JP2017536407A - 抗癌性組成物 - Google Patents
抗癌性組成物 Download PDFInfo
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- JP2017536407A JP2017536407A JP2017529774A JP2017529774A JP2017536407A JP 2017536407 A JP2017536407 A JP 2017536407A JP 2017529774 A JP2017529774 A JP 2017529774A JP 2017529774 A JP2017529774 A JP 2017529774A JP 2017536407 A JP2017536407 A JP 2017536407A
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- hpmcas
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- solid dispersion
- eudragit
- poly
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- 229960000604 valproic acid Drugs 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
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Abstract
Description
a)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LG、
b)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LF、
c)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LG、又は
d)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LF、を含む固体分散体である。
a)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LG、
b)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LF、
c)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LG、又は
d)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LF、からなる固体分散体である。
a)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
b)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
c)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、又は
d)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、を含む固体分散体からなる粒子である。
a)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
b)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
c)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、又は
d)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、からなる固体分散体からなる粒子である。
a)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
b)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
c)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、又は
d)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、を含む固体分散体を含む粒子である。
a)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
b)ARN−509、Eudragit(登録商標)E 100、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)E 100及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)E 100:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、
c)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LG;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LG)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LGの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、又は
d)ARN−509、Eudragit(登録商標)L 100−55、及びHPMCAS LF;特に、ARN−509:(Eudragit(登録商標)L 100−55及びHPMCAS LF)の重量比は1:2又は1:3である、より特に、Eudragit(登録商標)L 100−55:HPMCAS LFの重量比は、25:75〜75:25の範囲である、又は25:75、50:50、若しくは75:25である(50:50が好ましい)、からなる固体分散体を含む粒子である。
a)ARN−509、ポリ(メタ)アクリレート共重合体、及びHPMCASを混合する工程と、
b)任意選択的に、こうして得られた混合物と添加剤とをブレンドする工程と、
c)こうして得られたブレンド物を均一な溶融物が得られるまで加熱する工程と、
d)こうして得られた溶融物を1つ以上のノズルを介して押し出す工程と、
e)溶融物をそれが固化するまで冷却する工程と、を含む。
異なる(結晶)形態のARN−509を調製するために、参照により本明細書に組み込まれる国際公開第2013/184681号を参照する。異なる(結晶又は非晶質)形態のARN−509を使用して、本発明による固体分散体、粒子、又は製剤を調製することができる。
ARN−509の形態Bの特性評価
粉末XRD
PANalytical(Philips)X’PertPRO MPD回折計上でX線粉末回折(XRPD)分析を行なった。機器にはCu LFF X線管が備えられている。
好適なマイクロATRアクセサリを使用して試料を分析した。
化合物を、標準的なアルミニウムのTA−Instrumentの試料皿中に移した。試料皿を適した覆いで密閉し、RCS冷却装置が備えられたTA−Instruments Q1000 MTDSC上でDSC曲線を記録した。以下のパラメータを用いた:
ARN−509:Eudragit(登録商標)L 100−55:HPMCAS LGのSDP:1:0.75:2.25(ジクロロメタン/メタノール40/60中の混合物から噴霧乾燥)
ARN−509:Eudragit(登録商標)L 100−55:HPMCAS LG:1:2.25:0.75のSDP(ジクロロメタン/メタノール50/50中の混合物から噴霧乾燥)
溶解方法
錠剤を300mLのペプシン不含模擬胃液(Simulated Gastric Fluid sine pepsin)の中に15分間入れ、パドルの回転速度を100rpm(1分当たりの回転数)とし、その後900mLの絶食時模擬腸液(Fasted State Simulated Intestinal fluid)の中に入れ、パドルの回転速度を100rpmとした。ARN−509の溶解%を、UHPLC紫外線(UV)検出を用いて242nmにて測定した。
Claims (24)
- ARN−509、ポリ(メタ)アクリレート共重合体、及びHPMCASを含む固体分散体。
- 前記分散体がARN−509、ポリ(メタ)アクリレート共重合体、及びHPMCASからなる、請求項1に記載の固体分散体。
- 前記固体分散体中のARN−509:(ポリ(メタ)アクリレート共重合体及びHPMCAS)の重量比が、1:1〜1:5の範囲内である、請求項1又は2に記載の固体分散体。
- 前記固体分散体中のARN−509:(ポリ(メタ)アクリレート共重合体及びHPMCAS)の重量比が1:3である、請求項3に記載の固体分散体。
- 前記固体分散体中のポリ(メタ)アクリレート共重合体とHPMCASとの重量比が、5:95〜95:5の範囲である、請求項1〜4のいずれか一項に記載の固体分散体。
- 前記固体分散体中のポリ(メタ)アクリレート共重合体とHPMCASとの重量比が、25:75〜75:25の範囲である、請求項5に記載の固体分散体。
- 前記固体分散体中のポリ(メタ)アクリレート共重合体とHPMCASとの重量比が、50:50である、請求項6に記載の固体分散体。
- ARN−509が非晶質形態で存在する、請求項1〜7のいずれか一項に記載の固体分散体。
- 前記分散体が固溶体である、請求項1〜8のいずれか一項に記載の固体分散体。
- 前記ポリ(メタ)アクリレート共重合体がEudragit(登録商標)L 100−55である、請求項1〜9のいずれか一項に記載の固体分散体。
- 前記HPMCASがHPMCAS LGである、請求項1〜10のいずれか一項に記載の固体分散体。
- 噴霧乾燥によって得る、請求項1〜11のいずれか一項に記載の固体分散体。
- 高温溶融押出によって得る、請求項1〜11のいずれか一項に記載の固体分散体。
- 請求項1〜13のいずれか一項で定義されている固体分散体からなる粒子。
- 請求項1〜13のいずれか一項で定義されている固体分散体を含む粒子。
- 製薬的に許容される担体と、請求項1〜13のいずれか一項に記載の固体分散体と、を含む、医薬製剤。
- 製薬的に許容される担体と、請求項14又は15に記載の粒子と、を含む、医薬製剤。
- 前記製剤が錠剤である、請求項16又は17に記載の製剤。
- 経口投与に適している、請求項18に記載の製剤。
- ARN−509、ポリ(メタ)アクリレート共重合体、及びHPMCASを好適な溶媒中で混合する工程と、前記混合物を噴霧乾燥させる工程と、を含む、請求項12に記載の固体分散体を調製するためのプロセス。
- 前記適切な溶媒が、ジクロロメタンとメタノールの混合物である、請求項20に記載のプロセス。
- 前記混合物中のジクロロメタンとメタノールとの重量比が50:50である、請求項21に記載のプロセス。
- 前立腺癌の治療のための薬剤を調製するための、請求項16〜19のいずれか一項に記載の医薬製剤の使用。
- 前記薬剤が経口投与用である、請求項23に記載の使用。
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