ES2077086T3 - Vesiculas de membrana sintetica que contienen peptidos de fusion funcionalmente activos como sistemas de suministro de farmacos. - Google Patents
Vesiculas de membrana sintetica que contienen peptidos de fusion funcionalmente activos como sistemas de suministro de farmacos.Info
- Publication number
- ES2077086T3 ES2077086T3 ES91101414T ES91101414T ES2077086T3 ES 2077086 T3 ES2077086 T3 ES 2077086T3 ES 91101414 T ES91101414 T ES 91101414T ES 91101414 T ES91101414 T ES 91101414T ES 2077086 T3 ES2077086 T3 ES 2077086T3
- Authority
- ES
- Spain
- Prior art keywords
- weight
- membrane
- detergent
- layer
- supply systems
- 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 - Lifetime
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
- A61K9/1277—Preparation processes; Proliposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6839—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting material from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
- A61K47/6913—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome the liposome being modified on its surface by an antibody
-
- 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
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Immunology (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Feedback Control In General (AREA)
- Fittings On The Vehicle Exterior For Carrying Loads, And Devices For Holding Or Mounting Articles (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Abstract
LAS VESICULAS FOSFOLIPIDAS BICAPA CONTIENEN AL MENOS UN MEDICAMENTO FARMACEUTICAMENTE ACTIVO Y COMPRENDEN MARCADORES ESPECIFICOS DE CELULAS EN LA MEMBRANA QUE TIENE AL MENOS UN 90% DE ACTIVIDAD BIOLOGICA CUANDO SE MIDEN DE ACUERDO CON LA INVESTIGACION ANTIVIRICA 14, 39-50 DE LUESCHERY GLUECK. EN LA MEMBRANA, EL CONTENIDO DE COLESTEROL ES PREFERENTEMENTE MENOR DEL 2% EN PESO, EL CONTENIDO DE DETERGENTE PREFERENTEMENTE MENOR DE 1PPB. EL DIAMETRO DE LA VESICULA ES PREFERENTEMENTE DE 8 NM APROXIMADAMENTE. EL FOSFOLIPIDO EN LA MEMBRANA PUEDE COMPRENDER DEL 70 A 95% EN PESO DE FOSFATIDICOLINA Y PREFERENTEMENTE DEL 10 AL 20% EN PESO DE FOSFATIDILETANOLAMINA; PREFERIBLEMENTE DEL 6 AL 8% EN PESO DE UN RETICULADOR PREFERIBLEMENTE DE UN DERIVADO SULFOSUCINIMIDILA, Y AL MENOS UN PEPTIDO DE FUSION ESPECIFICA CELULAR ESTA ENLAZADO A LA MEMBRANA. LAS VESICULAS SE UTILIZAN PARA LA PREPARACION DE FARMACOS CONTRA EL SIDA Y LOS CARCIHOMAS. EL PROCESO PARA LA PREPARACION DE VESICULAS BICAPA FOSFOLIPIDAS COMPRENDE HEMAGLUTININA COMO MARCADOR ESPECIFICO CELULAR CON AL MENOS UN PEPTIDO DE FUSION. LA HEMAGLUTININA SE SEPARA DE UNA CAPA DE VIRUS POR MEDIO DE UN DETERGENTE NORONICO, PREFERIBLEMENTE ESTEN MONODODECILO GLICOL OCTAETILENO. SE EXTRAE MEDIANTE EL TRATAMIENTO REPETITIVO DE LA SOLUCION CON UN TOTAL DE ALREDEDOR DE 15 G DE MICROPORTADORES EN BOLAS DE POLIESTIRENO POR 100 MG DE DETERGENTE.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP91101414A EP0497997B1 (en) | 1991-02-02 | 1991-02-02 | Synthetic membrane vesicles containing functionally active fusion peptides as drug delivery systems |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2077086T3 true ES2077086T3 (es) | 1995-11-16 |
Family
ID=8206362
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES91101414T Expired - Lifetime ES2077086T3 (es) | 1991-02-02 | 1991-02-02 | Vesiculas de membrana sintetica que contienen peptidos de fusion funcionalmente activos como sistemas de suministro de farmacos. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6040167A (es) |
| EP (1) | EP0497997B1 (es) |
| JP (1) | JP3404037B2 (es) |
| KR (1) | KR100205693B1 (es) |
| AT (1) | ATE125154T1 (es) |
| AU (1) | AU657730B2 (es) |
| BG (1) | BG61215B1 (es) |
| BR (1) | BR9204116A (es) |
| CA (1) | CA2079685C (es) |
| DE (1) | DE69111414T2 (es) |
| DK (1) | DK0497997T3 (es) |
| ES (1) | ES2077086T3 (es) |
| FI (1) | FI109969B (es) |
| GE (1) | GEP20002229B (es) |
| GR (1) | GR3017490T3 (es) |
| HK (1) | HK56696A (es) |
| HU (1) | HU215533B (es) |
| NO (1) | NO306194B1 (es) |
| PL (2) | PL296382A1 (es) |
| RO (1) | RO114736B1 (es) |
| RU (1) | RU2125868C1 (es) |
| WO (1) | WO1992013525A1 (es) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5603872A (en) * | 1991-02-14 | 1997-02-18 | Baxter International Inc. | Method of binding recognizing substances to liposomes |
| DK0525132T3 (da) * | 1991-02-14 | 1996-02-05 | Baxter Int | Binding af genkendende stoffer til liposomer |
| US7097839B1 (en) * | 1993-10-26 | 2006-08-29 | Thomas Jefferson University | ST receptor binding compounds and methods of using the same |
| US5879656A (en) * | 1993-10-26 | 1999-03-09 | Thomas Jefferson University | Methods of treating metastatic colorectal cancer with ST receptor binding compounds |
| WO1995032706A1 (en) * | 1994-05-31 | 1995-12-07 | Inex Pharmaceuticals Corp. | Virosome-mediated intracellular delivery of therapeutic agents |
| US6861053B1 (en) * | 1999-08-11 | 2005-03-01 | Cedars-Sinai Medical Center | Methods of diagnosing or treating irritable bowel syndrome and other disorders caused by small intestinal bacterial overgrowth |
| US5908777A (en) * | 1995-06-23 | 1999-06-01 | University Of Pittsburgh | Lipidic vector for nucleic acid delivery |
| AU6691496A (en) * | 1995-08-01 | 1997-02-26 | Advanced Therapies, Inc. | Enhanced artificial viral envelopes for cellular delivery of therapeutic substances |
| CZ299809B6 (cs) * | 1996-05-08 | 2008-12-03 | Nika Health Products Limited | Lipidový vácek mající kladne nabitou membránu z lipidové dvojvrstvy pro prenos genetického materiálu a zpusob jeho prípravy |
| EP1141007B1 (en) * | 1998-12-14 | 2013-05-15 | Dendreon Corporation | Compositions and methods for enhancement of major histocompatibility complex class i restricted antigen presentation |
| US7148324B1 (en) | 1998-12-14 | 2006-12-12 | Dendreon Corporation | Compositions and methods for enhancement of major histocompatibility complex class I restricted antigen presentation |
| JP2004513059A (ja) | 1998-12-24 | 2004-04-30 | ユセベ,ソシエテ アノニム | ペプチド産物、方法及び組成物 |
| MXPA02001417A (es) * | 1999-08-09 | 2002-08-12 | Lexigen Pharm Corp | Complejos multiples de citosina-anticuerpo. |
| CZ20021216A3 (cs) * | 1999-10-08 | 2002-10-16 | Nika Health Products Limited | Lipidové váčky obsahující DOSPER |
| JP4112860B2 (ja) * | 1999-12-17 | 2008-07-02 | ショット アクチエンゲゼルシャフト | 乗員の拘束システムの誘導作動式点火カプセルおよび点火カプセル用のテスト回路 |
| US20040028687A1 (en) * | 2002-01-15 | 2004-02-12 | Waelti Ernst Rudolf | Methods and compositions for the targeted delivery of therapeutic substances to specific cells and tissues |
| US20040176283A1 (en) * | 2002-04-01 | 2004-09-09 | Robinson John A. | Methods and compositions for the design of synthetic vaccines |
| AU2003233981A1 (en) * | 2002-04-29 | 2003-11-17 | Biotesys Gmbh | Transport system in biological systems |
| EP1447080A1 (en) * | 2003-02-13 | 2004-08-18 | Bestewil Holding B.V. | Method for producing virosome-like particles |
| US8658203B2 (en) | 2004-05-03 | 2014-02-25 | Merrimack Pharmaceuticals, Inc. | Liposomes useful for drug delivery to the brain |
| LT3173073T (lt) | 2004-05-03 | 2025-01-10 | Ipsen Biopharm Ltd. | Liposomos, skirtos vaistų pristatymui |
| WO2007048019A2 (en) * | 2005-10-20 | 2007-04-26 | The Penn State Research Foundation | Delivery system for diagnostic and therapeutic agents |
| WO2009016433A2 (en) * | 2006-09-15 | 2009-02-05 | Ottawa Health Research Institute | Oncolytic rhabdovirus |
| EP4647126A3 (en) | 2015-10-16 | 2026-02-11 | Ipsen Biopharm Ltd. | Stabilizing camptothecin pharmaceutical compositions |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3173713D1 (en) * | 1980-09-05 | 1986-03-20 | Frappier Armand Inst | Formation of an immunosome exclusively made of viral antigens reconstituted on an artificial membrane |
