JPH07126177A - Therapeutic agent for colitis ulcerosa - Google Patents
Therapeutic agent for colitis ulcerosaInfo
- Publication number
- JPH07126177A JPH07126177A JP5271771A JP27177193A JPH07126177A JP H07126177 A JPH07126177 A JP H07126177A JP 5271771 A JP5271771 A JP 5271771A JP 27177193 A JP27177193 A JP 27177193A JP H07126177 A JPH07126177 A JP H07126177A
- Authority
- JP
- Japan
- Prior art keywords
- therapeutic agent
- ulcerative colitis
- prevention
- bifidobacterium
- longum
- Prior art date
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Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、潰瘍性大腸炎の治療及
び再発防止に効果的な医薬に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medicine effective for treating ulcerative colitis and preventing recurrence.
【０００２】[0002]
【従来の技術】潰瘍性大腸炎（Ｕｌｃｅｒａｔｉｖｅ
ｃｏｌｉｔｉｓ）は、大腸の炎症性腸疾患（Ｉｎｆｌａ
ｍｍａｔｏｒｙ Ｂｏｗｅｌ Ｄｉｓｅａｓｅ）の代表
的な疾患であり、厚生省難病指定の一つとしてその病態
解明に多くの努力がなされているが未だその原因は明ら
かではない。本疾患は大腸の粘膜及び粘膜下層にび爛や
潰瘍を形成し、これによって腸内細菌叢も異常を呈して
いると考えられ、これらの細菌による感染、遺伝因子及
び免疫学的諸機能などが複雑に作用しあっているものと
思われる。2. Description of the Related Art Ulcerative colitis
colitis is an inflammatory bowel disease of the large intestine (Infla
It is a typical disease of the mammory bowel disease), and many efforts have been made to elucidate its pathological condition as one of the designations for the intractable disease of the Ministry of Health and Welfare, but its cause is not clear yet. It is thought that this disease forms sores and ulcers in the mucosa and submucosa of the large intestine, which may cause abnormalities in the intestinal microbiota. Infection with these bacteria, genetic factors, and various immunological functions may occur. It seems that they work in a complicated way.
【０００３】従って、本疾患の病因は、胃・十二指腸潰
瘍のそれとは決定的に異なり、それ故に現在行われてい
る薬物療法も胃・十二指腸潰瘍とは異なっている。胃・
十二指腸潰瘍には、Ｈ2受容体拮抗薬やプロトンポンプ
阻害剤が現在使用されており、優れた治癒成績が得られ
ている。そのため胃・十二指腸潰瘍の外科的手術も以前
に比べ激減している。[0003] Therefore, the etiology of this disease is decisively different from that of gastric-duodenal ulcer, and therefore the current drug therapy is also different from gastric-duodenal ulcer. stomach·
Duodenal ulcer, H 2 receptor antagonists and proton pump inhibitors are currently used, which provides excellent healing results. As a result, the number of surgical operations for gastric and duodenal ulcers has dramatically decreased compared to before.
【０００４】一方、潰瘍性大腸炎の薬物療法について
は、従来よりサラゾピリン（一般名Ｓａｌｉｃｙｌａｚ
ｏｓｕｌｆａｐｙｒｉｄｉｎｅ）が用いられてきたが、
厚生省特定疾患潰瘍性大腸炎班による薬物療法指針によ
れば、サラゾピリン単独療法よりプレドニゾロン注腸療
法を早期に併用することが肝要であるとされている〔厚
生省特定疾患消化吸収障害調査研究班、昭和５８年業績
集、１９８４、ｐ．１１〕。On the other hand, regarding drug therapy for ulcerative colitis, salazopyrin (generic name: Salicylaz) has been conventionally used.
ossulfapyridine) has been used,
According to the guideline for drug therapy by the Ministry of Health and Welfare specific disease ulcerative colitis group, it is important to use prednisolone enema therapy earlier than salazopyrin monotherapy [Ministry of Health and Welfare specific disease digestive and absorption disorder study group, Showa 1983 Achievements, 1984, p. 11].
