HK1088790B - Repellent - Google Patents

Description

Repellent

The present invention relates to the use of pyrethroid/pyrethrin arthropod repelling compositions in combination with agonists of arthropod nicotinic acetylcholine receptors to repel arthropods, preferably arthropods on animals, in an effective and sustained manner.

It is known to control parasitic insects in animals using topical formulations comprising permethrin, 3- (2, 2-dichlorovinyl) -2, 2-dimethylcyclopropanecarboxylic acid- (3-phenoxyphenyl) methyl ester, (CAS number [52645-53-1]) (see, for example, WO 95/17090, JP-07247203, EP-A-567368, EP-A-461962, US-5236954 and US-5074252).

Agonists of nicotinic acetylcholine receptors of insects are known, for example european patent publication nos. 464830, 428941, 425978, 386565, 383091, 375907, 364844, 315826, 259738, 254859, 235725, 212600, 192060, 163855, 154178, 136636, 303570, 302833, 696, 189972, 455000, 135956, 471372, 302389; german patent publication nos. 3639877, 3712307; japanese patent publication nos. 03220176, 02207083, 63307857, 63287764, 03246283, 049371, 03279359, 03255072; U.S. patent nos. 5034524, 4948798, 4918086, 5039686, 5034404404; PCT application numbers WO 91/17659, 92/4965; french patent application No. 2611114; brazilian patent application No. 8803621. It is also known to control parasitic insects on animals using spot-on formulations containing agonists or antagonists of the nicotinic acetylcholine receptors of insects (see, for example, WO 98/27817, EP-A-682869 and EP 0976328).

Also disclosed in the prior art are combinations of permethrin and agonists or antagonists of the nicotinic acetylcholine receptors of insects for killing parasites (see, for example, CN-1245637, WO 00/54591, US-6080796, EP-A-981955, US-6033731, JP-07089803). Arthropod repelling activity of type I pyrethroids was first disclosed in US-4178384 (Pyrethoid extract Repellent. Ensing, Kenneth J., 1979, US4178384 relates to repellents against cockroaches), Matthewson et al (1981, screening technologies for the evaluation of chemicals with activity enzymes Matthewson, Michael D., Hughes, Graham; Macpherson, Ian S., Bernard, Colett P., Pesticide Science, 12(4), 455-62) and Shemanhuk (1981, reaction of Permethrin, and Pyrethroid aggregation of type I pyrethroids (Silybum species), Pyrethroid type I and Pyrethroid type II, respectively, (16-P), Pethist et al, Pest, Pe.

A disadvantage of spot-on formulations, such as those based on permethrin, is their low toxicity to ticks, mosquitoes and flies.

In general, spot-on formulations based on agonists and antagonists of nicotinic acetylcholine receptors (see, e.g., WO 96/17520) have very good activity against insects. However, they have the disadvantage of being virtually ineffective against ticks and of not having a repellent activity against ticks.

This is why, until now, multiple treatments of animals with various formulations are still required in order to successfully control ticks and fleas, and to repel mosquitoes and flies. For ecological and economic reasons, it is desirable to replace these preparations with preparations which have good skin tolerance at low use volumes (e.g. 0.1ml/1.0kg [ body weight of animal treated ]), toxicity which is not feared by humans and a clearly distinguished long-lasting effect, in particular against ticks, fleas, mosquitoes and flies, of at least three to four weeks. Moreover, the above formulations will have sufficient storage stability under all climatic conditions, for example in the case of conventional spot-coated tubes, typically at least three years.

WO 02/087338 describes a formulation comprising permethrin and an agonist or antagonist of the insect nicotinic acetylcholine receptor for application to the skin which renders the skin and environment acceptable, user friendly, active against parasitic insects, particularly ticks and fleas.

Surprisingly, it has now been found that compositions comprising an active substance selected from the group consisting of pyrethroids/pyrethroids in combination with an active substance having an arthropod nicotinic receptor agonistic effect have very good repellent properties against arthropods such as ticks, mosquitoes and flies, the repellent effect of which exceeds that of formulations comprising pyrethroids/pyrethrins alone. The repellent effect is related to both the relative time of exposure to the ectoparasites of the treated animals and the exposure time required to achieve 100% mortality following exposure. As can be seen from in vitro comparative studies, the repellent effect cannot be attributed to the formulation.

Thus, the formulation of a composition of the above type, disclosed in detail below, not only enables control of parasites which have already infested animals, but, surprisingly, is also very effective in preventing acute infestation thereof and thus in preventing transmission of potential pathogens by arthropods, in particular ticks, mosquitoes and sucking flies.

The present invention relates to:

1. use of a pyrethroid or pyrethrin in combination with a nicotinic agonist for repelling an arthropod.

2. Use according to item 1, wherein the pyrethroid is selected from:

pyrethroid type I.I

Type II pyrethroids

Non-ester pyrethroids

IV, natural pyrethrins

3. The use of item 1, wherein the nicotinic agonist is selected from the group consisting of:

neonicotinoids V

Nithiazine VI

VII. Spinosad

4. The use according to item 1 for repelling ticks, fleas, mosquitoes and/or flies on a warm-blooded animal.

5. A method of repelling arthropods on warm-blooded animals, wherein a pyrethroid or pyrethrin is applied topically to warm-blooded animals in combination with a nicotinic agonist.

6. A method of repelling arthropods on locus or material where they are undesirable, wherein a pyrethroid or pyrethrin is applied in combination with a nicotinic agonist to the locus or material of the arthropod to be repelled.

The compositions of the present invention are preferably liquid and suitable for dermal application, especially known pour-on or spot-on formulations. Other forms of administration are also possible (see below).

The following amounts of pyrethroid or pyrethrin are typically included in the formulation:

pyrethroid type I.I, for example: permethrin: 15-75 wt.%, preferably 33-55 wt.%.

Type ii pyrethroids, for example: cypermethrin: 1 to 20% by weight, preferably 5 to 15% by weight.

Non-ester type pyrethroids, for example: ethofenprox and silafluofen: 15-75 wt.%, preferably 40-60 wt.%.

Natural pyrethrins, such as pyrethrin I, jasminum I, guaethrin I, pyrethrin II, jasminum II, guaethrin II: 25 to 75 wt.%, preferably 30 to 50 wt.%.

The compositions which can be used according to the invention comprise the active substances from the group of nicotinic agonists V-VII in the following amounts:

neonicotinoids: 1 to 25 wt.%, preferably 5 to 15 wt.%. Examples which may be mentioned are: imidacloprid, thiacloprid, clothianidin, nitenpyram, dinotefuran and thiamethoxam.

Nithiazine 20 to 40 wt.%, preferably 25 to 35 wt.%.

VII-Spinosad: 1 to 25 wt.%, preferably 5 to 15 wt.%. Examples which may be mentioned here are: spinosad 105, butyl spinosad 105.

In addition, the compositions used according to the invention generally comprise customary solvents and spreaders and, if desired, customary auxiliaries.

Given in weight percent means percent of the total weight.

Pyrethroids/pyrethrins are classified as type I pyrethroids, type II pyrethroids, non-ester pyrethroids and natural pyrethrins, as described in encyclopedia Referenceof Parasitology, second edition, Disease, Treatment, Therapy, (h. mehlhorn editions), 2001, pages 91-96, which is incorporated by reference.

Examples of type I pyrethroids are allethrin, esfenprox, permethrin, phenothrin, resmethrin, tetramethrin.

Examples of type II pyrethroids are: alpha cypermethrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, fenvalerate, flumethrin, cyfluthrin.

Examples of non-ester type pyrethroids are: such as ethofenprox, silafluofen.

Examples of natural pyrethrins are pyrethrin I, pyrethrin II, guaethrin I, guaethrin II, jasminum I, jasminum II.

Preferably, the mentioned agonists of the nicotinic acetylcholine receptors of insects are neonicotinoids.

Neonicotinoids are to be understood as meaning, in particular, compounds of the formula (I),

wherein:

r represents hydrogen, an optionally substituted group selected from acyl, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl or heterocycloalkyl;

a represents a monofunctional group selected from hydrogen, acyl, alkyl, aryl, or represents a difunctional group linked to the group Z;

e represents an electron withdrawing group;

x represents a group-CH ═ or ═ N-, the group-CH ═ can be substituted with H atoms attached to the group Z;

z represents a monofunctional group selected from the group consisting of alkyl, -O-R, -S-R,

Wherein

R represents identical or different radicals and has the abovementioned meaning,

or Z represents a bifunctional group linked to the group A or to the group X.

Particularly preferred are compounds of formula (I) wherein the radicals have the following definitions:

r represents hydrogen and an optionally substituted group selected from acyl, alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl.

Acyl radicals which may be mentioned are formyl, (C)_1-8-alkyl) carbonyl, (C)_6-10-aryl) carbonyl, (C)_1-8-alkyl) sulfonyl, (C)_6-10-aryl) sulfonyl, (C)_1-8-alkyl) - (C_6-10-aryl) phosphoryl, which may be further substituted.

Alkyl radicals which may be mentioned are C_1-10Alkyl, especially C_1-4Alkyl, in particular methyl, ethyl, isopropyl, sec-butyl or tert-butyl, which may be further substituted.

Aryl radicals in particular being C_6-10Aryl, examples which may be mentioned are phenyl, naphthyl, in particular phenyl.

Arylalkyl is especially (C)_6-10-aryl) - (C_1-4Alkyl), examples which may be mentioned are benzyl, phenethyl.

Heteroaryl groups which may be mentioned are those having up to 10 ring atoms and N, O, S, in particular N, as heteroatoms. The following may be mentioned in particular: thienyl, furyl, thiazolyl, imidazolyl, pyridyl, benzothiazolyl.

Heteroaralkyl is in particular heteroaryl- (C)_1-4-alkyl), wherein heteroaryl is as defined above. Examples which may be mentioned are heteroarylmethyl, heteroarylethyl having up to 6 ring atoms and N, O, S, in particular N, as heteroatoms.

Heterocyclyl is especially an unsaturated but not aromatic, or saturated heterocyclic ring having up to 6 ring atoms and comprising up to 3 heteroatoms selected from N, O, S, for example tetrahydrofuranyl.

Heterocycloalkyl, especially heterocyclyl-C_1-2-alkyl groups, such as: tetrahydrofurylmethyl and tetrahydrofurylethyl.

The following may be mentioned by way of example and preferably as substituents:

alkyl having preferably 1 to 4, in particular 1 or 2, carbon atoms, such as methyl, ethyl, n-and i-propyl and n-, i-and t-butyl; alkoxy having preferably 1 to 4, in particular 1 or 2, carbon atoms, such as methoxy, ethoxy, n-and i-propoxy and n-butoxy, i-butoxy and t-butoxy; alkylthio having preferably 1 to 4, in particular 1 or 2, carbon atoms, such as methylthio, ethylthio, n-and isopropylthio and n-butylthio, isobutylthio and tert-butylthio; haloalkyl having preferably 1 to 4, in particular 1 or 2, carbon atoms and preferably 1 to 5, in particular 1 to 3, halogen atoms which are identical or different and are preferably fluorine, chlorine or bromine as halogen atoms, in particular fluorine, such as trifluoromethyl; a hydroxyl group; halogen, preferably fluorine, chlorine, bromine and iodine, especially fluorine, chlorine and bromine; a cyano group; a nitro group; an amino group; monoalkylamino and dialkylamino preferably having 1 to 4, in particular 1 or 2, carbon atoms per alkyl radical, such as methylamino, methylethylamino, n-propylamino and isopropylamino and methyl-n-butylamino; a carboxyl group; alkoxycarbonyl having preferably 2 to 4, in particular 2 or 3, carbon atoms, such as carbomethoxy and carboethoxy; sulfo (-SO)₃H) (ii) a Alkylsulfonyl groups having preferably 1 to 4, in particular 1 or 2, carbon atoms, such as methylsulfonyl and ethylsulfonyl; arylsulfonyl having 6 or 10 aryl carbon atoms, such as phenylsulfonyl and heteroarylamino and heteroarylalkylamino, such as chloropyridylamino and chloropyridylmethylamino, are preferred.

A particularly preferably represents hydrogen and optionally substituted radicals from the group consisting of acyl, alkyl, aryl, R preferably having the abovementioned meaning. A also represents a bifunctional group. A group which may be mentioned is optionally substituted alkylene having 1 to 4, in particular 1 to 2, carbon atoms, where the substituents may be those mentioned above as further examples and where the alkylene may be interrupted by heteroatoms selected from N, O, S.

A and Z may form a saturated or unsaturated heterocyclic ring bonded to the atom to which they are attached. The heterocyclic ring may also comprise 1 or 2 identical or different heteroatoms and/or heterogroups. The heteroatom is preferably oxygen, sulphur or nitrogen and the heterogroup is preferably an N-alkyl group, wherein the alkyl group in the N-alkyl group preferably comprises 1 to 4, in particular 1 or 2, carbon atoms. Alkyl groups which may be mentioned are methyl, ethyl, n-and i-propyl and n-, i-and t-butyl. Heterocycles comprise 5 to 7, preferably 5 or 6 ring atoms.

Examples of heterocycles which may be mentioned are pyrrolidine, piperidine, piperazine, hexamethyleneimine, hexahydro-1, 3, 5-triazine, morpholine and oxadiazine, which are optionally substituted, preferably by methyl.

E represents an electron-withdrawing group, and may be mentioned in particular NO₂CN, haloalkylcarbonyl, e.g. halo-C having 1 to 9 halogen atoms_1-4-alkylcarbonyl, in particular COCF₃And C and_1-4alkylsulfonyl and halogeno C having 1 to 9 halogen atoms_1-4Alkylsulfonyl, especially SO₂CF₃。

X represents-CH or-N ═

Z represents optionally substituted alkyl, -OR, -SR, -NRR, wherein R and the substituents preferably have the above definitions.

Z is capable of forming not only the above-mentioned ring but also atoms and groups bonded thereto

Together, in place of X, a saturated or unsaturated heterocyclic ring may be formed. The heterocyclic ring may also comprise 1 or 2 and the same or different heteroatoms and/or heterogroups. The hetero atom is preferably oxygen, sulfur or nitrogen, andthe radical is preferably an N-alkyl radical, where the alkyl or N-alkyl radical comprises preferably 1 to 4, in particular 1 or 2, carbon atoms. Alkyl radicals which may be mentioned are methyl, ethyl, n-and i-propyl and n-, i-and t-butyl. Heterocycles comprise 5 to 7, preferably 5 or 6 ring atoms.

Examples of heterocycles which may be mentioned are pyrrolidine, piperidine, piperazine, hexamethyleneimine, morpholine and N-methylpiperazine.

Particularly preferred compounds which may be mentioned for use according to the invention are compounds of the general formulae (II), (III) and (IV).

Wherein

n represents a number of 1 or 2,

m represents 0, 1 or 2

The substituents represent one of the above-mentioned substituents, in particular halogen, more particularly chlorine, A, Z, X and E having the meaning indicated above.

The following compounds may be mentioned in particular:

the following particularly preferred compounds may be mentioned in particular:

in addition to nicotinic agonists of the neonicotinoid class, other nicotinic agonists may also be used in the present invention.

Examples which may be mentioned in this context are spinosyns, in particular spinosyns A and D

As described by Boeck et al in EP 375316A1 and Deamicis et al in WO 97/00265A 1; the above documents are incorporated herein by reference.

Spinosyns are also understood herein as synthetic or semi-synthetic derivatives of natural spinosyns or derivatives prepared by genetically modified varieties, for example, the species saccharomyces pombe disclosed in WO 02/77004 and WO 02/77005; the above documents are incorporated herein by reference.

Examples which may be mentioned are compounds of the formulae I and II in which R³Is glycoside (R)³＝R¹)，R⁴Is H, OH or an alkoxy group (typically having 1 to 8, preferably 1 to 4 carbon atoms); r⁵Is H, methyl, R⁶And R⁷Is H or in combination forms a double bond or an epoxy group, R in formula I⁸Is trans-1-butenyl, 1, 3-butadienyl, butyl, 3-hydroxybutenyl, propyl, 1-propenyl, 1, 2-epoxy-1-butyl, 3-oxo-1-butenyl, CH₃CH(OCH₃)CH＝CH-，CH₃CH＝CHCH(CH₂CO₂CH₃) -, or CH₃CH＝CHCH[CH₂CON(CH₃)₂]-；R⁹Is H or a glycoside (R)⁹＝R²)。

Other compounds which can be used as nicotinic receptor agonists and which can likewise be successfully combined with compounds of class 1 are, for example, nicotine or nithiazine

Surprisingly, the repellency effect and short-term contact kill (Kurz-Kontakt) mortality of the compositions used in the present invention, i.e., the pyrethroid/pyrethrin based actives in combination with the nicotinic agonist based actives, exceeded the expected activity on an individual ingredient basis. Thus, by using the above-mentioned agents, it is possible to reduce the amount of active substance used and prolong the persistent activity. Therefore, the application thereof has economic and ecological benefits.

The compositions used in the present invention are well suited for use in repelling parasites and preventing the spread of pathogens transmitted by such parasites. The parasite may be repelled directly from the human or animal or the environment. Furthermore, combinations of the above-mentioned active substances can also be used for protecting materials, i.e. repelling arthropods from undesired locations and materials.

Parasites which may be mentioned are:

from the order of the Anoplura, for example the genera Haemophilus, Chilophagus, Pilophagus, Anoplurus;

from the order of the mallophaga, for example, the genera louse (Trimenopon spp.), nithagus, eomnatus spp, gallinaceus, pediculosis, catus, louse, boehmeria;

from the order of the Diptera, for example Aedes, Culex, Arachnocephala, Chrysomyelia, Lutzomyia spp, Tabanus, Musca, Hygrophila, Drosophila, Chelidonius, Darthodoptera, Serratia, Chlorpyriproxyfen, Lepidogrypus, Cordylobia spp, Convolvulus, Chrysomyelia, Sarcophaga, Drosophila, Gastrophila, Eudermopsis (Oesteromyiaspp), Oedena spp, Dermanystochasmanis, Erythrochaga, Naemanophaga, Naemophila, Naemanophaga, Naemaphys, Naemaphysalis, Germanophaga, tick, and Phthirius.

From the order of the Siphonaptera, for example, Ctenocephalides, Ceriporia, Siphonaptera;

from the order of the phylotrichia, for example, Hyaloporus, Rhipicephalus, Ornithodiones, Haematolagi, Dermacentor, Harpridinus, Oenodicephalus, Hydracocephalus;

from the order of the Neurospora, for example, Dermatophagoides, and Dermatophagoides.

From the order of the Protozoa, for example, the genera Acarina, Sarcophaga, Demodex, and Sintsugamushi;

from the phylogenetic sub-order, for example, the genera Dermatophagoides, Prurites, Dermatophagoides, scabies, Dermatophagoides, Neoknectoptes spp.

According to the invention, the composition is used for repelling animals, in particular arthropods under warm-blooded animals, preferably ticks, fleas, mosquitoes and flies. It is also possible to use on the human body.

Examples of animals are farm animals or domestic animals: mammals such as: such as cattle, horses, sheep, pigs, goats, camels, buffalo, donkeys, rabbits, deer in the toe, elk, fur-bearing animals such as: mink, chinchilla, raccoon; birds such as: chickens, geese, turkeys, ducks, and ostriches.

They may also be laboratory and test animals, for example mice, rats, guinea pigs, hamsters, dogs and cats.

Can be used on pets, for example, particularly preferably on dogs and cats.

Since, as a rule, the treated animal also disperses a certain amount of the applied composition into the environment, for example by rubbing or scattering with debris, the composition according to the invention not only acts directly on the animal, but, correspondingly, also acts on its environment.

It is clear that the compositions used according to the invention comprise, in addition to the active substances mentioned above, other suitable active substances.

Examples which may be mentioned are growth-inhibiting active substances and synergists, such as pyriproxyfen {2- [ 1-methyl-2- (4-phenoxyphenoxy) ethoxy ] pyridine CAS number: 95737-68-1}, methoprene [ (E, E) -1-methylethyl 11-methoxy-3, 7, 11-trimethyl-2, 4-dodecenoate CAS number: 40596-69-8 and chlorsulfuron { 2-chloro-N- [ [ [4- (trifluoromethoxy) phenyl ] amino ] carbonyl ] benzamide CAS number: 64628-44-0}.

It is also contemplated that other repellent materials such as diethyltoluamide, Bayerel(CAS name: 1-piperidinecarboxylic acid, 2- (2-hydroxyethyl) -, 1-methylpropyl ester), 2- (octylthio) ethanol or ethyl 3- (N-acetyl-N-butylamino) propionate.

It is usually administered to the animal by the transdermal route, either directly or in the form of a suitable formulation.

Since the pyrethroid/pyrethroids repellency mechanism requires the possibility of contact with the active, it has been suggested to distribute the active over the entire surface to be protected, for example over all body parts of the animal to be treated. Penetration of the active substance into the skin is disadvantageous for the repellent effect, since the active substance no longer has the desired repellent activity after penetration into the skin.

The skin application is carried out, for example, by spraying, pouring (pouring and spot-coating).

Suitable formulations are:

liquid or diluted concentrate for application to the skin or body cavity, pour-on formulation, gel;

emulsions and suspensions, semi-solid formulations;

formulations in which the active substance is added to an ointment base or to an oil-in-water or water-in-oil emulsion base;

solid preparations such as powders, premixes or concentrates, granules, pellets, aerosols and shaped bodies containing active substance.

Solvents which may be mentioned are: physiologically acceptable solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycol, N-methylpyrrolidone, 2-pyrrolidone, and mixtures thereof.

The active substances can also be dissolved, if desired, in physiologically acceptable vegetable or synthetic oils.

Solubilizers which may be mentioned are: a solvent that promotes dissolution of the active substance in the main solvent or prevents precipitation thereof. Examples are polyvinylpyrrolidone, polyvinyl alcohol, polyethoxylated castor oil, polyethoxylated sorbitol esters.

The preservative is as follows: benzyl alcohol, chlorobutanol, p-hydroxybenzoate ester and n-butanol.

The liquid formulation can be administered directly. The concentrate is diluted to the use concentration before use.

The liquid formulation may be applied by spotting, rubbing, spreading or spraying onto the skin.

It is advantageous to add a thickener to the formulation. The thickening agent is: inorganic thickeners such as bentonite, silica gel, aluminium monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohol and copolymers thereof, acrylates or methacrylates.

The gel is applied or painted onto the skin or injected into a body cavity. The gel is prepared by mixing the solution with a sufficient amount of thickener to form a clear composition having a paste-like consistency, wherein the solution is prepared as described for the injection solution. The thickeners used are those described above.

Pour-on formulations are splashed or sprayed onto a defined area of the skin, the active substance penetrating the skin and acting systemically.

The pour-on formulations are prepared by dissolving, suspending or emulsifying the active substance in a solvent or solvent mixture suitable for skin tolerance. If desired, further auxiliaries such as colorants, absorption-promoting substances, antioxidants, opacifiers and/or stickers may also be added.

Solvents which may be mentioned are: water, alkanols, ethylene glycol, polyethylene glycol, polypropylene glycol, glycerol, aromatic alcohols such as benzyl alcohol, phenyl ethanol, 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 monobutyl ether, ketones such as acetone, methyl ethyl ketone, cyclic carbonates such as cyclopropyl carbonate, cyclic ethyl carbonate, aromatic and/or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-alkylpyrrolidones such as N-methylpyrrolidone, N-butyl or N-octylpyrrolidone, N-methylpyrrolidone, 2-pyrrolidone, 2-dimethyl-4-oxymethylene-1, 3-dioxolane and glycerol formal.

Colorants are colorants that are approved for use on animals and can be dissolved or suspended.

The absorption-promoting substance is, for example, DMSO, a spreading oil such as isopropyl myristate, dipropylene glycol pelargonate, silicone oil, or a copolymer thereof with a polyether, a fatty acid ester, a triglyceride, a fatty alcohol.

Antioxidants such as sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole, tocopherols.

Sunscreens are, for example

Stickers are, for example, cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.

Emulsions may be of the water-in-oil or oil-in-water type.

They are prepared by dissolving the active substance in a hydrophobic or hydrophilic phase and homogenizing it with the aid of suitable emulsifiers and, if desired, auxiliaries such as colorants, absorption-promoting substances, preservatives, antioxidants, opacifiers, thickeners, with the solvents of the other phases.

Hydrophobic phases (oils) which may be mentioned are: paraffin oil, silicone oil, natural vegetable oil such as sesame oil, oleum Armeniacae amarum, castor oil, synthetic triglyceride such as caprylic/capric acid diglyceride, and fatty acid ester containing chain length C_8-12The vegetable fatty acids or other fatty acids are selected from the group consisting of triglyceride mixtures of natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids which may contain hydroxyl groups, C₈/C₁₀Mono-and diglycerides of fatty acids.

Esters of fatty acids, e.g. ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, having a chain length C₁₆-C₁₈Esters of medium-chain branched fatty acids of saturated fatty alcohols, isopropyl myristate, isopropyl palmitate, chain length C₁₂-C₁₈Octanoic/decanoic acid esters, isopropyl stearate, oleyl oleate, decyl oleate, ethyl lactate, waxy fatty acid esters such as synthetic duck tail fat, dibutyl phthalate, diisopropyl adipate, ester mixtures relating to the latter, in particular fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetyl stearyl alcohol, oleyl alcohol.

Fatty acids such as oleic acid and mixtures thereof.

Hydrophilic phases which may be mentioned are:

water, alcohols such as propylene glycol, glycerin, sorbitol, and mixtures thereof.

Emulsifiers which may be mentioned are: nonionic surfactants such as polyethoxylated castor oil, polyethoxylated sorbitan monooleate, sorbitan monostearate, glyceryl monostearate, polyoxyethyl stearate, alkylphenyl polyglycol ethers;

amphoteric surfactants such as disodium N-lauryl- β -iminodipropionate or lecithin;

anionic surfactants such as sodium lauryl sulfate, fatty alcohol sulfate, mono/dialkyl polyglycol ether orthophosphate monoethanol amine salt;

cationic surfactants such as cetyltrimethylammonium chloride.

Further auxiliaries which may be mentioned are: thickening and emulsion-stabilizing substances such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, silica gels or mixtures of the stated substances.

Suspending agents are prepared by suspending the active substance in a vehicle fluid, optionally with the addition of further adjuvants such as wetting agents, colorants, absorption-promoting substances, preservatives, antioxidants, opacifiers.

Excipient fluids which may be mentioned are all homogeneous solvents and solvent mixtures.

Wetting agents (dispersants) which may be mentioned are the surfactants already mentioned above.

Further auxiliaries which may be mentioned are as already given above.

Semisolid formulations differ from the suspending agents and emulsifiable concentrates described above only in their high viscosity.

To prepare solid preparations, the active substances are brought into the desired dosage form by mixing with suitable excipients, if appropriate with the addition of auxiliaries.

Excipients which may be mentioned are all physiologically tolerable solid inert substances. Both inorganic and organic substances can be used. Inorganic substances are, for example, sodium chloride, carbonates, such as calcium carbonate, hydrogen carbonate, aluminum oxide, titanium oxide, silica, clays, precipitated silicon dioxide or silica gels, phosphates.

Organic substances are, for example, sugar, cellulose, food and feed products such as milk powder, animal feed, fine or coarse cereal feed, starch.

Adjuvants are preservatives, antioxidants and colorants, as already described above.

Further suitable auxiliaries are lubricants and glidants, for example magnesium stearate, stearic acid, talc, bentonite, disintegrants, for example starch or crosslinked polyvinylpyrrolidone, binders, for example starch, gelatin or linear polyvinylpyrrolidone, and also dry binders, for example microcrystalline cellulose.

The active substances can also be present in the form of a mixture preparation with synergists or with other active substances active against pathogenic endoparasites.

Particularly suitable for compositions containing permethrin are the formulations described in WO 02/087338.

They comprise: n-methylpyrrolidone in a content of 27.5 to 62.5 wt.%, preferably 35 to 50 wt.%, particularly preferably 40 to 45 wt.%.

The amount of antioxidant is from 0 to 0.5% by weight, preferably from 0.05 to 0.25% by weight, particularly preferably from 0.05 to 0.15% by weight. All conventional antioxidants can be considered, phenolic antioxidants such as butylhydroxytoluene, butylhydroxyanisole, tocopherol are preferred.

The content of the organic acid is 0 to 0.5% by weight, preferably 0.05 to 0.25% by weight, particularly preferably 0.05 to 0.15% by weight. All pharmaceutically acceptable organic acids, especially carboxylic acids, such as citric acid, tartaric acid, lactic acid, succinic acid, maleic acid are suitable. Particularly preferred organic acids are citric acid and maleic acid. Citric acid is most preferred. The amount of citric acid can vary in particular from 0.05 to 0.25, with amounts of 0.075 to 0.15% being particularly preferred.

The amount of co-solvent is from 2.5 to 10% by weight, preferably from 2.5 to 7.5% by weight, particularly preferably from 3.5 to 6.0% by weight.

Suitable cosolvents are organic solvents having a boiling point of > 80 ℃ and a flash point of > 75 ℃. Preferably, a co-solvent is used as a spreader. In this context, cosolvents which may be mentioned are prepared from higher-boiling aliphatic and aromatic alcohols, aliphatic polyethers, aliphatic and/or aromatic esters, cyclic and/or acyclic carbonates.

Co-solvents which can be used are preferably aliphatic acyclic or cyclic ethers or polyethers and fatty acid esters, especially triglycerides.

Mention may be made, by way of example, of ethers or polyethers, for example from diethylene glycol monoethyl ether, dipropylene glycol monomethyl ether, tetrahydrofurfuryl alcohol and tetrahydrofurfuryl ethoxylates, the last-mentioned two being particularly preferred; fatty acid esters and triglycerides, such as isopropyl myristate, Miglyol 810, Miglyol 812, Miglyol 818, Miglyol 829, Miglyol 840 and Miglyol 8810 (defined in terms of Miglyol, see, e.g., H.P. Fiedler Lexikon der Hilfsstuff fur Pharmazie, Kosmetik undangrenzende Gebiete, 1008-.

The compositions modified with the above-mentioned co-solvents are distinguished by very good resistance to the skin and eyes, good biological activity and superior low temperature stability properties in conventional single dose application tubes.

In addition to the above ingredients, the compositions of the present invention may contain other conventional pharmaceutically acceptable adjuvants. Examples which may be mentioned are spreaders and surfactants.

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 dimethylsiloxanes, and additionally their copolymers and terpolymers with ethylene oxide and propylene oxide, and formalin, fatty acid esters, triglycerides, fatty alcohols.

Surfactants which may be mentioned are: nonionic surfactants such as polyethoxylated castor oil, polyethoxylated sorbitan monooleate, sorbitan monostearate, glyceryl monostearate, polyoxyethyl stearate, alkylphenyl polyglycol ethers;

amphoteric surfactants such as disodium N-lauryl- β -iminodipropionate or lecithin;

anionic surfactants such as sodium lauryl sulfate, fatty alcohol sulfate, mono/dialkyl polyglycol ether orthophosphate monoethanol amine salt;

cationic surfactants such as cetyltrimethylammonium chloride.

The compositions used in the present invention can be prepared by conventional methods, for example by mixing the active substance with the other ingredients, with stirring, and making a solution. The solution may be filtered if desired. It can be encased in, for example, plastic tubing.

The formulations described in WO 02/087338 are preferably administered in a volume of 0.075 to 0.25ml/1.0kg [ body weight of the animal to be treated ], preferably 0.1 to 0.15ml/1.0kg [ body weight of the animal to be treated ].

They are particularly suitable for packaging and distribution in containers which are critical for storage, for example polypropylene polymer tubes with a wall thickness of 300-.

In addition, the compositions are very skin friendly, have low toxicity, and are environmentally friendly due to their biodegradability.

Examples

Example 1

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

10g Imidacloprid (1- [ 6-chloro-3-pyridyl ] methyl ] -N-nitro-2-imidazolidine

Imine) from Bayer AG company

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT (butylhydroxytoluene)

Example 2

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

10g Imidacloprid

40.8g N-Methylpyrrolidone

4.0g of water

0.1g citric acid

0.1g BHT

Example 3

The uniform spot coating liquid consists of the following components

45g of etofenprox containing 40% of the cis and 60% of the trans isomer

10g of Ti 435, Chlorothianidine, from Takeda AG

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 4

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

10g Diacloden (thiamethoxam) from Syngenta AG

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 5

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

10g of spinosyn (8.5g of spinosyn A; 1.5g of spinosyn D) were obtained from Dow

Agrosciences Inc

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 6

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

20g of nithiazine from Shell AG

34.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 7

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

10g of Ti 435, Chlorothianidine, from Takeda AG

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl alcohol

Example 8

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

10g Diacloden (thiamethoxam) from Syngenta AG

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 9

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

10g of spinosyn (8.5g of spinosyn A; 1.5g of spinosyn D), derived from

Dow Agrosciences Co Ltd

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 10

The uniform spot coating liquid consists of the following components

45g permethrin, containing 40% of the cis and 60% of the trans isomer

20g of nithiazine from Shell AG

29.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 11

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g Imidacloprid

79.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT (butylhydroxytoluene)

Example 12

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g Imidacloprid

75.8g N-Methylpyrrolidone

4.0g of water

0.1g citric acid

0.1g BHT

Example 13

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g of Ti 435, Chlorothianidine, from Takeda AG

79.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 14

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g Diacloden (thiamethoxam) from Syngenta AG

79.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 15

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g of spinosad 105(8.5g of spinosad A; 1.5g of spinosad D) to obtain

From Dow Agrosciences Inc

79.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 16

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

20g of nithiazine from Shell AG

69.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 17

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g of Ti 435, Chlorothianidine, from Takeda AG

74.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl alcohol

Example 18

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g Diacloden (thiamethoxam) from Syngenta AG

74.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 19

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

10g of spinosad 105(8.5g of spinosad A; 1.5g of spinosad D) to obtain

From Dow Agrosciences Inc

74.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 20

The uniform spot coating liquid consists of the following components

10g of alpha-cypermethrin

20g of nithiazine from Shell AG

64.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 21

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g Imidacloprid

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT (butylhydroxytoluene)

Example 22

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g Imidacloprid

40.8g N-Methylpyrrolidone

4.0g of water

0.1g citric acid

0.1g BHT

Example 23

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g of Ti 435, Chlorothianidine, from Takeda AG

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 24

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g Diacloden (thiamethoxam) from Syngenta AG

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 25

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g of spinosad 105(8.5g of spinosad A; 1.5g of spinosad D) to obtain

From Dow Agrosciences Inc

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 26

The uniform spot coating liquid consists of the following components

45g Ethofenprox

20g of nithiazine from Shell AG

34.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 27

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g of Ti 435, Chlorothianidine, from Takeda AG

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl alcohol

Example 28

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g Diacloden (thiamethoxam) from Syngenta AG

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 29

The uniform spot coating liquid consists of the following components

45g Ethofenprox

10g of spinosyn (8.5g of spinosyn A; 1.5g of spinosyn D), derived from

Dow Agrosciences Co Ltd

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 30

The uniform spot coating liquid consists of the following components

45g Ethofenprox

20g of nithiazine from Shell AG

29.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 31

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g Imidacloprid

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT (butylhydroxytoluene)

Example 32

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g Imidacloprid

40.8g N-Methylpyrrolidone

4.0g of water

0.1g citric acid

0.1g BHT

Example 33

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g of Ti 435, Chlorothianidine, from Takeda AG

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 34

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g Diacloden (thiamethoxam) from Syngenta AG

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 35

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g of spinosad 105(8.5g of spinosad A; 1.5g of spinosad D) to obtain

From Dow Agrosciences Inc

44.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 36

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

20g of nithiazine from Shell AG

34.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

Example 37

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g of Ti 435, Chlorothianidine, from Takeda AG

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl alcohol

Example 38

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g Diacloden (thiamethoxam) from Syngenta AG

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 39

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

10g of spinosad 105(8.5g of spinosyn A; 1.5g of spinosyn D) were obtained from

Dow Agrosciences Co Ltd

39.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

Example 40

The uniform spot coating liquid consists of the following components

45g of pyrethrum extract

20g of nithiazine from Shell AG

29.8g N-Methylpyrrolidone

0.1g citric acid

0.1g BHT

5.0g tetrahydrofurfuryl ethoxylate

A. Ticks were repelled by bioassay of moving targets. Compared with the prior art

Biometric determination of moving objects by the method of Dautel et al (1999)

Briefly, the following steps are carried out: each tick individual approached a warmed, slowly rotating, vertical cylinder via a horizontally mounted glass rod. Ticks are attracted by heating the cylinder to migrate to the attachment point of the rotating cylinder. If a repellent is used at the attachment point, the repellent effect may be measured by i) a reduction in the number of ticks based on migrating toward the cylinder, or ii) a reduction in the number of ticks migrating through the attachment point, or iii) an increase in the number of ticks prematurely dislodged from the attachment point. Untreated control cylinders were used for comparison. Both contact and remote acting repellents can be measured.

The test conditions are as follows:

each test was performed with 30 ticks. All ticks were tested individually one after the other in the same equipment. For each test series, a control test was performed with pure solvent without repellent to determine the basic behavior of the ticks. The critical behavior for the test was that at least 70% of the ticks migrated into the cylinder. A separate test cylinder was used for each test product. After each test series, all the devices used were carefully cleaned.

For the tests of hard Periploca ricini (Ixodes ricinus) and Rhipicephalus sanguineus (Rhipicephalus sanguineus), the following conditions were established.

Hard ticks perforatum:

standard cylinders and attachment zones were used (Dautel et al (1999)). The attachment zone is positioned 1-3mm above the surface of the cylinder. The glass rod with a diameter of 2mm is at a distance of 1 to a maximum of 1.5mm from the attachment zone.

The rotation speed of the cylinder is 3.9-4.1 s/rev, corresponding to 7.66-8.05cm/s with respect to the ticks. The surface temperature of the attachment zone was 34.6-35.5 ℃. Room temperature and atmospheric humidity are 19.1-22.3 ℃ and 43.4-78.1% r.h.

Rhipicephalus sanguineus:

adult rhipicephalus sanguineus moves more rapidly than the nymphs of scleroderma ricini. The attachment area on the cylinder must therefore be enlarged to ensure a contact time of at least 10 seconds, which is greater for more rapidly moving varieties. So that the entire cylinder serves here as an attachment point. In view of the poor attachment of ticks to the filter paper, the cylinder was covered with Molton cloth. The Molton is at a distance of 1-3mm from the glass rod (4mm diameter) so that ticks can migrate from the glass rod into the cylinder at any one time.

The rotation speed of the cylinder is 5.6-6.0 s/rev, corresponding to 5.23-5.61cm/s with respect to the ticks. The surface temperature of the attachment zone is 35-36 ℃. Room temperature and atmospheric humidity are 19.4-23.5 ℃ and 59.1-79.5% r.h.

Use of test substances

In all experiments, acetone was used as a solvent and for dilution. The test is run 1-2 hours before the start of the experiment, allowing sufficient time for the solvent to evaporate.

The active substance was applied to the filter paper using a disposable dropper. Evenly distributed over a large portion of the surface of the Molton cloth under nitrogen with the aid of a sparger. The exact volume used was determined by subsequent weighing.

MO bioassay

The tick alone was used in the test, actively climbed towards the top edge in a glass test tube, and rapidly transferred to badger brush (0 or 1) for transfer of the tick. The ticks were placed on the glass rod 1.5cm (Trimerus gracilis) or 2.5-4cm (Rhipicephalus sanguineus) from the end of the rod, with their heads facing the cylinder. The time of the experiment was timed to start with the tick crossing the mark 1cm (hard tick) or 2cm (rhipicephalus sanguineus) on the glass rod. Ticks dropped from the brush pen or from the glass rod before reaching the mark were not included in the measurement range.

The following time periods are recorded by the stop table:

time from crossing the mark to reaching the end of the glass rod

Time from arrival at the end of the glass rod to migration to the cylinder

The time for the tick to stay on the filter paper or the Molton cloth until it has scattered or left the treatment area

A maximum of 120 seconds is observed for each of the time periods described above. After 2 minutes, the ticks were removed and the time period was evaluated as 120 seconds.

The total repellency effect was calculated relative to the control by adding all ticks that did not migrate to the cylinder, and did not leave the attachment zone. All of the ticks were considered repelled. The repellent effect was calculated according to the following formula:

R＝100-pt/pc*100，

where R is the repellent effect, pt is the percentage of ticks that were not repelled, and pc is the percentage of control ticks that were not repelled.

Results of repellent experiments with Rhipicephalus sanguineus tick-comparison with the prior art (Exspot)From Schering-Plough company)

TABLE 1a: rhipicephalus sanguineus: residence time on the treated cylinder surface [ s ]]。

1 value refers to the amount of imidacloprid and 2 value is the amount of permethrin

Surprisingly, the formulation of example 1 was compared to a standard (Exspot containing permethrin only as active substance)) Compared with the prior art, the repellent has obvious more remarkable repellent effect. In example 1, the rate of tick migration onto the cylinder is more rapid than the standard. In this example, the repellent effect was improved by an average of 4 times as compared with the standard sample.

TABLE 1b: rhipicephalus sanguineus: time required for tick to migrate from glass rod end to cylinder [ s ]].

1 value refers to the amount of imidacloprid and 2 value is the amount of permethrin

Another indication of the enhanced repellency effect is the delay in migration from the glass rod to the cylinder. In addition, it was demonstrated that the ticks in example 1 averaged three times longer than the standard. The standards herein are within the control range.

TABLE 2: rhipicephalus sanguineus: determination of the MO bioassay: formulations of the invention and Prior Art (Exspot)From Schering-Plough company) and controls

It was confirmed that the preparation of example 1 of the present invention has a repellent effect of 100% in the corresponding dose range, compared to various controls, using the uniformly distributed preparation by topical application. Surprisingly, the known commercial products do not repel all ticks under the same conditions.

Results of repellent experiments with hard ticks Periploca Ricini-comparison with the prior art (Exspot)From Schering-Plough company)

TABLE 3: hard ticks perforatum: determination of the MO bioassay: formulations of the invention and Prior Art (Exspot)From Schering-Plough company) and controls

Surprisingly, the examples of the invention show that a significantly improved repellent effect is obtained even in the case of hard ticks, while ExspotHas no effective repellent effect on hard ticks. Especially at low doses on body surfaces further from the point of application and on all animals from the start of treatment to the end of the duration of activity, the examples of the invention showed the same repellency as the high dose in this range, whereas the curve of the repellent effect of the prior art has been reduced to y 6.

The formulations of the invention therefore show a significantly improved repellent effect compared to the prior art at the same dosage, by virtue of the probability of migration to the surface, the residence time on the surface and the effect of the lower dosage being important parameters.

B. Mortality of ticks was bioassayed by moving targets.

Method

A summary of the determination of the final mortality after a short time in the bioassay of moving targets: after exposure, the ticks were individually transferred to Eppendorf tubes with a puncture cap and stored at 90% r.h. and 20 ℃. After 24 hours and 7 days, the ticks were observed by means of a stereoscope. Ticks that are able to move in coordination are considered to be alive. Only slightly moving or non-walking ticks of the tarsal or oral parts are considered moribund. CO 2₂Ticks that remained immobile after stimulation or intense light pulses were considered dead.

The aim of this study was to reveal the relationship between exposure time (residence time on the treated cylinder surface in the MO bioassay) and mortality at different concentrations of different formulations, in comparison with the prior art.

Table 1:rhipicephalus sanguineus: mortality (d7) and contact time for different concentrations of the test formulation in the MO bioassay.

Table 2:hard ticks perforatum: mortality (d7) and contact time for different concentrations of the test formulation in the MO bioassay.

1 value refers to the amount of imidacloprid and 2 value is the amount of permethrin

The elimination rate of the Rhipicephalus sanguineus and the hard Periploca gracilis after contacting the surface of the cylinder is high. The average contact time required for this higher mortality is shorter for the formulations of the present invention than in the prior art.

Thus, the formulation of the present invention provides an additional protective effect, the repelled ticks being killed after a short contact time of significantly less than 1 minute, such that other hosts are no longer infested with repelled ticks.

Claims (6)

1. Use of a pyrethroid or pyrethrin in combination with a nicotinic agonist for repelling an arthropod on an animal.

2. Use according to claim 1, wherein the pyrethroid is selected from:

pyrethroid type I.I

Type II pyrethroids

Non-ester pyrethroids

And IV, natural pyrethrin.

3. The use of claim 1, wherein the nicotinic agonist is selected from the group consisting of:

neonicotinoids V

Nithiazine VI

Spinosad, vii.

4. Use according to claim 1 for repelling ticks, fleas, mosquitoes and/or flies on warm-blooded animals.

5. A method of repelling arthropods on animals in which a pyrethroid or pyrethrin is applied topically to the animal in combination with a nicotinic agonist.

6. The method of claim 5 wherein the animal is a warm-blooded animal.