DK201170008A

DK201170008A - Insecticide combination against fleas in mammals, especially cats and dogs

Info

Publication number: DK201170008A
Application number: DKPA201170008A
Authority: DK
Inventors: Philippe Jeannin
Original assignee: Merial Sas
Priority date: 1997-11-27
Filing date: 2011-01-07
Publication date: 2011-01-07
Also published as: DK177441B1

Abstract

Fremgangsmåde og præparat især til bekæmpelse af lopper på små pattedyr karakteriseret ved, at præparatet på den ene side omfatter mindst et insekticid af l-N-arylpyrazoltypen, især fipronil, og på den anden side mindst én forbindelse af den insektvækstregulerende (IGR) type i doser og forhold, som er parasiticidt effektive mod lopper, i en flydende vehikel, som er acceptabel for dyret og bekvemt til lokal anbringelse på huden, fortrinsvis lokaliseret til et lille overfladeareal.A method and composition in particular for controlling fleas on small mammals characterized in that the composition comprises at least one insecticide of the 1N-arylpyrazole type, especially fipronil, and on the other hand at least one compound of the insect growth regulating (IGR) type in doses and conditions which are parasitically effective against fleas in a liquid vehicle acceptable to the animal and convenient for local application to the skin, preferably located to a small surface area.

Description

Patentkrav 1. Præparat til langvarig beskyttelse mod lopper hos små pattedyr og især hos katte og hunde, kendetegnet ved, at det på den ene side omfatter mindst én forbindelse (Ά) tilhørende formlen (I) hvori:Patent claim 1. Composition for long-term protection against fleas in small mammals and especially in cats and dogs, characterized in that it comprises, on the one hand, at least one compound (Ά) of formula (I) wherein:

Ri er CN eller methyl eller et halogenatom; R2 er S(0) nR3 eller 4,5-dicyanoimidazol-2-yl eller halogenal kyl; R3 er alkyl eller halogenalkyl; R4 betegner et hydrogen- eller halogenatom; eller en NR5R6-, S(0)mR7-, C(0)R7-, C(0)0-R 7-, alkyl-, halogenalkyl- eller ORg-gruppe eller en -N=C(Rg) (R10) -gruppe; R5 og R6 indbyrdes uafhængigt betegner et hydrogenatom eller en alkyl-, halogenalkyl-, C(0)alkyl-, alkoxycarbonyl-eller S (0) r-CF3-gruppe; eller R5 og R6 sammen kan udgøre en divalent alkylgruppe, som kan være afbrudt af ét eller to divalente heteroatomer såsom oxygen eller svovl; R7 betegner en alkyl- eller halogenalkylgruppe;R 1 is CN or methyl or a halogen atom; R 2 is S (O) n R 3 or 4,5-dicyanoimidazol-2-yl or halogenoalkyl; R 3 is alkyl or haloalkyl; R4 represents a hydrogen or halogen atom; or an NR5R6, S (O) mR7-, C (O) R7-, C (O) O-R7, alkyl, haloalkyl or ORg group or an -N = C (Rg) (R10) -group; R5 and R6 independently represent a hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxycarbonyl or S (O) r-CF3 group; or R5 and R6 together may form a divalent alkyl group which may be interrupted by one or two divalent heteroatoms such as oxygen or sulfur; R7 represents an alkyl or haloalkyl group;

Rs betegner en alkyl- eller halogenalkylgruppe eller et hydrogenatom; R9 betegner en alkylgruppe eller et hydrogenatom;R 5 represents an alkyl or haloalkyl group or a hydrogen atom; R9 represents an alkyl group or a hydrogen atom;

Rio betegner en phenyl- eller heteroarylgruppe, som eventuelt er substitueret med ét eller flere halogenatomer, eller grupper såsom -OH, -O-alkyl, -S-alkyl, cyano eller alkyl;R 10 represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms, or groups such as -OH, -O-alkyl, -S-alkyl, cyano or alkyl;

