DK170573B1 - Med quinoloncarboxylsyrederivater belastede ionbytterharpikser, fremgangsmåde til deres fremstilling, deres anvendelse til fremstilling af antibakterielle lægemidler samt lægemidler og foderstoffer indeholdende dem - Google Patents
Med quinoloncarboxylsyrederivater belastede ionbytterharpikser, fremgangsmåde til deres fremstilling, deres anvendelse til fremstilling af antibakterielle lægemidler samt lægemidler og foderstoffer indeholdende dem Download PDFInfo
- Publication number
- DK170573B1 DK170573B1 DK316888A DK316888A DK170573B1 DK 170573 B1 DK170573 B1 DK 170573B1 DK 316888 A DK316888 A DK 316888A DK 316888 A DK316888 A DK 316888A DK 170573 B1 DK170573 B1 DK 170573B1
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- DK
- Denmark
- Prior art keywords
- exchange resins
- ion exchange
- carboxylic acid
- acid derivatives
- quinolone carboxylic
- Prior art date
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- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
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- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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Description
DK 170573 B1 i
Den foreliggende opfindelse angår ionbytterharpikser, som er baseret på svagt sure, kationiske ionbytterharpikser og belastet med quinoloncarboxylsyrederivater, en fremgangsmåde til deres fremstilling, deres anvendelse til fremstil-5 ling af antibakterielle lægemidler samt lægemidler og foderstoffer indeholdende dem.
Det har længe været kendt at binde farmaceutisk aktive stoffer til ionbytterharpikser, f.eks. for at gøre aktive stoffer med en udpræget egenlugt bedre anvendelige (CH-pa-10 tentskrift nr. 383.552). Det er også kendt at binde farmaceutisk aktive stoffer til ionbytterharpikser for at opnå en ensartet frigivelse af det aktive stof over et længere tidsrum (EP-offentliggørelsesskrift nr. 42.818).
Det er desuden kendt at binde anthelmintisk aktive 15 stoffer til ionbytterharpikser for at øve indflydelse på smagen af de aktive stoffer (DE-offentliggørelsesskrift nr. 3.028.082).
Med ionbytterharpikserne ifølge opfindelsen er der tilvejebragt stoffer, hvori den bitre smag af quinoloncarbox-20 ylsyrederivaterne er maskeret, og som samtidig giver en stærk virkning ved oral indgivelse på grund af en høj frigørelse af quinoloncarboxylsyrederivaterne.
Den foreliggende opfindelse angår ionbytterharpikser baseret på svagt sure, kationiske ionbytterharpikser, og de 25 her omhandlede ionbytterharpikser er ejendommelige ved, at de er belastet med quinoloncarboxylsyrederivater med formel (I) 0
FwVcooH
30 rsAAJJ (!)
A
hvor R-1 betyder 35 R4V V, DK 170573 B1 2 hvor R4 betyder hydrogen, methyl eller ethyl.
Opfindelsen angår desuden en fremgangsmåde til fremstilling af de her omhandlede ionbytterharpikser, som er baseret på svagt sure, kationiske ionbytterharpikser og 5 belastet med quinoloncarboxylsyrederivater med ovenstående t formel (I), og den her omhandlede fremgangsmåde er ejendommelig ved, at svagt sure, kationiske ionbytterharpikser behandles med opløsninger eller suspensioner af quinoloncarboxylsyrederivater med formel (I) i vand eller i polære opløs-10 ningsmidler.
Opfindelsen angår tillige anvendelsen af de her omhandlede ionbytterharpikser, som er baseret på svagt sure, kationiske ionbytterharpikser og belastet med quinoloncarboxylsyrederivater med ovenstående formel (I), til forbedring 15 af smagen af derivaterne samt til forsinket afgivelse af quinoloncarboxylsyrederivaterne med formel (I).
Opfindelsen angår endvidere lægemidler, herunder veterinærmidler, som er ejendommelige ved, at de indeholder de her omhandlede ionbytterharpikser, som er baseret på 20 svagt sure, kationiske ionbytterharpikser og belastet med quinoloncarboxylsyrederivater med ovenstående formel (I).