【０００５】しかし、これらの薬物療法によっても、未
だ完全に治療することは困難で、医学的にも「治癒」と
いう用語を用いることができず、欧米及び我が国では
「一時的に症状が良くなった状態」の意味で、「寛解
（Ｒｅｍｉｓｓｉｏｎ）」という言葉が用いられてい
る。However, even with these drug therapies, it is still difficult to completely treat them, and the term "cure" cannot be used medically, and in Europe and the United States, "temporary symptoms are improved." The term "remission" is used to mean "relieved state".
【０００６】更に、プレドニゾロンは、１９６０年代か
ら繁用されるようになったが、副作用としてプレドニゾ
ロン抵抗性の潰瘍性大腸炎の症例が見られるようになっ
た。この他にもプレドニゾロンの副作用は多数くある
が、そのうち重要なものの一つとして、感染を助長する
ことが挙げられる。即ち、外来病原菌の腸内増殖を亢進
させるというものである。このように、サラゾピリンや
プレドニゾロンでは寛解は得られるが治癒は出来ず、や
がて再発を繰り返し、高頻度に大腸癌が発症する（岡安
勲、藤原睦憲他：潰瘍性大腸炎に伴う大腸癌発生、胃と
腸、２８巻：１７１、１９９３）という欠点を有してい
た。[0006] Further, prednisolone has been widely used since the 1960s, but as a side effect, cases of prednisolone-resistant ulcerative colitis have come to be seen. There are many other side effects of prednisolone, and one of the important side effects is to promote infection. That is, it is to enhance intestinal growth of foreign pathogens. In this way, salazopyrin and prednisolone provide remission but cannot be cured, and then recurrence is repeated and colon cancer frequently occurs (Okayasu Osamu, Fujiwara Mutsunori et al .: Colon cancer associated with ulcerative colitis, gastric cancer). And intestine, 28: 171, 1993).
【０００７】最近、ウリナスタチン（多田正大他：難治
性潰瘍性大腸炎の新しい治療の試み、大腸肛門誌、４
２：５７８、１９８９）、魚油のエイコサペンタエン酸
（Ｓａｌｏｍｏｎ Ｐ．ｅｔ ａｌ．：Ｔｒｅａｔｍｅ
ｎｔ ｏｆ ｕｌｃｅｒａｔｉｖｅ ｃｏｌｉｔｉｓ
ｗｉｔｈ ｆｉｓｈ ｏｉｌ ｎ−３−ω−ｆａｔｔｙ
ａｃｉｄ−ａｎ ｏｐｅｎ ｔｒｉａｌ−．Ｊ．Ｃｌｉ
ｎ．Ｇａｓｔｒｏｅｎｔｅｒｏｌ．１２：１５７，１９
９０）などが潰瘍性大腸炎に有効との報告もあるが、確
立した治療法ではない。Recently, ulinastatin (Masahiro Tada et al .: A new treatment attempt for intractable ulcerative colitis, Colorectal anal magazine, 4
2: 578, 1989), fish oil eicosapentaenoic acid (Salomon P. et al .: Treatme.
nt of ulcerative colitis
with fish oil n-3-ω-fatty
acid-an open trial-. J. Cli
n. Gastroenterol. 12: 157, 19
Although 90) is reported to be effective for ulcerative colitis, it is not an established treatment method.
【０００８】[0008]
【発明が解決しようとする課題】従って、本発明の目的
は、安全であり、従来にない全く新しい作用機序をもっ
た潰瘍性大腸炎治療剤を提供することにある。SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a therapeutic agent for ulcerative colitis, which is safe and has a completely new mechanism of action that has never existed before.
