WO2002050042A2 - Use of pyrazol oximes as parasiticidal agents - Google Patents

Abstract

The invention relates to the use of pyrazol oximes for controlling parasitic arthropods, in particular fleas, on animals and to novel pharmaceutical formulations that are applied cutaneously.

Description

Use of pyrazole oximes as parasiticides

The present invention relates to the use of pyrazole oximes for combating parasitic arthropods, in particular fleas, on animals, and to new pharmaceutical formulations which can be applied dermally.

From the group of pyrazole oximes, compounds are known which have insecticidal, acaracidal and fungicidal activity. These compounds are described for example in EP 0 234 045, EP 0 944 319 and WO 095 07615. It can also be seen from the literature mentioned that, for example, 1,1-dimethylethyl-4- (1,3-dimethyl-5-phenoxy-1H) pyrazole derivatives are suitable for controlling parasites in animals. The disadvantage of the application techniques described so far is that they require a large amount of application, possibly lead to contamination of the environment and are therefore not suitable for the treatment of small animals, in particular cats and dogs.

New, user-friendly and environmentally friendly formulations for dermal use of pyrazoloximes have now been found, which are particularly suitable for the dermal control of parasitic arthropods of hobby animals, especially dogs and cats.

The invention relates to compositions comprising:

(a) Pyrazole oximes in a concentration of 5-40% by weight, based on the total weight of the formulation

(b) a solvent from the group consisting of benzyl alcohol and pyrrolidone solvent or a mixture thereof in a concentration of at least 20% by weight. The agents according to the invention can optionally additionally contain other solvents (cosolvents) from the group of aliphatic esters, aromatic esters and aliphatic lactones with a boiling point of at least 70 ° C. or aliphatic cyclic or acyclic ethers with a boiling point of at least 60 ° C. in a concentration of 2.5 to 75 wt .-% based on the total weight of the

Wording included.

Furthermore, the agents according to the invention can optionally stabilizers from the group of phenols, organic acids, amines and salts of the organic acids with the alkali or alkaline earth metals in a concentration of 0.05 to

2.5% by weight based on the total weight of the formulation.

Furthermore, the agents according to the invention optionally contain further auxiliaries (also called auxiliaries) from the group of thickeners, spreading agents, dyes, preservatives, adhesives, emulsifiers, in a concentration of 0.025 to 5% by weight, based on the total weight of the formulation.

Suitable pyrazole oximes with insecticidal and acaricidal activity are e.g. in EP-A-0 234 045 to which express reference is made.

Pyrazole oximes of the general formula (I) are preferably used

wherein

R ^{1 is} C ¹ -C ₄ -alkyl or phenyl, R ² is hydrogen, C \ -C ₅ alkyl, C _j -C 3 haloalkyl or phenyl,

R ³ denotes hydrogen, C j -C ₄ alkyl or phenyl,

R ^{4 is} hydrogen, C2-C, 4-alkylcarbonyl, benzoyl, naphthyl or a substituent of the formula

<- [in what

X represents hydrogen, halogen;

Ci-Ci2-alkyl, Ci-Cö-alkyl substituted with halogen, cyano, hydroxy, Ci-Cs-alkoxy or C2-Cg-alkoxycarbonyl; C ₃ -C 8 cycloalkyl; C3-C8-cycloalkyl substituted with 1 to 3 substituents selected from the group consisting of: C1-C4-alkyl, halogen and cyano; C2-C4 ~ alkenyl substituted with halogen, hydroxy, C2-C4-alkoxycarbonyl or C2-Cö-alkylcarbonyl; phenyl; hydroxy; CJ-C _Ö - alkoxy; C ₁ -C 4 alkoxy substituted with halogen or C2-Cg alkoxycarbonyl; Phenoxy optionally substituted with -CC ₃ haloalkyl; benzyloxy; C _j -C3 alkylenedioxy formed from two adjacent substituents X; Pyridyloxy optionally substituted with halogen or C _r C ₃ haloalkyl; -S (O) _p R ⁵ (wherein R ^{5 is} C _r C ₆ alkyl, C _r C ₅ haloalkyl or phenyl and p is 0, 1 or 2);

cyano; formyl; nitro; -COOR ⁶ (wherein R ⁶ is hydrogen, alkali metal, Cj-CiQ- alkyl, C ^ Cs-alkyl substituted by halogen, Ci ^ alkoxy, phenoxy, _C2-C4 alkoxycarbonyl or phenoxyphenyl; C -C ₇ - alkenyl; C ₃ -C ₇ alkynyl; C ₃ -C ₈ cycloalkyl; C ₃ -C ₈ cycloalkyl substituted with C _r C ₃ alkyl; phenyl; -S _n R ⁷ R ⁸ R ⁹ (where R ?, R ^§ and R ⁹ are identical or different and are C ₁ -C ₄ -alkyl or C ₃ -Cg-cycloalkyl)}; C ₂ -C ₆ alkylcarbonyl; C ₂ -C ₆ alkylcarbonyl substituted with cyano or C ₂ -C ₆ alkoxycarbonyl; Benzoyl optionally substituted with halogen or Ci-Cg-alkyl; C ₂ -C ₆ alkylthiocarbonyl; C ₃ -C ₇ alkoxycarbonylcarbonyl; -C (= O) NR ¹⁰ R ¹¹ (wherein R ¹⁰ and R * ^{l are the} same or different and represent hydrogen, C _j -Cg alkyl or phenyl); piperidinocarbonyl; Morpholinocarbonyl which is optionally mono- or disubstituted by C _j -C ₄ alkyl; -NR ¹² R ¹³ (wherein R ^{12 is} hydrogen or C _r C ₅ alkyl and R ^{13 is} formyl, C ₂ -Ci ₂ -alkoxycarbonyl or C ₂ -C ₅ alkoxycarbonyl substituted with halogen or C _j ^ -Al oxy) ; a substituent of the formula

(wherein R ^{14 is} hydrogen, C _r C alkyl or C ₂ -C ₆ alkoxyalkyl); -C (BR ¹⁵ ) (BRl6) (Rl7) (in which Rl5 and R ^{16 may be the} same or different and stand for C ₁ -C ₄ -alkyl or together form a C ₁ -C ₄ -alkylene radical, R ¹⁷ for C ₁ -C ₅ -alkyl, cyano or C ₂ -C ₆ -alkoxycarbonyl and B represents oxygen or sulfur; -C (OR ¹⁸ ) R ¹⁹ R ²⁰ (in which R ^{18 represents} hydrogen or C ₂ -C ₄ -alkylcarbonyl and R ¹⁹ and R ^{20 are the} same or different and are hydrogen or C _r C ₆ alkyl); -SiR ²¹ R ²² R ²³ (in which R ²¹ , R ²² and R ^{23 are the} same or different and are C 1 -C ₄ alkyl); or -O-SiR ²⁴ R ²⁵ R ²⁶ (in which R ²⁴ , R ²⁵ and R ^{26 are} identical or different and stand for C ₁ -C ₄ alkyl), and n is an integer from 1 to 5, where when n is an integer from 2 to 5, X can be the same or different];

