JP5314489B2 - 安定化されたガス−過飽和エマルジョン及び懸濁液 - Google Patents
安定化されたガス−過飽和エマルジョン及び懸濁液 Download PDFInfo
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- JP5314489B2 JP5314489B2 JP2009112785A JP2009112785A JP5314489B2 JP 5314489 B2 JP5314489 B2 JP 5314489B2 JP 2009112785 A JP2009112785 A JP 2009112785A JP 2009112785 A JP2009112785 A JP 2009112785A JP 5314489 B2 JP5314489 B2 JP 5314489B2
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- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
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- 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
- A61K9/10—Dispersions; Emulsions
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- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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Description
様々な用途が、出口部分又はその近辺でのキャビテーション初生を含む事のない方法で、高圧貯蔵所から周囲圧力環境へのガス−過飽和液体の放出から利益を受ける。
流出液での泡の欠如は、更に、ガス欠乏部位への障害のない放出を可能とする。ガス−過飽和エマルジョンが、空中に放出される時、出口部分又はその近辺でのキャビテーション初生の欠如が、流出液をして、ガスで過飽和とされていない様な挙動を許す。即ち、放出された流れは、ガス核の急速な成長により、出口部分付近で拡散噴霧に分解することなく、そのままで残る。
又、ゼラチンは、有効な担体を造る。例えば、5〜10重量%ゼラチンは、グルタルアルデヒド中で架橋されて水不溶性とされ、10×105Pa〜20×105Pa(10〜20bar)で酸素に暴露され、次いで、約一時間高静水圧、例えば、50〜1000MPa(0.5〜10kbar)で圧縮される。1×105Pa(1bar)の静水圧に放出しても、泡はゼラチン中に形成されず、>2000mmHgの表面pO2が、少なくとも20〜30分間維持された事が認められた。
この担体とは反対に、この担体中に懸濁される液体小滴又は固体粒子は、高いガス溶解度を持たなければならない。例えば、ペルフルオロ化学物質(PFC)の小滴は、ホットなゼラチン溶液をPFC小滴濃縮物に添加し、極僅か混合し、固化させる為に冷却する事によってゼラチン内に懸濁出来る。十分に高い酸素圧で、PFC小滴は、高濃度の酸素を吸収し、それらの小さな寸法の故に、1×105Pa(1bar)で安定性を維持する。同様に、ゼラチンは、粒子からの、及びゼラチンを通しての酸素欠乏部位への酸素のゆっくりとした拡散速度を用意する。この懸濁液が適用できる様な環境の一つに、生物学的組織がある。
又、任意の粒子又は小滴が、粒子又は小滴から担体への拡散速度を更に調節する半浸透性表面膜でマイクロ又はナノカプセル化できる。カプセル化は、周知の方法、例えば、コアセルベーション又は蒸着によって達成する事ができる。
PFC/グリセリン懸濁液(200ml)を、容量300mlのパー反応容器(Parr reactor vessel)に入れ、懸濁液を、羽根攪拌機で急速な混合の間に(約1600rpmで)、35〜105kg/cm2(500〜1500psi)の分圧の酸素に暴露した。高酸素分圧は、グリセリンを通過する酸素の拡散速度が遅い為に、何時間にもわたって懸濁液中に酸素を送り込む為に必要であった。
Claims (13)
- 酸素で過飽和されたエマルジョン又は懸濁液の調製方法であって、
前記エマルジョン又は懸濁液は担体相材料に懸濁された内相材料を含み、
内相は第1ガス溶解度を有し、前記内相材料はペルフルオロ化学物質であり、
担体相は第2ガス溶解度及び拡散速度を有し、前記担体相材料はグリセリン又は架橋された5〜10重量%ゼラチンを含む液体であり、
第1ガス溶解度、第2ガス溶解度及び拡散速度の組み合わせが、ガスをガス消耗環境へキャビテーション初生無しに送達する結果となるように、第1ガス溶解度は第2ガス溶解度よりも高く、
前記内相材料及び前記担体材料を提供する工程、
前記エマルジョン又は懸濁液を調製する工程及び
前記エマルジョン又は懸濁液を2×105Pa(2bar)より高い圧力の酸素に暴露することで酸素で過飽和する工程を含む、前記方法。 - 前記エマルジョン又は懸濁液が、5×105Pa〜20×105Pa(5bar〜20bar)の圧力の酸素に暴露することにより酸素で過飽和される、請求項1に記載の方法。
- 前記内相材料が、液体、粒子又はそれらの組み合わせから選択される、請求項1又は2に記載の方法。
- 前記内相材料が、0.1ミクロン〜10ミクロンの直径を有する微細小滴の形態である、請求項3に記載の方法。
- 担体相材料がグリセリンであり、内相が担体相に粒子の形態で懸濁されている、請求項1〜4いずれか1項に記載の方法。
- 担体相材料が架橋された5〜10重量%ゼラチンを含む液体であり、内相が担体相に微小液滴の形態で懸濁されている、請求項1に記載の方法。
- 前記エマルジョン又は懸濁液が、
(a)ペルフルオロ化学物質の水性エマルジョンを遠心分離に掛ける工程、
(b)上澄み液をデカントする工程、及び、
(c)ペルフルオロ化学物質の粒子を、ペルフルオロ化学物質よりも低いガス溶解度を有する液体中に再懸濁する工程、によって調製され、
前記担体相材料はグリセリン又は架橋された5〜10重量%ゼラチンを含む液体である、請求項1に記載の方法。 - 担体相材料が、グリセリンである、請求項7に記載の方法。
- 担体相材料が、架橋された5〜10重量%ゼラチンを含む液体である、請求項7に記載の方法。
- 急速に混合しながら、前記エマルジョン又は懸濁液を酸素に数時間暴露する事によって過飽和する、請求項1に記載の方法。
- 前記エマルジョン又は懸濁液を過飽和した後に高圧静水圧ポンプに送達する工程であってそれにより、ガスの分圧を更に増加する工程を含む、請求項1に記載の方法。
- 前記エマルジョン又は懸濁液が、0.1〜10ml/分で、外部環境に送達する管を通して加圧された容器の出口で押出される工程を含む、請求項1に記載の方法。
- 混合中に、前記エマルジョン又は懸濁液を、7kg/cm2〜105kg/cm2(100psi〜1500psi)の分圧の酸素に暴露する事によって、エマルジョンを酸素で過飽和する、請求項1に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/730,517 US5834519A (en) | 1996-10-11 | 1996-10-11 | Stabilized gas-supersaturated emulsions and suspensions |
US08/730,517 | 1996-10-11 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP10518560A Division JP2001502335A (ja) | 1996-10-11 | 1997-10-09 | 安定化されたガス―過飽和エマルジョン及び懸濁液 |
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Publication Number | Publication Date |
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JP2009167222A JP2009167222A (ja) | 2009-07-30 |
JP2009167222A5 JP2009167222A5 (ja) | 2012-05-17 |
JP5314489B2 true JP5314489B2 (ja) | 2013-10-16 |
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JP10518560A Withdrawn JP2001502335A (ja) | 1996-10-11 | 1997-10-09 | 安定化されたガス―過飽和エマルジョン及び懸濁液 |
JP2009112785A Expired - Fee Related JP5314489B2 (ja) | 1996-10-11 | 2009-05-07 | 安定化されたガス−過飽和エマルジョン及び懸濁液 |
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JP10518560A Withdrawn JP2001502335A (ja) | 1996-10-11 | 1997-10-09 | 安定化されたガス―過飽和エマルジョン及び懸濁液 |
Country Status (8)
Country | Link |
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US (7) | US5834519A (ja) |
EP (1) | EP0984771B1 (ja) |
JP (2) | JP2001502335A (ja) |
AU (1) | AU4757097A (ja) |
CA (1) | CA2268405A1 (ja) |
DE (1) | DE69738874D1 (ja) |
ES (1) | ES2312176T3 (ja) |
WO (1) | WO1998016203A1 (ja) |
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-
1996
- 1996-10-11 US US08/730,517 patent/US5834519A/en not_active Expired - Lifetime
-
1997
- 1997-07-08 US US08/889,635 patent/US5958377A/en not_active Expired - Lifetime
- 1997-07-08 US US08/889,634 patent/US5922305A/en not_active Expired - Lifetime
- 1997-10-09 CA CA002268405A patent/CA2268405A1/en not_active Abandoned
- 1997-10-09 JP JP10518560A patent/JP2001502335A/ja not_active Withdrawn
- 1997-10-09 ES ES97910113T patent/ES2312176T3/es not_active Expired - Lifetime
- 1997-10-09 DE DE69738874T patent/DE69738874D1/de not_active Expired - Lifetime
- 1997-10-09 AU AU47570/97A patent/AU4757097A/en not_active Abandoned
- 1997-10-09 WO PCT/US1997/018594 patent/WO1998016203A1/en active Application Filing
- 1997-10-09 EP EP97910113A patent/EP0984771B1/en not_active Expired - Lifetime
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1998
- 1998-09-01 US US09/144,956 patent/US6169117B1/en not_active Expired - Lifetime
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1999
- 1999-02-26 US US09/258,771 patent/US6197279B1/en not_active Expired - Lifetime
- 1999-02-26 US US09/258,758 patent/US6238645B1/en not_active Expired - Lifetime
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2001
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Also Published As
Publication number | Publication date |
---|---|
EP0984771A4 (en) | 2004-09-01 |
US20010028893A1 (en) | 2001-10-11 |
DE69738874D1 (de) | 2008-09-11 |
EP0984771A1 (en) | 2000-03-15 |
JP2001502335A (ja) | 2001-02-20 |
US5958377A (en) | 1999-09-28 |
CA2268405A1 (en) | 1998-04-23 |
WO1998016203A1 (en) | 1998-04-23 |
US5922305A (en) | 1999-07-13 |
US5834519A (en) | 1998-11-10 |
US6169117B1 (en) | 2001-01-02 |
EP0984771B1 (en) | 2008-07-30 |
US6238645B1 (en) | 2001-05-29 |
ES2312176T3 (es) | 2009-02-16 |
US6461590B2 (en) | 2002-10-08 |
AU4757097A (en) | 1998-05-11 |
US6197279B1 (en) | 2001-03-06 |
JP2009167222A (ja) | 2009-07-30 |
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