Opfindelsen angår endelig faste, oralt indgivelige lægemidler samt foderstoffer, som er ejendommelige ved, at de indeholder de her omhandlede ionbytterharpikser, som er 25 baseret på svagt sure, kationiske ionbytterharpikser og belastet med quinoloncarboxylsyrederivater med ovenstående formel (I).
I betragtning som ionbytterharpikser kommer svagt sure, kationiske typer, idet deres grundmasse kan være gel-30 formig eller makroporøs. I betragtning som basismonomere for ionbytterne kommer polymeriserbare monomere, som ved *
tilsvarende funktionalisering kan omdannes til kation- eller anionbytterharpikser. Som monomere kan f.eks. nævnes (meth)- A
acrylsyreestere, (meth)-acrylonitril samt styrenderivater.
35 Som yderligere comonomere anvendes til fremstilling af basis-polymerene polyvinylforbindelser, f.eks. divinylbenzen, DK 170573 B1 3 ethylenglycoldimethacrylat eller methylenbisacrylamid. Også kondensationsharpikser, som fører til kationbyttere, f.eks. de harpikser, som opstår ved omsætningen af phenol, formaldehyd med polyaminer, er egnede som bærerstoffer for quinolon-5 carboxylsyrederivaterne med formel (I).
De anvendelige ionbyttere er ikke hidtil ukendte. Fremstillingen af disse harpikser er f.eks. beskrevet i Ullmanns Enzyklopådie der techn. Chemie, bind 13, side 299-305, 4. oplag. De foretrukne, makroporøse harpikser kan 10 udvise forskellige porevolumener. Tværbindingsgraden af de egnede ionbytterharpikser bør fortrinsvis andrage op til 20%, især op til 12%. Kunstharpikserne foreligger i kornstørrelser fra 50-1300 μιη, fortrinsvis fra 100-300 μιη.
Specielt skal nævnes anvendelsen af formalede ionbyt-15 tere. Formalingen kan dertil ske før eller efter belastningen med quinoloncarboxylsyrerne med formel (I).
I handelen gængse ionbytterharpikser, som kan anvendes, er "Lewatit®", "Amberlite®" og "Dowex®".
Quinoloncarboxylsyrerne med formel (I) og deres frem-20 stilling er kendt (DE-offentliggørelsesskrift nr. 3.033.157).
Især skal som aktive stoffer nævnes følgende quinolon-carboxylsyrer: l-Cyclopropyl-6-fluor-l, 4-dihydro-4-oxo-7-(1-piperazinyl-eller 4-methyl- eller 4-ethyl-l-piperazinyl)-quinolon-3-25 -carboxylsyre.
Som specielt foretrukket skal nævnes ciprofloxazin og enrofloxazin.
Belastningsgraden af ionbytterharpikserne med quino-loncarboxylsyrederivaterne ligger i afhængighed af harpiks-30 typen mellem 10 og 150 vægtprocent af den tørrede ionbytter.
Afgivelsesforsøg viser, at det aktive stof frigøres særlig godt i væsker med pH-værdier fra 1-3.
Fremstillingen af ionbytterharpikserne, som er belastet med quinoloncarboxylsyrederivater med formel (I), sker 35 i vand eller polære organiske opløsningsmidler, f.eks. alkoholer, såsom methanol eller ethanol, ketoner, såsom acetone, DK 170573 B1 4 eller blandinger deraf. Især foretrækkes vand. Ionbytterhar-piks og aktivt stof omrøres derved f.eks. så længe (f.eks.
5-24 timer) i vand ved stuetemperatur eller forhøjet stuetemperatur, at det aktive stof er fuldstændigt bundet.
5 Som allerede nævnt kan de med quinoloncarboxylsyre- derivater med formel (I) belastede ionbyttere anvendes til fremstilling af lægemidler. Som sådanne skal fortrinsvis nævnes lægemidler til dyr.
Til dyr egnede lægemiddelpræparater er f.eks. sådanne, 10 ved hvilke smagsforbedringen spiller en rolle ved optagelsen, eller ved hvilke en forsinket frigivelse af aktivt stof efter anvendelsen er tilstræbt.
