JP2020510045A - ポネシモドを含有する医薬的組み合わせ - Google Patents
ポネシモドを含有する医薬的組み合わせ Download PDFInfo
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- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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Abstract
Description
の移植片対宿主病及び全身性エリテマトーデスなどの自己免疫疾患の治療に好適であると説明されている。PCT国際公開第02/080897号は、テリフルノミドが多発性硬化症の治療に有用であると開示している。特に、テリフルノミド(Aubagio(登録商標))は、多発性硬化症の再発形態の治療に承認されている。テリフルノミドは、例えば米国特許第6,894,184号で説明されるように、当該技術分野で既知の手順に従って調製することができる。2−シアノ−3−ヒドロキシブト−2−エン酸−(4−トリフルオロメチルフェニル)−アミドはZ−及びE−立体異性体間で相互転換可能であり、Z−エノールは最も安定しており、そのため最も優勢な形態である。
例えば第1の活性成分が1日1回投与され、第2の成分が1日2回投与される、実施形態4)の特別な事例では、1日に必要とされる2つの医薬組成物のうちの一方だけが第1及び第2の活性成分の両方を含有し、もう一方は第2の活性成分のみを含有する。好ましくは、第1及び第2の活性成分は1日1回投与される。
個別の医薬組成物は経口投与される。
+3+1、6+5+1、6+5+2+1、6+5+3+1、7+1、7+2+1、7+3+1、7+4+1、7+4+2+1、7+4+3+1、7+5+1、7+5+2+1、7+5+3+1、8+1、8+2+1、8+3+1、8+4+1、8+4+2+1、8+4+3+1、8+5+1、8+5+2+1、8+5+3+1、9+1、9+2+1、9+3+1、9+4+1、9+4+2+1、9+4+3+1、9+5+1、9+5+2+1、9+5+3+1、10+1、10+2+1、10+3+1、10+4+1、10+4+2+1、10+4+3+1、10+5+1、10+5+2+1、10+5+3+1、11+1、11+2+1、11+3+1、11+4+1、11+4+2+1、11+4+3+1、11+5+1、11+5+2+1、11+5+3+1、12+1、12+2+1、12+3+1、12+4+1、12+4+2+1、12+4+3+1、12+5+1、12+5+2+1、12+5+3+1、13+1、13+2+1、13+3+1、13+4+1、13+4+2+1、13+4+3+1、13+5+1、13+5+2+1、13+5+3+1、23+22、24+22、25+22、25+23+22、25+24+22、26+22、26+23+22、26+24+22、26+25+22、26+25+23+22、26+25+24+22、27+22、27+23+22、27+24+22、27+25+22、27+25+23+22、27+25+24+22、29+28、30+28、32+31、及び33+31。
濁剤などの経口投与用投薬形態が好ましい。2つの活性成分が個別の医薬組成物に含有されている事例では、上記の個別の医薬組成物は、同じ又は異なる投薬形態を用いて、同じか又は異なる投与経路によって投与されてもよい。最も好ましくは、ポネシモド、テリフルノミド、及びレフルノミドは、経口で、特に錠剤形態で投与される。
安全性プロファイルを改善させることができる。一実施形態では、医薬的組み合わせの2つの活性成分のうち1つのみが同位体標識される。本発明の好適な実施形態では、活性成分は同位体標識されず、又は一方の活性成分が同位体標識されず、もう一方の活性成分が1つ以上の重水素原子でのみ標識され、又は両方の活性成分がそれぞれ1つ以上の重水素原子でのみ標識される。最も好ましい実施形態では、活性成分は全く同位体標識されない。同位体標識された活性成分は、同位体標識された活性成分ではなく、好適な試薬又は出発物質の適切な同位体変形を用いることに関して説明される方法と同様に調製することができる。
実験的自己免疫性脳脊髄炎(EAE)の急性単相性モデルにおけるテリフルノミド及びポネシモドの有効性は、パイロット実験で判定することができる。
1. ビヒクル(0.5%メチルセルロース/0.5%Tween(登録商標)80/水)q.d.、0日目から
2. テリフルノミド(1mg/kg)q.d.、0日目から
3. ポネシモド(30mg/kg)q.d.、0日目から
4. テリフルノミド(1mg/kg)q.d.、0日目から+ポネシモド(30mg/kg)q.d.、0日目から
生存中(In life)及び終了エンドポイントは、第1のパイロット実験に関して説明され
たものと同じである。
Claims (12)
- ポネシモドである第1の活性成分と、テリフルノミド及びレフルノミドからなる群から選択される第2の活性成分と、を含有する医薬的組み合わせ。
- 前記第1の活性成分はポネシモドであり、前記第2の活性成分はテリフルノミドである、請求項1に記載の医薬的組み合わせ。
- 前記第1の活性成分はポネシモドであり、前記第2の活性成分はレフルノミドである、請求項1に記載の医薬的組み合わせ。
- 前記第1及び第2の活性成分は単一の医薬組成物に含有される、請求項1〜3のいずれか一項に記載の医薬的組み合わせ。
- 前記第1及び第2の活性成分は個別の医薬組成物に含有される、請求項1〜3のいずれか一項に記載の医薬的組み合わせ。
- 薬剤として使用するための、請求項1〜5のいずれか一項に記載の医薬的組み合わせ。
- リンパ球介在活性化免疫系に関連する疾病又は疾患の予防又は治療で使用するための、請求項1〜5のいずれか一項に記載の医薬的組み合わせ。
