HU190963B - Process for production of synergyc medical preparatives containing organic acids with oxitetracylin and antimicrobatic influence - Google Patents
Process for production of synergyc medical preparatives containing organic acids with oxitetracylin and antimicrobatic influence Download PDFInfo
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- HU190963B HU190963B HU841682A HU168284A HU190963B HU 190963 B HU190963 B HU 190963B HU 841682 A HU841682 A HU 841682A HU 168284 A HU168284 A HU 168284A HU 190963 B HU190963 B HU 190963B
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- oxytetracycline
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- 150000007524 organic acids Chemical class 0.000 title claims abstract 3
- 238000000034 method Methods 0.000 title claims description 8
- 235000005985 organic acids Nutrition 0.000 title 1
- 239000004100 Oxytetracycline Substances 0.000 claims abstract description 22
- 229960000625 oxytetracycline Drugs 0.000 claims abstract description 22
- 235000019366 oxytetracycline Nutrition 0.000 claims abstract description 22
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 claims abstract description 22
- 241001465754 Metazoa Species 0.000 claims abstract description 8
- 230000002195 synergetic effect Effects 0.000 claims abstract description 8
- 239000007788 liquid Substances 0.000 claims abstract description 5
- 239000007787 solid Substances 0.000 claims abstract description 4
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 claims abstract 5
- MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 claims description 17
- KYGZCKSPAKDVKC-UHFFFAOYSA-N Oxolinic acid Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC2=C1OCO2 KYGZCKSPAKDVKC-UHFFFAOYSA-N 0.000 claims description 15
- 229960000210 nalidixic acid Drugs 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 229960000321 oxolinic acid Drugs 0.000 claims description 12
- 244000309466 calf Species 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 7
- 241000282887 Suidae Species 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 244000144977 poultry Species 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- -1 naphthalidine carboxylic acid derivative Chemical class 0.000 claims 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 abstract description 6
- 239000004098 Tetracycline Substances 0.000 abstract description 3
- 235000019364 tetracycline Nutrition 0.000 abstract description 3
- 150000003522 tetracyclines Chemical class 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 2
- 229960002180 tetracycline Drugs 0.000 abstract 2
- 229930101283 tetracycline Natural products 0.000 abstract 2
- 239000004606 Fillers/Extenders Substances 0.000 abstract 1
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 1
- 210000004392 genitalia Anatomy 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 210000000056 organ Anatomy 0.000 abstract 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 229940124531 pharmaceutical excipient Drugs 0.000 abstract 1
- 230000000241 respiratory effect Effects 0.000 abstract 1
- 230000002485 urinary effect Effects 0.000 abstract 1
- 241000588724 Escherichia coli Species 0.000 description 32
- OWFJMIVZYSDULZ-PXOLEDIWSA-N (4s,4ar,5s,5ar,6s,12ar)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O OWFJMIVZYSDULZ-PXOLEDIWSA-N 0.000 description 21
- 241000283690 Bos taurus Species 0.000 description 10
- 241000282898 Sus scrofa Species 0.000 description 10
- 230000000844 anti-bacterial effect Effects 0.000 description 8
- 241000588779 Bordetella bronchiseptica Species 0.000 description 7
- 241000191967 Staphylococcus aureus Species 0.000 description 7
- 241000120569 Streptococcus equi subsp. zooepidemicus Species 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 241000588747 Klebsiella pneumoniae Species 0.000 description 6
- 241000186779 Listeria monocytogenes Species 0.000 description 6
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 6
- 241000186064 Trueperella pyogenes Species 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 241000606856 Pasteurella multocida Species 0.000 description 5
- 241000588767 Proteus vulgaris Species 0.000 description 5
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 229940127089 cytotoxic agent Drugs 0.000 description 5
- 229940007042 proteus vulgaris Drugs 0.000 description 5
- 241001293418 Mannheimia haemolytica Species 0.000 description 4
- 241000607142 Salmonella Species 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940051027 pasteurella multocida Drugs 0.000 description 4
- 241000588748 Klebsiella Species 0.000 description 3
- 241000204022 Mycoplasma gallisepticum Species 0.000 description 3
- 241000202938 Mycoplasma hyorhinis Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 241000588807 Bordetella Species 0.000 description 2
- 241000606860 Pasteurella Species 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- 235000013594 poultry meat Nutrition 0.000 description 2
- 230000002787 reinforcement Effects 0.000 description 2
- 208000004145 Endometritis Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010062233 Uterine infection Diseases 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 235000020346 chamomile tea Nutrition 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 244000000058 gram-negative pathogen Species 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 description 1
- 229960004444 piromidic acid Drugs 0.000 description 1
- RCIMBBZXSXFZBV-UHFFFAOYSA-N piromidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCCC1 RCIMBBZXSXFZBV-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
A találmány tárgya háziállatok mikrobiális eredetű megbetegedéseinek kezelésére alkalmas új szinergetikus hatású gyógyászati készítmények előállítására vonatkozik.BACKGROUND OF THE INVENTION This invention relates to novel synergistic pharmaceutical compositions for the treatment of microbial diseases in domestic animals.