Y is hydrogen, Ci-Cg-alkyl, -C-C4-haloalkyl, halogen, hydroxy, C1-C4-haloalkoxy, Cj-Cs-alkylenedioxy, phenoxy, which is optionally substituted with trifluoromethyl, -S (O) _q R ²⁷ (wherein R ^{27 is} C ₁ -C ₃ alkyl and q is 0, 1 or 2), hydroxycarbonyl, C2-C5-alkoxycarbonyl or -NR ²⁸ R ²⁹ (where R ²⁸ and R ^{29 are the} same or different and are hydrogen, C1 -C4- alkyl or benzyl which is optionally substituted by C2-C6-alkoxycarbonyl);

Z ^{1 represents} oxygen or sulfur;

Z ^{2 represents} oxygen, sulfur or a single bond;

Z ^{3 represents} aryl or heteroaryl

Q is Ci-Cg-alkylene, C _j- Cg-alkylene substituted with halogen or phenyl, C3-Ci ₂ -alkenylene, C3-Ci2-haloalkenylene or C3-Cg-alkynylene; and

m represents an integer from 1 to 3, where if m represents an integer 2 or 3, Y can be the same or different.

Depending on the substitution pattern, the compounds according to the invention can exist in stereoisomeric forms which either behave like image and mirror image (enantiomers) or do not behave like image and mirror image (diastereomers). The invention relates both to the enantiomers or diastereomers and to their respective mixtures. Like the diastereomers, the racemic forms can be uniformly standardized into the stereoisomers

Separate components. Furthermore, certain compounds can exist in tautomeric forms. This is known to those skilled in the art and such compounds are also within the scope of the invention.

The compounds according to the invention can optionally be present both as ice and as trans isomers. Even if only one of the isomers is shown, the ice and trans isomers are always meant according to the invention.

“Alkyl”, “alkenyl” and “alkynyl” in the context of the invention stand for a straight-chain or branched alkyl, alkenyl or alkynyl radical having 1 to 12 carbon atoms. A straight-chain or branched alkyl, alkenyl or alkynyl radical is preferred with 1 to 6, particularly preferably 1 to 4 carbon atoms. Examples of alkyl radicals are: methyl, ethyl, n-propyl, isopropyl, t-butyl, n-pentyl and n-hexyl. Examples of alkenyl radicals are: vinyl, Allyl, isopropenyl and n-

But-2-en-l-yl. Examples of alkynyl radicals are: ethynyl, n-prop-2-yn-l-yl and n-but-2-yn-l-yl.

In the context of the invention, “haloalkyl” stands for an alkyl radical as defined above in which one or more, preferably one, two or three, hydrogen atoms pass through

Halogen atoms (same or different) are replaced.

“Halogen” in the context of the invention stands for fluorine, chlorine, bromine and iodine.

In the context of the invention, “aryl” stands for an aromatic radical having 6 to 14, preferably 6 to 10, carbon atoms. Examples are phenyl and naphthyl, phenyl is particularly preferred.

Within the scope of the invention, “heteroaryl” stands for 5- to 10-membered, preferably 5- and 6-membered, aromatic rings containing heteroatoms with up to 4 heteroatoms selected from O, S and N and includes, for example: pyridyl, furyl, Thienyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolicenyl, indolyl, benzo [b] thienyl, benzo [b] furyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, etc. Particularly preferred is pyridyl.

Unless stated otherwise, substituted radicals carry one or more, preferably one, two or three, identical or different substituents.

Particularly preferred pyrazole oximes are the compounds of the general formula (Ia)

woπn

embedded image in which

R represents straight-chain or branched alkyl having up to 6 carbon atoms and

R ^{31 represents} aryl or heteroaryl, which can each be substituted by halogen.

Very particularly preferred examples of pyrazole oximes of the formula (Ia) are listed in Table 1 below: Table 1

The agents according to the invention contain the active substance in concentrations of 5 to 40% by weight, preferably 10 to 30% by weight, particularly preferably 15 to 25% by weight.

Possible solvents are:

Benzyl alcohol or pyrrolidone solvents such as 2-pyrrolidone, l- (-C ₂₀ alkyl) - pyrrolidones such. B. 1-ethylpyrrolidone, 1-octylpyrrolidone, 1-dodecylpyrrolidone, 1-isopropylpyrrolidone, 1-hexylpyrrolidone; l- (Cι- ₂₀ alkenyl) pyrrolidones such as

1-vinyl pyrrolidone, 1-cyclohexenyl pyrrolidone; 1 - (-Cι. ₆ -alkoxy-Cι_ ₆ -alkyl) -2-pyrrolidone such as l- (2-hydroxyethyl) pyrrolidone, l- (2-methoxyethyl) pyrrolidone, l- (3-methoxypropyl) -pyrrolidone and also 1-benzylpyrrolidone. Benzyl alcohol, 1-methylpyrrolidone, n-dodecyl- or n-octylpyrrolidone. These solvents can also be used as a mixture with one another.

They are present in a concentration of at least 20% by weight, preferably 50 to 70% by weight, based on the total weight of the formulation.

Other suitable solvents or cosolvents are aliphatic or aromatic esters and aliphatic lactones with a boiling point of at least 70 ° C. As such, e.g. called: benzyl benzoate, benzyl acetate, dipropylene glycol dibenzoate; n-alkyl succinates such as dimethyl, diethyl, dipropyl succinate;

Acetates of n-alkyl alcohols with more than 5 carbon atoms, such as octyl acetate; Furthermore, acetates of n-alkyl ethers such as dipropylene glycol methyl ether acetate, diethylene glycol ethyl acetate and citrates such as triethyl, trimethyl, tributyl citrate, and furthermore butyrolactone.

Benzyl benzoate, benzyl acetate, dimethyl, diethyl succinate and triethyl citrate are preferably used.

According to a preferred embodiment in the same way, aliphatic cyclic or acyclic ethers with a boiling point of at least 60 ° C. are also suitable as cosolvents. Dipropylene glycol monomethyl ether, dipropylene glycol monobuthyl ether, dipropylene glycol monopropyl ether, diethylene glycol dimethyl ether, diethylene glycol monomethyl or hexyl ether, diethylene glycol dibuthyl ether and THFA (tetrahydrofurfuryl alcohol) may be mentioned as such.

Aliphatic cyclic or acyclic ethers with a free OH group are preferred. Dipropylene glycol monomethyl ether, diethylene glycol monoethyl ether and THFA may be mentioned as such.

If one or more cosolvents are used, it is preferably in a concentration of 2.5 to 75% by weight, particularly preferably 5.0 to 50% by weight, very particularly preferably from 7.5 to 30% by weight, based in each case on the total weight of the formulation.

