JPH0320221A - Hepatopathy therapeutic agent - Google Patents
Hepatopathy therapeutic agentInfo
- Publication number
- JPH0320221A JPH0320221A JP1154069A JP15406989A JPH0320221A JP H0320221 A JPH0320221 A JP H0320221A JP 1154069 A JP1154069 A JP 1154069A JP 15406989 A JP15406989 A JP 15406989A JP H0320221 A JPH0320221 A JP H0320221A
- Authority
- JP
- Japan
- Prior art keywords
- therapeutic agent
- hepatopathy
- acetylpyrrole
- liver diseases
- liver
- 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
- 239000003814 drug Substances 0.000 title claims description 15
- 208000019423 liver disease Diseases 0.000 title claims description 13
- 229940124597 therapeutic agent Drugs 0.000 title claims description 12
- IGJQUJNPMOYEJY-UHFFFAOYSA-N 2-acetylpyrrole Chemical compound CC(=O)C1=CC=CN1 IGJQUJNPMOYEJY-UHFFFAOYSA-N 0.000 claims description 20
- 239000004480 active ingredient Substances 0.000 claims description 3
- 238000012360 testing method Methods 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 6
- 235000010980 cellulose Nutrition 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 206010067125 Liver injury Diseases 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 244000215068 Acacia senegal Species 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 231100000439 acute liver injury Toxicity 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- -1 etc.) Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960001855 mannitol Drugs 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910052776 Thorium Inorganic materials 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、肝疾患治療剤に関し、更に詳しくは２−アセ
チルピロールを有効成分とする肝疾患治療剤に関する．
従来の技術
２−アセチルビロールは公知の化合物であり、その物性
がディクショナリー・才プ・才−ガニツク●コンパウン
ズ（Ｄｉｃｔｉｏｎａｒｙ ｏｆ Ｏｒｇａｎｉｃ ｃ
ｏｍｐ一ｏｕｎｄｓ）（第５版， １９８２年）に記載
されている．また、その中枢神経抑制作用がジケーナル
・才プ・メデイシナルケミストリー（Ｊｏｕｒｎａｌ
ｏｆ Ｍｃｄｉｃｉｎ−ａｌ Ｃｈｅｍｉｓｔｒｙ）
［第１１巻．第１２５１〜１２５２ページ（１９６８年
）］に記載されている．しかしながら、２ーアセチルピ
ロールに肝疾患治療剤としての作用があることは知られ
ていない．
一方、従来の肝疾患の治療薬で２−アセチルピロールに
構造類似のものも知られていない．発明が解決しようと
する課題
本発明の目的は、薬効が高く安全性の高い優れた肝疾患
治療剤を提供することにある．課題を解決するための手
段
本発明者らは、前記目的を達成すべく鋭意努力した結果
、肝疾患治療剤の開発研究の過程で２−アセチルビロー
ルがマウスを用いた急性肝障害モデルにおいて、極めて
良好な治療効果を示すことを見いだし、本発明を完成し