Dette er f.eks. faste præparater, såsom pulvere, præblandinger eller koncentrater, granulater, pellets, tab-15 letter, boli og kapsler, suspensioner, som f.eks. anvendes oralt eller kutant. De fremstilles, ved at den med aktivt stof belastede harpiks suspenderes i en bærevæske, eventuelt under tilsætning af yderligere hjælpestoffer, såsom fugte-midler, farvestoffer, resorptionsfremmende stoffer, konser-20 veringsmidler, antioxidanter eller lysbeskyttelsesmidler.
Ved tilsætning af stoffer, som forøger viskositeten, kan disse suspensioner indgives som såkaldte "halvfaste" præparater, f.eks. salver. Især kan præparater af denne art anvendes til behandling af yversygdomme (Mastitis) eller 25 som orale pastaer hos katte, hunde og heste.
Til fremstilling af faste præparater blandes den med aktivt stof belastede harpiks med egnede bærestoffer, eventuelt under tilsætning af hjælpestoffer, og bringes på den ønskede form.
30 Som bærerstoffer skal nævnes alle fysiologisk accep table, faste, indifferente stoffer. Som sådanne tjener uorganiske og organiske stoffer. Uorganiske stoffer er f.eks. kogsalt, carbonater, såsom calciumcarbonat, hydrogencar- ^ bonater, aluminiumoxider, kiselsyrer, lerjordarter, fældet 35 eller kolloidalt siliciumdioxid, phosphater.
Organiske stoffer er f.eks. sukkerarter, cellulose, DK 170573 B1 5 nærings- og foderstoffer, såsom mælkepulver, dyremel, kornsortmel og -skrå, stivelser.
Hjælpestoffer er konserveringsstoffer, antioxidanter, farvestoffer, som allerede er omtalt i det foregående.
5 Yderligere egnede hjælpestoffer er smøre- og giide midler, f.eks. magnesiumstearat, stearinsyre, talkum, ben-toniter, henfaldsfremmende stoffer, såsom stivelse eller tværbundet polyvinylpyrrolidon, bindemidler, f.eks. stivelse, gelatine eller lineært polyvinylpyrrolidon, samt tørbinde-10 midler, såsom mikrokrystallinsk cellulose.
Til fremstilling af suspensioner fordeles de med aktivt stof belastede harpikser så homogent som muligt i et bæremedium, eventuelt under medvirken af andre hjælpestoffer, såsom fugtemidler, konserveringsmidler eller viskositets-15 forøgende stoffer.
Som bærervæsker skal nævnes alle homogene opløsningsmidler og opløsningsmiddelblandinger, men især vand.
Som fugtemidler (dispergeringsmidler) skal nævnes: 1. Anionaktive tensider, herunder emulgatorer, såsom 2 0 Na-laurylsulfat, fedtalkoholethersulfater, mono/- dialkylpolyglycoletherorthophosphorsyre-monoethanol-aminsalte, ligninsulfonater eller dioctylsulfosuc-cinat.
2. Kationaktive tensider, herunder emulgatorer, såsom 2 5 cetyltrimethylammoniumchlorid.
3. Ampholytiske tensider, herunder emulgatorer, såsom di-Na-N-lauryl-/?-iminodipropionat eller lecithin.
4. Ikke-ionogene tensider, herunder emulgatorer, såsom polyoxethyleret ricinusolie, polyoxyethyleret sor- 30 bitanmonooleat, sorbitanmonostearat, ethylalkohol, glycerolmonostearat, polyoxyethylenstearat, alkyl-phenolpolyglycolether, "Pluronic®".
Særlig foretrukket er de ikke-ioniske tensider.
Yderligere hjælpestoffer er f.eks.
35 farvestoffer, dvs. alle til anvendelse i dyr tilladte farvestoffer, som kan være opløst eller suspenderet, DK 170573 B1 6 antioxidanter, f.eks. sulfiter eller metabisulfiter, såsom ka1iummetabisulfit, ascorbinsyre, butylhydroxytoluen, butyl-hydroxyanisol, tocopherol, e fortykkelsesmidler eller viskositetsforøgende stoffer, f.eks.
5 uorganiske fortykkelsesmidler, såsom bentoniter, kolloidal C- kiselsyre, aluminiummonostearat, organiske fortykkelsesmidler, såsom cellulosederivater, polyvinylalkoholer og deres copolymere, acrylater og methacrylater, alginater, gelatine, polyvinylpyrrolidon, polyethylenglycoler, vokser, gummi 10 arabicum og xanthamgummi eller blanding af de anførte stoffer.
