JP3795543B2

JP3795543B2 - 5α-reductase inhibitor

Info

Publication number: JP3795543B2
Application number: JP32572993A
Authority: JP
Inventors: 孝徳山
Original assignee: 株式会社創研
Priority date: 1993-12-01
Filing date: 1993-12-01
Publication date: 2006-07-12
Anticipated expiration: 2021-07-12
Also published as: JPH07157436A

Description

【０００１】
【産業上の利用分野】
本発明は、米または発芽させた米を原料として得られる５α−リダクターゼ活性阻害剤に関するもので、本剤の利用分野としては、化粧品、医薬部外品、医薬品への応用が可能である。例えば、男性型脱毛症に対して、発毛促進が期待され、また、肌に対しては、皮脂分泌能をコントロールして、脂漏性状態を改善し、ニキビの防止に役立つものである。
【０００２】
【従来の技術】
植物からの抽出物が５α−リダクターゼ活性阻害作用を有することについては報告されている。例えば、特公平５−２９４３１、特開昭６０−２４３０２０、特開昭６２−２４６５１９、特開平２−３６１２５、特開平３−８３９３０などがある。しかし、米からの５α−リダクターゼ活性阻害剤についての報告は全くない。
【０００３】
【発明が解決しようとする課題】
５α−リダクターゼの生体内での働きは、（１）男性型脱毛症、（２）ニキビ、（３）前立腺肥大等に関係していることが知られている。すなわち、男性型脱毛症について述べると、弾性ホルモン（テストステロン）は頭の毛母細胞中で、５α−リダクターゼによりデハイドロテストステロン（ＤＨＴ）に変換され、このＤＨＴは毛母細胞核内でアデニルサイクラーゼ活性を著しく低下させて、細胞内サイクリックＡＭＰレベルの濃度を下げ、糖代謝に影響を及ぼしてＡＴＰの産生を減少させる。そのため生活細胞のエネルギー不足をきたし、蛋白質合成不全が起こり、毛球部は角化して休止期毛となり脱毛すると考えられている。また、ＤＨＴはにきびの発生、増悪、前立腺の肥大にも関与するものと考えられている〔Ｊ．ＳｔｅｒｏｉｄＢｉｏｃｈｅｍｉｓｔｒｙ，１１，６０９，（１９７９）〕。
【０００４】
したがって、テストステロンからジヒドロテストステロンの生成を抑制することのできる物質は、これらの症状を改善できるものとされ、５α−リダクターゼ活性阻害剤の開発が進んでいる。
本発明は、安全で安価であり、原料供給が安定しており、容易に加工ができ、長期間常用しても全く安全な米からの５α−リダクターゼ阻害剤を提供することを目的とするものである。
【０００５】
【課題を解決するための手段】
本発明者らは、動植物合和すの観点から、主食である米を中心に種々の植物成分の研究を進めてきた。その過程で、米には今まで予測できなかった数多くの可能性、効果があることが判明してきた。そこで、主食として用いられ、安全性が最も高いことが実証されている米をテーマとして取り上げ、米の総合利用研究を行ってきた。そのうちの一つのテーマとして、米からの５α−リダクターゼ活性阻害について鋭意研究を重ねてきた。その過程で、米および発芽させた米には、５α−リダクターゼ活性阻害剤としての効果を有する成分が含有されていることを見出し、本発明を完成するに至った。
即ち、本発明（１）は、白米の抽出物を有効成分として含有する５α−リダクターゼ阻害剤である。
本発明（２）は、白米の加水物を酵素分解または麹を作用させたものを有効成分として含有する５α−リダクターゼ阻害剤である。
本発明（３）は、白米を抽出するに当たり、その抽出前、抽出と同時または抽出後に酵素分解または麹を作用させたものを有効成分として含有する５α−リダクターゼ阻害剤である。
本発明（４）は、白米の抽出物あるいは酵素分解または麹を作用させたものに、アルコール発酵あるいは有機酸発酵を行ったものを有効成分として含有する５α−リダクターゼ阻害剤である。
本発明（５）は、５α−リダクターゼに起因する疾患が脱毛症である、前記発明（１）〜（４）のいずれか一つの５α−リダクターゼ阻害剤である。
本発明（６）は、５α−リダクターゼに起因する疾患がにきびである、前記発明（１）〜（４）のいずれか一つの５α−リダクターゼ阻害剤である。
本発明（７）は、白米を、白米、玄米または発芽米の形態で用いる、前記発明（１）〜（６）のいずれか一つの５α−リダクターゼ阻害剤である。
【０００６】
本発明において、米および発芽させた米に含有されている５α−リダクターゼ活性阻害効果を有する成分は、未だ解明するに至っていないが、米および発芽させた米を下記のように処理したものは、５α−リダクターゼ阻害効果を示すことが判明した。
▲１▼ 米または発芽させた米の抽出物をそのまま、あるいはこれを含有してなるもの。
▲２▼ 米および発芽させた米の加水物に酵素分解または麹を作用させたものをそのまま、あるいはこれを含有してなるもの。
▲３▼ 米または発芽させた米を抽出するに当たり、その抽出前、抽出と同時または抽出後に酵素分解または麹を作用させたものをそのまま、あるいはこれを含有してなるもの。
▲４▼ 米または発芽させた米の抽出物あるいは酵素分解または麹を作用させたものに、アルコール発酵あるいは有機酸発酵を行なったものをそのまま、あるいはこれを含有してなるもの。
【０００７】