た．
すなわち、本発明は２−アセチルピロールを有効成分と
する肝疾患治療剤である．
２−アセチルビロールの腹腔内投与の急性毒性値は、後
記試験例から明らかになるが、ＬＤ．．値が１０００ｍ
ｇ／ ｋｇ以上であり、安全性の高い薬物である．
また、２−アセチルピロールの投与量は、投与ルート、
投与対象の年齢及び症状などにより適宜選定されるが、
一般成人に対しては１日１〜１００ｍｇを１〜３回に分
けて投与する．投与方法は経口又は非経口のいずれでも
よく、その投与剤形としては、錠剤、顆粒剤、カプセル
剤、注射剤、輸液などである．上記各製剤は日本薬局方
製剤総則に従って製造する．各種添加剤としては、賦形
剤（デンプン、乳糖、シヨ糖、マンニトールなどのｍ類
、結晶セルロース、カルボキシメチルセルロースなどの
セルロース類など）、結合剤（ヒドロキシプロビルセル
ロース、ポリビニルビロリドン、結晶セルロースなど）
、滑沢剤（ステアリン酸マグネシウム、タルク、軽質無
水ケイ酸など）、崩壊剤、安定剤、湿潤剤、界面活性剤
、溶媒などである．
本発明の肝疾患治療剤は、単独で用いても優れた効果が
得られるが、他の肝疾患治療剤と併用して用いることも
できる．
発明の効果
本発明の肝疾患治療剤は既存の肝疾患治療剤に比べ化学
構造を異にする特異的なものであり、毒性が低い．この
ため、多量にかつ連続して投与が可能なので優れた効果
を得ることができる．実施例
以下、試験例及び実施例を示して本発明を更に具体的に
説明する．
（試験例１）
［四塩化炭素誘発急性肝障害に対する作用］（υ被馳動
物 ＩＣＲ系雄性マウス（７週齢、体重約３０ｇ）８匹
を１群として試験に供した．■試料 ２−アセチルピロ
ールを５％アラビアゴム溶液に懸濁して各種濃度（３０
、１ｏｏ及び３００ａｇ／ｋｇ）の被験薬を調製し、ジ
イソブロビル−１．３−ジチ才−ル−２−イリデンマロ
ネート３ｏ及び１００ｍｇ／ｋｇを５％アラビアゴム溶
液に懸濁したものを比較薬とし、５％アラビアゴム溶液
のみのものを対照とした．
■これらの試料をそれぞれｔｏｇ／ｈｇ体重の割合で個
別の動物に経口投与した．３０分後、オリーブ油で希釈
した四塩化炭素０．０３ａ！！／ｋｇを１ ０ｄ ／
ｋｇ体重の割合で個別の動物に経口投与し肝障害を発生
させた．１８時間の放置後、動物の股動静脈を切開して
採血し、３０００ｒ． ｐ． ｍで１０分間遠心分離す
ることにより血清を採取して、血清中のアラニンアミノ
トランスフェラーゼ（ＧＰＴ）及びアスパラギン酸アミ
ノトランスフェラーゼ（ＧＯＴ）活性を自動分析装置で
測定し、肝障害の指標とした．その結果を第１表に示し
た．
第１表
（注）ＧＰＴ値及びＧＯＴ値は平均値士標準誤差で示第
１表から明らかなように、２−アセチルビロールを３０
ｍｇ／ｋｇ以上腹腔内投−与した群では血清ＧＰＴ値及
びＧＯＴ値の上昇が顕著に抑制され、また、これらの値
は比較薬３０又は１００ｍｇ／ｋｇを腹腔内投与した群
より優れている．
（試験例２）
［急性毒性試験］
ＩＣＲ系雄性マウス（５週齢、体重約２５ｇ）１０匹を
１群として試験に供した．試験例１に準じて２ーアセチ
ルピロールを含有する試料を調製し、それらを動物に１
回腹腔内投与し、７日間観察してＬＤ．．値を求めた．
その結果、最高投与量の１０００ｍｇ／ｋｇでも死亡例
を全く認めなかった．従って、腹腔内投与のＬＤ．値は
１０００ｍｇ／ ｋｇ以上であった．（実施例１） 錠
剤
成分 配合量（ｍｇ）２−アセ
チルピロール ５０結晶セルロース
２４２ヒドロキシプロビルセルロース
５３００ｍｇ
上記処方で第１１改正日本薬局方製剤総則１３に従い錠
剤を製造した．
（実施例２） ！’ｉ粒剤
成分 配合量（ｍｇ）２−アセ
チルビロール １００バレイショデンプン
’４１ｋ （Ｈ乳糖
４８０（実施例３） ドライシロップ剤
成分
２−アセチルピロール
白糖
ｄ−マンニトール
ヒドロキシブロビルセルロース
力ルポキシメチノレセルロースナ
配合量（ｍｇ）
１００
４３０
４３０
２０
トリウム１０
１．０００ｍｇ
上記処方で第１１改正日本薬局方製剤総則ｌ４に従いド
ライシロップ剤を製造した．DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a therapeutic agent for liver diseases, and more particularly to a therapeutic agent for liver diseases containing 2-acetylpyrrole as an active ingredient. Conventional technology 2 - Acetylvirol is a well-known compound, and its physical properties are listed in the Dictionary of Organic Compounds.
