JP2004067590A - Female sex hormone production promoter and skin preparation for external use containing the same - Google Patents
Female sex hormone production promoter and skin preparation for external use containing the same Download PDFInfo
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- JP2004067590A JP2004067590A JP2002229024A JP2002229024A JP2004067590A JP 2004067590 A JP2004067590 A JP 2004067590A JP 2002229024 A JP2002229024 A JP 2002229024A JP 2002229024 A JP2002229024 A JP 2002229024A JP 2004067590 A JP2004067590 A JP 2004067590A
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Abstract
Description
【０００１】
【産業上の利用分野】本発明は、皮膚線維芽細胞が女性ホルモンであるエストロゲンを産生していることに着目し、その女性ホルモンを産生促進することにより、加齢に伴い皮膚機能が低下してカサカサした肌、ハリのない肌・シワの多い肌の改善を目的とした女性ホルモン産生促進剤、老化防止用皮膚外用剤に関する。
【０００２】
【従来の技術および発明が解決しようとする課題】近年、高齢化社会が進行するにつれて、高齢婦人の人口に占める比率は年々増加している。２０００年には、閉経後の女性の数が１，０００万人に達したと言われている。更年期を迎え、更年期障害で悩んでいる人が増えている。更年期の女性に特有の皮膚変化として、皮膚の乾燥（皮膚のカサカサ）、顔のシワを気にしている人は少なくない。これらの原因は、閉経後の女性における女性ホルモン（エストロゲン）の低下によるところが大きい。エストロゲンの低下により皮膚の厚さは急激に低下してくると共に弾力性が少なくなってくる。
【０００３】
これらを改善する方法として用いられているエストロゲン投与療法は、老化する皮膚に関係するこれらの変化の多くを予防するかまたは遅らせる（Ｃｒｅｉｄｉら、Ｅｆｆｅｃｔ ｏｆ ａ ｃｏｎｊｕｇａｔｅｄ ｅｓｔｒｏｇｅｎ ｃｒｅａｍ ｏｎ ａｇｉｎｇ ｆａｃｉａｌ ｓｋｉｎ， Ｍａｔｕｒｉｔａｓ， １９， Ｐ．２１１， １９９４）。皮膚におけるエストロゲンの効果として、皮膚の厚みの増加および小皺の消失、表皮の有糸分裂速度の増加、皮脂腺の大きさおよび活性の減少、毛髪成長速度の低下、コラーゲン・ターンオーバーの刺激、ならびに線維芽細胞のヒアルロン酸産生およびグリコサミノグリカン合成の増加などが知られている。（Ｐｕｇｌｉｅｓｅ， Ｍｅｎｏｐａｕｓａｌ ｓｋｉｎ， Ｓｋｉｎ Ｉｎｃ．， ３月／４月 １９９４年：ｐ．６９〜７７）。エストロゲンの不足を補う事が、女性の肌をみずみずしくしている秘密であると考えられる。また、皮膚科領域においては、Ｃｈｉｅｆｆｉは女性ホルモンの局所外用療法を行うことによって皮膚が１５年分若返らせることができると言っている（産婦人科ＭＯＯＫ Ｎｏ．３０．１９８５）。
【０００４】しかし、従来から行われているホルモン療法などのエストロゲン投与療法を行なう事によって乳癌などの副作用を引き起こす可能性があるなど安全性に問題があった。また、弱いエストロゲン様作用を持つ植物抽出物を用いてエストロゲン様作用剤が存在するが、これまでのものはいずれも効果が十分でなかったのが現状であった。
【０００５】従って、加齢によるシワを予防または改善する効果が絶大であり、しかも皮膚に弊害がなく、安全に使用できる老化防止に有効な皮膚外用剤の開発が望まれている。
【０００６】
【問題を解決する手段】そこで本発明者は、かかる実情に鑑み鋭意検討した結果、これまでエストロゲンは卵巣から分泌され、血液を介して各組織で働いていると考えられていたが、皮膚の線維芽細胞でもエストロゲンを産生する事を発見した。そして、そのエストロゲン産生能を活性化し、細胞外マトリックスの産生を増加させることにより、皮膚のハリ・シワの改善に顕著な作用を示すことを突き止めた。本発明では、弱いエストロゲン様作用ではなく、エストロゲン自身による作用であるので前記に示した老化予防または改善効果が優れていることを確認した。
【０００７】すなわち、本発明は、イソフラボン及び／又は前記一般式（化１）に表されるイソフラボン誘導体または生理的に許容されるその塩、及び／又は各種植物エキスから１種又は２種以上を配合することを特徴とする女性ホルモン産生促進剤である。
【０００８】
【発明の実施の形態】本発明の女性ホルモン産生促進剤は、前記式化１に表される化合物及び／又はその生理的に許容される塩及び／又は各種植物エキスからなる。式中に於ける置換基のアルキル基又はアシル基の炭化水素部分としては、炭素鎖１〜２０のものが好ましく、中でも１〜４の低鎖長の直鎖、分岐構造乃至は環状構造を有するものが更に好ましく、メチル基が特に好ましい。又、置換基中のグリコシル基またはグリコシド基としては、糖鎖１〜１０のものが好ましく、１または２のものが更に好ましい。具体的にはグルコシル基、グリコシド基、ラムノシルグルコシル基、ラムノシルグルコシド基、ラムノシル残基、ラムノシド残基などが例示できる。ここで、生理的に許容される塩としては、通常医薬や化粧料で使用されている塩であれば特段の限定無く使用でき、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム塩、マグネシウム塩等のアルカリ土類金属塩、アンモニウム塩、トリエチルアミン塩、トリエタノールアミン塩、モノエタノールアミン塩等の有機アミン塩、リジン塩、アルギニン塩などの塩基性アミノ酸塩などが好適に例示できる。本発明の女性ホルモン産生促進剤として好ましい化１に表される化合物としては、例えば、ダイゼイン（化１中Ｒ１＝Ｈ Ｒ２＝Ｈ Ｒ３＝ＯＨ）、ゲニステイン（化１中Ｒ１＝ＯＨ Ｒ２＝Ｈ Ｒ３＝ＯＨ）、グリシテイン（化１中Ｒ１＝Ｈ Ｒ２＝ＯＣＨ３ Ｒ３＝ＯＨ）、ダイジン（化１中Ｒ１＝Ｈ Ｒ２＝Ｈ Ｒ３＝ＯＣ６Ｈ１１Ｏ５）、ゲニスチン（化１中Ｒ１＝ＯＨ Ｒ２＝Ｈ Ｒ３＝ＯＣ６Ｈ１１Ｏ５）、グリシチン（化１中 Ｒ１＝Ｈ Ｒ２＝ＯＣＨ３ Ｒ３＝ＯＣ６Ｈ１１Ｏ５）等が好適に例示できる。これらの化合物は何れも文献において知られている化合物であり、多くのものは市販されていて購入することが可能であるし、市販されていないものであっても、常法に従って製造することが出来る。本発明は、この様に市販されているものや常法に従って製造されたものを使用することが出来るが、種々の植物から抽出することもできる。
【０００９】例えば、ダイゼインは、ジャーナル・オブ・ザ・ケミカル・ソサエテイー（Ｊ．Ｃｈｅｍ． Ｓｏｃ．）１９３３，２７４もしくは１９３４，１７６９などに記載の公知方法あるいはそれに準じる方法に従って製造することができる。また、マメ科のヒヨコマメ、デイコ、エニシダ、ダイズ、アズキ、クズ、クローバー、マキなどからアルコールやエーテルで抽出することもできる。
【００１０】ゲニステインは、例えばジャーナル・オブ・ザ・ケミカル・ソサエテイー（Ｊ．Ｃｈｅｍ． Ｓｏｃ．）１９２８，３１１５に記載の方法あるいはそれに準じる方法に従って製造することができる。また、マメ科のヒヨコマメ、デイコ、エニシダ、ダイズ、アズキ、クズ、クローバー、エンジュ、ルビナス、フジマメなどから有機溶媒を用いて抽出することもできる。
【００１１】本発明に用いられるダイズ属（Ｇｌｙｃｉｎｅ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、大豆（Ｇｌｙｃｉｎｅ Ｍａｘ