【０００９】[0009]
【課題を解決するための手段】本発明者らは、斯かる実
情に鑑み、デキストラン硫酸ナトリウムによって誘発さ
れる潰瘍性大腸炎モデルマウスを用いて種々の物質の投
与効果を調べた。このモデルは、その臨床症状、病理組
織像が極めて人間の潰瘍性大腸炎に似ているのみなら
ず、腸内細菌叢も人間の場合の如く、嫌気性菌が減少し
ていることが特徴である。但し本実験モデルは胃潰瘍や
十二指腸潰瘍は生じない。この実験モデルを用いて、鋭
意研究を行った結果、ビフィズス菌の菌体が、潰瘍性大
腸炎の予防及び治療に極めて有効であり、かつ副作用が
少ないことを見出し、本発明を完成した。In view of such circumstances, the present inventors investigated the effect of administration of various substances using dextran sulfate sodium-induced ulcerative colitis model mice. This model is characterized not only by its clinical symptoms and histopathological features very similar to those of human ulcerative colitis, but also by the decrease of anaerobic bacteria in the intestinal flora as in humans. is there. However, this experimental model does not cause gastric ulcer or duodenal ulcer. As a result of earnest research using this experimental model, it was found that the bifidobacteria cells were extremely effective in the prevention and treatment of ulcerative colitis and had few side effects, and completed the present invention.
【００１０】即ち、本発明は、ビフィズス菌の菌体を有
効成分とする潰瘍性大腸炎治療剤を提供するものであ
る。That is, the present invention provides a therapeutic agent for ulcerative colitis, which contains a bifidobacteria cell as an active ingredient.
【００１１】本発明の潰瘍性大腸炎治療剤の有効成分で
あるビフィズス菌の菌体は生菌でも死菌でもよいが、生
菌の方が望ましい。本発明では、ビフィドバクテリウム
属に属する全ての菌種が使用でき、この例としては、ヒ
ト由来のビフィドバクテリウム・ロンガム、ビフィドバ
クテリウム・ブレーベ、ビフィドバクテリウム・ビフィ
ダム等が挙げられる。具体的には、ビフィドバクテリウ
ム・ロンガムＡＴＣＣ１５７０７、ビフィドバクテリウ
ム・ロンガムＮｏ．７（工業技術院生命工学工業技術研
究所受託番号ＦＥＲＭ Ｐ−１３６１０）、ビフィドバ
クテリウム・ブレーベＡＴＣＣ１５７００、ビフィドバ
クテリウム・ビフィダムＡＴＣＣ１１１４６などが例示
されるが、就中、ビフィドバクテリウム・ロンガムＮ
ｏ．７（ＦＥＲＭ Ｐ−１３６１０）等が特に好まし
い。The bifidobacteria, which are the active ingredient of the therapeutic agent for ulcerative colitis of the present invention, may be live or dead, but live cells are preferred. In the present invention, all bacterial species belonging to the genus Bifidobacterium can be used, and examples of this include human-derived Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium bifidum, and the like. To be Specifically, Bifidobacterium longum ATCC15707, Bifidobacterium longum No. 7 (Institute of Biotechnology, Industrial Technology Institute, Accession No. FERM P-13610), Bifidobacterium breve ATCC15700, Bifidobacterium bifidum ATCC11146, etc., but among them, Bifidobacterium longum N
o. 7 (FERM P-13610) and the like are particularly preferable.
【００１２】本発明の潰瘍性大腸炎治療剤の有効成分で
あるビフィズス菌の菌体は次のようにして製造される。
ビフィズス菌は栄養要求性が高く、かつ嫌気性菌である
ことから、本菌を工業的に培養する際は、乳成分若しく
はその加水分解物、糖類（乳糖など）、酵母エキス等を
含有する培地を用いて、炭酸ガスを通気しながら嫌気的
に培養する必要がある。培養中は水酸化ナトリウム等で
中和し、pHを６．２近傍に維持する。得られた培養物は
遠心分離若しくは膜処理等を行って濃縮した後、−８０
℃で凍結するか、或いは凍結乾燥して保存する。この
際、ビフィズス菌の生菌を必要としない場合は、濃縮液
を噴霧乾燥、真空乾燥等を行ってもよい。Bifidobacteria, which are the active ingredients of the therapeutic agent for ulcerative colitis of the present invention, are produced as follows.