Suitable stabilizers are those from the group of phenols, and the following may be mentioned as examples: BHT (butylated hydroxytoluene), hydroxyanisole, vitamin E and their

Precursors. Examples of suitable organic acids are lactic acid, citric acid, acetic acid and their alkali metal and alkaline earth metal substrates such as sodium acetate and sodium citrate. Examples of suitable organic bases are triethanolamine and tributylamine. Their amounts can be varied widely from 0.01 to 2.5, preferably 0.05 to 1.5% by weight, based in each case on the total weight of the formulation.

The formulations according to the invention can be prepared by customary processes, for example by dissolving the active ingredient in the solvents or solvent mixtures, preferably at room temperature. If necessary, further auxiliaries are added.

Suitable additional auxiliaries are known to the person skilled in the art. Examples include: thickeners, spreading agents, dyes, preservatives, adhesives, emulsifiers, antioxidants and light stabilizers.

Examples of 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.

Spreading agents are, for example, spreading oils such as di-2-ethylhexyl adipate, isopropyl myristate, dipropylene glycol pelargonate, cyclic and acyclic silicone oils, such as dimetikones and also their copolymers and terpolymers with ethylene oxide, propylene oxide and formalin, fatty acid esters, triglycerides, fatty alcohols. Dyes are all dyes approved for use on animals, which can be dissolved or suspended.

Preservatives are, for example: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.

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

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;

ampholytic 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 orthophosphoric acid ester monoethanolamine salt;

cationic surfactants such as cetyltrimethylammonium chloride.

Antioxidants and light stabilizers are, for example: butylated hydroxytoluene, hydroxybutylanisole, tocophenol and vitamin E.

The formulation oranges according to the invention are suitable for combating ectoparasites, which are beneficial in animal husbandry and animal breeding, with a favorable toxicity to warm-blooded animals

Domestic and farm animals as well as zoo, laboratory, experimental and hobby animals occur. They are effective against normally sensitive and resistant species and against all or individual stages of development of the animals mentioned.

Ectoparasites in the sense of this invention are usually arthropods, preferably insects or arachnids. 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 e.g. 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 e.g. 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., Wohlfahrtia spp., Sarcophaga spp., Oestras spp., Hypodeπna 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, for example 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., De manyssus spp., Raillietia spp., Pneumonyssus spp., Stemostoma 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 ..

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 B. 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 agents according to the invention are particularly suitable for the treatment of cattle, dogs and cats, preferably for controlling ticks and / or

Fleas.

The application can be prophylactic as well as therapeutic.

In general, it has proven to be advantageous to add amounts of active ingredient from 2.5 to about 50 mg, preferably 5 to 45 mg, particularly preferably 10 to 40 mg, per kg of body. per weight of the animal to be treated to achieve good effectiveness.

The formulations according to the invention can also contain other active ingredients (Cowirk substances), for. B. May be mentioned: insecticides, attractants, sterilants,

Bactericides, acaricides, nematicides, fungicides. Insecticides include, for example, phosphoric acid esters, carbamates, carboxylic acid esters, chlorinated hydrocarbons, phenylureas, substances produced by microorganisms, etc.

Cheap co-active ingredients are e.g. the following:

Insecticides / acaricides / nematicides:

Abamectin, Acephate, Acetamiprid, Acrinathrin, Alanycarb, Aldicarb, Aldoxycarb, Alphacypermethrin, 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, Benfuracarb, Bensultap, Benzoximate, Betacyfluthrin, Bifenazate, Bifenthrin, Biethanomofufoxin, Bethanomethofinoxin, Bethenomethrin Butyl pyridaben

Cadusafos, Carbaryl, Carbofuran, Carbophenothion, Carbosulfan, Cartap, Chloethocarb, Chlorethoxyfos, Chlorfenapyr, Chlorfenvinphos, Chlorfluazuron, Chlormephos, Chlorpyrifos, Chlo yrifos M, Chlovaporthrin, Cis-Resmethrin, Clocytermochrhrine, Clispyrethrin, Clispyrethrin Clin Cyfluthrin, cyhalothrin, cyhexatin, cypermethrin, cyromazine,

Deltamethrin, Demeton M, Demeton S, Demeton-S-methyl, Diafenthiuron, Diazinon, Dichlorvos, Diflubenzuron, Dimethoat, Dimethylvinphos, Diofenolan, Disulfoton, Docusatsodium, Dofenapyn, Eflusilanate, Emamectin, Empenthrom, Esprinomine, Endosulfin, Endosulfin, Endosulfin, Endosulfin, Endosulfon Ethiofencarb, Ethion, Ethoprophos, Etofenprox,

Etoxazole, Etrimfos, Fenamiphos, Fenazaquin, Fenbutatin oxide, Femtrothion, Fenothiocarb, Fenoxacrim, Fenoxycarb, Fenpropathrin, Fenpyrad, Fenpyrithrin, Fenvalerate, Fipronil, Fluazinam, Fluazuron, Flubrocythrinate, Flucycloxuron, Flucythrinate, Flinezhrinate, Fumenzoxin, Flutenzhonate, Flumenzoxin, Flutenzhonate, Fumenzoxin, Flutenzhonate, Fumenzhonate, , Furathiocarb,

granulosis

Halofenozide, HCH, Heptenophos, Hexaflumuron, Hexythiazox, Hydroprene, Imidacloprid, Isazofos, Isofenphos, Isoxathion, Ivermectin, Kempolyederviruses Lambdacyhalothrin, Lufenuron

Malathion, Mecarbam, Metaldehyde, Methamidophos, Metharhician anisopliae, Metharhician flavoviride, Methidathione, Methiocarb, Methomyl, Methoxyfenozide, Metolcarb, Metoxadiazone, Mevinphos, Milbemectin, Monocrotophos, Moxidectin, Naledal, Oxamonethonamon, Nitomethon, Nitamon, Nitomethon, Nitom

Paecilomyces fumosoroseus, Parathion A, Parathion M, Permethrin, Phenthoat, Phorat, Phosalone, Phosmet, Phosphamidon, Phoxim, Pirimicarb, Pirimiphos A, Pirimiphos M, Profenofos, Promecarb, Propoxur, Prothiofos, Prothoat, Pyromhrhridosine, Pymmethrofinos, Pymmethrofinos , Pyridathione, pyrimidifen, pyriproxyfen,

Quinalphos, Ribavirin

Salithion, Sebufos, Selamectin, Silafluofen, Spinosad, Sulfotep, Sulprofos, Taufluvalinate, Tebufenozide, Tebufenpyrad, Tebupirimiphos, Teflubenzuron, Tefluthrin, Temephos, Temivinphos, Terbufos, Tetrachlorvinphos

