WO1996005819A1 - Remedy for portal hypertension - Google Patents
Remedy for portal hypertension Download PDFInfo
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- WO1996005819A1 WO1996005819A1 PCT/JP1995/001605 JP9501605W WO9605819A1 WO 1996005819 A1 WO1996005819 A1 WO 1996005819A1 JP 9501605 W JP9501605 W JP 9501605W WO 9605819 A1 WO9605819 A1 WO 9605819A1
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- portal hypertension
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
Definitions
- the present invention relates to a novel therapeutic agent for portal vein hypertension.
- the increased portal vein pressure associated with cirrhosis increased blood flow to the venous vein diverging from the portal vein, leading to bleeding from esophageal varices.
- bleeding caused by various surgical procedures is being treated quite effectively, but medical needs for drug therapy to prevent bleeding are increasing. high.
- vasopressin a ⁇ -blocker
- nitrite a ⁇ -blocker
- vasopressin lowers organ blood flow by its vasoconstriction, it also lowers portal venous blood flow, but it is not always easy to use.
- the present invention relates to the treatment of portal hypertension, and more specifically, the formula (I) (I)
- the present invention relates to a therapeutic agent for portal hypertension, which comprises as an active ingredient a compound represented by the formula or a pharmaceutically acceptable salt thereof.
- the compound represented by the formula (I), which is an active ingredient of the therapeutic agent for portal hypertension of the present invention, is known as a compound having a vasodilator action, an antithrombotic action, and the like.
- No. 152366 is not known to be effective as a therapeutic agent for portal hypertension.
- Salts of the compound (I) used as an active ingredient in the present invention include, for example, alkali salts such as sodium salts and potassium salts.
- Lithium metal salts for example, alkaline earth metal salts such as calcium salts, ammonium salts; ethanolamine salts, triethynoleamine salts, and dicyclohexylene salts
- examples thereof include a salt with an inorganic base such as an organic amine salt such as a silamine salt and a salt with an organic base.
- the compound (I) used as an active ingredient in the present invention contains stereoisomers, and a representative one thereof is (Sat) 1-1 (E) 14-ethynolate 2 — [(E) —Hydroxy imino] 1 5—2 Troll 3—Hexane amide (this compound is hereinafter referred to as FK 409).
- the compound (I) used as an active ingredient in the present invention and its pharmaceutically acceptable salt are nitric oxide (NO) donors, and the release reaction is considered. Is considered to degrade rapidly after absorption from the gastrointestinal tract and release NO.The concentration of NO in the portal vein system is high, making it an excellent therapeutic agent for portal hypertension. .
- the therapeutic agent for portal hypertension of the present invention can be prepared, for example, by mixing it with an organic or inorganic carrier or excipient suitable for external use, oral administration, or parenteral administration. It can be used in the form of a solid, semi-solid or liquid pharmaceutical preparation containing the active substance of the invention of the present invention.
- the active ingredient can be used, for example, in tablets, pellets, capsules, suppositories, injections, solutions, emulsions, suspensions, and any other form suitable for use. It can be mixed with conventional, non-toxic, pharmaceutically acceptable carriers.
- Carriers used include water, glucose, saccharose, arabia, gum, gelatin, mannitol, starch paste, magnesium trisilicate, tar Norek, corn starch, keratin, colloid silica, sugar potato starch, urea, and other solid, semi-solid or liquid preparations It is a suitable carrier and may also contain adjuvants, stabilizers, thickening and coloring agents and fragrances. Pharmaceutical preparations may also contain preservatives or bacteriostats to maintain the activity of the active ingredient stably in the desired preparation.
- the active substance in the drug may be the desired one depending on the extent or condition of the disease. It is contained in an amount sufficient to exert a therapeutic effect.
- the therapeutic agent for portal hypertension of the present invention In applying the therapeutic agent for portal hypertension of the present invention to humans, it is preferable to administer it intravenously, intramuscularly or orally.
- the dosage or therapeutically effective amount of the compound of interest for this invention will vary depending on the age and condition of the individual patient to be treated, but will usually be about 0.1 per day. ⁇ 100mgZ kg is administered, and generally, on average, about 0.5mg, 1rag, 5rag, lOrag, 50mg, 100mg, 250mg, 500mg power is administered at a time.
