200 ppm and 50 ppm) for several days, and then β-aminopropionitrile. And [ 3 H] -proline were added, and further cultured for 24 hours. A pepsin / acetic acid solution is added to the whole culture solution, digested at 4 ° C. for 16 hours, then a carrier is added to the digested solution, precipitated with 0.7 M saline, and redissolved under neutral conditions. Re-precipitated with 4.2M saline. The obtained precipitate was washed with 20 v / v% ethanol, and then the radioactivity of the precipitate was measured.
[0040]
[Table 3]
Figure 0004693963
[0041]
[Fibroblast proliferation effect]
According to the MTT method (J. Immunol. Medhods. 93, 157, 1986) by Tada et al., Various lotus germ extracts obtained in the above Examples 1 to 4 were fibrillated using human normal neonatal skin fibroblasts (NBIRGB). The blast proliferation effect was measured. The results are shown in Table 4. In addition, the control value using water is shown as 100.
[0042]
[Table 4]
Figure 0004693963
(Evaluation results)
As shown in Tables 2 to 4, lotus germ extracts using various aqueous solvents such as water, ethanol, a mixture of isopropanol and water, and a mixture of 1,3-butylene glycol and water have good estrogenic effects. Collagen production promoting action and fibroblast proliferation action were observed.
[0043]
[Rough skin improvement effect]
Next, the following evaluation test was conducted on the emulsion shown in Formulation Example 1. As a comparative example, an emulsion containing no lotus germ extract was prepared and used.
-Subjects: Twenty persons who were judged to have rough skin corresponding to grade 1 or 2 were selected as subjects from many healthy women aged 22 to 43 according to the following evaluation criteria.
Application test: Each subject was allowed to apply the emulsion shown in Preparation Example 1 for the right half of the face and the comparative emulsion on the left half once each morning and evening for 30 days.
・ Evaluation: After the application test was completed, a replica of the face was taken using Sylphlo (manufactured by Flexicl Developments Ltd.), a face replica was taken, and the state of the crest and keratin exfoliation were observed with an optical microscope at a magnification of 50 times. Skin condition was determined according to standards. The determination results are shown in Table 5.
[0044]
Figure 0004693963
[0045]
[Table 5]
Figure 0004693963
[0046]
As shown in Table 5, it can be seen that in the region where the emulsion which is the formulation example of the present invention is applied, the rough skin is remarkably improved as compared with the case where the emulsion which is the comparative example is applied.
[0047]
【The invention's effect】
According to the present invention, a novel estrogen-like agent that is highly safe and has the same action as estrogen, a collagen production promoter that promotes the production of collagen constituting the skin, and actively activates fibroblasts in human skin. A fibroblast proliferating agent can be provided. By applying these to cosmetic foods and skin cosmetics, it is possible to effectively prevent skin aging and greatly contribute to the maintenance of tension and gloss.

Claims (2)

ハスの種子から取り出した胚芽を、水と、エタノール、イソプロパノール、1,3−ブチレングリコール、グリセリン及びプロピレングリコールから選択される有機溶媒との混合溶媒で抽出して得られたハス胚芽抽出物からなることを特徴とするコラーゲン産生促進剤。  It consists of a lotus germ extract obtained by extracting a germ taken from a lotus seed with a mixed solvent of water and an organic solvent selected from ethanol, isopropanol, 1,3-butylene glycol, glycerin and propylene glycol. A collagen production promoter characterized by that. ハスの種子から取り出した胚芽を、水と、エタノール、イソプロパノール、1,3−ブチレングリコール、グリセリン及びプロピレングリコールから選択される有機溶媒との混合溶媒で抽出して得られたハス胚芽抽出物からなり、線維芽細胞増殖作用を有することを特徴とする線維芽細胞増殖剤。  It consists of a lotus germ extract obtained by extracting a germ taken from a lotus seed with a mixed solvent of water and an organic solvent selected from ethanol, isopropanol, 1,3-butylene glycol, glycerin and propylene glycol. And a fibroblast proliferating agent characterized by having a fibroblast proliferating action.
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