Ru og R12 indbyrdes uafhængigt hver især betegner et hydrogen- eller halogenatom eller eventuelt CN eller N02; R13 betegner et halogenatom eller en halogenalkyl-, halogenalkoxy-, S(0)qCF3- eller SF5-gruppe; m, n, q og r indbyrdes uafhængigt hver især er et helt tal lig med 0, 1 eller 2; X betegner et trivalent nitrogenatom eller en C-Ri2-gruppe, hvor carbonatomets andre tre valensstillinger udgør en del af den aromatiske ring; med det forbehold, at når Ri er methyl, er R3 enten halogenalkyl, R4 er NH2, Ru er Cl, Ri3 er CF3 og X er N; eller R2 er 4,5-dicyanoimidazol-2-yl, R4 er Cl, Ru er Cl, R13 er CF3 og X er =C-C1; og på den anden side mindst én ovicid forbindelse (B) af den insektvækstregulatoriske (IGR) type i et flydende vehikel, som er acceptabelt for dyret og egnet til lokal administration på huden. 2. Præparat ifølge krav 1, kendetegnet ved, at forbindelsen med formlen (I) er således, at:Ru and R 12 independently each represent a hydrogen or halogen atom or optionally CN or NO 2; R 13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SF5 group; m, n, q and r are each independently an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a C-Ri 2 group, wherein the other three valence positions of the carbon atom form part of the aromatic ring; with the proviso that when R 1 is methyl, R 3 is either haloalkyl, R 4 is NH 2, Ru is Cl, Ri 3 is CF 3 and X is N; or R2 is 4,5-dicyanoimidazol-2-yl, R4 is Cl, Ru is Cl, R13 is CF3 and X is = C-C1; and, on the other hand, at least one ovicidal compound (B) of the insect growth regulatory (IGR) type in a liquid vehicle acceptable to the animal and suitable for topical administration to the skin. Composition according to claim 1, characterized in that the compound of formula (I) is such that:

Ri er CN eller methyl; R2 er S (0) nR3; R3 er alkyl eller halogenalkyl; R4 betegner et hydrogen- eller halogenatom; eller en NR5R6-, S (0)mR7-, C(0)R7-, alkyl-, halogenalkyl- eller OR8-gruppe eller en -N=C(Rg) (R10) -gruppe; R5 og R6 indbyrdes uafhængigt betegner et hydrogenatom eller en alkyl-, halogenalkyl-, C(0)alkyl- eller S(0)r-CF3-gruppe; eller R5 og R6 sammen kan udgøre en divalent alky-lengruppe, som kan være afbrudt af ét eller to divalente heteroatomer såsom oxygen eller svovl; R7 betegner en alkyl- eller halogenalkylgruppe;R 1 is CN or methyl; R 2 is S (O) n R 3; R 3 is alkyl or haloalkyl; R4 represents a hydrogen or halogen atom; or an NR5 R6, S (O) mR7, C (O) R7, alkyl, haloalkyl or OR8 group or an -N = C (Rg) (R10) group; R5 and R6 independently represent a hydrogen atom or an alkyl, haloalkyl, C (O) alkyl or S (O) r-CF3 group; or R5 and R6 together may form a divalent alkylene group which may be interrupted by one or two divalent heteroatoms such as oxygen or sulfur; R7 represents an alkyl or haloalkyl group;

Rg betegner en alkyl- eller halogenalkylgruppe eller et hydrogenatom; R9 betegner en alkylgruppe eller et hydrogenatom;Rg represents an alkyl or haloalkyl group or a hydrogen atom; R9 represents an alkyl group or a hydrogen atom;

Rio betegner en phenyl- eller heteroarylgruppe, der eventuelt er substitueret med ét eller flere halogenatomer eller grupper såsom -OH, -0-alkyl, -S-alkyl, cyano eller alkyl;R 10 represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or groups such as -OH, -O-alkyl, -S-alkyl, cyano or alkyl;