- FK409 was used by weighing 10 mg, dissolving in 20 ml of physiological saline, and diluting with physiological saline below (2 nilZ kg).
- Ni cardipine which has a commercially available vasodilatory effect, was used, 50 mg of this was weighed, and suspended in 10 ml of 0.5% methyl senorelose. 2 ml / kg).
- test substances were administered through a tube inserted into the duodenum on a rat fasted about 17 hours ago.
- Liver tissue blood flow was measured with a probe from a multichannel laser flowmeter (PER I MED AB Made in Sweden) at about 1 cm from the edge of the outer left lobe. The contact was measured.
- PER I MED AB Made in Sweden a multichannel laser flowmeter
- the significance test was performed on the pre-dose value and the solvent (physiological saline) (Friedman + Dunnett test and K rusk 1-Wa11is + Dunnett t test, respectively).
- the agent of the present invention has an effect of effectively lowering portal vein pressure, and is useful as a new therapeutic agent for portal hypertension.
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Abstract
An excellent remedy for portal hypertension containing the compound represented by formula (I) or a medicinally acceptable salt thereof as the active ingredient.
Description
明 細 書 Specification
発明の名称 Title of invention
門脈圧亢進症治療剤 Agent for portal hypertension
技術分野 Technical field
こ の発明は、 新規な門脈 E亢進症治療剤に 関す る も の であ る 。 The present invention relates to a novel therapeutic agent for portal vein hypertension.
背景技術 Background art
肝硬変に伴 う 門脈圧上昇に よ り 、 門脈か ら 分岐 した静 脈への血流が増加 し食道静脈瘤か ら の出血に い た る。 現 在では、 種々 の外科的処置に よ り こ う した出血はかな り 有効に治療さ れる よ う に成っ て は い る が、 出血を予防す る ための薬物療法に対す る 医療ニー ズは高い。 The increased portal vein pressure associated with cirrhosis increased blood flow to the venous vein diverging from the portal vein, leading to bleeding from esophageal varices. At present, bleeding caused by various surgical procedures is being treated quite effectively, but medical needs for drug therapy to prevent bleeding are increasing. high.
こ れ ま でに、 こ う し た 目 的に は vasopressin, ^ 遮断 剤、 亜硝酸剤の投与が試み られて お り それな り の治療効 果 を示 し て い る。 To date, administration of vasopressin, a ^ -blocker, and nitrite have been attempted for these purposes, and have shown moderate therapeutic effects.
vasopressinは そ の血管収縮作用 に よ り 臓器血流を落 と し、 そ の結果門脈血流 も 低下 させ る が、 必ず し も使い やす い薬剤ではな い。 Although vasopressin lowers organ blood flow by its vasoconstriction, it also lowers portal venous blood flow, but it is not always easy to use.
遮断剤、 亜硝酸剤 も 臨床的に使用 さ れ一応その効果 は認め ら れて は い る も のの、 し っ か り した臨床試験での 成績は無い。 Although blockers and nitrites have also been used clinically and their effects have been observed for some time, no results have been reported in firm clinical trials.
発明の開示 Disclosure of the invention
こ の発明は門脈圧亢進症治療に関す る も のであ り 、 詳 細に は式 ( I )
(I)
で示 さ れ る化合物 ま た は医薬 と し て許容 さ れ る そ の塩を 有効成 分 と す る 門脈圧亢進症治療剤に 関す る も の であ る 。 The present invention relates to the treatment of portal hypertension, and more specifically, the formula (I) (I) The present invention relates to a therapeutic agent for portal hypertension, which comprises as an active ingredient a compound represented by the formula or a pharmaceutically acceptable salt thereof.
こ の発明の門脈圧亢進症治療剤の有効成分であ る 前記 式 （ I ) で示 さ れ る 化合物は血管拡張作用、 抗血栓症 作用等を有す る 化合物 と し て知 られて い る （特開昭 59— The compound represented by the formula (I), which is an active ingredient of the therapeutic agent for portal hypertension of the present invention, is known as a compound having a vasodilator action, an antithrombotic action, and the like. (Japanese Patent Laid-Open No. 59-
1 52366号公報参照） が、 門脈圧亢進症治療剤 と して有効 であ る こ と は知 られて いない。 No. 152366) is not known to be effective as a therapeutic agent for portal hypertension.