本発明で使用される米とは、ジャポニカ、インディカ米を問わず、うるち米、および餅米等の玄米および白米を指し、品種、種類は問わない。さらに、精白時に出てくる９２％以上の赤糠、あるいは９２％以下の白糠を使用してもよく、安価で経済的である。また、発芽させた米が使用される。なお、有効成分は、熱および光に対して安定であるため、上記の原料は、浸漬、蒸煮、焙煎（砂焙り、網焙り、熱風焙煎等全てを指す）、蒸煮焙煎、凍結乾燥等の表面変性、ＵＶ照射等の光変性、パットライス等の加圧焙煎、揚げる等の原料処理をしてもよく、また、効果も変わらなかった。
米および発芽させた米は、そのまま用いても有効であるが、実用上の面から粉砕して用いるのが好ましい。米および発芽させた米を粉砕して粉体化するには、粉砕機または精米機を用い一般的な方法で行なえばよい。
【０００８】
米を発芽させる場合、胚芽のついた米を水に浸漬あるいは水を噴霧して発芽させる。発芽させる時の温度は５〜７０℃である。ただし、発芽さえすれば、温度および時間は問わない。また、発芽中に水が腐敗する危険性がある場合は、腐敗しないように水を取り替えるか、何らかの防腐を行うのが好ましい。ここで、発芽とは、発芽する直前から発芽したものまで全てを指す。この発芽させた米を良く洗浄して用いる。この時、乾燥して用いてもよい。
米または発芽させた米を抽出、あるいは酵素分解または麹を作用させる場合、原料の米を粉砕して顆粒あるいは粉体化すると、表面積が大きくなるため効率がよくなる。粉砕しなくてもよいが、この場合には、米組織の分解および抽出に長時間を要する。
【０００９】
米または発芽させた米を抽出する場合、抽出温度は、高温が効率的であるが、低温でも十分に抽出を行うことができる。ただし、４０℃以下の低温の場合は、ＰＨを酸性あるいはアルカリ性にするか、防腐剤あるいはアルコールを加えて、米が腐敗しないように処理することが望ましい。抽出時間は、有効成分さえ抽出できれば、長くても短くてもよく、抽出温度により定めればよい。また、抽出は、加圧下または常圧下で行っても、減圧下で行ってもよい。
水抽出の場合、最も問題になるのは糊化現象である。糊状になれば、抽出効率が悪くなるばかりでなく、実作業においては困難を極める。これを防ぐためには、アミラーゼを加えて反応させるか、塩酸などで酸性にして澱粉を切ってやればよく、この方法を用いることにより、十分に解決でき、実用上も全く問題はない。
抽出物中の有効成分は、酸、アルカリに安定であるためか、酸分解抽出あるいはアルカリ分解抽出を行うのも有効である。この場合、必要により中和、脱塩を行う。
【００１０】
有機溶媒で抽出する場合も、米はなるべく微粉砕または粉体化して抽出することが望ましい。有機溶媒はアルコール、アセトン、ｎ−ヘキサン、メタノール等の一般的な有機溶媒でよいが、人体に対して有害なものは抽出後、溶媒を完全に除去する必要があるので安全なものがよい。
また、米あるいは発芽させた米を酵素分解、または麹を作用させてもよい。ここで言う酵素分解とは、澱粉分解酵素、蛋白分解酵素、脂肪分解酵素、繊維分解酵素、リグニン分解酵素、ペクチン分解酵素等米に働く酵素を１種または２種以上作用させることをいう。また、麹として麹菌の種類および米の品種、種類は問わない。
さらに、前記の抽出を行うに当り、抽出の前、抽出と同時または抽出の後に、上記の酵素分解および麹を作用させてもよい。
【００１１】
本発明においては、さらに上記の処理を行なうと同時または処理後、アルコール発酵あるいは乳酸発酵、酢酸発酵等の有機酸発酵を行うと、次のような点でも有効である。
まず、アルコール発酵を行なえば、塗布時にベタツキがないばかりか、濃縮がしやすく、有効成分の濃縮が容易になる。
なお、ベトツキが気になるものにおいては、酵母による通気発酵、合成吸着剤等で除糖をおこなってもよい。
また、９２％以上の赤糠部分を調べてみたところ、効果はあるが、弱いことが判明した。
【００１２】
以上のようにして得られた本発明品は、残渣を分離することなくそのまま、あるいは圧搾、濾過して用いる。そのまま用いるときは、殺菌あるいは除菌をして製品にする。なお、本発明品を配合する場合は、実際の用途に応じ、常法にしたがってクリーム、洗顔料、乳液、化粧水、クレンジング、パック、石鹸などの化粧料、軟膏剤、パスタ剤、ローション剤、チンキ剤、リエメント剤、ゼリー剤、エアゾール剤などの外用医薬品のような剤型にする。他の配合成分は、通常用いられるものいずれでもよく、さらに、他の薬効剤を併用してもよい。
【００１３】
次に、本発明品の５α−リダクターゼ活性阻害作用を調べた結果について記載する。
（１）５α−リダクターゼ活性阻害作用
Ｗｉｓｔａｒ雄性ラットの前立腺４ｇを、３倍容の０．２５Ｍショ糖を含む０．１ＭＨＥＰＥＳｂｕｆｆｅｒ（ＰＨ７．４）でホモジネードした後、ナイロン濾布で濾過し、さらに遠心分離した（３，０００ｒｐｍ、１０分間）沈殿を上記ｂｕｆｆｅｒ１０ｍｌに懸濁し、再び３，０００ｒｐｍで５分間遠心分離して得た沈殿物に、上記ｂｕｆｆｅｒ３ｍｌを加えて懸濁し、酵素溶液とした。
【００１４】
酵素活性の測定は、上記酵素溶液０．０３ｍｌに〔４−^１４Ｃ〕テストステロン（１５０ｎＭ）０．０１ｍｌ、ＮＡＤＰＨ（５０ｍＭ）０．０１ｍｌおよび試験検体０．０５ｍｌを加え、３７℃で６０分間インキュベートした。酵素反応はクロロホルムとメタノール（１：２）の混合液０．４ｍｌを加えて停止し、その後、２，０００ｒｐｍ３分間遠心分離して、得られた上清０．０５ｍｌをシリカゲル薄層プレートにスポットし、クロロホルム、メタノールおよび酢酸（９９．２：０．６：０．２）の混合液を用いて展開した。プレートをオートラジオグラフィーにかけ、生成したジヒドロテストステロンの放射活性をＴＬＣスキャナーを用いて測定し、酵素活性阻害率を算出した。その結果を表１に示す。
【００１５】
【表１】