Ru og R12 indbyrdes uafhængigt hver især betegner et hydrogen- eller halogenatom; R13 betegner et halogenatom eller en halogenalkyl-, halogenalkoxy-, S(0)qCF3- eller SF5-gruppe; m, n, q og r indbyrdes uafhængigt hver især er et helt tal lig med 0, 1 eller 2; X betegner et trivalent nitrogenatom eller en C-Ri2-gruppe, hvor carbonatomets andre tre valensstillinger udgør en del af den aromatiske ring; med det forbehold, at når Ri er methyl, så er R3 halogen-alkyl, R4 er NH2, Ru er Cl, Ri3 er CF3 og X er N. 3. Præparat ifølge krav 1 eller 2, kendetegnet ved, at forbindelsen med formlen (I) er således, at Ri er CN. 4. Præparat ifølge et af kravene 1-3, kendetegne t ved, at forbindelsen med formlen (I) er således, at Ri3 er halogenalkyl, fortrinsvis CF3. 5. Præparat ifølge et af kravene 1-4, kendetegne t ved, at forbindelsen med formlen (I) er således, at R2 er S(0)nR3, hvor n fortrinsvis er 1, R3 fortrinsvis er CF3 eller alkyl og især methyl eller ethyl, eller n er 0 og R3 fortrinsvis er CF3. 6. Præparat ifølge et af kravene 1-5, kendetegne t ved, at forbindelsen med formlen (I) er således, at X er C-Ri2, hvor Ri2 er et halogenatom. 7. Præparat ifølge et af kravene 1-6, kendetegne t ved, at forbindelsen med formlen (I) er således, at Ri er CN, R3 er halogenalkyl, R4 er NH2, Ru og Ri2 indbyrdes uafhængigt hver især er et halogenatom og/eller Ri3 halogenalkyl. 8. Præparat ifølge et hvilket som helst af kravene 1-7, kendetegnet ved, at forbindelsen med formlen (I) er: 1- [2, 6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazol 9. Præparat ifølge et hvilket som helst af kravene 1-7, hvor forbindelsen med formlen (I) er en af følgende forbindelser: 1: 1- [2, 6-Cl2-4-CF3-phenyl] -3-CN-4- [S-CF3] -5-NH2-pyrazol; 2 : 1- [2, 6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-C2H5] -5-NH2-pyrazol. 10. Præparat ifølge et af kravene 1-9, kendetegne t ved, at forbindelsen (B) er en forbindelse som efterligner juvenilhormoner, især: azadirachtin diofenolan fenoxycarb hydroprene kinoprene methoprene pyriproxyfen tetrahydroazadirachtin og 4-chlor-2-(2-chlor-2-methylpropyl)-5-(6-iod-3- pyridylmethoxy)pyridizin-3(2H) -on 11. Præparat ifølge et af kravene 1-9, kendetegne t ved, at forbindelsen (B) er en chitin-synteseinhibito-rer, især: chorfluazuron cyromazine diflubenzuron fluazuron flucycloxuron flufenoxuron hexaflumuron lufenuron tebufenozide teflubenzuron triflumuron 1-(2,6-difluorbenzoyl)-3-(2-fluor-4-(trifluormethyl)phenyl-urinstof, -(2,β-difluorbenzo-yl)-3-(2-fluor-4-(1,1,2,2- tetrafluorethoxy)-phenylurinstof og 1-(2,6-difluorbenzoyl) -3-(2-fluor-4-trifluormethyl)phenylurinstof. 12. Prparat ifølge et af kravene 1-9. kendetegnet ved, at forbindelse (B) er novaluron. 13. Præparat ifølge et af kravene 10-12, kendetegn e t ved, at forbindelsen af IGR-type er valgt blandt methoprener, pyriproxyfener, lufenuron, hydroprene, cyroma-zine og 1-(2,6-difluorbenzoyl)-3-(2-fluor-4- (trifluormethyl)phenylurinstof. 14. Præparat ifølge krav 13, kendetegnet ved, at forbindelsen af IGR-type er pyriproxyfene. 15. Præparat ifølge krav 13, kendetegnet ved, at forbindelsen af IGR-type er en methoprene. 16. Præparat ifølge et af kravene 1-15, kendetegne t ved, at forholdene på vægtbasis mellem forbindelser (A) med formlen (I), og forbindelser af type (B) er mellem 80/20 og 20/80. 17. Præparat ifølge et af kravene 1-16, kendetegne t ved, at det flydende vehikel og koncentrationen af forbindelserne (A) og (B) er indrettet til punktuel administrering af typen "spot-on" ved anbringelse på huden. 18. Præparat ifølge et hvilket som helst af kravene 1-16, kendetegnet ved, at det flydende vehikel og koncentrationen af forbindelserne (A) og (B) er indrettet til lokal administrering af "pour-on"-typen ved deponering på huden. 19. Præparat ifølge krav 17, kendetegnet ved, at det flydende vehikel og koncentrationen af forbindelserne (A) og (B) er indrettet til lokal administrering i en zone med et overfladeareal på mindre end 10 cm2, især mellem 5 og 10 cm , og specielt i 2 punkter og fortrinsvis lokaliseret mellem dyrets skuldre. 20. Præparat ifølge et af kravene 1-19, kendetegne t ved, at det indeholder en dosis fra 0,1 til 40 mg/kg af forbindelse (A) og fra 0,1 til 40 mg/kg af forbindelse (B). 21. Præparat ifølge krav 20, kendetegnet ved, at det indeholder en dosis fra 1 til 20 mg/kg, især fra 2 til 10 mg/kg af forbindelse (A) , og fra 1 til 30 mg/kg, især fra 2 til 20 mg/kg af forbindelse (B). 22. Præparat ifølge et hvilket som helst af kravene 1-21, kendetegnet ved, at det også omfatter en krystallisationsinhibitor (b), som fortrinsvis er til stede i et forhold fra 1 til 20% (vægt/vol) og fortrinsvis 5 til 15%. 23. Præparat ifølge krav 22, kendetegnet ved, at krystallisationsinhibitoren (b) er valgt blandt: polyvinylpyrrolidon, polyvinylalkoholer, copolymerer af vinylacetat og vinylpyrrolidon, polyethylenglycoler, benzylalkohol, mannitol, glycerol, sorbitol, poly-oxyethylenerede sorbitanestere; lecithin, natriumcarboxymethylcellulose, acrylderivater såsom methacrylater og lignende, anioniske tensider såsom alkalimetalstearater, især natrium-, kalium- eller ammoniumstearat; calciumstearat; triethanolaminstearat; natriumabietat; alkylsulfater, især natriumlaurylsulfat og natriumcetylsulfat; natriumdodecyIbenzensulfonat, natriumdioctylsulfosuccinat; fedtsyrer, især de der er afledt af kokosolie, kationiske tensider såsom vandopløselige, kvaternære ammoniumsalte med formlen N+R'R''R'''R'''',Y", hvori grupperne R er eventuelt hydroxylerede carbonhydrid-grupper, og Y~ er en anion af en stærk syre såsom halogenid-, sulfat- og sulfonat-anioner; cetyltrimethylammoniumbromid er blandt de kationiske tensider, der kan anvendes, aminsalte med formlen N+R'R''R''', hvori grupperne R er eventuelt hydroxylerede carbonhydridgrupper; octadecyl-amin-hydrochlorid er blandt de kationiske tensider, der kan anvendes, ikke-ioniske tensider såsom eventuelt polyoxyethylenerede sorbitanestere især polysorbat 80, polyoxyethylenerede alkylethere; polyethylenglycolstearat, poly-oxyethylenerede derivater af ricinusolie, polyglycerolestere, polyoxyethylenerede, fede alkoholer, polyoxyethylenerede fedtsyrer, copolymerer af ethylenoxid og propylenoxid, amfotere tensider såsom substituerede laurylforbindelser af betain, eller fortrinsvis en blanding af mindst to af disse krystallisationsinhibitorer. 24. Præparat ifølge et hvilket som helst af kravene 22 og 23, kendetegnet ved, at det omfatter et krystallisationsinhibitorpar dannet af kombinationen af et filmdannende middel af polymertype og et tensid, især i nærliggende eller identiske mængder inden for grænsen af de totale mængder af krystallisationsinhibitor. 25. Præparat ifølge krav 24, kendetegnet ved, at det filmdannende middel er valgt blandt: de forskellige polyvinylpyrrolidonkvaliteter, polyvinylalkoholer, og copolymerer af vinylacetat og vinylpyrrolidon og ved at tensidet er valgt blandt ikke-ioniske tensider, fortrinsvis polyoxyethylenerede sorbitanestere, især de forskellige polysorbatkvaliteter. 26. Præparat ifølge et hvilket som helst af kravene 1-25, kendetegnet ved, at det omfatter et organisk opløsningsmiddel (c) med en dielektrisk konstant på mellem 10 og 35, fortrinsvis 20 og 30, hvis indhold i det samlede præparat fortrinsvis udgør forskellen til 100% af præparatet. 27. Præparat ifølge krav 26, kendetegnet ved, at det organiske opløsningsmiddel (c) er valgt blandt acetone, acetonitril, benzylalkohol, butyldiglycol, dimethylacet-amid, dimethylformamid, dipropylenglycol-n-butylether, ethanol, isopropanol, methanol, ethylenglycol- monoethylether, ethylenglycol-monomethylether, monomethylacet-amid, dipropylenglycol-monomethylether, flydende polyoxyethylenglycoler, propylenglycol, 2-pyrrolidon, især N-methylpyrrolidon, diethylenglycol-monoethylether, ethylenglycol, diethylphthalat, eller en blanding af mindst to af disse opløsninger. 28. Præparat ifølge et hvilket som helst af kravene 26 og 27, kendetegnet ved, at det også omfatter et organisk coopløsningsmiddel (d) med et kogepunkt på under 100°C, fortrinsvis under 80°C, og med en dielektricitetskonstant på mellem 10 og 40, fortrinsvis mellem 20 og 30, hvilket coopløsningsmiddel er blandbart med vand og/eller med opløsningsmidlet (c), idet dette coopløsningsmiddel især er til stede i et coopløsningsmiddel(d)/opløsningsmiddel(c)-vægtforhold (vægt/vægt) på mellem 1/15 og 1/2. 29. Præparat ifølge krav 28, kendetegnet ved, at coopløsningsmidlet (d) er valgt blandt absolut ethanol, isopropanol og methanol. 30. Præparat ifølge et af kravene 1-29, kendetegne t ved, at det er fremstillet i form af et sæt, som i samme pakning separat kombinerer mindst én beholder indeholdende en forbindelse (A) og mindst én beholder for forbindelse (B), og en meddelelse, der specificerer, at beholderne skal anvendes skiftevis med et interval på især én måned. 31. Præparat ifølge et hvilket som helst af kravene Ι-ΙΟ, kendetegnet ved, at det giver beskyttelse i 2 til 3 måneder. 32. Præparat ifølge et hvilket som helst af kravene 17- 19 og 22-31, kendeteg-net ved, at det omfatter 5-10% 1- [2,6-Cl2-4-CF3-phenyl]-3-CN-4-[SO-CF3]-5- NH2-pyrazol og 5-20% pyriproxyfene. 33. Præparat ifølge et hvilket som helst af kravene 17-19 og 22-31, kendeteg-net ved, at det omfatter 10% 1- [2, 6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazol og 30% methoprene. 34. Anvendelse af på den ene side mindst én forbindelse (A) tilhørende til formlen (I),Ru and R 12 independently each represent a hydrogen or halogen atom; R 13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SF5 group; m, n, q and r are each independently an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a C-Ri 2 group, wherein the other three valence positions of the carbon atom form part of the aromatic ring; with the proviso that when R 1 is methyl, then R 3 is halo-alkyl, R 4 is NH 2, Ru is Cl, Ri 3 is CF 3 and X is N. 3. The composition of claim 1 or 2, characterized in that the compound of formula ( I) is such that R 1 is CN. Composition according to any one of claims 1-3, characterized in that the compound of formula (I) is such that R 1 is haloalkyl, preferably CF 3. Composition according to one of claims 1-4, characterized in that the compound of formula (I) is such that R 2 is S (O) n R 3, where n is preferably 1, R 3 is preferably CF 3 or alkyl and especially methyl or ethyl or n is 0 and R 3 is preferably CF 3. Composition according to one of Claims 1 to 5, characterized in that the compound of formula (I) is such that X is C-Ri 2, where Ri 2 is a halogen atom. Composition according to one of claims 1-6, characterized in that the compound of formula (I) is such that R1 is CN, R3 is haloalkyl, R4 is NH2, Ru and Ri2 are each independently a halogen atom and / or R13 is haloalkyl. Composition according to any one of claims 1-7, characterized in that the compound of formula (I) is: 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO -CF3] -5-NH2-pyrazole 9. A composition according to any one of claims 1-7, wherein the compound of formula (I) is one of the following compounds: 1: 1- [2,6-Cl2-4-CF3 -phenyl] -3-CN-4- [S-CF3] -5-NH2-pyrazole; 2: 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-C2H5] -5-NH2-pyrazole. Composition according to one of claims 1-9, characterized in that the compound (B) is a compound which mimics juvenile hormones, in particular: azadirachtin diophenolan phenoxycarb hydroprene quinoprene methoprene pyriproxyphen tetrahydroazadirachtin and 4-chloro-2- (2-chloro-2 -methylpropyl) -5- (6-iodo-3-pyridylmethoxy) pyridizin-3 (2H) -one 11. A composition according to any one of claims 1-9, characterized in that the compound (B) is a chitin synthesis inhibitor. , in particular: chorfluazuron cyromazine diflubenzuron fluazuron flucycloxuron flufenoxuron hexaflumuron lufenuron tebufenozide teflubenzuron triflumuron 1- (2,6-difluorobenzoyl) -3- (2-fluoro-4- (trifluoromethyl) -phenyl-urea, - (- -3- (2-fluoro-4- (1,1,2,2-tetrafluoroethoxy) phenylurea and 1- (2,6-difluorobenzoyl) -3- (2-fluoro-4-trifluoromethyl) phenylurea. A composition according to any one of claims 1-9, characterized in that compound (B) is novaluron 13. A composition according to any one of claims 10-12, characterized in that the IGR-type compound is selected from the group consisting of thoprenes, pyriproxyphenes, lufenuron, hydroprene, cyromazine and 1- (2,6-difluorobenzoyl) -3- (2-fluoro-4- (trifluoromethyl) phenylurea). Composition according to claim 13, characterized in that the IGR-type compound is the pyriproxyphene. Composition according to claim 13, characterized in that the IGR-type compound is a methoprene. Composition according to one of claims 1 to 15, characterized in that the weight-based ratio between compounds (A) of formula (I) and type (B) compounds is between 80/20 and 20/80. Composition according to one of claims 1 to 16, characterized in that the liquid vehicle and the concentration of compounds (A) and (B) are adapted for punctual "spot-on" administration by application to the skin. Preparation according to any one of claims 1-16, characterized in that the liquid vehicle and the concentration of compounds (A) and (B) are adapted for local administration of the "pour-on" type when deposited on the skin. A composition according to claim 17, characterized in that the liquid vehicle and the concentration of compounds (A) and (B) are adapted for local administration in a zone with a surface area of less than 10 cm 2, especially between 5 and 10 cm, and especially in 2 points and preferably located between the shoulders of the animal. Composition according to any one of claims 1-19, characterized in that it contains a dose of 0.1 to 40 mg / kg of compound (A) and from 0.1 to 40 mg / kg of compound (B). Composition according to claim 20, characterized in that it contains a dose of from 1 to 20 mg / kg, in particular from 2 to 10 mg / kg of compound (A), and from 1 to 30 mg / kg, especially from 2 to 10 mg. 20 mg / kg of compound (B). Composition according to any one of claims 1-21, characterized in that it also comprises a crystallization inhibitor (b) which is preferably present in a ratio of 1 to 20% (w / v) and preferably 5 to 15. %. Composition according to claim 22, characterized in that the crystallization inhibitor (b) is selected from: polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylene; lecithin, sodium carboxymethyl cellulose, acrylic derivatives such as methacrylates and the like, anionic surfactants such as alkali metal stearates, especially sodium, potassium or ammonium stearate; calcium stearate; triethanolamine; natriumabietat; alkyl sulfates, especially sodium lauryl sulfate and sodium cetyl sulfate; sodium dodecylbenzenesulfonate, sodium dioctylsulfosuccinate; fatty acids, especially those derived from coconut oil, cationic surfactants such as water-soluble quaternary ammonium salts of the formula N + R'R''R '' 'R' '' ', Y ", wherein the groups R are optionally hydroxylated hydrocarbon groups, and Y ~ is an anion of a strong acid such as halide, sulfate and sulfonate anions; octadecylamine hydrochloride, among the cationic surfactants that can be used, are nonionic surfactants such as optionally polyoxyethylene sorbitan esters, especially polysorbate 80, polyoxyethylene alkylated ethers; polyethylene glycol stearate, polyoxyethylene polyethylene, polyethylene polyoxyethylenated fatty acids, copolymers of ethylene oxide and propylene oxide, amphoteric surfactants such as substituted betaine lauryl compounds, or preferably a mixture of m set two of these crystallization inhibitors. Composition according to any one of claims 22 and 23, characterized in that it comprises a crystallization inhibitor pair formed by the combination of a polymer-type film-forming agent and a surfactant, especially in proximate or identical amounts within the limit of the total crystallization inhibitor amounts. . Composition according to claim 24, characterized in that the film-forming agent is selected from: the various polyvinylpyrrolidone grades, polyvinyl alcohols, and copolymers of vinyl acetate and vinylpyrrolidone and in that the surfactant is selected from nonionic surfactants, preferably polyoxyethylene sorbitan esters, especially the various polyvalent esters, . Composition according to any one of claims 1-25, characterized in that it comprises an organic solvent (c) having a dielectric constant of between 10 and 35, preferably 20 and 30, the content of which of the total composition preferably makes the difference. to 100% of the preparation. Composition according to claim 26, characterized in that the organic solvent (c) is selected from acetone, acetonitrile, benzyl alcohol, butyldiglycol, dimethylacetamide, dimethylformamide, dipropylene glycol-n-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethyl acetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, 2-pyrrolidone, especially N-methylpyrrolidone, diethylene glycol monoethyl ether, ethylene glycol, diethyl phthalate, or a mixture of at least two of these. Composition according to any of claims 26 and 27, characterized in that it also comprises an organic co-solvent (d) having a boiling point of less than 100 ° C, preferably below 80 ° C, and having a dielectric constant of between 10 and 40, preferably between 20 and 30, which co-solvent is miscible with water and / or with the solvent (c), said co-solvent being present in particular in a co-solvent (d) / solvent (c) weight ratio (w / w) of 1/15 and 1/2. Composition according to claim 28, characterized in that the co-solvent (d) is selected from absolute ethanol, isopropanol and methanol. Composition according to any one of claims 1-29, characterized in that it is made in the form of a set which separately combines in the same package at least one container containing a compound (A) and at least one container for compound (B). and a message specifying that the containers should be used alternately at intervals of one month in particular. Composition according to any one of claims Ι-ΙΟ, characterized in that it provides protection for 2 to 3 months. Composition according to any one of claims 17-19 and 22-31, characterized in that it comprises 5-10% 1- [2,6-Cl 2-4-CF 3 -phenyl] -3-CN 4- [SO-CF3] -5- NH2-pyrazole and 5-20% pyriproxyphenes. Composition according to any one of claims 17-19 and 22-31, characterized in that it comprises 10% 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole and 30% methoprene. Use of at least one compound (A) of formula (I), on the one hand,

hvoriin which

Ri er CN eller methyl eller et halogenatom; R2 er S(0)nR3 eller 4, 5-dicyanoimidazol-2-yl eller halogenal kyl ; R3 er alkyl eller halogenalkyl; R4 betegner et hydrogen- eller halogenatom; eller en NR5R6-, S(0)mR7-, C(0)R7-, C(0)0-R 7-, alkyl-, halogenalkyl- eller OR8--gruppe eller en -N=C (R9) (Ri0) -gruppe; R5 og R6 indbyrdes uafhængigt betegner et hydrogenatom eller en alkyl-, halogenalkyl-, C(0)alkyl-, alkoxycarbonyl-eller S (O) r-CF3-gruppe; eller R5 og R6 sammen kan udgøre en divalent alkylgruppe, som kan være afbrudt af ét eller to divalente heteroatomer såsom oxygen eller svovl; R7 betegner en alkyl- eller halogenalkylgruppe;R 1 is CN or methyl or a halogen atom; R 2 is S (O) n R 3 or 4,5-dicyanoimidazol-2-yl or halogenoalkyl; R 3 is alkyl or haloalkyl; R4 represents a hydrogen or halogen atom; or an NR5 R6, S (O) mR7-, C (O) R7-, C (O) O-R7, alkyl, haloalkyl or OR8 group or an -N = C (R9) (R10) ) -group; R5 and R6 independently represent a hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxycarbonyl or S (O) r-CF3 group; or R5 and R6 together may form a divalent alkyl group which may be interrupted by one or two divalent heteroatoms such as oxygen or sulfur; R7 represents an alkyl or haloalkyl group;

Rs betegner en alkyl- eller halogenalkylgruppe eller et hydrogenatom;R 5 represents an alkyl or haloalkyl group or a hydrogen atom;

Rg betegner en alkylgruppe eller et hydrogenatom;Rg represents an alkyl group or a hydrogen atom;

Ru og R12 indbyrdes uafhængigt hver især betegner et hydrogen- eller halogenatom eller eventuelt CN eller N02; R13 betegner et halogenatom eller en halogenalkyl-, halogenalkoxy-, S(0)qCF3- eller SF5-gruppe; m, n, q og r indbyrdes uafhængigt hver især er et helt tal lig med 0, 1 eller 2; X betegner et trivalent nitrogenatom eller en C-Ri2-gruppe, hvor carbonatomets andre tre valensstillinger udgør en del af den aromatiske ring; med det forbehold, at når Ri er methyl, er R3 enten halogenalkyl, R4 er NH2, Ru er Cl, R13 er CF3 og X er N; eller R2 er 4,5-dicyanoimidazol-2-yl, R4 er Cl, Ru er Cl, R13 er CF3 og X er =C-C1; og på den anden side mindst én ovicid forbindelse (B) af den insektvækstregulatoriske (IGR) type, til fremstilling af et præparat som er bestemt til lokal administrering til huden med henblik på langvarig beskyttelse mod lopper hos små pattedyr og især katte og hunde. 35. Anvendelse ifølge krav 34 til fremstilling af et præparat ifølge et hvilket som helst af kravene 1-33. 36. Anvendelse af et præparat ifølge et hvilket som helst af kravene 1-33 til bekæmpelse af ectoparasitter, især blodmider. 37. Fremgangsmåde til bekæmpelse af lopper hos små pattedyr og især hos katte og hunde i et langt tidsrum, k e n d e t egnet ved, at dyret behandles ved lokalt på huden at anbringe parasiticidt effektive doser og forhold af et præparat ifølge et hvilket som helst af kravene 1-33. 38. Fremgangsmåde ifølge krav 37, kendetegnet ved, at dyret behandles ved lokal punktvis anbringelse på huden af "spot-on"-typen. 39. Fremgangsmåde ifølge et hvilket som helst af kravene 37 og 38 til bekæmpelse af ectoparasitter, især blodmider.Ru and R 12 independently each represent a hydrogen or halogen atom or optionally CN or NO 2; R 13 represents a halogen atom or a haloalkyl, haloalkoxy, S (O) qCF3 or SF5 group; m, n, q and r are each independently an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a C-Ri 2 group, wherein the other three valence positions of the carbon atom form part of the aromatic ring; with the proviso that when R 1 is methyl, R 3 is either haloalkyl, R 4 is NH 2, Ru is Cl, R 13 is CF 3 and X is N; or R2 is 4,5-dicyanoimidazol-2-yl, R4 is Cl, Ru is Cl, R13 is CF3 and X is = C-C1; and, on the other hand, at least one ovicidal compound (B) of the insect growth regulatory (IGR) type, for the preparation of a composition intended for topical administration to the skin for long-term protection against fleas in small mammals and especially cats and dogs. Use according to claim 34 for the preparation of a composition according to any one of claims 1-33. Use of a composition according to any one of claims 1-33 for the control of ectoparasites, especially blood mites. 37. A method for controlling fleas in small mammals and especially in cats and dogs for a long period of time, characterized in that the animal is treated by applying topically to the skin parasitically effective doses and ratios of a composition according to any one of claims 1 -33. A method according to claim 37, characterized in that the animal is treated by localized spot-on application of the spot-on type skin. The method of any one of claims 37 and 38 for controlling ectoparasites, especially blood mites.