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JP2004189662A - Angiotensin converting enzyme inhibitor and antihypertension food - Google Patents

Angiotensin converting enzyme inhibitor and antihypertension food Download PDF

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Publication number
JP2004189662A
JP2004189662A JP2002358822A JP2002358822A JP2004189662A JP 2004189662 A JP2004189662 A JP 2004189662A JP 2002358822 A JP2002358822 A JP 2002358822A JP 2002358822 A JP2002358822 A JP 2002358822A JP 2004189662 A JP2004189662 A JP 2004189662A
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JP
Japan
Prior art keywords
converting enzyme
food
conchiolin
enzyme inhibitor
angiotensin converting
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JP2002358822A
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Japanese (ja)
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JP4376512B2 (en
Inventor
Keiji Takagi
啓二 高木
Kenji Shimomura
健次 下村
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Mikimoto Pharmaceutical Co Ltd
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Mikimoto Pharmaceutical Co Ltd
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  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract

<P>PROBLEM TO BE SOLVED: To develop an angiotensin converting enzyme inhibitor and an antihypertension food having a mild effects and allowing continuous intake. <P>SOLUTION: The angiotensin converting enzyme inhibitor and the antihypertension food, having activities for preventing or ameliorating hypertension are obtained by formulating one or more kinds selected from a shell of a seed of Jatoba (Hymenaea courbaril), a leaf of guava, Murraya koenigii, lagerstroemia speciosa, a leaf of Morus Bombycis, Tamarix chinensis Lour, Agrimonia pilosa, an extract of Mimusops elengi, conchiolin and a product obtained by treating a hydrolyzed product of the conshiolin with succinic anhydride. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

【0001】
【産業上の利用分野】本発明は、血圧を温和に低下にさせるアンギオテンシン変換酵素阻害剤および抗高血圧食品に関する。
【0002】
【従来の技術】近年食生活の変化などで生活習慣病が増加しているが、その中でも高血圧は最も多い疾患である。高血圧になると体内にアンギオテンシン2という血圧を上昇させる物質が増加します。このアンギオテンシン2は肺や血管内皮細胞、腎近位尿細管に存在するアンギオテンシン変換酵素によりアンギオテンシン1から作られます。この酵素を阻害することによって高血圧を防ぐことができる。カプトプリル、シラザプリル、エナラプリルのようなアンギオテンシン変換酵素阻害剤が知られている。
しかし、副作用として夜間の空咳があり、2割近い副作用発現率で、結局この副作用のためにこの薬剤の継続を中断せざるを得ないことがあった。
【0003】
ジャトバ(JATOBA)は、マメ科のオオイナゴマメ属の高木で和名オオイナゴマメ、学名 Hymenaea courbaril と呼ばれている。熱帯アメリカに分布し、高さ15〜40m、幹の径100〜200cm、樹皮は淡灰色から灰色である。材は木材として家具等に利用され、樹皮、樹脂、内皮は駆虫、健胃、気管支炎、膀胱炎、催尿、前立腺炎、淋病等に用いられている。豆果は食用とされている。このジャトバの実や樹皮などを水、エタノールなどで抽出した抽出物を美白化粧品に利用することは既に開示されている(特開平 9−12441号公報)。
【0004】
