JP5320083B2 - Antiulcerative colitis drug - Google Patents
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- JP5320083B2 JP5320083B2 JP2009004834A JP2009004834A JP5320083B2 JP 5320083 B2 JP5320083 B2 JP 5320083B2 JP 2009004834 A JP2009004834 A JP 2009004834A JP 2009004834 A JP2009004834 A JP 2009004834A JP 5320083 B2 JP5320083 B2 JP 5320083B2
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Description
本発明は、潰瘍性大腸炎治療薬に関する。詳細には、（１Ｓ，３Ｓ）−１−メチル−１，２，３，４−テトラヒドロ−β−カルボリン−３−カルボン酸（以下、（１Ｓ，３Ｓ）ＭＴＣＡとする）、（１Ｒ，３Ｓ）−１−メチル−１，２，３，４−テトラヒドロ−β−カルボリン−３−カルボン酸（以下、（１Ｒ，３Ｓ）ＭＴＣＡとする）のいずれか一つ又は両方を有効成分として含有する潰瘍性大腸炎治療薬に関する。 The present invention relates to a therapeutic agent for ulcerative colitis. Specifically, (1S, 3S) -1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (hereinafter referred to as (1S, 3S) MTCA), (1R, 3S) Ulcerability containing any one or both of -1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (hereinafter referred to as (1R, 3S) MTCA) as an active ingredient The present invention relates to a treatment for colitis.
潰瘍性大腸炎は、同様に炎症性腸疾患であるクローン病とともに難治性特定疾患の中では際だって患者数が多く、２００２年には国内で約８０，０００人であり、現在でも毎年およそ５，０００人増加している。潰瘍性大腸炎はその発症のピークが２０代であり、活動期と維持期を繰り返しながら進行する慢性の疾患である。活動期には腹痛、下痢、下血、発熱、貧血などの激しい症状を呈すだけでなく、維持期でも食餌療法が必要なために非常に患者のＱＯＬを低下させる。 Ulcerative colitis has a remarkably large number of refractory specific diseases as well as Crohn's disease, which is also an inflammatory bowel disease. In 2002, there were about 80,000 people in Japan, and even today, about 5 , 000 people are increasing. Ulcerative colitis has a peak of onset in the twenties and is a chronic disease that progresses while repeating an active period and a maintenance period. In addition to severe symptoms such as abdominal pain, diarrhea, diarrhea, fever, anemia in the active phase, dietary therapy is required even in the maintenance phase, which greatly reduces the patient's QOL.
また、クローン病の治療は経腸栄養が有効であり、現在広く臨床応用されているにもかかわらず、潰瘍性大腸炎では経腸栄養の有効性は明らかとなっていない。潰瘍性大腸炎はクローン病よりも病変部における炎症反応が強く、腸管の安静の観点から考えると成分栄養剤を基調とした経腸栄養療法が広く利用されるべきであるが、有効であるとする報告が少ない。そのため、１０％前後の患者では潰瘍性大腸炎が増悪すると中心静脈栄養を余儀なくされ、腸管の安静を保つために長期入院となってしまうことが少なくない。
さらに、潰瘍性大腸炎を完治させるための治療法がなく、現在の治療方針は外科手術、薬物療法、栄養療法などを組み合わせて維持期を長く保たせることとなっている。
In addition, enteral nutrition is effective in the treatment of Crohn's disease, and the effectiveness of enteral nutrition has not been clarified in ulcerative colitis despite the widespread clinical application. Ulcerative colitis has a stronger inflammatory response in the lesion than Crohn's disease, and enteral nutrition therapy based on component nutrients should be widely used from the viewpoint of resting the intestinal tract, but it is effective There are few reports to do. Therefore, in about 10% of patients, when ulcerative colitis worsens, central venous nutrition is forced, and in many cases, patients are hospitalized for a long time in order to keep the intestinal tract resting.
In addition, there is no cure to completely cure ulcerative colitis, and the current treatment policy is to maintain a long maintenance period by combining surgery, drug therapy, nutrition therapy, and the like.