omp-ounds) (5th edition, 1982). In addition, its central nervous system depressing effect has been reported in the journal
of Mcdicin-al Chemistry)
[Volume 11. No. 1251-1252 (1968)]. However, it is not known that 2-acetylpyrrole has any action as a therapeutic agent for liver diseases. On the other hand, there are no known conventional drugs for treating liver diseases that have a structure similar to 2-acetylpyrrole. Problems to be Solved by the Invention An object of the present invention is to provide an excellent therapeutic agent for liver diseases that is highly effective and safe. Means for Solving the Problems As a result of our earnest efforts to achieve the above object, the present inventors discovered that, in the course of research and development of therapeutic agents for liver diseases, 2-acetylvirol was used in an acute liver injury model using mice. They discovered that it has extremely good therapeutic effects and completed the present invention. That is, the present invention is a liver disease therapeutic agent containing 2-acetylpyrrole as an active ingredient. The acute toxicity value of intraperitoneal administration of 2-acetylvirol will become clear from the test examples described later, but LD. ．． value is 1000m
g/kg or more, making it a highly safe drug. In addition, the dosage of 2-acetylpyrrole is determined by the administration route,
The dosage will be appropriately selected depending on the age and symptoms of the recipient, but
For general adults, administer 1 to 100 mg per day in 1 to 3 divided doses. The administration method may be either oral or parenteral, and the dosage forms include tablets, granules, capsules, injections, and infusions. Each of the above preparations is manufactured in accordance with the Japanese Pharmacopoeia's general rules for preparations. Various additives include excipients (starch, lactose, sucrose, mannitol, celluloses such as crystalline cellulose, carboxymethyl cellulose, etc.), binders (hydroxypropylcellulose, polyvinylpyrrolidone, crystalline cellulose, etc.) Such)
, lubricants (magnesium stearate, talc, light silicic anhydride, etc.), disintegrants, stabilizers, wetting agents, surfactants, solvents, etc. Although the therapeutic agent for liver diseases of the present invention can provide excellent effects when used alone, it can also be used in combination with other therapeutic agents for liver diseases. Effects of the Invention The therapeutic agent for liver diseases of the present invention has a unique chemical structure different from existing therapeutic agents for liver diseases, and has low toxicity. Therefore, it can be administered in large quantities and continuously, resulting in excellent effects. EXAMPLES The present invention will now be explained in more detail with reference to test examples and examples. (Test Example 1) [Effect on carbon tetrachloride-induced acute liver injury] (υ Subject animals: Eight male ICR mice (7 weeks old, weight approximately 30 g) were subjected to the test as a group.■ Sample: 2-acetyl Pyrrole was suspended in a 5% gum arabic solution at various concentrations (30%
, 1oo and 300ag/kg) were prepared, and diisobrobyl-1,3-diti-2-ylidenemalonate 3o and 100mg/kg were suspended in a 5% gum arabic solution and used as a comparison drug. and a control containing only 5% gum arabic solution. ■These samples were orally administered to individual animals at a ratio of tog/hg body weight. After 30 minutes, 0.03a of carbon tetrachloride diluted with olive oil! ! /kg to 10d/
kg body weight was orally administered to individual animals to induce liver damage. After leaving for 18 hours, the animal's femoral artery and vein were incised and blood was collected. p. Serum was collected by centrifugation for 10 minutes at m, and alanine aminotransferase (GPT) and aspartate aminotransferase (GOT) activities in the serum were measured using an automatic analyzer and used as indicators of liver damage. The results are shown in Table 1. Table 1 (Note) GPT values and GOT values are expressed as average values and standard errors.As is clear from Table 1, 2-acetylvirol was
The increase in serum GPT and GOT values was significantly suppressed in the group administered intraperitoneally at a dose of 30 or 100 mg/kg or more, and these values were superior to the group administered intraperitoneally at 30 or 100 mg/kg. (Test Example 2) [Acute Toxicity Test] A group of 10 male ICR mice (5 weeks old, weight approximately 25 g) was subjected to the test. Samples containing 2-acetylpyrrole were prepared according to Test Example 1, and they were administered to animals for 1 time.
It was administered intraperitoneally and observed for 7 days. ．． I calculated the value. As a result, no deaths were observed even at the highest dose of 1000 mg/kg. Therefore, intraperitoneal administration of LD. The value was over 1000mg/kg. (Example 1) Tablet ingredients Blend amount (mg) 2-acetylpyrrole 50 crystalline cellulose
242 Hydroxyprobylcellulose 5300mg Tablets were manufactured according to the 11th revised Japanese Pharmacopoeia Preparation General Provisions 13 using the above formulation. (Example 2)! 'i Granule ingredients Amount (mg) 2-acetylvirol 100 Potato starch '41k (H-lactose
480 (Example 3) Dry syrup ingredient 2-Acetylpyrrole White sugar d-Mannitol Hydroxybrobyl Cellulose Lupoxymethyl cellulose Ingredients (mg) 100 430 430 20 Thorium 10 1.000 mg The above formulation was used in the 11th revision Japanese Pharmacy A dry syrup was manufactured according to the general rules for formula preparations 14.
Claims (1)
療剤。(1) A liver disease therapeutic agent containing 2-acetylpyrrole as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1154069A JPH0320221A (en) | 1989-06-16 | 1989-06-16 | Hepatopathy therapeutic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1154069A JPH0320221A (en) | 1989-06-16 | 1989-06-16 | Hepatopathy therapeutic agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0320221A true JPH0320221A (en) | 1991-01-29 |
Family
ID=15576214
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1154069A Pending JPH0320221A (en) | 1989-06-16 | 1989-06-16 | Hepatopathy therapeutic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0320221A (en) |
-
1989
- 1989-06-16 JP JP1154069A patent/JPH0320221A/en active Pending
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