表１に示したとおり、本発明品は、いずれも強い阻害作用を示した。この結果から、本発明品には５α−リダクターゼ阻害活性を有する物質を含むことが明らかとなった。そこで、次に代表例として、実施例３０より得た本発明品を用いて、５α−リダクターゼ活性が関係すると考えられている男性型脱毛症およびにきびについて、臨床試験での有効性を検討した。
【００１６】
（２）発毛効果
実施例３０より得た本発明品を用いて、男性型脱毛症患者６人（２５才〜４０才）に対する発毛の効果を検討した。１日２回（１回１ｍｌ）本発明品を塗布し、軽くマッサージした。塗布は３ヶ月間行い、塗布前と塗布後の脱毛進行度、硬毛の生え方、軟毛の生え方の各所見から、改善度および有効性の判定を行った。その結果を表２に示す。
【表２】

表２のとおり、発毛増毛の効果、すなわち、毛髪本数の増加、軟毛から硬毛への変化において、中等度の改善が１０名中４名、軽度の改善が３名認められた。３名については効果が認められなかった。軽度の改善以上を有効例とした場合、その有効率は７０％で、発毛、増毛の効果が証明された。なお、他の本発明品においても効果は認められた。
【００１７】
（３）ニキビに対する効果
（２）と同様に、実施例３０に基づく本発明品のニキビに対する効果を、ニキビ患者１３名を対象に検討した。本発明品を１日２回患部に塗布した。２週間の継続使用後、使用前と使用後の改善度の結果を表３に示す。
【表３】