Ｍｅｒｉｌｌ）、ツルマメ（Ｇｌｙｃｉｎｅ ｕｓｓｕｒｉｅｎｓｉｓ）が好ましく用いられる。
【００１２】本発明に用いられるバラ属（Ｒｏｓａ）に属する植物としては、同属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、バラ（Ｒｏｓａ ｈｙｂｒｉｄａ Ｈｏｒｔ）、カニナバラ（Ｒｏｓａ ｃａｎｉｎａ Ｌ．）、ダマスクローズ（Ｒｏｓａ ｄａｍａｓｃｅｎａ）が好ましく用いられる。
【００１３】サクラ属（Ｐｒｕｎｕｓ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、ソメイヨシノ（Ｐｒｕｎｕｓ×ｙｅｄｏｅｎｓｉｓ Ｍａｔｓｕｍ）またはヤマザクラ（Ｐｒｕｎｕｓ ｊａｍａｓａｋｕｒａ Ｓｉｅｂｏｌｉｄ ｅｘ Ｋｏｉｄｚ）または（Ｐｒｕｎｕｓ×ｌａｎｎｅｓｉａｎａ ｗｉｌｓ．）またはアーモンド（Ｐｒｕｎｕｓ
ｄｕｌｉｃｉｓ）が好ましく用いられる。
【００１４】ジャジクソウ属（Ｔｒｉｆｏｌｉｕｍ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、レッドクローバー（Ｔｒｉｆｏｌｉｕｍ
ｐｒａｔｅｎｓｅ Ｌ．）、クローバー（Ｔｒｉｆｏｌｉｕｍ ｒｅｐｅｎｓ
Ｌ．）が好ましく用いられる。
【００１５】レイリョウコウ属（Ｔｒｉｇｏｎｅｌｌａ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、フェヌグリーク コロハ（Ｔｒｉｇｏｎｅｌｌａ
ｆｏｅｎｕｍ−ｇｒａｅｃｕｍ Ｌ．）が好ましく用いられる。
【００１６】本発明に用いられるアヤメ属（Ｉｒｉｓ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、アヤメ（Ｉｒｉｓ ｓａｎｇｕｉｎｅａ Ｈｏｒｎｅｍ．ｖａｒ．Ｓａｎｇｕｉｎｅａ）、ハナショウブ（Ｉｒｉｓ ｅｎｓａｔａ
Ｔｈｕｎｂ．）、カキツバタ（Ｉｒｉｓ ｌａｅｖｉｇａｔａ
Ｆｉｓｃｈｅｒ）が好ましく用いられる。
【００１７】本発明に用いられるクワ属（Ｍｏｒｕｓ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、クワ（Ｍｏｒｕｓ ｂｏｍｂｙｃｉｓ Ｋｏｉｄｚ）、マグア（Ｍｏｒｕｓ ａｌｂａ Ｌ．）が好ましく用いられる。
【００１８】本発明に用いられるイノコズチ属（Ａｃｈｙｒａｎｔｈｅｓ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、ヒナタイノコズチ（Ａｃｈｙｒａｎｔｈｅｓ
ｆａｕｒｉｅｉ）、イノコズチ（Ａｃｈｙｒａｎｔｈｅｓ ｊａｐｏｎｉｃａ
Ｎａｋａｉ）が好ましく用いられる。
【００１９】本発明に用いられるヤマノイモ属（Ｄｉｏｓｃｏｒｅａ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、サンヤク（Ｄｉｏｓｃｏｒｅａ Ｒａｄｉｘ）、トコロ（Ｄｉｏｓｃｏｒｅａ Ｔｏｋｏｒｏ Ｍａｋｉｎｏ）、ヤマノイモ（Ｄｉｏｓｃｏｒｅａ
ｊａｐｏｎｉｃａ Ｔｈｕｎｂ．）、ナガイモ（Ｄｉｏｓｃｏｒｅａ
ｏｐｐｏｓｉｔａ Ｔｈｕｎｂ．）が好ましく用いられる。
【００２０】本発明に用いられるヒレハリソウ属（Ｓｙｍｐｈｙｔｕｍ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、コンフリー（Ｓｙｍｐｈｙｔｕｍ
ｏｆｆｉｃｉｎａｂｌｅ Ｌ．）が好ましく用いられる。
【００２１】本発明に用いられるシモツケソウ属（Ｆｉｌｉｐｅｎｄｕｌａ）に属する植物としては、同属に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、セイヨウナツユキソウ（Ｆｉｌｉｐｅｎｄｕｌａ
ｕｌｍａｒｉａ）が好ましく用いられる。
【００２２】本発明に用いられるウイキョウ属（Ｆｏｅｎｉｃｕｌｕｍ）に属する植物としては、同科に属する植物であれば特に限定されることなく用いられ得るが、本発明では特に、フェンネル（Ｆｏｅｎｉｃｕｌｕｍ ｖｕｌｇａｒｅ Ｍｉｌｌ．）が好ましく用いられる。
【００２３】本発明において、各属に属する植物は、生のままでも乾燥したものでも使用することができるが、使用性、製剤化等の点から乾燥粉末あるいは溶媒抽出物として用いることが好ましい。
【００２４】前記各種植物群の使用部位は、植物体全体を用いることができるが、好ましくは種子、果実、花、葉、茎、根、樹皮または木部等が用いられる。なお、この場合の「花」は、いわゆる花軸と花葉を含む、有性生殖に関与する諸器官を含んだものをいい、花弁、雄ずい、雌ずい、蕚片等を含む。
【００２５】各属に属する植物の抽出物は、常法により得ることができ、例えば各属に属する植物を抽出溶媒とともに浸漬または加熱還流した後、濾過し、濃縮して得ることができる。抽出溶媒としては、通常抽出に用いられる溶媒であれば任意に用いることができ、例えば、水、メタノール、エタノール、プロピレングリコール、１，３−ブチレングリコール、グリセリン等のアルコール類、含水アルコール類、クロロホルム、ジクロルエタン、四塩化炭素、アセトン、酢酸エチル、ヘキサン等の有機溶媒等を、それぞれ単独あるいは組み合わせて用いることができる。前記溶媒で抽出して得た抽出液をそのまま、あるいは濃縮したエキスを吸着法、例えばイオン交換樹脂を用いて不純物を除去したものや、ポーラスポリマーのカラムにて吸着させた後、メタノールまたはエタノールで溶出し、濃縮したものも使用することができる。また分配法、例えば水／酢酸エチルで抽出した抽出物等も用いられる。
【００２６】このようにして得た各属に属する植物またはその抽出物は、女性ホルモン産生促進作用を有する。
【００２７】前記各属に属する植物またはその抽出物を皮膚外用医薬や化粧料などの皮膚外用剤に配合して用いる場合、外用剤全量中に乾燥重量として０．０００５〜２０重量％配合するのが好ましく、より好ましくは０．００１〜１０重量％である。飲食品・内服剤として用いる場合は、乾燥重量で２０〜１０００ｍｇである。
【００２８】前記化１に表される化合物及び／又はその生理的に許容される塩を皮膚外用医薬や化粧料などの皮膚外用剤中に含有させて使用する場合は、皮膚外用剤全量に対して０．０００１〜５重量％、更に好ましくは０．００１〜１重量％を含有させるのが特に好ましい。飲食品・内服剤の場合は、成人一日あたり２０〜１０００ｍｇ程度を１回乃至は数回に分けて服用又は食するのが好ましい。
【００２９】本発明の女性ホルモン産生促進剤を皮膚外用剤・飲食品・内服剤に用いる場合、前記成分に加えて、さらに必要により、本発明の効果を損なわない範囲内で各種成分を配合することが出来る。例えば保湿剤、酸化防止剤、油分、紫外線防御剤、界面活性剤、増粘剤、アルコール類、粉末成分、色材、水性成分、水、各種皮膚栄養剤等、具体例示すと、ビタミンＢ２類、ビタミンＢ６類、ビタミンＣ類、ビタミンＤ類、ニコチン酸類、ビタミンＥ類、ビタミンＰ、ビオチン等のビタミン類、アミノ酸及びアミノ酸誘導体、ホホバ油、スクワラン等の油分、グリセリン、ソルビトール、１，３−ブチレングリコール等のグリコール類、コラーゲン、ヒアルロン酸等の高分子保湿剤、酸化防止剤、界面活性剤、エチルパラベン、フェノキシエタノール等の防腐剤、グリチルリチン酸誘導体等の消炎剤、各種植物抽出物、カルボキシビニルポリマー等の増粘剤、香料、水、アルコール、色剤、ポリエチレン等の樹脂粉末等を必要に応じて適宜配合することができる。
【００３０】本発明の適用範囲は、特に限定されない。つまり、本発明の有効成分が有する作用効果に応じて各作用効果を利用できる全ての剤に適用できる。そのまま用いても良いし、添加物として用いることも可能である。
【００３１】例えば、本発明にかかる有効成分を各種皮膚外用剤基剤などに配合して、クリーム、乳液、化粧水、パック剤、洗顔料などの各種基礎化粧料、ファンデーション、口紅、ほほ紅、白粉などの各種メーキャップ料、洗髪料、養毛剤、シャンプー、リンスなどの各種頭髪用化粧料、石鹸、美爪料、オーデコロンなどその他化粧料に対して広範囲に適用できる。また、前記各種化粧料の実施態様は、溶液、エマルジョン、軟膏、ゾル、ゲル、パウダー、スプレーなどの各種態様で適用できる。