| US4871488A (en) * | 1985-04-22 | 1989-10-03 | Albany Medical College Of Union University | Reconstituting viral glycoproteins into large phospholipid vesicles |
| US4663161A (en) * | 1985-04-22 | 1987-05-05 | Mannino Raphael J | Liposome methods and compositions |
| US5000960A (en) * | 1987-03-13 | 1991-03-19 | Micro-Pak, Inc. | Protein coupling to lipid vesicles |
| IL86650A0 (en) * | 1987-06-30 | 1988-11-30 | Biophor Corp | Animal derived cells and liposomes,having an antigenic protein incorporated into their membrane |
| AU6358890A (en) * | 1989-09-01 | 1991-04-08 | Board Of Regents, The University Of Texas System | Immunoliposomes for transmittal of activating signals to cells |
| AU652778B2 (en) * | 1990-10-15 | 1994-09-08 | Quest International B.V. | Treatment composition |
-
1991
- 1991-01-17 PL PL29638291A patent/PL296382A1/xx unknown
- 1991-02-02 AT AT91101414T patent/ATE125154T1/de not_active IP Right Cessation
- 1991-02-02 DE DE69111414T patent/DE69111414T2/de not_active Expired - Fee Related
- 1991-02-02 EP EP91101414A patent/EP0497997B1/en not_active Expired - Lifetime
- 1991-02-02 ES ES91101414T patent/ES2077086T3/es not_active Expired - Lifetime
- 1991-02-02 DK DK91101414.0T patent/DK0497997T3/da active
-
1992
- 1992-01-17 WO PCT/EP1992/000089 patent/WO1992013525A1/en not_active Ceased
- 1992-01-17 GE GEAP19921215A patent/GEP20002229B/en unknown
- 1992-01-17 RU SU5053247A patent/RU2125868C1/ru not_active IP Right Cessation
- 1992-01-17 AU AU11693/92A patent/AU657730B2/en not_active Ceased
- 1992-01-17 CA CA002079685A patent/CA2079685C/en not_active Expired - Fee Related
- 1992-01-17 RO RO92-01271A patent/RO114736B1/ro unknown
- 1992-01-17 US US07/930,593 patent/US6040167A/en not_active Expired - Fee Related
- 1992-01-17 JP JP50347192A patent/JP3404037B2/ja not_active Expired - Fee Related
- 1992-01-17 HU HU9203141A patent/HU215533B/hu not_active IP Right Cessation
- 1992-01-17 BR BR929204116A patent/BR9204116A/pt not_active Application Discontinuation
- 1992-01-17 PL PL92296382A patent/PL170169B1/pl not_active IP Right Cessation
- 1992-09-24 NO NO923703A patent/NO306194B1/no not_active IP Right Cessation
- 1992-09-29 BG BG96928A patent/BG61215B1/bg unknown
- 1992-10-01 KR KR1019920702402A patent/KR100205693B1/ko not_active Expired - Fee Related
- 1992-10-01 FI FI924418A patent/FI109969B/fi active
-
1995
- 1995-09-21 GR GR950402607T patent/GR3017490T3/el unknown
-
1996
- 1996-03-28 HK HK56696A patent/HK56696A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| GEP20002229B (en) | 2000-09-25 |
| JPH05505406A (ja) | 1993-08-12 |
| RO114736B1 (ro) | 1999-07-30 |
| AU657730B2 (en) | 1995-03-23 |
| KR100205693B1 (en) | 1999-07-01 |
| JP3404037B2 (ja) | 2003-05-06 |
| NO306194B1 (no) | 1999-10-04 |
| AU1169392A (en) | 1992-09-07 |
| FI109969B (fi) | 2002-11-15 |
| BG96928A (bg) | 1994-03-24 |
| EP0497997B1 (en) | 1995-07-19 |
| GR3017490T3 (en) | 1995-12-31 |
| HU215533B (hu) | 1999-01-28 |
| CA2079685C (en) | 2001-11-27 |
| FI924418A7 (fi) | 1993-04-03 |
| RU2125868C1 (ru) | 1999-02-10 |
| FI924418A0 (fi) | 1992-10-01 |
| DE69111414D1 (de) | 1995-08-24 |
| PL170169B1 (en) | 1996-10-31 |
| NO923703L (no) | 1992-11-26 |
| HK56696A (en) | 1996-04-12 |
| ATE125154T1 (de) | 1995-08-15 |
| NO923703D0 (no) | 1992-09-24 |
| PL296382A1 (en) | 1993-11-02 |
| US6040167A (en) | 2000-03-21 |
| HU9203141D0 (en) | 1992-12-28 |
| HUT66194A (en) | 1994-10-28 |
| BG61215B1 (en) | 1997-03-31 |
| BR9204116A (pt) | 1993-06-08 |
| DE69111414T2 (de) | 1996-02-01 |
| CA2079685A1 (en) | 1992-08-03 |
| WO1992013525A1 (en) | 1992-08-20 |
| EP0497997A1 (en) | 1992-08-12 |
| DK0497997T3 (da) | 1995-11-27 |
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