Bifidobacteria are highly auxotrophic and anaerobic, so when industrially culturing this bacterium, a medium containing milk components or their hydrolysates, sugars (lactose, etc.), yeast extract, etc. It is necessary to anaerobically culture the cells with aerated carbon dioxide. During the culture, neutralize with sodium hydroxide or the like to maintain the pH at around 6.2. The obtained culture is subjected to centrifugation, membrane treatment or the like to be concentrated, and then -80
Freeze at ℃ or freeze-dry and store. At this time, if the viable bacteria of Bifidobacteria are not required, the concentrated solution may be spray-dried, vacuum-dried or the like.
【００１３】本発明の潰瘍性大腸炎治療剤の有効成分で
あるビフィズス菌は以下に列記するように、古くから、
ヒトや動物の腸内細菌として健康維持に極めて重要な働
きをしていることが判明しており、またそれらの作用機
序についても明らかにされている〔光岡知足：腸内菌の
世界、叢分社（１９８０）〕。The bifidobacteria, which are the active ingredients of the therapeutic agent for ulcerative colitis of the present invention, have been used for a long time as listed below.
As human and animal intestinal bacteria, they have been found to play an extremely important role in maintaining health, and their mechanism of action has also been clarified [Mitsuoka Michioka: World of intestinal bacteria, plexus Spin-off (1980)].
【００１４】 （１）発癌物質など有害物質の生成を抑制する。 （２）病原菌の腸管感染を防ぐ。 （３）腸内有害菌の増殖を押さえる。 （４）ビタミンの合成（ビタミンＢ1、Ｂ2、Ｂ6、
Ｂ12、Ｋ）。 （５）消化・吸収を助ける。 （６）免疫能を高める。(1) To suppress the production of harmful substances such as carcinogens. (2) Prevent intestinal infection of pathogenic bacteria. (3) The growth of harmful bacteria in the intestine is suppressed. (4) Vitamin synthesis (vitamins B 1 , B 2 , B 6 ,
B 12 , K). (5) Helps digestion and absorption. (6) Immunity is enhanced.
【００１５】また、ビフィズス菌の菌体が抗潰瘍剤とし
て有用であることが知られている（特開平４−５２３６
号公報）。しかしながら、この抗潰瘍剤は、有効性試験
に潰瘍モデルとして、ラットの酢酸誘発胃潰瘍モデルや
アルコール性ストレス胃潰瘍モデルを使用しており、胃
・十二指腸潰瘍等の消化性潰瘍を対象とした抗潰瘍剤で
ある。前述のように消化性潰瘍と潰瘍性大腸炎とはその
病因が全く異なるものであり、従来ビフィズス菌と潰瘍
性大腸炎との関係を示唆した文献は存在しない。It is known that bifidobacteria are useful as antiulcer agents (Japanese Patent Laid-Open No. 4-5236).
Issue). However, this anti-ulcer drug uses an acetic acid-induced gastric ulcer model and an alcoholic stress gastric ulcer model in rats as an ulcer model in the efficacy test, and the anti-ulcer drug for peptic ulcer such as gastric / duodenal ulcer is used. Is. As described above, peptic ulcer and ulcerative colitis have completely different etiological factors, and there is no literature that suggests the relationship between bifidobacteria and ulcerative colitis.
【００１６】本発明の潰瘍性大腸炎治療剤は、その有効
成分がビフィズス菌の菌体であり、前記の理由でその安
全性は確立されているのでそのまま経口投与してもよい
が、必要に応じて当該菌体に賦形剤、結合剤、崩壊剤、
滑沢剤、被覆剤、乳化剤、分散剤、溶剤、安定化剤など
を適宜添加して、錠剤、顆粒剤、散剤、粉末剤、カプセ
ル剤等に製剤して使用してもよい。成人１日当たりの投
与量は、生菌で１×１０6 個以上、特に１×１０8 〜１
×１０13個に相当する量の菌体を投与するのが好ましい
が、症状により適宜増減可能である。The therapeutic agent for ulcerative colitis of the present invention has an active ingredient of bifidobacteria, and its safety has been established for the above reasons. Depending on the cells, excipients, binders, disintegrants,
A lubricant, a coating agent, an emulsifier, a dispersant, a solvent, a stabilizer and the like may be appropriately added, and the mixture may be used by formulating into tablets, granules, powders, powders, capsules and the like. The daily dose for an adult is 1 × 10 6 or more, and particularly 1 × 10 8 to 1 in viable bacteria.