こ の発明で有効成分 と し て使用す る化合物 （ I ) の医 薬 と し て 許容 さ れ る 塩 と し て は、 例 えば、 ナ ト リ ウ ム 塩、 カ リ ウ ム塩等のアルカ リ 金厲塩、 例えばカル シウム 塩等のアルカ リ 土類金属塩、 ア ン モ ニ ゥ ム塩 ； エ タ ノ ー ル ァ ミ ン塩、 ト リ エ チノレア ミ ン塩、 ジ シ ク ロ へ キ シル ァ ミ ン塩の よ う な有機ア ミ ン塩等の よ う な無機塩基 と の塩 ま たは有機塩基 と の塩が挙げ られ る。 Salts of the compound (I) used as an active ingredient in the present invention, which are acceptable as medicaments, include, for example, alkali salts such as sodium salts and potassium salts. Lithium metal salts, for example, alkaline earth metal salts such as calcium salts, ammonium salts; ethanolamine salts, triethynoleamine salts, and dicyclohexylene salts Examples thereof include a salt with an inorganic base such as an organic amine salt such as a silamine salt and a salt with an organic base.
ま た、 こ の発明で有効成分 と し て使用す る化合物（ I ) は立体異性体 を 含むが、 こ の う ち代表的な も のは （ 土 ） 一 ( E ) 一 4 ー ェチノレ ー 2 — [ ( E ) — ヒ ド ロ キ シ イ ミ ノ ] 一 5 — 二 ト ロ ー 3 —へキセ ン ア ミ ド （以下こ の化合 物を F K 409と 称す ） であ る 。
こ の発明で有効成分 と し て使用す る化合物 （ I ) お よ び医薬 と し て許容 さ れ る そ の塩は、 一酸化窒素 （ N O ) ド ナーであ り 、 こ の放出反応を考慮 し た場合、 消化管か ら 吸収後速やかに分解 し、 N Oを放出す る と 考 え られ、 門脈 系での N O濃度が高 く 、 門脈圧亢進症治療剤 と し てす ぐれ て い る 。 The compound (I) used as an active ingredient in the present invention contains stereoisomers, and a representative one thereof is (Sat) 1-1 (E) 14-ethynolate 2 — [(E) —Hydroxy imino] 1 5—2 Troll 3—Hexane amide (this compound is hereinafter referred to as FK 409). The compound (I) used as an active ingredient in the present invention and its pharmaceutically acceptable salt are nitric oxide (NO) donors, and the release reaction is considered. Is considered to degrade rapidly after absorption from the gastrointestinal tract and release NO.The concentration of NO in the portal vein system is high, making it an excellent therapeutic agent for portal hypertension. .
こ の発明の門脈圧亢進症治療剤は、 例えば、 外用、 経 口 投与 ま た は非経 口投与用 に適 した有機 も し く は無機担 体 ま た は賦形剤 と 混合 し て こ の発明の有効物質を含有す る 固体状、 半固体状 ま た は液状の医薬製剤の形で使用す る こ と がで き る 。 有効成分は、 例え ば、 錠剤、 ペ レ ツ ト 、 カプセル、 坐剤、 注射剤、 溶液、 ェマル ジ ヨ ン、 濁液お よ びそ の他の使用に適 した あ ら ゆ る形に用い る通 常の、 無毒性の医薬 と し て許容 され る担体 と 混合す る こ と 力、 'で き る。 The therapeutic agent for portal hypertension of the present invention can be prepared, for example, by mixing it with an organic or inorganic carrier or excipient suitable for external use, oral administration, or parenteral administration. It can be used in the form of a solid, semi-solid or liquid pharmaceutical preparation containing the active substance of the invention of the present invention. The active ingredient can be used, for example, in tablets, pellets, capsules, suppositories, injections, solutions, emulsions, suspensions, and any other form suitable for use. It can be mixed with conventional, non-toxic, pharmaceutically acceptable carriers.