【００３２】例えば、本発明にかかる有効成分を飲食品・内服剤等などに配合して、ガム、キャンディーなどの口腔用組成物、ソーセージ、ハムなどの畜産製品、蒲鉾、ちくわなどの加工水産ねり製品、洋菓子類、和菓子類、調味料、ふりかけ、各種飲料、健康食品、錠剤、カプセル、粉末などの各種態様で適用できる。
【００３３】
【実施例】次に、実施例を挙げて本発明をさらに詳細に説明するが、本発明の技術的範囲はこれによってなんら限定されるものでない。なお、配合量はすべて重量％である。
【００３４】実施例に先立ち、本発明の各属に属する植物由来の溶媒抽出物または前記化１に示すイソフラボン誘導体の女性ホルモン産生促進作用の試験方法について説明する。
【００３５】
（１）．試料（植物抽出物）の調製
【００３６】（製造例１）市販の大豆（Ｇｌｙｃｉｎｅ Ｍａｘ
Ｍｅｒｉｌｌ）２０ｇをアルコール２００ｍｌに６０℃で１日間浸して抽出を行い、ろ別して抽出物を得た。
【００３７】（製造例２） レッドクローバー（Ｔｒｉｆｏｌｉｕｍ
ｐｒａｔｅｎｓｅ Ｌ．）の葉２０ｇを５０％１，３−ブチレングリコール水溶液に６０℃１日間浸して抽出を行い、ろ別して抽出物を得た。
【００３８】（製造例３）フェヌグリーク コロハ（Ｔｒｉｇｏｎｅｌｌａ
ｆｏｅｎｕｍ−ｇｒａｅｃｕｍ）の種子２５ｇを５０％アルコール水溶液２００ｍｌに６０℃で１日間浸して抽出を行い、ろ別して抽出物を得た。
【００３９】（製造例４）乾燥したカッコン（Ｐｕｅｒａｒｉａｅ Ｒａｄｉｘ）２０ｇをアルコール４００ｍｌに１日間浸して抽出を行い、ろ別して抽出物を得た。
【００４０】（製造例５）ソメイヨシノ（Ｐｒｕｎｕｓ×ｙｅｄｏｅｎｓｉｓ Ｍａｔｓｕｍ）の樹皮１５ｇをアルコール２００ｍｌに６０℃で１日間浸して抽出を行い、ろ別して抽出物を得た。
【００４１】（製造例６）ヤマザクラ（Ｐｒｕｎｕｓ ｊａｍａｓａｋｕｒａ Ｓｉｅｂｏｌｉｄ ｅｘ Ｋｏｉｄｚ）の樹皮１５ｇをアルコール２００ｍｌに６０℃で１日間浸して抽出を行い、ろ別して抽出物を得た。
【００４２】（製造例７）セイヨウナツユキソウ（Ｆｉｌｉｐｅｎｄｕｌａ
ｕｌｍａｒｉａ）の花を乾燥したもの２０ｇを５０％１，３−ブチレングリコール水溶液に６０℃で１日抽出を行い、ろ別して抽出物を得た。
【００４３】（製造例８）カニナバラ（Ｒｏｓａ．Ｃａｎｉｎａ Ｌ．）の乾燥した果実を粉末にしたもの２０ｇを１，３−ブチレングリコール２００ｇに６０℃で１日間浸して抽出を行い、ろ別して抽出物を得た。
【００４４】（製造例９）アヤメ（Ｉｒｉｓ ｓａｎｇｕｉｎｅａ
Ｈｏｒｎｅｍ．ｖａｒ．Ｓａｎｇｕｉｎｅａ）根茎を乾燥し、粉末にしたもの２０ｇをアルコール２００ｍｌに６０℃で１日間抽出を行い、ろ別して抽出物を得た。
【００４５】（製造例１０）クワ（Ｍｏｒｕｓ ｂｏｍｂｙｃｉｓ
Ｋｏｉｄｚ）の根皮２０ｇをアルコール２００ｍｌに６０℃で１日間抽出を行い、ろ別して抽出物を得た。
【００４６】（製造例１１）ヒナタイノコズチ（Ａｃｈｙｒａｎｔｈｅｓ
ｆａｕｒｉｅｉ）の根２０ｇをアルコール２００ｍｌに６０℃で１日間抽出を行い、ろ別して抽出物を得た。
【００４７】（製造例１２）サンヤク（Ｄｉｏｓｃｏｒｅａ Ｒａｄｉｘ）の塊根を乾燥し、粉末にしたもの２０ｇを５０％アルコール水溶液２００ｍｌに６０℃で１日間抽出を行い、ろ別して抽出物を得た。
【００４８】（製造例１３）コンフリー（Ｓｙｍｐｈｙｔｕｍ
ｏｆｆｉｃｉｎａｂｌｅ）の根を乾燥し、粉末にしたもの４ｇを５０％アルコール水溶液２００ｍｌに６０℃で１日間抽出を行い、ろ別して抽出物を得た。
【００４９】（製造例１４）フェンネル（Ｆｏｅｎｉｃｕｌｕｍ ｖｕｌｇａｒｅ）の種１２ｇをアルコール２００ｍｌに６０℃で１日間抽出を行い、ろ別して抽出物を得た。
【００５０】前記製造例１〜１４で得た植物抽出物、または前記化１に示す物質を用いて以下の実験を行った。
【００５１】（２）細胞培養
正常ヒト２倍体線維芽細胞ＨＦＳＫＦ−ＩＩ（理化学研究所製）を、Ｈａｍ−Ｆ１２（大日本製薬社製）に１５（ｖ／ｖ）％の牛胎児血清を加えた培地で５％炭酸ガス下、３７℃で培養した。前記培地にて１×１０６ｃｅｌｌ／ｍＬに調整した細胞を、１５０ｃｍ２培養シャアーレに３ｍＬずつ播種し、１７ｍｌの前記培地を追加して５日間培養（３日目に培地交換）後、コンフルエントの状態でＦＢＳを含まないＨａｍ−Ｆ１２に交換し、前記製造例１〜１４の植物抽出液または前記化１に示す物質を下記に示す濃度になるように添加し、その後４８時間培養した。尚、コントロールは培地のみを添加した。
【００５２】（３）タンパクの定量
シャーレ中のタンパク量をＢＣＡ法にて測定し、細胞数の指標とした。
【００５３】（４）エストロゲン量の定量
前記で得られた培養上清を５，０００ｒ．ｐ．ｍ、１０分間遠心分離を行い、得られた上清を採取し、エストロゲンの測定を行った。エストロゲンの測定は、市販の１７−βエストラジオール測定キット（Ａｓｓａｙ Ｄｅｓｉｇｎｓ，Ｉｎｃ．）を用いてＥＬＩＳＡ法で行った。
【００５４】なお、本実施例で用いた植物抽出物や物質については、下記実験濃度では細胞毒性は認められなかった。
【００５５】１．女性ホルモン産生促進効果
女性ホルモン産生促進効果の評価はエストロゲン産生量（ｐｇ／ｍｌ）／タンパク濃度（ｍｇ／ｍｌ）により行った。エストロゲン産生量は、試料添加し、４８ｈｒ培養後の培地中のエストロゲン量から、試料添加直後の培地中のエストロゲン量を差し引いた値をエストロゲン産生量と定義した。結果を表１に示す。
【００５６】
【数１】
【表１】
【００５９】
【処方例】以下に本発明の処方例を挙げる。
【実施例２】化粧水 〈組成〉 （重量％）
大豆の抽出物 １．０ グリセリン ５．０ ポリオキシエチレンソルビタンモノラウレート（２０Ｅ．Ｏ） １．５ エタノール １０．０ メチルパラベン０．１ 精製水 残部
〔製法〕前記原料を精製水に加え均一に混合する。
【００６０】
【実施例３】化粧水 〈組成〉 （重量％）
レッドクローバーの抽出物 ０．０５ グリセリン ５．０ ポリオキシエチレンソルビタンモノラウレート（２０Ｅ．Ｏ） １．５ エタノール １０．０ メチルパラベン０．１ 精製水 残部
〔製法〕前記原料を精製水に加え均一に混合する。
【００６１】
【実施例４】） ジェル （組成） （重量％）
（１）エタノール １０．０ （２）ジプロピレリングリコール １５．０ （３）ポリオキシエチレン（５０モル）
オレイルアルコールエーテル ２．０ （４）カルボキシビニルポリマー １．０ （５）苛性ソーダ ０．１５ （６）Ｌ−アルギニン ０．１ （７）カッコンの抽出物 ５．０ （８）２−ヒドロキシ−４−メトキシ ベンゾフェノンスルホン酸ナトリウム ０．０５ （９）エチレンジアミンテトラアセテート・ ３ナトリウム・２水和物 ０．０５（１０）メチルパラベン ０．２（１１）香料 適 量（１２）精製水 残 余（製法）（１２）に（４）を均一に溶解した（水相）。一方、（１）に（７）と（３）を溶解し、これを水相に添加した。次いでここに、（２）、（８）〜（１１）を加えた後、（５）、（６）で中和させ増粘した。
【００６２】
【実施例５】美容液 （配 合 成 分） （重量％）
（Ａ相）
エタノール １０．０ ポリオキシエチレン（２０モル）オクチルドデカノール １．０ パントテニルエチルエーテル ０．１ フェヌグリーク コロハの抽出物 １．５ メチルパラベン ０．１５（Ｂ相）
水酸化カリウム ０．１（Ｃ相）
グリセリン ５．０ ジプロピレリングリコール １０．０ 亜硫酸水素ナトリウム０．０３ カルボキシビニルポリマー ０．２
精製水 残 余（製法）Ａ相、Ｃ相をそれぞれ均一に溶解し、Ｃ相にＡ相を加えて可溶化した。次いでＢ相を加え充填を行った。
【００６３】
【実施例６】乳液 〈組成〉 （重量％）
油相： スクワラン ８．０ ワセリン ２．０ ミツロウ ０．５