表３のとおり、有効率８４．６％で、高い有効性が証明された。また、他の本発明品においても効果は認められた。
なお、実施例およびそれに伴うデータは玄米の場合について記載したが、白米および９２％以下の白糠の場合も同様の効果が認められた。
【００１８】
【実施例】
（実施例１）
胚芽のついたままの米１ｋｇを２５℃の水につけ、３日間浸漬させ、米を発芽させた。この発芽米をよく洗浄した後、５０℃で２４時間乾燥し、その後、細かく微粉砕し、本発明品９９０ｇを得た。
（実施例２）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に水１５００ｍｌを添加、塩酸でＰＨを落とし１０日間放置した。その後、絞り機で絞り、得た清澄液を中和して、本発明品１２００ｍｌと残渣７６０ｇを得た。
（実施例３）
実施例１で得られた本発明品５００ｇを用いて、実施例３と同様の操作を行い、別の本発明品１１９０ｍｌを得た。
【００１９】
（実施例４）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に液化酵素１０ｇと水１５００ｍｌを添加した。その後、徐々に温度を上げていき、５分間煮沸抽出した後、冷却した。その後、絞り機で絞り、本発明品１４２０ｍｌと残渣５６０ｇを得た。
（実施例５）
実施例１で得られた本発明品５００ｇを用いて、実施例４と同様の操作を行い、別の本発明品１４００ｍｌを得た。
（実施例６）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に２Ｎ−ＮａＯＨ１５００ｍｌを添加して５日間放置した。その後、絞り機で絞り、清澄液１３５０ｍｌと残渣６５０ｇを得た。この清澄液を１０Ｎ−ＨＣｌで中和して、本発明品１４８０ｍｌを得た。
【００２０】
（実施例７）
実施例１で得られた本発明品５００ｇを用いて、実施例６と同様の操作を行い、別の本発明品１４９０ｍｌを得た。
（実施例８）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に９５％エタノール１５００ｍｌを添加して、５日間放置した。その後、絞り機で絞り、清澄液１３００ｍｌと残渣６５０ｇを得た。この清澄液に水２０００ｍｌを添加し、ロータリーエバプレーターで濃縮し、本発明品１５００ｍｌを得た。
（実施例９）
実施例１で得られた本発明品５００ｇを用いて、実施例８と同様の操作を行い、別の本発明品１５００ｍｌを得た。
【００２１】
（実施例１０）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に麹３００ｇ、水１５００ｍｌを加え、５５℃で２０時間放置した。その後、絞り機で絞り、本発明品１２３０ｍｌと残渣１０００ｇを得た。
（実施例１１）
実施例１で得られた本発明品５００ｇを用いて、実施例１０と同様の操作を行い、別の本発明品１２１０ｍｌを得た。
（実施例１２）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に蛋白分解酵素２ｇと水１５００ｍｌを加え、５０℃で２０時間放置した。その後、絞り機で絞り、本発明品１３１０ｍｌと残渣６７０ｇを得た。
【００２２】
（実施例１３）
実施例１で得られた本発明品５００ｇを用いて、実施例１２と同様の操作を行い、別の本発明品１３８０ｍｌを得た。
（実施例１４）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に脂肪分解酵素２ｇと水１５００ｍｌを加え、５０℃で２０時間放置した。その後、絞り機で絞り、本発明品１２９０ｍｌと残渣６８０ｇを得た。
（実施例１５）
実施例１で得られた本発明品５００ｇを用いて、実施例１４と同様の操作を行い、別の本発明品１３６０ｍｌを得た。
【００２３】
（実施例１６）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に繊維分解酵素２ｇと水１５００ｍｌを加え、５０℃で２０時間放置した。その後、絞り機で絞り、本発明品１３３０ｍｌと残渣６５０ｇを得た。
（実施例１７）
実施例１で得られた本発明品５００ｇを用いて、実施例１６と同様の操作を行い、別の本発明品１３７０ｍｌを得た。
（実施例１８）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に澱粉分解酵素２ｇと水１５００ｍｌを加え、５５℃で２０時間放置した。その後、絞り機で絞り、本発明品１３８０ｍｌと残渣６００ｇを得た。
【００２４】
（実施例１９）
実施例１で得られた本発明品５００ｇを用いて、実施例１８と同様の操作を行い、別の本発明品１４００ｍｌを得た。
（実施例２０）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物にペクチン分解酵素２ｇと水１５００ｍｌを加え、５０℃で２０時間放置した。その後、絞り機で絞り、本発明品１３２０ｍｌと残渣６６０ｇを得た。
（実施例２１）
実施例１で得られた本発明品５００ｇを用いて、実施例２０と同様の操作を行い、別の本発明品１３００ｍｌを得た。
【００２５】
（実施例２２）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に蛋白分解酵素２ｇ、脂肪分解酵素２ｇ、繊維分解酵素２ｇ、澱粉分解酵素２ｇ、ペクチン分解酵素２ｇと水１５００ｍｌを加え、５０℃で２０時間放置した。その後、絞り機で絞り、本発明品１４２０ｍｌと残渣５６０ｇを得た。
（実施例２３）
実施例１で得られた本発明品５００ｇを用いて、実施例２２と同様の操作を行い、別の本発明品１４４０ｍｌを得た。
（実施例２４）
実施例２２と同様の操作をして、米の酵素分解物２０００ｇを得た。その後、徐々に温度を上げていき、５分間煮沸抽出した後、冷却した。その後、絞り機で絞り、本発明品１４００ｍｌと残渣５５０ｇを得た。
【００２６】
（実施例２５）
実施例１で得られた本発明品５００ｇを用いて、実施例２４と同様の操作を行い、別の本発明品１４２０ｍｌを得た。
（実施例２６）
玄米を粉砕機にかけ、玄米の粉砕物５００ｇを得た。この粉砕物に麹３００ｇと４０％エタノール１５００ｍｌを加え、５５℃で４８時間放置した。その後、絞り機で絞り、清澄液１３００ｍｌと残渣８５０ｇを得た。その後、清澄液に１０００ｍｌの水を加水し、ロータリーエバプレーターで濃縮し、本発明品１３００ｍｌを得た。
（実施例２７）
実施例１で得られた本発明品５００ｇを用いて、実施例２６と同様の操作を行い、別の本発明品１３００ｍｌを得た。
【００２７】
（実施例２８）
実施例４と同様にして、米の抽出物２０００ｇを得た。この抽出物に蛋白分解酵素２ｇ、脂肪分解酵素２ｇ、繊維分解酵素２ｇ、澱粉分解酵素２ｇ、ペクチン分解酵素２ｇを添加し、５０℃で２４時間放置した。その後、絞り機で絞り、本発明品１４００ｍｌと残渣５８０ｇを得た。
（実施例２９）
実施例１で得られた本発明品５００ｇを用いて、実施例２８と同様の操作を行い、別の本発明品１３９０ｍｌを得た。
（実施例３０）
実施例２２と同様にして、米の酵素分解抽出物２０００ｇを得た。この酵素分解抽出物に酵母を添加し、１６日間アルコール発酵した。その後、絞り機で絞り、本発明品１８８０ｍｌと残渣８０ｇを得た。
【００２８】
（実施例３１）
実施例１で得られた本発明品５００ｇを用いて、実施例３０と同様の操作を行い、別の本発明品１８００ｍｌを得た。
（実施例３２）
実施例２２と同様にして、米の酵素分解抽出物２０００ｇを得た。この酵素分解抽出物を煮沸殺菌した後、３７℃まで冷却し、前もって乳酸菌を培養したスターター２００ｍｌを添加後、よく攪拌密封し、３７℃で２日間乳酸発酵を行った。その後、絞り機で絞り、本発明品１３８０ｍｌと残渣５９０ｇを得た。
（実施例３３）
実施例１で得られた本発明品５００ｇを用いて、実施例３２と同様の操作を行い、別の本発明品１４００ｍｌを得た。
【００２９】
（実施例３４）
実施例２２で得られた本発明品１０００ｍｌに９５％エタノール８０ｍｌを添加し、２０日間酢酸発酵を行った。その後、濾過をし、本発明品９９０ｍｌを得た。
（実施例３５）
実施例１で得られた本発明品５００ｇを用いて、実施例３４と同様の操作を行い、別の本発明品１０００ｍｌを得た。
以上の実施例で得た本発明品は、用途に応じて適宜に使用されるが、本発明品を配合して化粧水および乳液とする場合の実施例について、次に記載する。なお、配合例は以下の実施例に限定されるものではない。
【００３０】
（実施例３６）化粧水
実施例２２で得られた本発明品１０．０重量％
ソルビトール３．０重量％
グリセリン５．０重量％
精製水７６．４重量％
アラントイン０．１重量％
ポリオキシエチレンヒマシ油誘導体０．５重量％
エタノール５重量％
以上の配合材料を常法により混合溶解し、化粧水を得た。
【００３１】
（実施例３７）乳液
実施例３０で得られた本発明品２０．０重量％
ステアリン酸１．３重量％
セタノール０．７重量％
ミツロウ２．０重量％
ポリオキシエチレン（１１）モノオレイン酸エステル０．１重量％
グリセリンモノステアリン酸エステル０．８重量％
クインスシード抽出液（５％水溶液）１５．０重量％
ジプロピレングリコール５．０重量％
エタノール３．０重量％
メチルパラベン０．３重量％
香料０．３重量％
精製水５０．４重量％
精製水にジプロピレングリコールを加え、加熱攪拌し、温度を７０℃に保持し、これに本発明品、クインスシード抽出液、香料、エタノール以外の原料を加えて攪拌し、次に、ホモジナイザーで均一に乳化させる。得られた乳化液を冷却しながら攪拌下に、残りのものを徐々に加え、室温に冷却して乳液を得た。
【００３２】
【発明の効果】
本発明によれば、米を原料として、簡単に、全く安全で、５α−リダクターゼ活性阻害剤に対して効果を持ち、しかも、様々な分野で使用可能な５α−リダクターゼ活性阻害剤を見出したものである。すなわち、テストステロンからジヒドロテストステロンへの変換を阻害することにより、ジヒドロテストステロンの生成過剰による種々の疾患、例えば、男性型脱毛症、にきび、前立腺肥大症の予防治療剤として、その効果が期待されるものである。
米は今まで主食であったため、食以外の新規な分野での製法、利用用途はほとんど開発されていなかった。さらに、米は今まで主食とされてきたものであり、安全性も十分に実証されているものである。すなわち、本発明は、非常に優れた５α−リダクターゼ阻害剤を見出したばかりでなく、米の過剰生産といわれる現在、新たな利用用途を見出したこと、および米のイメージアップによる消費拡大を図り得ることは極めて有意義なことである。[0001]
[Industrial application fields]
The present invention relates to a 5α-reductase activity inhibitor obtained from rice or germinated rice as a raw material, and can be applied to cosmetics, quasi-drugs, and pharmaceuticals as a field of use of this agent. For example, hair growth promotion is expected for male pattern baldness, and for the skin, sebum secretion ability is controlled to improve the seborrheic state and to help prevent acne.
[0002]
[Prior art]
It has been reported that extracts from plants have an inhibitory activity on 5α-reductase activity. For example, JP-B-5-29431, JP-A-60-243020, JP-A-62-2246519, JP-A-2-36125, JP-A-3-83930 and the like. However, there are no reports on 5α-reductase activity inhibitors from rice.
[0003]
[Problems to be solved by the invention]