- 多発性硬化症の治療で使用するための、請求項1〜5のいずれか一項に記載の医薬的組み合わせ。
- 薬剤として使用するための、ポネシモド、及び少なくとも1つの治療的に不活性な賦形剤を含有する医薬組成物であって、前記医薬組成物は、テリフルノミド又はレフルノミド、及び少なくとも1つの治療的に不活性な賦形剤を含有する第2の医薬組成物との組み合わせで投与される、医薬組成物。
- 請求項7又は8に記載される疾病又は疾患の予防又は治療で使用するための、ポネシモド、及び少なくとも1つの治療的に不活性な賦形剤を含有する医薬組成物であって、前記医薬組成物は、テリフルノミド又はレフルノミド、及び少なくとも1つの治療的に不活性な賦形剤を含有する第2の医薬組成物との組み合わせで投与される、医薬組成物。
- 薬剤として使用するための、テリフルノミド又はレフルノミド、及び少なくとも1つの治療的に不活性な賦形剤を含有する医薬組成物であって、前記医薬組成物は、ポネシモド、及び少なくとも1つの治療的に不活性な賦形剤を含有する第2の医薬組成物との組み合わせで投与される、医薬組成物。
- 請求項7又は8に記載される疾病又は疾患の予防又は治療で使用するための、テリフルノミド又はレフルノミド、及び少なくとも1つの治療的に不活性な賦形剤を含有する医薬組成物であって、前記医薬組成物は、ポネシモド、及び少なくとも1つの治療的に不活性な賦形剤を含有する第2の医薬組成物との組み合わせで投与される、医薬組成物。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007511563A (ja) * | 2003-11-21 | 2007-05-10 | アクテリオン ファマシューティカルズ リミテッド | 新規チアゾリジン−4−オン誘導体 |
JP2008517059A (ja) * | 2004-10-19 | 2008-05-22 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | 炎症性腸疾患を治療するための(z)−2−シアノ−3−ヒドロキシ−ブタ−2−エン酸−(4’−トリフルオロメチルフェニル)−アミドの使用 |
JP2011514379A (ja) * | 2008-03-17 | 2011-05-06 | アクテリオン ファーマシューティカルズ リミテッド | 選択的s1p1レセプターアゴニストの投与法 |
WO2016091996A1 (en) * | 2014-12-11 | 2016-06-16 | Actelion Pharmaceuticals Ltd | Dosing regimen for a selective s1p1 receptor agonist |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES448386A1 (es) | 1975-06-05 | 1978-04-16 | Hoechst Ag | Procedimiento para la preparacion de anilidas de acido 5-me-til-isoxazol-4-carboxilico. |
DE2854439A1 (de) | 1978-12-16 | 1980-07-03 | Hoechst Ag | Ein isoxazolderivat, verfahren zu seiner herstellung, diese verbindung enthaltende mittel und verwendung |
US5268382A (en) | 1985-09-27 | 1993-12-07 | Hoechst Aktiengesellschaft | Medicaments to combat autoimmune diseases, in particular systemic lupus erythematosus |
DE3534440A1 (de) | 1985-09-27 | 1987-04-02 | Hoechst Ag | Arzneimittel gegen chronische graft-versus-host-krankheiten sowie gegen autoimmunerkrankungen, insbesondere systemischen lupus erythematodes |
WO2001060363A1 (en) * | 2000-02-15 | 2001-08-23 | Teva Pharmaceutical Industries Ltd. | A method for synthesizing leflunomide |
SI1381356T1 (sl) | 2001-04-05 | 2008-12-31 | Aventis Pharma Inc | Uporaba (Z)-2-ciano-3-hidroksi-but-2-enojska kislina-(4'-trifluorometilfenil)-amida za zdravljenje multiple skleroze |
GB0123571D0 (en) * | 2001-04-05 | 2001-11-21 | Aventis Pharm Prod Inc | Use of (Z)-2-cyano-3-hydroxy-but-2-enoic acid-(4'-trifluoromethylphenyl)-amide for treating multiple sclerosis |
US6894184B2 (en) | 2003-03-18 | 2005-05-17 | Aventis Pharma Deutschland Gmbh | Process for preparing 2-cyano-3-hydroxy-N-(phenyl)but-2-enamides |