De med aktivt stof belastede ionbytterharpikser kan sættes til foderet som sådanne eller i form af præblandinger eller foderkoncentrater.
15 Præblandinger og foderkoncentrater er blandinger af det aktive stof med et egnet bærestof.
Til bærestofferne hører enkeltfoderstoffer eller blandinger af disse samt de ovenfor anførte, indifferente bærestoffer.
20 De kan derudover indeholde yderligere hjælpestoffer, f.eks. stoffer, som regulerer strømmeevnen og blandbarheden, f.eks. kiselsyrer, bentoniter og ligninsulfonater. Derudover kan der være tilsat antioxidanter, såsom BHT, eller konserveringsmidler, såsom sorbinsyre eller calciumpropionat.
25 Desuden kan der i præblandingerne til støvbinding blandes væsker, såsom paraffinolier, planteolier og propylenglycoler.
De med aktivt stof belastede harpikser kan i formuleringerne foreligge alene eller i blanding med andre aktive stoffer, mineralsalte, sporgrundstoffer, vitaminer, 30 proteiner, farvestoffer, fedtstoffer eller smagsstoffer.
Andre aktive stoffer kan f.eks. være penicilliner, deres salte og derivater, f.eks. procainsaltet af penicillin--G eller derivater deraf, såsom oxacillin eller cloxacillin.
Indgivelsen af de med aktivt stof belastede ionbytter-35 harpikser sker fortrinsvis sammen med foderet.
Til foderet hører enkeltfoderstoffer af vegetabilsk DK 170573 B1 7 oprindelse, såsom hø, roer, korn, kornbiprodukter, enkeltfoderstoffer af animalsk oprindelse, såsom kød, fedtstoffer, mælkeprodukter, benmel, fiskeprodukter, desuden sådanne enkeltfoderstoffer som vitaminer, proteiner, aminosyrer, 5 f.eks. DL-methionin, salte, såsom kalk og kogsalt. Til foderet hører også supplerings-, færdig- og blandingsfoderstoffer. Disse indeholder enkeltfoderstoffer i en sammesætning, som garanterer en afvejet ernæring med henblik på energi-og proteinbehov samt behovet for vitaminer, mineralsalte og 10 sporgrundstoffer.
Koncentrationen af ionbytterne i foderet andrager normalt fra ca. 0,01 til ca. 500 ppm, fortrinsvis 10-2 00 ppm.
15 Fremstillinaseksempler Eksempel 1 100 ml af en suspension af 5 g enrofloxacin i demineraliseret vand omrøres sammen med 35 ml "Lewatit® CNP" i H+-form, indtil den vandige fase bliver klar. Efter fra-20 skillelse af harpiksen bestemmes den optagne mængde af enrofloxacin ved differensvejning af den tørrede harpiks før og efter belastningen. Ved dette forsøg bindes 3,5 g enrofloxacin.
25 Eksempel 2 500 ml "Lewatit® CNP" i H+-form omrøres natten over sammen med 3000 ml demineraliseret vand og 250 g enrofloxacin. Harpiksen isoleres fra den klare, vandige fase og vaskes to gange med et massevolumen vand ad gangen. Efter 48 timers 30 tørring i et vakuumtørreskab ved 60° C fås på denne måde ca. 1200 g af præparatet ifølge opfindelsen.
Eksempel 3 80 ml "Lewatit® CNP" i H+-form omrøres sammen med 35 500 ml demineraliseret vand og 8 g enrofloxacin ved 60'C.
Efter 3 timers omrøring er den vandige fase klar. Ionbytteren DK 170573 B1 8 har bundet alt det aktive stof.
Formulerinqseksempler 4. Præblanding til foderlægemidler.
5 Enrofloxacin-ionbytter 25 kg ifølge eksempel 2 * (25 g svarer til 2,5 g enrofloxacin)
Hvedemel 75 kg 10 100 kg
Fremstilling:
Stofferne blandes homogent i et blandeapparat.
5. Enrofloxacin-ionbytter 50 kg 15 ifølge eksempel 2 (50 g svarer til 5,0 g enrofloxacin)
Vegetabilsk olie 4 kg
Kalkstenmel 46 kg 20 100 kg
Kalkmelet blandes i forvejen med planteolien, og harpiksen med aktivt stof fordeles homogent deri.
