JP2011032277A - 徐放性組成物およびその製造方法 - Google Patents
徐放性組成物およびその製造方法 Download PDFInfo
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Abstract
【解決手段】本発明の徐放性組成物は、ポリマー、生物活性剤および放出速度決定剤を含み、放出速度決定剤が徐放性組成物中に分散されており、生物活性剤の放出速度を制御する。本発明の方法は、生物活性剤、ポリマーおよび放出速度決定剤を含む油相を提供すること;界面活性剤を含む水相を提供すること;油相を水相と混合し、制御放出効果を有する徐放性組成物を形成することを含む。
【選択図】なし
Description
80mgのオランザピン、200mgのPLGA(LA/GA比=50/50、M.W.=43000)および異なる量のビタミンE−TPGS(0、7、26、42重量%)を5mLのジクロロメタンに共溶解し、油相を形成した。油相を、0.1%ポリビニルアルコール(PVA)を含有する1000mLの冷却水相中に滴下し、1000rpmで乳化した。得られたo/w型エマルジョンを連続的に3時間、室温で攪拌した。ミクロスフィアを遠心分離によって回収し、F68、水で洗浄し、凍結乾燥した。次いで、ミクロスフィアを粒径および薬物カプセル封入効率について、マルチサイザーおよび高速液体クロマトグラフィー(HPLC)によって評価した。その結果、粒径は、68.4±28.3、71.6±27.3、91.0±35.8、101.9±42.8μmであり、カプセル封入効率は、0、7、26、42%(w/w)のビタミンE−TPGSを含有するミクロスフィアで、それぞれ77.7、83.5、85.9、85.2%であることが示された。
320mgのオランザピン、800mgのPLGA(LA/GA比=85/15、M.W.=53000)および異なる量のビタミンE−TPGS(0、4、15、26重量%)を15mLのジクロロメタンに共溶解し、油相を形成した。油相を、0.1%ポリビニルアルコール(PVA)を含有する2000mLの冷却水相中に滴下し、1000rpmで乳化した。攪拌、回収および解析の方法は、先に実施例1で規定したとおりである。その結果、粒径は、40.0±21.3、58.8±28.4、47.4±21.4、62.9±25.9μmであり、カプセル封入効率は、0、4、15、26%(w/w)のビタミンE−TPGSを含有するミクロスフィアで、それぞれ、77.2、74.7、87.6、83.7%であることが示された。
80mgのオランザピン、200mgのPLGA(LA/GA比=50/50、M.W.=43000)および42%(w/w)のビタミンE−TPGSを5mLのジクロロメタンに共溶解し、油相を形成した。油相を1000mLの冷却水相中に滴下し、次いで、1000rpmで乳化した。このとき、冷却水相は、0.05%PVAまたは0.5%ゼラチン含有0.05%PVAを含むものとした。得られたo/w型エマルジョンを連続的に3時間、室温で攪拌した。ミクロスフィアを遠心分離によって回収し、F68、水で洗浄し、凍結乾燥した。粒径および薬物カプセル封入効率の解析方法は、先に上記で規定したとおりである。その結果、粒径は、108.7±37.3、85.5±31.4μmであり、カプセル封入効率は、ゼラチンなしの0.05%PVA含有および0.5%ゼラチン含有0.05%PVA含有ミクロスフィアで、それぞれ、74.1、73.1%であることが示された。
320mgのオランザピン、800mgのPLGA(LA/GA比=85/15、M.W.=43000)および15w/w%のビタミンE−TPGSを15mLのジクロロメタンに共溶解し、油相を形成した。この実施例では、ジクロロメタンに、それぞれ、純粋なジクロロメタン(製剤番号1)、エタノール含有ジクロロメタン(DCM:エタノール=2:1、製剤番号2)、およびアセトン含有ジクロロメタン(DCM:アセトン=2:1、製剤番号3)を含めた。油相を、0.1%PVAを含有する2000mLの冷却水相中に滴下し、1000rpmで乳化した。攪拌、回収および解析の方法は、先に実施例1で規定のとおりである。その結果、粒径は、76.2±31.4、70.6±31.8、70.6±31.8μmであり、カプセル封入効率は、製剤番号1、2、3のミクロスフィアで86.8、89.7、88.5%であることが示された。
320mgのオランザピン、800mgのPLGAおよび15%(w/w)のビタミンE−TPGSを15mLのジクロロメタンに共溶解し、油相を形成した。このとき、PLGAは、それぞれ、85/15:50/50=3:1(製剤番号1)、85/15:50/50=1:3(製剤番号2)および75/20:50/50=4:1(製剤番号3)を含む、異なるLA/GA比を有した。油相を、0.1%PVAを含有する2000mLの冷却水相中に滴下し、1000rpmで乳化した。攪拌、回収および解析の方法は、先に実施例1で規定のとおりである。その結果、粒径は、62.2±32.0、59.1±24.9、41.1±19.1μmであり、カプセル封入効率は、製剤番号1、2、3のミクロスフィアで84.9、84.2、83.2%であることが示された。
320mgのオランザピン、800mgのPLGA(LA/GA比=75/25)および4%(w/w)のビタミンE−TPGSを15mLのジクロロメタンに共溶解し、油相を形成した。この実施例では、PLGAの分子量は、それぞれ、30000Da.および21000Da.であった。油相を、0.1%PVAを含有する2000mLの冷却水相中に滴下し、1000rpmで乳化した。攪拌、回収および解析の方法は、先に実施例1で規定のとおりである。その結果、粒径は、43.5±18.8、37.4±20.2μmであり、カプセル封入効率は、30000、21000Da.のPLGAで構成されたミクロスフィアで、それぞれ、80.8、77.6%であることが示された。