It is preferable to administer an amount of bacterial cells corresponding to × 10 13 cells, but the amount can be appropriately increased or decreased depending on the symptoms.
【００１７】[0017]
【実施例】以下、実施例を挙げて本発明を更に詳細に説
明するが、本発明はこれらに限定されるものではない。The present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
【００１８】実施例１ ビフィドバクテリウム・ロンガム（Ｂ．ｌｏｎｇｕｍ）
Ｎｏ．７を、カゼインの加水分解物３．０％、ラクトー
ス４．０％、酵母エキス０．５％を含む培地で炭酸ガス
を通気しながら３７℃で約１５時間培養した。培養中は
水酸化ナトリウム等で中和し、培地のpHを約６．２に維
持する。次に、本培養液を遠心分離又は膜処理等を行
い、約１０倍に濃縮する。本濃縮物の組成は、蛋白質１
９％、ラクトース１１％、酢酸６％、乳酸７％、灰分１
３％、ガラクトース７％、水分３２％、その他５％であ
った。Example 1 B. longum
No. 7 was cultured at 37 ° C. for about 15 hours in a medium containing 3.0% casein hydrolyzate, 4.0% lactose, and 0.5% yeast extract while aerating carbon dioxide. During the culture, the pH of the medium is maintained at about 6.2 by neutralizing with sodium hydroxide or the like. Next, the main culture solution is subjected to centrifugation, membrane treatment, or the like to be concentrated about 10 times. The composition of this concentrate is protein 1
9%, lactose 11%, acetic acid 6%, lactic acid 7%, ash 1
It was 3%, galactose 7%, water content 32%, and other 5%.
【００１９】本濃縮物を５ml容のプラスチック製アンプ
ルに分注後、ディープフリーザー（−８０℃）に保存
し、本発明の潰瘍性大腸炎治療剤を得た。The concentrate was dispensed into a plastic ampoule having a volume of 5 ml and stored in a deep freezer (-80 ° C) to obtain the therapeutic agent for ulcerative colitis of the present invention.
【００２０】試験例１ デキストラン硫酸ナトリウム（ＤＳＳ）により誘発され
る潰瘍性大腸炎モデルマウス〔Ｏｋａｙａｓｕ，Ｉ．ｅ
ｔ ａｌ．：Ａ Ｎｏｖｅｌ Ｍｅｔｈｏｄｉｎ ｔｈ
ｅ Ｉｎｄｕｃｔｉｏｎ ｏｆ Ｒｅｌｉａｂｌｅ Ｅ
ｘｐｅｒｉｍｅｎｔａｌ Ａｃｕｔｅ ａｎｄ Ｃｈｒ
ｏｎｉｃ Ｖｌｃｅｒａｔｉｖｅ Ｃｏｌｉｔｉｓ ｉ
ｎ Ｍｉｃｅ．Ｇａｓｔｒｏｅｎｔｅｒｏｌｏｇｙ，９
８：６９４−７０２（１９９０）〕を用いて、次の４群
にて実施例１で得られたＢ．ｌｏｎｇｕｍの凍結菌体の
投与効果を下記試験方法により調べた。Test Example 1 Model mouse for ulcerative colitis induced by dextran sodium sulfate (DSS) [Okayasu, I. e
t al. : A Novel Method th
e Induction of Reliable E
xperimental Acute and Chr
onic Vlcerative Colitis i
n Mice. Gastroenterology, 9
8: 694-702 (1990)] in the following 4 groups. The administration effect of frozen cells of longum was examined by the following test method.