A találmány szerinti gyógyászati készítmények előállítását az jellemzi, hogy az oxitetraciklint, az oxolinsavat vagy nalidixsavat 0,5-5 : 5-0,5 arányban egymással, valamint iners, szilárd és/vagy folyékony gyógyászati hordozóanyagokkal összekeverjük és gyógyászati felhasználásra alkalmas formában kikészítjük.The preparation of the pharmaceutical compositions of the present invention is characterized in that the oxytetracycline, oxolinic or nalidixic acid is mixed in a ratio of 0.5 to 5: 5 to 0.5, together with inert, solid and / or liquid pharmaceutical carriers and formulated for pharmaceutical use.
A szarvasmarha és sertésállományokban a fiatalkori megbetegedések jelentős veszteséget okoznak. Évente 8-10 000 szopós borjú és a megszületett malacok közel 10 százaléka hullik el szopós korban, elsősorban bakteriális fertőzések következtében. A megbetegedések főleg Gram-negatív kórokozók (E. coli, Klebsiella stb.) okozta infekciók, de gyakori a csökkent ellenállöképesség miatt kialakuló Strepto-, illetve Staphylococcosis is.In cattle and pigs, juvenile diseases cause significant losses. Every year, 8 to 10,000 suckling calves and nearly 10 percent of the born piglets die during the suckling age, mainly due to bacterial infections. The diseases are mainly infections caused by gram-negative pathogens (E. coli, Klebsiella, etc.), but also Strepto- and Staphylococcosis due to reduced resistance are common.
A széles körben használt tetraciklinek közül hazánkban az oxitetraciklint immár három évtizede alkalmazzák (Tetrán inj., Tetran comb. pulvis A.U.V.). Az OTC-vel szemben azonban jelentős rezisztencia-növekedés lépett fel. A Staphylococcus aureus kultúrákban mérve mintegy 20%-os (De Buyser, M. - Ollieuz, N.; Rec. Med. Vet., 755. 7-8. 639-643), sőt borjakból, csirkékből izolált törzsek esetén 50-100%-os (Heller, E. D. - Drabkin, N.: Brit. Vet. J., 1977.133. 6. 572-578) hatáscsökkenés miatt a készítmény önmagában elértéktelenedett.Among the widely used tetracyclines, oxytetracycline has been used in Hungary for three decades (Tetran inj., Tetran comb. Pulvis A.U.V.). However, there was a significant increase in resistance to OTC. In strains isolated from staphylococcus aureus, the strains isolated from strains isolated from calves and chickens are approximately 20% (De Buyser, M. - Ollieuz, N .; Rec. Med. Vet., 755-8. (Heller, ED - Drabkin, N .: Brit. Vet. J., 1977, 13, 6, 572-578), the preparation alone is depreciated.
A teljesebb hatás biztosítása érdekében az oxitetraciklint gyakran kombinációban is alkalmazzák (pl. neomycinnel együtt Neo-Te-Sol, Exuter M. és P. tabl. A.U.V., Neomast A.U.V., stb.).To provide a more complete effect, oxytetracycline is often used in combination (e.g. Neo-Te-Sol, Exuter M. and P. tabl. A.U.V., Neomast A.U.V., etc. in combination with neomycin).