320mgのオランザピン、800mgのPLGA(LA/GA比=85/15)および4%(w/w)のビタミンE−TPGSを15mLのジクロロメタンに共溶解し、油相を形成した。この実施例では、PLGAの分子量は、それぞれ53000および27000Da.を含んだ。攪拌、回収および解析の方法は、先に実施例1で規定のとおりである。その結果、粒径は、58.8±28.4、43.9±20.6μmであり、カプセル封入効率は、53000、27000Da.のPLGAで構成されたミクロスフィアで、それぞれ、74.7、77.0%であることが示された。
320mgのオランザピン、800mgのPLGA(LA/GA比=85/15、M.W.=53000)および異なる放出速度決定剤(Span(登録商標)80、Span(登録商標)85、オレイン酸、PEG−PCLジ−ブロックコポリマー、グリセリルトリカプリレート、Pluronic(登録商標)、Tween(登録商標)80)を15mLのジクロロメタンに共溶解し、油相を形成した。油相を、0.1%ポリビニルアルコール(PVA)を含有する2000mLの冷却水相中に滴下し、1000rpmで乳化した。攪拌、回収および解析の方法は、先に実施例1で規定のとおりである。その結果、粒径は、46.7±18.6、40.3±15.5、46.3±22.6、55.7±27.3、49.5±22.0、68.1±30.9、30.1±14.9μmであり、カプセル封入効率は、異なる放出速度決定剤で構成されたミクロスフィアで、それぞれ、86.9、78.2、79.4、87.2、69.5、85.2、75.5%であることが示された。
脚の筋肉の大きさが、用量投与および注射部位の評価を容易にするため、Sprague−Dawleyラットをデポー製剤の評価に選択した。
Claims (13)
- ポリマー、生物活性剤および放出速度決定剤を含み、該生物活性剤および該放出速度決定剤が該徐放性組成物中に分散されており、該放出速度決定剤により該生物活性剤の放出速度が制御され、
放出速度決定剤がd−α−トコフェリルポリエチレングリコールスクシネート(ビタミンE−TPGS)であり、
放出速度決定剤が、1〜50重量%の最終濃度を有し、
前記ポリマー、生物活性剤および放出速度決定剤を含有する油相と、乳化剤を含む水相とを混合する乳化工程により作製される遅延期のない徐放性組成物。 - 生物活性剤が、タンパク質、核酸、糖質、ペプチド、免疫原またはホルモンを含む請求項1記載の徐放性組成物。
- 生物活性剤が、小分子医薬物質、抗腫瘍剤、抗ヒスタミン薬、抗精神病薬、抗潰瘍剤、抗癌剤、心血管系の薬剤、気管支拡張薬、血管拡張薬、中枢神経系の薬剤または麻薬拮抗薬を含む請求項1記載の徐放性組成物。
- ポリマーが、生分解性ポリマーである請求項1記載の徐放性組成物。
- ポリマーが、リン脂質、レシチン、ポリグリコレート、ポリ(ラクチド)、ポリ(グリコリド)、ポリラクチド−コ−グリコリド(PLGA)、ポリグルタミン酸、ポリカプロラクトン(PCL)、ポリアミノ酸、ポリジオキサノン、ポリヒドロキシブチレート、ポリホスファゼン、ポリエステルウレタン、ポリカルボキシフェノキシプロパン−コ−セバシン酸、ポリオルトエステル、ポリカーボネート、ポリエステルアミド、ポリ無水物、ポリアセチル、ポリシアノアクリレート、ポリエーテルエステル、ポリ(アルキレンアルキレート)またはそのコポリマーを含む請求項1記載の徐放性組成物。
- 徐放性組成物が、連続的に生物活性剤を放出する請求項1記載の徐放性組成物。
- 徐放性組成物が、70%を超えるカプセル封入率の生物活性剤を有する請求項1記載の徐放性組成物。
- 徐放性組成物が、ミクロスフィア、微粒子またはマイクロカプセルである請求項1記載の徐放性組成物。
- 徐放性組成物が、5μmを超える直径を有する請求項1記載の徐放性組成物。
- 徐放性組成物が、筋肉内または皮下注射に使用される請求項1記載の徐放性組成物。
- 医薬有効量の徐放性組成物を投与することを含む、動物を処置する方法における使用のための請求項1記載の徐放性組成物。
- 動物が哺乳動物である請求項11記載の徐放性組成物。
- 動物がヒトである請求項11記載の徐放性組成物。
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JP2007500229A (ja) * | 2003-05-20 | 2007-01-11 | ジョンズ・ホプキンズ・ユニバーシティ | 腫瘍の治療のためのカテコールブタンの投与のための方法と組成物 |
JP2007524645A (ja) * | 2003-07-15 | 2007-08-30 | ピーアール ファーマシューティカルズ, インコーポレイテッド | 制御放出処方物の調製のための方法 |
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JP2007500229A (ja) * | 2003-05-20 | 2007-01-11 | ジョンズ・ホプキンズ・ユニバーシティ | 腫瘍の治療のためのカテコールブタンの投与のための方法と組成物 |
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