JPH1025247A - Preventive and therapeutic agent for gastritis and gastric and duodenal ulcer - Google Patents
Preventive and therapeutic agent for gastritis and gastric and duodenal ulcerInfo
- Publication number
- JPH1025247A JPH1025247A JP8198524A JP19852496A JPH1025247A JP H1025247 A JPH1025247 A JP H1025247A JP 8198524 A JP8198524 A JP 8198524A JP 19852496 A JP19852496 A JP 19852496A JP H1025247 A JPH1025247 A JP H1025247A
- Authority
- JP
- Japan
- Prior art keywords
- extract
- hop
- acid
- gastric
- gastritis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明はヘリコバクター・ピロリ
の増殖を阻害し、胃炎、胃・十二指腸潰瘍等の予防及び
治療に有効な薬剤に関する。The present invention relates to a drug which inhibits the growth of Helicobacter pylori and is effective for the prevention and treatment of gastritis, gastric / duodenal ulcer and the like.
【０００２】[0002]
【従来の技術】ヘリコバクター（Helicobacter）属菌の
一つであるヘリコバクター・ピロリ（H. pylori）は、
胃粘膜などに定着し増殖する。該菌の産生するウレアー
ゼは、体液中の尿素を加水分解しアンモニアを生成し、
このアンモニアは胃粘膜に作用して胃炎、胃潰瘍の増悪
因子として作用する。2. Description of the Related Art H. pylori, one of the genus Helicobacter,
Settles on the gastric mucosa and proliferates. Urease produced by the bacterium hydrolyzes urea in body fluids to produce ammonia,
This ammonia acts on the gastric mucosa and acts as an aggravating factor for gastritis and gastric ulcer.
【０００３】従来、胃潰瘍、十二指腸潰瘍の治療薬とし
ては胃酸分泌を抑制するＨ2受容体ブロッカーやプロト
ンポンプ阻害剤が主流であり治療効果も高いが、再発す
ることが多いことが知られている。また、胃や十二指腸
に存在するヘリコバクター・ピロリに対し抗菌活性を有
する薬剤である抗菌剤やビスマス製剤を用いる治療法が
試みられ効果を上げているが、耐性菌の出現や神経障害
等の副作用の可能性のために長期間の投与が困難であ
り、また評価も一定ではない（刈田幹夫、Prog.Med., 1
4, 2091-2095 (1994)）。[0003] Conventionally, as a remedy for gastric ulcer and duodenal ulcer, an H 2 receptor blocker or a proton pump inhibitor which suppresses gastric acid secretion has been mainstream and has a high therapeutic effect. . In addition, treatments using antibacterial agents and bismuth preparations, which are antibacterial agents against Helicobacter pylori, which are present in the stomach and duodenum, have been tried and are effective. Long-term administration is difficult due to the possibility, and the evaluation is not constant (Mikio Karita, Prog. Med., 1
4 , 2091-2095 (1994)).
【０００４】これまでの経験からその安全性が確認され
ている天然生薬中にヘリコバクター・ピロリに対する増
殖阻害活性も検討されつつあり、既にいくつかの情報が
開示されている（小橋恭一ら、特開平7-196522、特開平
7-196525、酒井達ら、特開平7-242560、及び菊池幹雄
ら、特開平8-119872）。また、茶の成分であるカテキン
に代表されるポリフェノール類がヘリコバクター・ピロ
リの増殖を抑制し、胃粘膜や十二指腸粘膜への接着を抑
制することが知られている（特開平5-139972）。[0004] In natural herbal medicines whose safety has been confirmed from past experience, the growth inhibitory activity against Helicobacter pylori is also being studied, and some information has already been disclosed (Kyoichi Kobashi et al., 7-196522, JP
7-196525, Sakai et al., JP-A-7-242560, and Kikuchi Mikio et al., JP-A-8-119872). It is also known that polyphenols represented by catechin, which is a component of tea, inhibit the growth of Helicobacter pylori and inhibit adhesion to gastric mucosa and duodenal mucosa (Japanese Patent Application Laid-Open No. 5-139972).
