JP3811197B2

JP3811197B2 - Helicobacter pylori disinfectant from rice

Info

Publication number: JP3811197B2
Application number: JP28393494A
Authority: JP
Inventors: 孝徳山
Original assignee: 株式会社創研
Priority date: 1994-10-25
Filing date: 1994-10-25
Publication date: 2006-08-16
Anticipated expiration: 2021-08-16
Also published as: JPH08119873A

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ヘリコバクター・ピロリ（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ）（以下、Ｈ．ｐｙｌｏｒｉと略記する）除菌剤に関するものである。
【０００２】
【従来の技術】
今からおよそ１１年前に、胃炎患者の胃粘膜に付着していた桿菌Ｈ．ｐｙｌｏｒｉが初めて分離されて以来、胃炎や消化性潰瘍患者らの胃粘膜から本菌が非常に高率に検出されることが確認され、胃粘膜障害因子の病因として、現在まで精力的に基礎的、臨床的研究がなされてきた。そして、Ｈ．ｐｙｌｏｒｉ感染が胃炎を惹起することのほかに、消化性潰瘍の治療や再発の重要な因子であるとする報告が多く、本菌を完全除菌することにより、胃潰瘍および十二指腸潰瘍の再発は、ほとんど完全に防止できるとの報告もなされている。
【０００３】
実際には、既に欧米を中心として２〜３剤の併用療法が試みられている。主にテトラサイクリン、ペニシリン、クラリスロマイシン、その他の抗生物質、ビスマス製剤、メトロニダゾール系薬剤、プロトンポンプ阻害剤などの組合せが用いられ、本菌の除菌効果だけを見れば、比較的良い成績が得られている。
【０００４】
しかし、これらの薬剤投与療法には、副作用という大きな問題があり、事実、前述の併用薬剤の増加に伴い、味覚障害、嘔気、嘔吐、下痢などの副作用の出現頻度も増加するとの報告もある。したがって、現段階でのＨ．ｐｙｌｏｒｉ除菌療法は、その使用量、使用期間などからの副作用にかなり問題があり、服薬コンプライアンスの面からも、あまり定着していないのが現状である。
【０００５】
一方、米は主食以外に、清酒、焼酎、みりん、酢、麹などとして用途開発され、古くから生活に欠かせないものとなっている。このほかには、美容的用途として糠袋が知られている。これらは、米を単なる主食であると見るか、またはせいぜい澱粉源として見ていなかったということによるものであると思われる。また、糠袋にしても、皮膚に良いとされ、慣例的にそのまま使用されてきたのみであり、有効成分という概念もなければ、その有効成分を利用するという考え方も全くなかったのである。
【０００６】
【発明が解決しようとする課題】
前述のように、Ｈ．ｐｙｌｏｒｉの除菌療法については、その副作用や服薬コンプライアンスの面からも、あまり定着していないのが事実である。したがって、全く副作用がなく、しかも、長期に亘って常用しても十分に安全なＨ．ｐｙｌｏｒｉ除菌剤が要求されている。
本発明は、安全で安価であって、原料供給が安定しており、加工が容易で長期に亘って常用しても全く安全な米からのＨ．ｐｙｌｏｒｉ除去剤を提供することを目的とするものである。
【０００７】
【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および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なってきた。そのうちの一つのテーマとして、米からのＨ．ｐｙｌｏｒｉ除菌剤について鋭意研究を重ねてきたのであるが、その過程で、米および発芽させた米には、Ｈ．ｐｙｌｏｒｉ除菌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。
【０００８】
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Ｈ．ｐｙｌｏｒｉ除菌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、Ｈ．ｐｙｌｏｒｉ除菌効果を示すことが判明した。
【０００９】
▲１▼ 発芽させた米の粉砕物をそのまま、あるいはこれを含有してなるもの。
▲２▼ 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。
▲３▼ 米または発芽させた米の加水物を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。
▲５▼ 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。
【００１０】
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。
【００１１】
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、一般的な方法で行えばよい。