グァバはバンジロウ或いは番石榴と呼ばれ、ふともも科、バンジロウ属の植物で、学名をプジジウム グアヤバ エル(Psidium Guajava L.)という。一般には、その実を生食、ジャム、ジュース等で食する。分布は、原産は熱帯アメリカであるが、熱帯、亜熱帯の各地で広く栽培され、日本では九州南部で栽培され、琉球諸島では野生化している。また、薬として腸炎、赤痢、消化不良性下痢に用いられている。
【0005】
ムラヤ コエニジ(Murraya koenigii)は双子葉植物網、離弁花亜網、ふうろそう目、ミカン科の植物でインドやスリランカに分布し、乾燥した低地に普遍的に見られる。薬用としては便秘、腹疝痛、下痢等に用いられてきた。
【0006】
オオバナサルスベリ(lagerstroemia speciosa)は、ミソハギ科サルスベリ属の植物でインドに生える半落葉高木である。このオオバナサルスベリの根は、下痢に、樹皮、葉は下剤として利用されている。
【0007】
桑葉は学名をモルス ボムビシス(Morus Bombycis)、モルス アルバ(Morus alba)等と称する桑の木の乾燥した葉を言う。モルス ボムビシスは日本各地、および南千島、朝鮮、中国、ベトナムからインド、カシミールの温帯から亜熱帯に分布する。山地にはえ、畑に栽植される落葉高木であり、クワまたはヤマグワと呼ばれる。モルス アルバは中国,朝鮮半島の原産で日本には古くより渡来し、庭園樹、街路樹、養蚕用に各地で栽植される落葉高木で、カラグワ、トウグワと呼ばれている。
【0008】
西河柳はギョリュウ科ギョリュウ属の学名をタマリックス チネンシス ロウア(Tamarix chinensis Lour)、通称ギョリュウと呼ばれる植物の葉のついた若枝である。この植物は原産は中国であるが、鑑賞用として日本に渡来し、庭等に植えられている落葉小高木である。用途としては、発汗、解熱、利尿、鎮咳、抗菌(肺炎球菌、α−レンサ球菌、白色ブドウ球菌、インフルエンザ)として用いられている。
【0009】
キンミズヒキ属の植物は双子葉植物網、離弁花亜網、ばら科に属する。日本ではキンミズヒキ(Agrimonia eupatoria )が本州・四国・九州・琉球に自生し、山野や道ばたにはえる多年草である。日本以外では朝鮮、台湾、シベリア、ヒマラヤの暖帯から温帯に分布している。この草は仙鶴草と称しその全草が利用されている。その目的は止血、止瀉、消炎、強壮薬として、吐血、血、便血、尿血、崩漏帯下、赤白痢疾等の諸出血症状に利用されている。しかし化粧料としては特開平1−313414号で頭部化粧料として、特開昭60−184024号で殺菌性組成物として利用されているにすぎない。
【0010】
ミムソプス エレンギ(Mimusops elengi )はインドからネパールのタライ地方に産するアカテツ科の常緑の小高木で、ミサキノハナと称し庭木としてもよく植えられている。樹皮は暗灰色で亀裂がある。葉は楕円形〜長楕円形で花は腋性で単生、または束生で小さく淡黄色で星形をしており、香りがよい。薬品的な利用は樹皮は収斂性で強壮剤となり、また熱にも処方される。葉は蛇に咬まれたときの治療にも使われる。熟した果実の果肉は収斂性があり、慢性下痢の治療に使われる。種子は打撲傷に使われ、地方によっては小児の便秘時の浣腸に用いられる。これらの利用に関しては特許は出願されていない。
【0011】
コンキオリンまたはその加水分解物(合わせてコンキオリンと称する)が保湿性に優れているためである。また、特開平4−36214号公報において、コンキオリンが酸化防止剤として有効なことが示されている。
【0012】
また、このコンキオリン加水分解物を無水コハク酸で処理した物は、加水分解の程度が少なくても、即ち分子量が大きくても水溶性が増し、保湿性もコンキオリン加水分解物より、さらに向上していることは特願平5−312222号に於いて、本発明者らが開示している。
【0013】
【発明が解決しようとする課題】
本発明者らは以上のような現状を鑑み、効果が緩和で継続的に摂取できるアンギオテンシン変換酵素阻害剤および抗高血圧食品を開発することにある。
【0014】
【課題を解決するための手段】
本発明者らは上記の問題を解決するために鋭意検討した結果、Jatoba(Hymenaea courbaril)の実の殻、グアバの葉、ムラヤ コエンジ、オオバナサルスベリ、桑葉、西河柳、仙鶴草、ミサキノハナの抽出物、コンキオリン、コンキオリン加水分解物を無水コハク酸で処理した物を利用することによって上記の問題が解決することがわかった。
【0015】
本発明に使用するJatoba(Hymenaea courbaril)の実の殻、グアバの葉、ムラヤ コエンジ、オオバナサルスベリ、桑茶、西河柳、仙鶴草、ミサキノハナの抽出物の方法としては、水或いは親水性有機溶媒、例えば、エタノール、メタノール、アセトン等で抽出する。しかしながら、人体に適用する原料の抽出であるから、水、或いはエタノール又はこれらの混合溶媒での抽出が好ましいのは当然である。また、場合によっては、グリセリン、1,3−ブチレングリコール、プロピレングリコール等の多価アルコール又は多価アルコールと水の混液も抽出に利用できる。さらにまた、凍結乾燥して粉体として利用することも利用方法によっては有効である。
【0016】
コンキオリンは貝殻や真珠類に含まれる硬蛋白質の一種でありアコヤ貝、イガイ、カラスガイ等に比較的多く含まれている。製造法としては特許1587730号、特許1560610号、特許1587734号等に記載されている。
【0017】
製造方法は、アコヤ貝、イガイ、カラスガイ等貝殻等より脱灰して蛋白質を得、これを通常の方法で必要な加水分解を加えればよい。以下にその一例を示すがこれに限定されることはない。アコヤ貝、イガイ、カラスガイ等貝殻等を粉砕して希塩酸等でカルシウム分を除去し、遠心分離、濾過デカンテーション等の固液分離手法によって不溶物を集め、これを精製水を加えてよく撹拌し、遠心分離、濾過等によって不溶物を集める。必要によりこれを繰り返す。
【0018】
