JP2023503505A - 置換ブテンアミド医薬組成物及びその製造方法 - Google Patents
置換ブテンアミド医薬組成物及びその製造方法 Download PDFInfo
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- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
(1)予備混合:(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩、充填剤、及び崩壊剤を均一に混合するステップと、
(2)湿式造粒:粘着剤溶液を添加して軟質材料を調製し、篩にかけて造粒し、湿状顆粒を製造するステップと、
(3)乾燥、整粒、総混合:湿状顆粒を乾燥した後に、篩にかけて整粒し、滑沢剤を加えて総混合し、前記医薬組成物を製造するステップと、を含む前記(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩の医薬組成物の製造方法を提供する。この医薬組成物は、さらに打錠して錠剤にするか、又はカプセルに充填してカプセル剤にすることができる。ステップ(1)の前記予備混合方法は、ジェットミル予備混合、篩分け予備混合、湿式造粒機予備混合を含み、ステップ(2)の前記粘着剤は、濃度が2~10wt%であり、純水で調製され、ステップ(2)の前記湿式造粒は、湿式造粒機又は流動床を用いて行うことができ、流動床で造粒し乾燥することが好ましく、ステップ(3)の前記乾燥は、送風乾燥又は流動床を用いて行うことができ、流動床を用いることが好ましく、乾燥後の顆粒の水分を1.5wt%以内にし、1wt%以内にすることが好ましい。
(1)予備混合:有効成分、充填剤及び崩壊剤を均一に混合するステップと、
(2)乾燥、総混合:乾燥後の粉末に滑沢剤を加えて総混合するステップと、を含み、ステップ(1)の前記予備混合方法は、ジェットミル予備混合、篩分け予備混合、湿式造粒機予備混合を含み、ステップ(2)の前記乾燥は、送風乾燥を用いて行うことができ、乾燥後の水分を3wt%又は1.5wt%以内にし、1wt%以内にすることが好ましい。
(1)予備混合:有効成分、充填剤及び崩壊剤を均一に混合するステップと、
(2)湿式造粒:粘着剤溶液を添加して軟質材料を調製し、20~30メッシュの篩にかけて造粒するステップと、
(3)乾燥、整粒、総混合:湿状顆粒を乾燥した後に、0~30メッシュの篩にかけて整粒し、滑沢剤を加えて総混合し、前記医薬組成物を製造するステップと、を含むことが好ましい。
一回使用量の処方組成を表7に示す。
(付記1)
(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩を5~50重量部、充填剤を40~120重量部、崩壊剤を2~20重量部、粘着剤を0~6重量部、滑沢剤を0.5~5重量部含有することを特徴とする、(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩の医薬組成物。
(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩を8~12重量部、充填剤を50~100重量部、崩壊剤を4~15重量部、粘着剤を0.3~5重量部、滑沢剤を0.3~6重量部含有することを特徴とする、付記1に記載の医薬組成物。
(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩を9~11重量部、充填剤を65~90重量部、崩壊剤を5~12重量部、粘着剤を0.5~3重量部、滑沢剤を0.5~4重量部含有することを特徴とする、付記1に記載の医薬組成物。
前記充填剤は、炭水化物から選ばれ、好ましくは糖類化合物であり、さらに好ましくは糖アルコールであることを特徴とする付記1~3のいずれか一つに記載の医薬組成物。
前記糖アルコールは、マンニトール、キシリトール、ソルビトール、乳糖であり、より好ましくはマンニトール、乳糖の1種又は複数種であることを特徴とする、付記1~3のいずれか一つに記載の医薬組成物。
前記崩壊剤は、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウムの一方又は両方であり、好ましくはカルボキシメチルスターチナトリウムであることを特徴とする、付記1~3のいずれか一つに記載の医薬組成物。
前記粘着剤は、ヒドロキシプロピルセルロース又はヒプロメロースの一方又は両方であり、好ましくはヒドロキシプロピルセルロースであり、さらに、前記滑沢剤は、ベヘン酸グリセリル、ステアリルフマル酸ナトリウム、タルクの1種以上であり、好ましくはベヘン酸グリセリルであることを特徴とする、付記1~3のいずれか一つに記載の医薬組成物。