潰瘍性大腸炎の薬物療法において、アミノサリチル酸（５−ＡＳＡ）やその誘導体であるメサラミンが用いられている。これらは、パーオキシナイトライトの基質であるスーパーオキサイド生成の抑制作用を有し、病巣部の白血球集積とミエロパーオキシダーゼを抑えることが知られている。しかし、重症例には無効であり、パーオキシナイトライトを直接抑制しないことがその原因であるとされている。
腸等の消化管は、ｍｕｃｏｓａｌ ｉｍｍｕｎｅ ｓｙｓｔｅｍに属する多数の免疫担当細胞（顆粒球、リンパ球、マクロファージ）を有し、豊富な微小循環血流を受ける場である。その一方で、酸、胆汁酸、消化酵素、細菌毒素にも直接接することから、激烈な酸化反応を受ける場でもある。従って、潰瘍性大腸炎の腸管粘膜の安静のために、パーオキシナイトライトを中心とした活性酸素種の抑制が有用であると考えられ、黒酢エキスに含まれる数種のフェノール性化合物が潰瘍性大腸炎に有効であることが確認されている（例えば、非特許文献１参照）。
そこで、本発明者らは、潰瘍性大腸炎に有効な特定の化合物を見つけるべく、パーオキシナイトライトを直接抑制する強力な抗酸化剤を探索し、潰瘍性大腸炎への有効性を検討することで、大腸炎治療薬を得ることを試みた。
In pharmacotherapy for ulcerative colitis, aminosalicylic acid (5-ASA) and its derivative mesalamine are used. These have an inhibitory effect on the production of superoxide, which is a substrate for peroxynitrite, and are known to suppress leukocyte accumulation and myeloperoxidase in the lesion. However, it is ineffective for severe cases, and the cause is that peroxynitrite is not directly suppressed.
The digestive tract such as the intestine has a large number of immunocompetent cells (granulocytes, lymphocytes, macrophages) belonging to the mucosal immunosystem, and is a place to receive abundant microcirculatory blood flow. On the other hand, it is also a place that undergoes an intense oxidation reaction because it directly contacts acids, bile acids, digestive enzymes, and bacterial toxins. Therefore, for the rest of the intestinal mucosa in ulcerative colitis, it is considered useful to suppress reactive oxygen species, mainly peroxynitrite, and several phenolic compounds contained in black vinegar extract contain ulcers. It has been confirmed that it is effective for ulcerative colitis (see, for example, Non-Patent Document 1).
Therefore, the present inventors searched for a powerful antioxidant that directly inhibits peroxynitrite in order to find a specific compound effective for ulcerative colitis, and examined its effectiveness for ulcerative colitis. Therefore, we tried to obtain a treatment for colitis.
本発明の目的は、潰瘍性大腸炎治療薬を提供することにある。詳細には、（１Ｓ，３Ｓ）ＭＴＣＡ、（１Ｒ，３Ｓ）ＭＴＣＡのいずれか一つ又は両方を有効成分として含有する潰瘍性大腸炎治療薬を提供することにある。 An object of the present invention is to provide a therapeutic agent for ulcerative colitis. Specifically, it is to provide a therapeutic agent for ulcerative colitis containing any one or both of (1S, 3S) MTCA and (1R, 3S) MTCA as an active ingredient.
本発明者は、上記課題を解決するために鋭意研究した結果、（１Ｓ，３Ｓ）ＭＴＣＡ及び（１Ｒ，３Ｓ）ＭＴＣＡが活性酸素を抑制し、潰瘍性大腸炎の治療への有効であることを見出し、本発明を完成するに至った。
（１Ｓ，３Ｓ）ＭＴＣＡ及び（１Ｒ，３Ｓ）ＭＴＣＡは、それぞれ下記化学式（Ｉ）及び（ＩＩ）で表され、味噌、大豆発酵食品、醤油、日本酒、ワイン、ビール、ブドウ酒、酢、及びレモン、オレンジ、バナナなどの果物に含まれていることが知られている。近年、（１Ｓ，３Ｓ）ＭＴＣＡ及び（１Ｒ，３Ｓ）ＭＴＣＡは、脂肪細胞分化抑制を示す大豆発酵食品には共通して含まれていること、インスリンによる糖の取り込みを阻害するのではなく、脂肪細胞分化のイニシエーションを阻害することにより脂肪細胞分化を抑制すると考えられることが報告されている（非特許文献２）。また、空腹時血糖値及び食後（満腹時）血糖値の上昇を抑制する効果があることも報告されている（特許文献１）。
しかしながら、（１Ｓ，３Ｓ）ＭＴＣＡ及び（１Ｒ，３Ｓ）ＭＴＣＡの潰瘍性大腸炎の治療への有用性については、これまで知られていなかった。
As a result of intensive studies to solve the above problems, the present inventor has shown that (1S, 3S) MTCA and (1R, 3S) MTCA suppress active oxygen and are effective in the treatment of ulcerative colitis. The headline and the present invention were completed.