【００２１】Ａ群：水＋培地（Ｎ＝９） Ｂ群：水＋Ｂ．ｌｏｎｇｕｍ Ｎｏ．７（Ｎ＝９） Ｃ群：ＤＳＳ＋培地（Ｎ＝１２） Ｄ群：ＤＳＳ＋Ｂ．ｌｏｎｇｕｍ Ｎｏ．７（Ｎ＝１
０）Group A: water + medium (N = 9) Group B: water + B. longum No. 7 (N = 9) C group: DSS + medium (N = 12) D group: DSS + B. longum No. 7 (N = 1
0)
【００２２】試験方法：ＣＢＡ／Ｊ ＮＣｒｊ９週令Ｓ
ＰＦ雌性マウスに、３％ＤＳＳ水溶液を７日間自由に飲
水させた。Ｂ．ｌｏｎｇｕｍ Ｎｏ．７は、生菌（３．
９×１０11cfu ）、死菌（＜１０cfu ）及び培地を、そ
れぞれ７日間毎日、一定時刻に胃ゾンデにて、０．２ml
／匹の用量を経口投与した。投与期間中に体重測定、便
鮮血反応、飲水量の測定を行った。最終投与翌日に血清
検査、大腸の長さの測定及び病理組織学的検査を行っ
た。病理組織学的検査結果は、炎症の強さに従って下記
に示す５段階スコア（Ｐａｔｈｏｌｏｇｙ Ｓｃｏｒ
ｅ）で示した。Test method: CBA / J NCrj 9 weeks S
PF female mice were allowed to drink 3% DSS aqueous solution freely for 7 days. B. longum No. 7 is a live bacterium (3.
0.2 ml each of 9 × 10 11 cfu), killed bacteria (<10 cfu), and medium for 7 days each day at a fixed time in a stomach tube.
A dose of 1 / mouse was administered orally. During the administration period, body weight, fecal fresh blood reaction, and water consumption were measured. The day after the final administration, serum test, measurement of colon length and histopathological examination were performed. The results of the histopathological examination are shown in the following five-level score (Pathology Score) according to the intensity of inflammation.
e).
【００２３】０：正常 １：好中球を含む炎症細胞の局所的な粘膜内浸潤 ２：炎症細胞浸潤による粘膜腺管の消失或いは陰窩膿瘍 ３：粘膜膿瘍 ４：粘膜膿瘍が標本上１mm以上の長さで連続している結
果を表１及び表２に示す（いずれも生菌）。0: normal 1: local infiltration of inflammatory cells including neutrophils into mucosa 2: disappearance of mucosal gland duct or crypt abscess due to infiltration of inflammatory cells 3: mucosal abscess 4: mucosal abscess on the specimen 1 mm or more The results of continuous lengths are shown in Tables 1 and 2 (both live).
【００２４】[0024]
【表１】 [Table 1]
【００２５】[0025]
【表２】 [Table 2]
【００２６】表１及び表２から明らかなように、Ｃ群と
Ｄ群において、Ｂ．ｌｏｎｇｕｍＮｏ．７菌体投与群で
は、非投与群に比較して大腸の長さは有意（ｐ＜０．０
１）に長く、即ち炎症の繰り返しや程度が低く、更に病
理組織学的にも、潰瘍性大腸炎に特徴的な陰窩膿瘍頻度
が有意（ｐ＜０．０５）に低く、粘膜固有層への炎症性
細胞浸潤の程度も有意（ｐ＜０．０５）に少ない。As is clear from Tables 1 and 2, in the C group and the D group, the B. longnum No. In the 7-microbial cell-administered group, the length of the large intestine was significant (p <0.0
1), that is, the inflammation is less repeated and less severe, and histopathologically, the frequency of crypt abscesses characteristic of ulcerative colitis is significantly low (p <0.05), and The degree of infiltration of inflammatory cells was significantly (p <0.05).