更にこのコンキオリンに2〜10%の塩酸水溶液を加えて、50〜110℃で5時間〜5日間加水分解して、コンキオリンの加水分解物としてもよい。これを単にコンキオリンということもある。
【0019】
希塩酸の代わりに希硫酸を用いて加水分解し、水酸化バリウムを用いて中和し、更に水酸化アルカリ液を用いてpH5〜6になるように中和した後、沈澱物を遠心分離、濾過等により取り除いた加水分解液を公知の濃縮方法または乾燥方法を用いて濃縮液または乾燥粉末とする。加水分解に当たっては、コンキオリンがアミノ酸にまで完全に分解してしまわないように酸濃度、温度、時間を制御すべきことは勿論である。
【0020】
コンキオリンの加水分解物を無水コハク酸で処理して得た物質の作成方法はコンキオリンの加水分解物の水溶液中で攪拌しつつ、pH6〜9に保ちつつ無水コハク酸を添加する。添加量はコンキオリンの加水分解の割合やすべてをスクシニル化する必要はないので目的等によって無水コハク酸の量は調整する。
【0021】
さらにコハク酸で処理したコンキオリンの加水分解物の作成方法は、上記の方法で作成した物質を無水コハク酸を加えてpHを6〜9に保って撹拌することにより、新たな利用方法のある化粧品原料ができる。この方法は低分子化の方法を問わず、実施できるので、コンキオリンの分解は通常の酸による方法をはじめ各種の方法を採用できる。
【0022】
上記のように処理した、Jatoba(Hymenaea courbaril)の実の殻、グアバの葉、ムラヤ コエンジ、オオバナサルスベリ、桑茶、西河柳、仙鶴草、ミサキノハナの抽出物、コンキオリン、コンキオリン加水分解物を無水コハク酸で処理した物、アコヤガイ糖蛋白の1種以上を配合することによって、アンギオテンシン変換酵素阻害剤や抗高血圧食品を作成する。剤形はとくに制限がなく、錠剤、散剤、液剤、錠剤、散剤、顆粒、糖衣錠、カプセル、懸濁液、アンプル、注射剤等の任意の剤形に、担体、賦形剤、結合剤、希釈剤と混合し作成する。また、スープ、果実ジュース、野菜ジュース、乳清飲料、清涼飲料などの飲料、アイスクリーム、ガム、キャンデー、、飴、洋菓子類、和菓子類、ジャム、マーマレード、チーズ、バター、ヨーグルトなどの飲食物の形態或いは他の飲食物との混合を行い、飲食物として利用することができる。
【0023】
【実施例】以下に、本発明で使用する製造例、実際の利用方法である実施例を記載するが、本発明はこれらの製造例及び実施例によって何ら限定されるものではない。
【0024】
製造例1
真珠500gを塩酸1kgを撹拌しながら徐々に加えて脱灰する。さらに1規定塩酸300gを撹拌しながら徐々に加えて脱灰し、これを濾過して不溶物を集めた。これに水で30倍に希釈した硫酸を100ml加えて、ガラス容器に密封し、110℃で24時間加熱分解した。冷却後、用いた硫酸の当量の90%の水酸化バリウムを充分撹拌しつつ、少量づつ加えた。さらに、pH5.8まで1%水酸化ナトリウム水溶液を加えた。次に200G、10分間、遠心分離した後さらに0.45ミクロンのメンブランフルターで濾過し、分解物を得た。これを凍結乾燥した。収量は8.9gであった。
【0025】
製造例2
製造例1を5.0gとり、精製水100mlに分散し、撹拌しつつ、無水コハク酸1gをpH6〜9に1規定水酸化ナトリウム水溶液で保ちながら15分おきに5回加えた。これを凍結乾燥した。収量は9.9gであった。
【0026】
製造例3
ジャトバJATOBAの実(乾燥品)を10gに50%エタノール水溶液300mlを加えて時々撹拌しつつ5日間放置した。これを濾過後エバポレートした後、凍結乾燥した。
【0027】
製造例4
乾燥した仙鶴草を10gに50%エタノール水溶液300mlを加えて時々撹拌しつつ5日間放置した。これを濾過後エバポレートした後、凍結乾燥した。
【0028】
製造例5
乾燥したミサキノハナ(Mimusops elengi )の樹皮を10gに50%メタノール水溶液300mlを加えて還流冷却管をつけ加熱する。これを凍結乾燥した。
【0029】
製造例6
グアバの葉(乾燥品)を10gに50%エタノール水溶液300mlを加えて時々攪拌しつつ5日間放置した。これを濾過後凍結乾燥した。
【0030】
製造例7
西河柳(乾燥品)を10gに50%エタノール水溶液300mlを加えて時々攪拌しつつ5日間放置した。これを濾過後凍結乾燥した。
【0031】
製造例8
オオバナサルスベリの葉(乾燥品)を10gに50%エタノール水溶液300mlを加えて時々撹拌しつつ5日間放置した。これを濾過後凍結乾燥した。
【0032】
製造例9
ムラヤ コエニジ(Murrara koenigii)の枝(乾燥品)を10gに50%エタノール水溶液300mlを加えて時々撹拌しつつ5日間放置した。これを濾過後凍結乾燥した。
【0033】
製造例10
桑 (Morus alba)の葉(乾燥品)を10gに50%エタノール水溶液300mlを加えて時々撹拌しつつ5日間放置した。これを濾過後凍結乾燥した。
【0034】
実施例−1 錠剤 (重量部)
製造例1 10.0
乳糖 30.0
コーンスターチ 26.0
結晶セルロース 30.0
ポリビニルピロリドン 3.0
ステアリン酸Mg 1.0
常法にしたがって上記各成分を用いて顆粒化し、圧縮成形して1錠500mg錠剤1000錠を調整した。
【0035】
実施例−2 飲料
製造例2 1g
キシリトール 10g
ビタミンB1塩酸塩 0.5mg
ビタミンB2 0.2mg
ビタミンC 500mg
ナイアシン 1.0mg
パントテン酸Ca 1.0mg
精製水 100g
常法にしたがって上記各成分を計り取り、混合した。
【0036】
実施例−3
実施例−1の製造例1を製造例3に替え、他は実施例−1と同様に作成した。
【0037】
実施例−4
実施例−2の製造例1を製造例4に替え、他は実施例−2と同様に作成した。
【0038】
実施例−5
実施例−1の製造例1を製造例5に替え、他は実施例−1と同様に作成した。
【0039】
実施例−6
実施例−2の製造例1を製造例6に替え、他は実施例−2と同様に作成した。
【0040】
実施例−7