25 6. Sammensætning af en oral pasta (f.eks. til hunde og katte).
Enrofloxacin-ionbytter 10 kg ifølge eksempel 2 30 (10 g svarer til 1 g enrofloxacin)
Kornstørrelsesmiddelværdi 0,1 mm Glycerol 10,0 g
Benzylalkohol 1,0 g ^
Aromastof 0,2 g
Methylhydroxypropylcellulosegel 2% ad 100 ml 35 • ·_ * " ! DK 170573 B1 9
Fremstilling:
En 2%·s methylhydroxypropylcellulosegel fremstilles på gængs måde. Deri opløses benzylalkohol og aromastof, og det aktive stof ifølge opfindelsen suspenderes deri.
5 7. Sammensætning til et granulat.
1. Enrofloxacin-ionbytter 100,0 g ifølge eksempel 2 (18,8 g svarer til 10,0 g enro- floxacin) 10 2. Mælkesukker 50,0 g 3. Majsstivelse 29,2 g 4. Gelatine 2,0 g 181,2 g 15 Stofferne 1, 2 og 3 blandes. Ud fra 4 fremstilles der en gelatineopløsning med 22,0 g vand. Med denne æltes blandingen. Den faste dej sønderdeles over et rivejern og tørres og sigtes derefter til den ønskede kornstørrelse.
20 8. Blanding.
Enrofloxacin-ionbytter 8,60 kg ifølge eksempel 2
Kalkstenmel 1,25 kg
Polyoxyethyleret ricinusolie 0.15 ker 25 10,00 kg
Kalkstenmelet blandes i forvejen med den polyoxy-ethylerede ricinusolie, hvorefter det aktive stof tilsættes og fordeles homogent.
30
Anvendelseseksempler A. Bestemmelse af koncentrationen af aktivt stof i blodserum hos svin, som med foderet har fået indgivet den med aktivt stof belastede ionbytter.
35 Svin med en gennemsnitsvægt på 14,8 kg får 2 gange dagligt hver gang 0,3 g griseopdrætsfoder, som er blandet 10 DK 170573 B1 med den angivne mængde enrofloxacin. 1 time efter hver fodring udtages der blod, og indholdet af aktivt stof i serum bestemmes. Der er fundet følgende værdier: * 5 Indhold af aktivt Spejl af aktivt stof, μg/ml Λ stof ppm 1 time efter 1. 1 time efter 2.
fodring fodring 100 0,3 0,5 200 0,6 0,6 10 400 1,1 1,0 B. Bestemmelse af accepterbarheden af medikeret foder af svin.
Svin med en gennemsnitsvægt på 14,8 kg får 2 gange 15 dagligt 0,3 g griseopdrætsfoder, som er blandet med det rene aktive stof enrofloxacin samt med en svagt sur kationisk ionbytterharpiks, som er belastet med aktivt stof. Efter de angivne tidsrum bestemmes restfoderet i truget. Derved er der målt følgende værdier: 20
Indhold af aktivt Antal Restfoder i % efter stof, ppm dyr 15 30 60 min.
0 9 5 0 0 400 (rent 25 aktivt stof) 12 80 70 70 400 (aktivt stof bundet på ionbytter) 11 10 0 0 4
Claims (5)
1. Ionbytterharpikser baseret på svagt sure, kationi-ske ionbytterharpikser, kendetegnet ved, at de er belastet med quinoloncarboxylsyrederivater med formel (I) 5 ;xxVc”
10 A hvor R3 betyder 15 *-0-. hvor R4 betyder hydrogen, methyl eller ethyl.
2. Fremgangsmåde til fremstilling af ionbytterharpikser, som er baseret på svagt sure, kationiske ionbytterhar- 20 pikser og belastet med quinoloncarboxylsyrederivater med den i krav 1 angivne formel (I), kendetegnet ved, at svagt sure kationiske ionbytterharpikser behandles med opløsninger eller suspensioner af quinoloncarboxylsyrederivater med formel (I) i vand eller i polære opløsningsmid-25 ler.
3. Anvendelse af ionbytterharpikser ifølge krav 1, som er baseret på svagt sure, kationiske ionbytterharpikser og belastet med quinoloncarboxylsyrederivater med den i krav 1 angivne formel (I), til forbedring af smagen af deri- 30 vaterne samt til forsinket afgivelse af quinoloncarboxyl-syrederivaterne med formel (I).
4. Lægemidler, herunder veterinærlægemidler, kendetegnet ved, at de indeholder ionbytterharpikser ifølge krav 1, som er baseret på svagt sure, kationiske 35 ionbytterharpikser og belastet med quinoloncarboxylsyrederivater med den i krav 1 angivne formel (I). DK 170573 B1
5. Faste, oralt indgivelige lægemidler samt foderstoffer, kendetegnet ved, at de indeholder ionbytter-harpikser ifølge krav 1, som er baseret på svagt sure, kat-ioniske ionbytterharpikser og belastet med quinoloncarboxyl-5 syrederivater med den i krav 1 angivne formel (I). 10 15 20 25 30 * 35
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3719764 | 1987-06-13 | ||
DE19873719764 DE3719764A1 (de) | 1987-06-13 | 1987-06-13 | Ionenaustauscherharze beladen mit chinoloncarbonsaeurederivaten, ihre herstellung und verwendung |
Publications (3)
Publication Number | Publication Date |
---|---|
DK316888D0 DK316888D0 (da) | 1988-06-10 |
DK316888A DK316888A (da) | 1988-12-14 |
DK170573B1 true DK170573B1 (da) | 1995-10-30 |
Family
ID=6329624
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Application Number | Title | Priority Date | Filing Date |
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DK316888A DK170573B1 (da) | 1987-06-13 | 1988-06-10 | Med quinoloncarboxylsyrederivater belastede ionbytterharpikser, fremgangsmåde til deres fremstilling, deres anvendelse til fremstilling af antibakterielle lægemidler samt lægemidler og foderstoffer indeholdende dem |
Country Status (27)
Country | Link |
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US (1) | US5152986A (da) |
EP (1) | EP0295495B1 (da) |
JP (1) | JP2572815B2 (da) |
KR (1) | KR950014238B1 (da) |
CN (2) | CN1054040C (da) |
AR (1) | AR243084A1 (da) |
AT (1) | ATE68694T1 (da) |
AU (1) | AU599239B2 (da) |
BR (1) | BR8802853A (da) |
CA (1) | CA1318078C (da) |
CZ (1) | CZ279867B6 (da) |
DD (1) | DD271061A5 (da) |
DE (2) | DE3719764A1 (da) |
DK (1) | DK170573B1 (da) |
ES (1) | ES2040290T3 (da) |
FI (1) | FI90494C (da) |
GR (1) | GR3002988T3 (da) |
HU (1) | HU199824B (da) |
IE (1) | IE60209B1 (da) |
IL (1) | IL86697A (da) |
MX (1) | MX168987B (da) |
NZ (1) | NZ224975A (da) |
PL (1) | PL155652B1 (da) |
PT (1) | PT87647B (da) |
RU (1) | RU1828394C (da) |
SK (1) | SK278495B6 (da) |
ZA (1) | ZA884154B (da) |
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SE8902315D0 (sv) * | 1989-06-27 | 1989-06-27 | Pharmacia Ab | Anjonbytare |
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DE69224071T2 (de) * | 1991-09-17 | 1998-05-07 | Alcon Lab Inc | Chinolan-antibiotika und polystyrolsulfonat enthaltende zusammensetzungen |
ES2100806B1 (es) * | 1994-07-27 | 1998-02-16 | Gentec S A | Procedimiento de obtencion de particulas de 1-ciclopropil-7-(4-etil-1-piperazinil)-6-fluoro-1,4-dihidro-4-oxo-3-acido quinolin carboxilico recubiertas. |
DE19633480A1 (de) * | 1996-08-20 | 1998-02-26 | Bayer Ag | Oral applizierbare Formulierungen von Chinolon- und Naphthyridoncarbonsäuren |