使用 さ れ う る担体は水、 ぶ ど う 糖、 扎糖、 ア ラ ビア ゴ ム、 ゼラ チ ン、 マ ンニ ト ール、 でん粉ペース ト 、 マグネ シ ゥ ム ト リ シ リ ケ 一 ト 、 タ ノレク 、 と う も ろ こ しでん粉、 ケ ラ チ ン、 コ ロ イ ド シ リ カ、 し ゃ がい も でん粉、 尿素そ の他、 固体状、 半固体状 ま た は液体状の、 製剤製造上適 し た担体であ り 、 さ ら に補助剤、 安定剤、 濃厚化剤お よ び着色剤な ら びに芳香剤を使用 し て も よ い。 医薬製剤は ま た有効成分の活性を 所望の製剤中安定に維持す る ため に保存剤ま たは静菌剤を含有 し て い る こ と も で き る。 薬 剤中の有効物質は疾患の程度 ま たは状態に応 じ て所望の
治療効果を発揮す る の に充分な量含有さ れ る 。 Carriers used include water, glucose, saccharose, arabia, gum, gelatin, mannitol, starch paste, magnesium trisilicate, tar Norek, corn starch, keratin, colloid silica, sugar potato starch, urea, and other solid, semi-solid or liquid preparations It is a suitable carrier and may also contain adjuvants, stabilizers, thickening and coloring agents and fragrances. Pharmaceutical preparations may also contain preservatives or bacteriostats to maintain the activity of the active ingredient stably in the desired preparation. The active substance in the drug may be the desired one depending on the extent or condition of the disease. It is contained in an amount sufficient to exert a therapeutic effect.
こ の発明の門脈圧亢進症治療剤を 人に適用す る に当つ て は、 静脈内、 筋肉 内 ま たは経 口投与に よ り 行 う のが好 ま し い。 こ の発明の 目 的化合物の投与量 ま たは治療有効 量は、 処置すべ き そ れぞれ個々 の患者の年齢 と 条件 と に よ っ て変化す る が、 通常は 1 日 約 0. 1~ lOOmgZ kg投与さ れ、 一般的 に は平均 1 回約 0, 5mg、 1 rag, 5 rag, lOrag, 50mg、 lOOmg, 250mg、 500mg力、'投与 さ れ る 。 In applying the therapeutic agent for portal hypertension of the present invention to humans, it is preferable to administer it intravenously, intramuscularly or orally. The dosage or therapeutically effective amount of the compound of interest for this invention will vary depending on the age and condition of the individual patient to be treated, but will usually be about 0.1 per day. ~ 100mgZ kg is administered, and generally, on average, about 0.5mg, 1rag, 5rag, lOrag, 50mg, 100mg, 250mg, 500mg power is administered at a time.
次の こ の発明の試験例を示す。 The following are test examples of this invention.
試験例 （ 門脈圧に対す る作用 ） Test example (action on portal pressure)
[方法 ] [Method ]
1 . 使用動物 1. Animals used
雄性ウ ィ ス タ ー 系 （ Crj ： Wistar. SPF， 日 本チ ャ ール ズ • リ バ一， 出荷時週令 ： 6 週令 出荷時体重 ： 180〜 200 g ) を 7 日 以上予備飼育 し、 実験に用 いた。 Male Wistar strains (Crj: Wistar. SPF, Japanese Charles • River, weekly shipping: 6 weeks old, shipping weight: 180-200 g) were bred for 7 days or more. Used for experiments.
2 . 被験物質の調製 2. Preparation of test substance
FK409は、 10mgを 秤量 し 20mlの生理食塩液に溶解 し、 以下生理食塩液で希釈 し て用 いた （ 2 nilZ kg) 。 FK409 was used by weighing 10 mg, dissolving in 20 ml of physiological saline, and diluting with physiological saline below (2 nilZ kg).
対 照 と し て 、 市 販 の 血 管 拡 張 作 用 を 有 す る Ni cardipineを 用 い、 こ れ を 50mgを秤量 し、 0.5%メ チル セノレ ロ ー ス 10mlで懸濁 し て用 いた （ 2 ml/ kg) 。 As a control, Ni cardipine, which has a commercially available vasodilatory effect, was used, 50 mg of this was weighed, and suspended in 10 ml of 0.5% methyl senorelose. 2 ml / kg).
なお両被検物質の投与は、 約 17時間前に絶食 した ラ ッ ト で、 十二指腸内に刺入 し たチ ュ ーブを通 し て行っ た。 The test substances were administered through a tube inserted into the duodenum on a rat fasted about 17 hours ago.