実施例−1の製造例1を製造例7に替え、他は実施例−1と同様に作成した。
【0041】
実施例−8
実施例−2の製造例1を製造例8に替え、他は実施例−2と同様に作成した。
【0042】
実施例−9
実施例−1の製造例1を製造例9に替え、他は実施例−1と同様に作成した。
【0043】
実施例−10
実施例−2の製造例1を製造例10に替え、他は実施例−2と同様に作成した。
【0044】
以下に有効性を確認した試験について説明する。
アンギオテンシン変換酵素阻害試験
試験方法
1mg/mlの試料溶液0.5mlに5mMのヒプリルーヒスチジルーロイシンを含む100mMの HEPES緩衝液(pH8.3)0.25mlを加えて37℃で3分間インキュベートした後、3.0mU/mlのアンギオテンシン−1変換酵素(ACE)0.25mlを加えて37℃で30分間反応させた。0.1Nの水酸化ナトリウム溶液2.0mlを加えて反応を停止させた後、遊離したヒスチジルーロイシンの蛍光誘導体を形成させるため0.2% o−フタルアルデヒドのメタノール溶液0.1mlを加えて4℃で15分間遮光放置した。1.5Mのリン酸溶液0.4mlを加えて反応液を中和させた後、励起波長360nm、蛍光波長480nmの蛍光強度(C)を測定した。試料を含まないもの(A)、試料とACEを含まないもの(B)、ACEを含まないもの(D)についても同様の操作を行い、これらの蛍光強度から次式によりヒスチジルロイシン生成阻害率、すなわちACE阻害率を算出した。
阻害率(%)={1−(C−D)/(A−B)}×100
【0045】
結果を以下にに示す。

Figure 2004189662
【0046】
実施例をそれぞれ血圧の高い人10人づつに6ヶ月間使用してもらい使用前と使用後に血圧を測定して最高血圧の低下を見た。(1日当り、錠剤は10錠、飲料は100ml飲食してもらった)
以下にその結果を示す。(10名の平均値である。)
Figure 2004189662
【0047】
【効果】上記のようにアンギオテンシン変換酵素を阻害し、実施例を飲食すると、血圧が低下し、有用であることがわかった。なお、副作用はなく安全性も高いことがわかった。[0001]
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an angiotensin converting enzyme inhibitor and an antihypertensive food which moderately lowers blood pressure.
[0002]
2. Description of the Related Art In recent years, lifestyle-related diseases have increased due to changes in dietary habits. Among them, hypertension is the most common disease. When hypertension occurs, angiotensin 2 is a substance that increases blood pressure in the body. This angiotensin 2 is made from angiotensin 1 by angiotensin converting enzyme which is present in lungs, vascular endothelial cells and renal proximal tubules. Inhibiting this enzyme can prevent hypertension. Angiotensin converting enzyme inhibitors such as captopril, cilazapril, and enalapril are known.
However, there was a night cough as a side effect, and the incidence of side effects was close to 20%, and eventually the continuation of this drug had to be interrupted due to this side effect.
[0003]
Jatoba (Jatoba) is a Takagi tree belonging to the genus Oochoenma of the leguminous family, and is called the Japanese name Ooyamae bean, scientific name Hymenaea courbaril. Distributed in tropical America, the height is 15 to 40 m, the diameter of the trunk is 100 to 200 cm, and the bark is light gray to gray. The wood is used for furniture and the like as wood, and the bark, resin, and endothelium are used for anthelmintic, healthy stomach, bronchitis, cystitis, urination, prostatitis, gonorrhea and the like. Beans are edible. It has already been disclosed to use an extract obtained by extracting Jatoba fruit or bark with water, ethanol or the like for whitening cosmetics (Japanese Patent Laid-Open No. 9-12441).
