JP4634008B2 - 2h−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)−及びその生理学的に許容される酸付加塩の新規使用 - Google Patents
2h−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)−及びその生理学的に許容される酸付加塩の新規使用 Download PDFInfo
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- JP4634008B2 JP4634008B2 JP2002589005A JP2002589005A JP4634008B2 JP 4634008 B2 JP4634008 B2 JP 4634008B2 JP 2002589005 A JP2002589005 A JP 2002589005A JP 2002589005 A JP2002589005 A JP 2002589005A JP 4634008 B2 JP4634008 B2 JP 4634008B2
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- flibanserin
- dihydro
- parkinson
- benzimidazol
- trifluoromethyl
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Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
第19回国際神経精神薬理学会(CINP)(ワシントンD.C.)、1994、Abs 0−24−10
活性成分として
−(I)2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{ 4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル} エチル)−又はその生理学的に許容される酸付加塩、及び、
−(II)少なくとも1種の抗パーキンソン病薬
を1種以上の薬学的に許容される賦形剤と共に含む医薬組成物に関する。
−運動障害性の副作用をあまり起こさずに、それ以外の薬剤のパーキンソン病に対する有効性を改善すること、及び/又は、
−パーキンソン病を制御するのに必要なそれ以外の薬剤を投与して運動障害性の副作用を軽減すること
が可能になる。
−(I)2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{ 4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル} エチル)−又はその生理学的に許容される酸付加塩、及び、
−(II)少なくとも1種の従来の抗パーキンソン病薬、又は、
従来のドーパミンアゴニスト、及び、
−(III)従来のドーパミン脱炭酸酵素遮断剤
を1種以上の薬学的に許容される賦形剤と共に含んでいてよい。
(I)一般式(I)に記載の物質又はその生理学的に許容される酸付加塩、
(II)従来の抗パーキンソン病薬、及び、必要に応じて活性量の
(III)従来のドーパ脱炭酸酵素遮断剤
のそれぞれ活性量を、1種以上の薬学的な担体、希釈剤又は賦形剤と共に含む医薬組成物に関する。薬学的な投与のために、上記成分は、固形、液状又はスプレー状の従来の医薬品に組み入れられてよい。この組成物は、例えば、経口投与、直腸内投与、非経口投与又は経鼻吸入に適した形態であってよい。好ましい形態には、例えば、カプセル、錠剤、コート錠、アンプル、坐薬及び点鼻薬が含まれる。
フリバンセリン塩酸 15重量部
乳糖 182重量部
コーンスターチ 50重量部
ステアリン酸マグネシウム 3重量部
上記成分を準備する。始めにフリバンセリン、乳糖及びコーンスターチを混合し、水で均一に湿らせた。湿って固まった部分を選別し、トレー乾燥機で乾燥させた後、混合物を再び篩にかけてステアリン酸マグネシウムを加えた。その後、この混合物を250mgずつプレスして錠剤にした。各錠剤は15mgのフリバンセリン塩酸を含有する。
フリバンセリン塩酸 1重量部
レボドパ 50重量部
ベンセラジド 10重量部
乳糖 200重量部
タルク 10重量部
ステアリン酸マグネシウム 5重量部
上記成分を用いて、通常の方法により錠剤を得る。各錠剤はフリバンセリン塩酸0.2mg、レボドパ10mg、及び、ベンセラジド2mgを含有する。
フリバンセリン塩酸 15重量部
乳糖 183重量部
ステアリン酸マグネシウム 2重量部
上記成分により均一な混合物を調製し、この混合物を200mgずつ硬質ゼラチンカプセルに充填する。
フリバンセリン塩酸 1重量部
脂肪酸の半合成グリセリド 49重量部
上記成分を準備し、脂肪酸の半合成グリセリドを溶解して、均一な溶解物を得る。その後、均一に撹拌しながら粉末フリバンセリン塩酸を上記溶解物に混合する。冷却後、この脂肪質の練薬をあらかじめ作っておいた坐薬用型にプレスする。各坐薬の重量は1200mgで、24mgのフリバンセリン塩酸を含有する。
Bonifati−V;Fabrizio−E;Cipriani−R;Vanacore−N;Meco−G
レボドパ誘導性運動障害におけるブスピロン(Buspirone in levodopa−induced dykinesias.)
Clin−Neuropharmaco1.1994 Feb;17(1);73−82
持続性の遅発性ジスキネジアの霊長類モデルにおけるミトコンドリアの超微細構造と密度(Mitochondrial ultrastructure and density in a primate model of persistant tardive dyskinesia)
Life−Sci.2000 Feb 25;66(14);1345−50
ブスピロン;その薬理学的特性、及び、抗不安薬としての治療的有効性の予備調査(Buspirone.A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic.)
Drugs.1986 Aug;32(2);112−29
クロザピンの作用機構の概要(An overview of the mechanism of action of clozapine.)
J−Clin−Psychiatry.1994 Sep;55 Suppl B;47−52
血漿クロザピン濃度、及び、パーキンソン病におけるL−DOPA誘導性精神病の治療:クロザピンの高い潜在効果(Plasma clozapine levels and the treatment of L−DOPA−induced psychosis in Parkinson’s disease.A high potency effect of clozapine.)
Neurophysopharmacology.1995 Feb;12(1);39−45
培養におけるドーパミン作動性ニューロンに対する6−ヒドロキシドーパミンとドーパミンの毒性(Toxicity of 6−hydroxydopamine and dopamine for dopaminergic neurons in culture.)
J−Neurosci−Res.1990 Aug:26(4);428−35
慢性的なL−DOPA投与は、1−メチル−4−フェニル−1,2,3,6−テトラヒドロピリジンで処置したコモンマーモセット(Callithrix jacchus)において運動障害を誘導する(Chronic L−DOPA administration induces dyskinesias in the 1−methyl−4−phenyl−1,2,3,6−tetrahydropyridine−treated common marmoset(Callithrix Jacchus).)
Mov−Disord.1995 Nov;10(6);731−40
DATATOP;10年間に渉る神経保護に関する調査、パーキンソン病研究グループ(DATATOP;a decade of neuroprotective inquiry.Parkinson Study Group.)
パーキンソニズムのデプレニル及びトコフェロール抗酸化治療(Deprenyl And Tocophero1 Antioxidative Therapy Of Parkinsonism.)
Ann−Neuro1.1998 Sep;44(3 Suppl 1);S160−6
in vitro及びin vivoで証明された5−HT1A受容体アゴニスト、Bay X 3702の神経保護効果(Neuroprotective effect of 5−HT1A receptor agonist, Bay X 3702,demonstrated in vitro and in vivo.)
Eur−J−Pharmacol.1998 0ct 23;359(2−3);251−60
Claims (11)
- 2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)又はその生理学的に許容される酸付加塩の、特発性パーキンソン病患者のレボドパ誘導性運動障害を治療する錐体外路系運動障害治療薬の製造のための使用。
- 2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)又はその生理学的に許容される酸付加塩からなる、特発性パーキンソン病患者のレボドパ誘導性運動障害に対する錐体外路系運動障害治療薬。
- 2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)又はその生理学的に許容される酸付加塩を、1回経口投与単位0.01〜100mg含有することを特徴とする請求項2に記載の治療薬。
- 2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)又はその生理学的に許容される酸付加塩を、1回経口投与単位0.1〜50mg含有することを特徴とする請求項2又は3に記載の治療薬。
- 2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)又はその生理学的に許容される酸付加塩を、1回経口投与単位1〜20mg含有することを特徴とする請求項2〜4いずれか1項に記載の治療薬。
- 2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)は、塩酸、硫酸、マレイン酸又はフマル酸を用いて作られた、生理学的に許容される酸付加塩の形態であることを特徴とする請求項2〜5のいずれか1項に記載の治療薬。
- 特発性パーキンソン病患者のレボドパ誘導性運動障害を軽減する効果を有する薬学的複合薬の製造のための、少なくとも1種の従来の抗パーキンソン病薬とともに配合される、2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)又はその生理学的に許容される酸付加塩の使用。
- 前記少なくとも1種の抗パーキンソン病薬は、レボドパ、アマンタジン、ビペリデン、メチキセン、ブディピン(budipine)、メトクロプラミド、セレギリン及び/又は少なくとも1種の従来のドーパミンアゴニストを含む群より選択される
ことを特徴とする請求項7に記載の使用。 - 前記従来のドーパミンアゴニストは、アポモルヒネ、ブロモクリプチン、α−ジヒドロ−エルゴクリプチン、カベルゴリン、リスリド、ペルゴリド、プラミペキソール及びロピニロールを含む
ことを特徴とする請求項8に記載の使用。 - 前記従来の抗パーキンソン病薬は、ドーパ脱炭酸酵素遮断剤を含むことを特徴とする請求項7〜9いずれか1項に記載の使用。
- 2H−ベンズイミダゾール−2−オン、1,3−ジヒドロ−1−(2−{4−[3−(トリフルオロメチル)フェニル]−1−ピペラジニル}エチル)(フリバンセリン)は、塩酸、硫酸、マレイン酸又はフマル酸を用いて作られた、生理学的に許容される酸付加塩の形態である
ことを特徴とする請求項1及び7〜10いずれか1項に記載の使用。
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EP01111195A EP1256343B1 (en) | 2001-05-11 | 2001-05-11 | Flibanserin for the treatment of extrapyramidal movement disorders |
