IL90098A - Water-soluble preparations of n-phenyltriazine coccidiostats their preparation and use - Google Patents
Water-soluble preparations of n-phenyltriazine coccidiostats their preparation and useInfo
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- IL90098A IL90098A IL9009889A IL9009889A IL90098A IL 90098 A IL90098 A IL 90098A IL 9009889 A IL9009889 A IL 9009889A IL 9009889 A IL9009889 A IL 9009889A IL 90098 A IL90098 A IL 90098A
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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
- A61K31/33—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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- 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
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- 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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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Polysaccharides And Polysaccharide Derivatives (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
Active substance preparations characterised by a) up to 10000 ppm, based on the weight of the preparation, of one or more coccidiostats of the general formulae I and II <IMAGE> in which R<1>, R and R' are, independently of one another, hydrogen or C1-C4-alkyl, R<2> is together with R<3> a double bond or independently thereof hydrogen or C1-C4-alkyl, R<3> is together with R<2> a double bond or independently thereof hydrogen or C1-C4-alkyl, W is oxygen or sulphur, X is, in each case independently of one another, halogen such as fluorine, chlorine and bromine, C1-C4-alkyl, trifluoromethyl, cyano, thiocyanato, C1-C4-alkylthio, nitro or C1-C4-alkoxy, n is 0, 1, 2, 3 or 4, preferably 0 to 2, Y is hydrogen, C1-C6-alkyl, C1-C6-halogenoalkyl, benzyl, phenyl or phenyl which is substituted by at least one radical from the group comprising alkyl, alkoxy, halogenoalkyl, halogenoalkoxy, halogen, alkylthio, alkylsulphinyl, alkylsulphonyl, halogenoalkylthio, halogenoalkylsulphinyl and halogenoalkylsulphonyl, each with 1 to 4 C atoms in the alkyl radical, or is thienyl or halothienyl and Z is a direct bond or a divalent group of the formula O, S, SO, SO2, NH, NR<0> in which R<0> is hydrogen or C1-C4-alkyl, or C(CN)(R<+>) in which R<+> is hydrogen or methyl, b) a water-miscible, physiologically acceptable, anionic or non-ionic surfactant or a mixture of a plurality of these surfactants and c) 0 to 80% by weight, based on the preparation, of a physiologically acceptable, water-soluble organic solvent and d) 0 to 70% by weight, based on the preparation, of water, are suitable, by reason of their solubility in water, for the treatment of coccidiosis in livestock via the drinking water thereof.
Description
WATER-SOLUBLE PREPARATIONS OF N-PHENYLTRIAZINE COCCIDIOSTATS, THEIR PREPARATION AND USE. >ΟΟΟΙ»Ί>ΡΙΡ i>TKio?»afl- N ?® ο*ω O»O>OD οη>κοη ana e>ia>wi onwn HOECHST AKTIENGESELLSCHAFT HOE 88/F 104 Dr. LO/sch Description Water-soluble preparations of coccidiostats The invention relates to liquid preparations of coccidiostats, which can be administered to livestock with the drinking water.
N-Phenyltriazines of the general formulae I and II W R' in which R1, R and R' denote, independently of one another, hydrogen or C1-C4-alkyl, R^ denotes together with R^ a double bond or indepen- dently thereof hydrogen or C1-C4-alkyl, R^ denotes together with R2 a double bond or independently thereof hydrogen or C1-C4-alkyl, W denotes oxygen or sulfur, X denotes, independently of the others, halogen such as fluorine, chlorine and bromine, C1-C4-alkyl, trifluoromethyl, cyano, thiocyanato, C^-C4-alkylthio, nitro or C1-C4-alkoxy, n denotes 0, 1, 2, 3 or 4, preferably 0 to 2, Y denotes hydrogen, (^-Cg-alkyl, C^-Cg-halogenoalkyl, benzyl, phenyl or phenyl which is substituted by a least one radical from the group comprising alkyl, alkoxy, halogenoalkyl , halogenoalkoxy, halogen, alkylthio, alkylsulfinyl, alkylsulfonyl , halogenoalkylthio, halogenoalkylsulfinyl and halogenoalkyl- sulfonyl, each alkyl radical having 1 to 4 carbon atoms , or denotes thienyl or halothienyl , and Z denotes a direct bond or a divalent group of the formula 0, S, SO, S02, NH, NR° in which R° is hydrogen or C1-C4-alkyl, or denotes C(CN)(R+) in which R+ is hydrogen or methyl, have been disclosed as substances active against coc-cidiosis and similar diseases of livestock; compare, for example, the European Patent Applications with the publication numbers 0,215,354. 0,154,885 (US-A 4,640,917), 0,170,316 and 0,232,932 as well as German Offenlegungsschriften Nos. 2,413,722, 2,718,799 and 2,722,537 (US-A 4,198,407) as well as US Patent No. 3,905,971.
In Israeli Patent No. 81421 - Janssen - there are described antiprotozoal compositions and it is alleged that certain of these anticoccidial compositions can also be administered via drinking water.
For the treatment of coccidiosis it has hitherto been necessary for the active substances to be added in solid crystalline form to the livestock feed. It has not hitherto been possible to find a form generally suitable to be used for a treatment via the drinking water. On the other hand, it is exactly the treatment via the drinking water, where this is possible, which often corresponds in an ideal manner to the requirements of the livestock keeper, especially in the management of active livestock. Thus, for example, it often occurs that livestock suffering from coccidiosis refuse feed intake whereas there is still a readiness to take in drinking water. Therapy of the coccidiosis via the feed which contains active substance is therefore often impeded or impossible.
In order to ensure reliable administration via the drinking water, the active substance must be present in a stable and effective form homogeneously distributed in the water. The active substances of the above-mentioned formulae (I) and (II) are insoluble in water. They sediment out, entirely or partially, from a suspension prepared in the concentration for use even during the period of use, the concentration for use varying with the species and severity of the disease and being as a rule 1 to 500 ppm, usually and preferably 2 to 100 ppm, especially 2 to 30 ppm. The period of use depends on the details of the livestock feeding. However, the drinking water to which the active substance has been added should form a stable aqueous solution or suspension for at least 24 hours, and for longer than 24 hours if possible. Thus, for the cocci-diostats of the formula (I) and (II), it is not pos-sible to prepare without the use of auxiliaries an aqueous form for use with a defined content of active substance which is stable over this period.
The active substances of the formulae (I) and (II) dis-solve readily in various organic solvents, for example in acetone, alcohols, dimethyl sulfoxide, ethyl acetate or N-methylpyrrolidone. However, when these solutions are diluted with water to a concentration for administration the active substances precipitate out again immediately or after a short time.
DE-A 3,300,793 discloses water-miscible solutions of the active substance of the formula (II) in which R denotes hydrogen, R' denotes methyl, n denotes 1, X denotes 3-methyl, denotes 0 and Y-Z denotes 4-triflu-oromethylthiophenoxy. These solutions of active substance which contain one or more polar solvents and substances having an alkaline reaction can be diluted with water to the concentration for administration of the active substances without the active substance precipitating out within 24 hours.
This method for the preparation of stable aqueous solutions of active substances cannot be applied to active substances of the general formula (I).
DE-A 3,300,793 furthermore discloses that solubilization in aqueous medium by addition of solubilizers such as, for example, polyoxyethylated castor oil or poly-oxyethylene sorbitan fatty acid esters is unsuccessful with the said active substance of the formula (II). Although the precipitation out of the active substance is delayed by some hours, it is not delayed for a period of 24 hours.
Nor is it possible to dissolve active substances of the general formula (I) in the concentration required for administration in water which contains solubilizers in the customary concentration i.e. that which does not interfere with use (0.5 to 5% by weight).
Thus, there is a need for preparations of coccidiostats which can be diluted with drinking water to the concen-tration for administration of the active substances without the active substances precipitating out within a short time.
The invention relates to preparations containing one or more active substances of the abovementioned formulae (I) and (II), which contain a) up to 10,000 ppm, based on the weight of the preparation, of active substances, b) a water-miscible, physiologically acceptable anionic or nonionic surfactant or a mixture of several of these surfactants, c) 0 to 80% by weight, based on the preparation, of a physiologically acceptable water-soluble organic solvent, and d) 0 to 70% by weight, based on the preparation, of water .
When the preparations according to the invention are diluted with drinking water to the concentration for administration of the coccidiostats , of 1 to 500 ppm, preferably 2 to 100 ppm, especially 2 to 30 ppm, the resulting aqueous solutions of active substance remain stable for a lengthy period, i.e. for up to several days and, at the least, for longer than 24 hours. The stability of the solutions is surprising because the proportion of the solubilizers in the drinking water is as a rule in fact considerably below the abovementioned customary concentration of 0.5 to 5% by weight at which, when present in the drinking water, it is no longer possible subsequently to dissolve the active substances with the formation of a stable aqueous solution. The concentration of the solubilizer in the drinking water, i.e. after the dilution of the active substance preparations according to the invention, is preferably 0.001 to 0.1% by weight, especially 0.001 to 0.01% by weight, of solubilizer.
The water-miscible solution concentrates (preparations) according to the invention have revealed a possible way, which is economic and easily achievable in industry, for preparing stable aqueous solutions of active substances which are not otherwise soluble in water in the concentration for administration.
Of particular interest are preparations according to the invention which contain an active substance of the abovementioned formula (I) in which R1 denotes hydrogen or C1-C4-alkyl, preferably hydrogen or methyl, denotes together with a double bond, or R* and RJ denote, independently of one another, hydrogen or Ci-C4~alkyl, especially hydrogen or methyl, X denotes, each independently of the others, chlorine, bromine, C1-C4-alkyl, preferably methyl, triflu- oromethyl or C^-C^alkoxy, n denotes 0, 1 or 2 Y denotes hydrogen, C1-C4-halogenoalkyl, especially C^- C3~alkyl having one or more fluorine atoms as sub- stituents, phenyl or phenyl which is substituted by at least one radical from the group comprising methyl, methoxy, trifluoromethyl, chlorine, methyl- thio, methylsulfinyl, methylsulfonyl, trifluoro- methylthio, trifluoromethylsulfinyl or trifluoro- methylsulfonyl, and Z denotes a direct bond or oxygen.
Preferred preparations according to the invention con-tain an active substance a) of the formula (la) in which R1 denotes hydrogen or methyl, denotes together with a double bond, or R^ and R^ denote, independently of one another, hydrogen or methyl, X' denotes hydrogen, chlorine or trifluoromethyl, and Y-Z- denotes hydrogen, especially tetrafluoroethoxy or hexafluoropropoxy, or C1-C4- alkylsulfonylphenoxy, especially 4-methylsulfonylphe- noxy.
Also of particular interest are preparations according to the invention containing an active substance a) of the formula (II) in which R and R' denote, independently of one another, hydrogen or methyl, W denotes oxygen, X denotes, each independently of the others, chlorine, C1-C4-alkoxy, C1-C4-alkyl or trifluoromethyl, n denotes 0, 1 or 2, Y denotes phenyl or phenyl which is substituted by at least one substituent from the group comprising chlorine, trifluoromethyl, trifluoromethoxy, triflu- oromethylthio, trifluoromethylsulfinyl or triflu- oromethylsulfonyl, and Z denotes oxygen.
Preferred preparations containing an active substance a) of the formula (II) are those in which in formula (II) R1 denotes hydrogen, denotes methyl, W denotes oxygen, X denotes 3-methyl, n denotes 1, and the group Y-Z- denotes the radical 4-trifluoromethylthiophenoxy.
Suitable auxiliaries b) in the preparation according to the invention are anionic and nonionic surfactants which are miscible with water and in which the active substance is soluble in an adequate concentration and which are physiologically acceptable. Suitable nonionic surfactants belong, for example, to the group of ethers or esters of olxgoethylene glycol ethers with compounds from the group of C^-C^g fatty alcohols, Cj^-C^g fatty acids, ci2~Ci8 hydroxy fatty acids, Ci2~Ci8 hydroxy fatty acid esters, sugar alcohols, sugar fatty acid esters and other polyalcohols such as glycerol, glycerol fatty acid esters, sorbitan fatty acid esters or glycerol/sorbitan fatty acid esters. Examples of nonionic surfactants of these types are POE sorbitan monolaurate, POE sorbitol, POE castor oil, POE hydrogenated castor oil, POE lauryl alcohol, POE myristyl alcohol, POE cetyl alcohol, POE stearyl alcohol and POE oleyl alcohol, POE glycerol/sorbitan fatty acid esters, POE fatty acid esters with fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid or oleic acid, POE triglycerides, where in each case POE denotes one or more polyoxyethylene chains which, as a rule, are formed by oxyethylation of the designated basic structures.
Preferred nonionic surfactants have an HLB value (hydrophilie/lipophilic balance) of more than 14. Preferred nonionic surfactants are POE sorbitan fatty acid esters, for example POE (20) sorbitan monolaurate (the number in parentheses denotes in each case here and hereinafter the total number of ethyleneoxy units contained in the surfactant molecule), POE ( 20 ) sorbi-tan monostearate , POE ( 20 ) sorbitan monooleate, POE ( 20 ) sorbitan monopalmitate, as well as fatty alcohol oxyethylates such as, for example, the ethers POE( 12)lauryl alcohol, POE( 20)stearyl alcohol, POE( 20)oleyl alcohol, POE( 20)cetyl alcohol, POE( 23)lauryl alcohol, as well as fatty acid oxyethy-lates such as the esters POE ( 40 ) stearic acid or POE ( 50 ) stearic acid. Examples of anionic surfactants are fatty alcohol sulfates, fatty acid salts and fatty alcohol ether sulfates, preferably fatty alcohol ether sulfates such as sodium lauryl ether sulfate.
The preparations according to the invention can contain up to 80% by weight, based on the preparation, of a physiologically acceptable water-soluble organic solvent.
Examples of suitable solvents are lower aliphatic alcohols, such as ethyl alcohol and isopropyl alcohol, polyhydric alcohols such as glycerol, propylene glycol and polyethylene glycols , block copolymers of ethylene oxide and propylene oxide, as well as arylalkanols such as benzyl alcohol. Also suitable are ketones, for example acetone and methyl ethyl ketone, or esters such as ethyl lactate.
In contrast to the water-miscible solutions from DE-A 3 , 300 , 793 , it is unnecessary to add basic substances to the preparations according to the invention. In general, the pH of a preparation according to the invention - inasfar as it can be measured in the presence of residual water - is in a range below pH 8 .
After dilution with the drinking water to the concentration for administration, the drinking water ought to be virtually neutral or have a slightly acid reaction, preferably have pH 6 to 7 .
The preparations according to the invention can also contain other auxiliaries such as preservatives, antioxidants, further suspension stabilizers, thickening agents such as methylcellulose and colloidal silica, as well as builders for livestock nutrition, colorants and flavorings, as well as physiologically tolerated acids or buffer substances. The proportion of the said auxiliaries ought not as a rule to constitute more than 20% by weight, preferably not more than 10% by weight, of the preparation.
The preparations can contain water even during production, i.e. before the dilution with water or the drink-ing water. The level of this water content depends, in general, on the solubilizer used and on the organic solvent which is used where appropriate. However, as a rule, water contents of less than 10% by weight, based on the weight of the preparation, are preferred.
Preferred preparations according to the invention are composed of a) 100 to 8000 ppm, especially 2000 to 6000 ppm, based on the preparation, of an active substance of the formula (I) or (II), b) an anionic or nonionic surfactant having an HLB of more than 14, c) 0 to 60% by weight, especially 0% by weight, based on the preparation, of a physiologically acceptable water-soluble organic solvent, d) 0 to 10% by weight, especially 0 to 5% by weight, based on the preparation, of water.
The invention also relates to the process for the pro-duction of a preparation according to the invention, which comprises dissolving one or more active substances of the abovementioned formulae (I) and (II) in a water-miscible, physiologically acceptable anionic or nonionic surfactant, or in a mixture of several of - - these surfactants, and, where appropriate, In the presence of up to 80% by weight, based on the preparation, of a physiologically acceptable water-soluble organic solvent and, where appropriate, in the presence of up to 70% by weight, based on the preparation, of water, with the resulting preparation containing up to 10,000 ppm active substance.
The preparations according to the invention can be pro-duced, for example, in such a manner that all the components of the preparation are weighed into a vessel and then stirred, while heating, until a clear solution is produced. It is also possible, for example, to stir the mixture of the components for some time, where appropriate at elevated temperature, then to filter the mixture and to use the filtrate further in the case where no clear solution is produced without filtration.
The invention also relates to the use of the prepara-tion according to the invention for the production of drinking waters containing active substances for the treatment and prophylaxis of coccidiosis in livestock, which comprises adding the preparations according to the invention to the drinking water.
The amount of preparation which is added to the drinking water depends on the efficacy of the individual coccidiostat used, on the species and on the severity of the disease. As a rule, sufficient preparation is added to the drinking water to result in a concentration of the active substance of 1 to 500 ppm, preferably 2 to 100 ppm, especially 2 to 30 ppm, in the drinking water.
It is expedient to add the preparations according to the invention to the drinking water only a relatively short time before the use thereof. The active substance preparations according to the invention are, as a rule, stable on storage for several months. The dilute solu- tions prepared from the concentrated preparations for administration as drinking water are, as a rule, stable for several days but for a minimum of 24 hours.
Trials on livestock demonstrated the satisfactory tolerability and complete efficacy of the drinking waters prepared using active substance preparations according to the invention.
Preparation examples Using the active substances of the formulae (I) and (II) which are indicated in Tables la) and lb) which follow, and using the auxiliaries and ratios of amounts indicated in Table 2, the particular active substances are dissolved with heating.
Tables la) and a) No Formula R1 R2 R3 X' y-z- w l la H - - CI CF2HCF2-0 W 2 la H - - CI CF3-CHF-CF2-0 W 3 la H H H CI 4-(CH3S02)-C6H40- W 4 la H CH3 H CI 4-(CH3S02)-C6H40- W 5 la CH3 - - CF3 H W 6 la CH3 H H CF3 H W7 la CH3 - - H CF3-CHF-CF2-0- b) No. Formula W R R' YZ n X w 8 II O H CH3 4-CF3S-C6H40 1 3-CH3 Table 2 Active Ex. substance Surfactant 1 4 parts 1 1000 parts POE (20) sorbitan monolaurate 2 1 part W 1 100 parts 3 1 part W 1 1000 parts 4 4 parts W 2 1000 parts 5 4 parts W 3 1000 parts 6 4 parts W 4 1000 parts 7 4 parts W 5 1000 parts 8 4 parts W 6 1000 parts 9 4 parts W 7 1000 parts 10 4 parts W 8 1000 parts 11 1 part W 8 100 parts 12 1 part W 8 1000 parts 13 1 part W 3 1000 parts 14 6 parts w 1 1000 parts 15 4 parts w 1 1000 parts sodium lauryl ether sulfate 16 4 parts w 3 1000 parts 17 4 parts w 8 1000 parts 18 4 parts w 1 1000 parts of a 1:1 mixture of POE (20) sorbitan monolaurate and sodium lauryl ether sulfate 19 4 parts W 1 1000 parts of a 1:1 mixture of sodium lauryl ether sulfate and POE (20) sorbitan monolaurate 20 4 parts W 1 1000 parts of a 2:8 mixture of POE (20) sorbitan monolaurate and ethanol 21 4 parts W 5 1000 parts POE (23) lauryl alcohol 22 4 parts W 5 1000 parts POE (20) oleyl alcohol 23 4 parts W 5 1000 parts POE (20) sorbitan monooleate Therapy examples To treat coccidiosis in livestock, preparations 1 to 23 (Table 2) were diluted with water to the concentration for administration and administered to the livestock ad libitum.
Therapy trials were carried out, for example, with a mixed isolate of Eimeria tenella and Eimeria acervulina (Tab. 3) and with a sensitive strain of Eimeria tenella (Tab. 4). 3-Day old Lohmann selected Leghorn chickens which were housed in batteries received medicated drinking water ad libitum from D+2 (2 days after infection) to D+3. On DO (day of infection) the medicated groups (12 birds/group) and the infection controls were infected, specifically with 1 x 10^ sporulated oocysts for each bird. One group served as uninfected control without medication. Commercially available chick-rearing feed was available ad libitum.
The following parameters were investigated to assess the coccidiostatic or coccidiocidal effect (cf. J. Johnson, W.M. Reid, Anticoccidial Drugs: Lesion Scoring Techniques in Battery and Floor-Pen Experiments with Chickens, Exp. Parasitol. 28, 30-36 (1970)): Findings in feces on D+4, D+6; Determination of the mortality from coccidiosis; Weight gain: DO to D+7; Gross-pathological lesions in the intestinal tract (lesion scores: 0-4) between D+4 and D+7.
The results are compiled in Tables 3 and 4.
Effective therapy is evident in particular from the smaller mean number of gross-pathological lesions (lesion scores) in the intestinal tract of the birds by comparison with the infected control. Analogous results are obtained with the other preparations from Table 2.
Table 3 Therapy trial (chicks) with a mixed isolate of E. tene Preparation ACTIVE FINDINGS IN MORTALITY WEI No. SUBSTANCE FECES ON COCC. DO CONTENT mg/1 D+4 D+6 Birds/total Gra 6 5 0 0-1 0 / 12 28. 2.5 0 0-1 0 / 12 25. infected control 0 2 3 2 / 12 9. without medication uninfected control 0 0 0 0 / 12 26. without medication Table 4 Therapy trial (chicks) with one strain of Eimeria ten Preparation ACTIVE FINDINGS IN MORTALITY WEI No. SUBSTANCE FECES ON COCC. DO CONTENT mg/1 D+4 D+6 Birds/total Gra 4 10 0 0 0 / 12 37. infected control 0 2-3 2 4 / 12 20. without medication uninfected control 0 0 0 0 / 12 39. without medication
Claims (1)
1. CLAIMS An substance preparation contains up to based on weight of of one or more of the general f or II In which R and Independently of one hydrogen or denotes together a double bond or Independently thereof hydrogen or Ct denotes together with R3 a double bond or Independently thereof hydrogen or W denotes oxygen or X each independently of the chlorine and t nitro or n denotes 3 or preferably 0 to y denotes phenyl or phenyl which is substituted by at least one radical from the group comprising and each alkyl radical having 1 to 4 carbon or denotes thlenyl or and Z denotes a direct linkage or a divalent group of the formula SOa In which Is hydrogen or or denotes In which is hydrogen or a physiologically acceptable anionic or nonlonic surfactant or mixture of several of these and 0 to by based on the a physiologically acceptable organic 0 to by based on the of which In the presence water has a pH below 0 and which after dilution to the use concentration as aqueous solution ready for a virtually neutral or slightly An substance preparation s claimed in claim which contains an active of the formula claimed In claim In which denotes hydrogen or preferably hydrogen or R2 denotes together with R3 a double or and Independently of one hydrogen or especially hydrogen or X each Independently of the preferably or denotes 1 or 2 denotes especially having one or more fluorine atoms as phenyl or phenyl which le substituted by at least one radical from the group comprising or and Z denotes a direct linkage or An active substance preparation as claimed In claim 1 or which contains an active substance of the formula II as claimed In claim 1 in which R and Independently of one hydrogen or W denotes X each Independently of the or n denotes 1 or Y denotes phenyl or which Is substituted by at least one from the group comprising trlfluoromethylsulflnyl or and Z denotes An active substance preparation as claimed in one or more of claims 1 to which contains an active substance of the formula In which denotes hydrogen or denotes together with R3 a double or and R3 Independently of one hydrogen or denotes chlorine or and denotes especially or afluoropi or especially An preparation as claimed In one or more claims 1 to which Is of to based on of an active substance of the formula or an anionic or nonlonlc surfactant having an of more than 0 to by based on the of a physiologically acceptable organic 0 to by based on the of An active substance preparation as claimed in one or more of claims 1 to wherein the nonlonlo surfactant Is a surfactant from the group of ethers or esters of ollgopolyglyool ethers with fatty fatly hydroxy fatty acids and sugar alcohols and sugar fatty An active substance preparation as claimed in claim wherein the surfactant an oxyethylate of a fatty acid process for the production ol ihe active substance preparations as defined one or more of claims 1 to which comprises dissolving one or more active substances of the formulae and In a physiologically acceptable anionic or or In a mixture of several of these where In the presence of up to by based on the of a physiologically acceptable organic solvent where In the presence of up to by based on the of wllh the resulting preparation containing up to ppm active The use of the active substance preparation defined In at least one of claims 1 to 7 for the preparation of aqueous solutions ready for drinking for the treatment of coccldlosls In The use as claimed claim wherein the preparation Is diluted with water to a content of 1 to 600 ppm active ZEDE O B x 33116 T e l A v i v insufficientOCRQuality
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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DE3814323A DE3814323A1 (en) | 1988-04-28 | 1988-04-28 | WATER-SOLUBLE PREPARATIONS BY COCCIDIOSTATICA |
Publications (1)
Publication Number | Publication Date |
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IL90098A true IL90098A (en) | 1995-11-27 |
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ID=6353066
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL9009889A IL90098A (en) | 1988-04-28 | 1989-04-27 | Water-soluble preparations of n-phenyltriazine coccidiostats their preparation and use |
Country Status (19)
Country | Link |
---|---|
EP (1) | EP0339555B1 (en) |
JP (1) | JPH01313430A (en) |
KR (1) | KR900015740A (en) |
AT (1) | ATE83661T1 (en) |
AU (1) | AU619004B2 (en) |
BG (1) | BG60542B2 (en) |
BR (1) | BR8901913A (en) |
DD (1) | DD283773A5 (en) |
DE (2) | DE3814323A1 (en) |
DK (1) | DK204689A (en) |
ES (1) | ES2043934T3 (en) |
HU (1) | HU205716B (en) |
IL (1) | IL90098A (en) |
NZ (1) | NZ228898A (en) |
PH (1) | PH27515A (en) |
PL (1) | PL279153A1 (en) |
PT (1) | PT90387B (en) |
RU (1) | RU1780510C (en) |
ZA (1) | ZA893077B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3288132B2 (en) * | 1992-06-25 | 2002-06-04 | サントリー株式会社 | Substituted 1,2,4-triazine-3,5-dione and anticoccidial composition containing the same as an active ingredient |
ES2941529T3 (en) | 2018-02-26 | 2023-05-23 | AlzeCure Pharma AB | Triazine derivatives for the treatment of neurotrophin-related diseases |
GB201810668D0 (en) | 2018-06-28 | 2018-08-15 | Stiftelsen Alzecure | New compounds |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3361627A (en) * | 1958-06-20 | 1968-01-02 | Harris Trust And Savings Bank | Phenothiazine compositions |
DE3300793A1 (en) * | 1983-01-12 | 1984-07-12 | Bayer Ag, 5090 Leverkusen | Coccidiosis |
DE3408924A1 (en) * | 1984-03-12 | 1985-09-26 | Hoechst Ag, 6230 Frankfurt | SUBSTITUTED 2-PHENYL-HEXAHYDRO-1,2,4-TRIAZINE-3,5-DIONE, METHOD FOR THE PRODUCTION THEREOF, MEANS CONTAINING IT AND THEIR USE |
EP0179583A1 (en) * | 1984-10-04 | 1986-04-30 | Merck & Co. Inc. | A system for enhancing the water dissolution rate and solubility of poorly soluble drugs |
DE3531919A1 (en) * | 1985-09-07 | 1987-03-19 | Hoechst Ag | SUBSTITUTED 2-PHENYL-HEXAHYDRO-1,2,4-TRIAZINE-3,5-DIONE, METHOD FOR THE PRODUCTION THEREOF, MEANS CONTAINING IT AND THEIR USE |
-
1988
- 1988-04-28 DE DE3814323A patent/DE3814323A1/en not_active Withdrawn
-
1989
- 1989-04-21 BR BR898901913A patent/BR8901913A/en not_active Application Discontinuation
- 1989-04-24 BG BG088223A patent/BG60542B2/en unknown
- 1989-04-25 AT AT89107413T patent/ATE83661T1/en not_active IP Right Cessation
- 1989-04-25 DE DE8989107413T patent/DE58903076D1/en not_active Expired - Fee Related
- 1989-04-25 ES ES89107413T patent/ES2043934T3/en not_active Expired - Lifetime
- 1989-04-25 EP EP89107413A patent/EP0339555B1/en not_active Expired - Lifetime
- 1989-04-26 PH PH38564A patent/PH27515A/en unknown
- 1989-04-26 KR KR1019890005474A patent/KR900015740A/en not_active Application Discontinuation
- 1989-04-26 NZ NZ228898A patent/NZ228898A/en unknown
- 1989-04-26 DD DD89327990A patent/DD283773A5/en not_active IP Right Cessation
- 1989-04-26 ZA ZA893077A patent/ZA893077B/en unknown
- 1989-04-26 RU SU894613974A patent/RU1780510C/en active
- 1989-04-27 HU HU892014A patent/HU205716B/en not_active IP Right Cessation
- 1989-04-27 PL PL27915389A patent/PL279153A1/en unknown
- 1989-04-27 PT PT90387A patent/PT90387B/en not_active IP Right Cessation
- 1989-04-27 DK DK204689A patent/DK204689A/en not_active Application Discontinuation
- 1989-04-27 AU AU33735/89A patent/AU619004B2/en not_active Ceased
- 1989-04-27 IL IL9009889A patent/IL90098A/en not_active IP Right Cessation
- 1989-04-27 JP JP1106104A patent/JPH01313430A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
RU1780510C (en) | 1992-12-07 |
PT90387A (en) | 1989-11-10 |
HU205716B (en) | 1992-06-29 |
DE58903076D1 (en) | 1993-02-04 |
KR900015740A (en) | 1990-11-10 |
DD283773A5 (en) | 1990-10-24 |
ZA893077B (en) | 1989-12-27 |
PH27515A (en) | 1993-08-18 |
PT90387B (en) | 1994-10-31 |
ES2043934T3 (en) | 1994-01-01 |
DK204689D0 (en) | 1989-04-27 |
BR8901913A (en) | 1989-11-28 |
ATE83661T1 (en) | 1993-01-15 |
JPH01313430A (en) | 1989-12-18 |
DE3814323A1 (en) | 1989-11-09 |
PL279153A1 (en) | 1989-12-27 |
AU3373589A (en) | 1989-11-02 |
BG60542B2 (en) | 1995-08-28 |
AU619004B2 (en) | 1992-01-16 |
EP0339555A3 (en) | 1990-01-31 |
NZ228898A (en) | 1992-02-25 |
EP0339555A2 (en) | 1989-11-02 |
HUT51490A (en) | 1990-05-28 |
EP0339555B1 (en) | 1992-12-23 |
DK204689A (en) | 1989-10-29 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
FF | Patent granted | ||
KB | Patent renewed | ||
RH | Patent void |