(1S, 3S) MTCA and (1R, 3S) MTCA are represented by the following chemical formulas (I) and (II), respectively, and are miso, soybean fermented food, soy sauce, sake, wine, beer, wine, vinegar, and lemon. It is known to be contained in fruits such as oranges and bananas. In recent years, (1S, 3S) MTCA and (1R, 3S) MTCA are commonly contained in fermented soy foods that show adipocyte differentiation inhibition, and do not inhibit sugar uptake by insulin. It has been reported that it is thought that adipocyte differentiation is suppressed by inhibiting initiation of cell differentiation (Non-patent Document 2). It has also been reported that there is an effect of suppressing an increase in fasting blood glucose level and postprandial (full stomach) blood glucose level (Patent Document 1).
However, the usefulness of (1S, 3S) MTCA and (1R, 3S) MTCA for the treatment of ulcerative colitis has not been known so far.
即ち、本発明は、上記化学式（Ｉ）及び（ＩＩ）で表される（１Ｓ，３Ｓ）ＭＴＣＡ、（１Ｒ，３Ｓ）ＭＴＣＡのいずれか一つ又は両方を有効成分として含有する潰瘍性大腸炎治療薬に関する。 That is, the present invention provides a treatment for ulcerative colitis comprising as an active ingredient any one or both of (1S, 3S) MTCA and (1R, 3S) MTCA represented by the above chemical formulas (I) and (II). Regarding drugs.
本発明により、（１Ｓ，３Ｓ）ＭＴＣＡ、（１Ｒ，３Ｓ）ＭＴＣＡのいずれか一つ又は両方を有効成分として含有する潰瘍性大腸炎治療薬が提供される。有効成分である（１Ｓ，３Ｓ）ＭＴＣＡ、（１Ｒ，３Ｓ）ＭＴＣＡのいずれか一つ又は両方は、潰瘍性大腸炎の治療において有用な経腸栄養剤の開発等に用いることもできる。 According to the present invention, a therapeutic agent for ulcerative colitis containing any one or both of (1S, 3S) MTCA and (1R, 3S) MTCA as an active ingredient is provided. Any one or both of (1S, 3S) MTCA and (1R, 3S) MTCA which are active ingredients can also be used for the development of enteral nutrients useful in the treatment of ulcerative colitis.
本発明の化学式（Ｉ）及び（ＩＩ）で表される（１Ｓ，３Ｓ）ＭＴＣＡ及び（１Ｒ，３Ｓ）ＭＴＣＡは、上述のようにそれぞれ既知の化合物であり、参考文献１等の方法に従い製造することができる。その製造方法は特に制限されるものではないが、例えば、Ｌ−トリプトファンに約１０倍量のアセトアルデヒド水溶液を加えてこれを８時間にわたってエタノール中で還流させて結晶を得る。この結晶をろ過して再結晶化させ、その母液を定法により濃縮し、さらに固化した後に、エタノール等のアルコールで洗浄する。この一連の工程により、（１Ｓ，３Ｓ）ＭＴＣＡ及び（１Ｒ，３Ｓ）ＭＴＣＡが得ることができる。
参考文献１：Ｗｈａｌｅｙ Ｗ．Ｍ．，Ｇｏｖｉｎｄａｃｈａｒｉ Ｔ．Ｒ． Ｏｒｇ．Ｒｅａｃｔ．，６，７４（１９５１）
(1S, 3S) MTCA and (1R, 3S) MTCA represented by the chemical formulas (I) and (II) of the present invention are known compounds as described above, and are produced according to the method of Reference 1 and the like. be able to. The production method is not particularly limited. For example, about 10 times the amount of acetaldehyde aqueous solution is added to L-tryptophan, and this is refluxed in ethanol for 8 hours to obtain crystals. The crystals are filtered and recrystallized, and the mother liquor is concentrated by a conventional method, further solidified, and then washed with an alcohol such as ethanol. Through this series of steps, (1S, 3S) MTCA and (1R, 3S) MTCA can be obtained.