【００２７】試験例２ 潰瘍性大腸炎患者の糞便では病期・重症度の如何に拘わ
らず、又、未治療或いはサラゾピリン投与例の何れの場
合にも、健常人のそれと比較して全患者共通して総菌数
及び嫌気性菌、特にＢｉｆｉｄｏｂａｃｔｅｒｉｕｍが
著しく減少することが報告されている〔（１）弁野義
己、光岡知足：ＩｎｆｌａｍｍａｔｏｒｙＢｏｗｅｌ
Ｄｉｓｅａｓｅにおける腸内細菌叢の特徴、最新医学３
８巻：１４７６、１９８３、（２）下山孝、他：ＩＢＤ
に対する治療による腸内細菌の変動、最新医学３８巻：
１４８２、１９８３、（３）中谷林太郎、他：潰瘍性大
腸炎の細菌叢：サラゾピリン及び抗生物質非投与例なら
びに大腸切除例における検討、最新医学３８巻：２４６
１、１９８３）。このような事実に基づき、ＤＳＳによ
り誘発された潰瘍性大腸炎モデルマウスに、Ｂ．ｌｏｎ
ｇｕｍの菌体（生菌）を投与した際の腸内フローラの変
動について検索した。Test Example 2 The stools of patients with ulcerative colitis were common to all patients regardless of stage or severity, and in both cases of untreated or salazopyrine administration, compared with those of healthy subjects. It has been reported that the total number of bacteria and anaerobic bacteria, especially Bifidobacterium, are remarkably decreased [(1) Yoshino Benno, Chimitsu Mitsuoka: Inflammatory Bowel.
Characteristics of intestinal flora in Disease, latest medicine 3
Volume 8: 1476, 1983, (2) Takashi Shimoyama, et al .: IBD
Fluctuations of Intestinal Bacteria Due to Treatment for, Current Medicine 38:
1482, 1983, (3) Rintaro Nakatani, et al .: Bacterial flora of ulcerative colitis: Examination in cases without salazopyrin and antibiotics and colon resection, latest medical science 38: 246
1, 1983). Based on these facts, ulcerative colitis model mice induced by DSS were subjected to B. lon
A change in the intestinal flora when the gum cells (live cells) were administered was searched.
【００２８】Ａ群：水＋培地（Ｎ＝５） Ｂ群：水＋Ｂ．ｌｏｎｇｕｍ Ｎｏ．７（Ｎ＝５） Ｃ群：ＤＳＳ＋培地（Ｎ＝９） Ｄ群：ＤＳＳ＋Ｂ．ｌｏｎｇｕｍ Ｎｏ．７（Ｎ＝１
０）Group A: water + medium (N = 5) Group B: water + B. longum No. 7 (N = 5) C group: DSS + medium (N = 9) D group: DSS + B. longum No. 7 (N = 1
0)
【００２９】ＣＢＡ／Ｊマウス（♀、成獣）を用い、個
体識別のためにマーキングし、群飼い飼育した。被検物
質（水、培地、ＤＳＳ、Ｂ．ｌｏｎｇｕｍ Ｎｏ．７）
は７日間連続投与した。ＤＳＳは３％水溶液で自由摂取
させ、Ｂ．ｌｏｎｇｕｍ Ｎｏ．７はその凍結菌体約
３．９×１０11cfu を胃ゾンデを用いて７日間毎日強制
経口投与した。対照に用いた水と培地も各々同様に投与
した。結果を表３に示す。CBA / J mice (♀, adult) were used for marking for individual identification and group breeding. Test substance (water, medium, DSS, B. longum No. 7)
Was administered for 7 consecutive days. DSS was freely ingested as a 3% aqueous solution, and B. longum No. For No. 7, about 3.9 × 10 11 cfu of the frozen bacterial cells was forcibly orally administered daily for 7 days using a gastric sonde. Water and medium used as controls were similarly administered. The results are shown in Table 3.
【００３０】[0030]
【表３】 [Table 3]
【００３１】被検物質の投与前にはフローラの検索に用
いた全てのマウスの糞便中にＢ．ｌｏｎｇｕｍ Ｎｏ．
７は検出されなかったが、被検物質投与後では、Ｂ．ｌ
ｏｎｇｕｍ Ｎｏ．７投与群のＢ群（健常マウス）で平
均１０8cfu／ｇ、Ｄ群（ＤＳＳ投与群）で１０7cfu／ｇ
レベルでそれぞれＢ．ｌｏｎｇｕｍ Ｎｏ．７が検出さ
れた。即ち、投与したＢ．ｌｏｎｇｕｍ Ｎｏ．７菌は
生存しており、総菌数の減少は全く見られず、又Ｂｉｆ
ｉｄｏｂａｃｔｅｒｉｕｍの減少を、コントロール群に
比して最小限にとどめている。つまり多量のＢ．ｌｏｎ
ｇｕｍ Ｎｏ．７菌を経口投与しても腸内では菌交代現
象を起こすことなく、他の腸内細菌叢とバランス良く共
生していることが判明した。Prior to the administration of the test substance, B. coli was found in the feces of all the mice used for the flora search. longum No.