【０００５】[0005]
【発明が解決しようとする課題】本発明の目的は、安全
性がその長期間の使用によって確認されている天然生薬
から、ヘリコバクター・ピロリの生育を抑え、胃炎、胃
及び十二指腸潰瘍等の予防や治療に有効な薬剤を提供す
ることである。An object of the present invention is to provide a natural herbal medicine whose safety has been confirmed for a long period of time, to suppress the growth of Helicobacter pylori, to prevent gastritis, stomach and duodenal ulcers and the like. The purpose is to provide a therapeutically effective drug.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、上記課題
を解決するために広く天然生薬を検索したところ、ホッ
プの抽出物が、ヘリコバクター・ピロリの増殖を強く抑
制することを初めて見いだし、本発明を完成するに至っ
た。すなわち、本発明はヘリコバクター・ピロリの増殖
阻害作用を有するホップを胃炎、胃及び十二指腸潰瘍等
の予防や治療剤に配合することを特徴とし、好ましくは
ホップ抽出物、特に好ましくはα酸及び／又はβ酸を配
合する。Means for Solving the Problems The present inventors have searched extensively for natural crude drugs to solve the above problems, and found for the first time that hop extracts strongly inhibit the growth of Helicobacter pylori, The present invention has been completed. That is, the present invention is characterized in that hops having an inhibitory action on the growth of Helicobacter pylori are compounded in a prophylactic or therapeutic agent for gastritis, stomach and duodenal ulcer, etc., preferably hop extract, particularly preferably α-acid and / or Add β acid.
【０００７】[0007]
【発明の実施の形態】桑科の蔓性多年草であるホップ
（Humulus lupulus L.）は、全草、毬花またはビール醸
造で用いられているホップペレット、ホップエキス、イ
ソ化ホップエキスなどが利用できる。さらには、該活性
の有効成分であるα酸及びβ酸画分を抽出操作あるいは
種々の分画操作によって濃縮し用いることもできる。BEST MODE FOR CARRYING OUT THE INVENTION Hops (Humulus lupulus L.), which is a perennial plant of the mulberry family, use hop pellets, hop extracts, isomerized hop extracts, etc., which are used in whole plant, cone, or beer brewing. it can. Furthermore, the α- and β-acid fractions, which are active ingredients having the activity, can be concentrated and used by extraction or various fractionation operations.
【０００８】本発明において、抽出に使用する溶媒とし
ては水、アルコール、各種エステル類、エーテル類、各
種ケトン類、クロロフォルム等のハロゲン化炭化水素、
ヘキサン等の炭化水素などが使用できる。アルコールと
しては低級アルコール、例えばメチルアルコール、エチ
ルアルコール、ブチルアルコール、プロピルアルコール
などが使用でき、エステル類としては酢酸エチル、酢酸
アミルなどが、ケトン類としてはアセトンなどが使用で
きる。また、必要に応じて水を加え含水率を高めても良
い。抽出方法としては、当該生薬を常法に準じて加熱し
てあるいは加熱せずに抽出する方法が使用できる。In the present invention, water, alcohols, various esters, ethers, various ketones, halogenated hydrocarbons such as chloroform, etc.
Hydrocarbons such as hexane can be used. As alcohols, lower alcohols such as methyl alcohol, ethyl alcohol, butyl alcohol, and propyl alcohol can be used. As esters, ethyl acetate, amyl acetate, and the like can be used. As ketones, acetone and the like can be used. Further, if necessary, water may be added to increase the water content. As the extraction method, a method of extracting the crude drug with or without heating according to a conventional method can be used.
【０００９】本発明においては、ホップ抽出物あるいは
α酸及び／又はβ酸画分を濾液状のまま使用しても良
く、また濃縮して濃縮エキスの形で、さらには粉末状で
使用しても良い。粉末は、ドラム乾燥、減圧濃縮乾固、
凍結乾燥等により得られる。さらには、得られた抽出物
を水に懸濁し溶剤抽出を再度行うことにより、該活性成
分であるα酸及びβ酸の純度並びに含有量を上げること
ができる。該活性画分を種々のクロマトグラフィーを用
いて精製することができる。In the present invention, the hop extract or the α-acid and / or β-acid fraction may be used as a filtrate, or may be concentrated and used in the form of a concentrated extract, or in the form of a powder. Is also good. Powder is drum dried, concentrated under reduced pressure to dryness,
It can be obtained by freeze-drying or the like. Furthermore, the purity and content of the active ingredients α-acid and β-acid can be increased by suspending the obtained extract in water and performing solvent extraction again. The active fraction can be purified using various chromatography.
【００１０】本発明薬剤においては、ホップから得られ
る抽出物を単独で用いても良いし公知となっている種々
の胃腸薬に配合しても良い。従来から天然生薬として使
用されているので、安全性が高く、従って剤型や投与量
は任意に選定できる。本発明薬剤はそのまま抗菌薬剤と
して用いても良いが、薬学的に許容できる液状、固体状
の担体と配合し必要に応じて溶剤、分散剤、乳化剤、緩
衝剤、安定剤、賦形剤、結合剤、崩壊剤、滑沢剤等を加
えて、錠剤、顆粒剤、散剤、粉末剤、カプセル剤等に製
剤して使用するのが適当である。In the drug of the present invention, the extract obtained from hops may be used alone or may be mixed with various known gastrointestinal drugs. Since it has been conventionally used as a natural crude drug, its safety is high, and the dosage form and dosage can be arbitrarily selected. The drug of the present invention may be used as it is as an antibacterial drug, but may be blended with a pharmaceutically acceptable liquid or solid carrier and optionally used as a solvent, dispersant, emulsifier, buffer, stabilizer, excipient, or binder. It is appropriate to add tablets, granules, powders, powders, capsules, etc. to the preparations, and to use them with adding agents, disintegrants, lubricants and the like.
【００１１】本発明の薬剤は、成人一人、一日あたりの
好適投与量は、抽出エキスとして約１〜2000mg、好まし
くは10〜1000mgである。本薬剤は、そのまま経口投与す
るか、抽出エキスだけを任意の飲食品に添加し日常的に
摂取させることもできる。The preferred dose of the drug of the present invention per adult per day is about 1 to 2000 mg, preferably 10 to 1000 mg, as an extract. This drug can be administered orally as it is, or can be taken on a daily basis by adding only an extract to any food or drink.
【００１２】[0012]
【実施例】以下、実施例により具体的に説明するが、本
発明はこれらに限定されるものではない。 実施例１ ホップ毬花100gを粉砕し、メタノール400 ミリリットル
を加え２時間加熱還流し、抽出した。濾過して抽出液を
集めた。続いて濾過残渣にメタノール300 ミリリットル
を加え同様にして２回加熱還流し、抽出した。濾過して
抽出液を分け、先の抽出液と合わせた後、減圧濃縮して
溶媒を留去し抽出物26ｇを得た。EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto. Example 1 100 g of hop cones were pulverized, 400 ml of methanol was added, and the mixture was heated under reflux for 2 hours and extracted. The extract was collected by filtration. Subsequently, 300 ml of methanol was added to the filtration residue, and the mixture was heated and refluxed twice for extraction in the same manner. The extract was separated by filtration, combined with the above extract, concentrated under reduced pressure, and the solvent was distilled off to obtain 26 g of extract.
【００１３】実施例２ 実施例１で得た抽出物22ｇにｎ−ヘキサン300 ミリリッ
トルを加え攪拌しながら２時間還流抽出した。濾過して
抽出液を分離した。その後に、残渣に300 ミリリットル
のｎ−ヘキサンを加え再び同じ条件にて抽出を行った。
濾過後、濾液を集め先の濾液と併せて減圧濃縮し8.7gの
抽出物を得た。Example 2 300 ml of n-hexane was added to 22 g of the extract obtained in Example 1, and the mixture was refluxed for 2 hours while stirring. The extract was separated by filtration. Thereafter, 300 ml of n-hexane was added to the residue, and extraction was performed again under the same conditions.
After filtration, the filtrate was collected and concentrated under reduced pressure together with the filtrate to obtain 8.7 g of an extract.
【００１４】実施例３ 実施例２で得られた濾過残渣にクロロフォルム300 ミリ
リットルを加え攪拌しながら２時間抽出を行った。濾過
して濾液を分離した後、濾過残渣に再びクロロフォルム
300 ミリリットルを加え同様に攪拌抽出を行った。濾過
して濾液を集め、先の濾液と併せて減圧濃縮し６ｇの抽
出物を得た。一方、濾液を分離した後の濾過残渣を乾燥
することにより、5.6gの抽出残渣を得た。Example 3 300 ml of chloroform was added to the filtration residue obtained in Example 2 and extraction was carried out for 2 hours while stirring. After filtration to separate the filtrate, chloroform
300 ml was added and the mixture was stirred and extracted in the same manner. The filtrate was collected by filtration, and concentrated under reduced pressure together with the filtrate to obtain 6 g of an extract. On the other hand, the filtration residue after separating the filtrate was dried to obtain 5.6 g of an extraction residue.
