JPH07101863A - Therapeutic agent for hepatopathy - Google Patents
Therapeutic agent for hepatopathyInfo
- Publication number
- JPH07101863A JPH07101863A JP5247138A JP24713893A JPH07101863A JP H07101863 A JPH07101863 A JP H07101863A JP 5247138 A JP5247138 A JP 5247138A JP 24713893 A JP24713893 A JP 24713893A JP H07101863 A JPH07101863 A JP H07101863A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- methyl
- active ingredient
- therapeutic agent
- dose
- 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
- 208000019423 liver disease Diseases 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title claims abstract description 8
- 229940124597 therapeutic agent Drugs 0.000 title claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 abstract description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 2
- 238000001914 filtration Methods 0.000 abstract description 2
- 230000002378 acidificating effect Effects 0.000 abstract 1
- HIANJWSAHKJQTH-UHFFFAOYSA-N pemirolast Chemical compound CC1=CC=CN(C2=O)C1=NC=C2C=1N=NNN=1 HIANJWSAHKJQTH-UHFFFAOYSA-N 0.000 abstract 1
- 238000007363 ring formation reaction Methods 0.000 abstract 1
- 150000003536 tetrazoles Chemical class 0.000 abstract 1
- 229940125904 compound 1 Drugs 0.000 description 9
- -1 1H -Tetrazol-5-yl Chemical group 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 7
- 229920006008 lipopolysaccharide Polymers 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 206010067125 Liver injury Diseases 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 231100000234 hepatic damage Toxicity 0.000 description 6
- 230000008818 liver damage Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
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- 239000007788 liquid Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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- 239000003937 drug carrier Substances 0.000 description 2
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- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- VRIISDMNWVGFGS-UHFFFAOYSA-N 2-(hydroxymethoxycarbonyl)benzoic acid Chemical compound OCOC(=O)C1=CC=CC=C1C(O)=O VRIISDMNWVGFGS-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 208000007788 Acute Liver Failure Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 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
- 241000894006 Bacteria Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
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- 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 1
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- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 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
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
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- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
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- 238000011047 acute toxicity test Methods 0.000 description 1
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- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
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- 239000011248 coating agent Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
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- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 1
- 230000009390 immune abnormality Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 210000004185 liver Anatomy 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
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 229960002900 methylcellulose Drugs 0.000 description 1
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Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
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Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、９−メチル−３−（１
Ｈ−テトラゾール−５−イル）−４Ｈ−ピリド［１，２
−ａ］ピリミジン−４−オン又はそれの生理学的に許容
される塩を有効成分とする肝疾患治療剤に関するもので
ある。The present invention relates to 9-methyl-3- (1
H-tetrazol-5-yl) -4H-pyrido [1,2
-A] relates to a therapeutic agent for liver disease, which comprises pyrimidin-4-one or a physiologically acceptable salt thereof as an active ingredient.
【０００２】[0002]
【従来の技術】肝臓は、生体内代謝をつかさどる重要な
臓器であることは良く知られており、肝疾患はわが国の
死亡原因の第５位を占め、年間４万人が死亡している。
肝障害としては、中毒性肝障害、薬物性肝障害、ウイル
ス性肝障害が挙げられ、近年これらの肝障害の発症機構
に免疫異常の関与も考えられるようになっている。これ
らの肝障害に対して、種々の治療薬の開発が続けられて
いる。2. Description of the Related Art It is well known that the liver is an important organ that controls in vivo metabolism, and liver disease is the fifth leading cause of death in Japan, and 40,000 people die each year.
Examples of liver damage include toxic liver damage, drug-induced liver damage, and viral liver damage, and in recent years, it has been considered that immune abnormalities are involved in the pathogenic mechanism of these liver damages. Various therapeutic agents have been continuously developed for these liver disorders.
【０００３】[0003]
【発明が解決しようとする課題】本発明は、上述の肝疾
患の治療に効果のある物質を見いだすことを目的とす
る。DISCLOSURE OF THE INVENTION The object of the present invention is to find a substance effective for treating the above-mentioned liver diseases.
【０００４】[0004]
【課題を解決するための手段】本発明者は、上述の肝疾
患の治療に効果のある物質を見いだすべく、鋭意研究し
た結果、アレルギー反応抑制作用（特開昭５４−３６２
９４号公報）の知られている、９−メチル−３−（１Ｈ
−テトラゾール−５−イル）−４Ｈ−ピリド［１，２−
ａ］ピリミジン−４−オン（化合物１と略す）又はそれ
の生理学的に許容される塩に、従来知られていなかった
肝障害改善作用を見いだし本発明を完成した。Means for Solving the Problems The present inventor has diligently studied to find a substance effective for the treatment of the above-mentioned liver diseases, and as a result, has an allergic reaction inhibitory action (JP-A-54-362).