US5980882A (en) * | 1997-04-16 | 1999-11-09 | Medeva Pharmaceuticals Manufacturing | Drug-resin complexes stabilized by chelating agents |
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HN1999000174A (es) * | 1998-10-30 | 1999-10-13 | Bayer Ag | Formulacion medicamentosa acuisa para administracion oral. |
US6514492B1 (en) * | 1999-07-14 | 2003-02-04 | Schering-Plough Veterinary Corporation | Taste masking of oral quinolone liquid preparations using ion exchange resins |
ATE411047T1 (de) * | 1999-07-14 | 2008-10-15 | Schering Plough Ltd | Maskieren des geschmacks der oralen flüssigen chinolon-zubereitungen mit ionenaustauscherharzen |
US20020122824A1 (en) | 2001-01-24 | 2002-09-05 | Francisco Cabrera | Solid phase dispersion of quinolone-or naphthyridonecarboxylic acids |
KR100388501B1 (ko) * | 2001-05-24 | 2003-06-25 | 주식회사 한국미생물연구소 | 엔로플록사신의 쓴맛이 개선된 사료첨가제 조성물 및 그제조방법 |
DE10134719A1 (de) * | 2001-07-17 | 2003-02-06 | Bayer Ag | Pharmazeutische Zubereitungen enthaltend wirkstoffbeladene Ionentauscherharze |
US7052712B2 (en) | 2001-10-05 | 2006-05-30 | Rubicon Scientific Llc | Animal feeds including actives and methods of preparing same |
US6716448B2 (en) | 2001-10-05 | 2004-04-06 | Rubicon Scientific Llc | Domesticated household pet food including maintenance amounts of ivermectin |
US6866862B2 (en) | 2001-10-05 | 2005-03-15 | Rubicon Scientific | Animal feeds including heartworm-prevention drugs |
JP4619658B2 (ja) * | 2002-03-12 | 2011-01-26 | 富山化学工業株式会社 | 快い味の経口懸濁液および方法 |
DE10224086A1 (de) * | 2002-05-31 | 2003-12-11 | Bayer Ag | Pharmazeutische Zubereitungen zur oralen Anwendung enthaltend wirkstoffbeladene Ionentauscherharze sowie strukturviskose Gelbildner als Verdicker |
DE10328666A1 (de) * | 2003-06-26 | 2005-01-13 | Bayer Healthcare Ag | Tabletten enthaltend Geschmacks-und/oder Aromastoffe |
CN100410249C (zh) | 2003-09-10 | 2008-08-13 | 杏林制药株式会社 | 7-(4-取代-3-环丙基氨基甲基-1-吡咯烷基)喹诺酮羧酸衍生物 |
DE10351448A1 (de) * | 2003-11-04 | 2005-06-09 | Bayer Healthcare Ag | Geschmackstoffhaltige Arzneimittelformulierungen mit verbesserten pharmazeutischen Eigenschaften |
US20070036843A1 (en) * | 2005-01-28 | 2007-02-15 | Collegium Pharmaceutical, Inc. | Non-ionic non-aqueous vehicles for topical and oral administration of carrier-complexed active agents |
CA2688008A1 (en) | 2007-05-24 | 2008-11-27 | Kyorin Pharmaceutical Co., Ltd. | Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in substituent at 14-position |
JP2012139673A (ja) * | 2010-12-29 | 2012-07-26 | Dow Global Technologies Llc | アニオン交換樹脂におけるニトロソアミン形成を抑制する方法 |
JP5599381B2 (ja) * | 2010-12-29 | 2014-10-01 | ダウ グローバル テクノロジーズ エルエルシー | アニオン交換樹脂におけるニトロソアミン形成を抑制する方法 |
JP2012140596A (ja) * | 2010-12-29 | 2012-07-26 | Dow Global Technologies Llc | ニトロソアミン形成が制御されたアニオン交換樹脂 |
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GB857193A (en) * | 1957-03-14 | 1960-12-29 | Clinical Products Ltd | Resin-drug compounds |
US3051623A (en) * | 1959-04-24 | 1962-08-28 | Wallace & Tiernan Inc | Codeine and 2-methyl-3-o-tolyl-4-quin-azolone analgesic composition |
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AU5957480A (en) * | 1979-07-26 | 1981-01-29 | American Cyanamid Company | Diethyl carbamazine resinate |
DE3033157A1 (de) * | 1980-09-03 | 1982-04-01 | Bayer Ag, 5090 Leverkusen | 7-amino-1-cyclopropyl-4-oxo-1,4-dihydro-naphthyridin-3-carbonsaeuren, verfahren zu ihrer herstellung sowie diese enthaltende antibakterielle mittel |
