JPWO2011034039A1 - Helicobacter pylori disinfectant - Google Patents
Helicobacter pylori disinfectant Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/08—Oxides; Hydroxides
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- A—HUMAN NECESSITIES
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- A61K33/44—Elemental carbon, e.g. charcoal, carbon black
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
本発明に係るピロリ菌の除菌剤は、アンモニア又はアンモニウムイオンの吸着材を含むものであり、本発明に係るピロリ菌の除菌方法は、ピロリ菌に感染した胃内に本発明に係る除菌剤を導入するものである。ピロリ菌が胃内の強酸性環境で棲息できるのは、尿素からアンモニアを生成し、胃酸を中和しているためである。そこで、本発明では、アンモニア又はアンモニウムイオンの吸着材(活性炭、シリカゲル、アルミナ、ゼオライト、陽イオン交換材等)を含む除菌剤を胃内に導入し、アンモニア又はアンモニウムイオンを吸着することで、ピロリ菌が棲息し難い環境とし、ピロリ菌を除菌する。The sterilizing agent for Helicobacter pylori according to the present invention contains an adsorbent for ammonia or ammonium ions, and the sterilizing method for Helicobacter pylori according to the present invention includes a method for eradicating Helicobacter pylori in the stomach infected with Helicobacter pylori. Introducing fungicides. H. pylori can live in a strongly acidic environment in the stomach because it produces ammonia from urea and neutralizes gastric acid. Therefore, in the present invention, by introducing a disinfectant containing an adsorbent of ammonia or ammonium ions (activated carbon, silica gel, alumina, zeolite, cation exchange material, etc.) into the stomach and adsorbing ammonia or ammonium ions, The environment where Helicobacter pylori is difficult to live in is eradicated.
Description
本発明は、ヘリコバクター・ピロリ(Helicobacter pylori;以下、適宜「ピロリ菌」という。)の除菌剤及びそれを用いた除菌方法に関する。 The present invention relates to a disinfectant for Helicobacter pylori (hereinafter referred to as “H. pylori” as appropriate) and a disinfecting method using the disinfectant.
ピロリ菌は、慢性胃炎、胃及び十二指腸潰瘍の慢性化因子又は再発因子であり、世界の人口の50%が感染していると言われている。このピロリ菌は、自然環境においては動物の胃内のみで増殖可能であり、ヒト、サル、ネコ、ブタ、イヌに感染することが明らかになっている。ピロリ菌はウレアーゼ活性を有し、尿素からアンモニアを生成することで、胃酸を中和して胃内の強酸性環境で棲息していると考えられている。 H. pylori is a chronic or recurrent factor in chronic gastritis, stomach and duodenal ulcers, and is said to be infected by 50% of the world population. This H. pylori can grow only in the stomach of animals in the natural environment and has been shown to infect humans, monkeys, cats, pigs and dogs. Helicobacter pylori has urease activity and is considered to live in a strong acidic environment in the stomach by neutralizing gastric acid by producing ammonia from urea.
現在、ピロリ菌の除菌には、抗生物質(アモキシシリン、クラリスロマイシン)とプロトンポンプ阻害剤とを組み合わせた3投与剤併用療法が行われているが、抗生物質に対する耐性菌の出現により、この方法で完全に除菌することは難しくなりつつある(非特許文献1)。このため、新たな抗生物質(メトロニダゾール、レボフロキサン)を用いた2次、3次除菌法も試みられている。しかし、これらの除菌方法は人体にとって有用な腸内細菌の働きにも影響するため、下痢等の副作用を伴うといった問題がある。 Currently, three-drug combination therapy combining antibiotics (amoxicillin, clarithromycin) and proton pump inhibitors is being used to eliminate H. pylori. Due to the emergence of antibiotic-resistant bacteria, It is becoming difficult to completely sterilize by the method (Non-Patent Document 1). For this reason, secondary and tertiary sterilization methods using new antibiotics (metronidazole, levofloxane) have also been attempted. However, since these sterilization methods also affect the function of enteric bacteria useful for the human body, there is a problem that side effects such as diarrhea are involved.
