NZ228898A

NZ228898A - Water-soluble compositions of 1,2,4- and/or 1,3,5-triazines for use in drinking water for treatment of coccidiosis

Info

Publication number: NZ228898A
Application number: NZ228898A
Authority: NZ
Inventors: Dietrich Hiller; Theopil Hornykiewytsch; Wolfgang Raether
Original assignee: Hoechst Ag
Priority date: 1988-04-28
Filing date: 1989-04-26
Publication date: 1992-02-25
Also published as: HU205716B; ES2043934T3; AU619004B2; DE58903076D1; DD283773A5; EP0339555A2; AU3373589A; BG60542B2; BR8901913A; IL90098A; PT90387B; DK204689D0; DE3814323A1; RU1780510C; EP0339555A3; PL279153A1; PH27515A; KR900015740A; HUT51490A; ATE83661T1

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

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £28898 Priority Date(s Comntetfl Specification Filed: Class: ■(5)..AlftAhs.^A./^>.J.. ...... A /»i ir i • 1 1 / Pufcffcatlon iMto: . .....?.5.f|B.»SZ P.O. J ouKfa!, K' J£>, 22 8 8 9 8 N.Z. No, NEW ZEALAND Patents Act 1953 COMPLETE SPECIFICATION WATER-SOLUBLE PREPARATIONS OF COCCIDIOSTATS We, HOECHST AKTIENGESELLSCHAFT, a corporation organized under the laws of the Federal Republic of Germany of D-6230 Frankfurt am Main 80, Federal Republic of Germany, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement - 1 - (Followed by 1A) -1 fl- 22 8 8 9 8 IIODOIIpqi AKfDiDlICBCBtfcSCtUtfB HOB 89/g 104 Br, Iffi/irnhi Description Water-soluble preparations of coccidiostats The invention relates to liquid preparations of coccidiostats, which can be administered to livestock with the drinking water. 10 N-Phenyltriazines of the general formulae I and II 15 y - z (i) 20 25 30 35 (X)n 0 Y - Z / N \=. 0 (II) t\ W R' in which R1, R and R' denote, independently of one another, hydrogen or C^-C^alkyl, R^ denotes together with R^ a double bond or independently thereof hydrogen or C^-C^-alkyl, O O RJ denotes together with R a double bond or independently thereof hydrogen or C^-C^-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^-C^alkylthio, nitro or C^-C^alkoxy, n denotes 0, 1, 2, 3 or 4, preferably 0 to 2, Y denotes hydrogen, C^-Cg-alkyl, C^-Cg-halogenoalkyl, - 2 - 22 8 8 9 8 benzyl, phenyl or phenyl which is substituted by at least one radical from the group comprising alkyl, alkoxy, halogenoalkyl, halogenoalkoxy, halogen, alkylthio, alkylsulfinyl, alkylsulfonyl, halogeno-alkylthio, 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, SO2/ 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 coccidiosis 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. 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 - 3 - <>2 8 8 9 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 5 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. 10 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-15 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-20 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 25 again immediately or after a short time. (EP-A 116,175) 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 30 denotes 3-methyl, W 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 35 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 - 4 - 22 8 8 9 8 active substances of the general formula (I). (EP-A 116,175) 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 concentration 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 - 5 - 22 8 8 9 8 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 C^-C^-alkyl, preferably hydrogen or methyl, R denotes together with RJ a double bond, or R and R denote, independently of one another, hydrogen or C1-C4-alkyl, especially hydrogen or methyl, X denotes, each independently of the others, chlorine, bromine, C^-C^-alkyl, preferably methyl, triflu-oromethyl or C1-C4-alkoxy, n denotes 0, 1 or 2 Y denotes hydrogen, C^-C^-halogenoalkyl, especially C1-C3~alkyl having one or more fluorine atoms as sub- - 6 - 22 8 8 98 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-5 methylthio, trifluoromethylsulfinyl or trifluoro methyl sulfonyl, and Z denotes a direct bond or oxygen. Preferred preparations according to the invention con-10 tain an active substance a) of the formula (la) 15 Y - (la) in which R1 denotes hydrogen or methyl, R"4 denotes together with RJ a double bond, or 20 and R^ denote, independently of one another, hydro gen or methyl, X' denotes hydrogen, chlorine or trifluoromethyl, and Y-Z- denotes hydrogen, C^-C^-halogenoalkoxy, especially tetrafluoroethoxy or hexafluoropropoxy, or C^-C^-25 alkylsulfonylphenoxy, especially 4-methylsulfonylphe- noxy. Also of particular interest are preparations according to the invention containing an active substance a) of 30 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, 35 C^-C^-alkoxy, C^-C^-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- - 7 - 22 8 8 9 8 oromethylthio, trifluoromethylsulfinyl or trifluoromethyl sulfonyl, 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, R^ 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 oligoethylene glycol ethers with compounds from the group of alcohols, ^attY acids, Ci2-Ci8 fattY acids, ci2~cl8 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 - 8 - 2 28 8 9 8 (the number in parentheses denotes in each case here and hereinafter the total number of ethyleneoxy units contained in the surfactant molecule), POE (20) sorbitan 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, P0E(20)oleyl alcohol, POE(20)cetyl alcohol, POE(23)lauryl alcohol, as well as fatty acid oxyethylates 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^^oA 1^? ^^er-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. - 9 - Ll 8 8 9 8 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 drinking 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 production 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 - 10 - 22 8 8 9 8 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 5 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-10 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 15 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-20 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. 25 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 30 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. 35 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 - 11 - 22 8 8 9 8 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. 10 Preparation examples 15 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 lb) 20 25 30 a) No Formula R1 R2 R3 X' Y-Z- w 1 la h - - ci cf2hcf2-o w 2 la h - - ci cf3-chf-cf2-o w 3 la h h h ci 4-(ch3s02)-c6h40- w 4 la h ch 3 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-o- b) No. Formula w R R' YZ n X w 8 II 0 h ch3 4-cf3s- ■c6h40 1 3-ch3 - 12 - 22 88 9 8 Table 2 Active Ex. substance Surfactant 1 4 parts W 1 1000 parts POE (20) sorbitan mono 5 laurate 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 10 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 " 15 11 1 part W 8 100 parts " 12 1 part W 8 1000 parts " 13 1 part W 3 1000 parts H 14 6 parts W 1 1000 parts " 15 4 parts w 1 1000 parts sodium lauryl ether 20 sulfate 16 4 parts w 3 1000 parts H 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 25 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 30 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 35 monooleate Therapy examples To treat coccidiosis in livestock, preparations 1 to 23 - 13 - 228898 (Table 2) were diluted with water to the concentration for administration and administered to the livestock ad libitum. 5 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 10 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 105 sporulated oocysts for each bird. One group served as uninfected control 15 without medication. Commercially available chick-rear-ing feed was available ad libitum. The following parameters were investigated to assess the coccidiostatic or coccidiocidal effect (cf. J. 20 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; 25 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. 30 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 35 comparison with the infected control. Analogous results are obtained with the other preparations from Table 2. </div>

Claims

<div class="application article clearfix printTableText" id="claims"> - 14 - Table 3 Therapy trial (chicks) with a mixed isolate of E. tenella and E. acervulina Preparation No. ACTIVE SUBSTANCE CONTENT mg/1 FINDINGS IN FECES ON D+4 D+6 MORTALITY COCC. Birds/total WEIGHT DO to Gram GAIN D+7 % LESION SCORES (means) D+4 to D+7 Cecum Duodenum 6 5 2.5 0 0 0-1 0-1 0/12 0/12 28.1 25.7 106.4 97.3 0.1 0.3 0.2 1.1 infected control without medication 0 2 3 2/12 9.1 34.5

1.9 2.0 uninfected control without medication 0 0 0 0/12 26.4 100 0 0 Table 4 Therapy trial (chicks) with one strain of Eimeria tenella Preparation No. ACTIVE SUBSTANCE CONTENT mg/1 FINDINGS IN FECES ON D+4 D+6 MORTALITY COCC. Birds/total WEIGHT DO to Gram GAIN D+7 % LESION SCORES (means) D+4 to D+7 Cecum 4 10 0 0 0/12 37.1 94.6 0.4 infected control without medication 0

2-3 2 4/12 20.9 53.3 2.3 uninfected control without medication 0 0 0 0/12 39.2 100 0 - 15 - 228898 what //we claim is: PwtoawtMOibaAn* OOlfP m 1. An active substance preparation which contains a) up to 10^000 ppm* based on the weight of the preparation> of one or more coccidiostats of the general formulae I and II y - z - (X)n 0 R (I) 29 J AN W92 - . (X)n 0 y - z /-t~\ V-N7 Soy* >=o // n W in which (II) R , R and R' denote, independently of one another, hydrogen or CJ-C4-alkyl, R2 denotes together with R3 a bond or independently thereof hydrogen or C^-C4-alkyl, R3 denotes together With R2 a bond or independently thereof hydrogen or C^-C^-alkyl, W denotes oxygen or sulfur, X denotes, each independently of the others, halogen, cl"c4- alkyl* trifluoromethylt cyano, thiocyanato, C^-C^-alkylthio, nitro or C^-C4-alkoxy, n denotes 0, 1* 2t 3 or 4, Y denotes hydrogen* C^-Cg-allcyl* C^-Cg-halogeno- alkyl, benzyl» phenyl or phenyl which is substituted by at least one radical from the group . /of consisting/alkyl, alkoxy, halogenoalkyl, halogeno-alkoxy, halogen, alkylthio, alkylsulfinyl, alkyl- - 16 - 228898 sulfonyl, halogenoalkylthio* halogenoalkylsulfinyl and halogenoalkylsulfonyl* each alkyl radical having 1 to 4 carbon atoms, or denotes thienyl or halothienyl, and Z denotes a direct bond or a divalent group 0, S, SO, S02* NH, NR° in which R° is hydrogen or C^-C^alkyl, or denotes C(CN)(R+) in which R+ is hydrogen or methyl, 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 weightt based on the preparation, of water. An active Substance preparation as claimed in claim 1, which contains an active substance of the formula (I) as claimed in claim 1, in which R* denotes hydrogen( or C^-C^-alkyl, R2 denotes together with R3 a bond, or 9 o R* and RJ denote, independently of one another* hydrogen or 0^-04-alkyl, X denotes, each independently of the others, chlorine, bromine; C^-C^alkyl, trifluoromethyl or C^-C^alkoxy, n denotes 0, 1 or 2, Y denotes hvdrogen, C^-C^halogenoalkyl, phenyl or phenyl which is substituted by at least one radical from the group consisting/0 Diethyl, methoxy, trifluoromethyl, chlorine* methylthio* methylsulfinyl* methyl-sulfonyl* ^trifluoromethylthio, trifluoromethyl-sulfinyl / trifluoromethylsulfonyl, and Z denotes a direct bond or oxygen.

3. An active substance preparation as claimed in - 17 - 228898 claim 1 or 2, which contains an active substance of the formula II as claimed in claim 1, in which R and R' denote; independently of one another, hydrogen or methyl* W denotes oxygen, X denotes, each independently of the others, chlorine, C-^-C^alkoxy, C^-C^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 coniisting of chlorine* trifluoromethyl, trifluoromethoxy, trifluoromethylthio* trifluoromethylsulfinyl and trif liioromethylsulfonyl; and Z denotes oxygen. An active substance preparation as claimed in atiy one of claims 1 to 3, which contains an active substance a) of the formula (la) in which R* denotes hydrogen or methyl; R^ denotes together With R^ a bond, or R2 and R3 denote; independently of one another, hydrogen or methyl* X' denotes hydrogen; chlorine or trifluoromethyl; and Y-Z- denotes hydrogen, Cj-C^-halogenoalkoxy, i or C^-C

4-alkylsulfonylphenoxy; An active substance preparation as claimed in any one of claims 1 to 4; which is composed of a) 100 to 8000 ppm; based on the preparation, of an 18 228898 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, based on the preparation, of a physiologically acceptable water-soluble organic solvent, d) 0 to 10% by weight, based on the preparation, of 6. An active substance preparation as claimed in any one of claims 1 to 5, wherein the nonionic surfactant is a surfactant from the group of ethers or esters of oligopolyglycol ethers with fatty acids, C^-C^g ^attY alcohols, Ci2~*-18 hydroxy fatty acids and esters, sugar alcohols and sugar fatty acid esters. 7. An active substance preparation as claimed in claim 6, wherein the surfactant is an oxyethylate of a sorbitan fatty acid ester. 8. A process for the production of the active substance preparations as defined in any one of claims 1 to 7, 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. 9. The use of the active substance preparation defined in any one of claims 1 to 7 for the preparation of drinking water for the treatment of coccidiosis in livestock. 10. The use as claimed in claim 9, wherein the water. preparation is diluted with water to a conten to 500 ppm active substance. \^6jaN>992' 228898 - 19 - 11. A preparation according to claim 1 substantially as herein described or exemplified. 12. A process according to claim 8 substantially as herein described or exemplified. HOECHST AKTIENGESELLSCHAFT -By their attorneys HENRY HUGHES LTD f v «*\ i "6 JAM J99211 P r vf </div>