WO2003077655A1 - Controlling parasites on animals by using halogen pyrimidines - Google Patents

Abstract

The invention relates to the systemic and non-systemic control of parasites on animals by using halogen pyrimidines.

Description

 Control of parasites on animals using halopyrimidines

The present invention relates to the systemic and non-systemic control of parasites in animals using halopyrirnidines.

GB-A-2 253 624 discloses pyrimidine fungicides, DE 44 43 641 AI discloses substituted substituted carboxamides with fungicidal activity, EP-A-0 398 692 discloses alkoxyiminoacetamide derivatives also with fungicidal activity, EP-A-0 647 631 finally discloses Naphthyl ether and its use as fungicides and insecticides.

Furthermore, fungicidal halopyrimidines are described in WO 98/21189. It has now surprisingly been found that the halopyrimidines described there are particularly suitable for systemic and / or non-systemic control of parasites (e.g. fleas, lice or flies) on animals.

The parasiticidal effect only became apparent in special biological test systems, which made the active ingredient available to the parasite in an application-oriented method. In lice, fleas and mites, it is known that the ner bond is absorbed not only via the body surface (contact) but also via the host's ingested and / or surrounding body fluid (oral intake). Certain compounds that are particularly effective against these parasites only show their activity in in vitro feeding systems.

The invention relates to: Compounds of formula (I)

in welcher

in which

Z represents optionally substituted cycloalkyl, aryl or heterocyclyl,

R represents hydrogen or alkyl,

Q represents oxygen or sulfur,

X represents halogen and

L ¹ , lX, lX and i are the same or different and each independently represent hydrogen, halogen, cyano, nitro, each optionally substituted by halogen-substituted alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl,

to fight parasites on animals.

In the definitions, the saturated or unsaturated hydrocarbon chains, such as alkyl, alkanediyl, alkenyl or alkynyl, are in each case straight-chain or branched, also in combination with heteroatoms, such as, for example, in alkoxy, alkylthio or alkylimino. Aryl stands for aromatic, mono- or polycyclic hydrocarbon rings, such as phenyl, naphthyl, anthranyl, phenanthryl, preferably phenyl or naphthyl, especially phenyl.

Heterocyclyl stands for saturated or unsaturated, as well as aromatic, ring-shaped compounds in which at least one ring member has a heteroatom, i.e. is an atom other than carbon. If the ring contains several heteroatoms, these can be the same or different. Heteroatoms are preferably oxygen, nitrogen or sulfur. If appropriate, the ring-shaped compounds together with other carbocyclic or heterocyclic, fused or bridged rings together form a polycyclic ring system. Mono- or bicyclic ring systems are preferred, in particular mono- or bicyclic aromatic ring systems.

Cycloalkyl stands for saturated, carbocyclic, ring-shaped compounds which optionally form a polycyclic ring system with other carbocyclic, fused or bridged rings.

The above-mentioned compounds and their preparation are described in detail in WO 98/21189, reference is hereby expressly made to this document.

The compounds according to the invention can optionally be in the form of mixtures of various possible isomeric forms, in particular stereoisomers, such as e.g. E- and Z-. Both the E and the Z isomers and any mixtures of these isomers are claimed.

The invention preferably relates to compounds of the formula (I) in which for cycloalkyl having 3 to 7 carbon atoms which is optionally mono- to disubstituted by halogen, alkyl or hydroxyl; for heterocyclyl with 3 to 7 ring members optionally substituted by alkyl having 1 to 4 carbon atoms; or is in each case optionally mono- to tetrasubstituted, identical or differently substituted phenyl or naphthyl, the possible substituents preferably being selected from the following list: halogen, cyano, nitro, amino, hydroxyl, formyl, carboxy, carbamoyl, thiocarbamoyl; in each case straight-chain or branched alkyl, hydroxyalkyl, oxoalkyl, alkoxy,

Alkoxyalkyl, alkylthioalkyl, dialkoxyalkyl, alkylthio, alkylsulfinyl or alkylsulfonyl each having 1 to 8 carbon atoms; each straight-chain or branched alkenyl or alkenyloxy each having 2 to 6 carbon atoms; each straight-chain or branched haloalkyl, haloalkoxy, haloalkylthio. Haloalkylsulfinyl or haloalkylsulfonyl each having 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms; in each case straight-chain or branched haloalkenyl or haloalkenyloxy each having 2 to 6 carbon atoms and 1 to 11 identical or different halogen atoms; each straight-chain or branched alkylamino, dialkylamino, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, dialkylaminocarbonyloxy, alkenylcarbonyl or alkynylcarbonyl, with 1 to 6 carbon atoms in the respective hydrocarbon chains;

Cycloalkyl or cycloalkyloxy each having 3 to 6 carbon atoms; each optionally monosubstituted to tetrasubstituted, identically or differently, by fluorine, chlorine, oxo, methyl, trifluoromethyl or ethyl and in each case doubly linked alkylene having 3 or 4 carbon atoms, oxyalkylene having 2 or 3 carbon atoms or dioxyalkylene having 1 or 2 carbon atoms; A 'or a group <', in which

A

A * for hydrogen, hydroxy or alkyl with 1 to 4 carbon atoms or

Cycloalkyl with 1 to 6 colile atoms and

AX for hydroxy, amino, methylamino, phenyl, benzyl or for alkyl or alkoxy with 1 to 4 carbon atoms which is optionally substituted by cyano, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino or phenyl, or for alkenyloxy or alkynyloxy each with 2 to 4 carbon atoms stands,

and in each case optionally in the ring part monosubstituted to trisubstituted by halogen, and / or straight-chain or branched alkyl or alkoxy having 1 to 4 carbon atoms, phenyl, phenoxy, phenylthio, benzoyl, benzoylethenyl, cinnamoyl, heterocyclyl or phenylalkyl, phenylalkyloxy, phenylalkylthio, or heterocyclylalkyl, or heterocyclylalkyl, with 1 to 3 carbon atoms in each alkyl part,

R represents hydrogen or methyl,

Q represents oxygen or sulfur,

X represents fluorine, chlorine, bromine or iodine and

lX, XX, lX> and L ^ are the same or different and are each independently hydrogen, halogen, cyano, nitro, each optionally substituted by 1 to 5 halogen atoms, alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl each having 1 to 6 carbon atoms ,

The invention relates in particular to compounds of the formula (I) in which for cyclopentyl or cyclohexyl which is optionally mono- to disubstituted by fluorine, chlorine, methyl, ethyl or hydroxyl; for thienyl, pyridyl or furyl optionally substituted by methyl or ethyl; or is in each case optionally monosubstituted to tetrasubstituted, identical or differently substituted phenyl or naphthyl, the possible substituents preferably being selected from the list below:

Fluorine, chlorine, bromine, iodine, cyano, nitro, amino, hydroxy, formyl, carboxy,

Carbamoyl, thiocarbamoyl

Methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, 1-, 2-, 3-, neo-pentyl, 1-, 2-, 3-, 4- (2nd -Methylbutyl), 1-, 2-, 3-hexyl, 1-, 2-, 3-, 4-, 5- (2-methylpentyl), 1-, 2-, 3- (3-methylpentyl), 2- Ethyl butyl, 1-, 3-, 4- (2,2-dimethylbutyl), 1-, 2- (2,3-

Dimethylbutyl), hydroxymethyl, hydroxyethyl, 3-oxobutyl, methoxymethyl, dimethoxymethyl,

Methoxy, ethoxy, n- or i-propoxy,

Methylthio, ethylthio, n- or i-propylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl,

Vinyl, allyl, 2-methylallyl, propen-1-yl, crotonyl, propargyl, vinyloxy, allyloxy, 2-methylallyloxy, propen-1-yloxy, crotonyloxy, propargyloxy;

Trifluoromethyl, trifluoroethyl,

Difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, trifluoromethylthio, difluorochloromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl, Methylamino, ethylamino, n- or i-propylamino, dimethylamino, diethylamino,

Acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, benzylaminocarbonyl, acryloyl, propioloyl,

Cyclopentyl, cyclohexyl,

each optionally optionally up to four times, the same or different, substituted by fluorine, chlorine, oxo, methyl or trifluoromethyl, in each case twice linked propanediyl, ethyleneoxy, methylenedioxy, ethylenedioxy

Al or a grouping '', where ι ^ ^■

Ä

A ^ represents hydrogen, methyl or hydroxy and

AX stands for hydroxy, methoxy, ethoxy, amino, methylamino, phenyl, benzyl or hydroxyethyl, and

phenyl, phenoxy, phenylthio, benzoyl, benzoylethenyl, cinnamoyl, benzyl, phenylethyl, phenylpropyl, benzyloxy, in each case optionally in the ring part monosubstituted to triple by halogen, and / or straight-chain or branched alkyl or alkoxy having 1 to 4 carbon atoms.

Benzylthio, 5,6-dihydro-l, 4,2-dioxazin-3-ylmethyl, triazolylmethyl, benzoxazol-2-ylmethyl, l, 3-dioxan-2-yl, benzimidazol-2-yl, dioxol-2- yl, oxadiazolyl, R represents hydrogen or in particular methyl,

Q represents oxygen or sulfur,

X represents fluorine or chlorine and

lX, lX, i and L ^ are the same or different and are each independently hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n- or i-propyl, n-, i-, s- or t -Butyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl or

Ethylsulfonyl, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl.

In a very particularly preferred group of compounds, Z represents optionally substituted phenyl.

Another particularly preferred group of compounds

L and lX> independently of one another for methyl and in particular hydrogen and

iX and L ^ for hydrogen.

In particular, compounds of the formula (I) are preferred in which X represents fluorine.

The general or preferred radical definitions given above apply both to the end products of the formula (I) and correspondingly to the starting materials or intermediates required in each case for the preparation. The radical definitions specified for these radicals in the respective combinations or preferred combinations of radicals are independently replaced by radical definitions of other preferred ranges, regardless of the combination specified in each case.

These radical definitions can be combined with one another as desired, that is to say also between the specified ranges of preferred compounds.

In the case of favorable warm-blooded toxicity, the active substances mentioned are suitable for systemic and / or non-systemic control of parasites which occur in animal husbandry and animal breeding in domestic and farm animals as well as zoo, laboratory, experimental and hobby animals. They are effective against all or individual stages of development of the pests and against resistant and normally sensitive types of pests.

Parasites are in particular species liropods, particularly preferably insects. The preparations according to the invention are preferably used to control ectoparasites.

The above-mentioned ectoparasites include: tick ticks, leather ticks, mite mites, running mites, flies (stinging and licking), parasitic fly larvae, lice, hair lice, featherlings and fleas. These parasites include:

From the order of the Anoplurida e.g. Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp ..

From the order of the Mallophagida and the subordinates Amblycerina and Ischnocerina, for example Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Trichodectes spp., Felicola spp .. From the order Diptera and the subordinates Nematocerina and Brachycerina, for example Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp. , Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wo lfal rtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp., Melophagus spp ..

From the order of the Siphonapterida e.g. Pulex spp., Ctenocephalides spp.,

Xenopsylla spp., Ceratophyllus spp ..

From the order of the Heteropterida e.g. Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp ..

From the order of the Blattarida e.g. Blatta orientalis, Periplaneta americana, Blattella germanica, Supella spp ..

From the subclass of Acaria (Acarida) and the orders of the Meta and Mesostigmata e.g. Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp.,

Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp., Varroa spp ..

From the order of the Actinedida (Prostigmata) and Acaridida (Astigmata) e.g.

Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypppectoles spp ., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp., Laminosioptes spp .. The active ingredients are also suitable for combating parasitic protozoa. The parasitic protozoa include:

Mastigophora (Flagellata) such as Trypanosomatidae e.g. Trypanosoma b. brucei, T.b. gambiense, T.b. rhodesiense, T. congolense, T. cruzi, T. evansi, T. equinum, T. lewisi, T. percae, T. simiae, T. vivax, Leishmania brasiliensis, L. donovani, L. tropica, e.g. Trichomonadidae e.g. Giardia lamblia, G. canis.

Sarcomastigophora (Rhizopoda) such as Entamoebidae e.g. Entamoeba histolytica, Hartmanellidae e.g. Acanthamoeba sp., Hartmanella sp.

Apicomplexa (Sporozoa) such as Eimeridae e.g. Eimeria acervulina, E. adenoides, E. alabahmensis, E. anatis, E. anseris, E. arloingi, E. ashata, E. auburnensis, E. bovis, E. brunetti, E. canis, E. chinchillae, E. clupearum , E. columbae, E. contorta, E. crandalis, E. debliecki, E. dispersa, E. ellipsoidales, E. falciformis, E. faurei, E. flavescens, E. gallopavonis, E. hagani, E. intestinalis, E. iroquoina, E. irresidua, E. labbeana, E. leucarti, E. magna, E. maxima, E. media, E. meleagridis, E. meleagrimitis, E. mitis, E. necatrix, E. ninakohlyakimovae, E. ovis, E. parva, E. pavonis, E. perforans, E. phasani, E. piriformis, E. praecox, E. residua, E. scabra, E. spec, E. stiedai, E. suis, E. tenella, E. truncata, E. truttae, E. zuernii, Globidium spec, Isospora belli, I. canis, I. felis, I. ohioensis, I. rivolta, I. spec, I. suis, Neospara caninum, Neospora hughesi; Cystisospora spec., Cryptosporidium spec. how

Toxoplasmadidae e.g. Toxoplasma gondii such as Sarcocystidae e.g. Sarcocystis bovicanis, S. bovihommis, S. neurona, S. ovicanis, S. ovifelis, S. spec, S. suihominis such as Leucozoidae e.g. Leucozytozoon simondi, such as Plasmodiidae e.g. Plasmodium berghei, P. falciparum, P. malariae, P. ovale, P. vivax, P. spec, such as Piroplasmea e.g.

Babesia argentina, B. bovis, B. canis, B. spec, Theileria parva, Theileria spec, such as

Adeleina e.g. Hepatozoon canis, H. spec.

Furthermore Myxospora and Microspora eg Glugea spec. Nosema spec Furthermore Pneumocystis carinii, and Ciliophora (Ciliata) such as Balantidium coli, Ichthiophtliirius spec, Trichodina spec, Epistylis spec

The compounds according to the invention are also active against protozoa which occur as parasites in insects. Parasites of the tribe should be mentioned as such

Microsporida, especially the genus Nosema. Nosema apis is particularly worth mentioning for the honeybee.

Livestock and breeding animals include mammals such as Cattle, horses, sheep, pigs, goats, camels, water buffalos, donkeys, rabbits, fallow deer, reindeer;

Fur animals such as Mink, chinchilla, raccoon; such as. Chickens, geese, turkeys, ducks.

Laboratory and experimental animals include mice, rats, guinea pigs, golden hamsters, dogs and cats.

The pets include dogs and cats.

The application can be prophylactic as well as therapeutic.

The active substances for systemic control of parasites are preferably used directly or in the form of suitable preparations enterally, parenterally, dermally or nasally, in particular orally, transdermally, by means of pour-on formulations or as an injection.

The enteral application of the active ingredients happens, for. B. orally in the form of powder, tablets, capsules, pastes, drinkers, granules, orally administrable solutions, suspensions and emulsions, boluses, medicated feed or drinking water. The dermal application happens for. B. in the form of diving (dipping), spraying (spraying) or pouring (pour-on or spot-on). Parenteral use happens z. B. in the form of injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.

Injection solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly additives such as solubilizers, acids,

Bases, buffer salts, antioxidants, preservatives can be added. The solutions are sterile filtered and filled.

Examples of solvents which may be mentioned are: physiologically compatible solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol,

Propylene glycol, polyethylene glycols, N-methyl-pyrrolidone, and mixtures thereof.

If appropriate, the active compounds can also be dissolved in physiologically tolerable vegetable or synthetic oils which are suitable for injection.

Examples of solubilizers are: solvents which promote the dissolution of the active ingredient in the main solvent or prevent it from precipitating. Examples are polyvinylpyrroHdon, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

Examples of preservatives which may be mentioned are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.

Examples of suitable preparations for oral administration are: tablets, homogeneous solutions, emulsions, suspensions.

Oral solutions are applied directly. Concentrates are used orally after previous dilution to the application concentration. Oral solutions and concentrates are prepared as described above for the injection solutions, and sterile work can be dispensed with. Suitable preparations for transdermal application are known to be active substance-containing solutions which may contain substances which promote resorption. Resorption-promoting substances are, for example, DMSO (dimethyl sulfoxide), DMF (dimethylformamide), triglycerides and long-chain aliphatic fatty acid esters.

Said preparations contain the active ingredient in concentrations of 0.1 to 65% by weight, preferably from 1.0 to 40% by weight.

For systemic parasite control in animals, it has generally proven advantageous to use amounts of about 0.5 to 100 mg of active ingredient / l g of body weight

To achieve good effect.

The dermal application happens e.g. in the form of bathing, diving (dipping), spraying (spraying), pouring on (pour-on or spot-on), washing, shampooing, watering, powdering or by means of solid preparations.

Suitable preparations are:

Solutions or concentrates for administration after dilution, sprays, spot on, pour on solutions for direct application, infusion formulations, gels;

Emulsions and suspensions for dermal use and solid or semi-solid preparations;

Formulations in which the active ingredient is processed in an ointment base or in an oil in water or water in oil emulsion base;

Solutions for use on the skin are dripped on, spread on, rubbed in, sprayed on, sprayed on or applied by dipping (dipping), bathing or washing.

The solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives.

The following may be mentioned as solvents: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzyl benzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol, diethylene glycol, monobutylene glycol, ketone Methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide,

N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-1, 3-dioxolane.

The active ingredients can optionally also be dissolved in physiologically compatible vegetable or synthetic oils.

The following may be mentioned as solubilizers: solvents which promote the solution of the active ingredient in the main solvent or prevent it from precipitating. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol. It may be advantageous to add thickeners when preparing the solutions. Thickeners are: inorganic thickeners such as bentonites, colloidal silica, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and metacrylates.

Gels that are applied or spread on the skin are produced by adding enough thickening agent to solutions that have been prepared as described above to produce a clear mass with an ointment-like consistency. The thickeners specified above are used as thickeners.

Pour-on formulations are poured or sprayed onto limited areas of the skin, the active ingredient being distributed over the surface of the body. Pour-on formulations are also conceivable in which the active ingredient penetrates the skin and has a systemic effect.

Pour-on formulations are prepared by dissolving, suspending or emulsifying the active ingredient in suitable skin-compatible solvents or solvent mixtures. If necessary, further auxiliaries such as dyes, antioxidants, light stabilizers and adhesives are added. In the case of systemically acting pour-on formulations, substances which promote absorption can advantageously also be added.

Dyes are all dyes approved for use on animals, which can be dissolved or suspended.

Excipients are also spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols. Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol.

Light stabilizers are e.g. Substances from the class of benzophenones or novantisolic acid.

Adhesives are e.g. Cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.

Resorption promoting substances are e.g. B. DMSO, spreading oils such as isopropyl myristate,

Dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Emulsions can be used orally, dermally or as injections. They are either of the water in oil type or the oil in water type.

They are produced by dissolving the active ingredient either in the hydrophobic or in the hydrophilic phase and homogenizing it with the solvent of the other phase with the aid of suitable emulsifiers and, if necessary, other auxiliaries such as dyes, absorption-promoting substances, preservatives, antioxidants, light stabilizers, viscosity-increasing substances ,

The following may be mentioned as hydrophobic phase (oils): paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid bigylceride, triglyceride mixture with vegetable fatty acids of chain length C ₈ . ₁₂ or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids which may also contain hydroxyl groups, mono- and diglycerides of C ₈ / CIO fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length C ₆ -C ₈ , isopropyl myristate, isopropyl palmitate, caprylic / capric acid esters of saturated fatty alcohols of chain length Ci2 ~ Cι, isopropyl stearate, oleic acid oleyl ester, oleic acid decyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as dibutyl phthalate, adipic acid diisopropyl ester, the latter related to fatty alcohols, ethodecyl alcohol, C 2 -alkidyl alcohol, isodecyl alcohol, isodecyl alcohol, C 2 -alcohol ethane, isodecyl alcohol, C 2 -alcohol ethane, isodecyl alcohol, C 2 -alcohol ethane, isodecyl alcohol, C 2 -id esters, such as esters, esters, -alcohol, oleyl alcohol.

Fatty acids such as Oleic acid and its mixtures.

The following can be mentioned as the hydrophilic phase: water, alcohols, e.g. Propylene glycol, glycerin, sorbitol and their mixtures.

The following may be mentioned as emulsifiers: nonionic surfactants, e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether; mpholytic surfactants such as di-Na-N-lauryl-β-iminodipropionate or lecithin;

anionic surfactants, such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether phophosphoric acid ester monoethanolamine salt; cationic surfactants such as cetylline ylammonium chloride.

Other auxiliaries that may be mentioned are: viscosity-increasing and emulsion-stabilizing substances such as carboxymethyl cellulose, methyl cellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic acid anhydride, Polyethylene glycols, waxes, colloidal silica or mixtures of the listed substances.

Suspensions can be used orally, dermally or as an injection. They are produced by adding the active ingredient in a carrier liquid, if necessary with the addition of other auxiliaries such as wetting agents, dyes, absorption-promoting substances,

Preservatives, antioxidants or light protection agents suspended. All homogeneous solvents and solvent mixtures may be mentioned as carrier liquids.

The surfactants specified above may be mentioned as wetting agents (dispersants).

Further additives mentioned are those mentioned above.

Semi-solid preparations can be administered orally or dermally. They differ from the suspensions and emulsions described above only in their higher viscosity.

To prepare solid preparations, the active ingredient is mixed with suitable carriers, if appropriate with the addition of auxiliaries, and brought into the desired shape.

All physiologically compatible solid inert substances may be mentioned as carriers. All of these serve inorganic and organic substances. Inorganic substances are e.g. Table salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays, precipitated or colloidal silicon dioxide, phosphates.

Excipients are preservatives, antioxidants, dyes, which have already been listed above.

Other suitable auxiliaries are lubricants and lubricants such as Magnesium stearate, stearic acid, talc, bentonite.

Ready-to-use preparations contain the active ingredient in concentrations of 1 ppm - 80 percent by weight, preferably from 0.01 - 65 percent by weight. Preferred amounts of material are 1 to 50 percent by weight, particularly preferably 5 to 40

Weight. Preparations which are diluted before use contain the active ingredient in concentrations of 0.5-90 percent by weight, preferably from 1 to 50 percent by weight.

In general, it has been found advantageous to use amounts from about 0.5 to about

100 mg, preferably 1 to 50 mg, of active ingredient per kg of body weight per day to achieve effective results.

Solid preparations include powders, premixes and concentrates, granules, pellets, tablets, boluses, capsules, aerosols and inhalants as well as moldings.

According to a preferred embodiment, the parasite control according to the invention is carried out non-systemically by means of dermal application.

Another preferred embodiment is the systemic application

Molded body called. Shaped bodies include Collars, pendants for collars (medallions), ear tags, ribbons for attachment to limbs or body parts, adhesive strips and foils, peel-off foils.

In general, it has proven advantageous to achieve solid formulations according to the invention which release amounts of active compound from 10 to about 300 mg, preferably 20 to 200 mg, particularly preferably 25 to 160 mg, per kg of body weight of the animal to be treated over the course of at least three months good effectiveness to apply.

Thermoplastic and flexible thermosetting plastics as well as elastomers and thermoplastic elastomers come into question for the production of the shaped bodies. Polyvinyl resins, polyurethanes, polyacrylates, epoxy resins, cellulose, cellulose derivatives, polyamides and polyesters which are sufficiently compatible with the abovementioned active ingredient may be mentioned as such. The polymers must have sufficient strength and

Have flexibility so as not to crack or become brittle during molding. she must be of sufficient durability to withstand normal wear and tear. In addition, the polymers must allow the active ingredient to migrate sufficiently to the surface of the molding.

Polyvinyl resins include polyvinyl halides such as polyvinyl chloride,

Polyvinyl chloride vinyl acetate and polyvinyl fluoride; Polyacrylate and polymethacrylate esters, such as polymethylacrylate and polymethylmetliacrylate; and polyvinylbenzenes such as polystyrene and polyvinyltoluene. Special mention should be made of polyvinyl chloride.

The plasticizers suitable for the production of molded articles based on polyvinyl resin are usually used to plasticize solid vinyl resins. The plasticizer to be used depends on the resin and its compatibility with the plasticizer. Suitable plasticizers are, for example, esters of phosphoric acid, such as esters of phthalic acid, such as dimethyl phthalate and di-octyl phthalate, and esters of adipic acid, such as diisobutyl adipate. Others can

Esters such as the esters of azelaic acid, maleic acid, ricinoleic acid, myristic acid, palmitic acid, oleic acid, sebacic acid, stearic acid and trimellitic acid, as well as complex linear polyesters, polymeric plasticizers and epoxidized soybean oils can be used. The amount of plasticizer is about 10 to 50%, preferably about 20 to 45% by weight of the total composition.

The constituent bodies can also contain further constituents, such as stabilizing agents, lace-up agents, fillers and coloring materials, without changing the basic properties of the composition. Suitable stabilizers are antioxidants and agents that protect the tapes from ultraviolet radiation and unwanted degradation during processing, such as extrusion. Some stabilizers, such as epoxidized soybean oils, also serve as secondary plasticizers. For example, stearates, stearic acid and low molecular weight polyethylenes can be used as the reducing agent. These components can be present in a concentration up to about

5% by weight of the total composition can be used. In the production of the vinyl-based molded articles, the various constituents are mixed by known processes and compression-molded by known extrusion or injection molding processes.

From a technical point of view, the choice of the processing method for the production of the shaped bodies depends in principle on the rheological properties of the strip material and the shape of the desired strip. The processing methods can be set according to the processing technology or the type of shaping. In process technology, the processes can be subdivided according to the rheological conditions they run through. Thereafter, casting, pressing, injection molding and application are possible for viscous strip materials and injection molding, extrusion (extrusion), calendering, rolling and, if necessary, edging for elastoviscous polymers. Divided according to the type of shaping, the moldings according to the invention can be obtained by casting, dipping, pressing, injection molding, extruding, calendering,

Manufacture embossing, bending, deep drawing etc.

These processing methods are known and require no further explanation. In principle, the explanations given above for polyvinyl resins apply to other polymers.

The polyurethanes used as the carrier material are prepared in a manner known per se by reacting polyisocyanates with higher molecular weight compounds having at least two groups which are reactive toward isocyanates, and optionally low molecular weight chain extenders and / or monofunctional ones

Chain breakers manufactured.

In this context, the following should be noted:

Polyisocyanates containing isocyanurate groups, as described, for example, in US Pat. No. 3,001,973, in DE Patents 1,022,789, 1,222,067 and 1,027,394 and in DE-OSes 1,929,034 and 2,004,048; Polyisocyanates containing urethane groups, such as they are described, for example, in DE-PS 752 261 or in US-PS 3 394 164; polyisocyanates containing acylated urea groups according to DE-PS 1 230 778; Polyisocyanates containing biuret groups, as described, for example, in DE-PS 1 101 394, in US Pat. Nos. 3 124 605 and 3 201 372, and in GB-PS 889 050; polyisocyanates prepared by telomerization reactions, as described, for example, in US Pat. No. 3,654,106; Polyisocyanates containing ester groups, as mentioned, for example, in British Pat. Nos. 965,474 and 1,072,956, in US Pat. No. 3,567,763 and in German Pat. No. 1,231,688; Reaction products of the above-mentioned isocyanates with acetals according to DE-PS 1 072 385 and polyisocyanates containing polymeric fatty acid residues according to US-PS 3 455 883.

It is also possible to use the distillation residues obtained in industrial isocyanate production and containing isocyanate groups, optionally dissolved in one or more of the aforementioned polyisocyanates. It is also possible to use any mixtures of the aforementioned polyisocyanates.

Preferred polyisocyanates are generally the tolylene diisocyanates and the diphenylmethane diisocyanates.

Polyhydroxyl compounds already containing urethane or urea groups, as well as optionally modified natural polyols such as castor oil, carbohydrates or starch, polyester amides and polyamides count, for example. the predominantly linear condensates obtained from polyvalent saturated and unsaturated carboxylic acids or their anhydrides and polyvalent saturated and unsaturated amino alcohols, diamines, polyamines and their mixtures can be used for this purpose.

Addition products of alkylene oxides on phenol-formaldehyde resins or also on urea-formaldehyde resins can also be used according to the invention.

Representatives of these connections are e.g. in High Polymers, Vol. XVI, "Polyurethanes, Chemistry and Technology", written by Saunders-Frisch, Interscience Publishers,

New York, London, Volume 1, 1962, Pages 32-42 and Pages 44-54 and Volume II, 1964, Pages 5 -6 and 198 - 199, as well as in the plastics manual, volume VE, Vieweg-Höchtlen, Carl-Hanser-Verlag, Munich, 1966, e.g. on pages 45 - 71.

Of course, mixtures of the above-mentioned compounds with at least two isocyanate-reactive hydrogen atoms with a molecular weight of 400-10,000, e.g. Mixtures of polyethers can be used.

When selecting the higher molecular weight polyol component used for the production of the polyurethane, it should be noted that the finished polyurethane should not be swellable in water. The use of an excess of polyhydroxyl compounds with ethylene oxide units (polyethylene glycol polyether or polyester with diethylene or triethylene glycol as the diol component) should therefore be avoided.

Thermoplastic elastomers are particularly emphasized for the production of the shaped bodies. These are materials that contain elastomeric phases in thermoplastically processable polymers either physically mixed in or chemically bound. A distinction is made between polymer blends in which the elastomeric phases are part of the polymer structure. By building the thermoplastic

Elastomers are hard and soft areas side by side. The hard areas form a crystalline network structure or a continuous phase whose spaces are filled with elastomeric segments. Because of this structure, these materials have rubber-like properties.

There are 5 main groups of thermoplastic elastomers:

1. Copolyester

2. Polyether Block Amides (PEBA) 3. Thermoplastic Polyurethanes (TPU)

4. Thermoplastic polyolefins (TPO) 5. Styrene block copolymers

Suitable copolyesters (segmented polyester elastomers) are composed, for example, of a large number of recurring, short-chain ester units and long-chain ester units which are combined by ester linkages, the short-chain ester units accounting for about 15-65% by weight of the copolyester and having the formula (11).

in which

R represents a divalent radical of a dicarboxylic acid which has a molecular weight of less than about 350,

D represents a divalent radical of an organic diol that has a molecular weight below about 250.

The long-chain ester units make up about 35-85% by weight of the copolyester and have the formula (111)

in which

R represents a divalent radical of a dicarboxylic acid which has a molecular weight of less than about 350,

G represents a divalent residue of a long chain glycol which has an average molecular weight of about 350 to 6000. Nerfaliren for the synthesis of such copolyesters are known from DOS 2239 271, DOS 2 213 128, DOS 2 449 343 and US-P 3 023 192.

Suitable copolyesters are, for example, under the trade name ^® Hytrel from Du Pont,

^® Pelpren from Toyobo ^® , Arnitel from Akzo, ^® Ectel from Eastman Kodak and ^® Riteflex from Hoechst.

Suitable polyether block amides are, for example, those which consist of polymer chains which are composed of repeating units corresponding to the formula (IN).

in welcher

in which

A is the polyamide chain derived from a polyamide with 2 carboxyl end groups by loss of the latter and

B is the polyoxyalkylene glycol chain derived from a polyoxyalkylene glycol with terminal OH groups by loss of the latter, and

n is the number of units forming the polymer chain.

The end groups are preferably OH groups or residues of compounds which terminate the polymerization.

The dicarboxylic acid polyamides with the terminal carboxyl groups are obtained in a known manner, for example by polycondensation of one or more lactams or / and one or more amino acids, moreover by polycondensation of one Dicarboxylic acid with a diamine, in each case in the presence of an excess of an organic dicarboxylic acid, preferably with terminal carboxyl groups. These carboxylic acids become part of the polyamide chain during the polycondensation and attach themselves in particular to the end of the chain, resulting in a cc-codicarboxylic acid polyamide. Dicarboxylic acid also acts as a chain terminator, which is why it is also used in excess.

The polyamide can be obtained starting from lactams and / or amino acids with a KoHenwasserstoifkette consisting of 4-14 C atoms, such as of Caprolactam, Oenantholactam, Dodekalactam, Undekanolactam, Dekanolactanϊ, 11-Amino-undekano or 12-A-rninododecanoic acid.

Examples of polyamides, such as those formed by polycondensation of a dicarboxylic acid with a diamine, are the condensation products of hexamethylenediamine with adipic, azelaic, sebacic, and 1,12-dodecanedioic acid, and the condensation products of nonamemylenediamine and adipic acid.

In the case of the dicarboxylic acids used for the synthesis of the polyamide, that is to say on the one hand for fixing one carboxyl group at each end of the polyamide chain and on the other hand as chain terminating agent, those having 4-20 C atoms come into play

Question, especially alkanedioic acids, such as succinic, adipic, cork, azelaic, sebacic, undecanedio or dodecanedioic acid, further cycloaliphatic or aromatic dicarboxylic acid, such as terephthalic or isphthalic or cyclohexane-l, 4-dicarboxylic acid.

The polyoxyalkylene glycols containing terminal OH groups are unbranched or branched and have an alkylene radical with at least 2 carbon atoms. In particular, these are polyoxyethylene, polyoxypropylene and polyoxytetramethylene glycol, as well as copolymers thereof. The average molecular weight of these OH group-terminated polyoxyalkylene glycols can be in a wide range, advantageously between 100 and 6000, in particular between 200 and 3000.

The proportion by weight of the polyoxyalkylene glycol, based on the total weight of the polyoxyalkylene glycol and dicarboxylic acid polyamide used to produce the PEBA polymer, is 5-85%, preferably 10-50%.

Processes for the synthesis of such PEBA polymers are known from FR-PS 7 418 913 (No. of the publication 2 273 021), DOS 2 802 989, DOS 2 837 687, DOS 2 523 991,

EP-S 0 095 893, DOS 2 712 987 and DOS 2 716 004 are known.

Those PEBA polymers which, in contrast to those previously described, have a statistical structure are particularly suitable. Suitable and preferably suitable PEBA polymers are, for example, under the trade names PEBAX from Atochem, ^® Vestamid

Hüls AG,, ^s, Grilamid from EMS-Chemie and ^ Kellaflex from DSM.

The application can be prophylactic as well as therapeutic.

In the case of collars, the concentration of the active ingredients is preferably 1 to

50%; in the case of medallions, pendants and ear tags preferably 2.5 to 35%, in the case of foils, adhesive strips preferably 0.1 to 15%.

The active substances can be present in the corresponding preparations (formulations) in a mixture with synergists or other active substances (co-active substances).

For example, insecticides, attractants, sterilants, bactericides, acaricides, nematicides, fungicides, etc. may be included as additional active ingredients. As insecticides such. B. called: phosphorus-containing compounds, ie phosphoric or phosphonic acid esters, natural or synthetic pyrethroids, carbamates, amidines, juvenile hormones and juvenoid synthetic active ingredients, chlorinated hydrocarbons, phenylureas, substances produced by microorganisms and others. The phosphoric or phosphoric acid esters include:

0-ethyl-0- (8-clιmolyl) phenyl thiophosphate (Quintiofos), 0.0-diethyl 0- (3-chloro-4-methyl-7-coumarinyl) thiophosphate (Coumaphos),

0.0-diethyl-0-phenylglyoxylonitrile oxime thiophosphate (phoxime), 0.0-diethyl-O-cyanochlorobenzaldoxime thiophosphate (chlorophoxime), 0.0-die yl-0- (4-bromo-2,5- dicblorophenyl) -phosphorothionate (Bromophos-ethyl), 0,0,0 ', 0'-Tettaemyl-S, S'-meÜιylene-di (phosphoroditMonat) (Ethion), 2,3-p-dioxanedithiol-S, S-bis (0,0-diethylphosphorodithionat,

2-chloro-1 - (2,4-dicl lorphenyl) vinyl diethyl phosphate (Clilorfenvinphos), 0.0-dimethyl-0- (3-me yl-4-methyl-methylphenyl) -t monophosphoric acid ester (FentM

The carbamates include:

2-isopropoxyphenylmemylcarbamate (propoxur),

1 -naphthyl-N-methylcarbamate (carbaryl).

The synthetic pyrethroids include compounds of the formula (I)

in welcher

in which

1 1 R and R are halogen, optionally halogen-substituted alkyl, optionally halogen-substituted phenyl,

R ^{3 represents} hydrogen or CN, R> 4 represents hydrogen or halogen,

R ^{5 represents} hydrogen or halogen,

Synthetic pyrethroids of the formula (I) in which are preferred

R ^{1 represents} halogen, in particular fluorine, chlorine, bromine,

R ² for halogen, in particular fluorine, chlorine, bromine, trihalomethyl, phenyl,

Chlorophenyl stands,

R ^{3 represents} hydrogen or CN,

R ^{4 represents} hydrogen or fluorine,

R ^{5 represents} hydrogen.

Synthetic pyrethroids of the formula (I) in which are particularly preferred

R ^{1 represents} chlorine,

R ^{2 represents} chlorine, trifluoromethyl, p-chlorophenyl,

R ^{3 represents} CN,

R ^{4 represents} hydrogen or fluorine,

R ^{5 represents} hydrogen.

Compounds of the formula (T) may be mentioned in particular R ^{1 represents} chlorine,

R ^{2 represents} chlorine or p-chlorophenyl,

R> 3 ^J stands for CN,

R> 4 represents fluorine in the 4-position,

R ^{5 represents} hydrogen.

The following may be mentioned in detail:

3 - [2- (4-chloro-phenyl) -2-chlorovinyl] -2,2-dimethyl-cyclo-propanecarboxylic acid [(cc-cyano-4-fluoro-3-phenoxy) benzyl] ester (flumethrin),

2,2-dime yl-3- (2,2-dicMorvinyl) -cyclopropanecarboxylic acid-oc-cyano (4-fluoro-3-phenoxy) -benzyl ester (cyflulhrin) and its enantiomers and stereomers,

oc-cyano-3-phenoxybenzyl (+) - cis, trans-3- (2,2-dibromovinyl) -2,2-dimethylcyclopropane carboxylate (deltamethrin),

2,2-DJnιethyl-3- (2,2-dicMorvmyl) -cyclopropanecarboxylic acid-oc-cyano-3-phenoxybenzyl ester (cypermetlirin),

3-phenoxybenzyl-cis, trans-3 - (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate (permethrin),

oc- (-Cl-phenyl) -isovaleric acid-oc-cyano-3-phenoxy-benzyl ester (Fenvalerate), 2-Cyano-3-phenoxybenzyl-2- (2-CuU-cc, oc, α: -ttifluor-p-toluidmo) -3-methylbutyrate (fluvalinate).

The amidines include:

3-methyl-2- [2,4-dimemylphenylimino] thiazoline,

2- (4-CMOR-2-memylphenylinιino) -3-memylthiazolidin,

2- (4-Cllor-2-methylphenylimino) -3 - (isobutyl-1-enyl) tbiazolidine

1,5-bis (2,4-dimethylphenyl) -3-methyl-1,3,5-triazapenta- 1,4-diene (Amitraz).

Juvenile hormones or juvenile hormone-like substances include substituted diaryl ethers, benzoyl ureas and triazine derivatives. Juvenile hormones and juvenile hormone-like substances include in particular compounds of the following formulas:

The substituted diaryl ethers include, in particular, substituted alkoxydiphenyl ethers or diphenylmethanes of the general formula (I)

wobei

in which

R ^{1 represents} hydrogen, halogen, alkyl, alkoxy, alkylthio, haloalkyl,

Haloalkoxy, haloalkylthio, dioxyalkylene, dioxyhalogenalkylene, CN, NO ₂ , alkenyl, alkynyl, alkoxyalkyl, alkoxyalkoxy, hydroxyalkoxy,

R> 2 represents the radicals specified for R, R ^{3 represents} the radicals specified for R ¹ ,

R ^{4 represents} hydrogen, alkyl, haloalkyl or halogen,

R ^{5 represents} the radicals indicated for R ⁴ ,

Het stands for optionally substituted heteroaryl which is not bound to the rest of the group via the heteroatom,

X, Y independently of one another represent -O-, -S-

Z represents -O-, -S-, -CH ₂ -, -CHCH ₃ -, -C (CH ₃ ) ₂ -,

m and n independently of one another represent 0, 1, 2, 3 but their sum is equal to or greater than 2.

Compounds of the formula (I) are particularly preferred

in which

R ^{1 is} hydrogen, methyl, trifluoromethyl, methoxy, trifluoromethoxy, chlorine, fluorine

R ^{2 represents} hydrogen,

R ^{3 represents} hydrogen, fluorine, chlorine, methyl,

R ^{4 represents} hydrogen or methyl,

R ^{5 represents} methyl, ethyl, trifluoromethyl or hydrogen, Het is pyridyl or pyridazinyl which are optionally substituted by fluorine, chlorine, methyl, NO ₂ , methoxy, methylmercapto,

X stands for O,

Y stands for O,

Z represents O, CH ₂ or - (CH ₃ ) ₂ -,

m represents 1,

n stands for 1.

The following connections are specifically mentioned:

wobeiBenzoyl ureas include compounds of the formula (V):

in which

R ^{1 represents} halogen,

R represents hydrogen or halogen,

R represents hydrogen, halogen or Cμ-alkyl,

R ⁴ for halogen, 1-5-halogen-Cι ^ -alkyl, Cμ- alkoxy, 1-5-halogen-Cι-φ-alkoxy, C ι- ₄ -AHylthio, 1-5-halogen-C _M -alkylthio, Phenoxy or pyridyloxy which may optionally be substituted by halogen, Ci-alkyl, 1-5-halogen-C _M -alkyl, C ^ -alkoxy, l-5-halogen-Cι ^ .- alkoxy, Cμ- alkylthio, 1-5 - Halogen -C-C ₄ alkylthio.

In particular, the following should be mentioned:

In addition, the following examples of other insecticides and acaricides and nematicides which can be used as co-active substances are mentioned:

Abamectin, Acephate, Acetamiprid, Acrinathrin, Alanycarb, Aldicarb, Aldoxycarb,

Alpha-cypermethrin, Alphamethrin, Amitraz, Avermectin, AZ 60541, Azadirachtin, Azamethiphos, Azinphos A, Azinphos M, Azocyclotin,

Bacillus popilliae, Bacillus sphaericus, Bacillus subtilis, Bacillus thuringiensis, Baculoviruses, Beauveria bassiana, Beauveria tenella, Bendiocarb, Berrfuracarb, Bensultap, Benzoximate, Betacyfluthrin, Bifenazate, Bifenthrin, Bioethanomhrin

Biopermethrin, Bistrifluron, BPMC, Bromophos A, Bufencarb, Buprofezin, Butathiofos, Butocarboxim, Butylpyridaben,

Cadusafos, Carbaryl, Carbofuran, Carbophenothion, Carbosulfan, Cartap, Chloethocarb, Chlorethoxyfos, Chlorfenapyr, Chlorfenvinphos, Chlorfluazuron, Chlormephos, Chlorpyrifos, Chlorpyrifos M, Chlovaporthrin, Chromafenozide, Cis-

Resmethrin, cispermethrin, clocythrin, cloethocarb, clofentezine, clothianidine, Cyanophos, cycloprene, cycloprothrin, cyfluthrin, cyhalothrin, cyhexatin,

Cypermethrin. cyromazine,

Deltamethrin, Demeton M, Demeton S, Demeton-S-methyl, Diafenthiuron, Diazinon,

Dichlorvos, Dicofol, Diflubenzuron, Dimethoat, Dimethylvinphos, Diofenolan, Disulfoton, Docusat-sodium, Dofenapyn,

Eflusilanate, Emamectin, Empenthrin, Endosulfan, Entomopfthora spp.,

Eprinomectin, Esfenvalerate, Ethiofencarb, Ethion, Ethoprophos, Etofenprox,

Etoxazole, Etrimfos,

Fenamiphos, Fenazaquin, Fenbutatin oxide, Fenitrothion, Fenothiocarb, Fenoxacrim, Fenoxycarb, Fenpropathrin, Fenpyrad, Fenpyrithrin, Fenpyroximate, Fenvalerate,

Fipronil, fluazinam, fluazuron, flubrocythrinate, flucycloxuron, flucythrinate,

Flufenoxuron, Flumethrin, Flutenzine, Fluvalinate, Fonophos, Fosmethilan,

Fosthiazate, Fubfenprox, Furathiocarb,

Granuloseviruses Halofenozide, HCH, Heptenophos, Hexaflumuron, Hexythiazox, Hydroprene,

Imidacloprid, indoxacarb, isazofos, isofenphos, isoxathion, ivermectin,

Kempolyederviren

Lambda cyhalothrin, lufenuron

Malathion, mecarbam, metaldehyde, methamidophos, metharhilic anisopliae, metharhilic flavoviride, methidathione, methiocarb, methoprene, methomyl,

Methoxyfenozide, metolcarb, metoxadiazone, mevinphos, milbemectin,

Milbemycin, monocrotophos,

Naled, Nitenpyram, Nithiazine, Novaluron

Omethoat, Oxamyl, Oxydemethon M Paecilomyces fumosoroseus, Parathion A, Parathion M, Permethrin, Phenthoat,

Phorat, Phosalone, Phosmet, Phosphamidon, Phoxim, Pirimicarb, Pirimiphos A,

Pirimiphos M, Profenofos, Promecarb, Propargite, Propoxur, Prothiofos, Prothoat,

Pymetrozine, pyraclofos, pyresmethrin, pyrethram, pyridaben, pyridathione,

Pyrimidifen, pyriproxyfen, quinalphos,

ribavirin Salithion, Sebufos, Selamectin, Silafluofen, Spinosad, Spirodiclofen, Sulfotep,

sulprofos,

Tau fluvalinate, tebufenozide, tebufenpyrad, tebupirimiphos, teflubenzuron,

Tefluthrin, Temephos, Temivinphos, Terbufos, Tetrachlorvinphos, Tetradifon Thetacypennethrin, Thiacloprid, Thiamethoxam, Thiapronil, Thiatriphos, Thiocyclam hydrogen oxalate, Thiodicarb, Thiofanox, Thuringinhrine, Tral

Triarathenes, triazamates, triazophos, triazuron, trichlophenidines, trichlorfon,

Triflumuron, trimethacarb,

Vamidothion, Vaniliprole, Verticillium lecanii

YI 5302

Zeta-cypermetbrin, Zolaprofos

(IR-cis) - [5- (phenylmethyl) -3-furanyl] methyl-3 - [(dihydro-2-oxo-3 (2H) -furanylidene) methyl] -2,2-dimethylcyclopropane carboxylate (3-phenoxyphenyl ) -methyl-2,2,3,3-tetramethylcyclopropanecarboxylate l - [(2-CMor-5-tMazolyl) methyl] tetr-ώydro-3,5-dimemyl-N-mtto-l, 3,5-ttiazin-2 (lH) - imin

2- (2-chloro-6-fluorophenyl) -4- [4- (l, l-dimethylethyl) phenyl] -4,5-dihydro-oxazol

2- (acetyloxy) -3-dodecyl-1,4-naphthalenedione 2-chloro-N- [[[4- (1-phenylethoxy) phenyl] aminoj-carbonyl] benzamide

2-chloro-N - [[[4- (2,2-dichloro-l, l-difluoroethoxy) -phenyl] -amino] -carbonyl] -benzamide

3-methylphenyl propyl carbamate

4- [4- (4-ethoxyphenyl) -4-methylpentyl] -1-fluoro-2-phenoxy-benzene

4-Chloro-2- (l, l-dimethylethyl) -5 - [[2- (2,6-dimethyl-4-phenoxyphenoxy) ethyl] thio] - 3 (2H) pyridazinone

4-chloro-2- (2-chloro-2-methylpropyl) -5 - [(6-iodo-3-pyridinyl) methoxy] -3 (2H) - pyridazinone

4-chloro-5- [(6-chloro-3-pyridinyl) methoxy] -2- (3,4-dichlorophenyl) -3 (2H) -pyridazinone

Bacillus thuringiensis strain EG-2348 benzoic acid [2-benzoyl-1 - (1, 1-dimethylethyl) hydrazide Butanoic acid 2,2-dimethyl-3- (2,4-dichlorophenyl) -2-oxo-l-oxaspiro [4.5] dec-3-en-4-yl ester

[3 - [(6-chloro-3-pyridinyl) methyl] -2-thiazolidinylidene] -cyanamide

Dihydro-2- (nitromethylene) -2H-1,3-thiazine-3 (4H) -carboxaldehyde ethyl- [2 - [[1,6-dihydro-6-oxo-1- (phenylmethyl) -4-pyridazinyl] oxy ] ethyl] carbamate

N- (3,4,4-trifluoro-1-oxo-3-butenyl) glycine

N- (4-chlorophenyl) -3- [4- (difluoromethoxy) phenyl] -4,5-dihydro-4-phenyl-lH-pyrazol-

1-carboxamide

N - [(2-CWor-5-tlu ^ olyl) methyl] -N'-methyl-N "-m ^ ro-guanidine N-methyl-N '- (1-methyl-2-propenyl) - 1,2 -hydrazindicarbothioamid

N-methyl-N'-2-propenyl-1, 2-hydrazinedicarbothioamide

O, O-diethyl [2- (dipropylamino) -2-oxoethyl] -ethylphosphoramidothioat

N-cyanomethyl-4-trifluoromethyl-nicotinamide

3,5-dichloro-1- (3,3-dichloro-2-propenyloxy) -4- [3- (5-trifluoromethylpyridin-2-yloxy) propoxy] benzene

A mixture with other known active ingredients, such as growth regulators, is also possible.

Co-active substance and synergist concentrations can be varied widely in each case from 0.1 to 25% by weight, preferably from 1 to 10% by weight.

With regard to the action against parasitic protozoa, the following are also interesting: mixtures or combinations of the compounds of the formula (I) with a polyether antibiotic or a synthetically produced coccidiosis agent.

The following may be mentioned as synthetic coccidiosis or as polyether antibiotics for use in the mixtures according to the invention:

Amproliu, partly in combination with folic acid antagonists

robenidine Toltrazuril __

Monensin Salinomycin Maduramicin Lasalocid

Narasin Semduramicin.

Monensin, salinomycin and maduramicin are preferred from this list. The mixture with maduramicin should be particularly emphasized.

Ready-to-use preparations contain the active ingredients in concentrations of 10 ppm to 20 percent by weight, preferably 0.1 to 10 percent by weight.

Preparations that are diluted before use contain the active ingredient in

Concentrations from 0.5 to 90 percent by weight, preferably from 1 to 50 percent by weight.

In general, it has proven to be advantageous to administer amounts of about 0.5 to about 50 mg, preferably 1 to 20 mg, of active ingredient per kg of body weight per day in order to achieve effective results.

When mixed with other coccidiosis agents or polyether antibiotics, the active compounds according to the invention are present in a ratio of 1 to 0.1-10 to 1 to 1-10. The ratio 1 to 5 is preferred.

The active ingredients can also be administered together with the animal's feed or drinking water.

Feed and food contain 0.01 to 250 ppm, preferably 0.5 to

100 ppm of the active ingredient in combination with a suitable edible material. Such feed and food can be used for medicinal purposes as well as for prophylactic purposes.

Such feed or food is produced by mixing a concentrate or a premix containing 0.5 to 30%, preferably 1 to 20% by weight of an active ingredient in admixture with an edible organic or inorganic carrier with conventional feed. Edible carriers are e.g. Corn meal or corn and soybean meal or mineral salts, which preferably contain a small amount of an edible dust control oil, e.g. Corn oil or soybean oil.

The premix obtained in this way can then be added to the complete feed before it is fed to the animals.

An example of use in coccidiosis is:

For the healing and prophylaxis of, for example, coccidiosis in poultry, especially in chickens, ducks, geese and turkeys, 0.1 to 100 ppm, preferably 0.5 to 100 ppm, of an active ingredient with a suitable edible material, e.g. a nutritious feed, mixed. If desired, these amounts can be increased, especially if the active ingredient is well tolerated by the recipient. Accordingly, the administration can take place via the drinking water.

For the treatment of individual animals, for example in the case of the treatment of coccidiosis in mammals or toxoplasmosis, amounts of active compound from 0.5 to 100 mg / kg of body weight are preferably administered daily in order to achieve the desired results. Nevertheless, it may be necessary at times to deviate from the amounts mentioned, in particular depending on the body weight of the test animal or the type of administration method, but also because of the animal species and its individual response to the active ingredient or the type of formulation and the time or the distance, to which it is administered. In certain cases, it may be sufficient to use less than the minimum amount, while in other cases the upper limit mentioned must be exceeded. When administering larger quantities, it may be advisable to divide them into several individual administrations during the day.

The activity of the compounds according to the invention can e.g. in cage experiments with the following experimental arrangement, in which the animals are treated with the respective individual components and with the mixtures of the individual components.

An active ingredient-containing feed is prepared in such a way that the required amount of active ingredient with a nutritionally balanced animal feed, e.g. is thoroughly mixed with the chick feed specified under.

If a concentrate or a premix is to be prepared which is ultimately to be diluted in the feed to the values mentioned in the experiment, generally about 1 to 30%, preferably about 10 to 20% by weight of active ingredient with an edible organic or inorganic carrier , e.g. Corn and soy flour or mineral salts containing a small amount of an edible defatting oil, e.g. Contain corn oil or soybean mixed. The premix thus obtained can then be added to the whole poultry feed prior to administration.

The following composition is an example of the use of the substances according to the invention in poultry feed.

52.00% feed grain meal, namely: 40% corn, 12% wheat

17.00% soybean meal extr.

5.00% corn gluten feed

5.00% wheat feed flour

3.00% fish meal

3.00% mixture of mineral fabrics

3.00% alfalfa grass green flour 2.50% vitamin premix

2.00% wheat germ, crushed

2.00% soybean oil

2.00% meat bone meal

1.50% whey powder

1.00% molasses

1.00% brewer's yeast, bound to beer spent grains

100.00%

Such feed contains 18% crude protein, 5% crude fiber, 1% Ca, 0.7% P and 1200 i.E. per kg. Vitamin A, 1200 i.E. Vitamin D3, 10 mg vitamin E, 20 mg zinc bacitracin.

The active ingredient is added to this feed in amounts of e.g. 1 to 20 ppm (w / w) added. Suitable dosages of the active ingredient are e.g. 1 ppm; 2.5 ppm; 5 ppm (each expressed as parts by weight "(w / w)").

In the following examples, compound A

used (see Example 24 in WO 98/21189) Examples

example 1

Cat flea test / oral intake Ctenocephalides felis (oral)

Test animals: adults of Ctenocephalides felis solvent: dimethyl sulfoxide (DMSO)

To produce a suitable formulation, a suitable active ingredient solution is prepared from 20 mg of active ingredient with 1 ml of DMSO. 20 μl of this formulation are added to 4 ml of citrated bovine blood and stirred.

20 sober adult fleas (Ctenocephalides felis, strain "Georgi") are in one

Chamber (0 5 cm) inserted, which is closed at the top and bottom with gauze. A metal cylinder is placed on the chamber, the underside of which is sealed with paraffin. The cylinder contains the 4 ml blood drug formulation that can be taken up by the fleas through the parafilm membrane. While the blood is heated to 37 ° C, a temperature of

25 ° C set. Controls are mixed with the same volume of DMSO without the addition of a compound. Triple determinations are carried out.

After 24 h, the mortality is determined in%. Compounds that achieve at least 25% flea kill within 24 hours are considered effective.

Test results:

Claims

Patent claims 1. Compounds of formula (I)

.0 o _H3C (I) in which Z represents optionally substituted cycloalkyl, aryl or heterocyclyl, R represents hydrogen or alkyl, stands for oxygen or sulfur, X stands for halogen and L ^, to combat parasites on animals. Uses of compounds according to address 1 for the production of medicines to combat parasites in animals. Method for combating parasites on animals, in which a suitable amount of active ingredient according to approach 1 is applied to the animals.