It is known that the action of 5α-reductase in vivo is related to (1) male pattern baldness, (2) acne, (3) prostatic hypertrophy, and the like. That is, when describing male pattern alopecia, the elastic hormone (testosterone) is converted to dehydrotestosterone (DHT) by 5α-reductase in the hair matrix of the head, and this DHT is adenyl cyclase activity in the hair matrix. Is significantly reduced, reducing the concentration of intracellular cyclic AMP levels, affecting glucose metabolism and reducing ATP production. Therefore, it is thought that the energy of living cells is deficient, protein synthesis failure occurs, the hair bulb part keratinizes and becomes telogen hair. DHT is also considered to be involved in acne development, exacerbations, and prostate enlargement [J. Steroid Biochemistry, 11, 609, (1979)].
[0004]
Therefore, substances capable of suppressing the production of dihydrotestosterone from testosterone can improve these symptoms, and the development of 5α-reductase activity inhibitors is progressing.
An object of the present invention is to provide a 5α-reductase inhibitor from rice that is safe and inexpensive, has a stable raw material supply, can be easily processed, and is completely safe even after regular use over a long period of time. It is.
[0005]
[Means for Solving the Problems]
The inventors of the present invention have been researching various plant components, mainly rice, which is a staple food, from the viewpoint of combining plants and animals. In the process, it has been found that rice has many possibilities and effects that could not have been predicted before. Therefore, we have taken up the theme of rice, which is used as a staple food and has proven to be the safest, and has conducted comprehensive rice research. As one of the themes, we have conducted extensive research on the inhibition of 5α-reductase activity from rice. In the process, it was found that rice and germinated rice contain a component having an effect as a 5α-reductase activity inhibitor, and the present invention was completed.
That is, the present invention (1) is a 5α-reductase inhibitor containing a white rice extract as an active ingredient.
This invention (2) is a 5 (alpha) -reductase inhibitor containing as an active ingredient what hydrolyzed white rice hydrolyzed or koji acted.
The present invention (3) is a 5α-reductase inhibitor containing, as an active ingredient, an enzyme that has been subjected to enzymatic degradation or koji before, during, or after extraction of white rice.
The present invention (4) is a 5α-reductase inhibitor containing, as an active ingredient, a product obtained by subjecting a white rice extract or enzymatic degradation or koji to action to alcohol fermentation or organic acid fermentation.
The present invention (5) is the 5α-reductase inhibitor according to any one of the inventions (1) to (4), wherein the disease caused by 5α-reductase is alopecia.
The present invention (6) is the 5α-reductase inhibitor according to any one of the inventions (1) to (4), wherein the disease caused by 5α-reductase is acne.
The present invention (7) is the 5α-reductase inhibitor according to any one of the inventions (1) to (6), wherein white rice is used in the form of white rice, brown rice or germinated rice.
[0006]
In the present invention, the ingredients having an inhibitory effect on 5α-reductase activity contained in rice and germinated rice have not yet been elucidated, but those obtained by treating rice and germinated rice as follows: It was found to show 5α-reductase inhibitory effect.
(1) Rice or germinated rice extract as it is or containing it.
(2) A rice or hydrolyzed rice hydrolyzate that has been subjected to enzymatic degradation or koji is used as it is or contains it.
(3) When extracting rice or germinated rice, it is the one that has been subjected to enzymatic degradation or koji before or simultaneously with or after the extraction, or contains this.
(4) Rice or germinated rice extract or enzyme-decomposed or koji-treated one obtained by subjecting it to alcohol fermentation or organic acid fermentation as it is or containing it.
[0007]
The rice used in the present invention refers to brown rice and white rice such as sticky rice and brown rice, regardless of japonica and indica rice, regardless of the variety and type. Furthermore, it is possible to use 92% or more of red cocoon that appears during whitening, or 92% or less of white cocoon, which is inexpensive and economical. In addition, germinated rice is used. In addition, since the active ingredient is stable to heat and light, the above-mentioned raw materials are dipping, steaming, roasting (pointing to all of sand roasting, net roasting, hot air roasting, etc.), steaming roasting, freeze drying Material treatment such as surface modification such as UV irradiation, photo modification such as UV irradiation, pressure roasting such as Patrice, frying, etc., and the effect was not changed.
Rice and germinated rice are effective when used as they are, but are preferably pulverized for practical use. In order to pulverize rice and germinated rice into powder, a general method may be used using a pulverizer or a rice mill.
[0008]
When germinating rice, the germinated rice is immersed in water or sprayed with water. The temperature at the time of germination is 5-70 degreeC. However, the temperature and time are not limited as long as germination occurs. In addition, when there is a risk of water rot during germination, it is preferable to replace the water so that it does not rot or to perform some preservative. Here, germination refers to everything from just before germination to germination. The germinated rice is washed thoroughly before use. At this time, you may dry and use.