前記塩は、塩酸塩、ベンゼンスルホン酸塩、メタンスルホン酸塩又はマレイン酸塩であり、さらに塩酸塩、ベンゼンスルホン酸塩、メタンスルホン酸塩又はマレイン酸塩の半水和物、一水和物であり、好ましくはマレイン酸塩の一水和物であり、好ましくは前記医薬組成物の水分含有量が5wt%又は3wt%又は1.5wt%以内であることを特徴とする、付記1~3のいずれか一つに記載の医薬組成物。
(1)予備混合:(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミドのマレイン酸塩、充填剤、及び崩壊剤を均一に混合するステップと、
(2)湿式造粒:粘着剤溶液を添加して軟質材料を調製し、篩にかけて造粒し、湿状顆粒を製造するステップと、
(3)乾燥、整粒、総混合:前記湿状顆粒を乾燥した後に、篩にかけて整粒し、滑沢剤を加えて総混合し、医薬組成物を製造するステップと、
を含むことを特徴とする、付記1~8のいずれか一つに記載の医薬組成物の製造方法。
ステップ(2)の前記粘着剤は、濃度が2~10wt%であり、純水で調製され、ステップ(3)の前記乾燥後の顆粒の水分は、1.5wt%以内、好ましくは1wt%以内であることを特徴とする、付記9に記載の医薬組成物の製造方法。
Claims (10)
- (E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩を5~50重量部、充填剤を40~120重量部、崩壊剤を2~20重量部、粘着剤を0~6重量部、滑沢剤を0.5~5重量部含有することを特徴とする、(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩の医薬組成物。
- (E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩を8~12重量部、充填剤を50~100重量部、崩壊剤を4~15重量部、粘着剤を0.3~5重量部、滑沢剤を0.3~6重量部含有することを特徴とする、請求項1に記載の医薬組成物。
- (E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミド又はその塩を9~11重量部、充填剤を65~90重量部、崩壊剤を5~12重量部、粘着剤を0.5~3重量部、滑沢剤を0.5~4重量部含有することを特徴とする、請求項1に記載の医薬組成物。
- 前記充填剤は、炭水化物から選ばれ、好ましくは糖類化合物であり、さらに好ましくは糖アルコールであることを特徴とする請求項1~3のいずれか一項に記載の医薬組成物。
- 前記糖アルコールは、マンニトール、キシリトール、ソルビトール、乳糖であり、より好ましくはマンニトール、乳糖の1種又は複数種であることを特徴とする、請求項1~3のいずれか一項に記載の医薬組成物。
- 前記崩壊剤は、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウムの一方又は両方であり、好ましくはカルボキシメチルスターチナトリウムであることを特徴とする、請求項1~3のいずれか一項に記載の医薬組成物。
- 前記粘着剤は、ヒドロキシプロピルセルロース又はヒプロメロースの一方又は両方であり、好ましくはヒドロキシプロピルセルロースであり、さらに、前記滑沢剤は、ベヘン酸グリセリル、ステアリルフマル酸ナトリウム、タルクの1種以上であり、好ましくはベヘン酸グリセリルであることを特徴とする、請求項1~3のいずれか一項に記載の医薬組成物。
- 前記塩は、塩酸塩、ベンゼンスルホン酸塩、メタンスルホン酸塩又はマレイン酸塩であり、さらに塩酸塩、ベンゼンスルホン酸塩、メタンスルホン酸塩又はマレイン酸塩の半水和物、一水和物であり、好ましくはマレイン酸塩の一水和物であり、好ましくは前記医薬組成物の水分含有量が5wt%又は3wt%又は1.5wt%以内であることを特徴とする、請求項1~3のいずれか一項に記載の医薬組成物。
- (1)予備混合:(E)-N-(3-シアノ-7-エトキシ-4-(3-エチニルフェニルアミノ)キノリン-6-イル)-4-(ジメチルアミノ)ブタ-2-エンアミドのマレイン酸塩、充填剤、及び崩壊剤を均一に混合するステップと、
(2)湿式造粒:粘着剤溶液を添加して軟質材料を調製し、篩にかけて造粒し、湿状顆粒を製造するステップと、
(3)乾燥、整粒、総混合:前記湿状顆粒を乾燥した後に、篩にかけて整粒し、滑沢剤を加えて総混合し、医薬組成物を製造するステップと、
を含むことを特徴とする、請求項1~8のいずれか一項に記載の医薬組成物の製造方法。 - ステップ(2)の前記粘着剤は、濃度が2~10wt%であり、純水で調製され、ステップ(3)の前記乾燥後の顆粒の水分は、1.5wt%以内、好ましくは1wt%以内であることを特徴とする、請求項9に記載の医薬組成物の製造方法。
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