AU619004B2 - Water-soluble preparations of coccidiostats - Google Patents

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

Form COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952-69 COMPLETE SPECIFICATION ORIGINAL) 619004 C1'.ss Itnt. Class Application Number: Lodged: Complete Specification Lodged: .00Accepted: so. Published: P 0 t Rtl?,edl Art: ,IJa~pofApplicant: HOECHST AKTIENGESELLSCHAFT *"Prssfpliat 5 Brnnsrse -6230 Frankfurt/Main 80, Federal Republic of Germany :Actual Inventor: Address for Service: DIETRICH HILLER, THEOPIL HORNYKIEWYTSCH and WOLFGANG RAETHER EDWD. WATERS SONS, 50 QUEEN STREET, MELBOURNE, AUSTRALIA, 3000.

Complete Specification for the invention entitled: WATER-SOLUBLE PREPARATIONS OF COCCIDIOSTATS The following statement is a full description of this invention, including the best method of performing it known to :-Us :i I I i i

V

HOECHST ARTIENGESELLSCHAFT 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 1 0

R

X) oo Z N 0 (I) W R' in which

R

I

R and R' denote, independently of one another, hydrogen or C 1

-C

4 -alkyl, 2 denotes together with R 3 a double bond or independently thereof hydrogen or C 1

-C

4 -alkyl,

R

3 denotes together with R 2 a double bond or independently thereof hydrogen or C 1

-C

4 -alkyl, W denotes oxygen or sulfur, X denotes, independently of the others, halogen such as fluorine, chlorine and bromine, C 1

-C

4 -alkyl, trifluoromethyl, cyano, thiocyanato, C 1

-C

4 -alkylthio, nitro or C 1

-C

4 -alkoxy, n denotes 0, 1, 2, 3 or 4, preferably 0 to 2, Y denotes hydrogen, C 1

-C

6 -alkyl, C 1

-C

6 -halogenoalkyl, :i I 2 benzyl, phenyl or phenyl which is substituted by at least one radical from the group comprising alkyl, alkoxy, halogenoalkyl, halogenoalkoxy, halogen, alkylthio, alkylsulfinyl, alkylsulfonyl, 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 of the formula O, S, SO, S02, NH, NR O in which R O is hydrogen or C 1

-C

4 -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 S 15 publication numbers 0,215,354, 0,154,885 (US-A 4,640,917), 0,170,316 and 0,232,932 as well as German O 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

I:

3 in the water. The active substances of the abovementioned formulae 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- Sdiostats of the formula and 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 and (II) dissolve 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, W denotes 0 and Y-Z denotes 4-trifluoromethylthiophenoxy. 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 4 active substances of the general formula DE-A 3,300,793 furthermore discloses that solubilization in aqueous medium by addition of solubilizers such as, for example, polyoxyethylated castor oil or polyoxyethylene 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 S. general formula 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).

*e e :I'96 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.

so$: The invention relates to preparations containing one or more active substances of the abovementioned formulae and 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 i: i- i I 5 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 S 15 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 in which

R

1 denotes hydrogen or C 1

-C

4 -alkyl, preferably hydrogen or methyl,

R

2 denotes together with R 3 a double bond, or R2 and R denote, independently of one another, hydrogen or C 1

-C

4 -alkyl, especially hydrogen or methyl, X denotes, each independently of the others, chlorine, bromine, C 1

-C

4 -alkyl, preferably methyl, trifluoromethyl or C 1

-C

4 -alkoxy, n denotes 0, 1 or 2 Y denotes hydrogen, C 1

-C

4 -halogenoalkyl, especially C l

C

3 -alkyl having one or more fluorine atoms as subi i 6 stituents, phenyl or phenyl which is substituted by at least one radical from the group comprising methyl, methoxy, trifluoromethyl, chlorine, methylthio, methylsulfinyl, methylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl, and Z denotes a direct bond or oxygen.

Preferred preparations according to the invention contain an active substance a) of the formula (Ia) X' 0 R Y Z N0 (Ia) 15

N

X1( in which R 2 3

R

1 denotes hydrogen or methyl,

R

2 denotes together with R 3 a double bond, or

R

2 and R 3 denote, independently of one another, hydrogen or methyl, X' denotes hydrogen, chlorine or trifluoromethyl, and Y-Z- denotes hydrogen, C 1

-C

4 -halogenoalkoxy, especially tetrafluoroethoxy or hexafluoropropoxy, or C1-C 4 alkylsulfonylphenoxy, especially 4-methylsulfonylphenoxy.

Also of particular interest are preparations according to the invention containing an active substance a) of the formula (II) in which 4 R and R' denote, independently of one another, hydrogen or methyl, W denotes oxygen, X denotes, each independently of the others, chlorine,

C

1

-C

4 -alkoxy, C 1

-C

4 -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, triflui i 7 oromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl, and Z denotes oxygen.

Preferred preparations containing an active substance a) of the formula (II) are those in which in formula (II) R 1 denotes hydrogen, R 2 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 *S 15 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 C 12

-C

18 fatty alcohols, C 12

-C

18 fatty acids, C 12

-C

18 hydroxy fatty acids, C 12

-C

18 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

OSS

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 (hydrophilic/lipophilic balance) of more than 14.

Preferred nonionic surfactants are POE sorbitan fatty acid esters, for example POE (20) sorbitan monolaurate 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, alcohol, POE(20)cetyl alcohol, POE(23)lauryl alcohol, as well as fatty acid oxyethylates such as the esters POE(40)stearic acid or 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.

o 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 J 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 o as ethyl lactate.

In contras- 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.

i I 9

S.

S

0 OS *r S

S

0 0 0@ 00 0

S.

S

0*

*SS@

S

0Se OS S 0 0 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 by weight, of the preparation.

The preparations can contain water even during production, i.e. before the dilution with water or the drink- 15 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 25 formula 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 and (II) in a water-miscible, physiologically acceptable anionic or nonionic surfactant, or in a mixture of several of i OK 10 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 produced, 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 0S Se 15 appropriate at elevated temperature, then to filter the *mixture and to use the filtrate further in the case .oO. where no clear solution is produced without filtration.

S

The invention also relates to the use of the preparation according to the invention for the production of goes 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 drinkr. ing water depends on the efficacy of the individual Sococcidiostat used, on the species and on the severity of the disease. As a rule, sufficient preparatin 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- -51 11 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 0e 15 Ge

C

*c C Using the active substances of the formulae and (II) which are indicated in Tables la) and Ib) 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 Ib) elke 0 so 0G

S

006 S. S

C

S

a) No W 1 W2 W3 W4 25 W 5 W6 W7 Formula Ia Ia Ia Ia Ia Ia Ia Formula

II

R

1

H

H

H

H

CH

3

CH

3

CH

3

W

0

R

2

R

3

X'

Cl Cl H H Cl

CH

3 H Cl

CF

3 H H CF 3

H

Y-Z-

CF

2

HCF

2

-O

CF

3

-CHF-CF

2

-O

4-(CH 3

SO

2

)-C

6

H

4 0- 4-(CH 3

SO

2

)-C

6

H

4 0-

H

CF

3

-CHF-CF

2 O b) No W8

I

R' YZ

CH

3 4-CF 3

S-C

6

H

4 0

X

3-CH 3 1

I

12 Table 2 Active Ex. substance Surfactant 1 4 parts W 1 1 part W 1 part W 4 parts W 4 parts W 4 parts W 4 parts W 4 parts W 4 parts W 4 parts W 1 part W 1 part W 1 part W 6 parts W 4 parts W 1000 parts 100 parts 1000 parts 1000 parts 1000 parts 1000 parts 1000 parts 1000 parts 1000 parts 1000 parts 100 parts 1000 parts 1000 parts 1000 parts 1000 parts POE (20) sorbitan monolaurate 01 sodium lauryl ether sulfate 0.

0

S.

0

S

0 0000 0 5 00 S 00

S

0 00r 50 4 parts 4 parts 4 parts 19 4 parts W 1 1000 parts 1000 parts 1000 parts of a 1:1 mixture of POE (20) sorbitan monolaurate and sodium lauryl ether sulfate 1000 parts of a 1:1 mixture of sodium lauryl ether sulfate and POE (20) sorbitan monolaurate 1000 parts of a 2:8 mixture of POE (20) sorbitan monolaurate and ethanol 1000 parts POE (23) lauryl alcohol 1000 parts POE (20) oleyl alcohol 1000 parts POE (20) sorbitan monooleate 4 parts W 1 4 parts 4 parts 4 parts Therapy examples To treat coccidiosis in 1.vestock, preparations 1 to 23 -13 (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. 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 105 sporulated oocysts for each bird. One group served as uninfected control 15 without medication. Commercially available chick-rearing feed was available ad libitum.

S' The following parameters were investigated to assess 0* 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; 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.

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.

-ii

CC

S

0

S

SCC

S S S *5S 6 6 6 C CC 606 SC: 6.6 6 6 C C S C CO .5 0 eCg S4 S :i Table 3 Therapy trial (chicks) with a mixed isolate of E. tenella and E. acervulina Preparation ACTIVE FINDINGS IN MORTALITY WEIGHT GAIN LESION SCORES No. SUBSTANCE FECES ON COCC. DO to D+7 (means) CONTENT mg/l D+4 D+6 Birds/total Gram D+4 to D+7 Cecum Duodenum 6 5 0 0-1 0 12 28.1 106.4 0.1 0.3 0 0-1 0 12 25.7 97.3 0.2 1.1 infected control 0 2 3 2 12 9.1 34.5 1.9 without medication uninfected control 0 0 0 0 12 26.4 100 0 0 without medication Table 4 Therapy trial (chicks) with one strain of Eimeria tenella Preparation ACTIVE FINDINGS IN MORTALITY WEIGHT GAIN LESION SCORES No. SUBSTANCE FECES ON COCC. DO to D+7 (means) CONTENT mg/1 D+4 D+6 Birds/total Gram D+4 to D+7 Cecum 4 10 0 0 0 12 37.1 94.6 0.4 infected control 0 2-3 2 4 12 20.9 53.3 2.3 without medication uninfected control 0 0 0 0 12 39.2 100 0 without medication 1

Claims (9)

1. An active substance preparation which contains Up te nn hprm, Anflfir ho 4h) C <-IM- pr ipfl 4- f one or more coccidiostats of the /q r general formulae I and II 1 (X)n o Y Z 0 (I) N H R R 3 (x N 0 (II) N W R' in which I R R and R' denote, independently of one another, hydrogen or C 1 -C 4 -alkyl, R 2 denotes together with R 3 a double bond or independently thereof hydrogen or C 1 -C 4 -alkyl, R 3 denotes together with R 2 a double bond or independently thereof hydrogen or C 1 -C 4 -alkyl, W denotes oxygen or sulfur, X denotes, each independently of the others, halogen such as fluorine, chlorine and bromine, C 1 -C 4 alkyl, trifluoromethyl, cyano, thiocyanato, C 1 -C 4 alkylthio, nitro or C 1 -C 4 -alkoxy, n denotes 0, 1, 2, 3 or 4, preferably 0 to 2, Y denotes hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -halogeno- alkyl, benzyl, phenyl or phenyl which is substituted by at least one radical from the group comprising alkyl, alkoxy, halogenoalkyl, halogeno- Sr/ alkoxy, halogen, alkylthio, alkylsulfinyl, alkyl- cipitating out witnin z: nours. This method for the preparation of stable aqueous solutions of active substances cannot be applied to .IIII. -16 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 of the formula O, S, SO, SO 2 NH, NRO in which RO is hydrogen or C 1 -C 4 -alkyl, or denotes in which R+ is hydrogen or methyl, in which preparation the amount of the compound(s) of the formula I and/or II does not exceed 10,000 ppm, based on the weight of the preparation, 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.

2. An active substance preparation as claimed in claim 1, which contains an active substance of the formula as claimed in claim 1, in which R1 denotes hydrogen or C1-C 4 -alkyl, preferably hydrogen or methyl, R2 denotes together with R 3 a double bond, or .i iR2 and R3 denote, independently of one another, hydrogen or C 1 -C4-alkyl, especially hydrogen or methyl, *s o X denotes, each independently of the others, chlorine, bromine, C 1 -C 4 -alkyl, preferably methyl, trifluoromethyl or C1-C 4 -alkoxy, n denotes 0, 1 or 2 "O Y denotes hydrogen, C 1 -C 4 -halogenoalkyl, especially C 1 -C 3 -alkyl having one or more fluorine atoms as substituents, phenyl or phenyl which is substituted by at least one radical from the group comprising methyl, methoxy, trifluoromethyl, chlorine, methylthio, methylsulfinyl, methylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl, and Z denotes a direct bond or oxygen.

3. An active substance preparation as claimed in 1 S17 17 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 1 -C 4 -alkoxy, C 1 -C 4 -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, trifluoromethylthio, trifluoromethylsulfinyl or G* trifluoromethylsulfonyl, and Z denotes oxygen.

4. An active substance preparation as claimed in one or more of claims 1 'o 3, which contains an active substance a) of the formula (Ia) X' 0 R R1 R Y Z 0n o (Ia) N 3 in which SR 1 denotes hydrogen or methyl, R 2 denotes together with R3 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, C 1 -C 4 -halogenoalkoxy, especially tetrafluoroethoxy or hexafluoropropoxy, or C 1 -C 4 -alkylsulfonylphenoxy, especially 4- methylsulfonylphenoxy.

An active substance preparation as claimed in one or more of claims 1 to 4, which is composed of a) 100 to 8000 ppm, based on the preparation, of an it i. 18 18 active substance of the formula 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 water.

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 C12-C18 fatty acids, C12-C18 fatty alcohols, C12-C18 hydroxy fatty acids and esters, sugar alcohols and sugar fatty acid esters. S

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 one or more of claims 1 to 7, which comprises dissolving one or more active substances of the abovementioned formulae and (II) in a water-miscible, physiologically S* 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. *0 S

9. A method of preparation of drinking water for the treatment of coccidiosis in livestock comprising adding in an effective quantity an active substance preparation as claimed in any one of claims 1 to 7 to an appropriate volume of drinking water. The method as claimed in claim 9, wherein the preparation is diluted with water I to a content of 1 to 500 ppm active substance. .m4. b) an anionic or nonionic surfactant having an HL of more than 14, c) 0 to 60% by weight, based on the preparation of a physiologically acceptable water-s uble organic solvent, d) 0 to 10% by weight, based on the prepar ion, of water. 6. An active substance preparation as claime in one or more of claims 1 to 5, wherein e nonionic surfactant is a surfactant from the g oup of ethers or esters of oligopolygl.ycol ether with C12-C18 fatty acids, C 12 -C 18 fatty alcohols C 12 -C 18 hydroxy fatty acids and esters, sugar a cohols and sugar S° fatty acid esters. 7. An active substance preparatio as claimed in claim m, 6, wherein the surfactant i/ an oxyethylate of a sorbitan fatty acid ester. 8. A process for the productio of the active substance preparations as defined i one or more of claims 1 to 7, which comprises d* solving one or more active substances of the abo ementioned formulae and (II) in a water-misci le, physiologically acceptable So anionic or nonionic surfactant, or in a mixture of several of th se surfactants, and, where appropriate, in e presence of up to 80% by weight, based on the preparation, of a physiologically acceptable wa r-soluble organic solvent and, where *so appropriate, in the presence of up to 70% by weight, based on he preparation, of water, with the resulting preparation containing up to 10,000 ppm active sbstance. 9. The us of the active substance preparation defined in at least one of claims 1 to 7 for the preparation of rinking water for the treatment of coccidiosis in/livestock. he use as claimed in claim 9, wherein the S/preparation is diluted with water to a content of 1 CO to 500 ppa active substance. DATED this 26th day of April 1989. E HOECHST AKTIENGESELLSCHAFT EDWD. WATERS SONS MELBOURNE. VIC. 3000. L_