【００１２】
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よく洗浄して用いる。この時、乾燥して用いてもよい。
【００１３】
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。
【００１４】
米または発芽させた米を水抽出する場合、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。
【００１５】
また、米の浸漬水あるいは浸漬水の中ですりつぶした液を用いてもよい。すなわち、米の成分が出てくる方法ならば何でもよい。
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。
【００１６】
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。
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。
【００１７】
米あるいは発芽させた米を酵素分解する場合、まず、米あるいは発芽させた米に加水した後、酵素を添加する。加水量は収率、作業性、最終使用目的などに応じて適宜選定する。また、加水温度は酵素あるいは麹の至適温度が効率的であるが、低温でも長時間おけば酵素分解は十分に行われる。ただし、４０℃以下の低温の場合は、なんらかの防腐を行うことが必要である。また、分解さえすれば温度は高温でもよい。分解時間は温度等に左右されるが、分解さえ行われれば短くても長くてもよい。
【００１８】
ここで使用する酵素は、澱粉分解酵素、蛋白分解酵素、脂肪分解酵素、繊維分解酵素、リグニン分解酵素およびペクチン分解酵素のうち１種または２種以上である。また、麹を使用する場合においては、加水量、作用温度、作用時間は、酵素分解の場合と同様である。使用する麹は、一般に使用される麹でよく、麹菌の種類および品種は問わない。
【００１９】
さらに、前記の抽出を行うに当たり、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。ここで、抽出と同時に酵素分解あるいは麹を作用させる場合、具体的には、有機溶媒中で酵素分解あるいは麹を作用させるか、減圧抽出下で酵素分解あるいは麹を作用させるなどの方法により行う。
【００２０】
本発明においては、上記の各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えば、さらに有効的である。
このアルコール発酵を行う場合、上記のようにして得られた抽出物、酵素分解物（酵素分解、抽出を組み合わせて得られるものも含む）または麹を作用させたものをそのまま、または圧搾、濾過して得た液をアルコール発酵させる。なお、酵素分解とアルコール発酵は同時に行ってもよい。すなわち、米または発芽させた米に加水後、酵素または麹、さらに酒母または酵母を添加して、糖化、アルコール発酵を行う。大量に製造する場合、糖化と発酵のバランスを考えながら、清酒醸造に準じて３段階あるいは何段階にも分けて、米または発芽させた米を添加するのが望ましい。特に少量を処理する場合においては、一度に添加するのが有効である。この際、腐敗が心配な場合は、酸を添加するか、発酵の阻害にならない適当な防腐を施す。
【００２１】
アルコール発酵を行うと、ベトツキがなくなること、濃縮がしやすく有効成分の濃縮が容易になることなどの利点もある。
乳酸発酵を行う場合は、アルコール発酵の場合と同様で、この場合は、酒母または酵母の代わりに乳酸菌を添加して乳酸発酵を行う。乳酸発酵は一般的な常法によって行い、乳酸菌の種類および乳酸発酵の条件は問わない。
【００２２】
次に、酢酸発酵の場合は、上記のようにして得られた発酵物をそのまま、あるいは希釈してアルコール４〜５％にした後、酢酸菌を添加して酢酸発酵を行う。また、アルコールのないものは、アルコールを添加して酢酸発酵を行えばよい。酢酸発酵は一般的な常法によって行い、酢酸菌の種類および酢酸発酵の条件は問わない。
【００２３】
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とする。なお、必要により酵母による通気発酵、アルコール沈殿、合成吸着剤等で除糖を行なってもよい。
【００２４】
本発明品のＨ．ｐｙｌｏｒｉ除菌効果について調べた結果を以下に記載する。
（１）本発明品に対するＨ．ｐｙｌｏｒｉの感受性試験
本発明品に対するＨ．ｐｙｌｏｒｉの感受性試験については、寒天平板希釈法に従って行った。
【００２５】
すなわち、１０％の仔牛血清添加Ｂｒｕｃｅｌｌａｂｒｏｔｈ（ＢＢＬ社）を用い、本発明品濃度が４０，２０，１０，５，２．５，１．３，０．６（％）となるように添加した寒天平板培地を作製した。これに一定量の菌数のＨ．ｐｙｌｏｒｉを接種し、微好気的環境下において３７℃で１週間培養を行った。菌の発育を阻止した本発明品の最小濃度を最小発育阻止濃度（ＭＩＣ：％）として示した。
なお、本実験で用いた菌株は、胃炎患者からの臨床分離株Ａと胃潰瘍患者からの臨床分離株Ｂ、標準株のＮＴＣＣ１１６３７、ＮＴＣＣ１１９１６の４種類である。
結果を表１に示した。
【００２６】
【表１】