[0004]
Guava is called a banjirou or banshio tsumugi. It is a plant belonging to the genus Tungaceae, genus Vanjiro, and its scientific name is Psidium Guajava L. In general, the fruit is eaten with raw food, jam, juice or the like. Origin is tropical America, but it is widely cultivated in the tropics and subtropics, cultivated in southern Kyushu in Japan, and wild in the Ryukyu Islands. It is also used as a medicine for enteritis, dysentery and indigestive diarrhea.
[0005]
Murraya koenigii is a dicotyledonous net, a petal flower net, a diptera, and a citrus family plant that is distributed in India and Sri Lanka and is commonly found in dry lowlands. For medicinal purposes, it has been used for constipation, stomach pain, diarrhea, and the like.
[0006]
Lagerstroemia sp. Is a semi-deciduous tree that grows in India and is a plant belonging to the genus Sarsbergi. The roots of the giant clam are used for diarrhea and the bark and leaves are used as laxatives.
[0007]
Mulberry leaves are the dried leaves of mulberry trees whose scientific names are named Morus Bombycis, Morus alba and the like. Morse bombibisis is distributed throughout Japan, from the Minami Kuril, Korea, China, Vietnam to India, and from Kashmir to the temperate zone to the subtropics. A deciduous tree that grows in the mountains and is planted in a field, called mulberry or yamagua. Mors Alba is native to China and the Korean peninsula, and has come to Japan since ancient times. It is a deciduous tree that is planted in various places for garden trees, street trees, and sericulture, and is called Karagua and Touguwa.
[0008]
Nishikawayanagi is a young branch with leaves of a plant called Garyoridae, which has the scientific name of the genus Gyoryaceae, Tamarix chinensis Lour. Although this plant is originally from China, it is a small deciduous tree that came to Japan for viewing and was planted in gardens. Applications include sweating, antipyretic, diuretic, antitussive, antibacterial (pneumococcus, α-streptococcus, white staphylococci, influenza).
[0009]
The plant belonging to the genus Kimihiki belongs to the dicotyledonous network, the petal flower net, and the rose family. In Japan, Akimonia eupatoria grows naturally in Honshu, Shikoku, Kyushu, and Ryukyu, and is a perennial that grows on the mountains and roadsides. Outside Japan, it is distributed in the warm to temperate zones of Korea, Taiwan, Siberia and the Himalayas. This grass is called Senzaku grass and the whole grass is used. Its purpose is hemostasis, antistasis, anti-inflammation, tonic, and it is used for various bleeding symptoms such as vomiting, blood, stool blood, urinary blood, cerebral hemorrhage, and dysentery. However, as cosmetics, they are only used as head cosmetics in JP-A-1-313414 and as bactericidal compositions in JP-A-60-184024.
[0010]
Mimusops elengi is an evergreen small tree of the Acetaceae family from India to the Tarai region of Nepal, and is often planted as a garden tree. The bark is dark gray and cracked. The leaves are oval to oblong, and the flowers are fertile and single, or bunch are small, pale yellow and star-shaped, and have a good fragrance. For chemical use, the bark is astringent and tonic, and is also prescribed for heat. The leaves are also used for treatment when bitten by a snake. Ripe fruit pulp is astringent and is used to treat chronic diarrhea. Seeds are used for bruising, and in some regions they are used for enema during constipation in children. No patent has been filed for these uses.
[0011]
This is because conchiolin or a hydrolyzate thereof (referred to collectively as conchiolin) is excellent in moisture retention. JP-A-4-36214 discloses that conchiolin is effective as an antioxidant.
[0012]
In addition, the product obtained by treating this conchiolin hydrolyzate with succinic anhydride has increased water solubility even when the degree of hydrolysis is small, that is, the molecular weight is large, and the moisture retention is further improved than the conchiolin hydrolyzate. This is disclosed by the present inventors in Japanese Patent Application No. 5-312222.
[0013]
[Problems to be solved by the invention]
In view of the current situation as described above, the present inventors have developed an angiotensin converting enzyme inhibitor and an antihypertensive food that can be continuously ingested with moderate effects.
[0014]
[Means for Solving the Problems]
As a result of diligent studies to solve the above problems, the present inventors have extracted Jatoba (Hymenaea courbaril) husks, guava leaves, Muraya coenji, Greater crape myrtle, mulberry leaves, Nishikawa Yanagi, Sentsukusa, Misakinohana. It has been found that the above problem can be solved by using a product obtained by treating a product, conchiolin, or a hydrolyzate of conchiolin with succinic anhydride.
