JP3241720B2 - 封入すべき外来物質に対する取り込み容量が増加されたリポソームの製造方法 - Google Patents
封入すべき外来物質に対する取り込み容量が増加されたリポソームの製造方法Info
- Publication number
- JP3241720B2 JP3241720B2 JP50206292A JP50206292A JP3241720B2 JP 3241720 B2 JP3241720 B2 JP 3241720B2 JP 50206292 A JP50206292 A JP 50206292A JP 50206292 A JP50206292 A JP 50206292A JP 3241720 B2 JP3241720 B2 JP 3241720B2
- Authority
- JP
- Japan
- Prior art keywords
- liposome
- liposomes
- lipid
- encapsulated
- substance
- 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.)
- Expired - Fee Related
Links
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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0447—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
- A61K49/0461—Dispersions, colloids, emulsions or suspensions
- A61K49/0466—Liposomes, lipoprotein vesicles, e.g. HDL or LDL lipoproteins, phospholipidic or polymeric micelles
-
- 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—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1277—Preparation processes; Proliposomes
- A61K9/1278—Post-loading, e.g. by ion or pH gradient
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP90810969 | 1990-12-11 | ||
| EP90810969.7 | 1990-12-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05504150A JPH05504150A (ja) | 1993-07-01 |
| JP3241720B2 true JP3241720B2 (ja) | 2001-12-25 |
Family
ID=8205973
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50206292A Expired - Fee Related JP3241720B2 (ja) | 1990-12-11 | 1991-12-09 | 封入すべき外来物質に対する取り込み容量が増加されたリポソームの製造方法 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5393530A (enExample) |
| EP (1) | EP0514523B1 (enExample) |
| JP (1) | JP3241720B2 (enExample) |
| KR (1) | KR0137783B1 (enExample) |
| AT (1) | ATE131724T1 (enExample) |
| AU (1) | AU635456B2 (enExample) |
| CA (1) | CA2072559C (enExample) |
| DE (1) | DE69115682T2 (enExample) |
| DK (1) | DK0514523T3 (enExample) |
| ES (1) | ES2081605T3 (enExample) |
| GR (1) | GR3018506T3 (enExample) |
| HU (1) | HUT62458A (enExample) |
| IE (1) | IE72163B1 (enExample) |
| IL (1) | IL99835A (enExample) |
| IN (1) | IN172269B (enExample) |
| IS (1) | IS1685B (enExample) |
| MX (1) | MX9102516A (enExample) |
| NZ (1) | NZ240817A (enExample) |
| WO (1) | WO1992010166A1 (enExample) |
| ZA (1) | ZA918489B (enExample) |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5352435A (en) * | 1989-12-22 | 1994-10-04 | Unger Evan C | Ionophore containing liposomes for ultrasound imaging |
| US20020150539A1 (en) | 1989-12-22 | 2002-10-17 | Unger Evan C. | Ultrasound imaging and treatment |
| US5542935A (en) * | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
| US5469854A (en) * | 1989-12-22 | 1995-11-28 | Imarx Pharmaceutical Corp. | Methods of preparing gas-filled liposomes |
| US5580575A (en) * | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
| US5205290A (en) | 1991-04-05 | 1993-04-27 | Unger Evan C | Low density microspheres and their use as contrast agents for computed tomography |
| US5874062A (en) | 1991-04-05 | 1999-02-23 | Imarx Pharmaceutical Corp. | Methods of computed tomography using perfluorocarbon gaseous filled microspheres as contrast agents |
| CA2146963A1 (en) * | 1992-10-16 | 1994-04-28 | Andreas Sachse | Process and device for producing liquid, dispersed systems |
| US5869305A (en) * | 1992-12-04 | 1999-02-09 | The University Of Pittsburgh | Recombinant viral vector system |
| US6217849B1 (en) | 1993-09-29 | 2001-04-17 | Bracco Research S.A. | Liposome suspensions as blood pool imaging contrast agents |
| US7083572B2 (en) | 1993-11-30 | 2006-08-01 | Bristol-Myers Squibb Medical Imaging, Inc. | Therapeutic delivery systems |
| WO1995026205A1 (en) * | 1994-03-28 | 1995-10-05 | Nycomed Imaging A/S | Liposomes |
| ES2165971T3 (es) * | 1995-02-24 | 2002-04-01 | Bracco Research Sa | Suspensiones de liposomas como agentes de contraste para la imagineria de la sangre. |
| US6521211B1 (en) | 1995-06-07 | 2003-02-18 | Bristol-Myers Squibb Medical Imaging, Inc. | Methods of imaging and treatment with targeted compositions |
| US5738868A (en) * | 1995-07-18 | 1998-04-14 | Lipogenics Ltd. | Liposome compositions and kits therefor |
| US6447800B2 (en) | 1996-01-18 | 2002-09-10 | The University Of British Columbia | Method of loading preformed liposomes using ethanol |
| CA2252617A1 (en) | 1996-05-01 | 1997-11-06 | Imarx Pharmaceutical Corp. | Methods for delivering compounds into a cell |
| US20020052310A1 (en) * | 1997-09-15 | 2002-05-02 | Massachusetts Institute Of Technology The Penn State Research Foundation | Particles for inhalation having sustained release properties |
| US20010051131A1 (en) * | 1996-06-19 | 2001-12-13 | Evan C. Unger | Methods for delivering bioactive agents |
| US5846517A (en) | 1996-09-11 | 1998-12-08 | Imarx Pharmaceutical Corp. | Methods for diagnostic imaging using a renal contrast agent and a vasodilator |
| DE19639811A1 (de) * | 1996-09-27 | 1998-04-02 | Artur Herzog Dr Mesmer | Verwendung einer Liposomenlösung zur Verstärkung der Wirksamkeit und/oder Verminderung der Toxizität von Arzneimitteln |
| GB9624918D0 (en) * | 1996-11-29 | 1997-01-15 | Nycomed Imaging As | Particulate components |
| US6537246B1 (en) | 1997-06-18 | 2003-03-25 | Imarx Therapeutics, Inc. | Oxygen delivery agents and uses for the same |
| WO1998044910A1 (en) | 1997-04-09 | 1998-10-15 | Philipp Lang | NEW TECHNIQUE TO MONITOR DRUG DELIVERY NONINVASIVELY $i(IN VIVO) |
| US7452551B1 (en) | 2000-10-30 | 2008-11-18 | Imarx Therapeutics, Inc. | Targeted compositions for diagnostic and therapeutic use |
| DE19731591C2 (de) * | 1997-07-17 | 1999-09-16 | Schering Ag | Pharmazeutische Mittel enthaltend perfluoralkylgruppenhaltige Trijodaromaten und ihre Verwendung in der Tumortherapie und interventionellen Radiologie |
| US6306432B1 (en) * | 1997-09-08 | 2001-10-23 | Chiron Corporation | High and low load formulations of IGF-I in multivesicular liposomes |
| US6106858A (en) * | 1997-09-08 | 2000-08-22 | Skyepharma, Inc. | Modulation of drug loading in multivescular liposomes |
| PT1014946E (pt) | 1997-09-18 | 2010-07-06 | Pacira Pharmaceuticals Inc | COMPOSIÃES ANESTéSICAS LIPOSSOMAIS DE LIBERTAÃO SUSTENTADA |
| ATE554748T1 (de) | 1997-11-14 | 2012-05-15 | Pacira Pharmaceuticals Inc | Herstellung von multivesikulären liposomen |
| US20010003580A1 (en) | 1998-01-14 | 2001-06-14 | Poh K. Hui | Preparation of a lipid blend and a phospholipid suspension containing the lipid blend |
| DE19813773A1 (de) * | 1998-03-27 | 1999-09-30 | Clemens Unger | Verfahren zur Herstellung von liposomalen Wirkstoffformulierungen |
| US6277413B1 (en) | 1998-07-17 | 2001-08-21 | Skyepharma, Inc. | Biodegradable compositions for the controlled release of encapsulated substances |
| US6511676B1 (en) | 1999-11-05 | 2003-01-28 | Teni Boulikas | Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes |
| JP5078212B2 (ja) | 2000-06-02 | 2012-11-21 | ブラッコ・スイス・ソシエテ・アノニム | 内皮細胞を標的とするための化合物、それを含む組成物およびその使用方法 |
| DE10121903A1 (de) * | 2001-04-27 | 2002-10-31 | Nimbus Biotechnologie Gmbh | System für die Membranpermeationsmessung |
| JP2004532252A (ja) * | 2001-05-31 | 2004-10-21 | スカイファーマ インコーポレーテッド | リポソームおよびミクロスフェア中のナノ懸濁物のカプセル化 |
| EP1275378B1 (en) * | 2001-07-10 | 2009-04-15 | Canon Kabushiki Kaisha | Particulate construct comprising polyhydroxyalkanoate and method for producing it |
| JP3990880B2 (ja) * | 2001-07-10 | 2007-10-17 | キヤノン株式会社 | ポリヒドロキシアルカノエート被覆リポソームの製造方法 |
| US20030129224A1 (en) * | 2001-11-13 | 2003-07-10 | Paul Tardi | Lipid carrier compositions and methods for improved drug retention |
| EP1443900B1 (en) | 2001-11-13 | 2012-05-23 | Celator Pharmaceuticals, Inc. | Lipid carrier compositions with enhanced blood stability |
| ES2290333T3 (es) * | 2001-11-13 | 2008-02-16 | Celator Pharmaceuticals, Inc. | Composiciones de vehiculos lipidicos y metodos para la retencion mejorada de farmacos. |
| US20050129750A1 (en) * | 2003-12-15 | 2005-06-16 | Yu-Fang Hu | Process for producing liposome suspension and product containing liposome suspension produced thereby |
| EP1547580A1 (en) * | 2003-12-23 | 2005-06-29 | MediGene Oncology GmbH | Loading of a camptothecin drug into colloidal nanoparticles |
| EP1547582A1 (en) * | 2003-12-23 | 2005-06-29 | MediGene Oncology GmbH | Method of producing lipid complexed camptothecin-carboxylate |
| CN1960707B (zh) | 2004-06-03 | 2012-11-14 | 博莱科瑞士股份有限公司 | 用于治疗和/或诊断用途的脂质集合体 |
| JP2008515929A (ja) * | 2004-10-08 | 2008-05-15 | アルザ コーポレイション | 脂質連結部分を予備形成した脂質集合体にマイクロ波を使用して挿入する方法 |
| WO2006081354A2 (en) * | 2005-01-26 | 2006-08-03 | Celator Pharmaceuticals, Inc. | Lipid carrier compositions with reduced polydispersity |
| US20070031342A1 (en) * | 2005-06-22 | 2007-02-08 | Nektar Therapeutics | Sustained release microparticles for pulmonary delivery |
| ES2275443B1 (es) | 2005-11-30 | 2008-06-01 | Italfarmaco, S.A. | Procedimiento de preparacion de liposomas. |
| JP5080779B2 (ja) * | 2006-10-25 | 2012-11-21 | テルモ株式会社 | リポソーム製剤の製造方法 |
| US20090136937A1 (en) * | 2007-05-09 | 2009-05-28 | Coleman Matthew A | Methods and systems for monitoring production of a target protein in a nanolipoprotein particle |
| EP2224963A1 (en) * | 2007-11-19 | 2010-09-08 | CeramOptec GmbH | Pegylated compounds for age-related macular degeneration |
| US9688718B2 (en) | 2008-01-11 | 2017-06-27 | Lawrence Livermore National Security, Llc | Nanolipoprotein particles comprising hydrogenases and related products, methods and systems |
| US8883729B2 (en) * | 2008-05-22 | 2014-11-11 | Lawrence Livermore National Security, Llc | Nanolipoprotein particles and related compositions, methods and systems |
| US9303273B2 (en) | 2008-05-09 | 2016-04-05 | Lawrence Livermore National Security, Llc | Nanolipoprotein particles comprising a natural rubber biosynthetic enzyme complex and related products, methods and systems |
| US9445975B2 (en) * | 2008-10-03 | 2016-09-20 | Access Business Group International, Llc | Composition and method for preparing stable unilamellar liposomal suspension |
| US9192685B2 (en) | 2008-10-07 | 2015-11-24 | Bracco Suisse S.A. | Targeting construct comprising anti-polymer antibody and contrast/therapeutic agents binding to the same |
| EP2184054A1 (en) * | 2008-11-08 | 2010-05-12 | Lipoxen Technologies Limited | Small Interfering RNA Delivery |
| US10151037B2 (en) | 2009-01-12 | 2018-12-11 | Lawrence Livermore National Security, Llc | Electrochemical flow-cell for hydrogen production and nicotinamide dependent target reduction, and related methods and systems |
| WO2011038068A1 (en) | 2009-09-23 | 2011-03-31 | Formatech, Inc. | Methods for the preparation of liposomes |
| US10143652B2 (en) | 2009-09-23 | 2018-12-04 | Curirx Inc. | Methods for the preparation of liposomes |
| WO2012097346A1 (en) | 2011-01-13 | 2012-07-19 | Variation Biotechnologies, Inc. | Compositions and methods for treating viral infections |
| US9644038B2 (en) | 2011-12-21 | 2017-05-09 | The Regents Of The University Of California | Apolipoprotein nanodiscs with telodendrimer |
| CA2894442C (en) | 2012-01-12 | 2020-01-21 | Variation Biotechnologies Inc. | Compositions and methods for treating viral infections |
| US20150079077A1 (en) * | 2012-01-27 | 2015-03-19 | Variation Biotechnologies, Inc. | Methods and compositions for therapeutic agents |
| MX364310B (es) * | 2013-11-05 | 2019-04-22 | Gustavo A Garcia Sanchez | Método para preparar una formulación inmunosupresora. |
| EP3138555B1 (en) | 2014-04-30 | 2020-10-28 | FUJIFILM Corporation | Liposome composition and production method therefor |
| JP6276847B2 (ja) * | 2014-04-30 | 2018-02-07 | 富士フイルム株式会社 | リポソーム組成物及びその製造方法 |
| IL296875A (en) | 2014-12-31 | 2022-12-01 | Lantheus Medical Imaging Inc | Fat-wrapped gas microsphere preparations and related methods |
| PT3291797T (pt) | 2015-05-04 | 2020-10-19 | Versantis AG | Método para preparar vesículas de gradiente de ph transmembranar |
| WO2017035326A1 (en) | 2015-08-25 | 2017-03-02 | Lawrence Livermore National Security, Llc | Stable nanolipoprotein particles and related compositions methods and systems |
| US11279749B2 (en) | 2015-09-11 | 2022-03-22 | Lawrence Livermore National Security, Llc | Synthetic apolipoproteins, and related compositions methods and systems for nanolipoprotein particles formation |
| MA43184A (fr) | 2015-11-02 | 2021-04-14 | Fujifilm Corp | Composition liposomale et son procédé de production |
| TWI740937B (zh) | 2016-05-04 | 2021-10-01 | 美商藍瑟斯醫學影像公司 | 用於製備超音波顯影劑之裝置及方法 |
| US9789210B1 (en) | 2016-07-06 | 2017-10-17 | Lantheus Medical Imaging, Inc. | Methods for making ultrasound contrast agents |
| CA3032810A1 (en) | 2016-08-02 | 2018-02-08 | Curirx Inc. | Methods for the preparation of liposomes |
| WO2018204495A1 (en) | 2017-05-02 | 2018-11-08 | Synthetic Genomics, Inc. | Nanolipoprotein particles and related compositions methods and systems for loading rna |
| US11207422B2 (en) | 2017-05-02 | 2021-12-28 | Lawrence Livermore National Security, Llc | MOMP telonanoparticles, and related compositions, methods and systems |
| DK3811949T3 (da) | 2018-06-20 | 2024-10-07 | Fujifilm Corp | Kombineret medicin omfattende gemcitabin-indkapslet liposomsammensætning og immun-checkpoint-blokade |
| CA3144443A1 (en) * | 2019-06-28 | 2020-12-30 | Moleculin Biotech, Inc. | Method of reconstituting liposomal annamycin |
| US11980636B2 (en) | 2020-11-18 | 2024-05-14 | Jazz Pharmaceuticals Ireland Limited | Treatment of hematological disorders |
| US11033495B1 (en) | 2021-01-22 | 2021-06-15 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12151024B2 (en) | 2021-01-22 | 2024-11-26 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US11278494B1 (en) | 2021-01-22 | 2022-03-22 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US11357727B1 (en) | 2021-01-22 | 2022-06-14 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| GB2627096A (en) | 2021-10-14 | 2024-08-14 | Pacira Pharmaceuticals Inc | Bupivacaine multivesicular liposome formulations and uses thereof |
| US12251468B1 (en) | 2024-05-20 | 2025-03-18 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12156940B1 (en) | 2024-05-20 | 2024-12-03 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12251472B1 (en) | 2024-05-20 | 2025-03-18 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5186117A (en) * | 1975-01-27 | 1976-07-28 | Tanabe Seiyaku Co | Johoseibiryushiseizainoseiho |
| CA1270198C (en) * | 1984-08-08 | 1990-06-12 | Marcel B Bally | ENCAPSULATION OF ANTINEOPLASTIC AGENTS IN LIPOSONES |
| JPS6150912A (ja) * | 1984-08-16 | 1986-03-13 | Shionogi & Co Ltd | リポソ−ム製剤の製造法 |
| JPS63211222A (ja) * | 1987-02-27 | 1988-09-02 | Terumo Corp | リポソ−ムの製法 |
| US4963297A (en) * | 1987-12-22 | 1990-10-16 | The Liposome Company, Inc. | Spontaneous vesticulation of multilamellar liposomes |
| CH672733A5 (enExample) * | 1987-05-22 | 1989-12-29 | Bracco Ind Chimica Spa | |
| US4870160A (en) * | 1987-08-19 | 1989-09-26 | Regents Of The University Of Minnesota | Polypeptides with laminin activity |
| IE63518B1 (en) * | 1987-11-18 | 1995-05-03 | Vestar Inc | Multiple step entrapment/loading procedure for preparing lipophilic drug-containing liposomes |
| CA1330199C (en) * | 1987-12-22 | 1994-06-14 | Thomas D. Madden | Spontaneous vesiculation of multilamellar liposomes |
| ATE108651T1 (de) * | 1988-05-20 | 1994-08-15 | Liposome Co Inc | Aktives mittel: lipid-komplex mit hohem verhältnis. |
| IL91664A (en) * | 1988-09-28 | 1993-05-13 | Yissum Res Dev Co | Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release |
-
1991
- 1991-10-22 IS IS3773A patent/IS1685B/is unknown
- 1991-10-23 IL IL9983591A patent/IL99835A/en not_active IP Right Cessation
- 1991-10-24 IN IN809MA1991 patent/IN172269B/en unknown
- 1991-10-24 ZA ZA918489A patent/ZA918489B/xx unknown
- 1991-11-29 NZ NZ240817A patent/NZ240817A/xx unknown
- 1991-12-09 AU AU90629/91A patent/AU635456B2/en not_active Ceased
- 1991-12-09 HU HU922595A patent/HUT62458A/hu unknown
- 1991-12-09 KR KR1019920701929A patent/KR0137783B1/ko not_active Expired - Fee Related
- 1991-12-09 ES ES92901231T patent/ES2081605T3/es not_active Expired - Lifetime
- 1991-12-09 DE DE69115682T patent/DE69115682T2/de not_active Expired - Lifetime
- 1991-12-09 AT AT92901231T patent/ATE131724T1/de not_active IP Right Cessation
- 1991-12-09 CA CA002072559A patent/CA2072559C/en not_active Expired - Lifetime
- 1991-12-09 WO PCT/EP1991/002377 patent/WO1992010166A1/en not_active Ceased
- 1991-12-09 EP EP92901231A patent/EP0514523B1/en not_active Expired - Lifetime
- 1991-12-09 DK DK92901231.8T patent/DK0514523T3/da active
- 1991-12-09 JP JP50206292A patent/JP3241720B2/ja not_active Expired - Fee Related
- 1991-12-10 IE IE428991A patent/IE72163B1/en not_active IP Right Cessation
- 1991-12-11 MX MX9102516A patent/MX9102516A/es not_active IP Right Cessation
-
1992
- 1992-12-09 US US07/861,889 patent/US5393530A/en not_active Expired - Lifetime
-
1995
- 1995-12-21 GR GR950403587T patent/GR3018506T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ240817A (en) | 1993-01-27 |
| AU9062991A (en) | 1992-07-08 |
| EP0514523A1 (en) | 1992-11-25 |
| EP0514523B1 (en) | 1995-12-20 |
| IS1685B (is) | 1998-02-24 |
| MX9102516A (es) | 1992-06-01 |
| GR3018506T3 (en) | 1996-03-31 |
| KR0137783B1 (ko) | 1998-05-15 |
| DE69115682D1 (de) | 1996-02-01 |
| IS3773A7 (is) | 1992-06-12 |
| HUT62458A (en) | 1993-05-28 |
| ES2081605T3 (es) | 1996-03-16 |
| IE914289A1 (en) | 1992-06-17 |
| DE69115682T2 (de) | 1996-05-15 |
| IN172269B (enExample) | 1993-05-29 |
| CA2072559C (en) | 1997-03-18 |
| IL99835A (en) | 1995-11-27 |
| JPH05504150A (ja) | 1993-07-01 |
| AU635456B2 (en) | 1993-03-18 |
| US5393530A (en) | 1995-02-28 |
| KR920703014A (ko) | 1992-12-17 |
| ZA918489B (en) | 1992-07-29 |
| WO1992010166A1 (en) | 1992-06-25 |
| IE72163B1 (en) | 1997-03-26 |
| ATE131724T1 (de) | 1996-01-15 |
| CA2072559A1 (en) | 1992-06-12 |
| IL99835A0 (en) | 1992-08-18 |
| DK0514523T3 (da) | 1996-01-29 |
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