CS235997B2 - Method of 1-(3-methyl-4-trifluormethylthiophenoxy)fenyl)-3-methyl-1,3,5-triazine-2,4,6-(1h,3h,5h)-trion solutions production - Google Patents
Method of 1-(3-methyl-4-trifluormethylthiophenoxy)fenyl)-3-methyl-1,3,5-triazine-2,4,6-(1h,3h,5h)-trion solutions production Download PDFInfo
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- CS235997B2 CS235997B2 CS84177A CS17784A CS235997B2 CS 235997 B2 CS235997 B2 CS 235997B2 CS 84177 A CS84177 A CS 84177A CS 17784 A CS17784 A CS 17784A CS 235997 B2 CS235997 B2 CS 235997B2
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- Prior art keywords
- methyl
- solvent
- water
- triazine
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- 238000000034 method Methods 0.000 title claims description 9
- 239000002904 solvent Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 5
- 239000002798 polar solvent Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical group NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 229940031098 ethanolamine Drugs 0.000 claims 1
- 239000000243 solution Substances 0.000 description 26
- 239000013543 active substance Substances 0.000 description 12
- -1 polyoxyethylene Polymers 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 239000003651 drinking water Substances 0.000 description 6
- 235000020188 drinking water Nutrition 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 208000003495 Coccidiosis Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010023076 Isosporiasis Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- MBIQENSCDNJOIY-UHFFFAOYSA-N 2-hydroxy-2-methylbutyric acid Chemical compound CCC(C)(O)C(O)=O MBIQENSCDNJOIY-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000003021 water soluble solvent Substances 0.000 description 2
- FEOHYDSNGHIXOM-WLDMJGECSA-N (3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)-2-methyloxane-2,4,5-triol Chemical compound CC1(O)[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO FEOHYDSNGHIXOM-WLDMJGECSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N Arginine Chemical compound OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical group CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- URWAJWIAIPFPJE-UHFFFAOYSA-N Rickamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(CN)O2)N)C(N)CC1N URWAJWIAIPFPJE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 229930194936 Tylosin Natural products 0.000 description 1
- 239000004182 Tylosin Substances 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019728 animal nutrition Nutrition 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940100242 glycol stearate Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229950007634 kitasamycin Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- XYJOGTQLTFNMQG-KJHBSLKPSA-N leucomycin V Chemical compound CO[C@H]1[C@H](O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(O)C2)[C@@H](C)O1 XYJOGTQLTFNMQG-KJHBSLKPSA-N 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 1
- 229960004059 tylosin Drugs 0.000 description 1
- 235000019375 tylosin Nutrition 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dispersion Chemistry (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
- Detergent Compositions (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Fodder In General (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Enzymes And Modification Thereof (AREA)
- Feed For Specific Animals (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
- Cosmetics (AREA)
Abstract
Description
Předložený vynález se týká způsobu výroby roztoků 1-r3-metthl-4-(4*-trifluormethylthiofenoxy)fenyl]-3-methy1-1)3,5-triszin-2,4,6-(1H,3H, 5H)-trionu maltových s vodou, které se poulívají při po otírání kokcidióz.The present invention relates to a process for the preparation of solutions of 1- [3-methyl-4- (4'-trifluoromethylthiophenoxy) phenyl] -3-methyl-l) 3,5-triszine-2,4,6- (1H, 3H, 5H) - trion mortar with water, which are used when wiping coccidiosis.
