JP2811464B2 - Intestinal medicine - Google Patents
Intestinal medicineInfo
- Publication number
- JP2811464B2 JP2811464B2 JP1109797A JP10979789A JP2811464B2 JP 2811464 B2 JP2811464 B2 JP 2811464B2 JP 1109797 A JP1109797 A JP 1109797A JP 10979789 A JP10979789 A JP 10979789A JP 2811464 B2 JP2811464 B2 JP 2811464B2
- Authority
- JP
- Japan
- Prior art keywords
- endothelin
- intestinal
- mouse
- present
- intestinal medicine
- 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.)
- Expired - Lifetime
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
【発明の詳細な説明】 産業上の利用分野 この発明は新規な整腸剤に関するものである。さらに
詳細にはマウス・エンドセリンβを有効成分として含有
する整腸剤に関するものである。Description: TECHNICAL FIELD The present invention relates to a novel intestinal medicine. More specifically, the present invention relates to an intestinal preparation containing mouse endothelin β as an active ingredient.
従来の技術およびこの発明が解決しようとする問題点 この発明の発明者等の一部は先に、ブタの血管内皮細
胞の培養上清から血管収縮作用を有するエンドセリンを
分離し、その化学構造を明らかにした（ネィチャー（Na
ture）332,411〜415（1988））。更にヒト・エンドセリ
ンｃ−DNAを用いて、遺伝子組換え技術によりマウスか
ら新たに、エンドセリンα及びエンドセリンβの遺伝子
を発見するに至り（第11回日本分子生物学会講演要旨集
1988年12月20日）、そのアミノ酸配列情報をもとに各ペ
プチドを化学的に合成して、その血管収縮作用を確認し
た。2. Description of the Related Art Prior art and problems to be solved by the present invention Some of the inventors of the present invention first separated endothelin having a vasoconstrictive action from a culture supernatant of porcine vascular endothelial cells, and analyzed its chemical structure. Revealed (Nature (Na
ture) 332, 411-415 (1988)). Furthermore, they have newly discovered endothelin α and endothelin β genes from mice by genetic recombination using human endothelin c-DNA (The 11th Annual Meeting of the Molecular Biology Society of Japan)
(December 20, 1988) Based on the amino acid sequence information, each peptide was chemically synthesized to confirm its vasoconstrictive action.
このような知見に基ずきマウス・エンドセリンβの新
しい薬理作用の開発研究を企図した。Based on such findings, we aimed to develop new pharmacological effects of mouse endothelin β.
発明の構成および効果 この発明者等は種々研究の結果、マウス・エンドセリ
ンβが優れた腸管収縮作用を有することを見出し、さら
に鋭意研究の末この発明を完成した。Constitution and effect of the present invention As a result of various studies, the present inventors have found that mouse endothelin β has an excellent intestinal contraction effect, and completed the present invention after further intensive studies.
この発明の整腸剤の有効成分であるマウス・エンドセ
リンβは次のアミノ酸配列で示すことができる。Mouse endothelin β, which is an active ingredient of the intestinal preparation of the present invention, can be represented by the following amino acid sequence.
（−ｓ−ｓ−結合の位置:1位と15位及び３位と11位のシ
ステイン残基の間でそれぞれ形成される） このマウス・エンドセリンβは上記遺伝子組換え技術
やペプチド合成法などのペプチド製造のための常法によ
り製造することができる。次にこの発明の整腸剤の有効
成分であるマウス・エンドセリンβの腸管収縮作用につ
いて下記試験例により説明する。 (Position of -ss- bond: formed between cysteine residues at positions 1 and 15 and at positions 3 and 11) This mouse endothelin β is produced by the above-mentioned gene recombination technique or peptide synthesis method. It can be produced by a conventional method for producing a peptide. Next, the intestinal contraction effect of mouse endothelin β, which is an active ingredient of the intestinal preparation of the present invention, will be described with reference to the following test examples.
試験例（マウス回腸収縮作用） ICR雄性マウスの回腸を摘出し、95％酸素−５％二酸
化炭素を通気した37℃のタイロード栄養液を入れたマグ
ヌスバスの中で懸垂する。回腸に0.5gの緊張を負荷し、
張力トランスデューサーで等張性張力を測定する。な
お、マグヌスバスは予めシリコン処理を施しておく。張
力が0.5gでほぼ一定になった時点で10-6Mアセチルコリ
ンを添加し、収縮を惹起させた後、ただちに標本を新し
いタイロード栄養液にて洗浄する。この標本を新しいタ
イロード栄養液にて洗浄する。この操作を３回繰り換え
した後、10-5Mアセチルコリンを添加して惹起される収
縮力を測定し、この値を100％とする。この標本を洗浄
した後にマウス・エンドセリンβを添加した後、腸管収
縮作用を測定した。その結果、マウス・エンドセリンβ
は10-7Mの濃度で54.5±3.6％の腸管収縮作用を示した。Test example (mouse ileal contraction action) The ileum of an ICR male mouse is removed and suspended in a Magnus bath containing a Tyrode nutrient solution at 37 ° C in which 95% oxygen-5% carbon dioxide has been aerated. Load the ileum with a strain of 0.5 g,
Measure isotonic tension with a tension transducer. The Magnus bath is subjected to a silicon treatment in advance. When the tension becomes almost constant at 0.5 g, 10 -6 M acetylcholine is added to induce contraction, and the sample is immediately washed with a new Tyrode nutrient solution. The specimen is washed with fresh Tyrode nutrient solution. After repeating this operation three times, 10-5 M acetylcholine is added and the induced contractile force is measured, and this value is defined as 100%. After washing the specimen, mouse endothelin β was added, and the intestinal contraction action was measured. As a result, mouse endothelin β
Showed an intestinal contraction effect of 54.5 ± 3.6% at a concentration of 10 −7 M.
以上の試験例か明らかなように、この発明の整腸剤の
有効成分であるマウス・エンドセリンβは優れた腸管収
縮作用を有し、例えば便秘等の腸管疾病の治療剤として
有用である。As is clear from the above test examples, mouse endothelin β, which is an active ingredient of the intestinal preparation of the present invention, has an excellent intestinal contraction action, and is useful as a therapeutic agent for intestinal diseases such as constipation.
マウス・エンドセリンβは通常、ペプチド製剤に常用
の担体と混合してヒトに非経口的、すなわち注射剤、注
入剤として投与することができる。Mouse endothelin β can be generally administered to a human parenterally, ie, as an injection or infusion, by mixing with a carrier commonly used in peptide preparations.
投与量は患者の年齢、病気の種類、投与方法により異
なるが、一般的には、例えば静脈注射の場合標準体重60
kgの人につき、10μｇ〜1mgの範囲から最適投与量が適
宜選択される。The dose varies depending on the age of the patient, the type of the disease, and the method of administration.
The optimal dose is appropriately selected from the range of 10 μg to 1 mg per kg person.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 齋田 要 茨城県つくば市東１丁目１番３号 工業 技術院微生物工業技術研究所内 (72)発明者 友井 正明 大阪府東大阪市西岩田３丁目５番65号 (56)参考文献 特開 平２−76583（ＪＰ，Ａ) (58)調査した分野(Int.Cl.6，ＤＢ名) A61K 38/22 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ) ＷＰＩＤＳ（ＳＴＮ)──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Saita, 1-3-1 Higashi, Tsukuba City, Ibaraki Prefecture Inside the Research Institute of Microorganisms and Technology (72) Inventor, Masaaki Tomoi 3-5-Nishiiwata, Higashi-Osaka City, Osaka Prefecture No. 65 (56) References JP-A-2-76583 (JP, A) (58) Fields investigated (Int. Cl. 6 , DB name) A61K 38/22 CA (STN) REGISTRY (STN) WPIDS (STN)
Claims (1)
含有する整腸剤。[1] An intestinal preparation containing mouse endothelin β as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1109797A JP2811464B2 (en) | 1989-04-28 | 1989-04-28 | Intestinal medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1109797A JP2811464B2 (en) | 1989-04-28 | 1989-04-28 | Intestinal medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02286626A JPH02286626A (en) | 1990-11-26 |
| JP2811464B2 true JP2811464B2 (en) | 1998-10-15 |
Family
ID=14519464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1109797A Expired - Lifetime JP2811464B2 (en) | 1989-04-28 | 1989-04-28 | Intestinal medicine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2811464B2 (en) |
-
1989
- 1989-04-28 JP JP1109797A patent/JP2811464B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02286626A (en) | 1990-11-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |