JPH0525050A - Hepatitis therapeutic agent - Google Patents
Hepatitis therapeutic agentInfo
- Publication number
- JPH0525050A JPH0525050A JP20842791A JP20842791A JPH0525050A JP H0525050 A JPH0525050 A JP H0525050A JP 20842791 A JP20842791 A JP 20842791A JP 20842791 A JP20842791 A JP 20842791A JP H0525050 A JPH0525050 A JP H0525050A
- Authority
- JP
- Japan
- Prior art keywords
- colominic acid
- hepatitis
- acid
- body weight
- group
- 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.)
- Pending
Links
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、コロミン酸又はコロミ
ン酸部分加水分解物を有効成分とする肝炎治療薬に関す
る。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a therapeutic drug for hepatitis containing colominic acid or a partial hydrolyzate of colominic acid as an active ingredient.
【０００２】[0002]
【従来の技術】コロミン酸は、シアル酸（Ｎ−アセチル
ノイラミン酸、ＮｅｕＡｃで表わされる）を構成単位と
し、分子量１００００程度のホモポリマーであって、大
腸菌や髄膜炎双球菌などの血清型分類の基準となる多糖
体である。BACKGROUND ART Colominic acid is a homopolymer having sialic acid (represented by N-acetylneuraminic acid, NeuAc) as a constitutional unit and having a molecular weight of about 10,000, and is a serotype of Escherichia coli or N. meningitidis. It is a polysaccharide that serves as a standard for classification.
【０００３】コロミン酸は、エシエリヒア属菌のような
微生物を培養することにより、製造される〔特公昭４７
−２６３１９号、特開平１−１４４９８９号〕。さら
に、コロミン酸は、部分加水分解することにより、コロ
ミン酸より分子量の小さいオリゴマーを製造できる
〔Ｈ．ノモトら、Arch. Biochem. Biophys.,２１８巻、
３３５−３４１ページ（１９８２）〕。Colominic acid is produced by culturing microorganisms such as the genus Escherichia.
No. 26319, JP-A No. 1-144989]. Furthermore, colominic acid can be partially hydrolyzed to produce an oligomer having a smaller molecular weight than colominic acid [H. Nomoto et al., Arch. Biochem. Biophys., 218,
335-341 (1982)].
【０００４】しかるに、コロミン酸及びその部分加水分
解物の生理活性については、あまり研究されていない。However, the physiological activity of colominic acid and its partial hydrolysates has not been studied so much.
【０００５】ところで、コロミン酸の構成単位であるＮ
−アセチルノイラミン酸については、従来より抗ウィル
ス作用、抗炎症作用、抗アレルギー作用を示すことが報
告されている〔ロバート・エル・ハーシュ（Hess, E.
L.)他、ザ・ジャーナル・オブ・イムノロジー（The Jo
urnal of Immnology) 、１２７巻５号（１９８１年）Ｐ
１７４０〜Ｐ１７４３ピー・グールーグ（Gorog, P.
）他、エージェンツアンド アクションズ（Agents an
d Actions）、８巻５号（１９７８年）Ｐ５４３〜Ｐ５
４５イトウ ヒロミ他、薬理と治療 １３巻７号（１
９８５年）Ｐ４７９〜Ｐ４９４第６１回日本薬理学会
総会（昭和６３年３月２３日〜２６日、「モルモットに
おける N-acetylneuraminic acid（NANA）の抗アレルギ
ー作用」）など〕。By the way, N which is a constitutional unit of colominic acid
-Acetylneuraminic acid has previously been reported to exhibit antiviral, anti-inflammatory, and antiallergic effects [Robert El Hirsch (Hess, E.
L.) and others, The Journal of Immunology (The Jo
urnal of Immnology), Volume 127, Issue 5 (1981) P
1740 to P1743 Gorog, P.
), Agents an Actions
d Actions), Volume 8 Issue 5 (1978) P543-P5
45 Ito Hiromi et al., Pharmacology and Treatment Vol. 13 No. 7 (1
985) P479-P494 The 61st Annual Meeting of the Japanese Pharmacological Society (March 23-26, 1988, "Anti-allergic action of N-acetylneuraminic acid (NANA) in guinea pig").
【０００６】[0006]
【発明が解決しようとする課題】本発明の目的は、コロ
ミン酸及びコロミン酸の部分加水分解物を用いた新規な
医薬品を提供することにある。An object of the present invention is to provide a novel drug using colominic acid and a partial hydrolyzate of colominic acid.
【０００７】本発明者は、コロミン酸及びコロミン酸の
部分加水分解物が肝炎に対する抑制作用を有することを
見出し、本発明に到達した。The present inventor has found that colominic acid and a partial hydrolyzate of colominic acid have an inhibitory action against hepatitis, and arrived at the present invention.
【０００８】[0008]
【課題を解決するための手段】本発明は、コロミン酸、
下記一般式〔Ｉ〕で示される化合物又はその薬学的に許
容される塩を有効成分とする肝炎治療薬に関する。The present invention provides colominic acid,
The present invention relates to a therapeutic agent for hepatitis, which comprises a compound represented by the following general formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient.
【０００９】[0009]
【化２】 [Chemical 2]
【００１０】（式中、ｎは０〜１０の整数である）(In the formula, n is an integer of 0 to 10)
【００１１】以下本発明について説明する。一般式
〔Ｉ〕で示されるコロミン酸部分加水分解物は、市販の
コロミン酸からノモトらの方法（Arch. Biochem. Bioph
ys.,２１８巻、３３５−３４１ページ（１９８２）〕を
用いて得ることができる。即ち、塩酸を用いてコロミン
酸を部分加水分解し、次いで分解物を、ＤＥＡＥ−セフ
ァデックス（Sephadex）Ａ−２５クロマトグラフィー等
の精製手段を用いて分画することにより、ｎが０〜１０
のＮ−アセチルノイラミン酸ユニットが２〜１２のオリ
ゴマーを得ることができる。ｎは１〜７であることが好
ましい。The present invention will be described below. The partial hydrolyzate of colominic acid represented by the general formula [I] can be obtained from commercially available colominic acid by the method of Nomoto et al. (Arch. Biochem. Bioph
ys., 218, 335-341 (1982)]. That is, colominic acid is partially hydrolyzed using hydrochloric acid, and then the decomposed product is fractionated by using a purification means such as DEAE-Sephadex A-25 chromatography to obtain n of 0 to 10
It is possible to obtain an oligomer having 2 to 12 N-acetylneuraminic acid units. n is preferably 1 to 7.
【００１２】本発明には、一般式〔Ｉ〕の化合物の薬学
的に許容される塩も用いることができる。塩を形成する
対イオンとしては、ナトリウム、カリウム、アンモニウ
ム、アミン等を例示できるが、これらに限定されるもの
ではない。In the present invention, pharmaceutically acceptable salts of the compounds of general formula [I] can also be used. Examples of the counter ion that forms a salt include, but are not limited to, sodium, potassium, ammonium, amine and the like.
【００１３】本発明の肝炎治療薬は、0.１〜１００mg／
体重１Kgを経口投与、注射投与等することにより用いら
れる。The therapeutic drug for hepatitis of the present invention is 0.1 to 100 mg /
It is used by oral administration, injection administration, etc. with a body weight of 1 kg.
【００１４】[0014]
【発明の効果】本発明は、肝炎に対する抑制作用を有す
る肝炎治療薬を提供する。急性肝炎の主な原因はウィル
ス、アルコール、薬物等がある。本発明の肝炎治療薬
は、肝細胞に障害を起こさせるモデルにおいて有効性を
示しており、肝炎全般に対して治療効果を有する。INDUSTRIAL APPLICABILITY The present invention provides a hepatitis therapeutic drug having an inhibitory effect on hepatitis. The main causes of acute hepatitis are viruses, alcohol and drugs. The therapeutic agent for hepatitis of the present invention has been shown to be effective in a model causing damage to hepatocytes, and has a therapeutic effect on hepatitis in general.
【００１５】[0015]
【実施例】以下、本発明を実施例によりさらに説明す
る。尚、本実施例中、Ｎ−３、Ｎ−６、及びＮ−９は、
それぞれ、ｎが１、４及び７の一般式〔Ｉ〕のコロミン
酸部分加物のナトリウム塩である。EXAMPLES The present invention will be further described below with reference to examples. In the present embodiment, N-3, N-6, and N-9 are
Each is a sodium salt of a colominic acid partial additive of the general formula [I] in which n is 1, 4 or 7.
【００１６】実施例：ガラクトサミン肝炎に対する作用
（１）実験動物
体重２００〜２５０ｇのウィスター系雄性ラットを用い
た。Example: Effect on galactosamine hepatitis (1) Experimental animals Male Wistar rats weighing 200 to 250 g were used.
【００１７】（２）実験材料
Ｄ−ガラクトサミン塩酸塩はシグマ社より購入した。コ
ロミン酸限定分解物はコロミン酸を酸で加水分解後、分
離精製したものを使用した。(2) Experimental material D-galactosamine hydrochloride was purchased from Sigma. As the colominic acid limited decomposition product, one obtained by hydrolyzing colominic acid with an acid and then separating and purifying was used.
【００１８】（３）実験方法
ラットの腹腔内に体重１ｋｇ当たり２００ｍｇのガラク
トサミンを投与し、肝炎を発症させた。上記ラットに下
記のごとく、被験薬（II〜ＸIII 群）または生理食塩水
（Ｉ群）をガラクトサミン投与３０分前に皮下投与し
た。被験薬投与２４時間後に軽エーテル麻酔下で採血
し、血清中のグルタミン酸オキザロ酢酸トランスアミナ
ーゼ（ＧＯＴ）、グルタミン酸ピルビン酸トランスアミ
ナーゼ（ＧＰＴ）及びアルカリ性ホスファターゼ（ＡＬ
Ｐ）を測定した。(3) Experimental Method Rats were intraperitoneally administered with 200 mg of galactosamine per kg of body weight to develop hepatitis. The test drug (groups II to XIII) or physiological saline (group I) was subcutaneously administered 30 minutes before the administration of galactosamine to the rats as described below. Twenty-four hours after administration of the test drug, blood was collected under anesthesia with light ether, and serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), and alkaline phosphatase (AL) were collected.
P) was measured.
【００１９】Ｉ 群：生理食塩水 ５．０ｍｌ／（ラ
ット体重１ｋｇ当り）を投与
ＩＩ 群：Ｎ−３ ３０ｍｇ／（ラット体重１
ｋｇ当り）を投与
III 群：Ｎ−３ １００ｍｇ／（ラット体重１
ｋｇ当り）を投与
ＩＶ 群：Ｎ−３ ３００ｍｇ／（ラット体重１
ｋｇ当り）を投与
Ｖ 群：Ｎ−６ ３０ｍｇ／（ラット体重１ｋ
ｇ当り）を投与
ＶＩ 群：Ｎ−６ １００ｍｇ／（ラット体重１
ｋｇ当り）を投与
ＶＩＩ群：Ｎ−６ ３００ｍｇ／（ラット体重１
ｋｇ当り）を投与
ＶIII 群：Ｎ−９ ３０ｍｇ／（ラット体重１
ｋｇ当り）を投与
ＩＸ 群：Ｎ−９ １００ｍｇ／（ラット体重１
ｋｇ当り）を投与
Ｘ 群：Ｎ−９ ３００ｍｇ／（ラット体重１ｋ
ｇ当り）を投与
ＸＩ 群：コロミン酸 ３０ｍｇ／（ラット体重１
ｋｇ当り）を投与
ＸII 群：コロミン酸 １００ｍｇ／（ラット体重１
ｋｇ当り）を投与
ＸIII 群：コロミン酸 ３００ｍｇ／（ラット体重１
ｋｇ当り）を投与Group I: administration of physiological saline 5.0 ml / (per kg of rat body weight) Group II: N-3 30 mg / (rat body weight 1)
administered per kg Group III: N-3 100 mg / (rat body weight 1)
IV group: N-3 300 mg / (rat body weight 1)
per kg) V group: N-6 30 mg / (rat body weight 1 k
VI group: N-6 100 mg / (rat body weight 1)
per kg) VII group: N-6 300 mg / (rat body weight 1)
VIII group: N-9 30 mg / (rat body weight 1)
IX group: N-9 100 mg / (rat body weight 1)
X group: N-9 300 mg / (rat body weight 1 k)
per g) XI group: colominic acid 30 mg / (rat body weight 1
administered per kg XII group: colominic acid 100 mg / (rat body weight 1)
Xkg group: colominic acid 300 mg / (rat body weight 1)
per kg)
【００２０】（４）結果
ＩＩ〜ＸIII 群において、ガラクトサミン誘発肝炎に対
する各生化学値のＩ群（生理食塩水投与群）を１００％
とした時の抑制率を表−１に示した。コロミン酸及びコ
ロミン酸限定分解物はガラクトサミン投与によるＧＯ
Ｔ，ＧＰＴ及びＡＬＰの増加を用量依存的に抑制した。(4) Results In groups II to XIII, 100% of group I (physiological saline administration group) of each biochemical value for galactosamine-induced hepatitis
Table 1 shows the inhibition ratios when Colominic acid and colominic acid limited degradation products are GO by administration of galactosamine
The increase in T, GPT and ALP was suppressed in a dose-dependent manner.
【００２１】表−１ ラットのガラクトサミン誘発肝炎
に対するコロミン酸及び限定加水分解物の効果（抑制
％）
───────────────────────────────────
GOT(Karmen) GPT(Karmen) ALP(IU)
───────────────────────────────────
II (N-3: 30mg/kg) 2.34 1.65 2.89
III (N-3:100mg/kg) 8.96 9.18 1.65
ＩＶ (N-3:300mg/kg) 13.22 * 12.94 * 4.99
Ｖ (N-6: 30mg/kg) 5.53 2.45 10.22 *
ＶＩ (N-6:100mg/kg) 26.96 * 24.86 12.65 ***
ＶII (N-6:300mg/kg) 36.94 * 35.54 * 12.13 **
VIII (N-9: 30mg/kg) 4.55 3.59 8.65 *
ＩＸ (N-9:100mg/kg) 20.56 * 16.53 9.10 *
Ｘ (N-9:300mg/kg) 22.34 * 22.91 * 10.23 *
ＸＩ (コロミン酸：30mg/kg) 2.86 2.67 2.36
ＸII (コロミン酸：100mg/kg) 10.98 15.83 2.77
ＸIII(コロミン酸：300mg/kg) 15.63 * 14.96 * 5.66
───────────────────────────────────
*:0.01＜ｐ≦0.05 , **:0.001 ≦ｐ<0.01 , ***:p ≦0.