PCT/EP2002/005182 WO2002092088A2 (en) | 2001-05-11 | 2002-05-10 | Novel use of 2h-benzimidazol-2-one, 1,3-dihadro-1-(2{4-{3-(trifluoromethyl}phenyl]-1-piperazinyl}ethyl)- and its physiologically acceptable acid addition salts |
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US (1) | US8030314B2 (ja) |
EP (1) | EP1256343B1 (ja) |
JP (1) | JP4634008B2 (ja) |
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CA (1) | CA2444062C (ja) |
CY (1) | CY1105648T1 (ja) |
DE (1) | DE60121301T2 (ja) |
DK (1) | DK1256343T3 (ja) |
ES (1) | ES2267627T3 (ja) |
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DE10053397A1 (de) * | 2000-10-20 | 2002-05-02 | Schering Ag | Verwendung eines dopaminergen Wirkstoffes zur Behandlung von dopaminerg behandelbaren Erkrankungen |
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DE10064453A1 (de) * | 2000-12-16 | 2002-07-04 | Schering Ag | Verwendung eines dopaminergen Wirkstoffes zur Behandlung von dopaminerg behandelbaren Erkrankungen |
US7183410B2 (en) * | 2001-08-02 | 2007-02-27 | Bidachem S.P.A. | Stable polymorph of flibanserin |
US20030060475A1 (en) * | 2001-08-10 | 2003-03-27 | Boehringer Ingelheim Pharma Kg | Method of using flibanserin for neuroprotection |
DE10138273A1 (de) * | 2001-08-10 | 2003-02-27 | Boehringer Ingelheim Pharma | Arzneimittel mit neuroprotektiver Wirkung |
US10675280B2 (en) | 2001-10-20 | 2020-06-09 | Sprout Pharmaceuticals, Inc. | Treating sexual desire disorders with flibanserin |
UA78974C2 (en) | 2001-10-20 | 2007-05-10 | Boehringer Ingelheim Pharma | Use of flibanserin for treating disorders of sexual desire |
JP2006516549A (ja) * | 2002-12-23 | 2006-07-06 | メルク フロスト カナダ アンド カンパニー | パーキンソン病の治療用医薬組成物及び治療方法 |
BRPI0510074A (pt) * | 2004-04-22 | 2007-10-16 | Boehringer Ingelheim Int | composições farmacêuticas para o tratamento de distúrbios sexuais ii |
US20050239798A1 (en) * | 2004-04-22 | 2005-10-27 | Boehringer Ingelheim Pharmaceuticals, Inc. | Method for the treatment of premenstrual and other female sexual disorders |
US20060025420A1 (en) * | 2004-07-30 | 2006-02-02 | Boehringer Ingelheimn International GmbH | Pharmaceutical compositions for the treatment of female sexual disorders |
WO2006024471A1 (en) * | 2004-09-03 | 2006-03-09 | Boehringer Ingelheim International Gmbh | Method for the treatment of attention deficit hyperactivity disorder |
WO2006096434A2 (en) * | 2005-03-04 | 2006-09-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for the treatment and/or prevention of anxiety disorders |
WO2006096439A2 (en) * | 2005-03-04 | 2006-09-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for the treatment and/or prevention of schizophrenia and related diseases |
CA2599721A1 (en) * | 2005-03-04 | 2006-09-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for the treatment and/or prevention of depression |
WO2006119884A2 (en) * | 2005-05-06 | 2006-11-16 | Boehringer Ingelheim International Gmbh | Method for the treatment of drug abuse with flibanserin |
EP1888070A1 (en) * | 2005-05-19 | 2008-02-20 | Boehringer Ingelheim International GmbH | Method for the treatment of sexual dysfunctions due to medical conditions |
JP2008540673A (ja) * | 2005-05-19 | 2008-11-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 薬剤誘発性性機能不全の治療方法 |
ES2646326T3 (es) * | 2005-08-03 | 2017-12-13 | Sprout Pharmaceuticals, Inc. | Uso de flibanserina en el tratamiento de la obesidad |
US20070123540A1 (en) * | 2005-10-29 | 2007-05-31 | Angelo Ceci | Sexual desire enhancing medicaments comprising benzimidazolone derivatives |
CA2626134C (en) | 2005-10-29 | 2013-12-24 | Boehringer Ingelheim International Gmbh | Benzimidazolone derivatives for the treatment of premenstrual and other female sexual disorders |
US20070105869A1 (en) * | 2005-11-08 | 2007-05-10 | Stephane Pollentier | Use of flibanserin for the treatment of pre-menopausal sexual desire disorders |
US20090023712A1 (en) * | 2006-02-18 | 2009-01-22 | Boehringer Ingelheim International Gmbh | Pharmaceutical Compositions for the Treatment of Attention Deficit Hyperactivity Disorder Comprising Flibanserin |
US9066903B2 (en) | 2006-02-28 | 2015-06-30 | The United States Of America As Represented By The Department Of Veterans Affairs | Pharmacological treatment of Parkinson's disease |
DE602007004615D1 (de) | 2006-06-30 | 2010-03-18 | Boehringer Ingelheim Pharma | Flibanserin zur behandlung von harninkontinenz und assoziierten erkrankungen |
WO2008006838A1 (en) * | 2006-07-14 | 2008-01-17 | Boehringer Ingelheim International Gmbh | Use of flibanserin for the treatment of sexual disorders in females |
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CL2007002214A1 (es) | 2006-08-14 | 2008-03-07 | Boehringer Ingelheim Int | Composicion farmaceutica en la forma de comprimido, donde al menos la longitud del comprimido en el estado anterior de la aplicacion es al menos 7/12 del diametro pilorico del paciente y despues de ingerirlo en estado alimentado, la longitud del comp |
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DE102007009264A1 (de) * | 2007-02-26 | 2008-08-28 | Ellneuroxx Ltd. | 9-Alkyl-ß-Carboline zur Behandlung von neurodegenerativen Erkrankungen |
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EP0942732B1 (en) * | 1996-12-02 | 2004-11-17 | MERCK SHARP & DOHME LTD. | Use of nk-1 receptor antagonists for treating movement disorders |
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EP1256343A1 (en) | 2002-11-13 |
CA2444062A1 (en) | 2002-11-21 |
DE60121301D1 (de) | 2006-08-17 |
EP1256343B1 (en) | 2006-07-05 |
DK1256343T3 (da) | 2006-10-30 |
PT1256343E (pt) | 2006-11-30 |
WO2002092088A2 (en) | 2002-11-21 |
US20040180904A1 (en) | 2004-09-16 |
AU2002310813B2 (en) | 2008-04-03 |
DE60121301T2 (de) | 2007-07-19 |
CY1105648T1 (el) | 2010-12-22 |
CA2444062C (en) | 2011-02-22 |
ATE332138T1 (de) | 2006-07-15 |
ES2267627T3 (es) | 2007-03-16 |
WO2002092088A3 (en) | 2003-01-30 |
US8030314B2 (en) | 2011-10-04 |
JP2004529175A (ja) | 2004-09-24 |
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