USRE43833E1 (en) | 2003-11-21 | 2012-11-27 | Actelion Pharmaceuticals Ltd. | Thiazolidin-4-one derivatives |
DE102006017896A1 (de) | 2006-04-13 | 2007-10-25 | Tiefenbacher Pharmachemikalien Alfred E. Tiefenbacher Gmbh & Co. Kg | Leflunomid enthaltende pharmazeutische Zusammensetzungen |
DK2094676T3 (da) | 2006-11-23 | 2013-06-10 | Actelion Pharmaceuticals Ltd | Ny fremgangsmåde til fremstillingen af 2-iminothiazolidin-4-on-derivater |
US8912340B2 (en) | 2006-11-23 | 2014-12-16 | Actelion Pharmaceuticals Ltd. | Process for the preparation of 2-imino-thiazolidin-4-one derivatives |
GB0819182D0 (en) | 2008-10-20 | 2008-11-26 | Actelion Pharmaceuticals Ltd | Crystalline forms |
DK2477611T3 (en) | 2009-09-18 | 2017-07-10 | Sanofi Sa | (Z) -2-CYANO-3-HYDROXYBUT-2-ENIC ACID (4'-TRIFLUORMETHYLPHENYL) AMID TABLE FORMULATIONS WITH IMPROVED STABILITY |
US8747844B2 (en) | 2010-07-30 | 2014-06-10 | Saint Louis University | Methods of treating pain |
EP2600861A1 (en) | 2010-08-02 | 2013-06-12 | Sanofi-Aventis U.S. LLC | Use of teriflunomide for treating multiple sclerosis |
EP2692343A1 (en) * | 2012-08-03 | 2014-02-05 | Forward Pharma A/S | Combination therapy for treatment of multiple sclerosis |
CA2895172C (en) | 2012-08-17 | 2020-08-18 | Actelion Pharmaceuticals Ltd | Process for the preparation of|(2z,5z)-5-(3-chloro-4-((r)-2,3-dihydroxypropoxy)benzylidene)-2-(propylimino)-3-|(o-tolyl)thiazolidin-4-one and intermediate used in said process |
WO2016079687A1 (en) | 2014-11-18 | 2016-05-26 | Lupin Limited | Oral pharmaceutical composition of teriflunomide |
MA41139A (fr) | 2014-12-11 | 2017-10-17 | Actelion Pharmaceuticals Ltd | Combinaison pharmaceutique comportant un agoniste sélectif du récepteur sip1 |
WO2016205654A1 (en) | 2015-06-18 | 2016-12-22 | Aquarius Biotechnologies, Inc. | Compositions and methods for treating inflammatory disease or conditions |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007511563A (ja) * | 2003-11-21 | 2007-05-10 | アクテリオン ファマシューティカルズ リミテッド | 新規チアゾリジン−4−オン誘導体 |
JP2008517059A (ja) * | 2004-10-19 | 2008-05-22 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | 炎症性腸疾患を治療するための(z)−2−シアノ−3−ヒドロキシ−ブタ−2−エン酸−(4’−トリフルオロメチルフェニル)−アミドの使用 |
JP2011514379A (ja) * | 2008-03-17 | 2011-05-06 | アクテリオン ファーマシューティカルズ リミテッド | 選択的s1p1レセプターアゴニストの投与法 |
WO2016091996A1 (en) * | 2014-12-11 | 2016-06-16 | Actelion Pharmaceuticals Ltd | Dosing regimen for a selective s1p1 receptor agonist |
Non-Patent Citations (1)
Title |
---|
THER ADV CHRONIC DIS, vol. 7(1), JPN6021052326, 2016, pages 18 - 33, ISSN: 0004853972 * |
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