3 . 実験方法 3. Experimental method
ウ レ タ ン 1.2 g Z kg に p.で麻酔後大腿動脈に 力 ニ ュ ー
レ を挿入 し、 圧 ト ラ ン ス デュ ーサー を介 し て血圧を、 そ し て そ の圧波でタ コ メ ー タ を介 し て心拍数を測定 した。 腹 部 正 中 切 開 し て 十 二 指 腸 内 に 薬 物投 与 の た め の チ ュ ーブを留置 し た。 Urethane 1.2 g Force applied to femoral artery after anesthesia with p. The blood pressure was measured via a pressure transducer and the heart rate was measured via a tachometer at the pressure wave. A midline abdominal incision was made and a tube for drug administration was placed in the duodenum.
門脈圧測定は、 脾静脈、 上腸間膜静脈合流部末梢側で サ ー フ ロ ー留置針 （ 24 G X 3 、 内径 0.47mm 外径 0.67 mm 力 テ ー テノレ 長 19mm テノレモ杜） を挿入、 ァ ロ ンア ル フ ァ に て 固 定 し 、 圧 ト ラ ン ス デュ ーサ ー を 介 し て 行つ た。 Portal pressure measurements, splenic vein, superior mesenteric vein confluence portion Sa-safe peripheral side B over indwelling needle (24 GX 3, the inner diameter 0.47mm OD 0.67 mm force Te over Tenore length 19mm Tenoremo Mori) inserts, The fixation was carried out in Aronalfa and was carried out via a pressure transducer.
肝組織血流量 は 、 外側左葉の辺縁部か ら 約 1 cmの部 位に マ ル チ チ ャ ン ネ ノレ · レ ーザー血流計 （ PER I MED AB Made in Sweden) のプロ 一ブを接触させて測定 した。 Liver tissue blood flow was measured with a probe from a multichannel laser flowmeter (PER I MED AB Made in Sweden) at about 1 cm from the edge of the outer left lobe. The contact was measured.
有意差検定は、 投与前値お よ び溶媒 （生理食塩液） に 対 し て実施 し た （ それぞれ Friedman + Dunnet t 検定 お よ び K rusk 1 - Wa 11 i s + Dunne t t 検定 ） 。 The significance test was performed on the pre-dose value and the solvent (physiological saline) (Friedman + Dunnett test and K rusk 1-Wa11is + Dunnett t test, respectively).
験糸 α果 ] Test yarn α fruit]
次表に示す通 り であ る 。
It is as shown in the following table.
投与量 例 項目 投与前 投与後 （分） Dose Example Item Before administration After administration (min)
i. d. 数 i. d. Number
g/kg) 2 5 10 20 30 60 門脈圧 9.15 9.23 9.28 9.33 9.50 9.38 9.03 食塩 (mmHsz) ±0.34 土 0.40 土 0.43 ±0.48 ±0.35 ±0.21 ±0.10 g / kg) 2 5 10 20 30 60 Portal pressure 9.15 9.23 9.28 9.33 9.50 9.38 9.03 Salt (mmHsz) ± 0.34 Sat 0.40 Sat 0.43 ± 0.48 ± 0.35 ± 0.21 ± 0.10
4 Four
(溶媒） 変化率 0.00 0.76 1.29 1.82 3.89 2.69 -0.92 (%) 土 0.00 ±1.37 ±1.85 ±2.64 ±2.00 土 2.58 ±4.13 門脈 E 9.35 8.88 9.20 9.50 9.55 9.40 8.70 FK409 (mmHg) ±0.33 土 0.20 ±0.43 ±0.40 ±0.38 ±0.51 ±0.61 (Solvent) Change rate 0.00 0.76 1.29 1.82 3.89 2.69 -0.92 (%) Sat 0.00 ± 1.37 ± 1.85 ± 2.64 ± 2.00 Sat 2.58 ± 4.13 Portal vein E 9.35 8.88 9.20 9.50 9.55 9.40 8.70 FK409 (mmHg) ± 0.33 Sat 0.20 ± 0.43 ± 0.40 ± 0.38 ± 0.51 ± 0.61
4 Four
