DK168042B1 - COMPONENTS OF QUINOLONCARBOXYLIC ACIDS AND DERIVATIVES THEREOF, A PROCEDURE FOR THEIR PREPARATION AND ORAL BACTERICIDE PREPARATIONS, FEEDING AGENTS AND DRINKING WATER CONTAINING THESE PREPARATIONS AND PREPARING PREPARATIONS - Google Patents
COMPONENTS OF QUINOLONCARBOXYLIC ACIDS AND DERIVATIVES THEREOF, A PROCEDURE FOR THEIR PREPARATION AND ORAL BACTERICIDE PREPARATIONS, FEEDING AGENTS AND DRINKING WATER CONTAINING THESE PREPARATIONS AND PREPARING PREPARATIONS Download PDFInfo
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- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
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- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/105—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups polycyclic
- C07C65/11—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups polycyclic with carboxyl groups on a condensed ring system containing two rings
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- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/105—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups polycyclic
- C07C65/15—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups polycyclic with carboxyl groups on a condensed ring system containing more than two rings
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
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- 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
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- 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
- C07D471/06—Peri-condensed systems
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Description
DK 168042 B1DK 168042 B1
Den foreliggende opfindelse angår hidtil ukendte embonater af quinoloncarboxylsyrer og derivater deraf, en fremgangsmåde til deres fremstilling samt orale bactericide præparater til anvendelse i human- og veterinærmedicinen, 5 fodermidler og drikkevand indeholdende disse forbindelser og en fremgangsmåde til fremstilling af præparaterne.The present invention relates to novel embonates of quinolone carboxylic acids and derivatives thereof, a process for their preparation and oral bactericidal preparations for use in human and veterinary medicine, feed materials and drinking water containing these compounds, and a process for the preparation of the compositions.
Quinoloncarboxylsyrer, derivater deraf og deres salte er allerede kendt, jfr. DE offentliggørelsesskrift nr. 3.033.157. De udmærker sig ved fremragende baktericide egen-10 skaber. Deres orale anvendelse i form af opløsninger, suspensioner eller fodertilblandinger eller i drikkevand er dog begrænset af deres til dels bitre smag. Eksempelvis kan disse virksomme stoffer ikke uden videre gives oralt til dyr, f.eks. svin, med højt udviklet smagssans.Quinolone carboxylic acids, derivatives thereof and their salts are already known, cf. DE Publication No. 3,033,157. They are distinguished by excellent bactericidal properties. However, their oral use in the form of solutions, suspensions or feed additives or in drinking water is limited by their partly bitter taste. For example, these active substances cannot be administered orally to animals, e.g. pigs, with a highly developed sense of taste.
15 Embonsyre og dennes salte med bestemte virksomme stoffer til forhalet frigørelse af virksomt stof er kendt, jfr. US patentskrift nr. 2.397.903 og Pharmazeut. Chemie (E. Schroder et al.), Verlag G. Thieme, Stuttgart 1982, side 932. Det var imidlertid ikke kendt, at embonsyre kunne an-20 vendes til neutralisation af smagen af quinoloncarboxylsyrer og derivater deraf.15 Embonic acid and its salts with certain active substances for delayed release of active substance are known, cf. U.S. Patent No. 2,397,903 and Pharmazeut. Chemie (E. Schroder et al.), Verlag G. Thieme, Stuttgart 1982, page 932. However, it was not known that embonic acid could be used to neutralize the taste of quinolone carboxylic acids and derivatives thereof.
Fra US patentskrift nr. 3.733.410 kendes der farmaceutisk virksomme salte af embonsyren med baser, men ikke med amfotere forbindelser. På overraskende måde danner imid-25 lertid de i det følgende angivne quinoloncarboxylsyrer, selv om de er amfotere, stabile salte med embonsyre.U.S. Patent No. 3,733,410 discloses pharmaceutically effective salts of the embryonic acid with bases, but not with amphoteric compounds. Surprisingly, however, the quinolone carboxylic acids listed below, although amphoteric, form stable salts with embonic acid.
Der er således ifølge opfindelsen tilvejebragt embonater af quinoloncarboxylsyrer og derivater deraf med formlen (I) 30 ^ CH2 X Yn (I) r^rV'0” 35 111 2 DK 168042 B1 i hvilken n betyder 1 eller 2, og Y har den almene formel 5 0 (na)Thus, according to the invention, there are provided embonates of quinolone carboxylic acids and derivatives thereof of formula (I) 30 ^ CH 2 X Yn (I) r 'rV'0' 35 111 2 DK 168042 B1 in which n means 1 or 2 and Y has the general formula 5 (na)
R5-NR5-N
^ A^ A
10 i hvilken R2 betyder hydrogen eller alkyl med 1-4 C-atomer, R5 betyder hydrogen, methyl eller ethyl, 15 R6 betyder hydrogen eller methyl, og R7 betyder hydrogen eller methyl.10 wherein R 2 is hydrogen or alkyl of 1-4 C atoms, R 5 is hydrogen, methyl or ethyl, R 6 is hydrogen or methyl, and R 7 is hydrogen or methyl.
Ifølge opfindelsen har det endvidere vist sig, at embonaterne af quinoloncarboxylsyrer og derivater deraf med formlen (I) 20Furthermore, according to the invention, it has been found that the embonates of quinolone carboxylic acids and derivatives thereof of formula (I)
CH-p y YCH-p y Y
25 Ϊ 2 (I) i hvilken 30 n er 1 eller 2, og Y har den ovenfor angivne formel (Ila), kan fremstilles ved en fremgangsmåde, der er ejendommelig ved, at quinoloncarboxylsyrer og derivater deraf med formlen (Ila) omsættes med embonsyre med formlen (IV) 35 3 DK 168042 B1 9H2 (IV) .25 Ϊ 2 (I) in which 30 n is 1 or 2 and Y has the above formula (IIa) may be prepared by a process characterized by reacting quinolone carboxylic acids and derivatives thereof of formula (IIa) with embonic acid of formula (IV).
