JP4830019B2 - ナノスケールの活物質粒子の製造方法 - Google Patents
ナノスケールの活物質粒子の製造方法 Download PDFInfo
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Medicinal Preparation (AREA)
Description
固相溶媒としてミリスチルアルコール30gを250mL容量のビーカーに投入し、ゆっくり加熱して温度が100℃に達したとき、界面活性剤としてポリビニルピロリドン(K 30)1g及び活物質としてパクリタキセル(Paclitaxel)1gを入れ、生成された混合物を完全に溶かした後、室温でゆっくり冷却して固形物を得た。
実施例1で得られた固形粉末10gを耐圧反応器に投入した後、耐圧反応器の温度を25〜32℃に保持しながら二酸化炭素を投入し、圧力を約100気圧で加圧し、上記温度及びこの圧力条件を保持しながら、二酸化炭素を10時間加えて、ミリスチルアルコールを除去した。その結果、パクリタキセルとポリビニルピロリドンとの混合粉末を0.62g得た。
固相溶媒としてセチルアルコール21gを250mL容量のビーカーに投入し、ゆっくり加熱し、温度が100℃に達したとき、界面活性剤としてポリビニルピロリドン(K 30)0.56g及び活物質としてイトラコナゾール(Itraconazole)0.7gを入れ、完全に溶かした後、70℃に冷却し、そこにヒドロキシプロピルメチルセルロース400mgを、エタノール80%と水20%との混合溶媒に溶かして製造した溶液3.85mLを添加し、5分間、十分に撹拌した後、室温でゆっくり固めた。この固形物を室温で24時間減圧乾燥した。
1,6−ヘキサンジオール3gを容器に入れ、ゆっくり加熱し、温度が100℃に達したとき、界面活性剤としてヒドロキシプロピルメチルセルロース50mgを投入し、撹拌して完全に溶かした。ヒドロキシプロピルメチルセルロースが完全に溶けた後、80℃に冷却し、活物質としてイトラコナゾール100mgを添加し、完全に溶けるまで撹拌した。イトラコナゾールが完全に溶けて透明な液体になった後、ラクトース水溶液(1g/3mL)0.4gをゆっくり滴下し、5分間、十分に撹拌した後、これをステンレス鋼板に注ぎ、室温で固めて、減圧下で乾燥することによって、活物質が固相ジオールに微細粒子に均一に分布した固形物を製造した。
1,6−ヘキサンジオール3gを容器に入れ、ゆっくり加熱して温度が100℃に達したとき、界面活性剤としてポリビニルピロリドン(K 30)100mgを投入し、撹拌して完全に溶かした。ポリビニルピロリドンが完全に溶けた後、80℃に冷却し、活物質としてイトラコナゾール100mgを添加し、完全に溶ける時まで撹拌した。イトラコナゾールが完全に溶けて透明な液体になった後、ラクトース水溶液(1g/3mL)0.4gをゆっくり滴下し、5分間、十分に撹拌した後、これをステンレス鋼板に注ぎ、室温で固めて、減圧下で乾燥することによって、活物質が固相ジオールに微細粒子に均一に分布した固形物を製造した。
界面活性剤としてオイドラギットL−100(登録商標)100mgを使用することを除いては、実施例4と同様にして粉末を製造し、イトラコナゾールとオイドラギットL−100との混合粉末0.1gを得た。
界面活性剤としてオイドラギットS−100(登録商標)100mgを使用したことを除いては、実施例4と同様にして粉末を製造し、イトラコナゾールとオイドラギットS−100との混合粉末0.1gを得た。
Claims (14)
- (1)1つ以上の活物質と固相溶媒とを含む固相混合物を製造する工程;
(2)10〜20℃の温度で、上記混合物が入っている反応器内に、超臨界流体ガスを入れ、1つ以上の活物質と固相溶媒とを含む上記混合物を40〜90気圧の圧力で加圧する工程;及び
(3)上記反応器内を、10〜20℃の温度及び40〜90気圧の圧力を保持しながら、上記固相溶媒を超臨界流体ガスと共に上記反応器の外側に排出させて、上記固相溶媒を上記混合物から除去する工程;
を含むことを特徴とするナノスケールの活物質粒子の製造方法。 - 上記活物質は、生理活性を表す有機化合物、有機金属化合物、天然抽出物、ペプチド、タンパク質及び多糖類よりなる群から選択された一つ以上であることを特徴とする請求項1に記載の方法。
- 上記固相溶媒は、炭素数10〜22の飽和脂肪酸化合物、そのエステル化合物及びそのアルコール化合物;炭素数10〜22の飽和脂肪酸基を有するモノ−またはジ−グリセリド化合物;炭素数16以上の炭化水素化合物;炭素数10〜22のトリグリセリド化合物の脂肪酸還元化合物;炭素数6〜22の直鎖状または分枝状ジオール化合物;及びこれらの混合物よりなる群から選択された一つ以上であることを特徴とする請求項1に記載の方法。
- 上記固相溶媒は、ジオール化合物であることを特徴とする請求項1に記載の方法。
- 上記固相溶媒は、ジオール化合物とジオール以外の化合物との混合物であることを特徴とする請求項1に記載の方法。
- 上記工程(1)の1つ以上の活物質と固相溶媒とを含む固相混合物は、1つ以上の界面活性剤をさらに含むことを特徴とする請求項1に記載の方法。