表１に示すように、本発明品は、天然物でありながら２０〜０．６％とかなりの低濃度で、Ｈ．ｐｙｌｏｒｉの発育を阻止できるということが証明された。
【００２７】
（２）ヒトでの臨床試験
内視鏡下生検を行い、Ｈ．ｐｙｌｏｒｉが陽性であることを確認したボランティアに、各本発明品５０ｍｌを毎日朝晩２回、食後に経口摂取させ、４週間継続して行った。その後、再び内視鏡下生検を行い、Ｈ．ｐｙｌｏｒｉが陰性かあるいは陽性かを判定した。続いてこの時点で陰性であることが確認されたボランティアに対しては、さらに１年後、内視鏡下生検を行い、本菌の再出現の有無も判定した。
なお、各本発明品につきボランティア２０名で行い、除菌率（％）ならびに再出現率（％）は、次の式に基づく計算により求めた。
【００２８】
【数１】

【００２９】
【数２】

全ての判定は、専門の医師により行った。結果を表２に示した。
【００３０】
【表２】

【００３１】
表２に示すように、本発明品は、その単独投与により非常に高確率でＨ．ｐｙｌｏｒｉの除菌が可能であることが証明された。さらにその中でも、かなり有効な本発明品については、除菌後、少なくとも１年間は、本菌の再出現を抑制することも確認された。また、本臨床試験期間中あるいは試験後においても、本発明品投与による副作用は全く認められず、服薬コンプライアンスも良好であり、本発明品がＨ．ｐｙｌｏｒｉ除菌剤として非常に有効であることが証明された。
以上のように、本発明は、米という最も安全なものから、非常に優れた効果を有するＨ．ｐｙｌｏｒｉ除菌剤を得たのである。
【００３２】
【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。
【００３３】
（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２と同様の操作を行い、別の本発明品１１９０ｍｌを得た。
（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。
【００３４】
（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。
【００３５】
（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、ロータリーエバポレーターで濃縮し、本発明品１５００ｍｌを得た。
【００３６】
（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。
（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。
【００３７】
（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。
【００３８】
（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。
【００３９】
（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。
（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。
【００４０】
（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。
【００４１】
（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。
【００４２】
（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。
（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。
【００４３】
（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。
【００４４】
（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、ロータリーエバポレーターで濃縮し、本発明品１３００ｍｌを得た。
【００４５】
（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。
（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。
【００４６】
（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２４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。
【００４７】
（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２４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。
【００４８】
（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。
（実施例３４）
実施例２４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。
【００４９】
【発明の効果】
本発明によれば、継続的に内服することにより、簡単に全く安全で、しかも、Ｈ．ｐｙｌｏｒｉに対して優れた除菌効果を持つＨ．ｐｙｌｏｒｉ除菌剤が得られる。
米は今までほとんど主食であったため、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Ｈ．ｐｙｌｏｒｉ除菌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 disinfectant for Helicobacter pylori (hereinafter abbreviated as H. pylori) obtained from rice or germinated rice as a raw material.
[0002]
[Prior art]
About 11 years ago, Neisseria gonorrhoeae that had adhered to the gastric mucosa of gastritis patients. Since the first isolation of pylori, it was confirmed that this bacterium was detected at a very high rate from the gastric mucosa of patients with gastritis and peptic ulcers. Clinical research has been done. And H. In addition to the fact that pylori infection causes gastritis, there are many reports that it is an important factor in the treatment and recurrence of peptic ulcers. It has been reported that it can be completely prevented.
[0003]
Actually, a combination therapy of 2 to 3 drugs has already been tried mainly in Europe and the United States. Combinations of tetracycline, penicillin, clarithromycin, other antibiotics, bismuth preparations, metronidazole drugs, proton pump inhibitors, etc. are mainly used, and relatively good results can be obtained by looking at the sterilization effect of this bacterium. It has been.
[0004]
However, these drug administration therapies have a serious problem of side effects, and in fact, there are reports that the frequency of occurrence of side effects such as taste disorders, nausea, vomiting, and diarrhea increases with the increase of the aforementioned concomitant drugs. Therefore, the H.C. Pylori sterilization therapy has a considerable problem in side effects due to its use amount, duration of use, etc., and is not well established from the viewpoint of medication compliance.
[0005]
Rice, on the other hand, has been developed for sake, shochu, mirin, vinegar, koji, etc. in addition to staple foods, and has been indispensable for daily life. In addition, a bag is known as a cosmetic use. These may be due to seeing rice as a staple food or, at best, not as a starch source. Moreover, even if it is a bag, it is said that it is good for skin and has been used as it is, and there was no concept of an active ingredient, and there was no idea of using the active ingredient at all.
[0006]
[Problems to be solved by the invention]
As mentioned above, H.M. It is a fact that pylori eradication therapy is not well established in terms of side effects and compliance. Therefore, there is no side effect at all, and H. There is a need for a pylori disinfectant.
The present invention is safe and inexpensive, has a stable raw material supply, is easy to process, and is completely safe for long-term use. An object of the present invention is to provide a pylori removal agent.
[0007]
[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 benefits 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. One of them is H. from rice. Although extensive research has been conducted on the pylori disinfectant, in the process, rice and germinated rice are treated with H. pylori. The present inventors have found that a component having an effect as a pylori disinfectant is contained, and have completed the present invention.
[0008]
In the present invention, H. coli contained in rice and germinated rice. The component having the effect of sterilizing pylori has not yet been elucidated, but those obtained by treating rice and germinated rice as follows are described in H.P. It was found that pylori sterilization effect was exhibited.
[0009]
(1) A rice pulverized rice as it is or containing it.
(2) Rice or germinated rice extract as it is or containing it.
(3) Rice or sprouted rice hydrolyzate that has been subjected to enzymatic degradation or koji action, or that contains this.
{Circle around (4)} Extracting rice or germinated rice as it is, or containing it, that has been subjected to enzymatic degradation or koji before, simultaneously with or after extraction.