ιΓ^Τι^0”ιΓ ^ Τι ^ 0 "
\^\^m;OOH\ ^ \ ^ M; OOH
1010
Det har overraskende vist sig, at de her omhandlede, hidtil ukendte forbindelser i sammenligning med andre salte af quinoloncarboxylsyrer er smagsneutrale. De egner sig derfor fortrinligt til fremstilling af og anvendelse i oralt 15 indgivelige midler i humanmedicinen og veterinærmedicinen. Herudover egner de sig til fremstilling af medicineret dyrefoder eller præparater, der indgives sammen med drikkevand. Desuden kan disse derivater inden for humanmedicinen anvendes til oral indgivelse i form af f.eks. suspensioner, safter 20 og emulsioner i de tilfælde, hvor andre galeniske præparater, f.eks. tabletter eller kapsler, ikke kan anvendes.Surprisingly, it has been found that the compounds of the present invention, in comparison with other salts of quinolone carboxylic acids, are flavor neutral. Therefore, they are ideally suited for the preparation and use of orally administrable agents in human medicine and veterinary medicine. In addition, they are suitable for the manufacture of medicated animal feed or preparations that are administered with drinking water. Furthermore, these derivatives in human medicine can be used for oral administration in the form of e.g. suspensions, juices and emulsions in cases where other galenic preparations, e.g. tablets or capsules, cannot be used.
Opfindelsen angår således orale bactericide præparater til anvendelse inden for det medicinske og veterinærmedicinske område, og disse præparater er ejendommelige ved, at de 25 indeholder de her omhandlede embonater.The invention thus relates to oral bactericidal compositions for use in the medical and veterinary fields, and these compositions are characterized in that they contain the compositions of the present invention.
Fodermidler resp. drikkevand ifølge opfindelsen er tilsvarende ejendommelig(e) ved, at de(t) indeholder mindst ét præparat ifølge opfindelsen.Feed materials or drinking water according to the invention are similarly peculiar in that they contain at least one composition according to the invention.
Opfindelsen angår tillige anvendelsen af de nævnte 30 præparater i koncentrater til fremstilling af orale indgivelsesformer, og opfindelsen angår endelig også en fremgangsmåde til fremstilling af de nævnte præparater, hvilken fremgangsmåde er ejendommelig ved, at de her omhandlede embonater blandes med strække- og/eller fortyndingsmidler.The invention also relates to the use of said compositions in concentrates for the preparation of oral administration forms, and the invention also further relates to a process for the preparation of said compositions, characterized in that the compositions of the present invention are mixed with extenders and / or diluents. .
35 Særlig foretrukket er anvendelsen af de her omhandlede forbindelser inden for veterinærmedicinen.35 Particularly preferred is the use of the compounds of the present invention in veterinary medicine.
4 DK 168042 B14 DK 168042 B1
Dette er så meget mere overraskende, som der ved dannelse af andre salte ikke har kunnet opnås en indflydelse på smagen af quinoloncarboxylsyrer eller derivater deraf.This is all the more surprising, as the formation of other salts has not been able to influence the taste of quinolone carboxylic acids or derivatives thereof.
Specielt skal nævnes embonater af følgende quinolon-5 carboxylsyrer: l-cyclopropyl-6-fluor-l,4-dihydro-4-oxo-7-(1-piperaz inyl-eller 4-methyl- eller 4-ethyl-1-piperaziny 1 -) qu ino1in-3--carboxylsyre samt methyl- og ethylestere af disse forbindelser.In particular, mention should be made of embonates of the following quinolone-5 carboxylic acids: 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl or 4-methyl or 4-ethyl-1-piperazinyl) 1-) qu inolin-3-carboxylic acid as well as methyl and ethyl esters of these compounds.
10 Fremstillingen af embonaterne af quinoloncarboxylsyrer og derivater deraf med formlen (I) sker fortrinsvis ved, at der til quinoloncarboxylsyrer og derivater deraf med formlen (Ila) i et egnet opløsningsmiddel sættes embonsyre og eventuelt opvarmes.The preparation of the embonates of quinolone carboxylic acids and derivatives thereof of formula (I) is preferably effected by the addition of embonic acid to quinolone carboxylic acids and derivatives thereof of formula (Ila) in a suitable solvent.
15 Quinoloncarboxylsyre og embonsyre anvendes herved i forholdet 1:1 eller 1:2. Der anvendes fortrinsvis et overskud af embonsyre på 1-10%, fortrinsvis 1-5%, beregnet på den mængde embonsyre, der er nødvendig for de ovennævnte forhold.Quinolone carboxylic acid and embonic acid are hereby used in a 1: 1 or 1: 2 ratio. Preferably, an excess of embonic acid of 1-10%, preferably 1-5%, is used, based on the amount of embonic acid needed for the above conditions.
Desuden kan saltene af aminoquinoloncarboxylsyrer 20 med stærke syrer, f.eks. saltsyre, methansulfonsyre eller myresyre, omsættes med embonsyrens alkalimetal- eller jord-alkalimetalsalte.In addition, the salts of aminoquinolone carboxylic acids 20 with strong acids, e.g. hydrochloric acid, methanesulfonic acid or formic acid, react with the alkali metal or alkaline earth metal salts of the embonic acid.
Som opløsningsmidler, der kan komme på tale ved omsætningen, kan nævnes indifferente organiske opløsnings-25 midler, såsom alkoholer, f.eks. methanol, ethanol, ethere, såsom diethylether, men også diisopropylether, glycolethere, såsom glycolmonomethylether, carbonhydrider, såsom petroleums-ether, toluen, benzen, xylen og endvidere vand.As solvents that may be encountered in the reaction may be mentioned inert organic solvents such as alcohols, e.g. methanol, ethanol, ethers such as diethyl ether, but also diisopropyl ether, glycol ethers such as glycol monomethyl ether, hydrocarbons such as petroleum ether, toluene, benzene, xylene and further water.
Omsætningen sker ved en temperatur på 20 til 150 "C.The reaction is carried out at a temperature of 20 to 150 ° C.
30 Fortrinsvis arbejdes ved opløsningsmidlets kogepunktstemperatur. Det er også muligt at gennemføre omsætningen ved stuetemperatur .Preferably, the boiling temperature of the solvent is worked. It is also possible to carry out the reaction at room temperature.
De virksomme stoffer anvendes fortrinsvis i form af præparater, der er egnet til oral indgivelse til menne-35 sker og dyr.The active substances are preferably used in the form of compositions suitable for oral administration to humans and animals.