0.032 変化率 0.00 -4.94 -1.63 1.57 2.24 0.49 -6.92 mg/kg (%) 土 0.00 ±1.55 +2.79 ±2.02 +3.32 ±4.02 +6.02 門脈圧 8.83 8.28 8.45 8.58 8.75 8.73 8.40 FK409 (mmHg) ±0.18 ±0.23 +0.33 ±0.31 ±0.26 土 0.34 ±0.57 0.032 Change 0.00 -4.94 -1.63 1.57 2.24 0.49 -6.92 mg / kg (%) Sat 0.00 ± 1.55 +2.79 ± 2.02 +3.32 ± 4.02 +6.02 Portal pressure 8.83 8.28 8.45 8.58 8.75 8.73 8.40 FK409 (mmHg) ± 0.18 ± 0.23 +0.33 ± 0.31 ± 0.26 Sat 0.34 ± 0.57
4 Four
0. Img/kg 変化率 0.00 -6.25 -4.35 -2.92 -0.90 -1.25 -5.07 0.Img / kg Change 0.00 -6.25 -4.35 -2.92 -0.90 -1.25 -5.07
±0.00 土 1.42 ±2.00 +1.78 土 1.28 ±2.06 土 4.90 門脈圧 9.00 8.18 8.50 8.60 9.15 9.40 9.40 ± 0.00 Sat 1.42 ± 2.00 +1.78 Sat 1.28 ± 2.06 Sat 4.90 Portal pressure 9.00 8.18 8.50 8.60 9.15 9.40 9.40
FK409 (mmHg) ±0.71 土 0.62 土 0.66 ±0.62 ±0.34 ±0.50 ±0.63 FK409 (mmHg) ± 0.71 Sat 0.62 Sat 0.66 ± 0.62 ± 0.34 ± 0.50 ± 0.63
4 Four
0.32 変化率 0.00 -9.01 -5.30 -4.03 3.43 6.13 5.06 mg/kg (Z) ±0.00 ±2.15 ±3.32 ±3.67 ±8.10 ±8.54 ±4.78 0.32 Change 0.00 -9.01 -5.30 -4.03 3.43 6.13 5.06 mg / kg (Z) ± 0.00 ± 2.15 ± 3.32 ± 3.67 ± 8.10 ± 8.54 ± 4.78
*(##) (#) * (##) (#)
門脈圧 10.28 7.88 8.75 9.18 9.58 9.75 9.38 FK409 (ramHg) 土 0.43 ±0.13 ±0.52 ±0.31 ±0.43 ±0.45 ±0.63 Portal pressure 10.28 7.88 8.75 9.18 9.58 9.75 9.38 FK409 (ramHg) Sat 0.43 ± 0.13 ± 0.52 ± 0.31 ± 0.43 ± 0.45 ± 0.63
4 Four
t (#tt) 本 (#， t (# tt ) books (#,
1. Omg/kg 変化率 0.00 -23.06 -14.96 -10.60 -6.76 -5.02 -8.76 ( ) 土 0.00 ±2.51 土 2.55 ±1.28 ±2.62 土 3.24 ±5.09 1.Omg / kg Change 0.00 -23.06 -14.96 -10.60 -6.76 -5.02 -8.76 () Sat 0.00 ± 2.51 Sat 2.55 ± 1.28 ± 2.62 Sat 3.24 ± 5.09
Nicar 門脈圧 8.03 8.08 8.13 8.30 8.40 8.53 8.93 dipine (mmHg) 土 0.75 ±0.76 土 0.65 +0.78 ±0.71 ±0.59 ±0.47 Nicar Portal pressure 8.03 8.08 8.13 8.30 8.40 8.53 8.93 dipine (mmHg) Sat 0.75 ± 0.76 Sat 0.65 +0.78 ± 0.71 ± 0.59 ± 0.47
4 Four
3.2mg/kg 変化率 0.00 0.59 1.72 3.42 5.00 7.17 13.10 (X) 土 0.00 ±0.59 土 1.72 ±0.45 +1.40 ±3.43 ±7.25 3.2mg / kg Change 0.00 0.59 1.72 3.42 5.00 7.17 13.10 (X) Sat 0.00 ± 0.59 Sat 1.72 ± 0.45 +1.40 ± 3.43 ± 7.25
Nicar 門脈圧 8.93 8.83 9.03 8.88 8.43 8.45 8.85 dipine (mmHg; ±0.49 土 0.43 ±0.40 ±0.39 ±0.46 ±0.51 ±0.40 Nicar Portal pressure 8.93 8.83 9.03 8.88 8.43 8.45 8.85 dipine (mmHg; ± 0.49 Sat 0.43 ± 0.40 ± 0.39 ± 0.46 ± 0.51 ± 0.40
4 Four
10rag/kg 変化率 0.00 -1.02 1.32 -0.34 -5.61 -5.41 -0.60 (%) 土 0.00 ±0.96 土 1.72 ±2.15 ±0.35 ±0.52 ±2.57
*, ** ： 溶媒に対 し て 各々 5 % , 1 %で有意 （ Kruskal—10rag / kg Change 0.00 -1.02 1.32 -0.34 -5.61 -5.41 -0.60 (%) Sat 0.00 ± 0.96 Sat 1.72 ± 2.15 ± 0.35 ± 0.52 ± 2.57 *, **: Significant at 5% and 1%, respectively, relative to the solvent (Kruskal-
