JP2001512461A - 連続ミクロスフェア製法 - Google Patents
連続ミクロスフェア製法Info
- Publication number
- JP2001512461A JP2001512461A JP53596898A JP53596898A JP2001512461A JP 2001512461 A JP2001512461 A JP 2001512461A JP 53596898 A JP53596898 A JP 53596898A JP 53596898 A JP53596898 A JP 53596898A JP 2001512461 A JP2001512461 A JP 2001512461A
- Authority
- JP
- Japan
- Prior art keywords
- phase
- dispersed phase
- continuous
- emulsion
- dispersed
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960004824 triptorelin Drugs 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
-
- 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
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 次の工程を含む、ポリマー物質を含む活性剤の生産を要望される平均粒度及 び活性剤充填量を持つ第1の集団から、本質的に同じ平均粒度及び活性剤充填量 を持つ第2の集団に規模拡大する方法。 a) 連続相及び前記活性剤及びポリマーを含んだ分散相を反応容器への注入、 及び前記容器における前記連続相中での前記分散相のエマルジョンの形成のため の前記相の混合。 b) 前記反応容器から溶媒除去容器へのエマルジョンの連続的輸送、及びそこ における前記エマルジョンからの溶媒の除去。 c) 前記要望平均粒度及び活性剤充填量を持つ前記第1集団の獲得。;及び、 その後の d) ポリマー物質を含む活性剤の要望される第2のより大きな集団を生産する ための工程(a)及び(b)を連続的に実行するために適する持続時間の選択、 及び前記第2集団を獲得するために十分な持続時間での工程(a)及び(b)の 連続的実施。 2. 第1の集団の要望の平均粒度及び活性剤充填量が工程(a)及び(b)の実 施による獲得され、並びに要望の平均粒度及び活性剤充填量を獲得するための反 応容器への連続相の供給速度、反応容器への分散相の供給速度、及び連続及び分 散相の混合される強度から選択された少 なくとも1つのパラメーターを調節する請求項1の方法。 3. 第2集団を生産するために、分散相が反応容器に流速が約4ml/min〜約400m l/minで注入され、及び連続相が反応容器に流速が約1000ml/min〜約20,000ml/mi nで注入される請求項1の方法。 4. 第2集団を生産するために、連続相及び分散相が5:1〜500:1の比率で 反応器に注入される請求項1の方 法。 5. 第2集団を生産するために、連続相及び分散相が40:1〜200:1の比率で 反応器に注入される請求項1の方法。 6. 第2集団を生産するためにエマルジョンを形成する工程が約10秒以内にポリ マーの凝固を引き起こすように適応させた強さでの前記分散相及び連続相の強力 な混合を含む請求項1の方法。 7. 第2集団を生産するためのエマルジョンを形成する工程が約5秒以内にポリ マーの凝固を引き起こすように適応させた強さでの分散相及び連続相の強力な混 合を含む請求項1の方法。 8. 反応容器がインペラーを含み、及び第2集団を生産するためのエマルジョン を形成する工程が約10秒以内にポリマーの凝固を引き起こすように適応させた強 さでのインペラーの分散相及び連続相の強力な混合を含む請求項1の方法。 9. 約5秒以内に凝固が発生する請求項8の方法。 10. 反応器での分散相の滞留時間が約5秒以下である請求項8の方法。 11. インペラーを毎分約6,000〜10,000回転で運転することを含む請求項8の 方法。 12. 次の工程を含む、ポリマー物質を含む活性剤を生産する方法。 a) 活性剤及びポリマー物質を含む分散相の形成。 b) 将来エマルジョンを形成する前記分散相への連続相の供給。 c) 反応容器へ分散相供給速度での分散相の注入、及び前記反応容器への連 続相供給速度での連続相の注入、エマルジョン形成のための手段を含む前記反応 容器、並びに前記連続相での前記分散相のエマルジョンの形成。 d) 前記エマルジョンの前記反応容器から溶媒除去のための溶媒除去容器へ の連続的輸送。 13. 分散相が反応容器に流速が約4ml/min〜約400ml/minで供給され、及び連 続相が反応容器に流速が約1000ml/min〜約20,000ml/minで注入される請求項12の 方法。 14. 分散相が親水性ペプチド活性剤及びラクチドグリコリドのコポリマーを含 み、並びに分散及び連続相を平均粒度が約5μm〜約40μmに、及び少なくとも約 9%の活性剤充填量の供給に効果的な方法での分散及び供給相の乳 化を含む請求項12の方法。 15. 分散相が親水性ペプチド活性剤及びラグチドグリコリドのコポリマーを含 み、並びに分散及び連続相を平均粒度が約5μm〜約40μmに、及び少なくとも約 15%の活性剤充填量の供給に効果的な方法での分散及び供給相の乳化を含む請求 項12の方法。 16. 連続相及び分散相が5:1〜500:1の比率で反応器に注入される請求項1 2の方法。 17. 連続相及び分散相が40:1〜200:1の比率で反応器に注入される請求項1 2の方法。 18. エマルジョンを形成手段がインペラーを含む請求項12の方法。 19. エマルジョンを形成手段がインペラーを含み、混合がインペラーを毎分約 5,000回転以上で運転することにより混合が行われる請求項12の方法。 20. エマルジョンを形成手段インペラーを含み、インペラーがインペラーから 軸方向に延長した円柱帯の直径を定義する直径を持つ所であり、分散相が軸方向 の延長柱帯に注入される請求項12の方法。 21. エマルジョンを形成手段が約10秒以内に分散相ポリマーの凝固を引き起こ すのに効果的な混合体を形成し、及び分散相が混合帯の状態で反応容器に注入さ れる請求項12の方法。 22. 分散相が均質溶液である請求項12の方法。 23. 分散相がエマルジョンである請求項12の方法。 24. 反応器での分散相の平均滞留時間が約5秒未満である請求項12の方法。 25. 分散相ポリマーの凝固を約10秒以内に発生させるように適応したやり方の 分散及び連続相の乳化を含む請求項12の方法。 26. 分散相ポリマーの凝固を約5秒以内に発生させるように適応したやり方の 分散及び連続相の乳化を含む請求項12の方法。 27. エマルジョン形成の手段がインペラーを含み、及びエマルジョン形成の工 程がインペラーを毎分約6,000回転以上から約10,0000回転までで運転される請求 項12の方法。 28. 製造工程がミクロスフェアの要望の集団を形成するのに十分な期間実施さ れ、その工程の初期に生産されたミクロスフェアが工程の終期に生産されたミク ロスフェアと実質的に同一な粒度及び活性剤充填量を持つ請求項12の方法。 29. 請求項12の方法で作成されたミクロスフェア。 30. 請求項14の方法で作成されたミクロスフェア。 31. 請求項25の方法で作成されたミクロスフェア。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US08/800,924 | 1997-02-13 | ||
US08/800,924 US5945126A (en) | 1997-02-13 | 1997-02-13 | Continuous microsphere process |
PCT/US1998/002874 WO1998035654A1 (en) | 1997-02-13 | 1998-02-11 | Continuous microsphere process |
Publications (2)
Publication Number | Publication Date |
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JP2001512461A true JP2001512461A (ja) | 2001-08-21 |
JP4869458B2 JP4869458B2 (ja) | 2012-02-08 |
Family
ID=25179722
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP53596898A Expired - Fee Related JP4869458B2 (ja) | 1997-02-13 | 1998-02-11 | 連続ミクロスフェア製法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US5945126A (ja) |
EP (1) | EP0994695B1 (ja) |
JP (1) | JP4869458B2 (ja) |
CA (1) | CA2278744C (ja) |
ES (1) | ES2414679T3 (ja) |
WO (1) | WO1998035654A1 (ja) |
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Also Published As
Publication number | Publication date |
---|---|
EP0994695A1 (en) | 2000-04-26 |
EP0994695A4 (en) | 2006-02-01 |
EP0994695B1 (en) | 2013-04-03 |
US5945126A (en) | 1999-08-31 |
JP4869458B2 (ja) | 2012-02-08 |
CA2278744C (en) | 2006-03-28 |
CA2278744A1 (en) | 1998-08-20 |
WO1998035654A1 (en) | 1998-08-20 |
ES2414679T3 (es) | 2013-07-22 |
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