JP6855488B2 - 食道癌を治療するためのキノリン誘導体の使用とその治療方法、医薬組成物及びキット - Google Patents
食道癌を治療するためのキノリン誘導体の使用とその治療方法、医薬組成物及びキット Download PDFInfo
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- JP6855488B2 JP6855488B2 JP2018535145A JP2018535145A JP6855488B2 JP 6855488 B2 JP6855488 B2 JP 6855488B2 JP 2018535145 A JP2018535145 A JP 2018535145A JP 2018535145 A JP2018535145 A JP 2018535145A JP 6855488 B2 JP6855488 B2 JP 6855488B2
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- esophageal cancer
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
(1)前記疾病を罹患中或いは表出している病理学的又は症候学的人体における当該疾病の抑制(即ち、前記病理学的及び/又は症候学的のさらなる進行の阻止)、又は
(2)前記疾病を罹患中或は表出している病理学的又は症候学的人体における当該疾病の改善(即ち、前記病理学的及び/又は症候学的反転)、
を含む。
WO2008112407における実施例24の方法を参照して、1-[[4-(4-フルオロ-2-メチル-1H-インドール-5-イルオキシ)-6-メトキシキノリン-7-イルオキシ]メチル]シクロプロパンアミンを製造した後、WO2008112407の明細書「塩生成の実施例」の製造方法を参照して、標題の化合物を製造した。或は、中国特許出願CN102344438Aに開示される方法を参照して製造した。
原料名 容量(1000粒)
化合物Iの二塩酸塩 14.16g(12gの化合物Iに相当)
マンニトール 89g
微結晶セルロース 138.4g
ヒドロキシプロピルセルロース 5.9g
ステアリン酸マグネシウム 0.99g
化合物Iの二塩酸塩を粉砕し、80メッシュのふるいにかけた後、マンニトール、ヒドロキシプロピルセルロースと均一に混合した。続いて、処方量の微結晶セルロースを加え、均一に混合してから0.8mmのふるいにかけた。最後に、処方量のステアリン酸マグネシウムを加えて均一に混合し、カプセルに充填した。
1)病歴
47歳女性、2012年3月に嚥下障害;胃鏡より、切歯から28〜31cmの食道に半円形のカリフラワー様の腫瘤が認められ;病理学より、低分化癌、扁平上皮癌が認められた。2012年4月19日のCTより、両肺に多発する結節と腫瘤が認められ、大きなものは約2.9x2.1cm、左鎖骨上及び食道の隣に多発するリンパ節が認められ、大きなものは左鎖骨上に、約3.3×3.2cm。2012年4月28日から2012年9月まで、パクリタキセルリポソーム+ネダプラチン+フルオロウラシルによる化学療法を6サイクル実施し、PR(部分緩解)と評価。2012年9月から2012年11月まで、テガフール・ギメラシル・オテラシルカリウムの経口投与による治療を維持し、2012年11月の再検査に病変の進行が認められた。2012年11月30日から2013年2月28日まで、ゲムシタビン+カルシウムレボフォリナート/フルオロウラシルによる化学療法を2サイクル、ビノレルビン+カペシタビンによる化学療法を2サイクル実施した後、PD(疾病の進行)と評価。2013年3月19日から2013年4月19日まで、漢方薬「益金生」を使用し、PD(疾病の進行)と評価。2013年5月6日から2013年6月15日まで、胸部放射線療法DT60Gを評価なしに実施し、2013年7月19日から2014年2月まで、ドセタキセル+ネダプラチン/オキサリプラチンによる化学療法を8サイクル実施し、PD(疾病の進行)と評価。
化合物Iの二塩酸塩のカプセルの投与前の画像学的評価:標的病変の長径和82mm;
化合物Iの二塩酸塩のカプセルの第2の投与サイクルの終わりの画像学的評価:標的病変の長径和78mm;
化合物Iの二塩酸塩のカプセルの第6の投与サイクルの終わりの画像学的評価:標的病変の長径和75mm。
全体的な耐容性は良好であった。偶発的なI°の高コレステロール血症、I°の咽頭痛、I°の食欲不振、I°の蛋白尿、I°の食欲不振、I°の手足皮膚反応、及びI°の甲状腺刺激ホルモン亢進のみ発生した。
Claims (12)
- 前記進行食道癌及び/又は転移性食道癌は、食道扁平上皮癌及び/又は食道腺癌である請求項1に記載の使用。
- 前記進行食道癌及び/又は転移性食道癌は、タキサン系抗腫瘍薬、ビンブラスチン抗腫瘍薬、白金錯体及び/又はピリミジン拮抗薬による治療に失敗したものであり、好ましくは、前記タキサン系抗腫瘍薬は、パクリタキセル及びドセタキセルから選択され、前記ビンブラスチン抗腫瘍薬は、ビンブラスチン、ビンクリスチン、ビンデシン及びビノレルビンから選択され、前記白金錯体は、ミリプラチン、シスプラチン、カルボプラチン、ネダプラチン及びオキサリプラチンから選択され、前記ピリミジン拮抗薬は、シタラビン、アンシタビン、カペシタビン、ゲムシタビン、フルオロウラシル、テガジフール、ドキシフルリジン、テガフール及びカルモフールから選択される、請求項1又は2に記載の使用。
- 前記進行食道癌及び/又は転移性食道癌は、パクリタキセル及び/又は白金錯体による治療に失敗したものである、請求項3に記載の使用。
- 化合物Iの薬学上許容され得る塩は塩酸塩であり、好ましくは二塩酸塩である請求項1〜4のいずれか1項に記載の使用。
- 前記進行食道癌及び/又は転移性食道癌は、食道扁平上皮癌及び/又は食道腺癌である請求項6に記載の医薬組成物。
- 前記進行食道癌及び/又は転移性食道癌は、タキサン系抗腫瘍薬、ビンブラスチン抗腫瘍薬、白金錯体及び/又はピリミジン拮抗薬による治療に失敗したものであり、好ましくは、前記タキサン系抗腫瘍薬は、パクリタキセル及びドセタキセルから選択され、前記ビンブラスチン抗腫瘍薬は、ビンブラスチン、ビンクリスチン、ビンデシン及びビノレルビンから選択され、前記白金錯体は、ミリプラチン、シスプラチン、カルボプラチン、ネダプラチン及びオキサリプラチンから選択され、前記ピリミジン拮抗薬は、シタラビン、アンシタビン、カペシタビン、ゲムシタビン、フルオロウラシル、テガジフール、ドキシフルリジン、テガフール及びカルモフールから選択される、請求項6又は7に記載の医薬組成物。
- 前記進行食道癌及び/又は転移性食道癌は、パクリタキセル及び/又は白金錯体による治療に失敗したものである、請求項8に記載の医薬組成物。
- 化合物Iの薬学上許容され得る塩は塩酸塩であり、好ましくは二塩酸塩である請求項6〜9のいずれか1項に記載の医薬組成物。
- 化合物I又は薬学上許容され得るその塩の1日あたりの投与量は、2mg〜20mg、5mg〜20mg、8mg〜20mg、10mg〜16mg、10mg〜14mg、10mg、12mg、14mg及び16mgのいずれかである請求項6〜10のいずれか1項に記載の医薬組成物。
- 化合物I又は薬学上許容され得るその塩を、間隔を空けた投薬方式で投与され、前記の間隔を空けた投薬には投薬期と投薬停止期が含まれ、日数計算した場合の投薬期と投薬停止期との比は、2:0.5〜5、好ましくは2:0.5〜3、より好ましくは2:0.5〜2、更に好ましくは2:0.5〜1であり、間隔を空けた投薬方式として好ましくは、2週間連続投薬後に2週間投薬を停止する方式、2週間連続投薬後に1週間投薬を停止する方式、及び、5日間連続投薬後に2日間投薬を停止する方式、のいずれかであり、上記の間隔を空けた投薬方式は複数回反復可能であることを特徴とする請求項6〜11のいずれか1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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CN201610013628.4 | 2016-01-08 | ||
CN201610013628 | 2016-01-08 | ||
PCT/CN2017/070352 WO2017118401A1 (zh) | 2016-01-08 | 2017-01-06 | 喹啉衍生物用于治疗食管癌的用途及其治疗方法、药物组合物和试剂盒 |
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JP2019501185A JP2019501185A (ja) | 2019-01-17 |
JP6855488B2 true JP6855488B2 (ja) | 2021-04-07 |
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US11419862B2 (en) | 2018-03-14 | 2022-08-23 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Quinoline derivative for treatment of nasopharyngeal carcinoma |
CN111643502A (zh) * | 2019-03-04 | 2020-09-11 | 正大天晴药业集团股份有限公司 | 喹啉衍生物联合化疗药物用于治疗非小细胞肺癌 |
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US8148532B2 (en) * | 2007-03-14 | 2012-04-03 | Guoqing Paul Chen | Spiro substituted compounds as angiogenesis inhibitors |
WO2008138184A1 (fr) * | 2007-05-14 | 2008-11-20 | Shanghai Hengrui Pharmaceutical Co.Ltd. | Dérivés de pyrrolo-azacycles, leur procédé de fabrication et leur utilisation en tant qu'inhibiteurs de protéine kinases |
WO2009064657A1 (en) * | 2007-11-13 | 2009-05-22 | Phoenix Biotechnology Inc. | Method of determining the probability of a therapeutic response in cancer chemotherapy with cardiac glycoside |
CN103664892B (zh) * | 2010-08-01 | 2015-09-02 | 正大天晴药业集团股份有限公司 | 喹啉衍生物的结晶 |
CN105213394B (zh) * | 2014-06-06 | 2019-04-09 | 正大天晴药业集团股份有限公司 | 具有抗肿瘤活性的喹啉衍生物 |
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RU2018126829A3 (ja) | 2020-04-06 |
CN115025090A (zh) | 2022-09-09 |
CN108601778A (zh) | 2018-09-28 |
RU2018126829A (ru) | 2020-01-20 |
US10561647B2 (en) | 2020-02-18 |
RU2734260C2 (ru) | 2020-10-13 |
EP3400942B1 (en) | 2022-04-13 |
JP2019501185A (ja) | 2019-01-17 |
US20190022082A1 (en) | 2019-01-24 |
EP3400942A1 (en) | 2018-11-14 |
WO2017118401A1 (zh) | 2017-07-13 |
ES2913097T3 (es) | 2022-05-31 |
EP3400942A4 (en) | 2019-10-16 |
CA3010654A1 (en) | 2017-07-13 |
AU2017205749A1 (en) | 2018-08-02 |
AU2017205749B2 (en) | 2021-12-23 |
KR20180100614A (ko) | 2018-09-11 |
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