【００１５】実施例４ 実施例１、２及び３で得られた各抽出物のH. pyloriに
対する増殖抑制試験をin vitroで行った。ブルセラ寒天
培地（Brucella agar）にＢＳＡ fraction Vを0.5mg 添
加した寒天平板培地に被検菌液108 cfu/mlを0.1ml 塗抹
した。次に試料を所定の濃度になるよう希釈調製した溶
液20μl を感受性測定用ペーパーディスクに吸収させ、
先に調製した寒天培地上に置き37℃で３日間微好気条件
下（Ｏ2５％、ＣＯ2 １５％、Ｎ2 ８０％）で培養し
た。ディスク周辺の生育阻止帯の有無を観察し、発育阻
止帯の認められた最少濃度をDisc-MICとした。その結果
を表１に示す。菌株番号ＣＬＯ１及びＣＬＯ２は臨床分
離株、ＣＬＯ36はマクロライド耐性臨床分離株、ＮＣＴ
Ｃ11916 及びＮＣＴＣ11637 は標準株である。ＮＣＴＣ
は英国の菌株寄託機関（National Collection of Type
Cultures, London, England）の略称である。Example 4 A growth inhibition test for each extract obtained in Examples 1, 2 and 3 against H. pylori was performed in vitro. 0.1 ml of the test bacterial solution (10 8 cfu / ml) was spread on an agar plate medium obtained by adding 0.5 mg of BSA fraction V to Brucella agar medium (Brucella agar). Next, absorb 20 μl of the solution prepared by diluting the sample to a predetermined concentration on a sensitivity measurement paper disc,
The plate was placed on the previously prepared agar medium and cultured at 37 ° C. for 3 days under microaerobic conditions (O 2 5%, CO 2 15%, N 2 80%). The presence or absence of a growth inhibition zone around the disk was observed, and the minimum concentration at which the growth inhibition zone was recognized was defined as Disc-MIC. Table 1 shows the results. Strain numbers CLO1 and CLO2 are clinical isolates, CLO36 is a macrolide resistant clinical isolate, NCT
C11916 and NCTC11637 are standard strains. NCTC
Is the National Collection of Type
Cultures, London, England).
【００１６】[0016]
【表１】 [Table 1]
【００１７】実施例５ 実施例４で得られた結果から抽出物ＭＩＣ以上を胃の中
で維持すればH.pyloriの増殖を抑制することができると
考えられる。ホップ抽出物配合剤の調製を以下のように
行った。 組成 ホップ抽出エキス（ヘキサン抽出物） 300 mg 結晶セルロース 300 mg ステアリン酸マグネシウム 70 mg 乳糖 30 mg 700 mg／錠 上記組成物を混合乾燥し打錠した。Example 5 From the results obtained in Example 4, it is considered that the growth of H. pylori can be suppressed if the extract MIC or higher is maintained in the stomach. The preparation of the hop extract formulation was performed as follows. Composition Hop extract (hexane extract) 300 mg Crystalline cellulose 300 mg Magnesium stearate 70 mg Lactose 30 mg 700 mg / tablet The above composition was mixed, dried and tableted.
【００１８】打錠した錠剤を1.5 リットルの水にて２時
間十分攪拌しながら溶解した。この溶液の20μl を実施
例４で測定したと全く同様にしてH. pyloriに対する増
殖抑制作用を試験した結果、増殖抑制が認められた。成
人の胃の容積は約1.5 リットルであり上記錠剤を１回に
１錠服用すれば、胃の中の平均濃度は200 μg/mlとなり
実施例４で得られた値0.013 ％（130 μg/ml）以上とな
るので、該菌の増殖を抑制できる。The compressed tablets were dissolved in 1.5 liters of water with sufficient stirring for 2 hours. 20 μl of this solution was tested for its growth inhibitory effect on H. pylori in exactly the same manner as in Example 4, and as a result, growth inhibition was observed. The volume of an adult stomach is about 1.5 liters, and if one tablet is taken at a time, the average concentration in the stomach is 200 μg / ml, the value obtained in Example 4 being 0.013% (130 μg / ml). ), The growth of the bacterium can be suppressed.
【００１９】実施例６ 実施例２で得られたヘキサン抽出画分５ｇをシリカゲル
（メルク社製、art.9385）を用いたカラムクロマトグラ
フィーを行いα酸及びβ酸の分離を行った。内径４セン
チメートル、長さ40センチメートルのカラム管に上記シ
リカゲルを充填しヘキサン／酢酸エチルの混合溶媒で活
性画分を溶出した。酢酸エチルの濃度を順次増加させ、
ヘキサン／酢酸エチル＝９：１でβ酸を主要成分とする
画分がまたヘキサン／酢酸エチル＝１：15でα酸画分が
溶出された。各溶出された画分の主成分の確認は高速液
体クロマトグラフィー（島津社製ＬＣ−８Ａ、ＯＤＳカ
ラム（２ｃｍ×25cm）、移動相80〜95％アセトニトリル
／水、流速10ml／分）で分取した後、マススペクトル、
ＩＲスペクトル、ＮＭＲスペクトルを測定して行った。Example 6 5 g of the hexane-extracted fraction obtained in Example 2 was subjected to column chromatography using silica gel (manufactured by Merck, art. 9385) to separate α-acid and β-acid. The silica gel was packed in a column tube having an inner diameter of 4 cm and a length of 40 cm, and the active fraction was eluted with a mixed solvent of hexane / ethyl acetate. Increasing the concentration of ethyl acetate sequentially,
A fraction containing β-acid as a main component was eluted with hexane / ethyl acetate = 9: 1, and an α-acid fraction was eluted with hexane / ethyl acetate = 1: 15. The main component of each eluted fraction was confirmed by high-performance liquid chromatography (LC-8A, Shimadzu Corporation, ODS column (2 cm x 25 cm), mobile phase 80-95% acetonitrile / water, flow rate 10 ml / min). After that, mass spectrum,
The measurement was performed by measuring an IR spectrum and an NMR spectrum.