そこで、最近になり、副作用の少ない除菌方法として、3投与剤併用療法に加えて糖とタンパク質の褐色反応生成物投与剤を併用する方法(特許文献1)、ピロリ菌の胃壁への定着を阻害するフコイダンを投与する方法(特許文献2)、ピロリ菌の増殖を抑制するβ1−4結合を有する糖類を投与する方法(特許文献3)、等が提案されている。また、プロバイオティクス(乳酸菌等)との併用治療も報告されている(非特許文献2)。しかし、これらの作用メカニズムは必ずしも明確になっているとは言い難く、また、除菌方法としても未だ確立されてはいない。 Therefore, recently, as a sterilization method with few side effects, in addition to the three-dose combination therapy, a method of using a brown reaction product administration agent of sugar and protein (Patent Document 1), fixing of Helicobacter pylori to the stomach wall A method of administering fucoidan for inhibition (Patent Document 2), a method of administering a saccharide having a β1-4 bond that suppresses the growth of H. pylori (Patent Document 3), and the like have been proposed. Moreover, combined treatment with probiotics (lactic acid bacteria etc.) has also been reported (Non-patent Document 2). However, it is difficult to say that these mechanisms of action have been clarified and have not yet been established as a sterilization method.
そこで、本発明は、副作用の少ない新規なピロリ菌の除菌剤及びそれを用いた除菌方法を提供することを目的とする。 Therefore, an object of the present invention is to provide a novel sterilizing agent for H. pylori with few side effects and a sterilizing method using the same.
本発明者らは、ピロリ菌が胃内の強酸性環境で棲息できるのは、尿素からアンモニアを生成し、胃酸を中和しているためであるという点に着目して鋭意研究を行った。その結果、アンモニア又はアンモニウムイオンの吸着剤を胃内に導入し、ピロリ菌が棲息し難い環境とすることで、ピロリ菌の除菌が可能であることを見出し、本発明を完成するに至った。具体的には、本発明は以下のとおりである。 The present inventors have conducted earnest research focusing on the fact that H. pylori can live in a strongly acidic environment in the stomach because ammonia is produced from urea and gastric acid is neutralized. As a result, it was found that by introducing an adsorbent of ammonia or ammonium ions into the stomach and making it difficult for H. pylori to live, it was found that H. pylori can be sterilized and the present invention was completed. . Specifically, the present invention is as follows.
(1) アンモニア又はアンモニウムイオンの吸着材を含むヘリコバクター・ピロリの除菌剤。
(2) 前記アンモニア又はアンモニウムイオンの吸着材が、活性炭、シリカゲル、アルミナ、ゼオライト、及び陽イオン交換材からなる群から選択される少なくとも1種である上記(1)記載の除菌剤。
(3) ヘリコバクター・ピロリに感染した胃内に上記(1)又は(2)記載の除菌剤を導入するヘリコバクター・ピロリの除菌方法。(1) A Helicobacter pylori disinfectant containing an ammonia or ammonium ion adsorbent.
(2) The disinfectant according to (1), wherein the ammonia or ammonium ion adsorbent is at least one selected from the group consisting of activated carbon, silica gel, alumina, zeolite, and a cation exchange material.
(3) A method for sterilizing Helicobacter pylori, wherein the sterilizing agent according to (1) or (2) is introduced into a stomach infected with Helicobacter pylori.
本発明によれば、副作用の少ない新規なピロリ菌の除菌剤及びそれを用いた除菌方法を提供することができる。 According to the present invention, it is possible to provide a novel sterilizing agent for Helicobacter pylori with few side effects and a sterilizing method using the same.
本発明に係るピロリ菌の除菌剤は、アンモニア又はアンモニウムイオンの吸着材を含むものである。また、本発明に係るピロリ菌の除菌方法は、ピロリ菌に感染した胃内に本発明に係る除菌剤を導入するものである。 The disinfectant for Helicobacter pylori according to the present invention contains an adsorbent for ammonia or ammonium ions. Moreover, the sterilization method of Helicobacter pylori according to the present invention introduces the disinfectant according to the present invention into the stomach infected with Helicobacter pylori.