Thetacypermethrin, Thiamethoxam, Thiapronil, Thiatriphos, Thiocyclam hydrogen oxalate, Thiodicarb, Thiofanox, Thuringiensin, Tralocythrin, Tralomethrin, Triarathene, Triazamate, Triazophos, Triazuron, Trichlophenidon, Triflliononidium, Triflionilonitride, Triflliononitride

YI 5302 Zetacypermethrin, zolaprofos

(IR-cis) - [5- (Phenylmemyl) -3-furanyl] methyl-3 - [(dihydro-2-oxo-3 (2H) -furanylidene) methyl] -2,2-dimethylcyclopropane carboxylate (3rd -Phenoxyphenyl) -methyl-2,2,3,3-tetramethylcyclopropanecarboxylat

1 - [(2-chloro-5-thiazolyl) methyl] tetrahydro-3,5-dimethyl-N-mtro-1,3,5-triazin-2 (1H) - imine

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- (l-phenylethoxy) phenyl] amino] carbonyl] benzamide

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

3-methylphenyl propylcarbamate

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

4-Chloro-2- (l, 1-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-l- (l, l-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-l-oxo-3-butenyl) -glycine

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

1-carboxamide

N - [(2-chloro-5-thiazolyl) methyl] -N'-methyl-N "-nitroguanidine N-methyl-N '- (1-methyl-2-propenyl) -1, 2-hydrazinedicarbothioamide

N-methyl-N'-2-propenyl-1, 2-hydrazine dicarbothioamide O, O-diethyl [2- (dipropylamino) -2-oxoethyl] -ethylphosphoramidothioat

fungicides:

Aldimorph, ampropylfos, ampropylfos potassium, andoprim, anilazine, azaconazole, azoxystrobin,

Benalaxyl, benodanil, benomyl, benzamacril, benzamacrylisobutyl, bialaphos,

Binapacryl, biphenyl, bitertanol, blasticidin-S, bromuconazole, bupirimate,

buthiobate,

Calcium polysulfide, capsimycin, captafol, captan, carbendazim, carboxin, carvone, quinomethionate (quinomethionate), chlobenthiazon, chlorfenazole, chloroneb,

Chloropicrin, chlorothalonil, chlozolinate, clozylacon, cufraneb, cymoxanil,

Cypro-conazol, Cyprodinil, Cyprofuram,

Debacarb, dichlorophene, diclobutrazole, diclofluanide, diclomezin, dicloran,

Diethofencarb, Difenoconazol, Dimethirimol, Dimethomorph, Diniconazol, Diniconazol-M, Dinocap, Diphenylamin, Dipyrithione, Ditalimfos, Dithianon,

Dodemorph, Dodine, Drazoxolon,

Ediphenphos, Epoxiconazole, Etaconazole, Ethirimol, Etridiazole,

Famoxadone, fenapanil, fenarimol, fenbuconazole, fenfuram, fenitropan,

Fenpiclonil, Fenpropidin, Fenpropimoφh, Fentinacetat, Fentinhydroxyd, Ferbam, Ferimzon, Fluazinam, Flumetover, Fluoromid, Fluquinconazol, Flurprimidol,

Flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminum, fosetyl

Sodium, fthalide, fuberidazole, furalaxyl, furametpyr, furcarbonil, furconazole,

Furconazolcis, Furmecyclox,

Guazatin, hexachlorobenzene, hexaconazole, hymexazole,

Imazalil, imibenconazole, iminoctadine, iminoctadineal besilate, iminoctadine triacetate,

Iodocarb, Ipconazole, Iprobefos (IBP), Iprodione, Irumamycin, Isoprothiolan,

Isovaledione,

Kasugamycin, Kresoximmethyl, copper preparations such as: copper hydroxide, copper phthalate, copper oxychloride, copper sulfate, copper oxide, oxy-copper and

B ordeaux mix, Mancopper, Mancozeb, Maneb, Meferimzone, Mepanipyrim, Mepronil, Metalaxyl,

Metconazole, methasulfocarb, methfuroxam, metiram, metomeclam, metsulfovax,

Mildiomycin, myclobutanil, myclozolin,

Nickel dimethyldithiocarbamate, nitrothalisopropyl, Nuarimol, Ofurace, Oxadixyl, Oxamocarb, Oxolinicacid, Oxycarboxim, Oxyfenthiin,

Paclobutrazole, pefurazoate, penconazole, pencycuron, phosdiphen, pimaricin,

Piperalin, polyoxin, polyoxorim, probenazole, prochloraz, procymidon, propamocarb,

Propanosine sodium, propiconazole, propineb, pyrazophos, pyrifenox, pyrimethanil,

Pyroquilon, Pyroxyfur, Quinconazol, Quintozen (PCNB),

Sulfur and sulfur preparations,

Tebuconazole, tecloftalam, tecnazen, tetcyclacis, tetraconazole, thiabendazole,

Thicyofen, Thifluzamide, Thiophanatemethyl, Thiram, Tioxymid, Tolclofosmethyl,

Tolylfluanid, Triadimefon, Triadimenol, Triazbutil, Triazoxid, Trichlamid, Tricyclazol, Tridemoφh, Triflumizol, Triforin, Triticonazol,

uniconazole

Validamycin A, vinclozolin, viniconazole,

Zarilamid, Zineb, Ziram as well

Dagger G, OK-8705,

OK-8801, - (1, 1-dimethylethyl) -ß- (2-phenoxy ethyl) - 1 H- 1, 2,4-triazole-1-ethanol, - (2,4-dichloφhenyl) -ß-fluoro- b-propyl-1H-1, 2,4-triazole-1-ethanol, α- (2,4-dichloφhenyl) -ß-methoxy-a-methyl-lH-l, 2,4-triazole-l-ethanol, - (5-methyl-l, 3-dioxan-5-yl) -ß - [[4- (trifluoromethyl) phenyl] methylene] -lH-l, 2,4-triazol-1-ethanol,

(5RS, 6RS) -6-hydroxy-2,2,7,7-tetramethyl-5- (lH-l, 2,4-triazol-l-yl) -3-octanone,

(E) -a- (methoxyimino) -N-methyl-2-phenoxy-phenylacetamide,

{2-Methyl-l - [[[l- (4-methylphenyl) ethyl] amino] carbonyl] propyl} carbamic acid 1-isopropyl ester

1 - (2,4-dichloφhenyl) -2- (1H-l, 2,4-triazole-1-yl) -ethanone-O- (phenylmethyl) -oxime, 1 - (2-methyl-1-naphthalenyl) -lH-pyrrole-2,5-dione, l- (3,5-dichloφhenyl) -3- (2-propenyl) -2,5-pyrrolidinedione, l - [( Diiodomethyl) sulfonyl] -4-methyl-benzene, l - [[2- (2,4-dichloro-henyl) -l, 3-dioxolan-2-yl] methyl] -lH-imidazole, l - [[2- (4-Chloφhenyl) -3-phenyloxiranyl] methyl] -lH-l, 2,4-triazole,