When rice or germinated rice is extracted or subjected to enzymatic degradation or koji, if the raw rice is pulverized into granules or powders, the surface area increases and efficiency increases. Although it is not necessary to grind, in this case, it takes a long time to decompose and extract the rice tissue.
[0009]
When extracting rice or germinated rice, a high extraction temperature is efficient, but sufficient extraction can be performed even at a low temperature. However, in the case of a low temperature of 40 ° C. or less, it is desirable to make the pH acidic or alkaline, or add a preservative or alcohol so that the rice is not spoiled. The extraction time may be long or short as long as the active ingredient can be extracted, and may be determined by the extraction temperature. The extraction may be performed under pressure, normal pressure, or reduced pressure.
In the case of water extraction, the most serious problem is the gelatinization phenomenon. If it becomes paste-like, not only extraction efficiency will worsen but it will be extremely difficult in actual work. In order to prevent this, the reaction may be performed by adding amylase or acidifying with hydrochloric acid or the like to cut the starch. By using this method, the problem can be solved sufficiently and there is no problem in practical use.
It is also effective to perform acid decomposition extraction or alkali decomposition extraction because the active ingredient in the extract is stable to acid and alkali. In this case, neutralization and desalting are performed as necessary.
[0010]
Also when extracting with an organic solvent, it is desirable to extract rice by pulverizing or pulverizing it as much as possible. The organic solvent may be a common organic solvent such as alcohol, acetone, n-hexane, methanol or the like, but those that are harmful to the human body are preferably safe because the solvent must be completely removed after extraction.
In addition, rice or germinated rice may be subjected to enzymatic degradation, or koji. The term “enzymatic degradation” as used herein means that one or more enzymes acting on rice such as starch degrading enzyme, proteolytic enzyme, lipolytic enzyme, fiber degrading enzyme, lignin degrading enzyme, and pectin degrading enzyme are allowed to act. Moreover, the kind of koji mold, rice varieties and kinds are not limited.
Furthermore, in performing the said extraction, you may make said enzyme decomposition | disassembly and soot act before extraction, simultaneous with extraction, or after extraction.
[0011]
In the present invention, when the above-described treatment is further performed, or when the organic acid fermentation such as alcohol fermentation, lactic acid fermentation, or acetic acid fermentation is performed simultaneously or after the treatment, the following points are also effective.
First, if alcohol fermentation is performed, not only is there no stickiness at the time of application, it is easy to concentrate and the active ingredient is easily concentrated.
In addition, in the thing which is worried about stickiness, you may desugar by aeration fermentation by yeast, a synthetic adsorbent, etc.
In addition, when the red cocoon portion of 92% or more was examined, it was found that although there was an effect, it was weak.
[0012]
The product of the present invention obtained as described above is used as it is, or after being squeezed and filtered without separating the residue. When it is used as it is, it is sterilized or sterilized to make a product. In addition, when blending the product of the present invention, according to the actual application, cosmetics such as creams, face wash, milky lotion, skin lotion, cleansing, pack, soap, etc., ointment, pasta agent, lotion agent, Make the dosage form like external medicines such as tincture, rimentation, jelly and aerosol. Any other commonly used ingredients may be used, and other medicinal agents may be used in combination.
[0013]
Next, the results of examining the 5α-reductase activity inhibitory action of the product of the present invention will be described.
(1) Inhibition of 5α-reductase activity 4 g of prostate from Wistar male rats was homogenized with 0.1 MHEPES buffer (PH7.4) containing 3 volumes of 0.25M sucrose, then filtered through a nylon filter cloth, and The centrifuged precipitate (3,000 rpm, 10 minutes) was suspended in 10 ml of the above buffer, and again 3 ml of the above buffer was added to the precipitate obtained by centrifuging again at 3,000 rpm for 5 minutes to prepare an enzyme solution. .
[0014]
The enzyme activity was measured by adding 0.01 ml of [4- ¹⁴ C] testosterone (150 nM), 0.01 ml of NADPH (50 mM) and 0.05 ml of a test sample to 0.03 ml of the enzyme solution, and incubating at 37 ° C. for 60 minutes. . The enzymatic reaction was stopped by adding 0.4 ml of a mixture of chloroform and methanol (1: 2), and then centrifuged at 2,000 rpm for 3 minutes, and 0.05 ml of the resulting supernatant was spotted on a silica gel thin layer plate. , Chloroform, methanol and acetic acid (99.2: 0.6: 0.2). The plate was subjected to autoradiography, the radioactivity of the produced dihydrotestosterone was measured using a TLC scanner, and the enzyme activity inhibition rate was calculated. The results are shown in Table 1.
[0015]
[Table 1]