0 5 DK 168042 B1 Sådanne præparater er følgende:0 5 DK 168042 B1 Such preparations are as follows:
Orale opløsninger, koncentrater til oral indgivelse efter fortynding, emulsioner og suspensioner til oral indgivelse, 5 præparater, hvori det virksomme stof er indarbejdet i et salvegrundlag eller i et olie-i-vand- eller vand-i-olie-emulsionsgrundlag, faste præparater som pulvere, præmixer eller koncentrater, granulater, pellets, tabletter, boli og kapsler.Oral solutions, concentrates for oral administration after dilution, emulsions and suspensions for oral administration, 5 compositions in which the active substance is incorporated in an ointment base or in an oil-in-water or water-in-oil emulsion base, solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, boli and capsules.
-io Orale opløsninger kan fremstilles ved, at det virksomme stof opløses i et egnet opløsningsmiddel, og der eventuelt tilsættes tilsætninger, såsom opløsningsformidlende stoffer, syrer, baser, pufferstoffer, anti-oxidanter og konserveringsmidler. Opløsningen filtreres 15 og aftappes eventuelt sterilt.Oral solutions can be prepared by dissolving the active ingredient in a suitable solvent and optionally adding additives such as solvents, acids, bases, buffers, antioxidants and preservatives. The solution is filtered and optionally drained sterile.
Som opløsningsmidler kan nævnes: fysiologisk acceptable opløsningsmidler, såsom vand, alkohol, ethanol, butanol, benzylalkohol, glycerol, propylen-alkohol, polyethylenglycol, N-alkyl-pyrrolidon samt 20 blandinger deraf.Solvents include: physiologically acceptable solvents such as water, alcohol, ethanol, butanol, benzyl alcohol, glycerol, propylene alcohol, polyethylene glycol, N-alkyl pyrrolidone, and 20 mixtures thereof.
De virksomme stoffer kan eventuelt også opløses i fysiologisk acceptable vegetabilske eller syntetiske olier.The active substances may also be dissolved in physiologically acceptable vegetable or synthetic oils.
Som opløsningsformidlende stoffer kan nævnes: 25 opløsningsmidler, der fremmer opløsningen af det virksomme stof eller hindrer udfældning af dette, f.eks. polyvinylpyrrolidon, polyoxyethyleret ricinusolie og polyoxyethylerede sorbitanestere.Solvent agents include: 25 solvents which promote the dissolution of the active substance or prevent the precipitation thereof, e.g. polyvinylpyrrolidone, polyoxyethylated castor oil and polyoxyethylated sorbitan esters.
Konserveringsmidler er f.eks. benzylalkohol, tri-30 chlorbutanol, p-hydroxybenzoesyreester.Preservatives are e.g. benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester.
Orale opløsninger anvendes direkte. Koncentrater anvendes oralt efter forudgående fortynding til anvendelseskoncentrationen .Oral solutions are used directly. Concentrates are used orally after prior dilution to the application concentration.
Oralt anvendelige emulsioner er enten af vand-i- -olie-typen eller olie-vand-typen.Orally applicable emulsions are either water-in-oil type or oil-water type.
35 6 DK 168042 B1 0 De^ fremstilles ved, at man opløser det virksomme stof i en fase og homogeniserer denne ved hjælp af egnede emulgatorer og eventuelt yderligere hjælpestoffer, såsom farvestoffer, resorptionsfremmende stoffer, konserveringsmidler, antioxidanter, lysbeskyttelses- 5 midler-og viskositetsforøgende stoffer.They are prepared by dissolving the active substance in a phase and homogenizing it by suitable emulsifiers and optionally additional adjuvants such as dyes, resorbents, preservatives, antioxidants, light preservatives and viscosity enhancers. substances.
Som hydrofob fase (olie) kan nævnes: paraffinolier, siliconeolier, naturlige planteolier, såsom sesamolie, mandelolie, ricinusolie, syntetiske trigly-cerider, såsom capryl/caprinsyre-biglycerid, triglycerid-10 blandinger med plantefedtsyrer med en kædelængde på 8-12 carbonatomer eller andre specielt udvalgte naturlige fedtsyrer, partialglyceridblandinger af mættede eller umættede, eventuelt også hydroxylgruppe-holdige fedtsyrer, mono- og diglycerider af Cg_-^q-fedtsyrer, 15Hydrophobic phase (oil) may be mentioned: paraffin oils, silicone oils, natural plant oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid biglyceride, triglyceride mixtures with plant fatty acids having a chain length of 8-12 carbonates other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated, optionally also hydroxyl group-containing fatty acids, mono- and diglycerides of Cg _- fatty acids, 15
Fedtsyreestere, såsom ethylstearat, di-n-butyl--adipat, laurinsyrehexylester, dipropylen-glycolpelargonat, estere af en forgrebet fedtsyre med middel kædelængde med mættede C^g_^g-fedtalkoholer, isopropylmyristat, ^ isopropylpalmitat, capryl/caprinsyreestere af mættede fedtalkoholer med en kædelængde på 12-18 carbonatomer, isopropylstearat, oliesyreoleylester, oliesyredecylester, ethyloleat, mælkesyreethylester, voksagtige fedtsyreestere, såsom kunstigt andegatkirtelfedt, dibutyl- phthalat, adipinsyrediisopropylester og esterblandinger 25 beslægtet med sidstnævnte.Fatty acid esters such as ethyl stearate, di-n-butyl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, esters of a mid-chain fatty acid saturated fatty acid with saturated C a chain length of 12-18 carbon atoms, isopropyl stearate, oleic acid oleic ester, oleic acid decyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as artificial duck gland fat, dibutyl phthalate, adipic acid diisopropyl ester and ester mixtures.
Fedtalkoholer, såsom isotridecylalkohol, 2-octyl-dodecanol, cetylstearyl-alkohol og oleylalkohol.Fatty alcohols such as isotridecyl alcohol, 2-octyl dodecanol, cetylstearyl alcohol and oleyl alcohol.
Fedtsyrer, f.eks. oliesyre, og deres blandinger.Fatty acids, e.g. oleic acid, and their mixtures.
Som hydrofil fase kan nævnes: vand, alkoholer f.eks. propylenglycol, glycerol, sorbitol og blandinger deraf.As hydrophilic phase can be mentioned: water, alcohols e.g. propylene glycol, glycerol, sorbitol and mixtures thereof.
