JP2013006858A - 胃腸障害および関連障害の治療におけるコレシストキニン−1(cck1)受容体アンタゴニスト - Google Patents
胃腸障害および関連障害の治療におけるコレシストキニン−1(cck1)受容体アンタゴニスト Download PDFInfo
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- JP2013006858A JP2013006858A JP2012194326A JP2012194326A JP2013006858A JP 2013006858 A JP2013006858 A JP 2013006858A JP 2012194326 A JP2012194326 A JP 2012194326A JP 2012194326 A JP2012194326 A JP 2012194326A JP 2013006858 A JP2013006858 A JP 2013006858A
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- receptor antagonist
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- gastrointestinal
- dyspepsia
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Classifications
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
【解決手段】コレシストキニン−1(CCK1)受容体アンタゴニストおよびCCK1受容体アンタゴニストとプロトンポンプインヒビター(PPI)からなる医薬組成物。
【選択図】なし
Description
本発明は、従来の制酸療法が全く効果を奏さない胃腸障害および関連障害を患っている患者の治療のためのコレシストキニン−1(CCK1)受容体アンタゴニストおよびCCK1受容体アンタゴニストとプロトンポンプインヒビター(PPI)との併用に関する。本発明は、CCK1アンタゴニストの臨床投与が、従来の制酸療法が全く効果を奏さない胃腸障害および関連障害を患っている患者の治療に有効であることを初めて記載する。さらに、これらの患者は、未解決の消化不良型症状において予期せぬ改善を実証している。
本発明は、従来の制酸療法が全く効果を奏さない胃腸障害および関連障害を患っている患者の治療のためのコレシストキニン−1(CCK1)受容体アンタゴニストおよびCCK1受容体アンタゴニストとプロトンポンプインヒビター(PPI)との併用に関する。好ましくは、CCK1受容体アンタゴニストおよびプロトンポンプインヒビターは、併用した場合の治療的に有効な量で投与され、有利な効果を提供する。
他に特記しない限り、以下の定義は、本明細書および請求の範囲を通して適用される。これらの定義は、用語がそれ自体で用いられるか、他の用語と組み合わせて用いられるかに関わらず、適用される。したがって、「アルキル」の定義は、「アルキル」ならびに「アルコキシ」の「アルキル」部分に適用される。
式(I)で示される化合物は、これもまた本発明の範囲内である塩および溶媒和物を形成することができる。
I
[式中、R1は、2−ナフチル、3,4−ジクロロフェニルおよび3,4−ジメチルフェニルから選ばれる;
R2は、ペンチル基または4個の炭素原子を有するアルコキシアルキル基である]
、およびその医薬的に許容しうる塩によって表すことができる。
デキシロキシグルミド (R−4−(3,4−ジクロロベンゾイルアミノ)−5−(N−3−メトキシプロピル−ペンチルアミノ)−5−オキソ−ペンタン酸);
ロキシグルミド (R,S−4−(3,4−ジクロロベンゾイルアミノ)−5−(N−3−メトキシプロピル−ペンチルアミノ)−5−オキソ−ペンタン酸);
ロルグルミド (R,S−4−[(3,4−ジクロロベンゾイル)アミノ]−5−(ジペンチルアミノ)−5−オキソペンタン酸);
アミグルミド ((R)−4−(2−ナフタミド)−N,N−ジペンチルグルタミン酸);
ならびにその多形、溶媒和物、医薬的に許容しうる塩および混合物;
が挙げられるが、これらに限定されるものではない。
ラットの急性逆流性食道炎における効果
試験前に、体重175−200 gの雄性ラットを24時間絶食させる。水は、自由に取らせる。エーテル麻酔下、腹部を正中切開し、幽門および境界縁(噴門洞と胃体の間の遷移領域)を同時に結索する。その結果として、胃液を保持するための胃の総容量は、大きく減少し、食道への胃液の逆流が起こる。幽門および境界縁の結索に続いて、試験化合物を十二指腸内に投与し(5 ml/kg)、腹部を縫合して閉じる。3時間後、エーテルの過剰投与によりラットを屠殺し、胃食道部分を摘出する。次の基準にしたがう病変インデックスを用いて、胸部食道における病変を肉眼で得点化する:病変なし 0;浮腫 1;発赤 2;出血部の長さ<20 mm 3;出血部の長さ20−30 mm 4;出血部の長さ30−40 mm 5;出血部の長さ>40 mmまたは穿孔 6。
消化不良症状の軽減におけるデキシロキシグルミドの安全性および効力
消化不良症状の軽減におけるデキシロキシグルミドの安全性および効力を評価するために、我々は、機能性消化不良(FD)の病歴をもち、先立つ12ヶ月の間に少なくとも4週間にわたって適切な用量のPPIを投与された男性および女性患者において、プラセボを対照とした二重盲検試験を行うことを提案する。プロトンポンプインヒビター(PPI)で適切に処置されながらもFDの症状を持ち続ける患者のみが、参加する資格がある。下記の概要は、実験をさらに詳細に説明する。
Claims (2)
- (i)コレシストキニン−1受容体アンタゴニスト;(ii)プロトンポンプインヒビター(PPI);および(iii)医薬的に許容しうる担体または賦形剤を含む胃腸障害を治療するための医薬組成物であって、コレシストキニン−1受容体アンタゴニストが、医薬的有効量で存在する医薬組成物。
- コレシストキニン−1受容体アンタゴニストが、約10〜約1000 mgの用量で存在し、プロトンポンプインヒビターが、約1〜約60 mgの用量で存在する請求項1に記載の医薬組成物。
Applications Claiming Priority (2)
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US11/424,104 | 2006-06-14 | ||
US11/424,104 US7863330B2 (en) | 2006-06-14 | 2006-06-14 | Deloxiglumide and proton pump inhibitor combination in the treatment of gastrointestinal disorders |
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JP2009514781A Division JP2009539929A (ja) | 2006-06-14 | 2007-06-12 | 胃腸障害および関連障害の治療におけるコレシストキニン−1(cck1)受容体アンタゴニスト |
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JP2013006858A true JP2013006858A (ja) | 2013-01-10 |
JP5792137B2 JP5792137B2 (ja) | 2015-10-07 |
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JP2009514781A Pending JP2009539929A (ja) | 2006-06-14 | 2007-06-12 | 胃腸障害および関連障害の治療におけるコレシストキニン−1(cck1)受容体アンタゴニスト |
JP2012194326A Expired - Fee Related JP5792137B2 (ja) | 2006-06-14 | 2012-09-04 | 胃腸障害および関連障害の治療におけるコレシストキニン−1(cck1)受容体アンタゴニスト |
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JP2009514781A Pending JP2009539929A (ja) | 2006-06-14 | 2007-06-12 | 胃腸障害および関連障害の治療におけるコレシストキニン−1(cck1)受容体アンタゴニスト |
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US (2) | US7863330B2 (ja) |
EP (1) | EP2046319B1 (ja) |
JP (2) | JP2009539929A (ja) |
CA (1) | CA2655081C (ja) |
ES (1) | ES2425398T3 (ja) |
PT (1) | PT2046319E (ja) |
WO (1) | WO2007144345A2 (ja) |
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US7863330B2 (en) * | 2006-06-14 | 2011-01-04 | Rottapharm S.P.A. | Deloxiglumide and proton pump inhibitor combination in the treatment of gastrointestinal disorders |
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2006
- 2006-06-14 US US11/424,104 patent/US7863330B2/en not_active Expired - Fee Related
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2007
- 2007-06-12 CA CA2655081A patent/CA2655081C/en not_active Expired - Fee Related
- 2007-06-12 ES ES07730086T patent/ES2425398T3/es active Active
- 2007-06-12 EP EP07730086.1A patent/EP2046319B1/en not_active Not-in-force
- 2007-06-12 PT PT77300861T patent/PT2046319E/pt unknown
- 2007-06-12 WO PCT/EP2007/055761 patent/WO2007144345A2/en active Application Filing
- 2007-06-12 JP JP2009514781A patent/JP2009539929A/ja active Pending
-
2010
- 2010-11-19 US US12/950,603 patent/US20110065797A1/en not_active Abandoned
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CA2655081A1 (en) | 2007-12-21 |
ES2425398T3 (es) | 2013-10-15 |
JP5792137B2 (ja) | 2015-10-07 |
US20110065797A1 (en) | 2011-03-17 |
WO2007144345A3 (en) | 2008-09-12 |
EP2046319A2 (en) | 2009-04-15 |
CA2655081C (en) | 2015-03-17 |
US20070293574A1 (en) | 2007-12-20 |
JP2009539929A (ja) | 2009-11-19 |
EP2046319B1 (en) | 2013-05-22 |
WO2007144345A2 (en) | 2007-12-21 |
US7863330B2 (en) | 2011-01-04 |
PT2046319E (pt) | 2013-07-10 |
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