DE68903065T2 - Aus gingko biloba extrahierter biologischer regulator, wirksam in verschiedenen pathologien. - Google Patents
Aus gingko biloba extrahierter biologischer regulator, wirksam in verschiedenen pathologien.Info
- Publication number
- DE68903065T2 DE68903065T2 DE8989401191T DE68903065T DE68903065T2 DE 68903065 T2 DE68903065 T2 DE 68903065T2 DE 8989401191 T DE8989401191 T DE 8989401191T DE 68903065 T DE68903065 T DE 68903065T DE 68903065 T2 DE68903065 T2 DE 68903065T2
- Authority
- DE
- Germany
- Prior art keywords
- substance
- bioparyl
- manufacture
- ribonuclease
- inhibit
- 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
- 244000194101 Ginkgo biloba Species 0.000 title claims description 12
- 102000006382 Ribonucleases Human genes 0.000 claims description 34
- 108010083644 Ribonucleases Proteins 0.000 claims description 34
- 239000000126 substance Substances 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 201000011510 cancer Diseases 0.000 claims description 15
- 238000000605 extraction Methods 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 12
- 239000000284 extract Substances 0.000 claims description 12
- 206010016654 Fibrosis Diseases 0.000 claims description 11
- 230000004761 fibrosis Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 230000002255 enzymatic effect Effects 0.000 claims description 7
- 238000005119 centrifugation Methods 0.000 claims description 6
- 229910052742 iron Inorganic materials 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 108060003951 Immunoglobulin Proteins 0.000 claims description 5
- 108010074605 gamma-Globulins Proteins 0.000 claims description 5
- 102000018358 immunoglobulin Human genes 0.000 claims description 5
- 238000011161 development Methods 0.000 claims description 4
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- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 17
- 238000000338 in vitro Methods 0.000 description 13
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- 238000003786 synthesis reaction Methods 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- 206010025323 Lymphomas Diseases 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 4
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- 239000002904 solvent Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000009471 action Effects 0.000 description 3
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- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 206010036030 Polyarthritis Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
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- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
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- 235000019441 ethanol Nutrition 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 208000008494 pericarditis Diseases 0.000 description 2
- 208000030428 polyarticular arthritis Diseases 0.000 description 2
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- 239000002244 precipitate Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000002227 vasoactive effect Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
- 206010067953 Radiation fibrosis Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- OHJMTUPIZMNBFR-UHFFFAOYSA-N biuret Chemical compound NC(=O)NC(N)=O OHJMTUPIZMNBFR-UHFFFAOYSA-N 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
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- 230000003727 cerebral blood flow Effects 0.000 description 1
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- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
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- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
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- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
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- 230000037311 normal skin Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 238000013518 transcription Methods 0.000 description 1
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- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Microbiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8809738A FR2634380B1 (fr) | 1988-07-19 | 1988-07-19 | Regulateur biologique, actif dans diverses pathologies |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE68903065D1 DE68903065D1 (de) | 1992-11-05 |
| DE68903065T2 true DE68903065T2 (de) | 1993-03-25 |
Family
ID=9368543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8989401191T Expired - Fee Related DE68903065T2 (de) | 1988-07-19 | 1989-04-26 | Aus gingko biloba extrahierter biologischer regulator, wirksam in verschiedenen pathologien. |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0352146B1 (enExample) |
| JP (1) | JPH0278628A (enExample) |
| CA (1) | CA1337177C (enExample) |
| DE (1) | DE68903065T2 (enExample) |
| DK (1) | DK355089A (enExample) |
| ES (1) | ES2052942T3 (enExample) |
| FR (1) | FR2634380B1 (enExample) |
| GR (1) | GR3006687T3 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3832056A1 (de) * | 1988-09-21 | 1990-03-22 | Scholle Helmut Dr Med | Verwendung eines ginkgo-extraktes |
| DE4030758A1 (de) * | 1990-09-28 | 1992-04-02 | Schwabe Willmar Gmbh & Co | Extrakt aus blaettern von ginkgo biloba, insbesondere zur intravenoesen injektion oder infusion, verfahren zu seiner herstellung und den extrakt enthaltende ampullenpraeparate |
| DE4308443C2 (de) * | 1993-03-17 | 1996-09-19 | Laves Hans Georg | Arzneimittel zur Behandlung von Retrovirusinfektionen |
| FR2754714B1 (fr) * | 1996-10-22 | 1999-01-22 | Roc Sa | Nouvelles utilisations d'extraits de ginkgo biloba pour la preparation de compositions pharmaceutiques,et methode de traitement cosmetique mettant en oeuvre un extrait de ginkgo biloba |
| FR2759371B1 (fr) * | 1997-02-07 | 1999-03-19 | Bio Merieux | Utilisation d'un polypeptide, pour obtenir une composition pour detecter, prevenir ou traiter une maladie degenerative et/ou auto-immune |
| US6030621A (en) * | 1998-03-19 | 2000-02-29 | De Long; Xie | Ginkgo biloba composition, method to prepare the same and uses thereof |
| KR100417172B1 (ko) * | 2000-08-04 | 2004-02-05 | 주식회사 안지오랩 | 은행엽 엑스를 유효성분으로 하는 혈관신생 억제제 |
| WO2002011745A1 (en) * | 2000-08-04 | 2002-02-14 | Angiolab, Inc. | Composition containing ginkgo biloba that inhibit angiogenesis and matrix metalloproteinase |
| FR2911782A1 (fr) * | 2007-01-31 | 2008-08-01 | Jacqueline Martin | Comment guerir du sida avec mentha pulegium et ginkgo biloba |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2117429C3 (de) * | 1971-04-08 | 1982-04-01 | Fa. Dr. Willmar Schwabe, 7500 Karlsruhe | Verfahren zur Herstellung eines Injektions- bzw. Infusionspräparates mit einem Gehalt an einem Wirkstoffgemisch aus den Blättern von Ginkgo biloba |
| FR2518406A1 (fr) * | 1981-12-22 | 1983-06-24 | Prodipharm | Nouveau procede d'obtention de substances vaso-actives extraites de feuilles de ginkgo |
-
1988
- 1988-07-19 FR FR8809738A patent/FR2634380B1/fr not_active Expired - Lifetime
-
1989
- 1989-04-26 ES ES89401191T patent/ES2052942T3/es not_active Expired - Lifetime
- 1989-04-26 EP EP89401191A patent/EP0352146B1/fr not_active Expired - Lifetime
- 1989-04-26 DE DE8989401191T patent/DE68903065T2/de not_active Expired - Fee Related
- 1989-06-22 CA CA000603639A patent/CA1337177C/en not_active Expired - Fee Related
- 1989-07-18 DK DK355089A patent/DK355089A/da not_active Application Discontinuation
- 1989-07-19 JP JP1184843A patent/JPH0278628A/ja active Pending
-
1992
- 1992-12-28 GR GR920403150T patent/GR3006687T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FR2634380B1 (fr) | 1990-10-12 |
| EP0352146A1 (fr) | 1990-01-24 |
| JPH0278628A (ja) | 1990-03-19 |
| DK355089A (da) | 1990-01-20 |
| GR3006687T3 (enExample) | 1993-06-30 |
| ES2052942T3 (es) | 1994-07-16 |
| DK355089D0 (da) | 1989-07-18 |
| DE68903065D1 (de) | 1992-11-05 |
| FR2634380A1 (fr) | 1990-01-26 |
| EP0352146B1 (fr) | 1992-09-30 |
| CA1337177C (en) | 1995-10-03 |
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