[0015]
As a method of the extract of Jatoba (Hymenea courbaril) husk, guava leaf, Muraya coenji, Greater crape myrtle, mulberry tea, Nishikawayanagi, Sentsukusa, Misakinohana used in the present invention, water or a hydrophilic organic solvent, For example, extraction is performed with ethanol, methanol, acetone or the like. However, since it is extraction of the raw material applied to a human body, naturally extraction with water, ethanol, or these mixed solvents is preferable. In some cases, polyhydric alcohols such as glycerin, 1,3-butylene glycol, and propylene glycol, or a mixture of polyhydric alcohol and water can also be used for extraction. Furthermore, lyophilization and use as a powder is also effective depending on the method of use.
[0016]
Conchiolin is a kind of hard protein contained in shells and pearls, and is relatively contained in pearl oysters, mussels and crows. Production methods are described in Japanese Patent No. 1587730, Japanese Patent No. 1560610, Japanese Patent No. 1587734, and the like.
[0017]
In the production method, a protein is obtained by decalcification from shells such as pearl oysters, mussels and mussels, and this is subjected to necessary hydrolysis by a usual method. One example is shown below, but is not limited thereto. Shells such as pearl oysters, mussels, and mussels are crushed and calcium content is removed with dilute hydrochloric acid, etc., and insoluble materials are collected by solid-liquid separation methods such as centrifugation and filtration decantation. Collect insoluble material by centrifugation, filtration, etc. Repeat as necessary.
[0018]
Furthermore, 2-10% hydrochloric acid aqueous solution may be added to this conchiolin and hydrolyzed at 50-110 ° C. for 5 hours to 5 days to obtain a conchiolin hydrolyzate. This is sometimes simply called conchiolin.
[0019]
Hydrolysis using dilute sulfuric acid instead of dilute hydrochloric acid, neutralization using barium hydroxide and neutralization to pH 5-6 using an alkali hydroxide solution, followed by centrifugation and filtration of the precipitate The hydrolyzed solution removed by the above method is made into a concentrated solution or a dry powder by using a known concentration method or drying method. In the hydrolysis, it goes without saying that the acid concentration, temperature and time should be controlled so that conchiolin does not completely decompose into amino acids.
[0020]
A method for preparing a substance obtained by treating a hydrolyzate of conchiolin with succinic anhydride is to add succinic anhydride while maintaining the pH at 6 to 9 while stirring in an aqueous solution of the hydrolyzate of conchiolin. The amount of succinic anhydride is adjusted depending on the purpose and the like because the amount added does not need to be succinylated or the rate of hydrolysis of conchiolin.
[0021]
Furthermore, the preparation method of the hydrolyzate of conchiolin treated with succinic acid is a cosmetic product with a new utilization method by adding the succinic anhydride to the substance prepared by the above method and stirring it while maintaining the pH at 6-9. Raw material is made. Since this method can be carried out regardless of the method of reducing the molecular weight, various methods including the usual acid method can be adopted for the degradation of conchiolin.
[0022]
Jatba (Hymenaea courbaril) husk, guava leaf, Muraya coenji, giant crape myrtle, mulberry tea, saiheyanagi, sensakusa, misaki nohana extract, conchiolin, conchiolin hydrolyzate treated as above An angiotensin converting enzyme inhibitor and an antihypertensive food are prepared by blending at least one kind of acid-treated pearl oyster glycoprotein. The dosage form is not particularly limited, and can be any form such as tablets, powders, liquids, tablets, powders, granules, dragees, capsules, suspensions, ampoules, injections, carriers, excipients, binders, dilutions. Prepare by mixing with the agent. In addition, beverages such as soup, fruit juice, vegetable juice, whey beverage, soft drink, ice cream, gum, candy, rice cake, Western confectionery, Japanese confectionery, jam, marmalade, cheese, butter, yogurt, etc. It can be used as food and drink by mixing with the form or other food and drink.
[0023]
EXAMPLES The production examples used in the present invention and examples which are actual utilization methods are described below, but the present invention is not limited by these production examples and examples.
[0024]
Production Example 1
500 g of pearls are gradually added with stirring 1 kg of hydrochloric acid to deash. Further, 300 g of 1N hydrochloric acid was gradually added while stirring to deash, and this was filtered to collect insoluble matters. 100 ml of sulfuric acid diluted 30 times with water was added thereto, sealed in a glass container, and thermally decomposed at 110 ° C. for 24 hours. After cooling, 90% barium hydroxide equivalent to the sulfuric acid used was added in small portions with good stirring. Further, 1% aqueous sodium hydroxide solution was added until pH 5.8. Next, it was centrifuged at 200 G for 10 minutes and then filtered through a 0.45 micron membrane filter to obtain a decomposition product. This was lyophilized. Yield was 8.9 g.
[0025]
Production Example 2
5.0 g of Production Example 1 was taken and dispersed in 100 ml of purified water. While stirring, 1 g of succinic anhydride was added 5 times every 15 minutes while maintaining 1-6 aqueous sodium hydroxide at pH 6-9. This was lyophilized. Yield was 9.9 g.
