LU83128A1 - PHARMACEUTICAL COMPOSITIONS CONTAINING A NAPHTYRIDINE DERIVATIVE - Google Patents
PHARMACEUTICAL COMPOSITIONS CONTAINING A NAPHTYRIDINE DERIVATIVE Download PDFInfo
- Publication number
- LU83128A1 LU83128A1 LU83128A LU83128A LU83128A1 LU 83128 A1 LU83128 A1 LU 83128A1 LU 83128 A LU83128 A LU 83128A LU 83128 A LU83128 A LU 83128A LU 83128 A1 LU83128 A1 LU 83128A1
- Authority
- LU
- Luxembourg
- Prior art keywords
- compound
- pharmaceutical compositions
- derivative
- naphtyridine
- compositions containing
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000026680 Metabolic Brain disease Diseases 0.000 claims description 2
- 230000003542 behavioural effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000009999 tuberous sclerosis Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 1
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 150000005054 naphthyridines Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- XYGBKMMCQDZQOZ-UHFFFAOYSA-M sodium;4-hydroxybutanoate Chemical compound [Na+].OCCCC([O-])=O XYGBKMMCQDZQOZ-UHFFFAOYSA-M 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SJZRECIVHVDYJC-UHFFFAOYSA-M 4-hydroxybutyrate Chemical compound OCCCC([O-])=O SJZRECIVHVDYJC-UHFFFAOYSA-M 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 241000283986 Lepus Species 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 230000000496 anti-anoxic effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000287 tissue oxygenation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940072358 xylocaine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
JLa. présente invention concerne des compositions pharmaceutiques contenant un dérivé de naphtyridine, utile dans le .traitement des troubles de la vigilance et des états dépressifs.JLa. The present invention relates to pharmaceutical compositions containing a naphthyridine derivative, useful in the treatment of disorders of alertness and depressive states.
Le dérivé de naphtyridine répond à la formule suivante 5 (I) . Il est obtenu à partir de la tryptamineThe naphthyridine derivative corresponds to the following formula 5 (I). It is obtained from tryptamine
- CH -CH -NH- CH -CH -NH
QçrQc
HH
10 par réaction avec l'acide cétoglutaxique COOH-(C^)2_CO-COOH, suivie d'une cyclisation, en milieu chlorhydrique , dû composé intermédiaire pbtenu10 by reaction with ketoglutaxic acid COOH- (C ^) 2_CO-COOH, followed by cyclization, in hydrochloric medium, due to intermediate compound pbtenu
CjoQ.CjoQ.
? ^COOH? ^ COOH
15 HOOCv^^ cyclisation conduisant au chlorhydrate-du composé (I) que l'on peut obtenir sous forme de base par alcalinisation à l'aide ' de l^CO^· L'exemple suivant illustre la préparation du composé (I).15 HOOCv ^^ cyclization leading to the hydrochloride of the compound (I) which can be obtained in the form of base by alkalization using l ^ CO ^ · The following example illustrates the preparation of the compound (I).
20 Préparation du chlorhydrate d'hexahydro-l,2,3,3a,4,5 6F-indolo £3,2,l-d.eJ£l,5J naphtyridinone-6.Preparation of hexahydro hydrochloride-1,2,3,3a, 4,5 6F-indolo £ 3,2, l-d.eJ £ l, 5J naphthyridinone-6.
1) Condensation de la tryptamine avec 1'acideO^-céto-glutarique.1) Condensation of tryptamine with O ^ -keto-glutaric acid.
A une solution de 73 g (0,456'mole) de tryptamine dans 1000 ml de mëthanol, on ajoute, tout en agitant, 100 g (0,685 mole) 25 d'acideQ^-céto-glutarique et on agite la solution obtenue pendant environ 16 heures S la temnérature du laboratoire. On 2 'concentre le milieu à sic cité ; on reprend le résidu obtenu par 1000 ml d'eau. On es&ore le composé et le sèche.To a solution of 73 g (0.456 mol) of tryptamine in 1000 ml of methanol, 100 g (0.685 mol) of Q-keto-glutaric acid are added, with stirring, and the solution obtained is stirred for approximately 16 hours S the laboratory temperature. 2 'is concentrated the medium to sic cited; the residue obtained is taken up in 1000 ml of water. We are the compound and dry it.
Le composé intermédiaire obtenu fond à 215°C.The intermediate compound obtained melts at 215 ° C.
2ί Cyclisation du composé intermédiaire.2ί Cyclization of the intermediate compound.
\ 5 On agite le mélange réactionnel constitué par 119 g du composé précédent dans 1200 ml d'éthanol. On chauffe la suspension à la température du reflux, puis on fait barboter du gaz HCl rapidement au départ, puis en léger bullage dès la dissolution. On maintient ces conditions pendant 5 heures.The reaction mixture consisting of 119 g of the preceding compound is stirred in 1200 ml of ethanol. The suspension is heated to the reflux temperature, then HCl gas is bubbled rapidly at the start, then by gentle bubbling upon dissolution. These conditions are maintained for 5 hours.
510 En fin de réaction, on refroidit, et filtre le précipité formé au cours de la réaction.510 At the end of the reaction, the mixture is cooled and the precipitate formed during the reaction is filtered.
On isole ainsi le chlorhydrate du composé (I) qui fond à 280°C. Les spectres IR et RMN sont en accord avec la structure.The hydrochloride of compound (I) is thus isolated, which melts at 280 ° C. The IR and NMR spectra are in agreement with the structure.
Pour libérer la base, on dissout le chlorhydrate dans de l'eau 15 et on alcalinise par addition de carbonate de sodium. On obtient un cristallisât qui essoré,fournit le composé (I) sous forme de hase. Il fond à 149°C après recristallisation dans de l'acétate d'éthyle.To release the base, the hydrochloride is dissolved in water and made alkaline by the addition of sodium carbonate. A crystallized product is obtained which is wrung out and provides the compound (I) in the form of a hase. It melts at 149 ° C. after recrystallization from ethyl acetate.
Le composé (I) s'est révélé actif en pharmacologie dans le 20 test de l’hypoxie hypobare.Compound (I) has been shown to be active in pharmacology in the hypobaric hypoxia test.
Hypoxie hypobare.Hypobaric hypoxia.
Des souris de souche CD1 sont maintenues dans une atmosphère appauvrie en oxygène, par réalisation d'un vide partiel (190 | mm de mercure correspondant à 5,25 % d'oxygène).CD1 strain mice are maintained in an oxygen-depleted atmosphere by performing a partial vacuum (190 µm of mercury corresponding to 5.25% oxygen).
25 Le temps de survie des animaux est noté. Ce temps est augmenté : par les agents capables de favoriser l'oxygénation tissulaire j et en particulier cérébrale. Les composés étudiés sont adminis trés, à plusieurs doses, par voie intrapéritonéale, 10 minutes avant l'essai. Les.pourcentages d'augmentation du temps de 30 survie par rapport aux valeurs obtenues chez les animaux témoins sont calculés. La dose active moyenne (DAM), dose qui augmente le temps de survie de 100% est déterminée graphiquement.The survival time of the animals is noted. This time is increased: by agents capable of promoting tissue oxygenation and in particular of the brain. The compounds studied are administered, in several doses, intraperitoneally, 10 minutes before the test. Percentages of increased survival time over values obtained in control animals are calculated. The average active dose (AMD), which increases the survival time by 100%, is determined graphically.
3 * • Cette dose est, pour le composé (I) de 6 à 9 mg/kg.3 * • This dose is, for compound (I), from 6 to 9 mg / kg.
La DA 100 de ce même composé, déterminée par voie orale, est de 21 mg/kg.The AD 100 of this same compound, determined orally, is 21 mg / kg.
De plus l'action du composé sur la durée du sommeil induit 5 par le 4-hÿdroxy-butyrate de sodium chez le rat curarisé a été déterminée.In addition, the action of the compound on the duration of sleep induced by sodium 4-hydroxy-butyrate in the curarized rat was determined.