Az oxolinsav Gram-negatív spektruma igen jó (Linzenmeier, Neussel: Warner-Chillcott Madrid 1972), E. coli fertőzésekben igen eredményesen alkalmazható. A 81 150 016 Lsz. japán szabadalmi leírás szerinti kombináció (oxolinic-, nalidixic acid + pipemidic-, piromidic acid) szintén E. coli okozta fertőzések kezelésére ajánlott.The Gram-negative spectrum of oxolinic acid is very good (Linzenmeier, Neussel: Warner-Chillcott Madrid 1972) and can be used very effectively in E. coli infections. No. 81,150,016. The Japanese patent combination (oxolinic, nalidixic acid + pipemidic, pyromidic acid) is also recommended for the treatment of E. coli infections.
A nalidixsav önmagában is jó mikrobiológiai effektivitással rendelkezik. Gyógyszerkombinációk előállítására irányuló vizsgálatok során megállapították, hogy trimetoprimmel szinergizmust eredményez (Bertoni, V.: Drug Exp. Clin. Rés. 1980. 6.Nalidixic acid alone has good microbiological efficacy. Studies on the preparation of drug combinations have shown that it produces synergism with trimethoprim (Bertoni, V .: Drug Exp. Clin.
4. 311-316).4. 311-316).
A találmány alapja az a felismerés, hogyha az oxitetraciklint oxolinsawal vagy nalidixsawal együtt alkalmazzuk, azon túl, hogy az egyes komponensek hatékonysága megmarad (mint. pl. az E. colira, Pasteurellára, Proteusra, Listeria monocytogenesre, Corynebacterium pyogenesre kifejtett hatás esetén) egyes törzseken mérve, kifejezett szinergizmus tapasztalható. A kombináció szinergetikus hatását mikrobiológiai vizsgálatokkal igazoljuk.The present invention is based on the discovery that when oxytetracycline is used in combination with oxolinic acid or nalidixic acid, the efficacy of the individual components is maintained (e.g., in some strains against E. coli, Pasteurella, Proteus, Listeria monocytogenes, Corynebacterium pyogenes). measured, there is a clear synergy. The synergistic effect of the combination is demonstrated by microbiological assays.
Az 1. táblázatban az oxitetraciklinnek egyes baktériumtörzsekre kifejtett bakteriosztatikus (MIC) és baktericid (MBC) hatását tüntetjük fel. A 2. táblázat az oxolinsavnak, ugyanezen törzsekre kifejtett antibakteriális értékeit tartalmazza mg/l-ben kifejezve. A 3. táblázat a nalidixsavnak ugyanezen törzsekre kifejtett antibakteriális értékeit mutatja be mg/l-ben kifejezve.Table 1 shows the bacteriostatic (MIC) and bactericidal (MBC) activity of oxytetracycline on certain bacterial strains. Table 2 shows the antibacterial values of oxolinic acid expressed in mg / l for the same strains. Table 3 shows the antibacterial values of nalidixic acid expressed in mg / l for the same strains.
7. táblázatTable 7
Kemoterápiás szer antibakteriális hatása mg/l-ben kifejezve oxitetraciklinAntibacterial activity of chemotherapeutic agent expressed as mg / l oxytetracycline
190 963190,963
3. táblázat folytatásaContinuation of Table 3
A kísérleteket a továbbiakban az oxitetraciklinnek oxolinsawal vagy nalidixsawal alkotott kombinációjával végeztük. A kombinációkkal végzett in vitro kísérletek egyértelműen igazolták a kombináció egyes baktériumtörzsekre kifejtett szinergista hatását (4-5. táblázat). Az 1 : 1 arányú oxitetraciklin-oxolinsav kompozíció a Streptococcus, a Klebsiella, valamint a Bordetella kultúrákon kétszeres, tízszeres, valamint negyvenszeres hatásfokozódást eredményez (6. táblázat). Az 1 : 1 arányú oxitetraciklin és nalidixsav hatásfokozódása 800-szoros is lehet (7. táblázat).The experiments were hereinafter carried out using a combination of oxytetracycline with oxolinic acid or nalidixic acid. The in vitro experiments with the combinations clearly demonstrated the synergistic effect of the combination on certain bacterial strains (Table 4-5). The 1: 1 oxytetracycline-oxolinic acid composition results in a doubling, 10-fold, and 40-fold potency in Streptococcus, Klebsiella, and Bordetella cultures (Table 6). The efficiency of oxytetracycline and nalidixic acid in a 1: 1 ratio can be up to 800-fold (Table 7).
A találmány szerinti eljárással előállítható szinergetikus hatású gyógyászati készítményeket perorális és parenterális alkalmazásra egyaránt kikészíthetjük.Pharmaceutical compositions having a synergistic effect according to the invention may be formulated for both oral and parenteral administration.