[0026]
Production Example 3
Jatoba JATOBA fruit (dried product) was added to 10 g of a 50% aqueous ethanol solution (300 ml) and allowed to stand for 5 days with occasional stirring. This was filtered and evaporated and then lyophilized.
[0027]
Production Example 4
300 g of 50% aqueous ethanol solution was added to 10 g of dried Senzaku grass and left for 5 days with occasional stirring. This was filtered and evaporated and then lyophilized.
[0028]
Production Example 5
The bark of dried Misakis elengi is added to 10 g of 300 ml of 50% aqueous methanol solution and heated with a reflux condenser. This was lyophilized.
[0029]
Production Example 6
To 10 g of guava leaf (dried product), 300 ml of 50% aqueous ethanol solution was added and left for 5 days with occasional stirring. This was filtered and freeze-dried.
[0030]
Production Example 7
Nishikawayanagi (dried product) was added to 10 g of 300 ml of 50% aqueous ethanol solution and allowed to stand for 5 days with occasional stirring. This was filtered and freeze-dried.
[0031]
Production Example 8
To 10 g of the leaf of the giant clam leaf (dried product), 300 ml of a 50% aqueous ethanol solution was added and allowed to stand for 5 days with occasional stirring. This was filtered and freeze-dried.
[0032]
Production Example 9
A branch (dry product) of Murara koenigii was added to 10 g of 300 ml of a 50% aqueous ethanol solution and allowed to stand for 5 days with occasional stirring. This was filtered and freeze-dried.
[0033]
Production Example 10
Mulberry (Morus alba) leaves (dried product) were added to 10 g of 300 ml of 50% aqueous ethanol solution and allowed to stand for 5 days with occasional stirring. This was filtered and freeze-dried.
[0034]
Example-1 Tablet (parts by weight)
Production Example 1 10.0
Lactose 30.0
Cornstarch 26.0
Crystalline cellulose 30.0
Polyvinylpyrrolidone 3.0
Mg stearate 1.0
According to a conventional method, each of the above components was granulated and compression-molded to prepare 1000 tablets of 500 mg tablets.
[0035]
Example-2 Beverage Production Example 2 1g
Xylitol 10g
Vitamin B1 hydrochloride 0.5mg
Vitamin B2 0.2mg
Vitamin C 500mg
Niacin 1.0mg
Pantothenic acid Ca 1.0mg
100 g of purified water
According to a conventional method, each of the above components was measured and mixed.
[0036]
Example-3
The production example 1 of Example-1 was replaced with the production example 3, and others were produced similarly to Example-1.
[0037]
Example-4
Production Example 1 of Example-2 was replaced with Production Example 4, and the others were produced in the same manner as Example-2.
[0038]
Example-5
The production example 1 of Example-1 was replaced with the production example 5, and others were produced similarly to Example-1.
[0039]
Example-6
Production Example 1 of Example-2 was replaced with Production Example 6, and the others were produced in the same manner as Example-2.
[0040]
Example-7
Production Example 1 of Example-1 was replaced with Production Example 7, and the others were produced in the same manner as Example-1.
[0041]
Example-8
Production Example 1 of Example-2 was changed to Production Example 8, and the others were produced in the same manner as Example-2.
[0042]
Example-9
Production Example 1 of Example-1 was replaced with Production Example 9, and the others were produced in the same manner as Example-1.
[0043]
Example-10
Production Example 1 of Example-2 was replaced with Production Example 10, and the others were produced in the same manner as Example-2.
[0044]
The test for which the effectiveness has been confirmed will be described below.
Angiotensin-converting enzyme inhibition test test method Add 0.25 ml of 100 mM HEPES buffer (pH 8.3) containing 5 mM Hipriluhistidylleucine to 0.5 ml of 1 mg / ml sample solution and incubate at 37 ° C. for 3 minutes. Then, 0.25 ml of 3.0 mU / ml angiotensin-1 converting enzyme (ACE) was added and reacted at 37 ° C. for 30 minutes. After adding 2.0 ml of 0.1N sodium hydroxide solution to stop the reaction, 0.1 ml of 0.2% o-phthalaldehyde methanol solution was added to form a free fluorescent derivative of histileuleucine. And left at 4 ° C. for 15 minutes. After neutralizing the reaction solution by adding 0.4 ml of 1.5 M phosphoric acid solution, the fluorescence intensity (C) at an excitation wavelength of 360 nm and a fluorescence wavelength of 480 nm was measured. The same operation was performed for the sample not containing the sample (A), the sample not containing the ACE (B), and the sample not containing the ACE (D). The rate, ie ACE inhibition rate, was calculated.
Inhibition rate (%) = {1− (C−D) / (A−B)} × 100
[0045]
The results are shown below.
Figure 2004189662
[0046]
Each of the ten examples with high blood pressure was used for 6 months, and blood pressure was measured before and after use to see a decrease in the maximum blood pressure. (10 tablets per day and 100 ml of drinks per day)
The results are shown below. (The average value of 10 people.)
Figure 2004189662
[0047]
[Effect] It was found that when angiotensin converting enzyme was inhibited as described above and the examples were consumed, blood pressure was lowered and useful. It was found that there were no side effects and safety was high.

Claims (1)

Jatoba(Hymenaea courbaril)の実の殻、グアバの葉、ムラヤ コエンジ、オオバナサルスベリ、桑葉、西河柳、仙鶴草、ミサキノハナの抽出物、コンキオリン、コンキオリン加水分解物を無水コハク酸で処理した物の1種以上を配合した、高血圧症の予防、改善作用を有するアンギオテンシン変換酵素阻害剤および抗高血圧食品1 of Jatoba (Hymenaea courbaril) husk, guava leaf, Muraya coenji, giant crape myrtle, mulberry leaf, Nishikawayanagi, Sentsukaku, Misakinohana extract, conchiolin, conchiolin hydrolyzate treated with succinic anhydride Angiotensin-converting enzyme inhibitor and antihypertensive food, which contain more than one species and have an effect of preventing and improving hypertension
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006273843A (en) * 2005-03-01 2006-10-12 Bizen Chemical Co Ltd Cyclooxygenase inhibitor and edible composition
JP2007161620A (en) * 2005-12-12 2007-06-28 Taisho Pharmaceut Co Ltd Method for producing agrimonia pilosa extract and beverage blended with the extract
WO2007119789A1 (en) * 2006-04-13 2007-10-25 Uha Mikakuto Co., Ltd. Agent for suppressing arteriosclerosis
WO2009054504A1 (en) * 2007-10-24 2009-04-30 Suntory Holdings Limited Ligand agent for peroxisome proliferator-activated receptor (ppar)
JP2014034562A (en) * 2012-08-10 2014-02-24 Lotte Kenko Sangyo:Kk Adiponectin production promoting agent
JP2019127439A (en) * 2018-01-22 2019-08-01 株式会社お茶村 Supplement comprising morus alba leaves

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0640929A (en) * 1992-07-21 1994-02-15 Kanpou Iyaku Kenkyu Shinko Zaidan Method for extracting extract of guava leaf
JPH09135671A (en) * 1995-11-15 1997-05-27 Kanagawa Pref Gov Processed mulberry leaf food and its production
JPH11332561A (en) * 1998-05-22 1999-12-07 Matsuura Yakugyo Kk Angiotensin converting enzyme inhibitor
JP2001316239A (en) * 2000-05-10 2001-11-13 Mikimoto Pharmaceut Co Ltd Skin care preparation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0640929A (en) * 1992-07-21 1994-02-15 Kanpou Iyaku Kenkyu Shinko Zaidan Method for extracting extract of guava leaf
JPH09135671A (en) * 1995-11-15 1997-05-27 Kanagawa Pref Gov Processed mulberry leaf food and its production
JPH11332561A (en) * 1998-05-22 1999-12-07 Matsuura Yakugyo Kk Angiotensin converting enzyme inhibitor
JP2001316239A (en) * 2000-05-10 2001-11-13 Mikimoto Pharmaceut Co Ltd Skin care preparation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BONET M A ET AL: "ETHNOBOTANICAL STUDY IN RIVER TENES VALLEY (CATALONIA, IBERIAN PENINSULA)", J ETHNOPHARMACOL, vol. 37, no. 3, JPN6009026433, 1992, pages 205 - 212, XP025813225, ISSN: 0001333594, DOI: 10.1016/0378-8741(92)90035-P *
DAR A ET AL: "HYPOTENSIVE EFFECT OF THE METHANOLIC EXTRACT OF MIMUSOPS ELENGI IN NORMOTENSIVE RATS", PHYTOMEDICINE, vol. 5, no. 5, JPN6009026432, 1999, pages 373 - 378, ISSN: 0001333595 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006273843A (en) * 2005-03-01 2006-10-12 Bizen Chemical Co Ltd Cyclooxygenase inhibitor and edible composition
JP2007161620A (en) * 2005-12-12 2007-06-28 Taisho Pharmaceut Co Ltd Method for producing agrimonia pilosa extract and beverage blended with the extract
WO2007119789A1 (en) * 2006-04-13 2007-10-25 Uha Mikakuto Co., Ltd. Agent for suppressing arteriosclerosis
JPWO2007119789A1 (en) * 2006-04-13 2009-08-27 ユーハ味覚糖株式会社 Arteriosclerosis inhibitor
WO2009054504A1 (en) * 2007-10-24 2009-04-30 Suntory Holdings Limited Ligand agent for peroxisome proliferator-activated receptor (ppar)
JP2014034562A (en) * 2012-08-10 2014-02-24 Lotte Kenko Sangyo:Kk Adiponectin production promoting agent
JP2019127439A (en) * 2018-01-22 2019-08-01 株式会社お茶村 Supplement comprising morus alba leaves

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