JP6887506B2 - ドネペジル又はその薬学的に許容可能な塩及びメマンチン又はその薬学的に許容可能な塩を含む認知症(dementia)及び認知機能障害の予防又は治療用薬学組成物及びその製造方法 - Google Patents
ドネペジル又はその薬学的に許容可能な塩及びメマンチン又はその薬学的に許容可能な塩を含む認知症(dementia)及び認知機能障害の予防又は治療用薬学組成物及びその製造方法 Download PDFInfo
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- JP6887506B2 JP6887506B2 JP2019539722A JP2019539722A JP6887506B2 JP 6887506 B2 JP6887506 B2 JP 6887506B2 JP 2019539722 A JP2019539722 A JP 2019539722A JP 2019539722 A JP2019539722 A JP 2019539722A JP 6887506 B2 JP6887506 B2 JP 6887506B2
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- pharmaceutically acceptable
- acceptable salt
- donepezil
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- memantine
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Description
以下、本発明の理解を助けるために好適な実施例を提示するが、下記の実施例は本発明を例示するものであるだけ、本発明の範疇及び技術思想の範囲内で多様な変更及び修正が可能であるのは当業者に明らかであり、このような変形及び修正が添付の特許請求範囲に属することは言うまでもない。
ドネペジル塩酸塩を10mgの含量で含むEisai Korea社のアリセプト10mgを使った。
メマンチン塩酸塩を10mgの含量で含むLundbeck Korea社のエビキサ20mg(10mg×2)を使った。
ドネペジル塩酸塩一水化物41.72g(10.4mg)、マンニトル480g(120mg)、ヒドロキシプロピルメチルセルロース20g(5mg)を混合する。これとは別に、精製水120gにヒドロキシプロピルセルロース20g(5mg)を添加して溶解させた後、前記ドネペジル塩酸塩混合物に添加し、スピードミキサーで混合させた後、前記混合物を60℃で2時間乾燥し、オシレーター20meshで濾過して定粒(d(0.1)9.6μm、d(0.5)141.8μm、d(0.9)784.3μm)する。
前記実施例1と同様な方法で実施するが、混合物をオシレーター16meshで濾過して定粒してドネペジル定粒物を収得して用いた。
前記実施例1と同様な方法で実施するが、混合物をオシレーター25meshで濾過して定粒してドネペジル定粒物を収得して用いた。
前記実施例1と同様な方法で実施するが、混合物をオシレーター30meshで濾過して定粒してドネペジル定粒物を収得して用いた。
前記実施例1と同様な方法で濾過されたドネペジル定粒物を製造する。
実施例1と同様な物質及び含量を使った。
実施例1と同様な物質及び含量を使った。
ドネペジル塩酸塩一水化物41.72g、マンニトル480g、ヒドロキシプロピルメチルセルロース20g、メマンチン80g、ヒドロキシプロピルセルロース20g、SD乳糖492g、Vivapur12 48gを20meshで濾過して混合した後、ステアリン酸マグネシウム16gを追加的に添加して混合した。その後、前記ドネペジルとメマンチンが混合された混合物をロータリー打錠機で圧縮して打錠した後、オパドライ40gコーティング基剤を用いてフィルムコーティングした。
試験例1.溶出試験
対照群1及び2と実施例1で製造された複合錠剤に対して下記の条件で溶出試験を実施した。
対照群1:対照群1(アリセプト10mg)単一溶出
対照群2:対照群2(エビキサ10mg×2錠)単一溶出
対照群1、2:対照群1(アリセプト10mg)及び対照群2(エビキサ10mg×2錠)を単純混合して同時複合溶出
実施例1:複合錠剤
実施例及び比較例で製造された複合錠剤を40及び75%相対湿度でアルミニウム(Alu−Alu)包装を適用して加速安全性試験を実施し、2週ごとに気体クロマトグラフィー法で時間による総不純物質含量(%)を分析した。
含量均一性測定は試験例1の溶出試験の分析法と同一であり、試験は大韓民国薬典一般試験法の製剤均一性試験法によって試験した。製剤均一性試験法は各製剤間の主成分含量の均一な程度を示すための試験法である。
判定値=M−平均含量+(2.4×標準偏差)
2)平均含量が98.5%未満のとき、M=98.5%
3)平均含量が101.5%を超えるとき、M=101.5%
図5aはSD乳糖の粒子サイズを示したグラフ、図5bは乳糖水化物の粒子サイズを示したグラフ、図5cは微結晶セルロースであるvivapur12の粒子サイズを示したグラフ、図5dは微結晶セルロースであるMCC102の粒子サイズを示したグラフである。
Claims (8)
- メマンチン又はその薬学的に許容可能な塩及び顆粒化したドネペジル又はその薬学的に許容可能な塩を含み、直接圧着された錠剤形態であることを特徴とする、認知症及び認知機能障害の予防又は治療用速放性医薬組成物であって、
前記顆粒化したドネペジル又はその薬学的に許容可能な塩は120μm〜200μmの粒子分布d(0.5)を有し、前記顆粒化したドネペジル又はその薬学的に許容可能な塩の粒子サイズは、20mesh以上50mesh未満が15〜25重量%、50mesh以上80mesh未満が25〜35重量%、80mesh以上200mesh未満が20〜30重量%、200mesh以上が15〜25重量%であり、
前記20mesh以上50mesh未満の粒子の含量が200mesh以上の粒子の含量より少ない、認知症及び認知機能障害の予防又は治療用速放性医薬組成物。 - 前記顆粒化したドネペジル又はその薬学的に許容可能な塩を1〜20重量%含有することを特徴とする、請求項1に記載の認知症及び認知機能障害の予防又は治療用速放性医薬組成物。
- 前記顆粒化したドネペジル又はその薬学的に許容可能な塩とメマンチン又はその薬学的に許容可能な塩とが、1:0.8〜5の重量比で混合されることを特徴とする、請求項1又は2に記載の認知症及び認知機能障害の予防又は治療用速放性医薬組成物。
- 前記顆粒化したドネペジル又はその薬学的に許容可能な塩は、20meshの粒子サイズが5〜15重量%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認知症及び認知機能障害の予防又は治療用速放性医薬組成物。
- 前記医薬組成物に賦形剤をさらに含むことを特徴とする、請求項1〜4のいずれか一項に記載の認知症及び認知機能障害の予防又は治療用速放性医薬組成物。
- 前記賦形剤は、乳糖及び微結晶セルロースが3〜20:1の重量比で混合されることを特徴とする、請求項5に記載の認知症及び認知機能障害の予防又は治療用速放性医薬組成物。
- 前記賦形剤は、80mesh以上の粒子を50重量%以上含有することを特徴とする、請求項1〜6のいずれか一項に記載の認知症及び認知機能障害の予防又は治療用速放性医薬組成物。
- ドネペジル又はその薬学的に許容可能な塩を湿式工程で顆粒化する段階と、
前記顆粒化したドネペジル又はその薬学的に許容可能な塩にメマンチン又はその薬学的に許容可能な塩を添加した混合物を直接圧着して均質化する段階とを含むことを特徴とする、認知症及び認知機能障害の予防又は治療用速放性医薬組成物の製造方法であって、
前記顆粒化したドネペジル又はその薬学的に許容可能な塩の粒子サイズは、20mesh以上50mesh未満が15〜25重量%、50mesh以上80mesh未満が25〜35重量%、80mesh以上200mesh未満が20〜30重量%、200mesh以上が15〜25重量%であり、
前記20mesh以上50mesh未満の粒子の含量が200mesh以上の粒子の含量より少ない、製造方法。
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CN103877046A (zh) | 2014-03-24 | 2014-06-25 | 张绪伟 | 一种盐酸多奈哌齐分散片及其制备方法 |
CN105326837A (zh) | 2015-10-09 | 2016-02-17 | 北京万全德众医药生物技术有限公司 | 一种盐酸美金刚缓释-多奈哌齐速释复方胶囊 |
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