- 上記界面活性剤は、合成界面活性剤、天然界面活性剤、脂質及び高分子よりなる群から選択された一つ以上であることを特徴とする請求項6に記載の方法。
- 上記工程(1)の1つ以上の活物質と固相溶媒とを含む固相混合物は、1つ以上の非界面活性剤型の凝集防止剤をさらに含むことを特徴とする請求項1に記載の方法。
- 上記非界面活性剤型の凝集防止剤は、単糖類、多糖類、食物繊維、ガム類及びタンパク質よりなる群から選択された一つ以上であることを特徴とする請求項8に記載の方法。
- 共溶媒が上記工程(1)でさらに使用されることを特徴とする請求項1に記載の方法。
- 上記共溶媒は、アルコール、水及びこれらの混合物よりなる群から選択された一つ以上であることを特徴とする請求項10に記載の方法。
- 上記共溶媒としてのアルコールは、炭素数2〜6の1つ以上のアルコールであることを特徴とする請求項11に記載の方法。
- 共溶媒としてのアルコールと水との混合物は、アルコール70〜80重量%と水20〜30重量%との1つ以上の混合溶液であることを特徴とする請求項11に記載の方法。
- 上記工程(3)で、反応器内の圧力は50〜80気圧であることを特徴とする請求項1〜13のいずれかに記載の方法。
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KR1020060040416A KR101342121B1 (ko) | 2006-05-04 | 2006-05-04 | 저온 및 저압 하에서 초임계유체를 이용한 나노수준의활성물질 입자 제조방법 |
KR1020060040317A KR101342119B1 (ko) | 2006-05-04 | 2006-05-04 | 디올 화합물을 이용한 나노수준의 활성물질 입자 제조 방법 |
PCT/KR2007/002172 WO2007129829A1 (en) | 2006-05-04 | 2007-05-03 | Method for preparing nano-scale particle of active material |
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CA2794960C (en) * | 2010-04-01 | 2016-10-18 | The Governors Of The University Of Alberta | Supercritical fluid treatment of high molecular weight biopolymers |
KR101794032B1 (ko) | 2011-09-21 | 2017-11-07 | (주)바이오시네틱스 | 나노입자 제조방법 |
TWI697337B (zh) * | 2013-08-07 | 2020-07-01 | 學校法人近畿大學 | 奈米粒子或奈米粒子組成物之製造方法,及支架或球囊導管之製造方法 |
EP2924022A1 (en) * | 2014-03-27 | 2015-09-30 | INDENA S.p.A. | Amorphous form of a thiocolchicine derivative |
CN105361183A (zh) * | 2015-11-06 | 2016-03-02 | 孟令刚 | 一种玛咖粒子粉的制备工艺 |
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JP2005502445A (ja) * | 2001-03-30 | 2005-01-27 | ピコリター インコーポレイテッド | 固体粒子の生成における集中音響エネルギー |
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JP2005502445A (ja) * | 2001-03-30 | 2005-01-27 | ピコリター インコーポレイテッド | 固体粒子の生成における集中音響エネルギー |
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CA2651346C (en) | 2015-02-17 |
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US20090202646A1 (en) | 2009-08-13 |
EP2013138A1 (en) | 2009-01-14 |
ES2458142T3 (es) | 2014-04-30 |
CN104958260A (zh) | 2015-10-07 |
JP2009535399A (ja) | 2009-10-01 |
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CA2651346A1 (en) | 2007-11-15 |
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