1 - [1 - [2 - [(2,4-dichlorophenyl) methoxy] phenyl] ethenyl] - 1H-imidazole, 1-methyl-5-nonyl-2- (phenylmethyl) -3-pyrrolidinol,

2 ^ 6 ^, -dibromo-2-memyl-4 ^, -trifluoromethoxy-4 ^l -trifluoromethyl-l, 3-thiazole-5-carboxanilide, 2,2-dichloro-N- [1 - (4-chloro-phenyl) - ethyl] - 1-ethyl-3-methyl-cyclopropanecarboxamide,

2,6-dichloro-5- (methylthio) -4-pyrimidinyl thiocyanate,

2,6-dichloro-N- (4-trifluoromethylbenzyl) -benzamide,

2,6-dichloro-N - [[4- (trifluoromethyl) phenyl] methyl] benzamide,

2- (2,3,3-triiod-2-propenyl) -2H-tetrazole, 2 - [(l -methylethyl) sulfonyl] -5- (trichloromethyl) -l, 3,4-thiadiazole,

2 - [[6-Deoxy-4-O- (4-O-methyl-ß-D-glycopyranosyl) -aD-glucopyranosyl] -amino] -4- methoxy-lH-pyrrolo [2,3-d] pyrimidine- 5-carbonitrile,

2-aminobutane,

2-bromo-2- (bromomethyl) pentandinitrile, 2-chloro-N- (2,3-dihydro-1,3,3-trimethyl-1H-inden-4-yl) -3-pyridinecarboxamide,

2-chloro-N- (2,6-dimethylphenyl) -N- (isothiocyanatomethyl) -acetamide,

2-phenylphenol (OPP),

3, 4-dichloro-1 - [4- (difluoromethoxy) phenyl] - 1H-pyrrole-2,5-dione,

3,5-dichloro-N- [cyan [(1-methyl-2-propynyl) -oxy] -methyl] -benzamide, 3 - (1, 1-dimethylpropyl-1-oxo-1 H-indene-2-carbonitrile .

3 - [2- (4-chloro-phenyl) -5-ethoxy-3-isoxazolidinyl-j-pyridine,

4-chloro-2-cyano-N, N-dimethyl-5- (4-methylphenyl) -lH-imidazol-l-sulfonamide,

4-methyl-tetrazolo [1,5-a] quinazolin-5 (4H) -one,

8- (1,1-dimethylethyl) -N-ethyl-N-propyl-1,4-dioxaspiro [4.5] decane-2-methanamine, 8-hydroxyquinoline sulfate,

9H-xanthene-9-carboxylic acid 2 - [(phenylamino) carbonyl] hydrazide, bis- (l-methylethyl) -3-methyl-4 - [(3-methylbenzoyl) -oxy] -2,5-thiophene dicarboxylate, ice-1 - (4-chloro-phenyl) -2- (1H-1, 2.4 -triazol- 1 -yl) -cycloheptanol, cis-4- [3- [4- (l, l-dimethylpropyl) phenyl-2-methylpropyl] -2,6-dimethyl-moφholin hydrochloride, ethyl - [(4th -chloφhenyi) azo] cyanoacetate,

potassium bicarbonate,

Methantetrathiol sodium salt,

Methyl-l- (2,3-dihydro-2,2-dimethyl-lH-inden-l-yl) -lH-imidazol-5-carboxylate,

Methyl N- (2,6-dimethylphenyl) -N- (5-isoxazolylcarbonyl) -DL-alaninate, methyl-N- (chloroacetyl) -N- (2,6-dimethylphenyl) -DL-alaninate,

N- (2,3-dichloro-4-hydroxyphenyl) -l-methyl-cyclohexanecarboxamide.

N- (2,6-dimethylphenyl) -2-methoxy-N- (tetrahydro-2-oxo-3-furanyl) acetamide,

N- (2,6-dimethylphenyl) -2-methoxy-N- (tetrahydro-2-oxo-3-thienyl) acetamide,

N- (2-chloro-4-nitrophenyl) -4-methyl-3-nitro-benzenesulfonamide, N- (4-cyclohexylphenyl) - 1, 4,5, 6-tetrahydro-2-pyrimidinamine,

N- (4-hexylphenyl) -l, 4,5,6-tetrahydro-2-pyrimidinamine,

N- (5-chloro-2-methylphenyl) -2-methoxy-N- (2-oxo-3-oxazolidinyl) -acetamide,

N- (6-methoxy) -3-pyridinyl) -cyclopropanecarboxamide,

N- [2,2,2-trichloro-l - [(chloroacetyl) amino] ethyl] benzamide, N- [3-chloro-4,5-bis (2-propynyloxy) phenyl] -N ' methoxy-methanimidamid,

N-formyl-N-hydroxy-DL-alanine sodium salt,

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

O-methyl-S-phenyl-phenylpropylphosphoramidothioate,

S-methyl-l, 2,3-benzothiadiazole-7-carbothioate, spiro [2H] -1-benzopyran-2, r (3Η) -isobenzofuran] -3'-one,

bactericides:

Bronopol, dichlorophene, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furan carboxylic acid, oxytetracycline, probenazole, streptomycin, tecloftalam, copper sulfate and other copper preparations. Hire amounts in the formulations according to the invention can be varied widely from 0.01 to 25% by weight, based on the total mass

The use of the co-active substances mentioned and synergists such as piperonyl butoxide with the pyrazole oximes mentioned is known and is described, for example, in

WO 00/02453, WO 95/33380, WO 95/07615 and EP 0736252.

The agents according to the invention are also characterized by a long-lasting effect. A long-lasting effect should be understood to mean that after at least one week a potency of 80% or more of the original potency can still be observed. The potency preferably does not drop below 80% of the original potency over 3 weeks.

The dermally applicable liquid formulations according to the invention are particularly suitable for carrying out spot-on treatments on dogs and cats. They are characterized by their excellent storage stability of 3-5 years in all climates - e.g. in the commercially available 1-10 ml single-tube plastic tubes with a wall thickness of 250-1000 μm - due to their simple applicability, very good biological effectiveness as well as environmental and warm-bloodedness compatibility.

Furthermore, it was found that the pyrazole oximes described above not only in the compositions described therein, containing benzyl alcohol and / or a pyrrolidone solvent, but also generally have an excellent action against ticks and especially fleas. According to a further aspect, the invention therefore relates to the use of the pyrazole oximes described above for controlling fleas on animals.

Pyrazole oximes which are preferred, particularly preferred and very particularly preferably used are those which have already been defined accordingly above. Of these, in particular, l, l-dimethylethyl {[[[(l, 3-dimethyl-5-phenoxy- 1 -pyrazol-4-yl) methylene] amino] oxy] methyl} benzoate (CAS No.: 134098-61 -6; common name Fenpyroximate / see Tab. 1, No. 1).

Fleas should be understood as the Siphonaptera order. The pyrazole oximes are preferably used to control Pulex spp. and especially

Ctenocephalides spp., Especially used by Ctenocephalides canis and Ctenocephalides felis.

The target animals for flea treatment are the livestock, laboratory and hobby animals already listed above as far as they are affected by fleas. Particularly preferred

Target animals are hobby animals, especially z. B. Dog and cat.

The application can be prophylactic as well as therapeutic. Systemic and non-systemic use are possible.

The active ingredients are used directly or in the form of suitable preparations, or with the aid of shaped bodies containing the active ingredient, e.g. Strips, plates, tapes, collars, ear tags, cast tape, marking devices. Dermal application is preferred.

Preparations suitable for animals are:

Solutions such as solutions for injection, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, infusion formulations, gels;

Emulsions and semi-solid preparations for oral or cutaneous use and for injection; Semi-solid preparations are, for example, suspensions, pastes.

Formulations in which the active ingredient is in an ointment base or in an oil in

Water or water in oil emulsion base is processed; solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, boluses, capsules; Aerosols and inhalants.

Solutions for injection are administered intravenously, intramuscularly and subcutaneously.

Injection 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 solutions are sterile filtered or if necessary prepared and filled aseptically.

The following may be mentioned as solvents: physiologically compatible solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycols, N-methyl-pyrrolidone, glycerol brmal, solketal (= isopropylidene glycerol), dimethylacetamide, 2-pyrrolidone, tetraglycol (= Polyethylene glycol ether of tetrahydrofurfuryl alcohol) and mixtures thereof.

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

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

Preservatives are, for example: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol, and organic acids with preserving properties such as benzoic acid, propionic acid or sorbic acid and their salts. The preservatives can optionally also be used as a combination of two or more agents. Oral solutions are used 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, whereby sterile work can be dispensed with.

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. Inorganic and organic substances serve as such. Inorganic substances are e.g. Table salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays, precipitated or colloidal silicon dioxide, phosphates.

Organic substances are e.g. Sugar, cellulose, food and feed such as

Milk powder, animal meal, cereal flour and meal, starches.

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, decomposition substances such as starch or cross-linked polyvinylpyrrolidone, binders such as e.g. Starch, gelatin or linear polyvinyl pyrrolidone as well as dry binders such as microcrystalline cellulose.

The active compounds can also be encapsulated in the form of their solid or liquid formulations mentioned above.

The active ingredients can also be used in the form of an aerosol. For this purpose, the active ingredient in a suitable formulation is finely distributed under pressure. It may also be advantageous to use the active substances in formulations which release the active substance with a delay.

The active ingredients are preferably administered together with the feed and / or the drinking water.

The feed includes single feed of vegetable origin such as hay, beets, cereals, grain by-products, single feed of animal origin such as meat, fats, dairy products, bone meal, fish products, furthermore the single feed such as

Vitamins, proteins, amino acids, e.g. DL-methionine, salts such as lime and table salt. The feed also includes supplementary, finished and compound feed. These contain feed materials in a composition that ensure a balanced diet in terms of energy and protein supply as well as the supply of vitamins, mineral salts and trace elements.

The concentration of the active substances in the feed is normally about 0.01 to 500 ppm, preferably 0.1 to 50 ppm.

The active ingredients can be added to the feed as such or in the form of premixes or feed concentrates.

Premixes and feed concentrates are mixtures of the active ingredient with a suitable carrier.

The carrier substances include feed materials or mixtures thereof.

They can also contain other auxiliaries, such as, for example, substances which regulate the flowability and miscibility, such as, for example, silicas, bentonites, lignin sulfonates. In addition, antioxidants such as BHT or preservatives such as sorbitan acid or calcium propionate can be added. Concentrates for application via drinking water must be formulated in such a way that a clear solution or a stable, homogeneous suspension results when mixed with the drinking water.

Water-soluble substances (feed additives) such as sugar or salts (e.g. citrates, phosphates, common salt, sodium carbonate) are therefore suitable as carriers.

They can also contain antioxidants and preservatives.

The preferred dermal application according to the invention takes place e.g. in the form of bathing, diving (dipping), spraying (spraying), pouring on (pour-on or spot-on), washing, shampooing, watering, powdering.

In addition to the agents already described above containing benzyl alcohol and / or pyrrolidone solvents, suitable preparations may also be mentioned: solutions or concentrates for administration after dilution, solutions for use on the skin, pour-on formulations, gels;

Emulsions and suspensions for dermal use and semi-solid

preparations;

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

Solid preparations such as powder, shaped bodies containing active ingredients.

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 solvents, acids, bases, buffer salts, antioxidants and preservatives.

The following may be mentioned as solvents: Physiologically compatible solvents such as

Water, alcohols such as ethanol, butanol, benzyl alcohol, glycerin, hydrocarbons, propylene glycol, polyethylene glycols, N-methyl-pyrrolidone, and mixtures thereof.

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 dissolution of the active ingredient in the main solvent or prevent its precipitation. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.

It can be advantageous to add thickeners to the preparation of 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 onto or sprayed onto limited areas of the skin, the active ingredient being distributed on the surface of the body.

Pour-on formulations are prepared by dissolving, suspending or emulsifying the active ingredient in suitable solvents or solvent mixtures that are harmful to the skin. If necessary, further auxiliaries such as dyes, antioxidants, light stabilizers and adhesives are added.

The following may be mentioned as solvents: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerin, 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, mono-butyl glycol, mono Acetone, methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethyl acetamide, N-methyl pyrrolidone, 2-dimethyl-4-oxy-methylene-1, 3-dioxolane.

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, for example, cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin. Emulsions are either water in oil or oil in water.

They are produced by dissolving the active ingredient either in the hydrophobic or in the hydrophilic phase and, with the aid of suitable emulsifiers and, if appropriate, other auxiliaries such as dyes, absorption-promoting substances,

Preservatives, antioxidants, light stabilizers, viscosity-increasing substances, homogenized with the solvent of the other phase.

The following may be mentioned as the 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 -i ₂ 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 / C ₁₀ fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, lauric acid hexyl ester, di-propylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length ₆ -C ₈ , isopropyl myristate, isopropyl palmitate, caprylic / capric alcohol ester of saturated fatty acids Chain length Cι ₂ - Cι ₈ , isopropyl stearate, oleic acid olylester, oleic acid decyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as dibutyl phthalate, diisopropyl adipate, the latter related ester mixtures including fatty alcohols such as isotridecyl alcohol, 2-octyl alcohol, 2-octyl alcohol, 2-octyl alcohol, 2-octyl alcohol, 2-octyl alcohol, 2-octyl alcohol.

Fatty acids such as Oleic acid and its mixtures.

The following can be mentioned as the hydrophilic phase:

Water, alcohols such as propylene glycol, glycerin, sorbitol and their mixtures. The following may be mentioned as emulsifiers: ionic surfactants, for example polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, so bitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether;

ampholytic surfactants such as di-Na-N-lauryl-β-iminodipropionate or lecithin;

anionic surfactants such as Na lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt; cationic surfactants such as cetyltrimethylammonium 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 anhydride, polyethylene glycols, waxes , colloidal silica or mixtures of the listed substances.

Suspensions are prepared by suspending the active ingredient in a carrier liquid, optionally with the addition of other auxiliaries such as wetting agents, dyes, substances requiring resorption, preservatives, antioxidants, light stabilizers.

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 for dermal administration 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 for flea treatment contain the active ingredient in concentrations of 1 ppm to 20 percent by weight, preferably 0.01 to 10 percent by 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 2.5 to about

50 mg, preferably 5 to 45 mg, of active ingredient per kg of body weight per day to achieve effective results.

For dermal use, the use in the form of the agents described in detail above containing benzyl alcohol and / or a is particularly emphasized

Pyrrolidone solvent. Furthermore, the application via molded bodies can be considered. Shaped bodies include collars, pendants for collars (medallions), ear tags, straps for attachment to limbs or body parts, adhesive strips and foils, peel-off foils.

Collars and medallions deserve special mention.

Thermoplastic and flexible thermosetting plastics as well as elastomers and thermoplastic elastomers come into question for the production of the molded 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 flexibility so that they do not crack or become brittle during molding. They must be of sufficient durability to withstand normal wear and tear. In addition, the polymers must allow sufficient migration of the active ingredient to the surface of the molded body.

The active substances can be present in the preparations and shaped bodies in a mixture with synergists or other active substances, which are already listed in detail above.

In the following examples, l, l-dimethylethyl {[[[((1,3-dimethyl-5-phenoxy-l-pyrazol-4-yl) methylene] amino] oxy] methyl} benzoate (gas no .: 134098- 61-6) (common name Fenpyroximate / see Tab. 1, No. 1). Examples

example 1

A spot on formulation consisting of 20.0 g Fenpyroximate 60.0 g benzyl alcohol

0.1g BHT (butylated hydroxytoluene)

19.9g benzyl benzoate

Example 2

A spot on formulation consisting of 25.0 g Fenpyroximate 45.0 g benzyl alcohol

0.1 g BHT 29.9 g dimethysuccinate

Example 3

A spot on formulation consisting of 20.0 g Fenpyroximate 65.0 g benzyl alcohol 0.1 g BHT 14.9 g dipropylene glycol monomethyl ether acetate Example 4

A spot on formulation consisting of 16.7 g Fenpyroximate 25.0 g methylpyrrolidone

0.1 g BHT

58.1 g benzyl benzoate 0.1 g citric acid

Example 5

A spot on formulation consisting of 16.7 g Fenpyroximate 25.0 g methylpyrrolidone 0.1 g hydroxybuthylanisole

58.2 g dipropylene glycol monomethyl ether acetate

Example 6

A spot on wording consisting of

16.7 g fenpyroximate

25.0 g methylpyrrolidone 0.1 g BHT

58.2 g triethyacetate

To carry out efficacy tests against fleas and ticks, dogs were treated with the formulations according to Examples 1-7. The treatment was dermal as a spot on as an application between the shoulder blades. The application rate for all animals was 20 mg of active ingredient / kg body weight. Efficacy against fleas in dogs

Ctenocephalides felis

On days -4 and -1 dogs are infested with approx. 100 adult, fasting Ctenocephalides felis per dog. The fleas are spread on the neck of the animal.

On day 0, the success of the infestation on the dog is checked by looking for fleas on the awake animal. The number of living fleas is recorded.

After the fleas have been counted, the animals are treated. The dogs in the control group are not treated. The drugs to be tested are administered to the animals dermally as a spot-on. The application takes place once on day 0. Only clinically healthy animals are used.

On day 1 and day 2, all dogs living fleas are checked. The results are recorded in the raw data.

On days 7, 16, 23 and 30 all dogs are reinfested with approx. 100 adult, sober Ctenocephalides felis per dog. One and two days after reinfestation all dogs fleas are checked. The results are logged in the raw data.

A formulation rank is considered highly effective if an efficacy> 95% and this is found on day 2 and on the second day after reinfestation

Effect lasts for at least 3 weeks.

A modified Abbott formula is used to calculate the effectiveness: 0 number of fleas KG - 0 number of fleas BG

Efficacy% = = X 100

0 number of fleas KG

Fenpyroximate in a dosage of 20 mg / kg in formulation examples 1 to 7, applied as a spot on, proved to be highly effective against Ctenocephalides felis.

Efficacy against ticks (Ixodes ricinus) in dogs

On day -1 dogs are sedated with 2% Rompun ^® (Bayer AG) (0.1 ml / kg body weight). After all dogs are sedated (after about 10-15 minutes) they will be in

Transport boxes transferred and 50 Ixodes ricinus (252, 25c?) Per dog placed on the neck of the animal. The animals are put back into the cage from the transport box after about 1 hour.

On day 0, the success of the infestation on the dog is checked by searching for ticks on the awake animal. Intensive searches are carried out in the head and ear area including the ear fold, in the area of the neck, on the lower abdomen, on the lower chest, on the side flank and between the toes and on the limbs. The number of live ticks sucked in is recorded. Dead ticks are removed.

After the ticks have been counted, the animals are treated. The dogs in the control group are not treated. The drugs to be tested are administered to the animals dermally as a spot-on. The application takes place once on day 0. Only clinically healthy animals are used.

On day 1 and day 2, all dogs are checked for live and dead sucking ticks. The results are recorded in the raw data. On day 2, all living and dead ticks are removed from the dog. On days 7, 14, 21 and 28 all dogs are reinfested with 50 Ixodes ricinus ($ 25, 25 c?) Per dog. One and two days after reinfestation, all dogs are checked for live and dead sucked ticks. The results are logged in the raw data. On the second day after reinfestation, all living and dead ticks are removed from the dog.

A formulation is considered highly effective if an efficacy> 85% is found on day 2 and on the second day after reinfestation and this effect lasts for at least 3 weeks.

A modified Abbott formula is used to calculate the effectiveness:

0 number of ticks KG - 0 number of ticks BG

Effectiveness% = ^ X 100

0 number of ticks KG

KG: control group

BG: treatment group

Fenpyroximate in a dosage of 20 mg / kg in formulation examples 1-7, applied as a spot on, proved to be highly effective against Ixodes ricinus.

