JPH1017478A - Preventing or therapeutic agent for ulcerative colitis - Google Patents
Preventing or therapeutic agent for ulcerative colitisInfo
- Publication number
- JPH1017478A JPH1017478A JP18892896A JP18892896A JPH1017478A JP H1017478 A JPH1017478 A JP H1017478A JP 18892896 A JP18892896 A JP 18892896A JP 18892896 A JP18892896 A JP 18892896A JP H1017478 A JPH1017478 A JP H1017478A
- Authority
- JP
- Japan
- Prior art keywords
- trehalose
- agent
- ulcerative colitis
- preventing
- active ingredient
- 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.)
- Granted
Links
Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は、トレハロースを有効成
分とする副作用の少ない優れた潰瘍性大腸炎の予防又は
治療剤に関する。The present invention relates to an excellent preventive or therapeutic agent for ulcerative colitis having trehalose as an active ingredient and having few side effects.
【0002】[0002]
【従来の技術】潰瘍性大腸炎は、大腸粘膜の粘膜層ある
いは粘膜下層にびらんや潰瘍を形成する非特異性炎症性
腸疾患であり、その臨床症状として下痢、血便、腹痛及
び体重減少などの特徴的所見が挙げられる。わが国にお
いては従来比較的まれな疾患であったが、近年食生活の
欧米化等に伴い患者数は年々急増している。その原因と
して、腸内細菌感染説、食餌アレルギー説、血管障害
説、自律神経障害説及び免疫異常説など種々の要因が考
えられているが、詳細は未だ不明であり、根本的治療法
が確立されていないのが現状である。現在のところ薬物
療法としては、ステロイドホルモン、サラゾスルファピ
リジン、免疫抑制剤などの単独投与あるいは併用投与が
行われている。しかしながら、治療効果が不十分である
ばかりか副作用発現も少なくなく、より予防又は治療効
果の優れた薬剤が望まれている。一方、トレハロース
は、臓器保存液、製剤添加剤、化粧品など広範にわたっ
て利用されているが、潰瘍性大腸炎に対して予防又は治
療効果があることは全く知られていない。2. Description of the Related Art Ulcerative colitis is a nonspecific inflammatory bowel disease that forms erosions or ulcers in the mucosal layer or submucosal layer of the colonic mucosa, and its clinical symptoms include diarrhea, bloody stool, abdominal pain and weight loss. Characteristic findings are listed. In Japan, the disease has been relatively rare in the past, but the number of patients has been increasing year by year due to the westernization of eating habits in recent years. Various causes, such as the theory of intestinal bacterial infection, the theory of food allergy, the theory of vascular disorders, the theory of autonomic nervous disorders, and the theory of immune abnormalities, are thought to be the causes, but details are still unknown and fundamental treatment has been established. It has not been done yet. At present, as drug therapy, steroid hormones, salazosulfapyridine, immunosuppressants and the like are administered alone or in combination. However, not only the therapeutic effect is insufficient, but also the occurrence of side effects is not so small, and there is a demand for a drug having a better preventive or therapeutic effect. On the other hand, trehalose is widely used in organ preservation solutions, formulation additives, cosmetics, and the like, but is not known to have any preventive or therapeutic effect on ulcerative colitis.
【0003】[0003]
【発明が解決しようとする課題】本発明は副作用が少な
く、且つ治療効果に優れた潰瘍性大腸炎の予防又は治療
剤を提供することにある。SUMMARY OF THE INVENTION An object of the present invention is to provide an agent for preventing or treating ulcerative colitis which has few side effects and is excellent in therapeutic effect.
【0004】[0004]
【課題を解決するための手段】そこで本発明者らは、か
かる問題を解決するために鋭意研究した結果、トレハロ
ースが潰瘍性大腸炎の予防又は治療に極めて有効である
ということを見出し、本発明を完成した。Means for Solving the Problems The present inventors have conducted intensive studies in order to solve such problems, and as a result, have found that trehalose is extremely effective in preventing or treating ulcerative colitis. Was completed.
【0005】すなわち、本発明は、トレハロースを有効
成分とする潰瘍性大腸炎の予防又は治療剤に関する。That is, the present invention relates to a prophylactic or therapeutic agent for ulcerative colitis comprising trehalose as an active ingredient.
【0006】更に、本発明の潰瘍性大腸炎の予防又は治
療剤は、緩解期の再燃、再発予防としても用いることが
できる。Further, the agent for preventing or treating ulcerative colitis of the present invention can also be used for preventing relapse and relapse during remission.
【0007】本発明に用いられるトレハロースは、酵
母、かび、海産動物、海草等の天然物中に広く分布する
非還元性の二糖類で、上記天然物からエタノールで熱抽
出して得る方法や微生物の発酵による方法が知られてい
る。また、化学構造的には、D−グルコースの還元性基
どうしが結合したもので、その結合様式からα,α−ト
レハロース、α,β−トレハロース又はβ,β−トレハ
ロースの3種の異性体が存在するが、いずれも本発明に
使用することができる。これらのうち天然に存在する
α,α−トレハロースを使用するのが好ましい。Trehalose used in the present invention is a non-reducing disaccharide widely distributed in natural products such as yeasts, molds, marine animals and seaweeds. A fermentation method is known. In terms of chemical structure, D-glucose is formed by bonding reducing groups, and from the bonding mode, three kinds of isomers of α, α-trehalose, α, β-trehalose or β, β-trehalose are formed. Although present, any can be used in the present invention. Of these, it is preferable to use naturally occurring α, α-trehalose.
【0008】上記本発明のトレハロースを有効成分とす
る潰瘍性大腸炎の予防及び治療剤は、これのみを含む製
剤として単独で投与してもよいが、医薬的に許容される
医薬補助剤と組み合わせた経口医薬組成物又は高カロリ
ー輸液剤と併用して用いるか、若しくは輸液製剤に添加
して非経口組成物として使用することができる。The above-mentioned agent for preventing and treating ulcerative colitis comprising trehalose as an active ingredient of the present invention may be administered alone as a preparation containing the same alone, but in combination with a pharmaceutically acceptable pharmaceutical adjuvant. It can be used in combination with an oral pharmaceutical composition or a high-calorie infusion or used as a parenteral composition by adding to an infusion preparation.
【0009】上記医薬組成物の投与剤型としては、各種
の形態が治療目的にに応じて選択でき、その代表的なも
のとして錠剤、丸剤、顆粒剤、カプセル剤、散剤、シロ
ップ剤等の経口剤、座剤、液剤、懸濁剤、乳剤等の非経
口剤が挙げられる。このような製剤は、薬理学的、製剤
学的に許容される添加物を必要により添加し、公知の方
法により製造することかできる。経口剤の製造に際して
は、例えば通常用いられる乳糖、白糖、澱粉、結晶セル
ロース、コーンスターチ等の賦形剤、カルボキシメチル
セルロース、寒天、ゼラチン末等の崩壊剤、ポリビニル
アルコール、メチルセルロース、ヒドロキシプロピルセ
ルロース等の結合剤、シリカ、ステアリン酸マグネシウ
ム、タルク等の滑沢剤、ヒドロキシプロピルメチルセル
ロース、白糖等のコーティング剤等を使用すればよい。
また、溶液剤、懸濁剤、シロップ剤等の経口液剤、注射
剤の製造に際しては、注射用蒸留水、生理食塩水等に溶
解ないし、懸濁し、例えば無機又は有機の酸あるいは塩
基等のpH調整剤、等張化剤、安定化剤、希釈剤等を必
要により添加すればよい。さらに、本発明の潰瘍性大腸
炎の予防及び治療剤には、各種のアミノ酸、糖、電解質
等を添加してもよい。As the dosage form of the pharmaceutical composition, various forms can be selected according to the purpose of treatment, and typical examples thereof include tablets, pills, granules, capsules, powders, syrups and the like. Parenteral preparations such as oral preparations, suppositories, liquid preparations, suspensions, and emulsions are included. Such a preparation can be produced by a known method by adding a pharmacologically or pharmaceutically acceptable additive as necessary. In the manufacture of oral preparations, for example, commonly used excipients such as lactose, sucrose, starch, crystalline cellulose, corn starch, etc., disintegrants such as carboxymethylcellulose, agar, gelatin powder, binding of polyvinyl alcohol, methylcellulose, hydroxypropylcellulose, etc. Agents, lubricants such as silica, magnesium stearate and talc, and coating agents such as hydroxypropylmethylcellulose and sucrose may be used.
In the production of oral solutions such as solutions, suspensions, and syrups, and injections, they are not dissolved or suspended in distilled water for injection, physiological saline, and the like. Adjusters, isotonic agents, stabilizers, diluents and the like may be added as necessary. Furthermore, various amino acids, sugars, electrolytes and the like may be added to the agent for preventing and treating ulcerative colitis of the present invention.
【0010】本発明における潰瘍性大腸炎の予防又は治
療剤は必要に応じ、トレハロースに加えて、他の薬効成
分を添加することができる。The medicament for preventing or treating ulcerative colitis according to the present invention may optionally contain other medicinal ingredients in addition to trehalose.
【0011】固形製剤として投与する場合にはトレハロ
ース濃度が0.5〜100w/w%、輸液製剤として投
与する場合には0.5〜20w/v%の範囲で適宜選択
できる。The trehalose concentration can be appropriately selected within the range of 0.5 to 100 w / w% when administered as a solid preparation, and 0.5 to 20 w / v% when administered as an infusion preparation.
【0012】本発明の潰瘍性大腸炎の予防及び治療剤の
投与量は、投与の方法、患者の年齢、体重、症状等によ
り異なるが通常成人に対して経口投与の場合、1日当た
り10〜1000mg/kg、好ましくは50〜300
mg/kgの範囲で適宜調節して投与することができ
る。The dose of the preventive and therapeutic agent for ulcerative colitis of the present invention varies depending on the method of administration, the age, body weight, symptoms, etc. of the patient, but usually 10 to 1000 mg per day for oral administration to adults. / Kg, preferably 50-300
The dose can be appropriately adjusted and administered in the range of mg / kg.
【0013】[0013]
【実施例】次に、実施例により本発明を具体的に説明す
るが、本発明はこれに限定されるものではない。Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.
【0014】〔実施例1〕7週齡のSD系雄性ラットを
用い、正常ラットを5匹無作為に抽出した後、大腸炎作
製のために残りの動物を各群間の平均体重に差が生じな
いように1群7〜10匹に群分けした。その後、3%デ
キストラン硫酸ナトリウム(以下、DDSと略す)水溶
液を吸水瓶に入れてラットに連日自由飲水させ、正常群
ではDDS水溶液の代わりに精製水を同様に自由飲水さ
せた。トレハロースの150mg/kgは、3%DDS
飲水開始日より1日2回、10日間経口投与した。また
正常群及び対照群には0.5%カルボキシメチルセルロ
ース水溶液を同様に経口投与した。被験物質最終投与の
翌日に動物を解剖し、大腸の長さ(結腸及び小腸)及び
大腸粘膜のびらん面積測定並びに血液学的検査(白血
球、赤血球、ヘモグロビン濃度、ヘマトクリット値)を
実施した。なお、大腸粘膜のびらん面積は我々の確立し
た方法(日薬理誌、102,343〜350(199
3))に従って測定した。Example 1 Seven-week-old SD male rats were used to randomly extract five normal rats, and the remaining animals were examined for colitis to determine the difference in average body weight between the groups. The animals were grouped into groups of 7 to 10 animals so that they did not occur. Thereafter, a 3% aqueous solution of dextran sulfate sodium (hereinafter abbreviated as DDS) was placed in a water-absorbing bottle and rats were allowed to freely drink water every day. In the normal group, purified water was similarly allowed to freely drink instead of the DDS aqueous solution. Trehalose 150mg / kg 3% DDS
Oral administration twice daily for 10 days from the start of drinking water. Similarly, a 0.5% aqueous solution of carboxymethylcellulose was orally administered to the normal group and the control group. The animals were dissected the day after the final administration of the test substance, and the length of the large intestine (colon and small intestine) and the erosion area of the large intestine mucosa were measured, and hematological examination (white blood cells, red blood cells, hemoglobin concentration, hematocrit value) was performed. In addition, the erosion area of the large intestine mucosa was determined by a method established by our company (Jpn Pharmacology, 102, 343-350 (199).
3)).
【0015】[0015]
【表1】 [Table 1]
【0016】表1に大腸の長さ及び大腸粘膜のびらん面
積測定の結果を示した。大腸粘膜のびらん形成は、トレ
ハロースの経口投与により著明に抑制された。さらに、
大腸炎の発症に伴って有意に短縮した大腸の長さ(大腸
壁肥厚の指標となる)も明らかに改善された。Table 1 shows the results of measuring the length of the large intestine and the erosion area of the large intestine mucosa. Erosion of the colonic mucosa was significantly suppressed by oral administration of trehalose. further,
The length of the large intestine, which was significantly shortened with the onset of colitis, which is an indicator of colon wall thickening, was also clearly improved.
【0017】[0017]
【表2】 [Table 2]
【0018】表2に血液学的検査の結果を示した。トレ
ハロースは、大腸炎発症の指標となる白血球数の増加を
有意に改善した。また潰瘍性大腸炎の特徴的な症状とし
て貧血が挙げられるが、その指標となるヘモグロビン濃
度及びヘマトクリット値の低下に対しても有意な改善を
示した。Table 2 shows the results of hematological examination. Trehalose significantly improved the increase in white blood cell count, an indicator of colitis onset. In addition, anemia is a characteristic symptom of ulcerative colitis, and a significant improvement was also shown with respect to a decrease in hemoglobin concentration and hematocrit level, which are indicators thereof.
【0019】以下に製剤例を示す。 〔製剤例1〕錠剤 常法により、以下の組成を有する錠剤を製造する。 1錠(200mg)中の組成 トレハロース 100mg コーンスターチ 45mg 乳糖 50mg ヒドロキシプロピルセルロース 4mg ステアリン酸マグネシウム 1mgThe preparation examples are shown below. [Formulation Example 1] Tablet A tablet having the following composition is produced by a conventional method. Composition in 1 tablet (200mg) Trehalose 100mg Corn starch 45mg Lactose 50mg Hydroxypropylcellulose 4mg Magnesium stearate 1mg
【0020】〔製剤例2〕カプセル剤 常法により、以下の組成を有するカプセル剤を製造す
る。 1カプセル(1錠200mg) トレハロース 100mg 乳糖 25mg コーンスターチ 65mg ヒドロキシプロピルセルロース 10mgFormulation Example 2 Capsules Capsules having the following composition are produced by a conventional method. 1 capsule (1 tablet 200mg) Trehalose 100mg Lactose 25mg Corn starch 65mg Hydroxypropylcellulose 10mg
【0021】〔製剤例3〕注射剤 常法により、以下の組成を有する注射剤を製造する。 1アンプル(1本20ml) トレハロース 8g 塩化ナトリウム 0.2g 蒸留水 適量[Formulation Example 3] Injection An injection having the following composition is produced by a conventional method. 1 ampoule (1 bottle 20ml) Trehalose 8g Sodium chloride 0.2g Distilled water qs
【0022】[0022]
【発明の効果】本発明の潰瘍性大腸炎予防治療剤は、大
腸粘膜のびらん形成を抑制することから、優れた効果を
発揮する。EFFECT OF THE INVENTION The agent for preventing or treating ulcerative colitis of the present invention exerts an excellent effect because it suppresses the formation of erosions in the colonic mucosa.
フロントページの続き (72)発明者 片岡 美紀子 滋賀県甲賀群甲西町大字針59−27−513 (72)発明者 武田 伝内 滋賀県大津市中庄1丁目17番14号822Continued on the front page (72) Inventor Mikiko Kataoka Shiga Prefecture Koga Gunko Nishimachi Oaza 59-27-513 (72) Inventor Takeda Dennai 1-1-17-14 Nakasho, Otsu City, Shiga Prefecture 822
Claims (1)
腸炎の予防又は治療剤。An agent for preventing or treating ulcerative colitis comprising trehalose as an active ingredient.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP18892896A JP3455633B2 (en) | 1996-06-28 | 1996-06-28 | Agent for preventing or treating ulcerative colitis |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP18892896A JP3455633B2 (en) | 1996-06-28 | 1996-06-28 | Agent for preventing or treating ulcerative colitis |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH1017478A true JPH1017478A (en) | 1998-01-20 |
JP3455633B2 JP3455633B2 (en) | 2003-10-14 |
Family
ID=16232351
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP18892896A Expired - Lifetime JP3455633B2 (en) | 1996-06-28 | 1996-06-28 | Agent for preventing or treating ulcerative colitis |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP3455633B2 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0955050A1 (en) * | 1998-04-20 | 1999-11-10 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Agent for anti-oseoporosis |
JP2005139172A (en) * | 2003-10-16 | 2005-06-02 | Sankyo Co Ltd | Salicylic acid-containing oral composition |
WO2006097263A2 (en) | 2005-03-12 | 2006-09-21 | bitop Aktiengesellschaft für biotechnische Optimierung | Orally used compatible solute containing agents |
JP2009197030A (en) * | 2000-11-07 | 2009-09-03 | Hayashibara Biochem Lab Inc | Mucosal immunomodulator and its use |
JP2016521686A (en) * | 2013-05-30 | 2016-07-25 | 蘇州科景生物医薬科技有限公司 | MULTIFUNCTIONAL COMPOSITION AND METHOD FOR PRODUCTION AND USE THEREOF |
JP2018188408A (en) * | 2017-05-11 | 2018-11-29 | 国立大学法人群馬大学 | Regulatory t-cell enhancer and medicine and food composition containing the same |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MD20150120A2 (en) | 2013-05-07 | 2016-03-31 | Bio Blast Pharma Ltd. | Treatment of protein aggregation myopathic and neurodegenerative diseases by parenteral administration of trehalose |
US9084720B2 (en) | 2013-05-07 | 2015-07-21 | BioBlast Pharma Ltd. | Compositions and methods for treating oculopharyngeal muscular dystrophy |
-
1996
- 1996-06-28 JP JP18892896A patent/JP3455633B2/en not_active Expired - Lifetime
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0955050A1 (en) * | 1998-04-20 | 1999-11-10 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Agent for anti-oseoporosis |
JP2009197030A (en) * | 2000-11-07 | 2009-09-03 | Hayashibara Biochem Lab Inc | Mucosal immunomodulator and its use |
JP2005139172A (en) * | 2003-10-16 | 2005-06-02 | Sankyo Co Ltd | Salicylic acid-containing oral composition |
WO2006097263A2 (en) | 2005-03-12 | 2006-09-21 | bitop Aktiengesellschaft für biotechnische Optimierung | Orally used compatible solute containing agents |
WO2006097263A3 (en) * | 2005-03-12 | 2007-02-22 | Bitop Ag | Orally used compatible solute containing agents |
JP2008537734A (en) * | 2005-03-12 | 2008-09-25 | ビトップ アクツィエンゲゼルシャフト フュール ビオテヒニシェ オプティミールング | Drugs containing compatible solutes for oral use |
US9089568B2 (en) | 2005-03-12 | 2015-07-28 | Bitop Ag | Method of using compatible solutes containing ectoine and/or hydroxyectoine |
JP2016521686A (en) * | 2013-05-30 | 2016-07-25 | 蘇州科景生物医薬科技有限公司 | MULTIFUNCTIONAL COMPOSITION AND METHOD FOR PRODUCTION AND USE THEREOF |
US9937198B2 (en) | 2013-05-30 | 2018-04-10 | Pinghu Sciscape Bio-Pharmaceutical Technology Co., Ltd. | Multi-functional composition and preparation method and application thereof |
JP2018188408A (en) * | 2017-05-11 | 2018-11-29 | 国立大学法人群馬大学 | Regulatory t-cell enhancer and medicine and food composition containing the same |
Also Published As
Publication number | Publication date |
---|---|
JP3455633B2 (en) | 2003-10-14 |
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