JP2022515615A - 慢性炎症性腸疾患の治療のためのpar-1アンタゴニストの使用 - Google Patents
慢性炎症性腸疾患の治療のためのpar-1アンタゴニストの使用 Download PDFInfo
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Abstract
Description
この研究の目的は、ウィスター系の雄の実験用ラットでの2,4,6-トリニトロベンゼンスルホン酸(TNBS)誘発炎症性腸疾患モデルにおいて、2種類のPAR-1アンタゴニスト、すなわち、ボラパキサルおよび3-2-(クロロ-フェニル)-1-[4-(4-フルオロ-ベンジル)-ピペラジン-1-イル]プロペノン(以下、CSIと称する)の有効性を評価することである。このモデルはWhittleら、2003年、Methods Mol. Biol.、第225巻、第209~222頁(非特許文献7)の刊行物に記載されている。
PAR-1アンタゴニストを用いた実験は、ボラパキサルおよびCSIに関する2つの研究でそれぞれ行う。
TNBS誘発大腸炎のこのモデルでは、研究の開始時点で、下痢および糞便内における血液の存在(DAI)などの重要かつ代表的な臨床症状が現れる。その後、いくらかの日常的な慢性性が確立され、これを異なるパラメータによって以下で評価する。
この研究の目的は、マウスでのデキストラン硫酸ナトリウム(Dextran Sulphate sodium:DSS)による炎症性腸疾患モデルにおいて、本発明によるPAR-1アンタゴニストである3-2-(クロロ-フェニル)-1-[4-(4-フルオロ-ベンジル)-ピペラジン-1-イル]プロペノン(CSI)の有効性を評価することである。このDSSモデルは、Choiら、2010年、J. Biomed. Biotechnol.,2010:943516;doi:10.1155/2010/943516(非特許文献10)の刊行物に記載されている。
マウスは、以下の表5に示すような5つの群に分配する。
0日目と比較したマウスの体重の変動を各群について以下の表6に示す。この表において、「Moy」は、群の異なる個体について得られた平均を指し、また、「esm」は平均に対する標準偏差を表す。
本質的に遠位回腸および大腸における活性物質の放出のための、経口投与に適した剤形における本発明による医薬組成物の実施例について以下で説明する。
本発明による医薬組成物は、以下の添加剤、すなわち、微結晶性セルロース、ステアリン酸マグネシウムと混合された、ボラパキサル、アトパキサール、または3-2-(クロロ-フェニル)-1-[4-(4-フルオロ-ベンジル)-ピペラジン-1-イル]プロペノンを含有する微粒剤の形態にある。
本発明による医薬組成物は、以下の添加剤、すなわち、炭酸ナトリウム、グリシン、ポビドン、微結晶性セルロース、シリカ、ステアリン酸カルシウム、二酸化チタン、酸化鉄と混合された、ボラパキサル、アトパキサール、または3-2-(クロロ-フェニル)-1-[4-(4-フルオロ-ベンジル)-ピペラジン-1-イル]プロペノンを含有するコアを含む錠剤の形態にある。
上記の処方の各々について、医薬組成物は、1回の単回投与で1日当たり1錠の割合で投与され得る。
滅菌した鉗子を使用して、単層で集密したヒト大腸上皮細胞Caco2上に傷をつける。
Claims (8)
- ボラパキサル、PAR-1受容体に対してアンタゴニスト活性を有するボラパキサル異性体、アトパキサール、3-2-(クロロ-フェニル)-1-[4-(4-フルオロ-ベンジル)-ピペラジン-1-イル]プロペノン、およびそれらの薬学的に許容される塩によって構成される群から選択されるPAR-1アンタゴニストであって、腸および大腸の慢性炎症性疾患に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものである、PAR-1アンタゴニスト。
- 腸および大腸の慢性炎症性疾患に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものであり、前記対象は哺乳動物であり、好ましくは人間である、請求項1に記載のPAR-1アンタゴニスト。
- クローン病に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものである、請求項1または2に記載のPAR-1アンタゴニスト。
- 活性物質としてPAR-1アンタゴニストと、少なくとも1種の薬学的に許容される添加剤とを含有する医薬組成物であって、前記PAR-1アンタゴニストは、ボラパキサル、PAR-1受容体に対してアンタゴニスト活性を有するボラパキサル異性体、アトパキサール、3-2-(クロロ-フェニル)-1-[4-(4-フルオロ-ベンジル)-ピペラジン-1-イル]プロペノン、およびそれらの薬学的に許容される塩によって構成される群から選択され、前記医薬組成物は、腸および大腸の慢性炎症性疾患に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものである、医薬組成物。
- 腸および大腸の慢性炎症性疾患に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものであり、前記対象は哺乳動物であり、好ましくは人間である、請求項4に記載の医薬組成物。
- クローン病に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものである、請求項4または5に記載の医薬組成物。
- 腸および大腸の慢性炎症性疾患に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものであり、前記組成物は、経口投与に適した剤形を有する、請求項4から請求項6のいずれか一項に記載の医薬組成物。
- 腸および大腸の慢性炎症性疾患に罹患している対象における腸の疼痛を低減するため、および/または腸の上皮組織を修復するために使用するためのものであり、前記PAR-1アンタゴニストは腸溶性コーティングで覆われたコアに含まれている、請求項4から請求項7のいずれか一項に記載の医薬組成物。
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Application Number | Priority Date | Filing Date | Title |
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FR1873359 | 2018-12-19 | ||
FR1873359A FR3090317B1 (fr) | 2018-12-19 | 2018-12-19 | Utilisation d’un antagoniste de par-1 pour le traitement d’une maladie inflammatoire chronique intestinale |
PCT/EP2019/086027 WO2020127539A1 (fr) | 2018-12-19 | 2019-12-18 | Utilisation d'un antagoniste de par-1 pour le traitement d'une maladie inflammatoire chronique intestinale |
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JP2022515615A true JP2022515615A (ja) | 2022-02-21 |