Claims

claims 1. Containing means: (a) Pyrazole oximes in a concentration of 5-40% by weight based on the total weight of the formulation (b) a solvent from the group consisting of benzyl alcohol and pyrrolidone solvent or mixtures thereof in a concentration of at least 20% by weight. 2. Composition according spoke 1, characterized in that it pyrazole oximes of the general formula (I)

wherein R ^{1 is} C ¹ -C ₄ -alkyl or phenyl, R ² is hydrogen, C ₁ -C ₅ -alkyl, represents C ₃ haloalkyl or phenyl, R ³ denotes hydrogen, C _j -C4-alkyl or phenyl, R ^{4 is} hydrogen, C ₂ -C ₄ alkylcarbonyl, benzoyl, naphthyl or one Substituents of the formula

[wherein X represents hydrogen, halogen; CC _j 2- lkyl, C _j -Cg-alkyl substituted with halogen, cyano, hydroxy, -C-C ₅ alkoxy or C ₂ -C6 alkoxycarbonyl; C3-Cg cycloalkyl; C3-Cg-Cycloalkyl substituted with 1 to 3 substituents selected from the group consisting of: Cj-C4 alkyl, halogen and cyano; C2-C4-alkenyl substituted with halogen, hydroxy, C2-C4-alkoxycarbonyl or C2-Cg-alkylcarbonyl; phenyl; hydroxy; Ci-Cg-alkoxy; -C-C4-alkoxy substituted with halogen or C2-Cg-alkoxy-carbonyl; Phenoxy optionally substituted with C 1 -C 3 haloalkyl; benzyloxy; Cι-C3-Alkylenedioxy formed from two adjacent substituents X; Pyridyloxy optionally substituted with halogen or C 1 -C 4 haloalkyl; -S (O) _p R ⁵ (where R ^{5 is} CJ-C _O -alkyl, Cj-Cs-haloalkyl or phenyl and p is 0, 1 or 2); cyano; formyl; nitro; -COOR ⁶ (where R ^{6 is} hydrogen, alkali metal, C _r C ₁₀ alkyl, Cj-Cs-alkyl substituted with halogen,

Phenoxy, C ₂ -C 4 alkoxycarbonyl or phenoxyphenyl; C2-C7 alkenyl; C ₃ -C ₇ alkynyl; C ₃ -C ₈ cycloalkyl; C ₃ -C ₈ cycloalkyl substituted with C _r C ₃ alkyl; phenyl; -S _n R ⁷ R ⁸ R ⁹ (where R ⁷ , R ⁸ and R ^{9 are the} same or different and are C1-C4-alkyl or C ₃ -C ₈ -cycloalkyl)}; C ₂ -C 6 alkylcarbonyl; C ₂ -C ₆ alkylcarbonyl substituted with cyano or C ₂ -C ₆ alkoxycarbonyl; Benzoyl optionally substituted with halogen or C _r C ₆ alkyl; C ₂ -C ₆ alkylthiocarbonyl; C ₃ -C ₇ alkoxycarbonylcarbonyl; -C (= O) NR ¹⁰ R ^π (where R ¹⁰ and R ^{11 are the} same or different and represent hydrogen, C _j -Cg alkyl or phenyl); piperidinocarbonyl; Moφholinocarbonyl, which is optionally mono- or disubstituted by C _r C ₄ alkyl; -NR ¹² R ¹³ (in which R ^{12 is} hydrogen or -CC-alkyl and R ^{13 is} formyl, C2-Ci2-alkoxycarbonyl or C2-C5-alkoxycarbonyl substituted with halogen or -C-C4-alkoxy); a substituent of the formula 10

(wherein R ^{14 is} hydrogen, C _r C ₄ alkyl or C ₂ -C ₆ alkoxyalkyl); -C (BR ¹⁵ ) (BR ¹⁶ ) (R ¹⁷ ) (where R ¹⁵ and R ^{16 are the} same 15 or can be different and represent C 1 -C 4 alkyl or together form a C 1 -C 4 alkylene radical, R ^{17 represents} C ₁ -C 5 alkyl, cyano or C ₂ -C 6 alkoxycarbonyl and B is oxygen or sulfur; -C (OR ¹⁸ ) R ¹⁹ R ²⁰ (in which R ^{18 is} hydrogen or C2-C4-alkylcarbonyl and R ¹⁹ 20 and R ^{20 are the} same or different and are hydrogen or C _{r is} C ₆ alkyl); -SiR ²¹ R ²² R ²³ (wherein R ²¹ , R ²² and R ^{23 are the} same or different and represent C _j ^ alkyl); or -O-SiR ²⁴ R ²⁵ R ²⁶ (in which R ²⁴ , R ²⁵ and R ^{26 are the} same or different and represent C _j ^ alkyl), and 25 n is an integer from 1 to 5, where if n is an integer from 2 to 5, X may be the same or different]; Hydrogen, -CC ₆ alkyl, C ₁ -C 4 haloalkyl, halogen, hydroxy, C ₁ -C 4 haloalkoxy, Cj-C3-alkylenedioxy, phenoxy, which is optionally substituted with trifluoromethyl, -S (O) _q R ²⁷ (in which R ^{27 is} C 1 -C 3 -alkyl and q is 0, 1 or 2), hydroxycarbonyl, C ₂ -C 5 -alkoxycarbonyl or -NR ²⁸ R ²⁹ (in which R ²⁸ and R ^{29 are} identical or different and are hydrogen, Cι- C ₄ - alkyl or benzyl, which is optionally substituted by C2-C6-alkoxycarbonyl); Z ^{1 represents} oxygen or sulfur; Z ^{2 represents} oxygen, sulfur or a single bond; Z ^{3 represents} aryl or heteroaryl Q is -C ₈ alkylene, C2-Cg-alkylene substituted with halogen or phenyl, C3-Ci2-al enylene, C3-Ci2-haloalkenylene or C3-C6-alkynylene; and m represents an integer from 1 to 3, where if m represents an integer 2 or 3, Y can be identical or different, or contains their stereoisomers. 3. Composition according to claim 1 or 2, characterized in that it further comprises a cosolvent selected from the group aliphatic esters, aromatic esters, aliphatic lactones with a boiling point of at least 70 ° C or aliphatic cyclic or acyclic ethers with a boiling point of at least 60 ° C in a concentration of 2.5 to Contains 75% by weight based on the total weight of the formulation. 4. A process for the preparation of the compositions according to claim 1, characterized in that the active ingredient is mixed with the solvent or solvents and, if appropriate, further auxiliaries are added. 5. Use of agents according to claim 1 for the dermal control of parasitic arthropods on animals. 6. A method for dermal control of parasitic arthropods on animals, in which the animals in question the required amount of Applied according to claim 1. 7. Use of pyrazole oximes for the preparation of agents for controlling fleas on animals. 8. Use according to claim 7 for the preparation of agents for controlling Ctenocephalides spp. on animals. 9. Use according to claim 8 for the preparation of agents for controlling Ctenocephalides canis and / or Ctenocephalides felis on animals. 10. Method for controlling Ctenocephalides spp. on animals in which an effective amount of a pyrazoloxime is applied to the animal in question.