As shown in Table 1, all of the products of the present invention exhibited a strong inhibitory action. From this result, it was revealed that the product of the present invention contains a substance having 5α-reductase inhibitory activity. Therefore, as a representative example, the effectiveness of the present invention obtained from Example 30 was examined in clinical trials for androgenetic alopecia and acne, which are considered to be associated with 5α-reductase activity.
[0016]
(2) Hair growth effect Using the product of the present invention obtained in Example 30, the effect of hair growth on 6 male pattern baldness patients (25 to 40 years old) was examined. The product of the present invention was applied twice a day (1 ml once) and gently massaged. The application was carried out for 3 months, and the degree of improvement and effectiveness were determined from the findings of the degree of hair removal before application and after application, how hair grows, and how hair grows. The results are shown in Table 2.
[Table 2]

As shown in Table 2, in the effect of hair growth, that is, in the increase in the number of hairs and the change from soft hair to hard hair, moderate improvement was observed in 4 out of 10 people, and mild improvement was observed in 3 people. The effect was not recognized about three people. When an effective example was mild improvement or more, the effective rate was 70%, and the effects of hair growth and hair growth were proved. The effect was also observed in other products of the present invention.
[0017]
(3) Effect on Acne As in (2), the effect of the product of the present invention based on Example 30 on acne was examined in 13 acne patients. The product of the present invention was applied to the affected area twice a day. Table 3 shows the results of improvement after use for 2 weeks before use and after use.
[Table 3]