Reference 1: Whaley W. M.M. , Govindachari T. R. Org. React. , 6, 74 (1951)
また、本発明の化学式（Ｉ）及び（ＩＩ）で表される（１Ｓ，３Ｓ）ＭＴＣＡ及び（１Ｒ，３Ｓ）ＭＴＣＡは、文献等の方法に従い味噌、大豆発酵食品、醤油、酢などの発酵食品から抽出することができる。
抽出した（１Ｓ，３Ｓ）ＭＴＣＡは、（１Ｓ，３Ｓ）ＭＴＣＡを１００％含むもの（純品）であることが好ましい。また、（１Ｒ，３Ｓ）ＭＴＣＡも、（１Ｒ，３Ｓ）ＭＴＣＡを１００％含むもの（純品）であることが好ましいが、何％かの（１Ｓ，３Ｓ）ＭＴＣＡを含むものであってもよい。
Moreover, (1S, 3S) MTCA and (1R, 3S) MTCA represented by the chemical formulas (I) and (II) of the present invention are fermented foods such as miso, soybean fermented food, soy sauce, vinegar and the like according to methods such as literature. Can be extracted from.
The extracted (1S, 3S) MTCA is preferably one containing 100% (1S, 3S) MTCA (pure product). Further, (1R, 3S) MTCA is also preferably one containing 100% (1R, 3S) MTCA (pure product), but may contain some% (1S, 3S) MTCA. .
本発明の潰瘍性大腸炎治療薬は、経口投与及び非経口投与することができる。本発明の潰瘍性大腸炎治療薬は、各投与経路に応じて、適切な薬学的に許容される賦形剤又は希釈剤などと組み合わせることにより薬学的製剤とすることもできる。 The therapeutic agent for ulcerative colitis of the present invention can be administered orally and parenterally. The therapeutic agent for ulcerative colitis of the present invention can be made into a pharmaceutical preparation by combining with an appropriate pharmaceutically acceptable excipient or diluent depending on each administration route.
経口投与に適した剤型としては、固体、半固体、液体又は気体等の状態のものが含まれ、具体的には、錠剤、カプセル剤、粉末剤、顆粒剤、溶液剤、懸濁剤、シロップ剤、エキリシル剤等を挙げることができるが、これらに限定されるものではない。 Dosage forms suitable for oral administration include those in a solid, semi-solid, liquid or gas state. Specifically, tablets, capsules, powders, granules, solutions, suspensions, Examples include syrups and elixirs, but are not limited thereto.
本発明の潰瘍性大腸炎治療薬を錠剤、カプセル剤、粉末剤、顆粒剤、溶液剤、懸濁剤等に製剤化するためには、既知の方法により、上記化学式（Ｉ）又は（ＩＩ）に示す化合物をバインダー、錠剤崩壊剤、潤滑剤等と混合し、必要に応じて、希釈剤、緩衝剤、保存剤、フレーバー剤等と混合することができる。一例を挙げると、上記バインダーには、セルロース、結晶セルロース、セルロース誘導体、コーンスターチ、ゼラチン等、錠剤崩壊剤には、コーンスターチ、馬鈴薯デンブン、カルボキシメチルセルロースナトリウム等、潤滑剤には、タルク、ステアリン酸マグネシウム等が含まれ、さらには、ラクトース、マンニトール等の従来用いられている添加剤等を用いることができる。 In order to formulate the therapeutic agent for ulcerative colitis of the present invention into tablets, capsules, powders, granules, solutions, suspensions and the like, the above-mentioned chemical formula (I) or (II) Can be mixed with a binder, a tablet disintegrating agent, a lubricant, and the like, and can be mixed with a diluent, a buffering agent, a preservative, a flavoring agent, and the like, if necessary. For example, cellulose, crystalline cellulose, cellulose derivatives, corn starch, gelatin, etc. for the binder, corn starch, potato denbun, sodium carboxymethyl cellulose, etc. for tablet disintegrating agents, talc, magnesium stearate, etc. for lubricants In addition, conventionally used additives such as lactose and mannitol can be used.
本発明の潰瘍性大腸炎治療薬は、注射による投与としては、皮下、皮内、静脈内、筋肉内等に投与することができる。これら注射用製剤は、それ自体は既知の方法により、本発明の式（Ｉ）及び／又は（ＩＩ）の化合物を、植物性油、合成樹脂酸グリセリド、高級脂肪酸エステル、プロピレングリコールのような水性又は非水性の溶媒中に溶解、懸濁又は乳化し、さらに、所望により、可溶化剤、浸透圧調製剤、乳化剤、安定剤及び保存料等の従来用いられている添加剤と共に製剤化することができる。 The therapeutic agent for ulcerative colitis of the present invention can be administered subcutaneously, intradermally, intravenously, intramuscularly, or the like. These injectable preparations are prepared by converting the compounds of formula (I) and / or (II) of the present invention into aqueous solutions such as vegetable oils, synthetic resin acid glycerides, higher fatty acid esters, and propylene glycol by methods known per se. Or dissolved, suspended or emulsified in a non-aqueous solvent, and if desired, formulated with conventionally used additives such as solubilizers, osmotic pressure regulators, emulsifiers, stabilizers and preservatives. Can do.
本発明の潰瘍性大腸炎治療薬を溶液、懸濁液、シロップ、エリキシル等の形態にするためには、注射用滅菌水や規定生理食塩水、エタノール等のアルコールのような薬学的に許容される溶媒を用いることができる。 In order to make the therapeutic agent for ulcerative colitis of the present invention into a solution, suspension, syrup, elixir or the like, it is pharmaceutically acceptable such as sterile water for injection, normal saline, alcohol such as ethanol. Can be used.
本発明の潰瘍性大腸炎治療薬は、化学式（Ｉ）及び（ＩＩ）の化合物のいずれか一つ又は両方を含有するものであればいずれのものも含まれる。その薬効に悪影響を及ぼさない範囲で薬学的に許容される他の活性を有する化合物と併用して薬学的製剤とすることもできる。 The therapeutic agent for ulcerative colitis of the present invention includes any one as long as it contains any one or both of the compounds of formulas (I) and (II). It can also be used in combination with other pharmaceutically acceptable compounds that do not adversely affect their medicinal effects to form pharmaceutical preparations.
本発明の潰瘍性大腸炎治療薬は、投与形態、投与経路、対象とする疾患の進行度等に応じて適宜設定、調節することができる。 The therapeutic agent for ulcerative colitis of the present invention can be appropriately set and adjusted according to the administration form, administration route, degree of progression of the target disease, and the like.
以下、本発明を実施例に基づいて説明するが、本発明はこれら実施例に限定されるものではない。 EXAMPLES Hereinafter, although this invention is demonstrated based on an Example, this invention is not limited to these Examples.
潰瘍性大腸炎動物実験モデルとして、従来我々が使用してきた高分子デキストラン硫酸（ＤＳＳ）を投与したモデルを用いた。６週齢のオスＢＡＬＢ／Ｃマウスを以下の２群に分け、高分子デキストラン硫酸（３．５％：重症潰瘍性大腸炎を発症する濃度）をそれぞれ１２日間、水に混ぜて自由飲水により経口摂取させた。マウスの腸管炎症の程度には腸内細菌が影響することが分かっているため、厳密なＳＰＦ環境下で飼育し、飲水、飼料は完全な滅菌操作を加えた。
実験群
I群：３．５％ ＤＳＳ ２６．２５ｍｇ／２５０ｍｌ、通常餌（ＣＥ−２）、
II群：３．５％ ＤＳＳ ２６．２５ｍｇ／２５０ｍｌ、１ｇ当たりにＭＴＣＡ（（１Ｓ，３Ｓ）−ＭＴＣＡ：（１Ｒ，３Ｓ）−ＭＴＣＡ＝３．５：１）を３．４２μｇ含有した餌。
As a model animal experiment model for ulcerative colitis, a model to which high molecular weight dextran sulfate (DSS) that has been used in the past was administered was used. Six-week-old male BALB / C mice are divided into the following two groups, and high-molecular dextran sulfate (3.5%: the concentration that causes severe ulcerative colitis) is mixed with water for 12 days, then orally by free drinking Ingested. Since it was known that enteric bacteria had an effect on the degree of intestinal inflammation in mice, they were raised in a strict SPF environment, and drinking water and feed were completely sterilized.
Experimental group
Group I: 3.5% DSS 26.25 mg / 250 ml, normal bait (CE-2),
Group II: Feed containing 3.42 μg of 3.5% DSS 26.25 mg / 250 ml MTCA (g) ((1S, 3S) -MTCA: (1R, 3S) -MTCA = 3.5: 1) per gram).
ＤＳＳ投与直前から１４日目まで連日体重を計測し、下痢や下血の状態をチェックし、実験終了日（２８日）まで生存率をチェックした。１４日目にネンブタール全身麻酔下で心臓から採血後、ｓａｃｒｉｆｉｃｅし直腸を採取した。腸管を回収後、Ｈ．Ｅ染色を施行し、腸病変の面積と重症度を評価した。 The body weight was measured every day from immediately before DSS administration to the 14th day, the diarrhea and diarrhea were checked, and the survival rate was checked until the end of the experiment (28 days). On the 14th day, blood was collected from the heart under Nembutal general anesthesia. After collecting the intestinal tract, E staining was performed to assess the area and severity of intestinal lesions.