前述したように、ピロリ菌が胃内の強酸性環境で棲息できるのは、尿素からアンモニアを生成し、胃酸を中和しているためである。そこで、本発明に係るピロリ菌の除菌方法では、アンモニア又はアンモニウムイオンの吸着材を含む除菌剤を胃内に導入し、アンモニア又はアンモニウムイオンを吸着することで、ピロリ菌が棲息し難い環境とし、ピロリ菌を除菌する。言い換えれば、本発明に係る除菌方法は、胃酸の中和を妨害することによってピロリ菌を除菌するものである。これは、抗生物質による直接的な除菌方法とは対照的に、間接的な除菌方法と言える。 As described above, H. pylori can live in a strongly acidic environment in the stomach because it produces ammonia from urea and neutralizes gastric acid. Therefore, in the method for sterilizing Helicobacter pylori according to the present invention, a sterilizing agent containing an adsorbent for ammonia or ammonium ions is introduced into the stomach, and the ammonia or ammonium ions are adsorbed, so that Helicobacter pylori is less likely to live. And sterilize H. pylori. In other words, the sterilization method according to the present invention sterilizes H. pylori by interfering with neutralization of gastric acid. This is an indirect sterilization method as opposed to a direct sterilization method with antibiotics.
特に、ピロリ菌は胃粘膜表面にのみ棲息しており、胃深部粘膜では発見されていない。その理由は、胃深部粘膜に存在する特異な糖タンパク質の糖鎖末端部分のcis−N−アセチル−D−グルコサミンがピロリ菌の増殖を抑制するためとされている(Science, vol.305, 2004, pp.1003−1006)。このようにピロリ菌は胃粘膜表面に棲息していることから、胃内に導入するのみで、除菌剤がピロリ菌の周囲まで到達すると考えられる。 In particular, Helicobacter pylori is resident only on the gastric mucosal surface and has not been found in the deep gastric mucosa. The reason is that cis-N-acetyl-D-glucosamine at the end of the sugar chain of a specific glycoprotein present in the deep gastric mucosa suppresses the growth of H. pylori (Science, vol. 305, 2004). , Pp. 1003-1006). Thus, since H. pylori is resident on the gastric mucosal surface, it is considered that the disinfectant reaches the periphery of H. pylori only by introducing it into the stomach.
上記アンモニア又はアンモニウムイオンの吸着材としては、アンモニア又はアンモニウムイオンに対する吸着能を有するものであれば特に限定されない。例えば、活性炭、シリカゲル、アルミナ、ゼオライト、及び陽イオン交換材からなる群から選択される少なくとも1種を用いることができる。これらの吸着材は、胃粘膜への付着性やアンモニア又はアンモニウムイオンに対する吸着能を高める観点から、粉末状又は微粒子状であることが好ましい。 The adsorbent for ammonia or ammonium ions is not particularly limited as long as it has adsorbability for ammonia or ammonium ions. For example, at least one selected from the group consisting of activated carbon, silica gel, alumina, zeolite, and cation exchange material can be used. These adsorbents are preferably in the form of powder or fine particles from the viewpoint of enhancing the adhesion to the gastric mucosa and the ability to adsorb ammonia or ammonium ions.
上記活性炭の原料となる炭素原料としては、オガ屑、木材、ヤシ穀、オイルカーボン、フェノール樹脂、セルロース、アクリロニトリル、石炭ピッチ、石油ピッチ等の公知の原料を用いることができる。 As a carbon raw material used as the raw material of the said activated carbon, well-known raw materials, such as sawdust, wood, coconut cereal, oil carbon, a phenol resin, a cellulose, an acrylonitrile, coal pitch, petroleum pitch, can be used.
この中でも、純度90%以上の高純度セルロースが好ましく、純度95%以上の高純度セルロースがより好ましい。高純度セルロースの素材としては、銅アンモニアレーヨン、ビスコースレーヨン、コットン、パルプ、リンター、ポリノジック、リヨセル(テンセル)等の公知の素材を用いることができる。 Among these, high-purity cellulose having a purity of 90% or more is preferable, and high-purity cellulose having a purity of 95% or more is more preferable. Known materials such as copper ammonia rayon, viscose rayon, cotton, pulp, linter, polynosic, and lyocell (Tencel) can be used as the high purity cellulose material.
活性炭を製造するには、上記の炭素原料を電気炉等により焼成する。焼成温度としては300〜1500℃が好ましく、500〜1000℃がより好ましい。なお、焼成温度の低い方がアンモニアの吸着能が高まる傾向がある。 In order to produce activated carbon, the above carbon raw material is fired in an electric furnace or the like. As a calcination temperature, 300-1500 degreeC is preferable and 500-1000 degreeC is more preferable. In addition, there exists a tendency for the one where a calcination temperature is lower to adsorb | suck ammonia.
なお、この活性炭は、賦活化処理を行ったものであっても賦活化処理を行っていないものであってもよい。 In addition, even if this activated carbon has performed the activation process, the thing which has not performed the activation process may be sufficient.
上記シリカゲル、アルミナ、ゼオライトとしては、従来からアンモニア又はアンモニウムイオンの吸着材として用いられているものを特に限定されずに用いることができる。
上記陽イオン交換材としては、強酸性陽イオン交換樹脂(官能基として−SO3Hを有する)、弱酸性陽イオン交換樹脂(官能基として−COOHを有する)等を用いることができる。As the silica gel, alumina, and zeolite, those conventionally used as adsorbents for ammonia or ammonium ions can be used without particular limitation.
As the cation exchange material, a strong acid cation exchange resin (having —SO 3 H as a functional group), a weak acid cation exchange resin (having —COOH as a functional group), or the like can be used.
これらの吸着材は、セルロース、ニトロセルロース、ゼラチン、ポリアクリロアミド、ポリメタクリレート等の親水性のポーラスポリマーで被覆されていてもよい。このように被覆することにより、胃粘膜細胞の損傷を防ぐことができる。 These adsorbents may be coated with a hydrophilic porous polymer such as cellulose, nitrocellulose, gelatin, polyacrylamide, or polymethacrylate. By covering in this way, damage to gastric mucosal cells can be prevented.
本発明に係る除菌剤を胃内に導入する方法としては、経口投与や内視鏡で観察しながら直接投与する方法等が挙げられる。
特に、経口投与する場合には、必要に応じて、散剤、顆粒剤、錠剤、糖衣錠、カプセル剤、液剤等への加工を行ってもよい。また、食品(ガム、キャンディー、ゼリー、ヨーグルト等)や飲料に混入させ、通常の飲食品と同様に摂取することも可能である。Examples of the method for introducing the disinfectant according to the present invention into the stomach include oral administration and direct administration while observing with an endoscope.
In particular, in the case of oral administration, processing into powders, granules, tablets, dragees, capsules, liquids and the like may be performed as necessary. It can also be mixed with foods (gum, candy, jelly, yogurt, etc.) and beverages and ingested in the same manner as ordinary foods and drinks.
本発明に係る除菌剤は、胃で消化されたり吸収されたりすることがなく、かつ、胃粘膜に損傷を与えることがない。したがって、継続的に一定期間、かつ、適量を胃内に導入することによって、副作用の心配なく、ピロリ菌を徐々に減らすことができる。特に、食品や医療用として用いられている材料を用いれば、安全で安価な除菌剤を提供することができる。
さらに、本発明に係る除菌剤のメカニズムから、抗生物質耐性(非感受性)菌に対しても除菌効果が期待できる。The disinfectant according to the present invention is not digested or absorbed in the stomach and does not damage the gastric mucosa. Therefore, H. pylori can be gradually reduced by introducing an appropriate amount into the stomach continuously for a certain period of time without worrying about side effects. In particular, if a material used for food or medical use is used, a safe and inexpensive disinfectant can be provided.
Furthermore, from the mechanism of the disinfectant according to the present invention, a disinfecting effect can be expected for antibiotic-resistant (insensitive) bacteria.
なお、本発明に係る除菌方法は単独で実施してもよいが、従来公知の除菌方法と併用するようにしても構わない。例えば、本発明に係る除菌方法で除菌した後に3投与剤併用療法による除菌を行うことで、抗生物質の使用量を減らす効果も期待できる(Hericobactor Research, vol.8, No.1, 24, pp.86−87)。 The sterilization method according to the present invention may be carried out alone or in combination with a conventionally known sterilization method. For example, the effect of reducing the amount of antibiotics can be expected by sterilization by the triple-drug combination therapy after sterilization by the sterilization method according to the present invention (Hericobacter Research, vol. 8, No. 1, 24, pp. 86-87).
以下、本発明の実施例について説明する。なお、本発明は下記の実施例に限定して解釈すべきではなく、特許請求の範囲における記載の範囲内で種々の変更が可能である。 Examples of the present invention will be described below. The present invention should not be construed as being limited to the following examples, and various modifications can be made within the scope of the claims.
[実施例1]
ピロリ菌の除菌効果を評価するために、以下の実験を行った。
本実験で使用したピロリ菌は、理化学研究所バイオリソースセンターより提供された菌株(Campylobacter pylori subsp. pylori、JCM No.12093)である。
培養ディッシュとしては以下(a),(b)の2種類を用いた。
(a)トリプチケースソイII 5%ヒツジ血液寒天培地(Becton Dickinson製、cat251239)
(b)ピロリ寒天培地(極東製薬製、code05561)
上記(a)の培養ディッシュは、ピロリ菌株をストックするための増殖に使用した。
また、上記(b)の培養ディッシュは、上記(a)の培養ディッシュで増殖されたピロリ菌に対し、以下に述べる各々の処理をした後で菌体(コロニー形成)の様子を観察するために使用した。このピロリ寒天培地は、培地に添加されている選択剤により、ピロリ菌以外の発育が抑制され、また、テトラゾリウムバイオレッドの添加によりピロリ菌のコロニーが紫色に着色するため確認が容易であるといった特徴がある。[Example 1]
In order to evaluate the sterilization effect of Helicobacter pylori, the following experiment was conducted.
The Helicobacter pylori used in this experiment is a strain (Campylobacter pylori subsp. Pylori, JCM No. 12093) provided by RIKEN BioResource Center.
As the culture dish, the following two types (a) and (b) were used.
(A) Trypticase Soi II 5% sheep blood agar medium (Becton Dickinson, cat251239)
(B) H. pylori agar medium (manufactured by Kyokuto Pharmaceutical Co., Ltd., code05561)
The culture dish (a) was used for growth to stock H. pylori strains.
The culture dish (b) is for observing the state of bacterial cells (colony formation) after each treatment described below for H. pylori grown in the culture dish (a). used. This H. pylori agar medium is characterized by the fact that growth other than H. pylori is suppressed by the selection agent added to the medium, and that the addition of tetrazolium biored makes the H. pylori colony colored purple. There is.
まず、ピロリ菌を0.7mLのPBSで混釈し、ピロリ寒天培地に植菌後、アネロパック微好気パウチ用セット(微好気培養、酸素濃度6〜12%、炭酸ガス濃度5〜8%;三菱ガス化学製、MGC A−18)を使用して、37℃で3日間培養した。培養後のコロニー形成の様子を図1に示す。 First, pylori is mixed with 0.7 mL of PBS, inoculated on H. pylori agar medium, and set for aneropack microaerobic pouch (microaerobic culture, oxygen concentration 6-12%, carbon dioxide concentration 5-8% Cultivated at 37 ° C. for 3 days using Mitsubishi Gas Chemical Co., Ltd., MGC A-18). The appearance of colony formation after culture is shown in FIG.
次に、ピロリ菌を0.7mLのPBSで混釈し、3つのピロリ寒天培地にそれぞれ植菌後、上記のアネロパック微好気パウチ用セットを使用して、37℃で1日間培養した。そして、1つのピロリ寒天培地には0.1M塩酸0.5mLを散布し、残り2つのピロリ寒天培地には、賦活化処理を行っていない活性炭粉末A又は活性炭粉末B(いずれも10mg)を分散させた0.1M塩酸0.5mLを散布して、さらに3日間培養した。
なお、活性炭粉末Aは1000℃で焼成したものであり、アンモニア吸着能が低く、活性炭粉末Bは500℃で焼成したものであり、アンモニア吸着能が高い。Next, H. pylori was mixed with 0.7 mL of PBS, inoculated on each of the three H. pylori agar media, and cultured at 37 ° C. for 1 day using the above set for aneropack microaerobic pouch. Then, 0.5 mL of 0.1M hydrochloric acid is sprayed on one H. pylori agar medium, and activated charcoal powder A or activated carbon powder B (both 10 mg) that has not been activated is dispersed in the remaining two H. pylori agar mediums. After spraying 0.5 mL of 0.1 M hydrochloric acid, the cells were further cultured for 3 days.
The activated carbon powder A is fired at 1000 ° C. and has a low ammonia adsorption capacity, and the activated carbon powder B is fired at 500 ° C. and has a high ammonia adsorption capacity.
培養後のコロニー形成の様子を図2A〜図2Cに示す。図2Aは活性炭粉末を分散させていないものであり、図2Bは活性炭粉末Aを分散させたものであり、図2Cは活性炭粉末Bを分散させたものである。図2B、図2Cにおいては、コロニーを丸で囲んでいる。また、それぞれにおけるコロニー面積(mm2)の総和を図3に示す。The appearance of colony formation after culture is shown in FIGS. 2A to 2C. 2A shows a case where activated carbon powder is not dispersed, FIG. 2B shows a case where activated carbon powder A is dispersed, and FIG. 2C shows a case where activated carbon powder B is dispersed. In FIG. 2B and FIG. 2C, the colony is circled. Moreover, the sum total of the colony area (mm < 2 >) in each is shown in FIG.
図1〜図3から分かるように、PBSや0.1M塩酸を散布した場合にはピロリ菌が増殖したが、活性炭粉末A,Bを分散させた0.1M塩酸を散布した場合にはコロニーの数や面積が減少した。また、この減少割合はアンモニア吸着能と正に相関していた。この結果から以下のことが示唆される。すなわち、ピロリ菌が塩酸中で繁殖するためには、尿素をウレアーゼで分解してアンモニアを発生させ、塩酸を中和する必要があるが、活性炭の存在下ではアンモニアが吸着されてしまうため、塩酸を中和できず、塩酸に晒し続けられることになり、繁殖が阻害される。 As can be seen from FIGS. 1 to 3, H. pylori grew when sprayed with PBS or 0.1M hydrochloric acid, but when 0.1M hydrochloric acid dispersed with activated carbon powders A and B was sprayed, Number and area decreased. Moreover, this reduction rate was positively correlated with the ammonia adsorption capacity. This result suggests the following. In other words, in order for H. pylori to grow in hydrochloric acid, it is necessary to decompose urea with urease to generate ammonia and neutralize hydrochloric acid. However, ammonia is adsorbed in the presence of activated carbon, so hydrochloric acid Can not be neutralized, it will continue to be exposed to hydrochloric acid, and breeding will be inhibited.
次に、培養条件を同一にするために、1つのピロリ寒天培地のみを用いて同様の実験を行った。
ピロリ菌を0.7mLのPBSで混釈し、1つのピロリ寒天培地に植菌後、上記のアネロパック微好気パウチ用セットを使用して、37℃で1日間培養した。そして、ピロリ寒天培地の4隅に直径7mmの穴を設け、その中に、市販品又は試作品の活性炭粉末5mgを分散させた0.1M塩酸0.2mL、又は0.1M塩酸0.2mLを満たし、さらに3日間培養した。Next, in order to make the culture conditions the same, the same experiment was performed using only one H. pylori agar medium.
H. pylori was mixed with 0.7 mL of PBS, inoculated on one H. pylori agar medium, and cultured at 37 ° C. for 1 day using the above set for aneropack microaerobic pouch. A hole with a diameter of 7 mm is provided at the four corners of the H. pylori agar medium, and 0.2 mL of 0.1 M hydrochloric acid or 5 mL of 0.1 M hydrochloric acid in which 5 mg of a commercially available product or a prototype activated carbon powder is dispersed. Filled and further cultured for 3 days.
培養後の増殖阻止域の様子を図4に示す。図4の(1)は高純度セルロースを500℃で焼成した活性炭粉末(試作品)を分散させたものであり、(2)は高純度セルロースを1000℃で焼成した活性炭粉末(試作品)を分散させたものであり、(3)は呉羽化学工業製の「クレメジン」を分散させたものであり、(4)は活性炭粉末を分散させていないものである。また、図4の(1)〜(3)における増殖阻止域の幅(mm)と、(1)〜(3)で用いた活性炭粉末のアンモニア吸着能(ppm)とを図5に示す。 The state of the growth inhibition zone after culture is shown in FIG. (1) in FIG. 4 is a dispersion of activated carbon powder (prototype) obtained by firing high-purity cellulose at 500 ° C., and (2) is an activated carbon powder (prototype) obtained by firing high-purity cellulose at 1000 ° C. (3) is obtained by dispersing “Kremezin” manufactured by Kureha Chemical Industry, and (4) is obtained by not dispersing activated carbon powder. Moreover, the width | variety (mm) of the growth inhibition area | region in (1)-(3) of FIG. 4 and the ammonia adsorption ability (ppm) of the activated carbon powder used by (1)-(3) are shown in FIG.
図4,図5から分かるように、穴の周辺にはコロニーの増殖阻止域が観察され、その幅はアンモニア吸着能と正に相関していた。なお、図4の(4)にも大きな増殖阻止域が観察されるが、これは、活性炭粉末5mgの容積に相当する分だけ塩酸量が多く、過剰な塩酸に晒され続けるためである。 As can be seen from FIGS. 4 and 5, a colony growth inhibition zone was observed around the hole, and its width positively correlated with the ammonia adsorption capacity. A large growth inhibition zone is also observed in (4) of FIG. 4 because the amount of hydrochloric acid is large by an amount corresponding to the volume of 5 mg of the activated carbon powder and is continuously exposed to excess hydrochloric acid.
次に、活性炭以外の吸着材として、シリカゲルを用いて同様の実験を行った。コントロールとしてはセルロースを用いた。
ピロリ菌を0.7mLのPBSで混釈し、3つのピロリ寒天培地にそれぞれ植菌後、上記のアネロパック微好気パウチ用セットを使用して、37℃で1日間培養した。そして、各ピロリ寒天培地にセルロース(旭化成製、セオラス101)10mg、又はシリカゲル(ケムコ製、LC−SORB SPW−B−Si)10mgを分散させた0.1M塩酸0.5mLを散布して、さらに3日間培養した。Next, the same experiment was performed using silica gel as an adsorbent other than activated carbon. Cellulose was used as a control.
H. pylori was mixed with 0.7 mL of PBS, inoculated on each of the three H. pylori agar media, and cultured at 37 ° C. for 1 day using the above set for aneropack microaerobic pouch. Then, 0.5 mg of 0.1M hydrochloric acid in which 10 mg of cellulose (manufactured by Asahi Kasei, Theolas 101) or 10 mg of silica gel (manufactured by Chemco, LC-SORB SPW-B-Si) is dispersed on each H. pylori agar medium, Cultured for 3 days.
培養後のコロニー形成の様子を図6A,図6Bに示す。図6Aはセルロースを分散させたものであり、図6Bはシリカゲルを分散させたものである。 The appearance of colony formation after culture is shown in FIGS. 6A and 6B. FIG. 6A shows a dispersion of cellulose, and FIG. 6B shows a dispersion of silica gel.
図6A,図6Bから分かるように、アンモニア又はアンモニウムイオンの吸着能を有さないセルロースでは増殖阻止効果が確認されなかったが、シリカゲルでは増殖阻止効果が確認された。これは、シリカゲルはアンモニア吸着能が低いが、アンモニアが塩酸と反応して生じるアンモニウムイオンを静電的相互作用により吸着できるためと考えられる。したがって、陽イオン交換材においても同様の効果が期待できる。 As can be seen from FIG. 6A and FIG. 6B, the growth inhibitory effect was not confirmed with cellulose that does not have the ability to adsorb ammonia or ammonium ions, but the growth inhibitory effect was confirmed with silica gel. This is presumably because silica gel has a low ammonia adsorption ability, but can adsorb ammonium ions generated by the reaction of ammonia with hydrochloric acid by electrostatic interaction. Therefore, the same effect can be expected in the cation exchange material.
[実施例2]
活性炭による除菌効果を調べるため、ピロリ菌の感染者2名の同意のもとで尿素呼気試験(UBT)を行った。
まず、試験協力者2名について尿素呼気試験を行い、呼気中の13Cを含む炭酸ガス濃度の比率から、胃中のピロリ菌量(UBT値:Δ13C(‰))を算出した。その後、高純度セルロースを1000℃で焼成した活性炭粉末(試作品)のカプセル2錠(1錠あたり180mgの活性炭粉末を含む)を1日3回、食後に経口摂取させ、3週間摂取後における呼気中の13Cを含む炭酸ガス濃度の比率から、胃中のピロリ菌量(UBT値:Δ13C(‰))を算出した。呼気試験装置としては、炭酸ガス同位体比分析装置(大塚電子製、POC one)を用いた。呼気のサンプリング及び操作はメーカの取扱説明書に従って行った。結果を下記表1に示す。[Example 2]
In order to examine the sterilization effect of activated carbon, a urea breath test (UBT) was conducted with the consent of two persons infected with H. pylori.
First, a urea breath test was conducted on two test cooperators, and the amount of Helicobacter pylori in the stomach (UBT value: Δ 13 C (‰)) was calculated from the ratio of the concentration of carbon dioxide containing 13 C in the breath. Thereafter, 2 capsules of activated carbon powder (prototype) calcined at 1000 ° C. (including 180 mg of activated carbon powder per tablet) were orally ingested 3 times a day after meal, and exhaled after 3 weeks. The amount of Helicobacter pylori in the stomach (UBT value: Δ 13 C (‰)) was calculated from the ratio of carbon dioxide gas concentration containing 13 C therein. As the breath test apparatus, a carbon dioxide isotope ratio analyzer (manufactured by Otsuka Electronics Co., Ltd., POC one) was used. Exhalation sampling and manipulation were performed according to the manufacturer's instructions. The results are shown in Table 1 below.
表1から分かるように、活性炭を3週間摂取することによりUBT値が摂取前の54〜27%に減少している。このことから、活性炭に有意な除菌効果があることが分かる。 As can be seen from Table 1, by taking activated carbon for 3 weeks, the UBT value is reduced to 54 to 27% before ingestion. This shows that activated carbon has a significant sterilization effect.
本発明は、ヘリコバクター・ピロリ(Helicobacter pylori;以下、適宜「ピロリ菌」という。)の除菌剤に関する。 The present invention, Helicobacter pylori (Helicobacter pylori;. Hereinafter, appropriately referred to as "H. pylori") about the sterilization agent.
そこで、本発明は、副作用の少ない新規なピロリ菌の除菌剤を提供することを目的とする。 Therefore, an object of the present invention is to provide a novel sterilizing agent for H. pylori with few side effects.
(1) アンモニア又はアンモニウムイオンの吸着材を含むヘリコバクター・ピロリの除菌剤。
(2) 前記アンモニア又はアンモニウムイオンの吸着材が、活性炭、シリカゲル、アルミナ、ゼオライト、及び陽イオン交換材からなる群から選択される少なくとも1種である上記(1)記載の除菌剤。
(1) A Helicobacter pylori disinfectant containing an ammonia or ammonium ion adsorbent.
(2) The disinfectant according to (1), wherein the ammonia or ammonium ion adsorbent is at least one selected from the group consisting of activated carbon, silica gel, alumina, zeolite, and a cation exchange material .
本発明によれば、副作用の少ない新規なピロリ菌の除菌剤を提供することができる。 According to the present invention, it is possible to provide a disinfecting agent with less side effects novel pylori.
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