001 , ガラクトサミン投与群との有意差Table 1 Effect of colominic acid and limited hydrolyzate on galactosamine-induced hepatitis in rats (% inhibition) ────────────────────────── ────────── GOT (Karmen) GPT (Karmen) ALP (IU) ──────────────────────────── ─────── II (N-3: 30mg / kg) 2.34 1.65 2.89 III (N-3: 100mg / kg) 8.96 9.18 1.65 IV (N-3: 300mg / kg) 13.22 * 12.94 * 4.99 V ( N-6: 30mg / kg) 5.53 2.45 10.22 * VI (N-6: 100mg / kg) 26.96 * 24.86 12.65 *** VII (N-6: 300mg / kg) 36.94 * 35.54 * 12.13 ** VIII (N- 9: 30mg / kg) 4.55 3.59 8.65 * IX (N-9: 100mg / kg) 20.56 * 16.53 9.10 * X (N-9: 300mg / kg) 22.34 * 22.91 * 10.23 * XI (colominic acid: 30mg / kg) 2.86 2.67 2.36 XII (colominic acid: 100 mg / kg) 10.98 15.83 2.77 XIII (colominic acid: 300 mg / kg) 15.63 * 14.96 * 5.66 ────────────────────── ─────── ─────── *: 0.01 <p ≦ 0.05, **: 0.001 ≦ p <0.01, ***: p ≦ 0.
001, significant difference from galactosamine administration group
Claims (2)
る化合物又はその薬学的に許容される塩を有効成分とす
る肝炎治療薬。 【化１】 （式中、ｎは０〜１０の整数である。）1. A therapeutic agent for hepatitis containing colominic acid, a compound represented by the following general formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical 1] (In the formula, n is an integer of 0 to 10.)
化合物又はその薬学的に許容される塩を有効成分とする
請求項１記載の肝炎治療薬。2. The therapeutic agent for hepatitis according to claim 1, which comprises a compound of the general formula [I] or a pharmaceutically acceptable salt thereof, wherein n is an integer of 1 to 7 as an active ingredient.
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20842791A JPH0525050A (en) | 1991-07-24 | 1991-07-24 | Hepatitis therapeutic agent |
| DK92103908.7T DK0502550T3 (en) | 1991-03-07 | 1992-03-06 | Colomic acid and partial hydrolysis products of colomic acid for the manufacture of medications for the treatment of hepatitis, nephritis and arthritis |
| AU11494/92A AU649110B2 (en) | 1991-03-07 | 1992-03-06 | Pharmaceutical preparation |
| AT92103908T ATE116546T1 (en) | 1991-03-07 | 1992-03-06 | COLOMIC ACID AND PRODUCTS OF PARTIAL HYDROLYSIS OF COLOMIC ACID FOR THE PRODUCTION OF MEDICINAL PRODUCTS FOR THE TREATMENT OF HEPATITIS, NEPHRITIS AND ARTHRITIS. |
| CA002062370A CA2062370A1 (en) | 1991-03-07 | 1992-03-06 | Pharmaceutical preparation |
| DE69201066T DE69201066T2 (en) | 1991-03-07 | 1992-03-06 | Colominic acid and products of partial hydrolysis of colominic acid for the manufacture of medicaments for the treatment of hepatitis, nephritis and arthritis. |
| EP92103908A EP0502550B1 (en) | 1991-03-07 | 1992-03-06 | Colominic acid and partial hydrolysis products of colominic acid for the preparation of medicaments for the treatment of hepatitis, nephritis and arthritis |
| KR1019920003815A KR920017660A (en) | 1991-03-07 | 1992-03-07 | medicine |
| US08/219,236 US5516764A (en) | 1991-03-07 | 1994-03-28 | Anti-inflammatory agent |
| US08/450,699 US5668115A (en) | 1991-03-07 | 1995-05-25 | Methods for inhibiting the chemotaxis of neutrophils |
| US08/450,930 US5763420A (en) | 1991-03-07 | 1995-05-25 | Method for modulating the immune system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20842791A JPH0525050A (en) | 1991-07-24 | 1991-07-24 | Hepatitis therapeutic agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0525050A true JPH0525050A (en) | 1993-02-02 |
Family
ID=16556041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20842791A Pending JPH0525050A (en) | 1991-03-07 | 1991-07-24 | Hepatitis therapeutic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0525050A (en) |
-
1991
- 1991-07-24 JP JP20842791A patent/JPH0525050A/en active Pending
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