Shora uvedená sloučenina, jejíž chemický strukturní vzorec je uveden dále,The above compound, whose chemical structural formula is given below,
je známa jako účinná látka proti onemocněním kokcideózou a podobným nemocem zvířat. Dosud se tato účinná látka přidávala v krystalické rozemleté formě ke krmivu pro- zvířata a tímto způsobem se provádělo ofleeření. Pro oSetřování prostřednictvím pitné vody, pro které existuje ns mnoha místech značná potřeba, nebylo vSak možno dosud nalézt žádnou upotřebitelnou aplikační formu. Aby bylo možno zajistit bezpečnou aplikaci pomocí pitné vody, misí se takováto účinná látka vystytovat asi po dobu 24 hodin homogenně rozptýlena ve vodě. Účinná látka se rozpou^í ve vodě jen do koncentrace asi é 5 ppm, tj. její rozpustnost ve - vodě je nedostatečná* Pokikl se účinná látka používá ve formě suspenze, pak tato látka v tomto časovém intervalu v konccntraci používané při aplikaci 8e(^jim^e^tt^;je·It is known as an active ingredient against coccidiosis and similar animal diseases. To date, the active ingredient has been added to the animal feed in crystalline ground form, and in this way, it has been subjected to an ablation procedure. However, no useful dosage form has yet been found for drinking water treatment, for which there is a great need in many places. In order to ensure safe application with the aid of drinking water, such an active substance is scored homogeneously dispersed in water for about 24 hours. The active substance dissolves in water only up to a concentration of about 5 ppm, i.e. its solubility in water is insufficient. If the active substance is used in the form of a suspension, the active substance is used in the concentration used during the application of 8e. jim ^ e ^ tt ^; is ·
Koncomtrace, ve které se účinná látka aplikuje, se může podle obtížnosti onemocnění pohybovat mezi 5 až 500 ppm, větSinou vSak mezi 20 a 200 ppm.Depending on the severity of the disease, the concentration in which the active ingredient is applied can vary between 5 and 500 ppm, but usually between 20 and 200 ppm.
Účinná látka vzorce I se dobře rozpouští v různých organických rozpouštědlech, jako například v acetonu, v ethy^ste™ kyseliny mléčné nebo v N-renhuУpyrгolidunu. Při zředění takovéhoto roztoku v pitné vodě pro zvířata na kom:aeraci používanou při aplikaci se vSak účinná látka ihned nebo po krátké době vyloučí. Také solubilizace pomocí solubilizátorů, jako například pomocí poíLyoxet^h^yl^c^i^tn^ého ^ο^ονά^- oleje nebo polyuxethylnn8orbitanu esterů mastných kyselte nevede k úspěchu. Vysrážení účinné látky se sice o cěkooik hodin zpomllí, nikoliv vSak po dobu 24 hodin..The active compound of the formula I dissolves well in a variety of organic solvents, such as acetone, ethyl lactic acid or N-renopyrrolidone. However, upon dilution of such a solution in the drinking water for animals to the aeration used in the application, the active substance is excreted immediately or after a short time. Also, solubilization with solubilizers, such as polyoxyethylene glycol oil or polyuxethylene sorbitan fatty acid esters, does not lead to success either. The precipitation of the active substance is delayed by a few hours, but not for 24 hours.
S překvapením í^íL^o nyní zjištěno, že roztoky účinné látky vzorce I msitelné s vodou, které obsahuj jedno nebo n^l^ooik polárních rozpouštědel a které reaguj alkalicky, se mohou ředit v pitné vodě pro zvířata na koncentrace používané při aplikaci a během 24 hodin se cevylučnuí.Surprisingly, it has now been found that water-miscible solutions of the active compound of formula I which contain one or more polar solvents and which react alkaline can be diluted in drinking water for animals to the concentrations used during application and they are excreted within 24 hours.
Předmětem předloženého vynálezu jsou tudíž roztoky (-[3-reetyl-4-(4/-tгifluoгrnthylthiugnncuy)-fnncУ.l-3-reeJhý-(»3»5-trezet-2,4,6-(1H,ЗH,5H1-triutu г18^п1сП s vodou, které obsahuj jedno nebo n^l^ooik polárních rozpouštědel a které reaguj alkalicky. *The present invention therefore relates to solution of (- [3-reetyl-4- (4 / -tгifluoгrnthylthiugnncuy) -fnncУ.l reeJhý-3 - ( »3» 5-TREZETA-2,4,6 (1H, ЗH, 5H1 - triacetate with water containing one or more polar solvents and reacting alkaline.
Způ8ub výroby roztok (-Cз-mrnhul-4-(4*-trtulucmmntUylUhiiecnuxy)fncyl]-Зmnthyl-(,3»5-trjazCn-2,4,6-(1H,HH, ЭН^г^си maltených s vodou podle tohoto vynálezu spočívá v tom, že se účinná látka rozpučí v polárním, popřípadě alkalicky reagujícím rozpouštědle místectném s vodou a tecto roztok se rozpuStěním nebo suspendováním alkalicky reagujících přísad upraví na pH 8 až ((.Způ8u B Preparation of solution Y (u mrnh -Cз-L-4- (4 * -trt at lucmmnt Uy liquor ii cnuxy e) FNC yl] -З Mn th y l - (3 »5-trjazCn-2 The 4,6- (1H, HH, ЭN ^ г ^ ^) mortar mixed with water according to the invention consists in dissolving the active ingredient in a polar or alkaline reacting solvent which is water-soluble and adjusting this solution by dissolving or suspending the alkaline reacting additives. to pH 8 to ((.
Při výrobě roztoků podle vynálezu se účinná látka rozpussí v polárním, ve vodě rozpustném rozpouštědle, - které bu3 reaguje alkalicky nebo se k němu přidá alkalická látka rozpustná ve vodě. Tato alkalická látka se výhodně rovněž rozpustí v rozpouštědle, může se vSak také suspendovat v rozpouštědle a rozpouštět se teprve v pitné vodě. Přioom má mít pitcá voda po přídavku roztoku účinné látky hodnotu pH více než 7, výhodně vSak hodnotu pH větší cež 8.In the preparation of the solutions according to the invention, the active ingredient is dissolved in a polar, water-soluble solvent, which is either reacted alkaline or a water-soluble alkali is added thereto. The alkali is preferably also dissolved in the solvent, but can also be suspended in the solvent and only dissolved in drinking water. In addition, the drinking water should have a pH of more than 7, preferably a pH of greater than 8, after addition of the active compound solution.
Roztok konc extrátu účinné látky nemá mít hodnotu pH vyšší než 11 a cižSÍ cež pH 8.The concentrate solution of the active ingredient should not have a pH greater than 11 and no more than pH 8.
Koncentrace účinné látky se může pohybovat v rozmezí od 0,5 do 50 výhodné je však v rozmezí od 1 do 25The concentration of active ingredient may be in the range of 0.5 to 50, but preferably in the range of 1 to 25
Jako rozpouštědla přicházejí v úvahu všechna ve vodě rozpustná rozpouštědla, ve kterých je účinná látka rozpustná v dostačující koncentraci a která jsou fyziologicky nezávadná.Suitable solvents are all water-soluble solvents in which the active substance is soluble in a sufficient concentration and which are physiologically harmless.
Takovými rozpouštědly jsou z řady alkoholů jednomocné a vícemocné alkoholy, jako například ethylalkohol, isopropylalkohol, benzylalkohol, glycerol, propylenglykol, polyS ethylenglykoly, póly(oxyethylen)póly(oxypropylen)ové polymery, bázické alkoholy, jako například mono-, di- a triethanolamin.Such solvents include monohydric and polyhydric alcohols such as ethanol, isopropanol, benzyl alcohol, glycerol, propylene glycol, polyS ethylene glycols, poly (oxyethylene) poles (oxypropylene) polymers, basic alcohols such as mono-, di- and triethanolamine.
Kromě toho jsou vhodnými rozpouštědly ketony, jako například aceton nebo methylethylketon a z řady esterů například ethylester mléčné kyseliny· Rovněž se mohou používat dalSí rozpouštědla, jako N-methylpyrrolidon, dimethylacetamid, dimethylformamid.In addition, suitable solvents are ketones, such as acetone or methyl ethyl ketone, and from a number of esters, for example ethyl lactic acid ester. Other solvents such as N-methylpyrrolidone, dimethylacetamide, dimethylformamide may also be used.
Jako bází к úpravě alkalické hodnoty pH se používá výhodně organických bází, jako například bázických aminokyselin, jako L- popřípadě D,L-argininu, L- popřípadě D,L-lysinu, avšak také cholinu, methylglukosaminu, glukosaminu, 2-amino-2-hydroxymethyl-1,3-propandiolu. Pro tento účel se hodí také diaminy, jako například N,N,N',N*-tetrakie-(2-hydroxypropylj_ ethylendiamin nebo polyether-tetrol na bázi ethylendiaminu (molekulová hmotnost 480 až 420, OH-index 432-467), které rovněž vytvářejí čiré roztoky v uvedeném rozmezí hodnot pH. Také anorganické báze se mohou používat pro uvedené účely, jako například amoniak nebo uhličitan sodný, popřípadě za přídavku vody·Organic bases such as basic amino acids, such as L- or D, L-arginine, L- or D, L-lysine, but also choline, methylglucosamine, glucosamine, 2-amino-2 are preferably used as bases for adjusting the alkaline pH. -hydroxymethyl-1,3-propanediol. Also suitable for this purpose are diamines such as N, N, N ', N ' -tetrakia- (2-hydroxypropyl) ethylenediamine or ethylenediamine-based polyether-tetrol (molecular weight 480-420, OH index 432-467), which they also form clear solutions within the above-mentioned pH range Inorganic bases can also be used for the stated purposes, such as ammonia or sodium carbonate, optionally with the addition of water.
Aplikují-li se zvířatům současně β prostředky proti kokcidióze látky a prostředky, které jsou vhodné к profylaxi nebo/a к medikaci, pak se mohou navíc přidávat к prostředku, aby v tomto prostředku sloužily jako bázická složka, jako je tomu například v případě aminoglykosidových antibiotik, jako je streptomycin, gentamycin, sisomycin, eomycin, nebo makrolidových antibiotik, jako je tylosin nebo kitasamycin nebo sodné soli sulfonamidů.In addition, if animals are co-administered with anti-coccidiosis agents and agents that are suitable for prophylaxis and / or medication, they may additionally be added to the composition to serve as a basic component in the composition, such as aminoglycoside antibiotics , such as streptomycin, gentamycin, sisomycin, eomycin, or macrolide antibiotics such as tylosin or kitasamycin or sodium sulfonamides.
Látky, které se jinak používají jako emulgátory nebo jako solubilizátory a které jsou rozpustné ve vodě na koloidní roztok, se mohou v tomto případě používat jako polární rozpouštědla, pokud se к nim přidá ještě bázická pomocná látka.Substances which are otherwise used as emulsifiers or as solubilizers and which are water-soluble to a colloidal solution can in this case be used as polar solvents if a basic excipient is added.
Jak již bylo shora uvedeno, nedaří se bez přídavku alkalicky účinných látek, udržet účinnou látku solubilizováním po delší dobu v roztoku v konečné koncentraci. Takovéto emulgátory se však mohou přidávat ke shora zmíněným roztokům vyráběným podle vynálezu, aby usnadnily například dispergování ve vodě nebo ke smáčení suspendovaných pomocných látek. Zde přicházejí v úvahu zejména polyoxethylované látky, jako například polyoxethylovaný ricinový olej, polyethylenglykol-eorbitan-monooleát, polyethylenglykol-nonylfenyl, polyethy1englykolstearát nebo polyethylenglykolether. Zvláště výhodné jsou zde bázické deriváty, jako pólyethylenglykolalkylaminy.As mentioned above, it is not possible to maintain the active ingredient by solubilization in solution at a final concentration for a long time without the addition of alkaline active ingredients. Such emulsifiers may, however, be added to the above-mentioned solutions produced according to the invention in order to facilitate, for example, dispersion in water or wetting of the suspended excipients. Particularly suitable are polyoxyethylated materials such as polyoxyethylated castor oil, polyethylene glycol eorbitan monooleate, polyethylene glycol nonylphenyl, polyethylene glycol stearate or polyethylene glycol ether. Particularly preferred are basic derivatives such as polyethylene glycol alkyl amines.
Roztoky popřípadě suspenze shora uvedeného typu mohou obsahovat také 0,1 až 20 hmotnostních, výhodně 0,1 až 10 % hmotnostních dalších pomocných látek používaných v takovýchto prostředcích, jako jsou antioxidační prostředky, další tensidy, stabilizátory suspenzí a zahušiovadla, jako je například methyleelulóza, koloidní kyselina křemičitá a další. Rovněž možný je přídavek barviva, aromatických látek a látek potřebných jako stavebních prvků pro výživu zvířat. V této souvislosti nutno uvést také kyseliny, které společně 8 předloženou bází tvoří pufrovaný systém nebo snižují hodnotu pH roztoku.The solutions or suspensions of the above type may also contain 0.1 to 20% by weight, preferably 0.1 to 10% by weight, of other excipients used in such formulations as antioxidants, other surfactants, suspension stabilizers and thickeners such as methyl cellulose, colloidal silicic acid and others. Addition of coloring matter, flavorings and substances needed as building blocks for animal nutrition is also possible. Acids which together form the buffered system or lower the pH of the solution should also be mentioned.
Následující příklady slouží k bližšímu objasnění vynálezu, jeho rozsah však v žádném případě neorneeuj.The following examples are intended to illustrate the invention in more detail, but do not limit its scope in any way.
Za úěelee výroby roztoků podle vynálezu se látky naváží do nádoby opatřené míchadlem a poté se míchají za zahřívání tak dlouho, dokud nevznikne čirý roztok. V uvedených příkladech je úěinná látka stál.á po tobu 1 méěíce při teplotě 50 °C. Zřed-li se roztoky z uvedených příkladů vodou v poměru 1:1000, je hodnota pH vody ve shora uvedeném rozsahu vyšší než 8.In order to produce the solutions of the invention, the substances are weighed into a vessel equipped with a stirrer and then stirred under heating until a clear solution is formed. The listed for kl and d ec h ú EINN à la Units stál.á after Tobu méěíce 1 when p te Lot of 50 ° C. When diluting the solutions of the examples with water in a ratio of 1: 1000, the pH of the water in the above range is greater than 8.
Příklad!Example!
2,5 g účinné látky se r^pusH za zahřívání v tritahш:lolодinu za vzniku 100 m roztoku. Čirý roztok má hodnotu pH 10,2.2.5 g of the active compound were added to the solution with heating in tritradiol to give a 100 m solution. The clear solution has a pH of 10.2.
Příklad 2Example 2
2,5 g účinné látky a 12,5 g mléčné kyseliny se doplní do 100 mL tгieahnooam^inee a směs se za míchání a zahřívání rozpussí. Ho (dno ta pH roztoku činí 8,3·2.5 g of the active ingredient and 12.5 g of lactic acid are added to 100 ml of tertiary amine and the mixture is dissolved with stirring and heating. Ho (the bottom and the pH of the solution is 8.3 ·
PPíklad 3EXAMPLE 3
10,0 g účinné látky se doplní do 100 ml monoothanolaminem a účinná látka se rozp^H. čirý roztok má hodnotu pH 11.10.0 g of the active substance are made up to 100 ml with monoothanolamine and the active substance is dissolved in. the clear solution has a pH of 11.
PPíklad 4 .EXAMPLE 4.
Hodnota pH roztoku 9,9.The pH of the solution was 9.9.
PPíklad 5EXAMPLE 5
5,0 g účinné látky5.0 g of the active substance
25,0 g D,L-lysinu jako báze do 100 ml polyethylenglykolu (molekulová hmoonost 400). Hodnota pH roztoku 9,8.25.0 g of D, L-lysine base to 100 ml of polyethylene glycol (molecular weight 400). The pH of the solution was 9.8.
PPíklad 6EXAMPLE 6
25,0 g účinné látky25.0 g of the active substance
10,0 ' g moonoehanolaminu do 100 ml N-eethalppyroliUins.10.0 g of moonoehanolamine to 100 ml of N-eethalppyrrolidine.
Hocdnota pH roztoku 10,8.The pH of the solution was 10.8.
Claims (6)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833300793 DE3300793A1 (en) | 1983-01-12 | 1983-01-12 | Coccidiosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS235997B2 true CS235997B2 (en) | 1985-05-15 |
Family
ID=6188113
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS84177A CS235997B2 (en) | 1983-01-12 | 1984-01-09 | Method of 1-(3-methyl-4-trifluormethylthiophenoxy)fenyl)-3-methyl-1,3,5-triazine-2,4,6-(1h,3h,5h)-trion solutions production |
Country Status (18)
| Country | Link |
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| EP (1) | EP0116175B1 (en) |
| JP (1) | JPS59139316A (en) |
| KR (1) | KR900007310B1 (en) |
| AT (1) | ATE40792T1 (en) |
| AU (1) | AU561923B2 (en) |
| CS (1) | CS235997B2 (en) |
| DE (2) | DE3300793A1 (en) |
| DK (1) | DK165668C (en) |
| ES (1) | ES8500058A1 (en) |
| FI (1) | FI81961C (en) |
| HU (1) | HU192529B (en) |
| IE (1) | IE56522B1 (en) |
| IL (1) | IL70641A (en) |
| MY (1) | MY101193A (en) |
| PH (1) | PH20973A (en) |
| PT (1) | PT77916B (en) |
| SU (1) | SU1276249A3 (en) |
| ZA (1) | ZA84219B (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3408768A1 (en) * | 1984-03-09 | 1985-09-12 | Bayer Ag, 5090 Leverkusen | IMMUNTIMULATING AGENTS |
| DE3703105A1 (en) * | 1987-02-03 | 1988-08-11 | Bayer Ag | MEDICINE AGAINST PROTOCOES IN INSECTS |
| DE3703103A1 (en) * | 1987-02-03 | 1988-08-11 | Bayer Ag | AGENT AGAINST FISH PARSITES |
| DE3814323A1 (en) * | 1988-04-28 | 1989-11-09 | Hoechst Ag | WATER-SOLUBLE PREPARATIONS BY COCCIDIOSTATICA |
| CZ146296A3 (en) * | 1995-06-02 | 1997-04-16 | American Cyanamid Co | 3-(3-aryloxyphenyl)-1-(substituted methyl)-s-triazine-2,4,6-oxo or thiotriones, process of their preparation and herbicidal agents |
| PT989851E (en) * | 1997-07-29 | 2002-12-31 | Upjohn Co | AUTO-EMULSING FORMULATION FOR LITHIOPHILIC ACIDIC COMPOUNDS |
| DE19824483A1 (en) | 1998-06-02 | 1999-12-09 | Bayer Ag | Semi-solid aqueous preparations for oral application of toltrazuril sulfone |
| DE102007025908A1 (en) * | 2007-06-01 | 2008-12-04 | Bayer Healthcare Ag | Formulations containing triazinones and iron |
| DE102009012423A1 (en) | 2009-03-10 | 2010-09-16 | Bayer Animal Health Gmbh | Preparation based on oil |
| EP2740469A1 (en) | 2012-12-07 | 2014-06-11 | Ceva Sante Animale | New treatments with triazines |
| EP2740470A1 (en) | 2012-12-07 | 2014-06-11 | Ceva Sante Animale | Treatment of Coccidiosis with intramuscular triazine composition |
| EP2740492A1 (en) | 2012-12-07 | 2014-06-11 | Ceva Sante Animale | Triazine formulations with a second active ingredient and surfactant(s) |
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| FR1476867A (en) * | 1966-03-04 | 1967-04-14 | Wellcome Found | Preparation of stable aqueous solutions containing a mixture of sulfaquinoxaline and diaveridine |
| DE2718799A1 (en) * | 1977-04-27 | 1978-11-09 | Bayer Ag | 1- (4-PHENOXY-PHENYL) -1,3,5-TRIAZINE DERIVATIVES, THE METHOD FOR THEIR MANUFACTURING AND THEIR USE AS A MEDICINAL PRODUCT AND GROWTH PROMOTER |
| EP0081142B1 (en) * | 1981-12-03 | 1986-06-25 | BASF Aktiengesellschaft | 1,3,5-triazinones, process for their preparation and their use in combating undesired plant growth |
-
1983
- 1983-01-12 DE DE19833300793 patent/DE3300793A1/en not_active Withdrawn
- 1983-12-30 DE DE8383113224T patent/DE3379195D1/en not_active Expired
- 1983-12-30 EP EP83113224A patent/EP0116175B1/en not_active Expired
- 1983-12-30 AT AT83113224T patent/ATE40792T1/en not_active IP Right Cessation
-
1984
- 1984-01-03 PT PT77916A patent/PT77916B/en unknown
- 1984-01-09 IL IL70641A patent/IL70641A/en not_active IP Right Cessation
- 1984-01-09 SU SU843688287A patent/SU1276249A3/en active
- 1984-01-09 PH PH30080A patent/PH20973A/en unknown
- 1984-01-09 CS CS84177A patent/CS235997B2/en unknown
- 1984-01-10 FI FI840082A patent/FI81961C/en not_active IP Right Cessation
- 1984-01-10 AU AU23172/84A patent/AU561923B2/en not_active Expired
- 1984-01-11 HU HU8475A patent/HU192529B/en not_active IP Right Cessation
- 1984-01-11 ZA ZA84219A patent/ZA84219B/en unknown
- 1984-01-11 IE IE47/84A patent/IE56522B1/en not_active IP Right Cessation
- 1984-01-11 ES ES528805A patent/ES8500058A1/en not_active Expired
- 1984-01-11 JP JP59002127A patent/JPS59139316A/en active Granted
- 1984-01-11 DK DK012184A patent/DK165668C/en not_active IP Right Cessation
- 1984-01-12 KR KR1019840000108A patent/KR900007310B1/en not_active Expired
-
1987
- 1987-09-29 MY MYPI87002276A patent/MY101193A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE3300793A1 (en) | 1984-07-12 |
| ATE40792T1 (en) | 1989-03-15 |
| FI840082L (en) | 1984-07-13 |
| ES528805A0 (en) | 1984-10-01 |
| PH20973A (en) | 1987-06-15 |
| KR900007310B1 (en) | 1990-10-08 |
| SU1276249A3 (en) | 1986-12-07 |
| IE840047L (en) | 1984-07-12 |
| IL70641A0 (en) | 1984-04-30 |
| HU192529B (en) | 1987-06-29 |
| DK165668B (en) | 1993-01-04 |
| DK12184A (en) | 1984-07-13 |
| DE3379195D1 (en) | 1989-03-23 |
| AU2317284A (en) | 1984-07-19 |
| JPS59139316A (en) | 1984-08-10 |
| KR840007355A (en) | 1984-12-07 |
| IL70641A (en) | 1987-01-30 |
| MY101193A (en) | 1991-07-31 |
| DK165668C (en) | 1993-06-01 |
| AU561923B2 (en) | 1987-05-21 |
| DK12184D0 (en) | 1984-01-11 |
| JPH0216730B2 (en) | 1990-04-18 |
| EP0116175A3 (en) | 1986-02-19 |
| FI81961B (en) | 1990-09-28 |
| ES8500058A1 (en) | 1984-10-01 |
| PT77916A (en) | 1984-02-01 |
| ZA84219B (en) | 1984-09-26 |
| EP0116175B1 (en) | 1989-02-15 |
| EP0116175A2 (en) | 1984-08-22 |
| FI81961C (en) | 1991-01-10 |
| IE56522B1 (en) | 1991-08-28 |
| PT77916B (en) | 1986-04-16 |
| FI840082A0 (en) | 1984-01-10 |
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