JP4933732B2 - 低温表面上で凍結させることによって得られる薬物粒子 - Google Patents
低温表面上で凍結させることによって得られる薬物粒子 Download PDFInfo
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- JP4933732B2 JP4933732B2 JP2004566896A JP2004566896A JP4933732B2 JP 4933732 B2 JP4933732 B2 JP 4933732B2 JP 2004566896 A JP2004566896 A JP 2004566896A JP 2004566896 A JP2004566896 A JP 2004566896A JP 4933732 B2 JP4933732 B2 JP 4933732B2
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- Prior art keywords
- solution
- organic solvent
- low temperature
- drug
- cold
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- Expired - Lifetime
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- 238000005507 spraying Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
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- 238000005092 sublimation method Methods 0.000 description 1
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
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Description
サイクロスポリンAは、POLI Industria Chimica S.P.A.から購入した医薬物質である。
粒度分析: 分析は、入手したままのバルク薬物粉末と例1〜60において製造した粉末について、水に再分散させた後に、Beckman Coulter Counterを用いて行った。
ナプロキセン、カルバマザピン及びケトプロフェンに関して、溶解媒体は、5.0重量%塩化ナトリウムを含む脱イオン水であった。
125mLの凍結乾燥ビンをドライアイス・アセトン浴中で−78℃まで冷却した。製造した溶液を、冷却した凍結乾燥ビン中にピペットでゆっくりと移した。次いで、凍結乾燥ビン中の凍結固体を、凍結乾燥ユニット上に置き、完全に乾燥するまで凍結乾燥させることによって、流動性の白色粉末0.9gを得た。処理の前後に測定した粒度分析結果及び溶解時間を表IIに示す。
図1に示した装置を用いた。シリンダー12をドライアイスで−78℃に冷却した。溶液をシリンダー12上に約10分間噴霧した。得られた凍結固体を、ナイフブレードアセンブリー14によって除去し、冷却した生成物捕集トレイ16中に回収した。回収した材料を、手で溶媒除去ユニットに移動した。本発明の方法の実施の前後において測定した粒度分析結果及び溶解時間を、表IIに示す。
図2に示した装置を用いた。ドライアイスを用いて、シリンダー12を−78℃に冷却した。添加用漏斗を用いて約10分間、この溶液をシリンダー12上に滴下した。得られた凍結固体を、ナイフブレードアセンブリー14を用いて除去し、冷却された生成物捕集トレイ16中に回収した。次いで、回収した生成物を手で溶媒除去工程に移動させた。本発明の方法の実施の前後において測定した粒度分析結果及び溶解時間を表IIに示す。
図2に示した装置を用いた。ドライアイスを用いて、シリンダー12を−78℃に冷却した。添加用漏斗を用いて約10分間、この溶液をシリンダー12上に滴下した。得られた凍結固体を、ナイフブレードアセンブリー14を用いて除去し、冷却した生成物捕集トレイ16中に回収した。回収した生成物を脱イオン水中に分散させた。次いで、分散された固体/水/溶媒スラリーを、溶媒除去工程に直接、取り入れた。本発明の方法の実施の前後において測定した粒度分析結果及び溶解時間を表IIに示す。
Claims (14)
- (a)水貧溶性の医薬物質及び少なくとも1種の凍結可能な有機溶媒を含む溶液を低温表面と接触させて、前記溶液を凍結させ;そして
(b)前記有機溶媒を除去する
ことを含んでなるミクロンサイズ又はサブミクロンサイズの薬物粒子の製造方法。 - 工程(a)の低温表面が凍結可能な有機溶媒の凍結点より低い温度である請求項1に記載の方法。
- 工程(a)の低温表面が少なくとも5℃より低い請求項1に記載の方法。
- 低温表面を冷却する工程を更に含む請求項1に記載の方法。
- 前記低温表面を、極低温固体、極低温気体、極低温液体又は極低温に達することができる熱伝導流体を用いて冷却する請求項4に記載の方法。
- 凍結可能な有機溶媒がアルコール、エーテル、ハロカーボン、炭化水素、ハロゲン化炭化水素、芳香族炭化水素、エステル、アセテート、有機酸、アミン、ケトン、スルホン、ニトリル、カーボネート及びそれらの組合せからなる群から選ばれる請求項1に記載の方法。
- 前記溶液が水を更に含む請求項1に記載の方法。
- 前記粒子を水中に分散させた後の粒子の体積平均の平均粒子サイズが0.05〜150ミクロンである請求項1に記載の方法。
- 得られる粒子が少なくとも2m2/gの表面積を有する請求項1に記載の方法。
- 得られる薬物粒子が未処理の薬物よりも少なくとも2倍速いインビトロ溶解速度を示す請求項1に記載の方法。
- 前記溶液が少なくとも1種の安定剤を更に含む請求項1に記載の方法。
- 前記安定剤がリン脂質、界面活性剤、ポリマー界面活性剤、ベシクル、コポリマー及びホモポリマー並びにバイオポリマーを含むポリマー、分散助剤並びにそれらの組合せからなる群から選ばれる請求項11に記載の方法。
- 工程(b)を昇華又は蒸発を用いて実施する請求項1に記載の方法。