３．結果
１．通常餌、ＭＴＣＡによる体重変化
はじめに、体重を指標としてＭＴＣＡが体重減少を抑制するか検討を行った。その結果、図１に示したように、ＭＴＣＡはｓａｃｒｉｆｉｃｅ時において、通常餌群に比較し有意に体重減少を抑制した。
２．通常餌、ＭＴＣＡによる下血の変化
体重と同様に下血の回数に関しても図２に示したように、ＭＴＣＡ投与により、有意に減少した。以上のことから、ＭＴＣＡは潰瘍性大腸炎による症状（体重減少と下血）を抑制することが明らかとなった。そこで次に、組織学的所見の検討を行った。
３．通常餌、ＭＴＣＡによる病理所見（Ｈ．Ｅ染色）
図３に示したように、通常餌では、腸上皮細胞は壊死し好中球を主体とした炎症細胞浸潤が認められたが、ＭＴＣＡにより腸上皮細胞の壊死は有意に抑制され、炎症細胞もわずかに認められたのみであった。
４．通常餌、ＭＴＣＡによる生存率
通常餌では、２８日までに全例死亡したが、ＭＴＣＡ投与により死亡は有意に抑制され、７５％で生存した。
以上の１．〜４．の結果より、潰瘍性大腸炎においては、ＭＴＣＡに治療効果を認めることが明らかになった。
3. Result 1. Changes in body weight due to normal diet and MTCA First, it was examined whether MTCA suppressed weight loss using body weight as an index. As a result, as shown in FIG. 1, MTCA significantly suppressed the weight loss at the time of safific compared to the normal diet group.
2. Changes in melena due to normal diet and MTCA As shown in FIG. 2, the number of melena as well as body weight was significantly reduced by MTCA administration. From the above, it was revealed that MTCA suppresses symptoms (weight loss and melena) due to ulcerative colitis. Next, the histological findings were examined.
3. Pathological findings with normal diet and MTCA (HE staining)
As shown in FIG. 3, in the normal diet, intestinal epithelial cells were necrotic and inflammatory cell infiltration mainly consisting of neutrophils was observed, but MTCA significantly suppressed the necrosis of intestinal epithelial cells, and inflammatory cells also Only a few were recognized.
4). Survival rate with normal diet and MTCA Although all patients died by the normal diet by 28 days, the death was significantly suppressed by administration of MTCA, and 75% survived.
1 above. ~ 4. From these results, it was revealed that MTCA has a therapeutic effect in ulcerative colitis.
５．ＭＴＣＡによるニトロチロシン産生抑制効果
ＭＴＣＡによる有効性のメカニズムを検討するため、活性酸素種であるニトロチロシンの染色を施行した。ニトロチロシンは、通常餌群においては病変部を主体に陽性であったが、ＭＴＣＡ投与群では減少していた。
以上の５．の結果より、ＭＴＣＡの有効性のメカニズムとして、活性酸素の抑制が示唆された。
5. Nitrotyrosine production inhibitory effect by MTCA In order to investigate the mechanism of effectiveness by MTCA, staining of nitrotyrosine, which is a reactive oxygen species, was performed. Nitrotyrosine was positive mainly in the lesion in the normal diet group, but decreased in the MTCA administration group.
Above 5. From these results, suppression of active oxygen was suggested as a mechanism of effectiveness of MTCA.
本発明の（１Ｓ，３Ｓ）ＭＴＣＡ、（１Ｒ，３Ｓ）ＭＴＣＡのいずれか一つ又は両方を有効成分として含有する潰瘍性大腸炎治療薬は、潰瘍性大腸炎の治療の為の経腸栄養剤等の開発にも有用である。
The therapeutic agent for ulcerative colitis containing any one or both of (1S, 3S) MTCA and (1R, 3S) MTCA of the present invention as an active ingredient is an enteral nutrient for the treatment of ulcerative colitis. It is also useful for development.
Claims (1)
(1S, 3S) -1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1R, 3S) -1-methyl-1,2,3,4-tetrahydro-β -The therapeutic agent for ulcerative colitis containing any one or both of carboline-3-carboxylic acid as an active ingredient.
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