US4369175A (en) * | 1981-07-27 | 1983-01-18 | Ciba-Geigy Corporation | Process for the manufacture of prolonged action vincamine preparations, the vincamine preparations so obtained, and medicaments containing them |
US4762709A (en) * | 1983-09-16 | 1988-08-09 | Pennwalt Corporation | Liquid prolonged release pharmaceutical formulations containing ionic constituents |
IT1175814B (it) * | 1984-03-09 | 1987-07-15 | Luso Farmaco Inst | Resine solfoniche ad attivita' terapeutica,loro preparazione e composizioni farmaceutiche che le contengono |
CA1236023A (en) * | 1984-07-18 | 1988-05-03 | Yegnaswami Raghunathan | Controlled release pharmaceutical preparations |
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DE3541972A1 (de) * | 1985-11-28 | 1987-06-04 | Immanuel Jeschke | Transportleitung fuer gas oder fluessigkeiten |
DE3542972A1 (de) * | 1985-12-05 | 1987-06-11 | Merck Patent Gmbh | Pharmakadepot |
DE3705621C2 (de) * | 1986-02-25 | 1997-01-09 | Otsuka Pharma Co Ltd | Heterocyclisch substituierte Chinoloncarbonsäurederivate |
-
1987
- 1987-06-13 DE DE19873719764 patent/DE3719764A1/de not_active Withdrawn
-
1988
- 1988-06-01 EP EP88108732A patent/EP0295495B1/de not_active Expired - Lifetime
- 1988-06-01 DE DE8888108732T patent/DE3865748D1/de not_active Expired - Lifetime
- 1988-06-01 AT AT88108732T patent/ATE68694T1/de not_active IP Right Cessation
- 1988-06-01 ES ES88108732T patent/ES2040290T3/es not_active Expired - Lifetime
- 1988-06-03 PT PT87647A patent/PT87647B/pt not_active IP Right Cessation
- 1988-06-06 JP JP63137596A patent/JP2572815B2/ja not_active Expired - Lifetime
- 1988-06-06 MX MX011773A patent/MX168987B/es unknown
- 1988-06-09 FI FI882747A patent/FI90494C/fi active IP Right Grant
- 1988-06-10 ZA ZA884154A patent/ZA884154B/xx unknown
- 1988-06-10 DD DD88316664A patent/DD271061A5/de not_active IP Right Cessation
- 1988-06-10 IE IE175788A patent/IE60209B1/en not_active IP Right Cessation
- 1988-06-10 HU HU883023A patent/HU199824B/hu unknown
- 1988-06-10 PL PL1988273001A patent/PL155652B1/pl unknown
- 1988-06-10 BR BR8802853A patent/BR8802853A/pt not_active Application Discontinuation
- 1988-06-10 CN CN88103473A patent/CN1054040C/zh not_active Expired - Lifetime
- 1988-06-10 AR AR88311097A patent/AR243084A1/es active
- 1988-06-10 CA CA000569162A patent/CA1318078C/en not_active Expired - Lifetime
- 1988-06-10 NZ NZ224975A patent/NZ224975A/xx unknown
- 1988-06-10 IL IL86697A patent/IL86697A/xx not_active IP Right Cessation
- 1988-06-10 DK DK316888A patent/DK170573B1/da not_active IP Right Cessation
- 1988-06-11 KR KR1019880007035A patent/KR950014238B1/ko not_active IP Right Cessation
- 1988-06-13 SK SK4096-88A patent/SK278495B6/sk unknown
- 1988-06-13 CZ CS884096A patent/CZ279867B6/cs not_active IP Right Cessation
- 1988-06-14 AU AU17643/88A patent/AU599239B2/en not_active Expired
-
1989
- 1989-10-24 US US07/426,123 patent/US5152986A/en not_active Expired - Lifetime
-
1991
- 1991-09-12 RU SU915001592A patent/RU1828394C/ru active
- 1991-10-24 GR GR91401492T patent/GR3002988T3/el unknown
-
1995
- 1995-02-28 CN CN95100860A patent/CN1081951C/zh not_active Expired - Lifetime
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