- (a)第1面及び対向する第2面を有する低温固体表面;
(b)水貧溶性の医薬物質及び少なくとも1種の凍結可能な有機溶媒を含む溶液を低温固体表面の第1面に適用して前記溶液が凍結するように構成した、低温固体表面の第1面の近傍に配置された適用手段;
(c)低温固体表面を冷却するように構成した、低温固体表面の第2面の近傍に配置された冷却手段;
(d)低温表面の第1面から凍結溶液を除去するための、低温表面の近傍の除去手段;
(e)凍結溶液から少なくとも1種の有機溶媒を除去するための溶媒除去手段;並びに
(f)前記凍結溶液を(b)から(d)の溶媒除去手段に移動させる手段
を含んでなる薬物粒子製造用装置。
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US44053503P | 2003-01-15 | 2003-01-15 | |
US60/440,535 | 2003-01-15 | ||
PCT/US2003/025338 WO2004064808A1 (en) | 2003-01-15 | 2003-08-12 | Drug particles obtained by freezing onto a cold surface |
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JP2006514076A JP2006514076A (ja) | 2006-04-27 |
JP4933732B2 true JP4933732B2 (ja) | 2012-05-16 |
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JP2004566896A Expired - Lifetime JP4933732B2 (ja) | 2003-01-15 | 2003-08-12 | 低温表面上で凍結させることによって得られる薬物粒子 |
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US (2) | US9175906B2 (ja) |
EP (1) | EP1589948A1 (ja) |
JP (1) | JP4933732B2 (ja) |
KR (1) | KR20050096936A (ja) |
CN (1) | CN1731984A (ja) |
AU (1) | AU2003296893A1 (ja) |
CA (1) | CA2513006A1 (ja) |
WO (1) | WO2004064808A1 (ja) |
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WO2006026502A1 (en) | 2004-08-27 | 2006-03-09 | The Dow Chemical Company | Enhanced delivery of drug compositions to treat life threatening infections |
EP1798504A1 (en) * | 2005-12-19 | 2007-06-20 | Koninklijke Philips Electronics N.V. | Method of making dried particles |
CN101511170B (zh) * | 2005-12-22 | 2014-03-26 | 奥克伍德药业有限公司 | 可升华持续释放传递系统和其制造方法 |
ES2435197T3 (es) | 2007-01-10 | 2013-12-16 | Board Of Regents, The University Of Texas System | Administración mejorada de composiciones de fármacos inmunosupresores para la administración por vía pulmonar |
EP2142177A4 (en) * | 2007-04-13 | 2013-08-28 | Christopher Culligan | FREEZE DOSAGE RELIEF SYSTEM AND PREPARATION METHOD |
EP2170283B1 (en) | 2007-06-22 | 2019-01-09 | Board of Regents, The University of Texas System | Formation of stable submicron peptide or protein particles by thin film freezing |
DK2252275T3 (en) | 2008-02-13 | 2018-03-05 | Univ Texas | CREATED NON-OPEN FLOCKS OF ANISOTROPIC PARTICLES FOR IMPROVED TRANSPORT INTO THE Lungs |
CN101618019B (zh) * | 2008-07-01 | 2011-08-03 | 上海通用药业股份有限公司 | 一种醋酸曲安奈德微粒及其制备方法和药物组合物 |
TWI580441B (zh) * | 2008-09-19 | 2017-05-01 | 愛爾康研究有限公司 | 穩定的藥學次微米懸浮液及其形成方法 |
CN102348948B (zh) * | 2009-03-11 | 2014-12-10 | 鲍利葛股份公司 | 干燥微纤维化纤维素的方法 |
EP3366280A1 (en) | 2010-03-12 | 2018-08-29 | Berg LLC | Intravenous formulations of coenzyme q10 (coq10) and methods of use thereof |
US10973763B2 (en) | 2011-06-17 | 2021-04-13 | Berg Llc | Inhalable pharmaceutical compositions |
EP2601973A1 (en) | 2011-12-09 | 2013-06-12 | Laboratoires SMB SA | Dry powder formulation of azole derivative for inhalation |