Som emulgatorer kan nævnes: tensider (omfattende emulgatorer og befugtningsmidler) , såsom 35 DK 168042 B1 0 7 1. ikke-ionogene emulgatorer, f.eks. polyoxyethyleret ricinusolie, polyoxyethyleret sorbitan-mono-oleat, sorbitanmonostearat, ethylalkohol, glycerol-mono-stearat, polyoxyethylstearat, alkylphenolpolyglycolethere, 5 2. amfolytiske emulgatorer, såsom di-Na-N-lauryl-3-imino- -dipropionat eller lecithin, 3. anionaktive emulgatorer, såsom Na-laurylsulfat, fedtalkoholethersulfater, mono/dialkylpolyglycol-etherorthophosphorsyreester-monoethanolaminsalt, 10 4. kationaktive emulgatorer, såsom cetyltrimethylammonium- chlorid.As emulsifiers may be mentioned: surfactants (comprising emulsifiers and wetting agents) such as non-ionic emulsifiers, e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan mono oleate, sorbitan monostearate, ethyl alcohol, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ethers, 2. ampholytic emulsifiers such as di-Na-N-lauryl-3-imino-dipropionate anionic emulsifiers such as Na-lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt, cation-active emulsifiers such as cetyltrimethylammonium chloride.
Egnede som yderligere hjælpestoffer er viskositetsforøgende og emulsionsstabiliserende stoffer, såsom carboxyiuethylcellulose, methylcellulose og andre cellulose-15 og stivelses-derivater, polyacrylater, alginater, gelatine, gummiarabicum, polyvinylpyrrolidon, polyvinylalkohol, copolymere af methylvinylether og maleinsyreanhydrid, polyethylenglycoler og voksarter, kolloid kiselsyre eller blandinger af de angivne stoffer.Suitable as further adjuvants are viscosity enhancers and emulsion stabilizers such as carboxyethyl cellulose, methyl cellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, methyl vinyl alcohol and polyhydric alcohols of the specified substances.
20 Oralt anvendelige suspensioner fremstilles ved at suspendere det virksomme stof i en bærevæske, eventuelt under tilsætning af yderligere hjælpestoffer, såsom fugte-midler, farvestoffer, resorptionsfremmende stoffer, konserveringsstoffer, antioxidanter og lysbeskyttelsesmidler.Orally usable suspensions are prepared by suspending the active substance in a carrier liquid, optionally with the addition of additional adjuvants such as wetting agents, dyes, resorbents, preservatives, antioxidants and light preservatives.
25 Som bærevæsker skal nævnes alle homogene opløsningsmidler og opløsningsmiddelblandinger.25 As carrier fluids, all homogeneous solvents and solvent mixtures should be mentioned.
Som fugtemidler (dispergeringsmidler) skal nævnes: Tensider (omfattende emulgatorer og fugtemidler) , såsom 30 1. anionaktive tensider, f.eks. Na-laurylsulfat, fedt- alkoholethersulfater, mono/dialkylpolyglycoletherortho-phosphorsyreester-monoethanolaminsalt, ligninsulfonater eller dioctylsulfosuccinat, 2. kationaktive tensider, f.eks. cetyltrimethylammonium- 35 chlorid, 0 8 DK 168042 B1 3. amfolytiske tensider, f.eks. di-Na-N-lauryl-3-iminodipro-pionat eller lecithin, 4. ikke-ionogene tensider, f.eks. polyoxyethyleret ricinusolie, polyoxyethyleret sorbitan-monooleat, sorbitan- -monostearat, ethylalkohol, glycerolmonostearat, 5 polyoxyethylenstearat, alkylphenolpolyglycolethere og "Pluronic ® "As wetting agents (dispersants) are to be mentioned: surfactants (comprising emulsifiers and wetting agents), such as 30 anionic surfactants, e.g. NaLauryl sulphate, fatty alcohol ether sulphates, mono / dialkyl polyglycol ether ortho phosphoric acid ester monoethanolamine salt, lignin sulphonates or dioctyl sulphosuccinate, 2nd cationic surfactants, e.g. cetyltrimethylammonium chloride, ampholytic surfactants, e.g. di-Na-N-lauryl-3-iminodipropionate or lecithin; 4. nonionic surfactants, e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, ethyl alcohol, glycerol monostearate, polyoxyethylene stearate, alkylphenol polyglycol ethers and "Pluronic®"
Som yderligere hjælpestoffer kan nævnes de ovenfor angivne.Additional aids may be mentioned above.
Halvfaste oralt indgivelige præparater adskiller sig kun fra de ovenfor beskrevne suspensioner og emulsioner ved deres højere viskositet.Semi-solid orally administered preparations differ only from the above-described suspensions and emulsions at their higher viscosity.
Til fremstilling af faste præparater blandes det virksomme stof med egnede bærestoffer, eventuelt under tilsætning af hjælpestoffer og bringes på den ønskede 10 form.To prepare solid compositions, the active substance is mixed with suitable carriers, optionally with the addition of excipients, and brought to the desired shape.
Som bærestoffer kan nævnes alle fysiologisk acceptable faste indifferente stoffer. Som sådanne anvendes uorganiske og organiske stoffer. Uorganiske 2o stoffer er f.eks. natriumchlorid, carbonater som cal-ciumcarbonat, hydrogencarbonater, aluminiumoxider, kiselsyrer, lerjordarter, fældet eller kolloidt siliciumoxid og phosphater.Carriers include all physiologically acceptable solid inert substances. As such, inorganic and organic substances are used. Inorganic 2O substances are e.g. sodium chloride, carbonates such as calcium carbonate, hydrogen carbonates, alumina, silica, clay soils, precipitated or colloidal silica and phosphates.
Organiske stoffer er f.eks. sukker, cellulose, 25 nærings- og fodermidler, såsom mælkepulver, kødmel, korn-mel-og-skrå, stivelse.Organic substances are e.g. sugar, cellulose, 25 foods and feedstuffs such as milk powder, meat flour, cereal flour and slant, starch.
Hjælpestoffer er konserveringsstoffer, antioxi-danter og farvestoffer, der allerede er anført ovenfor.Excipients are preservatives, antioxidants and dyes already listed above.
Yderligere egnede hjælpestoffer er smøremidler, 30 f.eks. magnesiumstearat, stearinsyre, talkum, bentoniter, smuldringsfremmende substanser, såsom stivelse eller tværbundet polyvinylpyrrolidon, bindemidler, f.eks. stivelse, gelatine eller lineært polyvinylpyrrolidon, samt tørbindemidler, såsom mikrokrystallinsk cellulose.Further suitable auxiliaries are lubricants, e.g. magnesium stearate, stearic acid, talc, bentonites, crumb promoting substances such as starch or cross-linked polyvinylpyrrolidone, binders, e.g. starch, gelatin or linear polyvinylpyrrolidone, as well as dry binders such as microcrystalline cellulose.
35 De virksomme stoffer kan i form af deres oven- 9 o DK 168042 B1 nævnte faste eller flydende præparater også foreligge indkapslet. Det kan også være fordelagtigt at anvende de virksomme stoffer i præparater, der frigør det virksomme stof med forsinkelse.The active substances may also be encapsulated in the form of their solid or liquid preparations mentioned above. It may also be advantageous to use the active substances in preparations which release the active substance with delay.
5 Indgivelsen af de virksomme stoffer sker fortrins vis sammen med foderet og/eller drikkevandet.5 The administration of the active substances is preferably done together with the feed and / or the drinking water.
Til foder hører enkelt-fodermidler af vegetabilsk oprindelse, såsom hø, roer, korn og kornbiprodukter, enkelt-fodermidler af animalsk oprindelse, såsom kød, 10 fedt, mælkeprodukter, benmel og fiskeprodukter, desuden enkeltfodermidler som vitaminer, proteiner, aminosyrer, f.eks. DL-methionin, salte, såsom calciumcarbonat og natriumchlorid. Til foder regnes også tilskuds-, færdig-og blandingsfodermidler. Disse indeholder enkeltfodermidler 15 i en sammensætning, der sikrer en afstemt ernæring med hensyn til energi- og proteinforsyning såvel som til forsyning af vitaminer, mineralsalte og sporelementer .Forage includes single feedingstuffs of vegetable origin, such as hay, beets, cereals and cereal by-products, single feedingstuffs of animal origin such as meat, fat, dairy products, bone meal and fish products, as well as single feedingstuffs such as vitamins, proteins, amino acids, e.g. . DL-methionine, salts such as calcium carbonate and sodium chloride. Supplements, ready-made and mixed feed are also included in the feed. These contain single feed ingredients 15 in a composition that ensures a balanced nutrition in energy and protein supply as well as in the supply of vitamins, mineral salts and trace elements.
Koncentrationen af det virksomme stof i foderet 20 udgør normalt ca. 0,01 - 500 dpm, fortrinsvis 0,1 - 50 dpm.The concentration of the active substance in the feed 20 usually amounts to approx. 0.01 to 500 ppm, preferably 0.1 to 50 ppm.
De virksomme stoffer kan sættes til foderet som sådanne eller i form af præmixer eller foderkoncentrater.The active substances can be added to the feed as such or in the form of premixes or concentrates.
Præmixer og foderkoncentrater er blandinger af det virksomme stof med et egnet bærestof. Til bærestof-25 ferne hører enkeltfodermidler eller blandinger deraf.Premixes and feed concentrates are mixtures of the active substance with a suitable carrier. The carriers include single feed agents or mixtures thereof.
De kan desuden indeholde yderligere hjælpestoffer, f.eks. stoffer, der regulerer strømmeevnen og blandbarheden, f.eks. kiselsyrer, bentoniter, ligninsulfonater. Derudover kan der være tilsat antioxidanter, såsom BHT, 30 eller konserveringsmidler, såsom sorbinsyre eller calciumpr opionat.They may also contain additional excipients, e.g. substances that regulate flowability and miscibility, e.g. silicic acids, bentonites, lignin sulfonates. In addition, antioxidants such as BHT, or preservatives such as sorbic acid or calcium propionate may be added.
Koncentrater, der indgives via drikkevand, skal præpareres således, at der ved blandingen med drikkevandet dannes en klar opløsning eller en homogen suspension.Concentrates administered via drinking water must be prepared so that a clear solution or homogeneous suspension is formed in the mixture with the drinking water.
35 Egnede bærestoffer er således vandopløselige o 10 DK 168042 B1 substanser (fodertilsætningsmidler), såsom sukker eller salte (f.eks. citrater, phosphater, natriumchlorid, natriumcarbonat) .Thus, suitable carriers are water-soluble substances (feed additives) such as sugars or salts (e.g., citrates, phosphates, sodium chloride, sodium carbonate).
Disse kan ligeledes indeholde antioxidanter og 5 konserveringsmidler.These may also contain antioxidants and preservatives.
De virksomme stoffer kan foreligge alene i præparaterne eller i blanding med andre virksomme stoffer, mineralsalte, sporelementer, vitaminer, proteiner, farvestoffer, fedtstoffer eller smagsstoffer.The active substances may be present alone in the compositions or in admixture with other active substances, mineral salts, trace elements, vitamins, proteins, dyes, fats or flavors.
10 De virksomme stoffer har virkning over for human- og dyrepathogene mikroorganismer.10 The active substances have an effect on human and animal pathogenic microorganisms.
Til disse hører: 1. Spirochaetaceae (f.eks. Treponema, Leptospira, Borrelia), 2. Spirillaceae, 15 3. Micrococcaceae (f.eks. Staphylococcer af biotype A-F,These include: 1. Spirochaetaceae (e.g., Treponema, Leptospira, Borrelia), 2. Spirillaceae, 3. 3. Micrococcaceae (e.g., Staphylococci of biotype A-F,
St. hyicus), 4. Streptococcaceae (f.eks. Streptococcus uberis, Str. egui, Str. agalactiae, Str. dysgalactiae, Streptokokker af Lancefield type A-N), 20 5. Pseudomonaceae (f.eks. Pseudomonas malei, Ps. cepacia,St. hyicus), 4. Streptococcaceae (e.g., Streptococcus uberis, Str. egui, Str. agalactiae, Str. dysgalactiae, Streptococcus of Lancefield type A-N), 20 5. Pseudomonaceae (e.g., Pseudomonas malei, Ps. cepacia,
Ps. aeruginosa, Ps. maltophilia),Ps. aeruginosa, Ps. maltophilia),
Brucella, såsom Brucella abortus, B. melitensis. B. suis, Bordetella, såsom Bordetella bronchiseptica, Moraxella, Acinetobacter), 25 6. Enterobactericeae (f.eks. Salmonella type B-E, Shigella, E. coli, Klebsiella, Proteus, Citrobacter, Edwardsiella, Hæmophilus, Providencia, Yersinia)., 7. Vibrionaceae (f.eks. Vibrio, såsom Vibrio cholerae),Brucella, such as Brucella abortus, B. melitensis. B. suis, Bordetella, such as Bordetella bronchiseptica, Moraxella, Acinetobacter), 6. Enterobactericeae (e.g., Salmonella type BE, Shigella, E. coli, Klebsiella, Proteus, Citrobacter, Edwardsiella, Hemophilus, Providencia, Yersinia). 7. Vibrionaceae (e.g., Vibrio, such as Vibrio cholerae),
Pasteurella, såsom Pasteurella multocida, Aeromonas, 30Pasteurella, such as Pasteurella multocida, Aeromonas, 30
Actmobacillus, Streptobacillus, 8. Bacteroidaceae (f.eks. Bacteroides, Fusobacterium), 9. Erysiphylotrix, Listeria, såsom Listeria monocytogenes, 10. Bacillaceae (f.eks. Bacillus, Clostridium type A-D, såsom Clostridium perfringens), Lactobacillaceae, såsom 35 anaerobe kokker, f.eks. Peptostreptokokker og peptokokker, o 11 DK 168042 B1 11. Coryneforme bakterier (f.eks. Corynebacterium pyogenes), 12. Mycobacteriaceae (f.eks. Mycobacterium bovis, avium, M. tuberculosis), 13. Actinomyceae (f.eks. Actinomyces bovis, A. israelii), 5 14. Norcardiaceae (f.eks. forcardia facinica, N. asteroides), 15. Rickettsiaceae (f.eks. Coxiella, Rickettsia), 16. Bartonellaceae (f.eks. Bartonella), 17. Chlamydiaceae (f.eks. Chlamydia psittaci), 18. Mycoplasmataceae (f.eks. Mycoplasma mycoides, 10 M. agalactiae, M. gallisepticum).Actmobacillus, Streptobacillus, 8. Bacteroidaceae (e.g., Bacteroides, Fusobacterium), 9. Erysiphylotrix, Listeria, such as Listeria monocytogenes, 10. Bacillaceae (e.g., Bacillus, Clostridium type AD, such as Clostridium perfringens), Lactobacillaceae, anaerobic cooks, e.g. Peptostreptococci and peptococci, 11. Coryneform bacteria (eg Corynebacterium pyogenes), 12. Mycobacteriaceae (eg Mycobacterium bovis, avium, M. tuberculosis), 13. Actinomyceae (eg Actinomyces bovis , A. israelii), 5 14. Norcardiaceae (e.g., forcardia facinica, N. asteroides), 15. Rickettsiaceae (e.g., Coxiella, Rickettsia), 16. Bartonellaceae (e.g., Bartonella), 17. Chlamydiaceae (e.g., Chlamydia psittaci), 18. Mycoplasmataceae (e.g., Mycoplasma mycoides, 10 M. agalactiae, M. gallisepticum).
Human- og dyrepatogene mikroorganismer kan fremkalde følgende sygdomsbilleder som mono- eller blandingsinfektioner i følgende organsystemer hos dyr.Human and animal pathogenic microorganisms can induce the following disease images as mono- or compound infections in the following organ systems in animals.
Lunger og trachealrum (brysthule), fordøjelses-15 systemer, såsom mave og tarm, bryst og yver, genitalsystemet, såsom uterus, bløddele, såsom hud, muskler, negle, kløer, hove, det aktive og passive bevægelsesapparat, såsom knogler, muskler, sener, led, urogenitalsystemet, såsom nyrer, urinleder, urinrør, nervesystemet, 20 ørerne og øjnene.Lungs and tracheal space (thoracic cavity), digestive systems such as stomach and intestines, breast and udder, genital system such as uterus, soft parts such as skin, muscles, nails, claws, hooves, the active and passive movement apparatus such as bones, muscles, tendons, joints, urogenital system, such as kidneys, ureter, urethra, nervous system, 20 ears and eyes.
Som allerede nævnt anvendes de virksomme stoffer til bekæmpelse af bakterielle sygdomme hos mennesker og dyr.As already mentioned, the active substances are used to control bacterial diseases in humans and animals.
Til dyr hører: 25 pattedyr, f.eks. kvæg, heste, svin, får, geder, hunde, katte, kameler, pelsdyr, såsom nertz, chinchilla, dyr i zoologiske haver og laboratoriedyr, f.eks, mus og rotter, fugle, f.eks. gæs, høns, kalkuner, ænder, duer, 30 zoologiske fugle, laboratoriefugle, f.eks. papegøjer og undulater, fisk, f.eks. karper, foreller, laks, suder, ål, endvidere prydfisk og akvariefisk, krybdyr, f.eks. krokodiller og slanger.Animals include: 25 mammals, e.g. cattle, horses, pigs, sheep, goats, dogs, cats, camels, fur animals such as nertz, chinchillas, zoos and laboratory animals, eg, mice and rats, birds, e.g. geese, chickens, turkeys, ducks, pigeons, 30 zoos, laboratory birds, e.g. parrots and budgies, fish, e.g. carp, trout, salmon, south, eel, ornamental and aquarium fish, reptiles, e.g. crocodiles and snakes.
35 Til bakterielle sygdomme hos dyr hører f.eks.35 Bacterial diseases in animals include e.g.
svinedysenteri, f jerkræspirochastosis, leptospirose hos DK 168042 B1 0 12 kvæg, svin, hest og hund, campylobacter-enteritis hos kvæg, champylobacter-abort hos får og svin, campylobacter--hepatitis hos høns, hudinfektioner, pyodermier hos hund, otitis externa, mastitis hos kvæg, får og ged, 5 streptokokmastitis, streptokokinfektioner hos hest, svin og andre dyr, pneumokokinfektion hos kalve, og hos andre dyr, malleus, konjunktivitis, enteriti, pneumonier, brucellose hos kvæg, får, svin, rhinitis atroficans hos svin, salmonellose hos kvæg, hest, får, høne og andre 10 dyr, septikæmier, eschericia-coli infektion hos svin, metritis-mastitis-agalacti-(MMA)-syndrom, klebsiella--infektioner, pseudotuberkulose, infektiøs pleuropneumoni, primære pasteurelloser, fødselslammelse, nekrobacillose hos kvæg og husdyr, leptospirose, rosen hos svin og 15 andre dyrearter, listeriose, miltbrand, clostridioser, tetanusinfektioner, botulisme, infektioner med coryne-bacterium pyogenes, tuberkulose hos kvæg, svin, fjerkræ, og andre dyrearter, paratuberkulose hos drøvtyggere, norkardiose, Q-feber, ornitosepsittacosis, encephalomye-20 litis, mykoplasmose hos kvæg og andre dyr, enzootisk pneumoni hos svin.swine dysentery, ferocarpirochastosis, leptospirosis in DK 168042 B1 0 12 cattle, pigs, horses and dogs, campylobacter enteritis in cattle, champylobacter abortion in sheep and pigs, campylobacter - hepatitis in chickens, skin infections, pyodermas in dogs, otitis cattle, sheep and goat mastitis, 5 streptococcal mastitis, streptococcal infections in horses, pigs and other animals, pneumococcal infection in calves, and in other animals, malleus, conjunctivitis, enteritis, pneumonias, brucellosis in cattle, sheep, pigs, rhinitis atrophicans salmonellosis in cattle, horses, sheep, hens and other 10 animals, septicemia, swine eschicia coli infection, metritis-mastitis-agalacti (MMA) syndrome, klebsiella infections, pseudotuberculosis, infectious pleuropneumonia, primary pasteurellosis, paralysis, necrobacilosis in cattle and livestock, leptospirosis, pig in pigs and 15 other animal species, listeriosis, anthrax, clostridiosis, tetanus infections, botulism, infections with coryne-bacterium pyogenes, tube rculose in cattle, pigs, poultry, and other animal species, paratuberculosis in ruminants, norcardiosis, Q fever, ornithocepsittacosis, encephalomyelitis, mycoplasmosis in cattle and other animals, enzootic pneumonia in pigs.
25 30 35 0 13 DK 168042 B125 30 35 0 13 DK 168042 B1
Eksempel 1 Salt AExample 1 Salt A
(n i formel (I) er 1) 5(n in formula (I) is 1) 5
En suspension af 62,1 g (0,173 mol) 1-cyclopropyl--6-fluor-l, 4-dihydro-4-oxo-7- (4-ethyl-l-piperazinyl)-quino-lin-3-carboxylsyre og 67,3 g (0,173 mol) embonsyre ("pamoic acid", 4,4-methylen-bis-(3-hydroxy)-2-naphtoe-10 syre, Fluka nr. 45150) tilbagesvales i 800 ml glycolmono-methylether i 30 minutter. Bundfaldet fraskilles kolde ved sugning, vaskes med ethanol og tørres til konstant vægt ved 120°C under vakuum. Der fås 127,6 g (98,6% af det teoretiske) af salt A med sønderdelingspunktet 15 232-235°C.A suspension of 62.1 g (0.173 mol) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (4-ethyl-1-piperazinyl) quinoline-3-carboxylic acid and 67.3 g (0.173 mole) of embonic acid ("pamoic acid", 4,4-methylene-bis- (3-hydroxy) -2-naphthoic acid, Fluka No. 45150) is refluxed in 800 ml of glycol monomethyl ether for 30 minutes. minutes. The precipitate is separated cold by suction, washed with ethanol and dried to constant weight at 120 ° C under vacuum. 127.6 g (98.6% of theory) of salt A are obtained with the decomposition point of 15 232-235 ° C.
Eksempel 2Example 2
Salt BSalt B
20 (n i formel (I) er 2)(N of formula (I) is 2)
En suspension af 71,8 g (0,2 mol) l-cyclopropyl-6--fluor-1,4-dihydro-4-oxo-7-(4-ethyl-l-piperazinyl)-quino-lin-3-carboxylsyre (1) og 40 g (0,103 mol) embonsyre (2) 25 i 500 ml glycolmonomethylether tilbagesvales i 1 time.A suspension of 71.8 g (0.2 mole) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (4-ethyl-1-piperazinyl) -quino-lin-3 carboxylic acid (1) and 40 g (0.103 mol) of embonic acid (2) in 500 ml of glycol monomethyl ether are refluxed for 1 hour.
Bundfaldet fraskilles koldt ved sugning, udvaskes med ethanol og tørres til konstant vægt ved 120°C under vakuum. Der fås 107,2 g (96,9% af det teoretiske udbytte) af salt B ved sønderdelingspunktet 226-228°C.The precipitate is cold separated by suction, washed with ethanol and dried to constant weight at 120 ° C under vacuum. 107.2 g (96.9% of theoretical yield) of salt B is obtained at decomposition point 226-228 ° C.
30 C% H% N% F%30% C% H% N% F%
Analyse for c6iH60F2N6°12 (1106)Analysis for c16 H60 F2 N6 ° 12 (1106)
Beregnet: 66,16 5,42 7,59 3,43Calcd: 66.16 5.42 7.59 3.43
Fundet: 66,0 5,6 7,5 3,4 35 DK 168042 B1 0 14Found: 66.0 5.6 7.5 3.4 DK 168042 B1 0 14
Analogt med de ovennævnte forskrifter fremstilles følgende salte af l-cyclopropyl-6-fluor-l,4-dihydro-4--oxo-7-(4-ethyl-l-piperazinyl)quinolincarboxylsyre: salte med baserne NaOH, KOH og CaiOH^* og salte med syrerne 5 HC1, HBr, HN03/ CH3S03H og CH3COOH.By analogy to the above-mentioned regulations, the following salts are prepared from 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (4-ethyl-1-piperazinyl) quinoline carboxylic acid: salts with the bases NaOH, KOH and CaiOH * and salts with the acids 5 HCl, HBr, HNO 3 / CH 3 SO 3 H and CH 3 COOH.
Alle disse salte udviser ved en gennemført smagsprøve en tydeligt bitter smag.All these salts exhibit a distinctly bitter taste upon completion of a taste test.
Saltene i eksempel 1 og 2 udviser derimod ingen smag.The salts of Examples 1 and 2, on the other hand, exhibit no taste.