Wal 1 i s + Dunne t t検定 ) Wal 1 is + Dunne t t test)
#. ## ： 投与前値 に 対 し て 5 %， 1 %有意 （ Fr iedman + #. ##: Significant 5% and 1% of the value before administration (Friedman +
Dunnet t検定 ） 平均値 土 標準誤差 Dunnet's t-test) Mean Sat Standard error
産業上の利用可能性 Industrial applicability
以上の よ う に、 こ の発明の薬剤は門脈圧を 有効に低下 さ せ る 作用 を有 し、 新 し い門脈圧亢進症治療剤 と して有 用であ る 。
As described above, the agent of the present invention has an effect of effectively lowering portal vein pressure, and is useful as a new therapeutic agent for portal hypertension.
Claims
1 . 式 1 set
で示 さ れ る化合物 ま た は医薬 と し て許容 さ れ る そ の塩を 有効成分 と す る 門脈圧亢進症治療剤。 A therapeutic agent for portal hypertension comprising, as an active ingredient, a compound represented by the formula: or a pharmaceutically acceptable salt thereof.
2 . 化合物が （ 土 ） 一 （ E ) — 4 — ェチノレ 一 2 — [ ( E ) — ヒ ド ロ キ シ ィ ミ ノ ] 一 5 — 二 ト ロ ー 3 — へキ セ ンア ミ ド であ る 請求項 1 記載の治療剤。 2. The compound is (Sat) 1 (E) — 4 — Etino 1 2 — [(E) — Hydroximimino] 1 5 — 2 Tro 3 — Hexenamide The therapeutic agent according to claim 1.
3 . 式 3 expression
で示 さ れ る 化合物 ま たは医薬 と し て許容 さ れ る その塩を 門脈圧亢進症患者に投与す る こ と を特徴 と す る 門脈圧亢 進症の治療法。 A method for treating portal hypertension, which comprises administering to a patient with portal hypertension a compound represented by the formula or a pharmaceutically acceptable salt thereof.
4 . 門脈圧亢進症治療剤を製造す る ための式 4. Formula for producing a therapeutic agent for portal hypertension
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6/195182 | 1994-08-19 | ||
| JP19518294 | 1994-08-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996005819A1 true WO1996005819A1 (en) | 1996-02-29 |
Family
ID=16336820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1995/001605 WO1996005819A1 (en) | 1994-08-19 | 1995-08-11 | Remedy for portal hypertension |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1996005819A1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59152366A (en) * | 1982-12-31 | 1984-08-31 | Fujisawa Pharmaceut Co Ltd | Novel nitroaliphatic compound, its preparation and use |
-
1995
- 1995-08-11 WO PCT/JP1995/001605 patent/WO1996005819A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59152366A (en) * | 1982-12-31 | 1984-08-31 | Fujisawa Pharmaceut Co Ltd | Novel nitroaliphatic compound, its preparation and use |
Non-Patent Citations (1)
| Title |
|---|
| PROC. NATL. ACAD. SCI. U.S.A., Vol. 90, No. 21, (1993), pages 10130-10134. * |
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