【００２０】実施例７ 実施例６で得られたβ酸画分、イソ化ホップエキスから
得られるイソα酸及びα酸とβ酸の混合物（60：40）の
Helicobacter pyloriに対する増殖阻害活性を実施例４
に記載の方法と全く同様にして測定した。結果を表２に
示す。Example 7 The β-acid fraction obtained in Example 6, the iso-α-acid obtained from the isomerized hop extract and the mixture of α-acid and β-acid (60:40)
Example 4 Growth Inhibitory Activity against Helicobacter pylori
The measurement was performed in exactly the same manner as described in the above section. Table 2 shows the results.
【００２１】[0021]
【表２】 [Table 2]
【００２２】実施例８ 実施例７によって明らかとなったα酸及びβ酸画分を用
いて実施例５と同様にしてα酸及びβ酸混合物を配合し
た錠剤を作製した。錠剤の組成は実施例５に記載のホッ
プ抽出エキスの代わりにα酸及びβ酸混合物を用いて作
製した。打錠した錠剤を1.5 リットルの水にて２時間十
分攪拌しながら溶解した。この溶液の20μl を実施例４
で測定したと全く同様にしてH. pyloriに対する増殖抑
制作用を試験した結果、増殖抑制が認められた。Example 8 A tablet containing a mixture of α-acid and β-acid was prepared in the same manner as in Example 5 using the α-acid and β-acid fractions identified in Example 7. The composition of the tablets was prepared using a mixture of α-acid and β-acid instead of the hop extract described in Example 5. The compressed tablets were dissolved in 1.5 liters of water with sufficient stirring for 2 hours. 20 μl of this solution was used in Example 4.
As a result of a test of the growth inhibitory effect on H. pylori in exactly the same manner as that described above, growth inhibition was observed.
【００２３】[0023]
【発明の効果】上述したように、本発明によれば菌類、
特にヘリコバクター・ピロリの生育を抑制し、胃炎、胃
及び十二指腸潰瘍の予防や治療に有効な薬剤を提供でき
る。本発明の薬剤は健胃生薬として知られるホップから
得られる抽出物であるので、安全性も高く、長期投与も
可能である点で優れている。As described above, according to the present invention, fungi,
In particular, it can provide a drug that suppresses the growth of Helicobacter pylori and is effective in preventing and treating gastritis, stomach and duodenal ulcer. Since the drug of the present invention is an extract obtained from hops known as stomach crude drugs, it is excellent in safety and high in long-term administration.
Claims (3)
pylori）の増殖阻害作用を有するホップを配合するこ
とを特徴とする胃炎、胃・十二指腸潰瘍の予防及び治療
剤。[Claim 1] Helicobacter pylori
A prophylactic and therapeutic agent for gastritis and gastric / duodenal ulcer, which comprises hops having an inhibitory effect on the growth of pylori).
る請求項１記載の予防及び治療剤。2. The preventive and therapeutic agent according to claim 1, further comprising a hop extract.
ることを特徴とする請求項１記載の予防及び治療剤。3. The preventive and therapeutic agent according to claim 1, wherein the hop extract is an α-acid and / or a β-acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8198524A JPH1025247A (en) | 1996-07-10 | 1996-07-10 | Preventive and therapeutic agent for gastritis and gastric and duodenal ulcer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8198524A JPH1025247A (en) | 1996-07-10 | 1996-07-10 | Preventive and therapeutic agent for gastritis and gastric and duodenal ulcer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH1025247A true JPH1025247A (en) | 1998-01-27 |
Family
ID=16392582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8198524A Pending JPH1025247A (en) | 1996-07-10 | 1996-07-10 | Preventive and therapeutic agent for gastritis and gastric and duodenal ulcer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH1025247A (en) |
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- 1996-07-10 JP JP8198524A patent/JPH1025247A/en active Pending
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