As shown in Table 3, the effectiveness rate was 84.6%, and high effectiveness was proved. The effect was also observed in other products of the present invention.
In addition, although the Example and the data accompanying it were described about the case of brown rice, the same effect was recognized also in the case of white rice and 92% or less of white rice.
[0018]
【Example】
Example 1
1 kg of rice with germs was placed in water at 25 ° C. and immersed for 3 days to germinate the rice. After thoroughly washing the germinated rice, it was dried at 50 ° C. for 24 hours, and then finely pulverized to obtain 990 g of the product of the present invention.
(Example 2)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 1500 ml of water was added, pH was dropped with hydrochloric acid, and the mixture was allowed to stand for 10 days. Thereafter, the clarified liquid obtained by squeezing with a squeezer was neutralized to obtain 1200 ml of the present product and 760 g of a residue.
Example 3
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 3 was performed to obtain 1190 ml of another product of the present invention.
[0019]
(Example 4)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. 10 g of liquefied enzyme and 1500 ml of water were added to this pulverized product. Thereafter, the temperature was gradually increased, followed by boiling extraction for 5 minutes and then cooling. Thereafter, the product was squeezed with a squeezer to obtain 1420 ml of the product of the present invention and 560 g of residue.
(Example 5)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 4 was performed to obtain 1400 ml of another product of the present invention.
(Example 6)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 1500 ml of 2N-NaOH was added and left for 5 days. Then, it squeezed with the squeezer and obtained 1350 ml of clarified liquids, and 650 g of residue. The clear solution was neutralized with 10N HCl to obtain 1480 ml of the product of the present invention.
[0020]
(Example 7)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 6 was performed to obtain another 1490 ml of the product of the present invention.
(Example 8)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 1500 ml of 95% ethanol was added and left for 5 days. Then, it squeezed with the squeezer and 1300 ml of clarified liquids and 650 g of residue were obtained. To this clarified liquid, 2000 ml of water was added and concentrated with a rotary evaporator to obtain 1500 ml of the product of the present invention.
Example 9
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 8 was performed to obtain 1500 ml of another product of the present invention.
[0021]
(Example 10)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 300 g of candy and 1500 ml of water were added, and the mixture was left at 55 ° C. for 20 hours. Then, it squeezed with the squeezer and obtained 1230 ml of this invention products and 1000 g of residue.
(Example 11)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 10 was performed to obtain 1210 ml of another product of the present invention.
(Example 12)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 2 g of proteolytic enzyme and 1500 ml of water were added and left at 50 ° C. for 20 hours. Then, it squeezed with the squeezer and obtained 1310 ml of this invention products and 670 g of residue.
[0022]
(Example 13)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 12 was performed to obtain 1380 ml of another product of the present invention.
(Example 14)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 2 g of lipolytic enzyme and 1500 ml of water were added and left at 50 ° C. for 20 hours. Thereafter, the product was squeezed with a squeezer to obtain 1290 ml of the product of the present invention and 680 g of residue.
(Example 15)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 14 was performed to obtain 1360 ml of another product of the present invention.
[0023]
(Example 16)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 2 g of a fiber-degrading enzyme and 1500 ml of water were added and left at 50 ° C. for 20 hours. Thereafter, the product was squeezed with a squeezer to obtain 1330 ml of the present product and 650 g of a residue.
(Example 17)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 16 was performed to obtain 1370 ml of another product of the present invention.
(Example 18)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 2 g of amylolytic enzyme and 1500 ml of water were added and left at 55 ° C. for 20 hours. Thereafter, the product was squeezed with a squeezer to obtain 1380 ml of the product of the present invention and 600 g of residue.
[0024]
(Example 19)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 18 was performed to obtain 1400 ml of another product of the present invention.
(Example 20)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 2 g of pectin-degrading enzyme and 1500 ml of water were added and left at 50 ° C. for 20 hours. Thereafter, the product was squeezed with a squeezer to obtain 1320 ml of the product of the present invention and 660 g of residue.
(Example 21)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 20 was performed to obtain 1300 ml of another product of the present invention.
[0025]
(Example 22)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 2 g of proteolytic enzyme, 2 g of lipolytic enzyme, 2 g of fiber degrading enzyme, 2 g of starch degrading enzyme, 2 g of pectin degrading enzyme and 1500 ml of water were added and left at 50 ° C. for 20 hours. Thereafter, the product was squeezed with a squeezer to obtain 1420 ml of the product of the present invention and 560 g of residue.
(Example 23)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 22 was performed to obtain 1440 ml of another product of the present invention.
(Example 24)
The same operation as in Example 22 was performed to obtain 2000 g of an enzymatic degradation product of rice. Thereafter, the temperature was gradually increased, followed by boiling extraction for 5 minutes and then cooling. Then, it squeezed with the squeezer and obtained 1400 ml of this invention products and 550 g of residue.
[0026]
(Example 25)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 24 was performed to obtain 1420 ml of another product of the present invention.
(Example 26)
Brown rice was put into a pulverizer to obtain 500 g of pulverized brown rice. To this pulverized product, 300 g of koji and 1500 ml of 40% ethanol were added and left at 55 ° C. for 48 hours. Then, it squeezed with the squeezer and 1300 ml of clarified liquids and 850 g of residue were obtained. Thereafter, 1000 ml of water was added to the clarified liquid and concentrated with a rotary evaporator to obtain 1300 ml of the product of the present invention.
(Example 27)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 26 was performed to obtain 1300 ml of another product of the present invention.
[0027]
(Example 28)
In the same manner as in Example 4, 2000 g of rice extract was obtained. To this extract, 2 g of proteolytic enzyme, 2 g of lipolytic enzyme, 2 g of fiber degrading enzyme, 2 g of starch degrading enzyme and 2 g of pectin degrading enzyme were added and left at 50 ° C. for 24 hours. Thereafter, the product was squeezed with a squeezer to obtain 1400 ml of the present product and 580 g of a residue.
(Example 29)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 28 was performed to obtain another 1390 ml of the product of the present invention.
(Example 30)
In the same manner as in Example 22, 2000 g of enzymatic decomposition extract of rice was obtained. Yeast was added to this enzymatic degradation extract, and alcohol fermentation was performed for 16 days. Thereafter, the product was squeezed with a squeezer to obtain 1880 ml of the product of the present invention and 80 g of residue.
[0028]
(Example 31)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 30 was performed to obtain 1800 ml of another product of the present invention.
(Example 32)
In the same manner as in Example 22, 2000 g of enzymatic decomposition extract of rice was obtained. The enzyme-degraded extract was sterilized by boiling, cooled to 37 ° C., added with 200 ml of a starter in which lactic acid bacteria had been cultured in advance, sealed well, and subjected to lactic acid fermentation at 37 ° C. for 2 days. Thereafter, the product was squeezed with a squeezer to obtain 1380 ml of the present product and 590 g of a residue.
(Example 33)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 32 was performed to obtain 1400 ml of another product of the present invention.
[0029]
(Example 34)
To 1000 ml of the product of the present invention obtained in Example 22, 80 ml of 95% ethanol was added, and acetic acid fermentation was performed for 20 days. Thereafter, filtration was performed to obtain 990 ml of the present product.
(Example 35)
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 34 was performed to obtain 1000 ml of another product of the present invention.
The product of the present invention obtained in the above examples is appropriately used depending on the application. Examples of the case where the product of the present invention is blended into a lotion and an emulsion are described below. In addition, a compounding example is not limited to a following example.
[0030]
(Example 36) The product of the present invention obtained in the lotion Example 22 10.0% by weight
Sorbitol 3.0% by weight
Glycerin 5.0% by weight
76.4% by weight of purified water
Allantoin 0.1% by weight
Polyoxyethylene castor oil derivative 0.5% by weight
Ethanol 5% by weight
The above blended materials were mixed and dissolved by a conventional method to obtain a lotion.
[0031]
(Example 37) Invention product obtained in the emulsion Example 30 20.0% by weight
Stearic acid 1.3% by weight
Cetanol 0.7% by weight
Beeswax 2.0% by weight
Polyoxyethylene (11) monooleate 0.1% by weight
Glycerin monostearate 0.8% by weight
Quince seed extract (5% aqueous solution) 15.0% by weight
Dipropylene glycol 5.0% by weight
Ethanol 3.0% by weight
Methylparaben 0.3% by weight
Fragrance 0.3% by weight
Purified water 50.4% by weight
Dipropylene glycol is added to purified water, heated and stirred, and the temperature is maintained at 70 ° C. The ingredients other than the present product, quince seed extract, fragrance, and ethanol are added and stirred, and then homogenizer is used. To emulsify. The remaining emulsion was gradually added with stirring while cooling the obtained emulsion, and cooled to room temperature to obtain an emulsion.
[0032]
【The invention's effect】
According to the present invention, a 5α-reductase activity inhibitor that has been easily and completely safe from rice and has an effect on a 5α-reductase activity inhibitor and can be used in various fields has been found. It is. That is, by inhibiting the conversion of testosterone to dihydrotestosterone, it is expected to be effective as a prophylactic and therapeutic agent for various diseases caused by excessive production of dihydrotestosterone, such as androgenetic alopecia, acne and benign prostatic hyperplasia It is.
Since rice has been a staple food until now, there has been almost no development of methods and uses in new fields other than food. Furthermore, rice has been regarded as a staple food until now, and its safety has been fully demonstrated. In other words, the present invention has not only found a very excellent 5α-reductase inhibitor, but has now found a new application, which is said to be overproduction of rice, and can increase consumption by improving the image of rice. Is very meaningful.

Claims

5α-reductase inhibitor (except for alopecia preventive and acne preventive and therapeutic agents) containing as an active ingredient a hydrolyzed white rice hydrolysate.

A 5α-reductase inhibitor (excluding alopecia preventive and acne preventive and therapeutic agents) containing, as an active ingredient, an enzyme-decomposed product before or after extraction, or after extraction.

Furthermore, the 5α-reductase inhibitor (excluding alopecia preventive and acne prevention agents and acne prevention and treatment agents) according to claim 1 or 2, which has been subjected to alcohol fermentation or organic acid fermentation.

The 5α-reductase inhibitor according to any one of claims 1 to 3, which is used for prevention and treatment of prostatic hypertrophy.