Les animaux utilisés sont des rats mâles de souche Charles River de 200 + 20 g. Les animaux, curarisés par l'allofërine à raison de 1 mg/kg par voie i.p. sont placés sous respiration > io artificielle à l'aide d'un masque appliqué sur le museau (fréquence respiratoire : 50/minute : volume respiratoire : 14 cc) .The animals used are male rats of the Charles River strain of 200 + 20 g. Animals curarized by allofërine at a rate of 1 mg / kg i.p. are placed under artificial respiration using a mask applied to the muzzle (respiratory rate: 50 / minute: respiratory volume: 14 cc).
*» L'oesophage est préalablement ligaturé afin d'éviter l'entrée de l'air dans l'estomac.* »The esophagus is previously ligated to prevent the entry of air into the stomach.
Des électrodes corticales front-pariétales et occipitales 15 permettent l'enregistrement de l'acitivité électrocorticogra-phique sur un polygraphe Grass modèle 79 P à la vitesse de 6 mm/sec.Front-parietal and occipital cortical electrodes 15 allow the recording of electrocorticographic activity on a Grass model 79 P polygraph at the speed of 6 mm / sec.
La préparation de l'animal est effectuée sous anesthésie locale (xylocaïne à 2%) . .Les rats sont maintenus tout au long 20 de l'expérience à température constante (37°5 C). Dix minutes après la fin de la préparation du rat, une dose de 200 mg/kg de 4-hydroxy-butyrate de Na est injectée par voie intraveineuse au niveau de la queue.The preparation of the animal is carried out under local anesthesia (xylocaine 2%). The rats are maintained throughout the experiment at constant temperature (37 ° C.). Ten minutes after the end of the preparation of the rat, a dose of 200 mg / kg of Na 4-hydroxy-butyrate is injected intravenously into the tail.
Une dose de 30 mg/kg du composé à étudier est administrée par 25 voie intrapêritànéale 3 minutes après l'administration du 4-hydroxy-butyrate de sodium.A dose of 30 mg / kg of the test compound is administered intraperitoneally 3 minutes after administration of sodium 4-hydroxybutyrate.
L'évaluation des tracés s'effectue par période de 15 minutes durant 75 minutes après l'injection de V 15 H‘B". Durant cette période d'analyse, la durée totale du "sommeil" est déterminée. 30 Une série de 15 témoins permet de préciser la durée du "sommeil G H B".The evaluation of the traces is carried out by period of 15 minutes for 75 minutes after the injection of V 15 H'B ". During this period of analysis, the total duration of" sleep "is determined. 30 A series of 15 cookies allows you to specify the duration of "GHB sleep".
L’analyse statistique des résultats est réalisée à l'aide du test "U" de Mann-Whitney.The statistical analysis of the results is carried out using the Mann-Whitney "U" test.
L'écart en % par rapport aux témoins est, pour le composé I, 35 de -38%.The difference in% compared to the controls is, for compound I, 35 of -38%.
4 9 ♦4 9 ♦
Par ailleurs le composé (I) a une DL 50, dose léthale 50 déterminée chez des souris de souche CD1 par méthode graphique, de 110 mg/kg par voie intrapéritonéale.Furthermore, compound (I) has an LD 50, lethal dose 50 determined in mice of CD1 strain by graphic method, of 110 mg / kg intraperitoneally.
Le composé (I) actif dans l'épreuve dhypoxie hypobare chez la 5 souris, possède donc une activité antianoxique et peut être utilisé en thérapeutique pour le traitement des troubles du comportement imputables à des dommages vasculaires cérébraux et à la sclérose cérébrale en gériatrie et pour le traitement * des encéphalopathies métaboliques.The compound (I) active in the hypobaric hypoxia test in mice, therefore has an antianoxic activity and can be used in therapy for the treatment of behavioral disorders attributable to cerebrovascular damage and to cerebral sclerosis in geriatrics and for the treatment * of metabolic encephalopathies.
10 Le composé (I) peut être administré par voie orale sous la forme de comprimés, gélules, capsules, dragées, solutions ou suspensions, ou par voie parentérale sous la forme de soluté.Compound (I) can be administered orally in the form of tablets, capsules, capsules, dragees, solutions or suspensions, or parenterally in the form of a solute.
La posologie quotidienne peut aller de 1 à 100 mg de composé (I).The daily dosage can range from 1 to 100 mg of compound (I).
15 Les compositions pharmaceutiques de l’invention contiennent le composé (I) , éventuellement en mélange avec d'autres substances actives, et les adjuvants, diluants, véhicules ou excipients usuels en pharmacie.The pharmaceutical compositions of the invention contain the compound (I), optionally in admixture with other active substances, and the adjuvants, diluents, vehicles or excipients customary in pharmacies.
La préparation pharmacologique ou galénique est effectuée 20 selon les méthodes classiques.The pharmacological or galenic preparation is carried out according to conventional methods.
* ~ / / -Λ L-'* ~ / / -Λ L- '
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8003011A FR2475394A1 (en) | 1980-02-12 | 1980-02-12 | PHARMACEUTICAL COMPOSITIONS CONTAINING HEXAHYDRO-1, 2, 3, 3A, 4, 5, 6H INDOLO (3, 2, 1 - D. E) (1, 5) NAPHTHYRIDINONE - 6 |
| FR8003011 | 1980-02-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU83128A1 true LU83128A1 (en) | 1982-09-10 |
Family
ID=9238471
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU83128A LU83128A1 (en) | 1980-02-12 | 1981-02-11 | PHARMACEUTICAL COMPOSITIONS CONTAINING A NAPHTYRIDINE DERIVATIVE |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS56127313A (en) |
| AU (1) | AU6714581A (en) |
| BE (1) | BE887468A (en) |
| DE (1) | DE3104884A1 (en) |
| FR (1) | FR2475394A1 (en) |
| GB (1) | GB2068731A (en) |
| IL (1) | IL62114A0 (en) |
| IT (1) | IT1135422B (en) |
| LU (1) | LU83128A1 (en) |
| NL (1) | NL8100645A (en) |
| ZA (1) | ZA81919B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LU84664A1 (en) * | 1983-02-25 | 1984-11-08 | Onmichem S A | ALKYL-4-INDOLONAPHTYRIDINES AND THEIR THERAPEUTIC APPLICATION |
| CA1329597C (en) * | 1986-12-22 | 1994-05-17 | Dagmar Hoeltje | Derivatives of tetrahydropyrido[1,2-a]indole |
| US5189041A (en) * | 1990-11-16 | 1993-02-23 | Syntex (U.S.A.) Inc. | Tricyclic 5-ht3 receptor antagonists |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2358146A1 (en) * | 1976-04-13 | 1978-02-10 | Synthelabo | Indolo-(1,5)-naphthyridine derivs. - having antianoxia and psychotropic activities |
-
1980
- 1980-02-12 FR FR8003011A patent/FR2475394A1/en active Granted
-
1981
- 1981-02-10 AU AU67145/81A patent/AU6714581A/en not_active Abandoned
- 1981-02-11 LU LU83128A patent/LU83128A1/en unknown
- 1981-02-11 ZA ZA00810919A patent/ZA81919B/en unknown
- 1981-02-11 DE DE19813104884 patent/DE3104884A1/en active Pending
- 1981-02-11 BE BE0/203762A patent/BE887468A/en unknown
- 1981-02-11 IT IT19667/81A patent/IT1135422B/en active
- 1981-02-11 GB GB8104135A patent/GB2068731A/en not_active Withdrawn
- 1981-02-11 NL NL8100645A patent/NL8100645A/en not_active Application Discontinuation
- 1981-02-11 IL IL62114A patent/IL62114A0/en unknown
- 1981-02-12 JP JP2000581A patent/JPS56127313A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| NL8100645A (en) | 1981-09-01 |
| GB2068731A (en) | 1981-08-19 |
| FR2475394B1 (en) | 1982-05-21 |
| IL62114A0 (en) | 1981-03-31 |
| FR2475394A1 (en) | 1981-08-14 |
| IT1135422B (en) | 1986-08-20 |
| DE3104884A1 (en) | 1982-01-14 |
| BE887468A (en) | 1981-08-11 |
| ZA81919B (en) | 1982-03-31 |
| JPS56127313A (en) | 1981-10-06 |
| IT8119667A0 (en) | 1981-02-11 |
| AU6714581A (en) | 1981-08-20 |
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