7 was not detected, but after administration of the test substance, B. l
ongum No. Average of 10 8 cfu / g in B group (healthy mice) of 7 administration groups and 10 7 cfu / g in D group (DSS administration group).
B. in each level. longum No. 7 was detected. That is, the administered B. longum No. Seven bacteria are alive, no decrease in total number is observed, and Bif
The reduction of idobacterium is minimized compared to the control group. That is, a large amount of B. lon
gum No. It was found that the oral administration of the 7 bacteria did not cause a bacterial alternation phenomenon in the intestine and coexisted in good balance with other intestinal bacterial flora.
【００３２】[0032]
【発明の効果】本発明の潰瘍性大腸炎治療剤は、大量経
口摂取しても安全なビフィズス菌の菌体を有効成分とし
ており、腸内細菌叢を改善し、宿主の健康に有利に作用
する従来にない、全く新しい作用機序をもった潰瘍性大
腸炎治療剤で、安全性と治療効果及び再発防止に優れて
いる。更にサラゾピリンやプレドニゾロンとの併用も可
能で、これら薬剤との集学的治療が理論的に期待でき
る。EFFECTS OF THE INVENTION The therapeutic agent for ulcerative colitis of the present invention contains, as an active ingredient, bifidobacteria cells which are safe even when ingested in large amounts, and improves intestinal bacterial flora, which has an advantageous effect on the health of the host. It is a therapeutic agent for ulcerative colitis that has a completely new mechanism of action that has never been seen before, and is excellent in safety, therapeutic effect and recurrence prevention. Further, it can be used in combination with salazopyrin or prednisolone, and a multidisciplinary treatment with these drugs can theoretically be expected.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 金子 勉 東京都東村山市栄町１−21−３ 明治乳業 株式会社中央研究所内 (72)発明者 竹友 直生 神奈川県小田原市成田540 明治乳業株式 会社ヘルスサイエンス研究所内 (72)発明者 角尾 肇 神奈川県小田原市成田540 明治乳業株式 会社ヘルスサイエンス研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Tsutomu Kaneko 1-21-3 Sakaemachi, Higashimurayama, Tokyo Meiji Dairy Co., Ltd. Central Research Institute (72) Inventor Naoki Taketomo 540 Narita, Odawara, Kanagawa Meiji Dairy Industries Health (72) Inventor Hajime Kakuo 540 Narita, Odawara-shi, Kanagawa Meiji Dairy Co., Ltd.
Claims (2)
瘍性大腸炎治療剤。1. A therapeutic agent for ulcerative colitis, which comprises bifidobacteria as an active ingredient.
ロンガムＦＥＲＭＰ−１３６１０である請求項１記載の
潰瘍性大腸炎治療剤。2. The bifidobacteria are Bifidobacterium
The therapeutic agent for ulcerative colitis according to claim 1, which is longum FERMP-13610.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27177193A JP3623977B2 (en) | 1993-10-29 | 1993-10-29 | Treatment for ulcerative colitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27177193A JP3623977B2 (en) | 1993-10-29 | 1993-10-29 | Treatment for ulcerative colitis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH07126177A true JPH07126177A (en) | 1995-05-16 |
| JP3623977B2 JP3623977B2 (en) | 2005-02-23 |
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ID=17504623
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP27177193A Expired - Lifetime JP3623977B2 (en) | 1993-10-29 | 1993-10-29 | Treatment for ulcerative colitis |
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| Country | Link |
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| JP (1) | JP3623977B2 (en) |
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