(5) Rice or germinated rice extract or enzyme-decomposed or rice bran that is subjected to alcoholic fermentation or organic acid fermentation as it is or contains it.
[0010]
The rice used in the present invention refers to brown rice and white rice such as glutinous rice and glutinous 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.
[0011]
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.
[0012]
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.
[0013]
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.
[0014]
When rice or germinated rice is extracted with water, 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 lower, it is desirable that the pH is made acidic or alkaline, or a preservative or alcohol is added to prevent the rice from being 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.
[0015]
Further, rice immersion water or a liquid ground in immersion water may be used. In other words, any method can be used as long as the rice components come out.
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.
[0016]
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.
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 which are harmful to the human body are preferably safe because the solvent needs to be completely removed after extraction.
[0017]
When enzymatically degrading rice or germinated rice, the enzyme is first added to the rice or germinated rice. The amount of water added is appropriately selected according to the yield, workability, end use purpose, and the like. In addition, although the optimum temperature of the enzyme or koji is efficient as the hydration temperature, the enzymatic decomposition is sufficiently carried out at a low temperature for a long time. However, in the case of a low temperature of 40 ° C. or lower, it is necessary to perform some preserving. Further, the temperature may be high as long as decomposition is performed. The decomposition time depends on temperature and the like, but may be short or long as long as decomposition is performed.
[0018]
The enzyme used here is one or more of starch degrading enzyme, proteolytic enzyme, lipolytic enzyme, fiber degrading enzyme, lignin degrading enzyme and pectin degrading enzyme. In addition, when using koji, the amount of water added, the working temperature, and the working time are the same as in the case of enzymatic degradation. The cocoon to be used may be a commonly used cocoon, and the kind and variety of the koji mold are not limited.
[0019]
Furthermore, when performing the said extraction, you may make said enzyme decomposition | disassembly and soot act before extraction, simultaneous with extraction, or after extraction. Here, when enzymatic degradation or soot is allowed to act simultaneously with extraction, specifically, enzymatic degradation or soot is allowed to act in an organic solvent, or enzymatic degradation or soot is allowed to act under reduced pressure extraction.
[0020]
In the present invention, it is more effective to perform organic acid fermentation such as alcohol fermentation, lactic acid fermentation, and acetic acid fermentation at the same time or after the above treatments.
When this alcoholic fermentation is performed, the extract obtained as described above, the enzyme degradation product (including those obtained by combining enzymatic degradation and extraction) or the product treated with koji are used as is, or pressed and filtered. The liquid obtained is fermented with alcohol. In addition, you may perform enzymatic degradation and alcohol fermentation simultaneously. That is, after water is added to rice or germinated rice, an enzyme or koji, and a liquor or yeast are added to perform saccharification and alcohol fermentation. When producing in large quantities, it is desirable to add rice or germinated rice in three or several stages according to sake brewing while considering the balance between saccharification and fermentation. In particular, when a small amount is processed, it is effective to add it at once. At this time, if there is a concern about decay, an acid is added or an appropriate preservative that does not inhibit fermentation is applied.
[0021]
When alcoholic fermentation is performed, there are advantages such as no stickiness and easy concentration of active ingredients.
When performing lactic acid fermentation, it is the same as that of alcoholic fermentation. In this case, lactic acid fermentation is performed by adding lactic acid bacteria in place of the liquor or yeast. Lactic acid fermentation is carried out by a common ordinary method, and the type of lactic acid bacteria and the conditions for lactic acid fermentation are not limited.
[0022]
Next, in the case of acetic acid fermentation, the fermented material obtained as described above is used as it is or diluted to alcohol 4 to 5%, and then acetic acid bacteria are added to carry out acetic acid fermentation. Moreover, what does not have alcohol should just add alcohol and perform acetic acid fermentation. The acetic acid fermentation is performed by a general ordinary method, and the kind of acetic acid bacteria and the conditions for the acetic acid fermentation are not limited.
[0023]
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 using as it is, sterilize or disinfect it to make a product. If necessary, sugar removal may be performed by aeration fermentation with yeast, alcohol precipitation, synthetic adsorbent, or the like.
[0024]
The H.O. The results of examining the pylori eradication effect are described below.
(1) H.D. Pylori susceptibility test The sensitivity test of pylori was performed according to the agar plate dilution method.
[0025]
That is, 10% calf serum-added Brucella broth (BBL) was added so that the concentration of the product of the present invention was 40, 20, 10, 5, 2.5, 1.3, 0.6 (%). An agar plate medium was prepared. To this, a certain amount of H.C. Pylori was inoculated and cultured at 37 ° C. for 1 week in a microaerobic environment. The minimum concentration of the product of the present invention that inhibited the growth of bacteria was shown as the minimum growth inhibitory concentration (MIC:%).
In addition, the strains used in this experiment are four types, clinical isolate A from gastritis patients, clinical isolate B from gastric ulcer patients, standard strains NTCC11637 and NTCC11916.
The results are shown in Table 1.
[0026]
[Table 1]

As shown in Table 1, the product of the present invention is a natural product, but at a considerably low concentration of 20 to 0.6%. It was proved that the growth of pylori can be prevented.
[0027]
(2) Endoscopic biopsy of human clinical trials. Volunteers that were confirmed to be positive for pylori were orally ingested 50 ml of each product of the present invention twice daily in the morning and evening, and continued for 4 weeks. Thereafter, an endoscopic biopsy was performed again. It was judged whether pylori was negative or positive. Subsequently, the volunteers who were confirmed to be negative at this time were further subjected to endoscopic biopsy one year later, and the presence or absence of reappearance of the fungus was also determined.
In addition, it carried out by 20 volunteers about each this invention product, and calculated | required the sanitization rate (%) and the reappearance rate (%) by calculation based on the following formula | equation.
[0028]
[Expression 1]

[0029]
[Expression 2]

All judgments were made by specialist doctors. The results are shown in Table 2.
[0030]
[Table 2]

[0031]
As shown in Table 2, the product of the present invention has a very high probability of H.P. It was proved that pylori can be sterilized. Furthermore, among them, it was confirmed that the product of the present invention that is quite effective suppresses the reappearance of the bacterium for at least one year after sterilization. In addition, even during or after this clinical trial, no side effects due to administration of the product of the present invention were observed, and compliance with medication was good. It proved to be very effective as a pylori disinfectant.
As described above, the present invention is an H.P. which has a very excellent effect from the safest rice called rice. A pylori disinfectant was obtained.
[0032]
【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, and the pH was lowered with hydrochloric acid and left 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.
[0033]
Example 3
Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 2 was performed to obtain 1190 ml of another product of the present invention.
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.
[0034]
(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.
[0035]
(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 was added 2000 ml of water and concentrated with a rotary evaporator to obtain 1500 ml of the product of the present invention.
[0036]
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.
(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.
[0037]
(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.
[0038]
(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.
[0039]
(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.
(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.
[0040]
(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.
[0041]
(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.
[0042]
(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.
(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.
[0043]
(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.
[0044]
(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.
[0045]
(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.
(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.
[0046]
(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 24, 2000 g of an enzymatic degradation 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.
[0047]
(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 24, 2000 g of an enzymatic degradation 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.
[0048]
(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.
(Example 34)
80 ml of 95% ethanol was added to 1000 ml of the product of the present invention obtained in Example 24, 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.
[0049]
【The invention's effect】
According to the present invention, it is easy and completely safe to take continuously, H. pylori has an excellent sterilizing effect against P. A pylori disinfectant is obtained.
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. That is, the present invention is very excellent in H.264. In addition to finding a pylori disinfectant, it is extremely meaningful to find a new application and to increase consumption by improving the image of rice.

Claims

A Helicobacter pylori sterilizing agent obtained by using a rice extract or a germinated rice extracted by acting a liquefaction enzyme as it is.

A Helicobacter pylori disinfectant containing rice hydrolyzate or enzyme-treated rice hydrolyzate.

A Helicobacter pylori sterilizing agent containing or containing rice that has been subjected to enzymatic degradation or koji before, during or after the extraction of rice.

Furthermore, the Helicobacter pylori disinfectant according to claim 2 or 3, which is obtained by using alcohol fermentation or organic acid fermentation as it is or containing it.