WO2014186754A2 (en) | 2013-05-16 | 2014-11-20 | Board Of Regents The University Of Texas System | Dry solid aluminum adjuvant-containing vaccines and related methods thereof |
PE20181295A1 (es) | 2015-09-01 | 2018-08-07 | First Wave Bio Inc | Metodos y composiciones para tratar afecciones asociadas a una respuesta inflamatoria anomala |
CA3083953A1 (en) | 2017-12-11 | 2019-06-20 | Board Of Regents, The University Of Texas System | Dry adjuvanted immune stimulating compositions and use thereof for mucosal administration |
CN110607552B (zh) * | 2018-10-30 | 2024-02-20 | 中国科学院化学研究所 | 一种利用水溶液制备单晶或无定型物的方法 |
CN110607553B (zh) * | 2018-10-30 | 2024-03-22 | 中国科学院化学研究所 | 一种制备粒径可调的药物或药物中间体单晶或无定型物的方法 |
US10980756B1 (en) | 2020-03-16 | 2021-04-20 | First Wave Bio, Inc. | Methods of treatment |
TW202200121A (zh) | 2020-03-16 | 2022-01-01 | 美商費斯特威弗生技股份有限公司 | 治療方法 |
CN111735281B (zh) * | 2020-06-05 | 2022-04-08 | 浙江科恩实验设备有限公司 | 一种快干式滴水架 |
CN112539606A (zh) * | 2020-12-01 | 2021-03-23 | 镇江波菲尔生物科技有限公司 | 一种生物医药用具有防静电功能的实验室冻干机 |
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- 2003-08-12 JP JP2004566896A patent/JP4933732B2/ja not_active Expired - Lifetime
- 2003-08-12 CN CNA038258234A patent/CN1731984A/zh active Pending
- 2003-08-12 EP EP03815476A patent/EP1589948A1/en not_active Withdrawn
- 2003-08-12 WO PCT/US2003/025338 patent/WO2004064808A1/en active Application Filing
- 2003-08-12 KR KR1020057013059A patent/KR20050096936A/ko not_active Application Discontinuation
- 2003-08-12 US US10/639,361 patent/US9175906B2/en active Active
- 2003-08-12 AU AU2003296893A patent/AU2003296893A1/en not_active Abandoned
- 2003-08-12 CA CA002513006A patent/CA2513006A1/en not_active Abandoned
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US3309777A (en) * | 1963-08-30 | 1967-03-21 | Robert S Hutton | Process for making uniformly constituted finely divided particulate material |
US5780295A (en) * | 1990-09-12 | 1998-07-14 | Life Cell Corporation | Apparatus for cryopreparation, dry stabilization and rehydration of biological suspensions |
WO2002060411A2 (en) * | 2001-01-30 | 2002-08-08 | Board Of Regents University Of Texas System | Process for production of nanoparticles and microparticles by spray freezing into liquid |
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CN1731984A (zh) | 2006-02-08 |
US20160074328A1 (en) | 2016-03-17 |
WO2004064808A1 (en) | 2004-08-05 |
CA2513006A1 (en) | 2004-08-05 |
KR20050096936A (ko) | 2005-10-06 |
US20040137070A1 (en) | 2004-07-15 |
JP2006514076A (ja) | 2006-04-27 |
AU2003296893A1 (en) | 2004-08-13 |
US9175906B2 (en) | 2015-11-03 |
EP1589948A1 (en) | 2005-11-02 |
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