94), known 9-methyl-3- (1H
-Tetrazol-5-yl) -4H-pyrido [1,2-
The present invention has been completed by finding a hitherto unknown hepatic disorder-improving action in a] pyrimidin-4-one (abbreviated as compound 1) or a physiologically acceptable salt thereof.
【０００５】本発明の有効成分、化合物１は２−シアノ
−３−（３−メチル−２−ピリジルアミノアクリル酸エ
チルを、例えば塩化アルミニウム存在下、アジ化ナトリ
ウムを用いてテトラゾール環形成し、ついで酸性下に濾
別することにより得ることができる。The active ingredient of the present invention, Compound 1, is ethyl 2-cyano-3- (3-methyl-2-pyridylaminoacrylate) which forms a tetrazole ring with sodium azide in the presence of aluminum chloride, and is then acidified. It can be obtained by filtering off below.
【０００６】化合物１の生理学的に許容される塩として
は、カリウム塩やナトリウム塩が挙げられる。Examples of the physiologically acceptable salt of Compound 1 include potassium salt and sodium salt.
【０００７】本発明の肝疾患治療剤は、経口又は非経口
で投与され、その用量は患者の年令、症状、体重又は性
別等により決定される。一般的には有効成分である化合
物１、またはその塩の一日用量は、経口で１ｍｇ〜５
ｇ、好ましくは５ｍｇ〜１ｇが、非経口で０．２ｍｇ〜
１ｇ、好ましくは１ｍｇ〜３００ｍｇが夫々適当であ
る。用法としては、かかる用量の範囲内で一日あたり１
〜４回、好ましくは１〜２回に分けて使用するのが適当
である。The therapeutic agent for liver diseases of the present invention is orally or parenterally administered, and the dose is determined according to the age, symptoms, body weight or sex of the patient. In general, the daily dose of Compound 1, which is an active ingredient, or a salt thereof is 1 mg to 5 mg orally.
g, preferably 5 mg to 1 g is parenterally 0.2 mg to
1 g, preferably 1 mg to 300 mg is suitable for each. As a usage, within the range of such dose, 1 per day
It is suitable to use it in four to four times, preferably in one to two times.
【０００８】本発明においては、有効成分の化合物１ま
たはその塩に生理的に無害な固体又は液体の製剤担体を
配合し、錠剤、丸剤、カプセル剤、散剤、細粒剤、顆粒
剤もしくは坐剤等の固形製剤または水剤、シロップ剤、
懸濁剤、乳剤もしくは注射剤等の液剤に調製することが
できる。固形製剤にあっては、腸溶性製剤又は徐放性製
剤等に調製してもよい。製剤担体としては、かかる形態
に通常用いられるものであればよく、これには、例え
ば、トウモロコシ澱粉、デキストリン、α−、β−もし
くはγ−シクロデキストリン、ブドウ糖、乳糖、ショ
糖、メチルセルロース、ヒドロキシプロピルセルロー
ス、カルボキシメチルセルロースカルシウム、結晶セル
ロース、アルギン酸ナトリウム、ウイテプソールＷ３
５、ウイテプソールＥ８５もしくは、ポリビニルアルコ
ー−ルなどの賦形剤、結合剤もしくは崩壊剤；タルク、
ステアリン酸、ステアリン酸マグネシウム、もしくは軟
質無水ケイ酸などの滑沢剤；セラック、酢酸フタル酸セ
ルロース、ポリビニルアセタルジエチルアミノアセテー
ト、カルボキシメチルエチルセルロース、ヒドロキシプ
ロピルメチルセルロースアセテートサクシネート、ハイ
ドロキシメチルフタル酸セルロースもしくはメチルメタ
アクリレートメタアクリル酸コポリマーなどの被覆剤；
グリセリン、プロピレングリコールもしくはマンニトー
ルなどの溶解補助剤；ポリオキシエチレンステアレート
もしくは、ポリオキシエチレンセチルアルコールエーテ
ルなどの乳化剤；アラビアゴムもしくはポリビニルピロ
リドンなどの懸濁化剤；必要に応じ、安定化剤、各種の
溶剤または適当な香料が挙げられる。In the present invention, compound 1, which is an active ingredient, or a salt thereof is mixed with a physiologically harmless solid or liquid pharmaceutical carrier to prepare tablets, pills, capsules, powders, fine granules, granules or suppositories. Solid preparations such as agents or liquids, syrups,
It can be prepared into a liquid preparation such as a suspension, emulsion or injection. Solid preparations may be prepared as enteric-coated preparations or sustained-release preparations. The pharmaceutical carrier may be one conventionally used in such a form, and examples thereof include corn starch, dextrin, α-, β- or γ-cyclodextrin, glucose, lactose, sucrose, methylcellulose, hydroxypropyl. Cellulose, carboxymethyl cellulose calcium, crystalline cellulose, sodium alginate, Witepsol W3
5, excipients such as Witepsol E85 or polyvinyl alcohol, binders or disintegrators; talc,
Lubricants such as stearic acid, magnesium stearate, or soft anhydrous silicic acid; shellac, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, carboxymethylethyl cellulose, hydroxypropylmethyl cellulose acetate succinate, cellulose hydroxymethylphthalate or methyl meta. Coating agents such as acrylate / methacrylic acid copolymers;
Dissolution aids such as glycerin, propylene glycol or mannitol; emulsifiers such as polyoxyethylene stearate or polyoxyethylene cetyl alcohol ether; suspending agents such as gum arabic or polyvinylpyrrolidone; stabilizers, if necessary Solvent or a suitable perfume.
【０００９】本発明を化合物１のカリウム塩（化合物１
−Ｋ）を用いた実験例及び製剤例をもって更に説明す
る。The present invention relates to the potassium salt of compound 1 (compound 1
-K) will be further described with reference to experimental examples and formulation examples.
【００１０】[0010]
［実験例１］急性肝不全モデルマウスに対する治療効果 ６週齢のＢＡＬＢ／Ｃ系雄性マウスを１群１０匹とし、
全群のマウスの尾静脈に、プロピオニバクテリウム・ア
クネス（Ｐｒｏｐｉｏｎｉｂａｃｔｅｒｉｕｍａｃｎｅ
ｓ）加熱死菌を１ｍｇ／マウスの割合で投与し、７日後
にサルモネラエンテリティデス（Ｓａｌｌｍｏｎｅｒａ
ｅｎｔｅｒｉｔｉｄｅｓ）由来のリポポリサッカライ
ド［（Ｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅ，Ｄｉｆ
ｃｏ社製）以下ＬＰＳと略す］を１μｇ／マウスの割合
で静脈内投与した。[Experimental Example 1] Therapeutic effect on acute liver failure model mice Six-week-old BALB / C male mice were used as one group consisting of 10 mice,
All groups of mice received tail veins of Propionibacterium acnes.
s) Heat-killed bacteria were administered at a rate of 1 mg / mouse, and 7 days later, Salmonella enteritidis (Sallmonera) was administered.
enteritides) -derived lipopolysaccharide [(Lipopolysaccharide, Dif
Co.) and hereinafter abbreviated as LPS] was intravenously administered at a rate of 1 μg / mouse.
【００１１】化合物１−Ｋを注射用蒸留水に溶解し、静
脈内投与においてはＬＰＳと同時に、また経口投与の場
合にはＬＰＳ投与１時間前に投与した。なお、化合物１
−Ｋを投与しない一群をコントロール群とした。ＬＰＳ
投与２４時間後に、マウスの生存率を調べた。コントロ
ール及び化合物１−Ｋの各投与量でのＬＰＳ投与２４時
間後の生存率を表１に示す。Compound 1-K was dissolved in distilled water for injection and was administered simultaneously with LPS for intravenous administration and 1 hour before LPS administration for oral administration. Compound 1
One group in which -K was not administered was used as a control group. LPS
The survival rate of the mice was examined 24 hours after the administration. Table 1 shows the survival rates 24 hours after LPS administration at each dose of the control and compound 1-K.
【００１２】[0012]
【表１】 [Table 1]
【００１３】化合物１−Ｋは静脈内投与では０．０３ｍ
ｇ／ｋｇ以上で、経口投与では１ｍｇ／ｋｇ以上で著し
い肝障害改善作用を示した。Compound 1-K is 0.03 m by intravenous administration
At a dose of g / kg or more, orally administered at a dose of 1 mg / kg or more, a remarkable hepatic disorder-improving effect was exhibited.
【００１４】［実験例２］急性毒性試験 ５週齢のＣＤ−１系雄性マウス及びＣＤ系雄性ラットを
用い、化合物１−Ｋの急性毒性（ＬＤ50）を試験した。
化合物１−ＫのＬＤ50値は、マウスでは経口投与で１３
１７ｍｇ／ｋｇ、静脈内投与で２２０ｍｇ／ｋｇであっ
た。また、ラットでは、経口投与で７５５ｍｇ／ｋｇ、
静脈内投与で３７２ｍｇ／ｋｇであった。[Experimental Example 2] Acute toxicity test Acute toxicity (LD 50 ) of Compound 1-K was tested using 5-week-old male CD-1 mice and male CD rats.
The LD 50 value of Compound 1-K was 13 in mice by oral administration.
The dose was 17 mg / kg and 220 mg / kg by intravenous administration. In rats, it was orally administered at 755 mg / kg,
It was 372 mg / kg by intravenous administration.
【００１５】［製剤例１］（錠剤の調製）[Formulation Example 1] (Preparation of tablets)
【００１６】[0016]
【表２】 [Table 2]
【００１７】上述の１）〜５）を混合し、水を添加を添
加して造粒し、ついで乾燥した。得られた顆粒を整粒し
た後、６）を加えて混合し、これを圧縮成形して１錠１
００ｍｇの錠剤を調製した。The above 1) to 5) were mixed, water was added thereto, and the mixture was granulated and then dried. After the obtained granules are sized, 6) is added and mixed, and this is compression molded to give 1 tablet 1
A 00 mg tablet was prepared.
【００１８】［製剤例２］（カプセル剤の調製）[Formulation Example 2] (Preparation of capsules)
【００１９】[0019]
【表３】 [Table 3]
【００２０】常法に従って、上述の成分を混合して顆粒
とした。これをカプセルに充填し、１個１００ｍｇのカ
プセル剤を調製した。According to a conventional method, the above components were mixed to give granules. This was filled in capsules to prepare 100 mg capsules.
【００２１】［製剤例３］（顆粒剤の調製）[Formulation Example 3] (Preparation of granules)
【００２２】[0022]
【表４】 [Table 4]
【００２３】上述の１）〜５）を混合し、水を加えて練
り合わせたのち押出造粒機を用いて円柱顆粒を調製し
た。The above 1) to 5) were mixed, water was added and kneaded, and then cylindrical granules were prepared using an extrusion granulator.
【００２４】[0024]
【発明の効果】化合物１及びその生理学的に許容される
塩は、肝障害改善作用に優れており、肝疾患の予防・治
療剤として有用である。INDUSTRIAL APPLICABILITY Compound 1 and its physiologically acceptable salts are excellent in the action of improving liver damage and are useful as prophylactic / therapeutic agents for liver diseases.
Claims (1)
−イル）−４Ｈ−ピリド［１，２−ａ］ピリミジン−４
−オン又はそれの生理学的に許容される塩を有効成分と
する肝疾患治療剤。1. The formula: 9-methyl-3- (1H-tetrazole-5 represented by
-Yl) -4H-pyrido [1,2-a] pyrimidine-4
-A therapeutic agent for liver diseases containing ON or a physiologically acceptable salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5247138A JPH07101863A (en) | 1993-10-01 | 1993-10-01 | Therapeutic agent for hepatopathy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5247138A JPH07101863A (en) | 1993-10-01 | 1993-10-01 | Therapeutic agent for hepatopathy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07101863A true JPH07101863A (en) | 1995-04-18 |
Family
ID=17159003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5247138A Pending JPH07101863A (en) | 1993-10-01 | 1993-10-01 | Therapeutic agent for hepatopathy |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07101863A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002072580A1 (en) * | 2001-02-26 | 2002-09-19 | Mitsubishi Pharma Corporation | Preventives and/or remedies for kidney diseases and kidney failure |
-
1993
- 1993-10-01 JP JP5247138A patent/JPH07101863A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002072580A1 (en) * | 2001-02-26 | 2002-09-19 | Mitsubishi Pharma Corporation | Preventives and/or remedies for kidney diseases and kidney failure |
| KR100885007B1 (en) * | 2001-02-26 | 2009-02-20 | 미쓰비시 타나베 파마 코퍼레이션 | Pharmaceutical composition for preventing or treating of kidney diseases and kidney failure |
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