10 15 20 25 30 3510 15 20 25 30 35
Claims (11)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3525335 | 1985-07-16 | ||
| DE19853525335 DE3525335A1 (en) | 1985-07-16 | 1985-07-16 | EMBONATES OF CHINOLON CARBONIC ACIDS AND THEIR DERIVATIVES |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK335386D0 DK335386D0 (en) | 1986-07-15 |
| DK335386A DK335386A (en) | 1987-01-17 |
| DK168042B1 true DK168042B1 (en) | 1994-01-24 |
Family
ID=6275883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK335386A DK168042B1 (en) | 1985-07-16 | 1986-07-15 | COMPONENTS OF QUINOLONCARBOXYLIC ACIDS AND DERIVATIVES THEREOF, A PROCEDURE FOR THEIR PREPARATION AND ORAL BACTERICIDE PREPARATIONS, FEEDING AGENTS AND DRINKING WATER CONTAINING THESE PREPARATIONS AND PREPARING PREPARATIONS |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0209000B1 (en) |
| JP (1) | JPH0772177B2 (en) |
| KR (1) | KR940002823B1 (en) |
| AR (1) | AR242570A1 (en) |
| AT (1) | ATE55600T1 (en) |
| AU (1) | AU582255B2 (en) |
| BR (1) | BR8603333A (en) |
| CA (1) | CA1262350A (en) |
| CS (1) | CS255878B2 (en) |
| DE (2) | DE3525335A1 (en) |
| DK (1) | DK168042B1 (en) |
| ES (1) | ES2000678A6 (en) |
| FI (1) | FI88389C (en) |
| GR (1) | GR861823B (en) |
| HU (1) | HU194151B (en) |
| IE (1) | IE58750B1 (en) |
| IL (1) | IL79399A (en) |
| NZ (1) | NZ216815A (en) |
| PL (1) | PL149651B1 (en) |
| ZA (1) | ZA865256B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3705621C2 (en) * | 1986-02-25 | 1997-01-09 | Otsuka Pharma Co Ltd | Heterocyclic substituted quinolonecarboxylic acid derivatives |
| DE19633480A1 (en) * | 1996-08-20 | 1998-02-26 | Bayer Ag | Orally administrable formulations of quinolone and naphthyridonecarboxylic acids |
| KR101173696B1 (en) * | 2003-02-10 | 2012-08-13 | 바이엘 파마 악티엔게젤샤프트 | Treatment of bacterial diseases of the respiratory organs by locally applying fluoroquinolones |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2397903A (en) * | 1944-09-19 | 1946-04-02 | Vick Chemical Company | Methylene-bis-2 hydroxy-3 naphthoates |
| US2641610A (en) * | 1950-10-27 | 1953-06-09 | May & Baker Ltd | Quaternary ammonium salts |
| JPS5762259A (en) * | 1980-09-05 | 1982-04-15 | Kyorin Pharmaceut Co Ltd | Preparation of substituted quinolinecarboxylic acid derivative |
| US4382937A (en) * | 1981-02-27 | 1983-05-10 | Dainippon Pharmaceutical Co., Ltd. | Naphthyridine derivatives and their use as anti-bacterials |
| HU188181B (en) * | 1981-06-11 | 1986-03-28 | Warner-Lambert Co,Us | Process for producing salts of naphtiridine and quinoline compounds of antimicrobial activity |
| DE3525108A1 (en) * | 1985-06-07 | 1986-12-11 | Bayer Ag, 5090 Leverkusen | ANTIBACTERIAL EFFECT OF CHINOLON CARBON ACID ESTERS |
-
1985
- 1985-07-16 DE DE19853525335 patent/DE3525335A1/en not_active Withdrawn
-
1986
- 1986-07-02 EP EP86109036A patent/EP0209000B1/en not_active Expired - Lifetime
- 1986-07-02 AT AT86109036T patent/ATE55600T1/en not_active IP Right Cessation
- 1986-07-02 DE DE8686109036T patent/DE3673476D1/en not_active Expired - Lifetime
- 1986-07-11 AU AU60062/86A patent/AU582255B2/en not_active Expired
- 1986-07-11 NZ NZ216815A patent/NZ216815A/en unknown
- 1986-07-11 JP JP61162170A patent/JPH0772177B2/en not_active Expired - Lifetime
- 1986-07-14 CS CS865351A patent/CS255878B2/en not_active IP Right Cessation
- 1986-07-14 FI FI862942A patent/FI88389C/en not_active IP Right Cessation
- 1986-07-14 CA CA000513667A patent/CA1262350A/en not_active Expired
- 1986-07-14 GR GR861823A patent/GR861823B/en unknown
- 1986-07-14 IL IL79399A patent/IL79399A/en not_active IP Right Cessation
- 1986-07-15 IE IE188986A patent/IE58750B1/en not_active IP Right Cessation
- 1986-07-15 ZA ZA865256A patent/ZA865256B/en unknown
- 1986-07-15 DK DK335386A patent/DK168042B1/en not_active IP Right Cessation
- 1986-07-15 PL PL1986260626A patent/PL149651B1/en unknown
- 1986-07-15 BR BR8603333A patent/BR8603333A/en unknown
- 1986-07-15 KR KR1019860005709A patent/KR940002823B1/en not_active IP Right Cessation
- 1986-07-15 HU HU862915A patent/HU194151B/en unknown
- 1986-07-16 AR AR86304525A patent/AR242570A1/en active
- 1986-07-16 ES ES8600335A patent/ES2000678A6/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FI862942A0 (en) | 1986-07-14 |
| GR861823B (en) | 1986-11-11 |
| DK335386A (en) | 1987-01-17 |
| DE3525335A1 (en) | 1987-01-22 |
| AR242570A1 (en) | 1993-04-30 |
| HU194151B (en) | 1988-01-28 |
| KR940002823B1 (en) | 1994-04-04 |
| JPS6219569A (en) | 1987-01-28 |
| IE861889L (en) | 1987-01-16 |
| IE58750B1 (en) | 1993-11-03 |
| IL79399A (en) | 1990-08-31 |
| BR8603333A (en) | 1987-02-24 |
| FI862942A (en) | 1987-01-17 |
| EP0209000A3 (en) | 1988-05-25 |
| ATE55600T1 (en) | 1990-09-15 |
| PL149651B1 (en) | 1990-03-31 |
| JPH0772177B2 (en) | 1995-08-02 |
| PL260626A1 (en) | 1987-06-15 |
| CS255878B2 (en) | 1988-03-15 |
| DE3673476D1 (en) | 1990-09-20 |
| FI88389C (en) | 1993-05-10 |
| ES2000678A6 (en) | 1988-03-16 |
| NZ216815A (en) | 1988-10-28 |
| DK335386D0 (en) | 1986-07-15 |
| ZA865256B (en) | 1987-03-25 |
| CS535186A2 (en) | 1987-07-16 |
| EP0209000B1 (en) | 1990-08-16 |
| KR870001210A (en) | 1987-03-12 |
| EP0209000A2 (en) | 1987-01-21 |
| AU582255B2 (en) | 1989-03-16 |
| CA1262350A (en) | 1989-10-17 |
| FI88389B (en) | 1993-01-29 |
| HUT42427A (en) | 1987-07-28 |
| AU6006286A (en) | 1987-01-22 |
| IL79399A0 (en) | 1986-10-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B1 | Patent granted (law 1993) | ||
| PUP | Patent expired |