A készítményeket úgy állítjuk elő, hogy a hatóanyagokat egymással homogenizáljuk, majd fokozatosan a vivőanyag kisebb mennyiségeivel összekeverjük. A vivőanyag egy vagy több, az állatgyógyászatban általában használatos adalékanyagokat is tartalmazhat.The formulations are prepared by homogenizing the active ingredients and then gradually mixing with smaller quantities of the carrier. The carrier may also contain one or more additives commonly used in veterinary medicine.
A készítményt perorálisan por vagy granula formájában ivóvízben vagy takarmányba keverve, parenterálisan előnyösen kapszula formában intrauterin, folyékony formában intracysternálisan alkalmazzuk.The composition is administered orally in powder or granule form in drinking water or in feed, parenterally, preferably in capsule form, intrauterine, in liquid form, intracysterally.
A találmány szerinti szinergetikus hatású gyógyszerkombinációt előnyösen szarvasmarha, borjú, sertés, malac, nyúl, kutyaThe synergistic drug combination of the present invention is preferably cattle, calf, pig, pig, rabbit, dog
- Proteus, E. coli, Streptococcus, Staphylococcus okozta méhgyulladásainak,- uterine infections caused by Proteus, E. coli, Streptococcus, Staphylococcus,
- borjú, malac E. coli, Klebsiella, Salmonella spp. okozta bélgyulladásainak,- calf, pig E. coli, Klebsiella, Salmonella spp. intestinal inflammation,
4. táblázatTable 4
Kemoterápiás szer antibakteriális hatása mgf-ben kifejezveAntibacterial activity of a chemotherapeutic agent expressed in mgf
5. táblázatTable 5
Kemoterápiás szer antibakteriális aktivitása mg/l-ben kifejezveAntibacterial activity of chemotherapeutic agent expressed in mg / l
Oxitetraciklin + nalidixsav (I : 1)Oxytetracycline + Nalidixic Acid (I: 1)
190 963190,963
6. táblázatTable 6
Hatásfokozódás kombinációbanEffectiveness in combination
- sertés E. coli, Salmonella okozta fertőzéseinek,- swine infection by E. coli caused by Salmonella,
- sertés Streptococcus, Staphylococcus, Pasteurella, Salmonella, Bordetella spp. okozta légzőszervi megbetegedéseinek,- porcine Streptococcus, Staphylococcus, Pasteurella, Salmonella, Bordetella spp. respiratory diseases,
- nyúl, baromfi E. coli, Salmonella spp. okozta emésztőszervi megbetegedéseinek gyógykezelésére javasoljuk a találmánynak az itt felsorolt és a kiviteli példákban megadott néhány megbetegedésre, állatfajra és kórokozóra való korlátozási szándék nélkül.- rabbit, poultry E. coli, Salmonella spp. For the treatment of gastrointestinal diseases caused by the invention, it is recommended that the invention not be limited to some of the diseases, animal species and pathogens listed and exemplified herein.
A hatóanyagokkal és a kombinációival szarvasmarhákból izolált polirezisztens E. coli (OK K 36 99), valamint sertés eredetű E. coli törzsön leveshígítási módszerrel passzázs vizsgálatokat végeztünk a rezisztencia kiváltására. Rezisztensnek tekintettük a gyógyszert és kombinációját, ha a vizsgált törzsek a 200 mg/1 töménységben is szaporodtak. Az eredményeket a 8. táblázat mutatja be.Passive assays were performed to isolate the polyresistant E. coli (OK K 36 99) and porcine E. coli strains isolated with bovine active substances and combinations thereof. The drug and its combination were considered resistant if the tested strains also increased at 200 mg / l. The results are shown in Table 8.
SOSALT
190 963190,963
8. táblázatTable 8
A vizsgálatokból megállapítható, hogy kombi- jo nációval a rezisztencia kialakulás jelentős mértékben késleltethető.Studies have shown that the combination can significantly delay the development of resistance.
A készítmény javasolt adagolása perorálisan átlagosan 5-20 mg/ttkg, parenterálisan intrauterin 1 : 1 arányú keverékből 2 g/állat kapszulában be- 2s helyezve.The composition for peroral administration suggested average of 5 to 20 mg / kg administered parenterally intrauterine 1: 1 mixture of 2 g / animal on capsule 2 and inserted.
Egyedi kezelés esetén: 20%-os hatóanyagtartalmú készítménybőlFor single treatment: from 20% active ingredient
- malacoknak 50-200 mg vizes szuszpenzióban napon át, 30 - piglets at 50 to 200 mg in an aqueous suspension day 30
- borjaknak 0,6-2,5 g vizes szuszpenzióban 3-4 napon át.- calves in a 0.6-2.5 g aqueous suspension for 3-4 days.
Tömeges kezelés esetén: 20%-os hatóanyagtartalmú készítményből takarmányba keverveIn case of bulk treatment: 20% by weight of the active substance in a compound feedingstuff
- sertéseknek 0,06-0,25%-os koncentrációban 35 5 napon át,- pigs at a concentration of 0,06 to 0,25% for 35 days,
- nyulaknak, baromfinak 0,04-0,15 %-os koncentrációban.- rabbits, poultry at a concentration of 0.04-0.15%.
A találmány szerinti eljárás foganatosítására az alábbi kiviteli példákat adjuk meg. 40 In order to carry out the process according to the invention, the following examples are given. 40
1. példa oxitetraciklin 500 mg oxolinsav 500 mg tejcukor 3000 mgExample 1 oxytetracycline 500 mg oxolinic acid 500 mg lactose 3000 mg
4000 mg4000 mg
A gyógyszerkeveréket ,0,5 1 langyos kamillateában szuszpendáltuk és borjaknak szájon át naponta két alkalommal adtuk be. 50 The drug mixture was suspended in 0.5 l lukewarm chamomile tea and administered orally twice daily to calves. 50
A gyógyszeres kezelést négy napon át folytattuk. Elővizsgálataink szerint az enteritisben megbetegedett borjak már a második adag bevitele után klinikailag gyógyultak voltak. A híg bélsárűrítés megszűnt, az állatok állapota jelentősen javult, étvágyuk fokozódott.Medication was continued for four days. According to our preliminary studies, calves with enteritis were clinically cured after the second dose. The dilute bowel movement ceased, the animals improved significantly and their appetite increased.
Az általunk kezelt 50 állat közül egy sem pusztult el.None of the 50 animals we treated died.
2. példa oxitetraciklin 1,0 g nalidixsav 1,0 gExample 2 Oxytetracycline 1.0 g nalidixic acid 1.0 g
A gyógyszerkeveréket kapszulába töltöttük és frissen ellett tehenek méhébe helyeztük, naponta 1 alkalommal, 3 napon át. A gyógyszeres kezelésben részesült tehenekben a méh involúciója zavarmentes volt. A méh tisztulása meggyorsult, a váladék jellege bakteriális infekcióra nem utalt.The drug mixture was filled into capsules and placed in the uterus of freshly calved cows, once daily for 3 days. In cows treated with medication, uterine involution was free of disturbances. Uterine clearance was accelerated, and the nature of the secretion did not indicate bacterial infection.
A készítmények előnye, hogy a szinergista hatás és a kisebb hatóanyagkoncentráció mellett eredményesen alkalmazható különösen szopós állatok fertőzéseinek gyógykezelésére.The compositions have the advantage that they can be used effectively in the treatment of infections of particularly lactating animals, with a synergistic effect and lower active ingredient concentration.