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JP2021536327A Pending JP2022515615A (ja) | 2018-12-19 | 2019-12-18 | 慢性炎症性腸疾患の治療のためのpar-1アンタゴニストの使用 |
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US (1) | US20220062247A1 (ja) |
EP (1) | EP3897633B1 (ja) |
JP (1) | JP2022515615A (ja) |
CA (1) | CA3124178A1 (ja) |
FR (1) | FR3090317B1 (ja) |
WO (1) | WO2020127539A1 (ja) |
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FR3134314A1 (fr) | 2022-04-08 | 2023-10-13 | Cvasthera | Composition pharmaceutique à base de vorapaxar et son utilisation pour le traitement des maladies inflammatoires intestinales |
Citations (4)
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JP2009541260A (ja) * | 2006-06-19 | 2009-11-26 | ピエール、ファーブル、メディカマン | シンナモイル−ピペラジン誘導体およびpar−1拮抗薬としてのそれらの使用 |
JP2010522169A (ja) * | 2007-03-23 | 2010-07-01 | シェーリング コーポレイション | トロンビン受容体アンタゴニストの使用による、経皮的インターベンション後の有害事象の低減 |
JP2013536827A (ja) * | 2010-09-01 | 2013-09-26 | ディスパル・インターナショナル・ビー.ブイ. | 溶出改善されたメサラジン錠 |
JP2016540799A (ja) * | 2013-12-16 | 2016-12-28 | ピエール、ファーブル、メディカマン | 骨盤・会陰部機能の病的状態を予防および/または治療するためのpar−1アンタゴニストの使用 |
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EP2062890B1 (en) | 2002-04-16 | 2011-01-05 | Schering Corporation | Tricyclic thrombin receptor antagonist |
KR101198452B1 (ko) | 2003-08-25 | 2012-11-06 | 메르크 파텐트 게엠베하 | 메소제닉 화합물, 전기-광학 디스플레이용 매질 및전기-광학 디스플레이 |
US20050193788A1 (en) | 2004-03-03 | 2005-09-08 | Alan Weiner | Method and apparatus locating a keyhole and orienting a key to the keyhole |
US20090017110A1 (en) | 2005-05-31 | 2009-01-15 | Capricorn Pharma Inc. | Modified release formulations of anti-irritability drugs |
US7888483B2 (en) * | 2006-07-18 | 2011-02-15 | Irm Llc | Antagonists of protease activated receptor-1 (PAR1) |
DE102009022895A1 (de) * | 2009-05-27 | 2010-12-02 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Piperidine |
IN2014MU00097A (ja) | 2014-01-10 | 2015-08-21 | Cadila Healthcare Ltd |
-
2018
- 2018-12-19 FR FR1873359A patent/FR3090317B1/fr not_active Expired - Fee Related
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2019
- 2019-12-18 CA CA3124178A patent/CA3124178A1/fr active Pending
- 2019-12-18 EP EP19827703.0A patent/EP3897633B1/fr active Active
- 2019-12-18 WO PCT/EP2019/086027 patent/WO2020127539A1/fr unknown
- 2019-12-18 JP JP2021536327A patent/JP2022515615A/ja active Pending
- 2019-12-18 US US17/415,376 patent/US20220062247A1/en active Pending
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JP2009541260A (ja) * | 2006-06-19 | 2009-11-26 | ピエール、ファーブル、メディカマン | シンナモイル−ピペラジン誘導体およびpar−1拮抗薬としてのそれらの使用 |
JP2010522169A (ja) * | 2007-03-23 | 2010-07-01 | シェーリング コーポレイション | トロンビン受容体アンタゴニストの使用による、経皮的インターベンション後の有害事象の低減 |
JP2013536827A (ja) * | 2010-09-01 | 2013-09-26 | ディスパル・インターナショナル・ビー.ブイ. | 溶出改善されたメサラジン錠 |
JP2016540799A (ja) * | 2013-12-16 | 2016-12-28 | ピエール、ファーブル、メディカマン | 骨盤・会陰部機能の病的状態を予防および/または治療するためのpar−1アンタゴニストの使用 |
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Also Published As
Publication number | Publication date |
---|---|
US20220062247A1 (en) | 2022-03-03 |
CA3124178A1 (fr) | 2020-06-25 |
EP3897633C0 (fr) | 2023-06-07 |
FR3090317B1 (fr) | 2021-05-07 |
FR3090317A1 (fr) | 2020-06-26 |
EP3897633A1 (fr) | 2021-10-27 |
EP3897633B1 (fr) | 2023-06-07 |
WO2020127539A1 (fr) | 2020-06-25 |
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