乳化剤： ソルビタンセスキオレエート ０．８ ポリオキシエチレンオレイルエーテル（２０Ｅ．Ｏ．） １．２
水相：ソメイヨシノの抽出物 ０．００５ カルボキシビニルポリマー ０．２ プロピレングリコール ０．５ 水酸化カリウム ０．１ エタノール ７．０メチルパラベン０．１精製水 残部
〔製法〕前記水相の原料を混合し、加熱して７０゜Ｃに保ち水層部とする。一方、他の成分を混合し、加熱溶解して７０゜Ｃとして油相部とする。この油相部を前述の水層部に加えて乳化し、３０゜Ｃまで冷却し乳液を得る。
【００６４】
【実施例７】乳液 〈組成〉 （重量％）
油相： スクワラン ８．０ ワセリン ２．０ ミツロウ ０．５
乳化剤： ソルビタンセスキオレエート ０．８ ポリオキシエチレンオレイルエーテル（２０Ｅ．Ｏ．） １．２
水相： ヤマザクラの抽出物 １０．０カルボキシビニルポリマー ０．２ プロピレングリコール ０．５ 水酸化カリウム ０．１ エタノール ７．０メチルパラベン０．１精製水 残部
〔製法〕前記水相の原料を混合し、加熱して７０゜Ｃに保ち水層部とする。一方、他の成分を混合し、加熱溶解して７０゜Ｃとして油相部とする。この油相部を前述の水層部に加えて乳化し、３０゜Ｃまで冷却し乳液を得る。
【００６５】
【実施例８】パック剤 〈組成〉 （重量％）
粉末： 酸化チタン８．０ カオリン７．０ 油分： オリーブ油 ３．０ 香料 適量 防腐剤 適量 水相： セイヨウナツユキソウ の抽出物 ０．００１ 酢酸ビニル樹脂エマルジョン１５．０ ポリビニルアルコール １０．０ グリセリン ５．０ エタノール ５．０ 精製水 残部
〔製法〕水相の原料を混合し、均一にする。さらに他成分を混合し、均一になるまで攪拌する。
【００６６】
【実施例９】パック剤 〈組成〉 （重量％）
粉末： 酸化チタン ８．０ カオリン ７．０ 油分： オリーブ油 ３．０ 香料 適量 防腐剤 適量 水相：カニナバラの抽出物 １．０ 酢酸ビニル樹脂エマルジョン １５．０ ポリビニルアルコール １０．０ グリセリン ５．０ エタノール ５．０ 精製水 残部
〔製法〕水相の原料を混合し、均一にする。さらに他成分を混合し、均一になるまで攪拌する。
【００６７】
【実施例１０】クリーム状ファンデーション 〈組成〉 （重量％）
油相： ステアリン酸 ０．２ モノステアリン酸グリセリン ５．０ セタノール１．０
モノラウリン酸プロピレングリコール ３．０ スクワラン ７．０ オクタン酸セチル ８．０ 顔料： 酸化チタン ８．０ カオリン ５．０ タルク ２．０ 着色顔料
適量 防腐剤 適量 香料 適量
水相：アヤメの抽出物 ３．０ トリエタノールアミン １．２ ソルビット ３．０ 精製水
残部〔製法〕顔料を混合し粉砕する。水相を調整し、これに混合した顔料を加え分散させた後、７５゜Ｃに加熱する。油相を調整し８０゜Ｃに加熱する。油相を水相に攪拌しながら加え乳化した後冷却し、５０゜Ｃで香料を加えさらに３０゜Ｃまで冷却しクリーム状ファンデーションを得る。
【００６８】
【実施例１１】クリーム状ファンデーション 〈組成〉 （重量％）
油相： ステアリン酸 ０．２ モノステアリン酸グリセリン ５．０ セタノール １．０ モノラウリン酸プロピレングリコール ３．０ スクワラン ７．０ オクタン酸セチル ８．０ 顔料： 酸化チタン ８．０ カオリン ５．０ タルク ２．０ 着色顔料 適量 防腐剤 適量 香料 適量
水相：クワの抽出物 ０．５トリエタノールアミン １．２ ソルビット ３．０ 精製水残部
〔製法〕顔料を混合し粉砕する。水相を調整し、これに混合した顔料を加え分散させた後、７５゜Ｃに加熱する。油相を調整し８０゜Ｃに加熱する。油相を水相に攪拌しながら加え乳化した後冷却し、５０゜Ｃで香料を加えさらに３０゜Ｃまで冷却しクリーム状ファンデーションを得る。
【００６９】
【実施例１２】乳液 〈組成〉 （重量％）
油相： スクワラン ８．０ ワセリン ２．０ ミツロウ ０．５
乳化剤： ソルビタンセスキオレエート ０．８ ポリオキシエチレンオレイルエーテル（２０Ｅ．Ｏ．） １．２
水相： ヒナタイノコズチの抽出物 ０．０５ サンヤクの抽出物０．１５ カルボキシビニルポリマー ０．２ プロピレングリコール ０．５ 水酸化カリウム ０．１ エタノール ７．０メチルパラベン０．１精製水 残部
〔製法〕前記水相の原料を混合し、加熱して７０゜Ｃに保ち水層部とする。一方、他の成分を混合し、加熱溶解して７０゜Ｃとして油相部とする。この油相部を前述の水層部に加えて乳化し、３０゜Ｃまで冷却し乳液を得る。
【００７０】
【実施例１３】乳液 〈組成〉 （重量％）
油相： スクワラン ８．０ ワセリン ２．０ ミツロウ ０．５
乳化剤： ソルビタンセスキオレエート ０．８ ポリオキシエチレンオレイルエーテル（２０Ｅ．Ｏ．） １．２
水相： コンフリーの抽出物 ０．１ フェンネルの抽出物 ０．５
カルボキシビニルポリマー ０．２ プロピレングリコール ０．５ 水酸化カリウム ０．１
エタノール ７．０メチルパラベン０．１精製水 残部
〔製法〕前記水相の原料を混合し、加熱して７０゜Ｃに保ち水層部とする。一方、他の成分を混合し、加熱溶解して７０゜Ｃとして油相部とする。この油相部を前述の水層部に加えて乳化し、３０゜Ｃまで冷却し乳液を得る。
【００７１】
【実施例１４】乳液 〈組成〉 （重量％）
油相： スクワラン ８．０ ワセリン ２．０ ミツロウ ０．５
乳化剤： ソルビタンセスキオレエート ０．８ ポリオキシエチレンオレイルエーテル（２０Ｅ．Ｏ．） １．２
水相： ゲニステイン ０．１ダイゼイン０．０１ グリシテイン １．０
カルボキシビニルポリマー ０．２ プロピレングリコール ０．５ 水酸化カリウム ０．１
エタノール ７．０メチルパラベン０．１精製水 残部
〔製法〕前記水相の原料を混合し、加熱して７０゜Ｃに保ち水層部とする。一方、他の成分を混合し、加熱溶解して７０゜Ｃとして油相部とする。この油相部を前述の水層部に加えて乳化し、３０゜Ｃまで冷却し乳液を得る。
【００７２】
【実施例１５】パン 〈組成〉 （重量％）
小麦粉 ９０．０ 食塩 １．０ ブドウ糖
７．０ ソメイヨシノ抽出物 ２．０ バター 適量 イースト菌 適量
〔製法〕前記材料を、十分に混ぜ合わせ、発酵を行った後、オーブンで焼き上げる。
【００７３】
【実施例１６】飲料 〈組成〉 （重量％）
ブドウ糖液糖 ３０．０ カニナバラ抽出物 １０．０ 香料 ０．５ 精製水 残部
〔製法〕前記材料を十分に混ぜ合わせる。
【００７４】
【実施例１７】錠剤〈組成〉 （重量％）
ダイゼイン ０．１ ショ糖 ９９．９
〔製法〕前記材料を十分に混ぜ合わせ、打錠する。
【００７５】前記実施例２〜１４の各皮膚外用剤、実施例１５〜１７の各飲食品は、いずれも女性ホルモン産生促進効果に優れるものであり、皮膚のシワを改善して、うるおいのある若々しい肌の状態を維持することができるものであった。
【００７６】
【発明の効果】以上詳述したように、本発明により、真皮線維芽細胞の産生するエストロゲン産生能を亢進させ、加齢によるエストロゲン量の低下を補うことによって、うるおいのある若々しい肌の状態を維持することのできる効果を有する。[0001]
The present invention focuses on the fact that dermal fibroblasts produce estrogen, a female hormone, and by promoting the production of female hormones, the skin function decreases with age. The present invention relates to a female hormone production promoter and an external preparation for preventing aging, for the purpose of improving rough skin, smooth skin, and wrinkled skin.
[0002]
2. Description of the Related Art In recent years, as the aging society progresses, the ratio of elderly women to the population is increasing year by year. It is said that the number of postmenopausal women reached 10 million in 2000. Menopause is approaching, and more and more people are suffering from menopause. Many of the menopause women are concerned about skin changes (dry skin) and wrinkles on their faces. These causes are largely due to a decrease in female hormones (estrogens) in postmenopausal women. Due to the decrease in estrogen, the thickness of the skin decreases rapidly and the elasticity decreases.
[0003]
Estrogen dosing therapy, used as a way to improve these, prevents or delays many of these changes associated with aging skin (Creidi et al., Effect of a conjugated estrogen cream on aging facial skin, Maturatas, 1992). , P. 211, 1994). The effects of estrogen on the skin include increasing skin thickness and eliminating fine lines, increasing epidermal mitosis rate, decreasing sebaceous gland size and activity, decreasing hair growth rate, stimulating collagen turnover, and fibers. It is known that blast cells produce hyaluronic acid and increase glycosaminoglycan synthesis. (Pugliese, Menopausal skin, Skin Inc., March / April 1994: pp. 69-77). Supplementing the estrogen deficiency is thought to be the secret that keeps women's skin fresh. In the field of dermatology, Chieffi says that topical therapy with female hormones can rejuvenate the skin for 15 years (Obstetrics and Gynecology MOOK No. 30.19985).
[0004] However, there has been a problem in safety, for example, that administration of estrogen administration therapy such as hormone therapy which has been conventionally performed may cause side effects such as breast cancer. In addition, there are estrogen-like agents using a plant extract having a weak estrogen-like effect, but at present, none of them have been sufficiently effective.
[0005] Therefore, there is a demand for the development of an external preparation for skin which is effective in preventing or improving wrinkles due to aging, has no harmful effects on the skin, and can be used safely and effective in preventing aging.
[0006]
Means for Solving the Problems The present inventors have conducted intensive studies in view of the above circumstances, and as a result, it has been thought that estrogen is secreted from the ovaries and works in various tissues through blood. They found that fibroblasts also produce estrogen. They have also found out that by activating its estrogen-producing ability and increasing the production of extracellular matrix, it has a remarkable effect on improving skin firmness and wrinkles. In the present invention, it is confirmed that the above-mentioned aging prevention or ameliorating effect is excellent because it is not a weak estrogen-like action but an action of estrogen itself.
That is, the present invention provides one or more isoflavones and / or isoflavone derivatives represented by the above general formula (Chemical Formula 1) or physiologically acceptable salts thereof, and / or various plant extracts. It is a female hormone production promoter characterized by being blended.
[0008]
BEST MODE FOR CARRYING OUT THE INVENTION The female hormone production promoter of the present invention comprises the compound represented by Formula 1 and / or a physiologically acceptable salt thereof and / or various plant extracts. In the formula, the hydrocarbon moiety of the alkyl group or the acyl group of the substituent is preferably one having a carbon chain of 1 to 20, particularly having a low chain length of 1 to 4 having a straight-chain, branched or cyclic structure. Are more preferred, and a methyl group is particularly preferred. The glycosyl group or glycoside group in the substituent is preferably one having a sugar chain of 1 to 10, more preferably one or two. Specific examples include a glucosyl group, a glycoside group, a rhamnosyl glucosyl group, a rhamnosyl glucoside group, a rhamnosyl residue, and a rhamnoside residue. Here, the physiologically acceptable salt can be used without particular limitation as long as it is a salt usually used in medicine or cosmetics, for example, an alkali metal salt such as a sodium salt and a potassium salt, a calcium salt, Preferable examples include alkaline earth metal salts such as magnesium salts, organic amine salts such as ammonium salts, triethylamine salts, triethanolamine salts and monoethanolamine salts, and basic amino acid salts such as lysine salts and arginine salts. Preferred compounds represented by Chemical Formula 1 as the female hormone production promoter of the present invention include, for example, daidzein (R1 = HR2 = HR3 = OH in Chemical Formula 1) and genistein (R1 = OH R2 = HR3 in Chemical Formula 1). = OH), glycitein (R1 = H R2 = OCH in Chemical Formula 1) 3 R3 = OH), daidzin (R1 = H R2 = H R3 = OC in Chemical Formula 1) 6 H 11 O 5 ), Genistin (R1 = OH R2 = H R3 = OC in Chemical Formula 1) 6 H 11 O 5 ), Glycitin (wherein R1 = H R2 = OCH 3 R3 = OC 6 H 11 O 5 ) Can be preferably exemplified. Each of these compounds is a compound known in the literature, and many are commercially available and can be purchased, and even if they are not commercially available, they can be produced according to a conventional method. I can do it. In the present invention, those commercially available or those produced according to a conventional method can be used, but can also be extracted from various plants.
For example, daidzein can be produced according to a known method described in Journal of the Chemical Society (J. Chem. Soc.) 1933, 274 or 1934, 1769 or a method analogous thereto. Moreover, it can also be extracted from chickpea, larva, sardine, soybean, soybean, adzuki bean, kudzu, clover, maki, etc. of legumes with alcohol or ether.
Genistein can be produced, for example, according to the method described in Journal of the Chemical Society (J. Chem. Soc.) 1928, 3115 or a method analogous thereto. Further, it can also be extracted from legumes such as chickpea, deco, enishida, soybean, adzuki bean, kuzu, clover, endu, rubinas, and fuji bean using an organic solvent.
The plant belonging to the genus Glycine used in the present invention can be used without particular limitation as long as it belongs to the same genus. In the present invention, particularly, soybean (Glycine Max) is used.
Merrill) and bean (Glycine ussuriensis) are preferably used.
The plant belonging to the genus Rose (Rosa) used in the present invention can be used without any particular limitation as long as it is a plant belonging to the same genus. In the present invention, in particular, rose (Rosa hybrida Hort), canina rose ( Rosa canina L.) and damask rose (Rosa damascena) are preferably used.
As a plant belonging to the genus Prunus, any plant belonging to the same genus can be used without any particular limitation. In the present invention, in particular, Yoshino cherry (Prunus × yedoensis Matsum) or yamazakura (Prunus jamasakura Siebolid) is used. ex Koidz) or (Prunus × lannesiana wils.) or almond (Prunus)
dulicis) is preferably used.
As a plant belonging to the genus Trifolium, any plant belonging to the same genus can be used without particular limitation. In the present invention, particularly, red clover (Trifolium) is used.
platen L. ), Clover (Trifolium repens)
L. ) Is preferably used.
As a plant belonging to the genus Trigonella, any plant belonging to the same genus can be used without particular limitation. In the present invention, particularly, a fenugreek fenugreek (Trigonella) is used.
foenum-graecum L .; ) Is preferably used.
As a plant belonging to the genus Iris (Iris) used in the present invention, any plant belonging to the same genus can be used without any particular limitation. In the present invention, in particular, iris (Iris sanguinea Hornem. Var. Sanguinea), Hanashobu (Iris ensata)
Thumb. ), Oyster grasshopper (Iris laevigata)
Fischer) is preferably used.
As the plant belonging to the genus Morus used in the present invention, any plant belonging to the same genus can be used without any particular limitation. In the present invention, in particular, mulberry (Morus bombycis Koidz), magua (Morus alba L.) is preferably used.
The plant belonging to the genus Achyranthes used in the present invention can be used without any particular limitation as long as it is a plant belonging to the same genus. In the present invention, the plant belonging to the genus Achyranthes is particularly preferred.
fauriei), Inokokochi (Achyranthes japonica)
Nakai) is preferably used.
The plant belonging to the genus Dioscorea used in the present invention can be used without any particular limitation as long as it belongs to the same genus. In the present invention, in particular, sanyak (Dioscorea Radix), tokoro ( Dioscorea Tokoro Makino), Yamanoimo (Dioscorea)
japonica Thunb. ), Chinese yam (Dioscorea)
opposita Thunb. ) Is preferably used.
The plant belonging to the genus Symphytum used in the present invention can be used without particular limitation as long as it is a plant belonging to the same genus. In the present invention, particularly, comfrey (Symphytum) is used.
officinable L. ) Is preferably used.
The plant belonging to the genus Filipendula used in the present invention can be used without particular limitation as long as it is a plant belonging to the same genus. In the present invention, in particular, in the present invention, Filipendula is used.
ulmaria) is preferably used.
The plant belonging to the genus Feniculum used in the present invention can be used without any particular limitation as long as it is a plant belonging to the same family. In the present invention, fennel (Foeniculum vulgare Mill.) Is particularly used. Is preferably used.
In the present invention, the plants belonging to each genus can be used either raw or dried, but are preferably used as a dry powder or a solvent extract from the viewpoints of usability, formulation and the like.
The site of use of the various plant groups may be the whole plant, but preferably seeds, fruits, flowers, leaves, stems, roots, bark or xylem. In this case, the “flower” refers to a flower containing various organs involved in sexual reproduction, including a so-called floral axis and a flower leaf, and includes petals, stamens, pistils, stalks and the like.
An extract of a plant belonging to each genus can be obtained by a conventional method. For example, a plant belonging to each genus can be obtained by immersing or heating under reflux with an extraction solvent, followed by filtration and concentration. As the extraction solvent, any solvent can be used as long as it is a solvent usually used for extraction. For example, water, methanol, ethanol, propylene glycol, 1,3-butylene glycol, alcohols such as glycerin, hydrous alcohols, chloroform And organic solvents such as dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane and the like can be used alone or in combination. The extract obtained by extraction with the solvent as it is, or the concentrated extract is subjected to an adsorption method, for example, one obtained by removing impurities using an ion-exchange resin, or after adsorbing on a porous polymer column, and then methanol or ethanol. Eluted and concentrated ones can also be used. In addition, a partitioning method, for example, an extract extracted with water / ethyl acetate and the like are also used.
The plants belonging to each genus or their extracts thus obtained have a female hormone production promoting action.
When the plant belonging to each of the above genera or its extract is used in the form of a skin external preparation such as a skin external medicine or cosmetic, 0.0005 to 20% by weight as dry weight is added to the total amount of the external preparation. And more preferably 0.001 to 10% by weight. When used as a food / drink or internal medicine, the dry weight is 20 to 1000 mg.
When the compound represented by Chemical Formula 1 and / or a physiologically acceptable salt thereof is contained in a skin external preparation such as a medicine for external use or a cosmetic, the total amount of the external preparation for skin is required. It is particularly preferable to contain 0.0001 to 5% by weight, more preferably 0.001 to 1% by weight. In the case of foods, drinks and internal medicines, it is preferable to take or eat about 20 to 1000 mg per day for adults, once or several times.
When the female hormone production-promoting agent of the present invention is used in an external preparation for skin, a food or drink, or an internal preparation, various components are further added, if necessary, as long as the effects of the present invention are not impaired. I can do it. For example, moisturizers, antioxidants, oils, UV protection agents, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrition agents, etc. 2 And vitamin B 6 , Vitamin C, vitamin D, nicotinic acid, vitamin E, vitamin P, vitamins such as biotin, amino acids and amino acid derivatives, oils such as jojoba oil and squalane, glycerin, sorbitol, 1,3-butylene glycol, etc. Glycols, collagen, hyaluronic acid and other polymeric humectants, antioxidants, surfactants, preservatives such as ethylparaben and phenoxyethanol, anti-inflammatory agents such as glycyrrhizic acid derivatives, various plant extracts, carboxyvinyl polymers, etc. Thickeners, fragrances, water, alcohols, coloring agents, resin powders such as polyethylene, and the like can be appropriately compounded as necessary.
The scope of the present invention is not particularly limited. That is, the present invention can be applied to all agents that can utilize each effect according to the effects of the active ingredient of the present invention. It may be used as it is or may be used as an additive.
For example, the active ingredient according to the present invention is blended with various bases for external preparations for skin, and various basic cosmetics such as cream, emulsion, lotion, pack, face wash, foundation, lipstick, blusher, It can be widely applied to various makeup products such as white powder, hair washing products, hair tonics, shampoos, rinses and other hair cosmetics, soaps, nail polish, colognes and the like. The embodiments of the various cosmetics can be applied in various aspects such as a solution, an emulsion, an ointment, a sol, a gel, a powder, and a spray.
For example, the active ingredient according to the present invention is blended in foods and drinks, oral preparations and the like, and oral compositions such as gums and candies, livestock products such as sausages and hams, and processed seafood pastes such as kamaboko and chikuwa. It can be applied in various forms such as products, Western confectionery, Japanese confectionery, seasonings, sprinkles, various beverages, health foods, tablets, capsules, powders and the like.
[0033]
EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the technical scope of the present invention is not limited thereto. In addition, all compounding amounts are weight%.
Prior to the examples, a test method for the female hormone production-promoting effect of a solvent extract derived from a plant belonging to each genus of the present invention or the isoflavone derivative represented by Chemical formula 1 will be described.
[0035]
(1). Preparation of sample (plant extract)
(Production Example 1) Commercially available soybean (Glycine Max)
20 g of Merill) was immersed in 200 ml of alcohol at 60 ° C. for 1 day to carry out extraction, followed by filtration to obtain an extract.
(Production Example 2) Red clover (Trifolium)
platen L. ) Leaves were immersed in a 50% 1,3-butylene glycol aqueous solution at 60 ° C. for 1 day to perform extraction, followed by filtration to obtain an extract.
(Production Example 3) Fenugreek fenugreek (Trigonella)
25 g of foenum-graecum seeds was immersed in 200 ml of a 50% alcohol aqueous solution at 60 ° C. for 1 day to carry out extraction, followed by filtration to obtain an extract.
(Preparation Example 4) 20 g of dried cuckoo (Puerariae Radix) was immersed in 400 ml of alcohol for 1 day to carry out extraction, followed by filtration to obtain an extract.
(Preparation Example 5) 15 g of bark of Yoshino cherry tree (Prunus x Yedensis Massum) was immersed in 200 ml of alcohol at 60 ° C for 1 day, extracted, and filtered to obtain an extract.
(Production Example 6) 15 g of bark of yamazakura (Prunus jamakura Siebolid ex Koidz) was immersed in 200 ml of alcohol at 60 ° C. for 1 day, and the mixture was filtered to obtain an extract.
(Production Example 7) Filipendula (Filipendula)
20 g of dried ulmaria flower was extracted in a 50% aqueous 1,3-butylene glycol solution at 60 ° C. for 1 day, and filtered to obtain an extract.
(Production Example 8) 20 g of powdered dried fruit of canina rose (Rosa. Canina L.) was immersed in 200 g of 1,3-butylene glycol for 1 day at 60 ° C., extracted and filtered. Got.
(Production Example 9) Iris sanguinea (Iris sanguinea)
Hornem. var. (Sanguinea) rhizome was dried and powdered 20 g was extracted in 200 ml of alcohol at 60 ° C. for 1 day and filtered to obtain an extract.
(Production Example 10) Mulberry (Morus bombycis)
20 g of root bark of Koidz) was extracted in 200 ml of alcohol at 60 ° C. for 1 day, and filtered to obtain an extract.
(Production Example 11) Acyranthes
20 g of Fauriei root was extracted with 200 ml of alcohol at 60 ° C. for 1 day and filtered to obtain an extract.
(Production Example 12) 20 g of powdered root of a dried yam (Dioscorea Radix) was extracted in 200 ml of a 50% aqueous alcohol solution at 60 ° C. for 1 day, and filtered to obtain an extract.
(Production Example 13) Comfrey (Symphytum)
officinable) was dried, and 4 g of the powder was extracted with 200 ml of a 50% aqueous alcohol solution at 60 ° C. for 1 day, and filtered to obtain an extract.
(Production Example 14) 12 g of seeds of fennel (Foeniculum vulgare) were extracted in 200 ml of alcohol at 60 ° C for 1 day, and filtered to obtain an extract.
The following experiments were carried out using the plant extracts obtained in Production Examples 1 to 14 or the substances shown in Chemical Formula 1.
(2) Cell culture
Normal human diploid fibroblast HFSKF-II (manufactured by RIKEN) was transformed with Ham-F12 (manufactured by Dainippon Pharmaceutical Co., Ltd.) in a medium containing 15% (v / v)% fetal bovine serum and 5% carbon dioxide gas. And cultured at 37 ° C. 1 × 10 6 Cells adjusted to cell / mL are 2 3 mL of the culture medium was inoculated, 17 ml of the medium was added, and the cells were cultured for 5 days (medium was changed on the third day). Or the substance shown in Chemical formula 1 above was added to the concentration shown below, and then cultured for 48 hours. As a control, only the medium was added.
(3) Quantification of protein
The amount of protein in the petri dish was measured by the BCA method and used as an index of the number of cells.
(4) Determination of the amount of estrogen
The culture supernatant obtained above was subjected to 5,000 r. p. After centrifugation for 10 minutes, the obtained supernatant was collected and estrogen was measured. The estrogen was measured by ELISA using a commercially available 17-β estradiol measurement kit (Assay Designs, Inc.).
The plant extracts and substances used in this example did not show any cytotoxicity at the following experimental concentrations.
1. Female hormone production promotion effect
The effect of promoting female hormone production was evaluated based on estrogen production (pg / ml) / protein concentration (mg / ml). The estrogen production amount was defined as the estrogen production value obtained by subtracting the estrogen amount in the medium immediately after the sample addition from the estrogen amount in the culture medium after the sample was added and cultured for 48 hours. Table 1 shows the results.
[0056]
(Equation 1)
[Table 1]
[0059]
[Prescription Examples] The following are prescription examples of the present invention.
Example 2 Lotion <Composition> (% by weight)
Soybean extract 1.0 Glycerin 5.0 Polyoxyethylene sorbitan monolaurate (20EO) 1.5 Ethanol 10.0 Methyl paraben 0.1 Purified water Remainder
[Production method] The raw materials are added to purified water and mixed uniformly.
[0060]
Example 3 Lotion <Composition> (% by weight)
Red clover extract 0.05 Glycerin 5.0 Polyoxyethylene sorbitan monolaurate (20EO) 1.5 Ethanol 10.0 Methyl paraben 0.1 Purified water Remainder
[Production method] The raw materials are added to purified water and mixed uniformly.
[0061]
Example 4) Gel (Composition) (% by weight)
(1) Ethanol 10.0 (2) Dipropylen glycol 15.0 (3) Polyoxyethylene (50 mol)
Oleyl alcohol ether 2.0 (4) Carboxyvinyl polymer 1.0 (5) Caustic soda 0.15 (6) L-arginine 0.1 (7) Extract of cuckoo 5.0 (8) 2-hydroxy-4- Sodium methoxybenzophenonesulfonate 0.05 (9) Ethylenediaminetetraacetate trisodium dihydrate 0.05 (10) Methylparaben 0.2 (11) Perfume appropriate amount (12) Purified water residue (production method) (12) ) Was uniformly dissolved in (4) (aqueous phase). On the other hand, (7) and (3) were dissolved in (1) and added to the aqueous phase. Next, after adding (2) and (8) to (11), the mixture was neutralized with (5) and (6) to increase the viscosity.
[0062]
[Example 5] Essence (combination component) (% by weight)
(A phase)
Ethanol 10.0 polyoxyethylene (20 mol) octyl dodecanol 1.0 pantothenyl ethyl ether 0.1 fenugreek fenugreek extract 1.5 methyl paraben 0.15 (phase B)
Potassium hydroxide 0.1 (C phase)
Glycerin 5.0 Dipropylen glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2
Purified water Residue (production method) A phase and C phase were each dissolved uniformly, and the A phase was added to the C phase for solubilization. Next, the phase B was added to perform filling.
[0063]
Example 6 Emulsion <Composition> (% by weight)
Oil phase: Squalane 8.0 Vaseline 2.0 Beeswax 0.5
Emulsifier: Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether (20EO) 1.2
Aqueous phase: Yoshino cherry extract 0.005 Carboxyvinyl polymer 0.2 Propylene glycol 0.5 Potassium hydroxide 0.1 Ethanol 7.0 Methyl paraben 0.1 Purified water Remainder
[Production method] The raw materials for the aqueous phase are mixed and heated to 70 ° C. to form an aqueous layer. On the other hand, other components are mixed and dissolved by heating to 70 ° C. to obtain an oil phase. The oil phase is added to the aqueous layer and emulsified, and cooled to 30 ° C. to obtain an emulsion.
[0064]
Example 7 Emulsion <Composition> (% by weight)
Oil phase: Squalane 8.0 Vaseline 2.0 Beeswax 0.5
Emulsifier: Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether (20EO) 1.2
Aqueous phase: Yamazakura extract 10.0 Carboxyvinyl polymer 0.2 Propylene glycol 0.5 Potassium hydroxide 0.1 Ethanol 7.0 Methyl paraben 0.1 Purified water Remainder
[Production method] The raw materials for the aqueous phase are mixed and heated to 70 ° C. to form an aqueous layer. On the other hand, other components are mixed and dissolved by heating to 70 ° C. to obtain an oil phase. The oil phase is added to the aqueous layer and emulsified, and cooled to 30 ° C. to obtain an emulsion.
[0065]
Example 8 Packing agent <Composition> (% by weight)
Powder: Titanium oxide 8.0 Kaolin 7.0 Oil: Olive oil 3.0 Appropriate amount of fragrance Preservatives Appropriate amount Aqueous phase: Extract of oilseed foliage 0.001 Vinyl acetate resin emulsion 15.0 Polyvinyl alcohol 10.0 Glycerin 5.0 Ethanol 5.0 Purified water Remainder
[Production method] The raw materials of the aqueous phase are mixed and made uniform. Further mix other ingredients and stir until uniform.
[0066]
Example 9 Packing agent <Composition> (% by weight)
Powder: Titanium oxide 8.0 Kaolin 7.0 Oil: Olive oil 3.0 Appropriate amount of fragrance Preservatives Appropriate amount Aqueous phase: Extract of Kaninabara 1.0 Vinyl acetate resin emulsion 15.0 Polyvinyl alcohol 10.0 Glycerin 5.0 Ethanol 5 2.0 purified water balance
[Production method] The raw materials of the aqueous phase are mixed and made uniform. Further mix other ingredients and stir until uniform.
[0067]
Example 10 Creamy Foundation <Composition> (% by weight)
Oil phase: Stearic acid 0.2 Glycerin monostearate 5.0 Cetanol 1.0
Propylene glycol monolaurate 3.0 Squalane 7.0 Cetyl octanoate 8.0 Pigment: Titanium oxide 8.0 Kaolin 5.0 Talc 2.0 Color pigment
Appropriate amount Preservatives appropriate amount Fragrance appropriate amount
Aqueous phase: Iris extract 3.0 Triethanolamine 1.2 Sorbit 3.0 Purified water
The remainder [Production method] The pigment is mixed and pulverized. The aqueous phase is adjusted, and the mixed pigment is added and dispersed, and then heated to 75 ° C. Adjust the oil phase and heat to 80 ° C. The oil phase is added to the aqueous phase while stirring, emulsified and cooled, and a fragrance is added at 50 ° C and further cooled to 30 ° C to obtain a creamy foundation.
[0068]
Example 11 Creamy Foundation <Composition> (% by weight)
Oil phase: Stearic acid 0.2 Glycerin monostearate 5.0 Cetanol 1.0 Propylene glycol monolaurate 3.0 Squalane 7.0 Cetyl octanoate 8.0 Pigment: Titanium oxide 8.0 Kaolin 5.0 Talc 2. 0 Color pigment appropriate amount Preservative appropriate amount Fragrance appropriate amount
Aqueous phase: mulberry extract 0.5 triethanolamine 1.2 sorbit 3.0 purified water residue
[Production method] A pigment is mixed and pulverized. The aqueous phase is adjusted, and the mixed pigment is added and dispersed, and then heated to 75 ° C. Adjust the oil phase and heat to 80 ° C. The oil phase is added to the aqueous phase while stirring, emulsified and cooled, and a fragrance is added at 50 ° C and further cooled to 30 ° C to obtain a creamy foundation.
[0069]
Example 12 Emulsion <Composition> (% by weight)
Oil phase: Squalane 8.0 Vaseline 2.0 Beeswax 0.5
Emulsifier: Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether (20EO) 1.2
Aqueous phase: Hinata japonicus extract 0.05 Sanyak extract 0.15 Carboxyvinyl polymer 0.2 Propylene glycol 0.5 Potassium hydroxide 0.1 Ethanol 7.0 Methyl paraben 0.1 Purified water Remainder
[Production method] The raw materials for the aqueous phase are mixed and heated to 70 ° C. to form an aqueous layer. On the other hand, other components are mixed and dissolved by heating to 70 ° C. to obtain an oil phase. The oil phase is added to the aqueous layer and emulsified, and cooled to 30 ° C. to obtain an emulsion.
[0070]
Example 13 Emulsion <Composition> (% by weight)
Oil phase: Squalane 8.0 Vaseline 2.0 Beeswax 0.5
Emulsifier: Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether (20EO) 1.2
Aqueous phase: Comfrey extract 0.1 Fennel extract 0.5
Carboxyvinyl polymer 0.2 Propylene glycol 0.5 Potassium hydroxide 0.1
Ethanol 7.0 methyl paraben 0.1 purified water balance
[Production method] The raw materials for the aqueous phase are mixed and heated to 70 ° C. to form an aqueous layer. On the other hand, other components are mixed and dissolved by heating to 70 ° C. to obtain an oil phase. The oil phase is added to the aqueous layer and emulsified, and cooled to 30 ° C. to obtain an emulsion.
[0071]
Example 14 Emulsion <Composition> (% by weight)
Oil phase: Squalane 8.0 Vaseline 2.0 Beeswax 0.5
Emulsifier: Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether (20EO) 1.2
Aqueous phase: genistein 0.1 daidzein 0.01 glycitein 1.0
Carboxyvinyl polymer 0.2 Propylene glycol 0.5 Potassium hydroxide 0.1
Ethanol 7.0 methyl paraben 0.1 purified water balance
[Production method] The raw materials for the aqueous phase are mixed and heated to 70 ° C. to form an aqueous layer. On the other hand, other components are mixed and dissolved by heating to 70 ° C. to obtain an oil phase. The oil phase is added to the aqueous layer and emulsified, and cooled to 30 ° C. to obtain an emulsion.
[0072]
Example 15 Bread <Composition> (% by weight)
Flour 90.0 Salt 1.0 Glucose
7.0 Yoshino cherry extract 2.0 Butter proper amount Yeast fungus proper amount
[Manufacturing method] The above ingredients are thoroughly mixed, fermented, and baked in an oven.
[0073]
Example 16 Beverage <Composition> (% by weight)
Glucose liquid sugar 30.0 Canina rose extract 10.0 Fragrance 0.5 Purified water Remainder
[Production method] The above-mentioned materials are sufficiently mixed.
[0074]
Example 17 Tablet <Composition> (% by weight)
Daidzein 0.1 sucrose 99.9
[Production method] The above-mentioned materials are sufficiently mixed and tableted.
The skin external preparations of Examples 2 to 14 and the foods and drinks of Examples 15 to 17 are all excellent in promoting the production of female hormones, and have improved skin wrinkles and moisture. It was possible to maintain a youthful skin condition.
[0076]
As described in detail above, the present invention enhances the estrogen-producing ability of dermal fibroblasts and compensates for the decrease in the amount of estrogen due to aging. It has the effect that the state can be maintained.
Claims (6)
Ｍｅｒｉｌｌ）、ジャジクソウ属に属する植物がレッドクローバー（Ｔｒｉｆｏｌｉｕｍｐｒａｔｅｎｓｅ Ｌ．）、レイリョウコウ属に属する植物がフェヌグリーク コロハ（Ｔｒｉｇｏｎｅｌｌａ
ｆｏｅｎｕｍ−ｇｒａｅｃｕｍ Ｌ．）、クズ属に属する植物がカッコン（Ｐｕｅｒａｒｉａｅ Ｒａｄｉｘ）、バラ属に属する植物がカニナバラ（Ｒｏｓａ ｃａｎｉｎａ Ｌ．）、サクラ属に属する植物がソメイヨシノ（Ｐｒｕｎｕｓ×ｙｅｄｏｅｎｓｉｓ Ｍａｔｓｕｍ）、及び／又はヤマザクラ（Ｐｒｕｎｕｓ ｊａｍａｓａｋｕｒａ
Ｓｉｅｂｏｌｉｄ ｅｘ Ｋｏｉｄｚ）、シモツケソウ属に属する植物がセイヨウナツユキソウ（Ｆｉｌｉｐｅｎｄｕｌａ
ｕｌｍａｒｉａ）、アヤメ属に属する植物がアヤメ（Ｉｒｉｓ ｓａｎｇｕｉｎｅａ
Ｈｏｒｎｅｍ．ｖａｒ．Ｓａｎｇｕｉｎｅａ）、クワ属に属する植物がクワ（Ｍｏｒｕｓ ｂｏｍｂｙｃｉｓ Ｋｏｉｄｚ）、イノコズチ属に属する植物がヒナタイノコズチ（Ａｃｈｙｒａｎｔｈｅｓ
ｆａｕｒｉｅｉ）、ヤマノイモ属に属する植物がサンヤク（Ｄｉｏｓｃｏｒｅａ Ｒａｄｉｘ）、ヒレハリソウ属に属する植物がコンフリー（Ｓｙｍｐｈｙｔｕｍ
ｏｆｆｉｃｉｎａｂｌｅ Ｌ．）、ウイキョウ属に属する植物がフェンネル（Ｆｏｅｎｉｃｕｌｕｍｖｕｌｇａｒｅ Ｍｉｌｌ．）であることを特徴とする請求項３記載の女性ホルモン産生促進剤。Soybean plant belongs to soybean (Glycine Max)
Merrill), a plant belonging to the genus Jazikousou is red clover (Trifolumplattens L.), and a plant belonging to the genus Rageko is a fenugreek fenugreek (Trigonella).
foenum-graecum L .; ), Plants belonging to the genus Kudzu (Puerariae Radix), plants belonging to the genus Rose are canna roses (Rosa canina L.), plants belonging to the genus Sakura are Yoshino cherry trees (Prunus × yedoensis Matsum), and / or Prunusjamas
Siebolid ex Koidz), a plant belonging to the genus Spiraea, Filipendula
ulmaria), a plant belonging to the genus Iris is iris (Iris sanguinea)
Hornem. var. A plant belonging to the genus Mulberry (Morus bombycis Koidz), and a plant belonging to the genus Inocochi to the plant belonging to the genus Acyranthes.
fauriei), a plant belonging to the genus Yanoimo (Dioscorea Radix), and a plant belonging to the genus Valeriana are comfrey (Symphytum).
officinable L. 4. The female hormone production promoter according to claim 3, wherein the plant belonging to the genus Fennel is fennel (Foeniculumvulgare Mill.).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002229024A JP2004067590A (en) | 2002-08-06 | 2002-08-06 | Female sex hormone production promoter and skin preparation for external use containing the same |
Applications Claiming Priority (1)
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| JP2005298450A (en) * | 2004-04-15 | 2005-10-27 | Taisho Pharmaceut Co Ltd | Composition for preventing or treating climacteric syndrome |
| WO2006038721A1 (en) * | 2004-10-07 | 2006-04-13 | Toyo Shinyaku Co., Ltd. | External preparation |
| WO2006135121A1 (en) * | 2005-06-17 | 2006-12-21 | Joon Shik Shin | Bone disease drug composition using herb medicines |
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| KR20150115729A (en) * | 2012-12-05 | 2015-10-14 | 지이 뉴트리언츠, 인크. | Use of fenugreek extract to enhance female libido |
| JP2016526019A (en) * | 2013-05-06 | 2016-09-01 | 株式会社アモーレパシフィックＡｍｏｒｅｐａｃｉｆｉｃ Ｃｏｒｐｏｒａｔｉｏｎ | Composition for preventing and treating climacteric symptoms comprising soybean extract containing cumestrol as active ingredient |
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| JPWO2006038721A1 (en) * | 2004-10-07 | 2008-05-15 | 株式会社東洋新薬 | Topical preparation |
| WO2006038721A1 (en) * | 2004-10-07 | 2006-04-13 | Toyo Shinyaku Co., Ltd. | External preparation |
| WO2006135121A1 (en) * | 2005-06-17 | 2006-12-21 | Joon Shik Shin | Bone disease drug composition using herb medicines |
| WO2007039976A1 (en) * | 2005-10-03 | 2007-04-12 | Fancl Corporation | Abnormal protein removing composition |
| JP2007176878A (en) * | 2005-12-28 | 2007-07-12 | Naris Cosmetics Co Ltd | NF-kappaB ACTIVATION INHIBITOR AND EXTERNAL PREPARATION COMPOSITION I CONTAINING THE SAME |
| JP2007261996A (en) * | 2006-03-28 | 2007-10-11 | Naris Cosmetics Co Ltd | Acrolein adduct-forming inhibitor, and skin external preparation and food and drink containing the same |
| JP2010111602A (en) * | 2008-11-05 | 2010-05-20 | Atm Kk | Antioxidant |
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| KR101195970B1 (en) | 2009-12-31 | 2012-11-05 | 한국콜마주식회사 | Isoflavone Aminoacid Derivatives For Anti-Oxidation And Anti-Wrinkle And The Manufacturing Method Thereof And Cosmetic Composition Thereof |
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| KR20150115729A (en) * | 2012-12-05 | 2015-10-14 | 지이 뉴트리언츠, 인크. | Use of fenugreek extract to enhance female libido |
| JP2016501243A (en) * | 2012-12-05 | 2016-01-18 | ジーイー ニュートリエンツ インコーポレイテッド | Use of fenugreek extract to enhance female sexual desire (Libido) |
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| KR101984352B1 (en) | 2012-12-05 | 2019-05-30 | 지이 뉴트리언츠, 인크. | Use of fenugreek extract to enhance female libido |
| JP2016526019A (en) * | 2013-05-06 | 2016-09-01 | 株式会社アモーレパシフィックＡｍｏｒｅｐａｃｉｆｉｃ Ｃｏｒｐｏｒａｔｉｏｎ | Composition for preventing and treating climacteric symptoms comprising soybean extract containing cumestrol as active ingredient |
| US10111856B2 (en) | 2013-05-06 | 2018-10-30 | Amorepacific Corporation | Composition for preventing or treating climacteric symptoms comprising soybean extract comprising coumestrol as an active ingredient |
| US10959981B2 (en) | 2013-05-06 | 2021-03-30 | Amorepacific Corporation | Composition for preventing or treating climacteric symptoms comprising soybean extract comprising coumestrol as an active ingredient |
| JP2017520606A (en) * | 2014-07-16 | 2017-07-27 | 株式会社アモーレパシフィックＡｍｏｒｅｐａｃｉｆｉｃ Ｃｏｒｐｏｒａｔｉｏｎ | Composition containing turkey oil |
| JP2018076271A (en) * | 2016-11-11 | 2018-05-17 | 株式会社ファンケル | Estrogen receptor production promoting composition |
| KR101892641B1 (en) * | 2017-11-20 | 2018-10-04 | (주)아모레퍼시픽 | Skin External Composition Containing Ulmus Davidiana Extract, Dioscorea Japonica Extract or Morus Alba Leaf Extract |
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