Claims (6)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU841682A HU190963B (en) | 1984-04-28 | 1984-04-28 | Process for production of synergyc medical preparatives containing organic acids with oxitetracylin and antimicrobatic influence |
| BE1/011244A BE902251A (en) | 1984-04-28 | 1985-04-22 | NOVEL PHARMACEUTICAL COMPOSITIONS HAVING ANTIMICROBIAL ACTIVITY AND PROCESS FOR THEIR PREPARATION. |
| CH1750/85A CH666817A5 (en) | 1984-04-28 | 1985-04-24 | ANTIMICROBIALLY ACTIVE DRUG PREPARATIONS AND METHOD FOR THE PRODUCTION THEREOF. |
| ES542611A ES8706028A1 (en) | 1984-04-28 | 1985-04-26 | Pharmaceutical combinations with a synergistic action |
| DE19853515214 DE3515214A1 (en) | 1984-04-28 | 1985-04-26 | Pharmaceutical combinations with a synergistic action |
| FR8506395A FR2563433B1 (en) | 1984-04-28 | 1985-04-26 | NOVEL PHARMACEUTICAL COMPOSITIONS COMPRISING OXYTETRACYCLINE AND AN ORGANIC ACID HAVING ANTIMICROBIAL ACTIVITY AND METHOD FOR THEIR PREPARATION |
| IT20514/85A IT1200460B (en) | 1984-04-28 | 1985-04-26 | COMPOSITIONS OF DRUGS EQUIPPED WITH ANTI-MICROBIAL ACTIVITY AND PROCEDURE FOR THEIR PREPARATION |
| NL8501198A NL8501198A (en) | 1984-04-28 | 1985-04-26 | NEW MEDICINAL PRODUCTS WITH ANTIMICROBIAL EFFECT AND METHOD FOR THE PREPARATION THEREOF. |
| SE8502039A SE467445B (en) | 1984-04-28 | 1985-04-26 | NEW PHARMACEUTICAL COMPOSITIONS WITH ANTI-MICROBIAL ACTIVITY AND PROCEDURES FOR THEIR PREPARATION |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU841682A HU190963B (en) | 1984-04-28 | 1984-04-28 | Process for production of synergyc medical preparatives containing organic acids with oxitetracylin and antimicrobatic influence |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT37349A HUT37349A (en) | 1985-12-28 |
| HU190963B true HU190963B (en) | 1986-12-28 |
Family
ID=10955662
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU841682A HU190963B (en) | 1984-04-28 | 1984-04-28 | Process for production of synergyc medical preparatives containing organic acids with oxitetracylin and antimicrobatic influence |
Country Status (9)
| Country | Link |
|---|---|
| BE (1) | BE902251A (en) |
| CH (1) | CH666817A5 (en) |
| DE (1) | DE3515214A1 (en) |
| ES (1) | ES8706028A1 (en) |
| FR (1) | FR2563433B1 (en) |
| HU (1) | HU190963B (en) |
| IT (1) | IT1200460B (en) |
| NL (1) | NL8501198A (en) |
| SE (1) | SE467445B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU200917B (en) * | 1987-07-20 | 1990-09-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing pharmaceutical compositions comprising quinoline or naphthyridinecarboxylic acid and tetracycline derivatives as active ingredient |
| EP0951902A1 (en) * | 1998-03-31 | 1999-10-27 | Edmund J.H. Campion | A feed mixture |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH642850A5 (en) * | 1978-10-20 | 1984-05-15 | Ausonia Farma Srl | PHARMACEUTICAL COMPOSITIONS WITH ANTIBACTERIAL ACTIVITY AGAINST GRAM-POSITIVE AND GRAM-NEGATIVE GERM INFECTIONS. |
-
1984
- 1984-04-28 HU HU841682A patent/HU190963B/en not_active IP Right Cessation
-
1985
- 1985-04-22 BE BE1/011244A patent/BE902251A/en not_active IP Right Cessation
- 1985-04-24 CH CH1750/85A patent/CH666817A5/en not_active IP Right Cessation
- 1985-04-26 SE SE8502039A patent/SE467445B/en not_active IP Right Cessation
- 1985-04-26 IT IT20514/85A patent/IT1200460B/en active
- 1985-04-26 FR FR8506395A patent/FR2563433B1/en not_active Expired
- 1985-04-26 NL NL8501198A patent/NL8501198A/en not_active Application Discontinuation
- 1985-04-26 DE DE19853515214 patent/DE3515214A1/en not_active Withdrawn
- 1985-04-26 ES ES542611A patent/ES8706028A1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| IT1200460B (en) | 1989-01-18 |
| SE8502039L (en) | 1985-10-29 |
| HUT37349A (en) | 1985-12-28 |
| SE467445B (en) | 1992-07-20 |
| FR2563433A1 (en) | 1985-10-31 |
| IT8520514A0 (en) | 1985-04-26 |
| DE3515214A1 (en) | 1985-10-31 |
| BE902251A (en) | 1985-10-22 |
| ES542611A0 (en) | 1987-06-01 |
| ES8706028A1 (en) | 1987-06-01 |
| NL8501198A (en) | 1985-11-18 |
| FR2563433B1 (en) | 1988-12-02 |
| CH666817A5 (en) | 1988-08-31 |
| SE8502039D0 (en) | 1985-04-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |