ITTO970260A1 - SKIN SOLUTION FOR DIRECT APPLICATION FOR PESTICIDE USE FOR CATTLE AND SHEEP. - Google Patents

Description

The present invention refers to a cutaneous solution for direct application containing an antiparasitic product and intended to be applied topically to cattle and sheep.

It also refers to the use of antiparasitic compounds for the preparation of this skin solution, as well as to a procedure for its treatment.

Cattle and sheep are affected by a high amount of parasites.

The main among these are made up of ticks belonging to the genus Boophilus, among which we can mention the species microplus, (in English "cattle tick"), decoloratus and anulatus.

The other main parasites of cattle and sheep are listed in decreasing order of importance:

- myiases such as Dermatobia hominis (called "Berne" in Brazil) and Cochlyomia hominivorax (lucilia bovina); the myiasis of sheep, such as Lucilia sericata, Lucilia cuprina (called "blowfly strike" in Australia, New Zealand and South Africa). These are flies whose larva is the parasite of the animal;

- flies proper, ie those whose adult constitutes the parasite, such as the Haematobia irritans ("horn fly");

- lice such as Linognathus vitulorum, etc;

- galls such as Sarcoptes scabiei and Psoroptes ovis.

Ticks, in particular those belonging to the genus Boophilus microplus, are very attached to the pastures, where they live, and are particularly difficult to fight.

Currently there are no truly effective methods to combat ticks, and even less is there an effective method to combat all the parasites mentioned above.

Documents-WO-A-87/3781, EP-A-295.117 and EP-A-500.209 describe a range of insecticides consisting of derivatives of N-phenylpyrazoles. These compounds are recommended in various fields such as agriculture, public health and veterinary medicine, as they possess activity against a large number of parasites, including those belonging to the Boophilus microplus genus. The general indication of these documents specifies that these insecticidal compounds can be administered via several routes: oral, parenteral, percutaneous and topical. Topical administration includes in particular oral formulations, pleasant excipients, dietary supplements, skin solutions ("pour-on"), solutions to be dissolved in powder (spray), baths, showers, water jets. , powders, fats, shampoos, creams, etc. Pour-on cutaneous solutions are intended for percutaneous administration. Example 9 of document EP-A-295.117 291 and example 291 of document EP-A-500.209 describe, for the percutaneous administration of the insecticide, a cutaneous solution of the "pour-on" type, having 15% of insecticide and 85% dimethylsulf oxide.

Document EP-A-296.381 also describes some pyrazolated compounds with insecticidal activity used in agriculture, public health and veterinary medicine. The parasite belonging to the genus Boophilus microplus is one of several targets mentioned. Also in this case, the forms of administration are very numerous and include, for example, solutions, emulsions, suspensions, powders, pastes, granulates and aerosols.

The problem arises of finding an effective means perfectly suited to the fight against parasites of cattle and sheep, in particular ticks! especially those belonging to the genus Boophilus microplus, found in cattle, and in particular the lice and "blowfly" found in sheep, in the conditions of these animals.

The applicant found that it was possible, by means of a particular topical formulation, to effectively combat the parasites belonging to the genus Boophilus -microplus of cattle. "of sheep.

The present invention therefore aims to provide a new composition perfectly effective against parasites belonging to the genus Bóophilus microplus and also against all the other parasites described above / such as in particular lice and "blowfly" of sheep, composition that is perfectly suited to the fight against these parasites in the breeding conditions of these animals.

Another object of the invention is to provide a formulation such that it has a long duration of efficacy, preferably greater than or equal to two months.

Another object of the invention is to provide a formulation which is simple and quick to use and which is perfectly compatible with use on flocks comprising a large number of animals.

A further object of the invention is to provide a formulation which is particularly appropriate in extensive farming in grazing environments and which is used to protect animals during the herding and final treatment period ("Feed Lot" in the United States). ie in the final rearing period, in which a large number of animals are gathered in a pen with a small surface area for an average period of two months before slaughter.

The present invention therefore relates to a skin solution for direct application, intended for the elimination of parasites from cattle and sheep, especially ticks, in particular those belonging to the genus Boophilus microplus found on cattle, and some lice and "blowfly" found in sheep, ranging from 0.05 to 25% in the weight / volume ratio, with respect to the total solution, of a compound of formula (I):

- Ri is CN homethyl or a halogen atom;

- R2 is S (0) nR3 or 4,5-dicianoimidazole 2-yl or haloalkyl;

- R3 is alkyl or haloalkyl;

- R <represents a hydrogen or halogen atom; or a radical NR5R6, S {0) mRi, C (0) O-R7, alkyl, haloalkyl or ORe or a radical -N = C (R9) (Rio);

- R5 and Re independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxylcarbonyl, S (0) rCF3 radical; wherein R5 and R6 can together form a divalent alkylene radical which can be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur;

- R7 represents an alkyl or haloalkyl radical;

- Ra represents an alkyl, haloalkyl radical or a hydrogen atom;

- R9 represents an alkyl radical or a hydrogen atom;

- Rio represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or by groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; ...

- Ru and R12 represent, independently of each other, a hydrogen or halogen atom, or possibly CN or N02;

- Ri3 represents a halogen atom or a haloalkyl, haloalkoxyl, S (O) qCF3 or SF5 group;

- m, n, q, r represent, independently from each other, an integer equal to 0, 1 or 2;

- X represents a trivalent nitrogen atom or a C-Ri2 radical, the other three valences, of the carbon atom belonging to the aromatic cycle;

provided that, when R1 is methyl, R3 is haloalkyl, R4 is NH2, Ru is Cl, Ri3 is CF3, and X is N; or R2 is 4,5-dicianoimidazole 2-yl, R4 is Cl, RJ3 is CF3 and X is = C-C1;

As part of a low quantity formulation designed to expand the compound (I) on the skin and hair for a contact action against parasites.

Preferably, in the formula (I):

- Ri, is CN or methyl;

- R2 is S (O) nR3;

- R3 is alkyl or haloalkyl;

- R «represents a hydrogen or halogen atom; or a radical NR5R6, S (0) mR7, C (0) R7, alkyl, haloalkyl or ORg or a radical -N = C (Rg) (Rio);

- Rs and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, S (O) rCF3 radical; or R5 and R6 can together form a divalent alkylene radical which can be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur;

- R? represents an alkyl or haloalkyl radical;

- Re represents an alkyl, haloalkyl radical or a hydrogen atom;

- Rg represents an alkyl radical or a hydrogen atom;

Rio 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;

- Rn and R12 ■ represent, independently of each other, a hydrogen or halogen atom;

- Rij represents an atom of. halogen or a haloalkyl, haloalkoxyl, S (O) qCF3 or SF5 group;

- m, n, q and r represent, independently from each other, an integer equal to 0, 1 or 2;

- X represents a trivalent nitrogen atom or a C-R12 radical, the other three valences of the carbon atom being part of the aromatic cycle;

provided that when Ri is methyl, R3 is then haloalkyl, R4 is NH2, Rn is Cl, RI3 is CF3, and X is N.

However, low concentrations ranging from 0.05 to 10% by weight / volume, more particularly from 0.1 to 2%, are preferable. In an optimal way, it is between 0.25 and 1.5%, in particular about 1%.

By cutaneous solution for application (in English "pour-on"), we mean a ready-to-use solution intended to be applied locally topically on the animal, preferably in various points on the back of the animal or following the line of the back, and intended to be applied in low quantities, preferably from 5 to 20 ml per 100 kg, preferably about 10 ml per 100 kg, with a total quantity ranging from 10 to 150 ml per animal, preferably limited to 50 ml .

The compound acts by simple contact, the parasite impregnating itself with the compound in contact with the hair and skin.

Thus, a product is remarkably available that is perfectly compatible with the constraints of use in extensive farming, in particular in terms of ease of use, and at the same time endowed with a spectrum of activity and efficacy, as well as a duration of efficacy. suitable for this type of breeding.

By acting on the concentration in compound (I), in particular in compound A, solutions are obtained having considerable activities, in particular two months of efficacy against parasites belonging to the genus Boophilus microplus, up to now. Moreover, the solution according to the invention allows to totally eliminate, in less than two days, an animal infested with parasites belonging to the genus Boophilus microplus.

As previously defined, the solution according to the present invention is applied topically on the back of the animal, in low quantity. Subsequently, a considerable diffusion of the compound of formula (I) is obtained through a distribution of the latter over the whole body of the animal. It has also been found that, in case of passage in water or exposure to rain, the animals remained protected,

The dose of the compound, of the formula (I) is preferably comprised between 0.1 and 2 mg / kg (weight of the animal), preferably between 0.25 and 1.5 mg / kg and in particular approximately 1 mg. / kg.

Si <1> the compounds of formula (I) will be particularly chosen; in which Ri is CN. Compounds will also be maintained in which R2 is S (0) nR3, preferably with n = 1, R3 being preferably CF or alkyl, for example methyl or ethyl, or n <'> = 0, R3 being preferably CF3, as well as those < '> in which X = C-RI2, RI2 being a halogen atom ·. Furthermore, compounds in which Rn is a halogen atom are preferable, as well as those in which R13 is haloalkyl, preferably CF3. Advantageously, within the scope of the present invention, compounds grouping two or more of these characteristics will be selected.

A preferential group of the compounds of the formula (I) consists of the compounds in which Ri is CN, R3 is haloalkyl, preferably CF3 or ethyl, R4 is NH2, Ru and R12 are, independently of each other, a halogen atom and / or R33 is haloalkyl.

The alkyl radicals of the definition of the compounds of the formula (I) generally comprise from 1 to 6 carbon atoms. The cycle formed by the alkylene divalent radical representing R5 and R6, as well as the nitrogen atom to which R5 and Rs are associated, is generally a 5, 6 or 7 ring cycle.

A compound of the formula {I) particularly preferential in the invention is 1- [2,6-Cl2 4-CF3 phenyl] 3-CN 4- [SO-CF3] 5-NH2 pyrazole, hereinafter referred to as compound A. This compound A will be used in particular in an amount ranging from 0.1 to 2% by weight, more particularly about 1% with respect to the total solution.

It is also possible to mention the two compounds which differ from the previous one for the following characteristics:

1 - n = 0, R3 = CF3

2 - n = 1, R3 = ethyl.

The preparation of the compounds of formula (I) can be carried out in accordance with one of the processes described in patent applications WO-A-87/3781, 93/6089 and 94/21606 or in European application EP-A-0.295, .117, or in accordance with any other procedure deriving from the competence of the specialist in the chemical synthesis sector. For the chemical realization of the products of the invention, it is believed that the skilled in the art has at his disposal, among other things, all the contents of "Chemical Abstracts" and of the documents cited therein.

The introduction of other insecticides into the solution according to the present invention does not go beyond the scope of the present invention.

Advantageously, the oily solutions according to the invention generally comprise a diluent or vehicle, and if the latter is not soluble in the diluent, also a solvent (organic solvent) of the compound of formula (I).

As an organic solvent that can be used in the context of the present invention, the following can be mentioned in particular: acetyltributyl citrate, fatty acid esters such as dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol , butyldiglycol, dimethylacetamide, dimethylformamide, dipropylene glycol nbutyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol nionomethyl ether, monomethylacetamide, glycol monomethylether, dipro-glycine liquid polyoxylethylene glycols, propylene glycol, 2-pyrrolidone, in particular N-methyl pyrrolidine, diethylene glycol monoethyl ether, ethylene glycol, diethyl phthalate or a mixture of at least two of them.

As a carrier or diluent, the following can be mentioned in particular:

vegetable oils such as soybean, peanut, castor, corn, cotton, olive, grape seed, sunflower oil, etc .; mineral oils such as petroleum jelly, paraffin, silicone, etc./ aliphatic or cyclic hydrocarbons, or for example medium-chain triglycerides (variants in particular from C8 to C12).

An emollient and / or application and / or film-forming agent will preferably be added, chosen in particular from:

- polyvinylpyrrolidone, polyvinyl alcohols, vinyl acetate and vinylpyrrolidone copolymers, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol, polyoxylethylene sorbitan esters; lecithin, sodium carboxylmethylcellulose, silicone oils, polydiorganoxyloxane oils, in particular polydimethylsiloxane oils (PDMS), for example with silanol functionality, or a 45V2 oil;

anionic surfactants such as alkaline stearates, in particular sodium, potassium or ammonium; calcium stearate, triethanolamine stearate; sodium abietate; alkyl sulphates, in particular sodium lauryl sulfate and sodium ketyl sulfate; sodium dodecylbenzenesulphonate, sodium dioctyl sulfoccinate; fatty acids, in particular those derived from copra oil;

- cationic surfactants such as water-soluble quaternary ammonium salts of the formula N <+> R'R "R '" R "" Y <">, in which the R radicals are hydrocarbonate radicals, possibly hydroxylated, and Y <~> is an anion of a strong acid such as halide, sulfate and sulfonate anions; ketyltrimethylammonium bromide is one of the cationic surfactants that can be used;

- the aramine salts of the formula N <+> R'R "R" ', in which the radicals R are hydrocarbonate radicals, optionally hydroxylated; octadecylamine hydrochloride is one of the cationic surfactants that can be used;

- non-ionic surfactants, such as sorbitan esters, optionally polyoxylethylenates, in particular Polysorbate 80, polyoxylethylenated alkyl ethers; polyoxylpropylated fatty alcohols such as polypropylene-15-stearyl ether; polyethylene glycol stearate, polyoxylethylene derivatives of castor oil, polyglycerol esters, polyoxylethylenated fatty alcohols, polyoxylethylenated fatty acids, ethylene oxide and propylene oxide copolymers;

amphoteric surfactants such as lauryl compounds substituted by betaine;

or a mixture of at least two of them.

The solvent will be used in proportion to the concentration of compound (I) and its solubility in this solvent.

For example, compound A has a solubility of 4.3% m / V in tributyl acetyl citrate. We will try to get the lowest possible volume.

The vehicle is the 100% complement.

The emollient is preferably used in an amount ranging from 0.1 to 10%, in particular from 0.25 to 5% by volume.

The present invention also relates to a process for the elimination, from cattle and sheep, of parasites, in particular those belonging to the genus Boophilus microplus, by means of a skin solution for direct application in accordance with the present invention, in order to obtain a long-lasting and broad spectrum efficacy, the solution being applied on the back of the animal, preferably following the line of the back or in several points.

According to a first embodiment, the procedure consists in applying the solution on the animals during grazing and / or before their entry into the pasture, the application being preferably renewed every month, preferably every two months.

According to a second embodiment, the procedure consists in applying the solution on the animals before they enter the "Feed Lot", this application being the last one before the animals are slaughtered.

Obviously, the method can also consist in combining these two embodiments, ie the first followed by the second.

In any case, the effectiveness advantageously allows any application to be stopped in the period between 1 and 3 months prior to slaughter, in particular in the period between 1.5 and 2.5 months, more particularly approximately two months prior to slaughter. .

The solutions according to the invention can be applied by any means known per se, preferably by means of a dispensing gun or a metering bottle.

The purpose of the method is not therapeutic, and in particular it is to clean the skin and hair of animals by eliminating the parasites that are present there, as well as their residues and their excrements. As a result, the animals are no longer pestered by parasites and their stings, which has positive consequences, for example, on their growth and the use of their food ration.

Another object of the invention is a therapeutic method using the external application according to the invention, intended for the treatment and prevention of parasites having pathogenic consequences.

The present invention also relates to the use of compounds (I), in particular compound A, for the manufacture of a skin solution for direct application, comprising compound (I) in low quantities and designed to expand the compound on the skin and on the hair, for a contact action against parasites of cattle and sheep, in particular of bovine ticks, such as those belonging to the genus Boophilus microplus, and of Blowfly and lice of sheep.

The use according to the invention aims at the realization of cutaneous solutions, such as those previously described.

The present invention will now be described in more detail by means of examples taken by way of non-limiting purposes and demonstrating the activity of the solutions according to the present invention, with reference to the attached drawings, in which:

- figure 1 is a graph illustrating the efficacy against the parasite belonging to the genus Boophilus microplus of cutaneous solutions according to the invention, charged at 0.25%, 0.5% and 1%, with respect to a witness, this graph including on the abscissas the time expressed in days later, the application of the skin solutions; and on the ordinates, on the left, the number of ticks identified on the animals to which the skin solutions are applied and, in the ordinates on the right, the number of ticks identified on the witnesses;

- figure 2 is a graph illustrating the population of ticks on the animals that received the placebo according to example 2, having on the abscissa the time expressed in days and on the ordinate the number of ticks; And

- Figure 3 compares the effectiveness of a 1% skin solution according to the invention of compound A (full rounds) with a 1% cutaneous solution of flumetrin (empty rounds) / having the time on the abscissa expressed in days and on the ordinate the number of ticks.

EXAMPLE 1: Preparation of the solutions according to the invention.

Compound A is dissolved in the solvent before being mixed with the other ingredients.

EXAMPLE 2:

Study of the efficacy of skin solutions according to the invention, respectively charged at 0.25, 0.50 and 1% of compound A, to combat the parasite Boophilus microplus.

The study was carried out on 16 castrated young males of the Hereford breed (the weight being staggered between 114 and 172 kg).

Three skin solutions were prepared according to example 1:

1. 1% of compound A

2. 0.5% of compound A

3. 0.25% of compound A

A placebo different from the cutaneous solutions conforming to the invention was created due to the absence of compound A.

During the studies, 1 ml of skin solution or placebo was used per 10 kg of the animal's weight.

The amount of the dose was applied to the line of the animal's back, from the head to the base of the tail.

Between days -24 and -1, the animals were artificially infested, on 11 occasions, with 2,500 Boophilus microplus larvae. The goal of a 24-day infestation is to ensure that all stages of Boophilus microplus (eggs, larvae, adults) are present on the animal. On day 0, the animals are given one of the skin solutions or the placebo.

Before the application of the skin solutions or the placebo, the ticks present on the various animals of the different groups are identified.

The following table indicates i. measured values, the weight of the animals and the dose of cutaneous solution or placebo that will be applied to each of these animals.

For the count, female ticks sated with sucked blood and detaching are considered. The results are <'> indicated in Figure 1.

A dose-dependent effect with 100% efficacy is obtained for the skin solution according to the invention having 1% compound A. However,. less concentrated solutions give remarkable results.

It is also noted a great rapidity of action of the solutions according to the invention, of which the 1% one allows to totally eliminate the parasite Boophilus microplus in less than two days.

EXAMPLE 3

Comparison of efficacy between a skin solution compliant with <'> the invention charged at 1% <'> of compound A and a skin solution charged with 1% flumetrin.

Animals of the same breed as those used in Example 1 were used.

On day 0, groups are treated with:

cutaneous solution having 1% of compound A;

cutaneous solution: having 1% fluraetrin (excipient ethylhexyl alcohol and mineral oil);

placebo (excipient identical to the solution according to the invention).

Table 2 below indicates, for each group, the weight of the animals, the dose of skin solution received and the dose of active substance applied.

From day 2 to day 32, the animals receive 5000 larvae of the parasite Boophilus microplus three times a week. From days 18 to 64, blood-laden female ticks that detach are collected and counted.

EXAMPLE 4:

Effectiveness study over time.

In this example, work was carried out with skin solutions according to the invention containing 0.25, 0.5 or 1% compound A.

The composition of these solutions is the same as those used for the previous examples. The cattle were previously infested in order to present all the stages of the parasite Boophilus microplus (infestation with 5000 larvae, 22 days, 15 days and 8 days with application of the skin solution).

After application of the skin solutions, the cattle are still infested with the larvae week by week for 13 weeks in order to determine the effectiveness of the three concentrations.

The results are reported in the following table 3:

It is therefore noted that considerable efficacy has been obtained, capable of reaching or exceeding two months.

Claims (32)

CLAIMS 1. Skin solution for direct application, intended for the elimination of parasites from cattle and sheep, especially ticks, in particular those belonging to the genus Boophilus microplus found on cattle, and some lice and "blowfly" found in sheep, ranging from 0, 05 at 25% in the weight / volume ratio, with respect to the total solution, of a compound of the formula (I): m which - Ri is CN or methyl or a halogen atom; - R2 is S {0) nR3 or 4,5-dicyanoimide, zole 2-yl or haloalkyl; - R3 is alkyl or haloalkyl; - R4 represents a hydrogen or halogen atom; or a radical NR5R6, S (0) mR7, C (0) O-R7, alkyl, haloalkyl or 0R8. or a radical -N = C (R9) (Rio); - R5 and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxyl carbonyl, S {0) rCF3 radical; wherein R5 and R6 can together form a divalent alkylene radical which can be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur; R7 represents an alkyl or haloalkyl radical; - Re represents an alkyl, haloalkyl radical or a hydrogen atom; R9 represents an alkyl radical or a hydrogen atom; Rio represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or by groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; - Rn and Ri2 represent, independently of each other, a hydrogen or halogen atom, or possibly CN or Ν02; - Ri3 represents a halogen atom or a haloalkyl, haloalkoxyl, S (O) qCF3 or SF5 group; - iti, n, q, · r represent, independently from each other, an integer equal to 0, 1 or 2; - X represents a trivalent nitrogen atom or a C-R12 radical, the other three valences of the carbon atom belonging to the aromatic cycle; provided that, when R1 is methyl, R3 is haloalkyl, R <is NH2, Rn is Cl, Rn is CF3, and X is N; or R2 is 4,5-dicianoimidazole 2-yl, R4 is Cl, R13 is CF3 and X is = C-C1; as part of a low quantity formulation designed to expand the compound (I) on the skin and hair for a contact action against parasites. 2. Solution according to claim 1, characterized in that the solution is designed to be applied in an amount varying from 5 'to 20 ml per 100 kg, preferably approximately ml per 100 kg of with a total quantity varying from - 10 - to 1155 (0 ml per animal, preferably limited to 50 ml. 3. Solution according to claim 1 or 2, characterized in that the compound of formula (I) is such that: - Ri is CN or methyl; - R2 is S (0) nR3; - R3 is alkyl or haloalkyl; - R4 represents a hydrogen or halogen atom; or a radical NR5R6 / S (0) mR7, C (0) R7, alkyl, haloalkyl or 0R8 or a radical -N = C (R9) (Rio); - R5 and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, S (O) rCF3 radical; or R5 and R6 can together form a divalent alkylene radical which can be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur; - R7 represents an alkyl or haloalkyl radical; - R8 represents an alkyl, haloalkyl radical or a hydrogen atom; R represents a '' alkyl radical o - Rio represents a phenyl or heteroaryl group possibly substituted by one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; - Rn and Rj2 represent, independently from each other, a hydrogen or halogen atom; - Ri3 represents a halogen atom or a haloalkyl, haloalkoxyl, S (O) qCF3 or SF5 group; - m, n, q and r represent, independently from each other, an integer equal to 0, 1 or 2; - X represents a trivalent nitrogen atom or a C-R12 radical, the other three valences of the carbon atom being part of the aromatic cycle; provided that when Ri is methyl, R3 is then haloalkyl, R4 is NH2, Rn is Cl, R13 is CF3, and X is N. 4. Solution according to one of claims 1 to 3, characterized in that the compound of formula (I) is such that R1 is CN. 5. Solution according to a. of claims 1 to 4, characterized in that the compound of formula (I) is such that R13 is haloalkyl, preferably CF3. Solution according to one of claims 1 to 5, characterized in that the compound of formula (I) is such that R2 is S (0) nR3, preferably with n = 1, R3 preferably being CF3 or alkyl, in particular methyl or ethyl, or n = 0, R3 preferably being CF3. 7. Solution according to one of claims 1 to 6, characterized in that the compound of formula (I) is such that X is C-R12, with R12 constituting a halogen atom. 8. Solution according to one of claims 1 to 7, characterized in that the compound of formula (I) is selected from those in which Ri '<'> is CN, R3 is haloalkyl, R4 is NH2, Rn and R12 are independently of each other, a halogen and / or Ri3 atom is haloalkyl. 9. Solution according to one of claims 1 to 3, characterized in that the compound of <1> formula (I) is: 1- [2,6-Cl24-CF3 phenyl] 3-CN 4- [SO-CF3 ] 5-NH2 pyrazole. Solution according to any one of claims 1 to 9, characterized in that it comprises from 0.05 to 10% by weight / volume, preferably from 0.1 to 2% of the compound of formula (I). Solution according to any one of claims 1 to 10, characterized in that it comprises from 0.25 to 1.5%, preferably approximately 1% of the compound of formula (I). Solution according to any one of claims 1 to 11, characterized in that it comprises a solvent of the compound (I) and a diluent, optionally an emollient agent. 13. Solution according to claim 12, 9 characterized in that the solvent is selected from the group comprising: acetyltributyl citrate, fatty acid esters such as dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol, butyldiglycol, dimethylacetamide, dimethylformamide, dipropylene glycol n-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, monomethyl ether dipropylene glycol, liquid polyoxylethylene glycols, propylene glycol, 2-pyrrolidone, in particular N-methyl pyrrolidine, diethylene glycol monoethyl ether, ethylene glycol, diethyl phthalate or a mixture of at least two of them. 14. Solution according to claim 12 or 13, characterized in that the diluent is selected from the group comprising: vegetable oils such as soybean, peanut, castor, corn, cotton, olive, grape seed oil , sunflower, etc .; mineral oils such as vaseline, paraffin, silicone, etc .; aliphatic or cyclic hydrocarbons, or for example medium chain triglycerides (variants in particular from C8 to C12). Solution according to one of claims 12 to 14, characterized in that the emollient <'> is selected from the group comprising: - polyvinylpyrrolidone, polyvinyl alcohols, vinyl acetate and vinylpyrrolidone copolymers, polyethylene glycols, benzyl alcohol. mannitol, glycerol, sorbitol, polyoxylethylenated sorbitan esters; lecithin, sodium carboxylmethylcellulose, silicone oils, polydiorganoxyloxane oils, in particular polydimethylsiloxane oils (PDMS), for example with silanol functionality, or a 45V2 oil; anionic surfactants such as alkaline stearates, in particular sodium, potassium or ammonium; calcium stearate, triethanolamine stearate; sodium abietate; alkyl sulphates, in particular sodium lauryl sulfate and sodium ketyl sulfate; sodium dodecylbenzenesulphonate, sodium dioctyl sulfoccinate; fatty acids, in particular those derived from copra oil; - cationic surfactants such as water-soluble quaternary ammonium salts of the formula N <+> R'R "R" 'R "" Y <">, in which the R radicals are hydrocarbonate radicals, possibly hydroxylated, and Y <~> is an anion of a strong acid such as halide, sulfate and sulfonate anions; ketyltrimethylammonium bromide is one of the cationic surfactants that can be used; the amine salts of the formula N <+> R'R "R '", in which the radicals R are hydrocarbonate radicals, optionally hydroxylated; octadecylamine hydrochloride is one of the cationic surfactants that can be used; - non-ionic surfactants, such as sorbitan esters, optionally polyoxylethylenates, in particular Polysorbate 80, ... polyoxylethylenated alkyl ethers; polyoxylpropylated fatty alcohols such as polypropylene-15-stearyl ether; polyethylene glycol stearate, polyoxylethylene derivatives of castor oil, polyglycerol esters, polyoxylethylenated fatty alcohols, polyoxylethylenated fatty acids, ethylene oxide and propylene oxide copolymers; amphoteric surfactants such as lauryl compounds substituted by betaine; or a mixture of at least two of them. Solution according to any one of claims 1 to 15, characterized in that it is an oily solution. 17. Solution according to any one of claims 1 to 16, characterized in that it is designed to ensure protection for a duration greater than or equal to two months. 18. Use of a compound corresponding to the following formula (I): in which : - Ri is CN or methyl or a halogen atom; - R2 is S (0) nR3 or 4,5-dicianoimidazole 2-yl or haloalkyl; - R3 is 'alkyl' or haloalkyl; - R4 represents a hydrogen or halogen atom; or a radical NR5R6, S (0) mR7, C (0) O-R7, alkyl, haloalkyl or ORe or a radical -N = C (R9) (Rio); - R5 and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, alkoxylcarbonyl, S (0) rCF3 radical; wherein R5 and R6 can together form a divalent alkylene radical which can be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur; , - R7. represents an alkyl or haloalkyl radical; - RB represents a radical ... alkyl, haloalkyl or a hydrogen atom; - R9 represents an alkyl radical or a hydrogen atom; - Rio represents a phenyl or heteroaryl group optionally substituted by one or more halogen atoms or by groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; - Rn and RI2 represent, independently of each other, a hydrogen or halogen atom, or possibly CN or N02; - R13 represents a halogen atom or a haloalkyl, haloalkoxyl, S (O) qCF3 or SF5 group; - m, n, q, r represent, independently from each other, an integer equal to 0, 1 or 2; - X represents a trivalent nitrogen atom or a C-R12 radical, the other three valences of the carbon atom belonging to the aromatic cycle; provided that, when R1 is methyl, R3 is haloalkyl, R <is NH2, Rn is Cl, R13 is CF3 / and X is N; or R2 is 4,5-dicianoimidazole 2-yl, R4 is Cl, Ri3 is CF3 and X is = C-C1; for the realization of a cutaneous solution for direct application comprising compound (I) in a modest quantity and designed to expand compound (I) on the skin and hair for a contact action against parasites of cattle and sheep, in particular the ticks of cattle, such as those of the genus Boophilus microplus and Blowfly and the lice of sheep. 19. Use according to claim 18, characterized in that the cutaneous solution is designed to be applied in an amount ranging from 5 to 20 ml, preferably about 10 ml, per 100 kg of the weight of the animal, with an amount total varying from 10 to 150 ml per animal, preferably limited to 5 'ml. 20. Use according to claim 18 or 19, characterized in that the compound of formula (I) is such that: - Ri is CN or methyl; - R2 is S (0) nR3; - R3 is alkyl or haloalkyl; - R4 represents a hydrogen or halogen atom; or a radical NR5R6, S (0) mR3, C (0) R7, alkyl, haloalkyl or ORB or a radical -N = C {R9) (Rio); - R5 and R6 independently represent the hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, S (O) rCF3 radical; or R5 and R6 can together form a divalent alkylene radical which can be interrupted by one or two divalent heteroatoms, such as oxygen or sulfur; - R7 represents an alkyl or haloalkyl radical; - Ra represents an alkyl, haloalkyl radical or a hydrogen atom; - R9 represents an alkyl radical or a hydrogen atom; Rio 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; - Rii and Ri2 represent, independently of each other, a hydrogen or halogen atom; - Ria represents a halogen atom or a haloalkyl, haloalkoxyl, S (0) qCF3 or SF5 group; - m, n, q and r represent, independently from each other, an integer equal to 0, 1 or 2; - X represents a trivalent nitrogen atom or a C-RI2 radical, the other three valences of the carbon atom being part of the aromatic cycle; provided that when Ri is methyl, R3 is then haloalkyl, R4 is NH2, Rii is Cl, Ri3 is CF3, and X is N. Use according to any one of claims 18 to 20, characterized in that the compound of formula (I) is such that Ri is CN. Use according to any one of claims 18 to 21, characterized in that the compound of formula (I) is such that R3 is haloalkyl, preferably CF3. 23. Use according to any one of claims 18 to 22, characterized in that the compound of formula (I) is such that R2 is S (0) nR3, preferably with n = 1, R3 preferably being CF3 or alkyl, in particular methyl or ethyl, or n = 0, R3 preferably being CF3. 24. Use in accordance with a. any of claims 18 to 23, characterized in that the compound of formula (I) is such that X consists of C-RI2, RI2 being a halogen atom. 25. Use according to any one of claims 18 to 20, characterized in that the compound of formula (I) is such that Ri is CN, R3 is haloalkyl, R4 is NH2, Ru and RI2 are, independently of each other , a halogen atom, and / or R13 is haloalkyl. 26. Use according to any one of claims 18 to 20, characterized in that the compound of formula (I) is: 1- [2,6-Cl2 4-CF3 phenyl] 3-CN 4- [SO-CF3] 5-NH2 pyrazole. 27. Use according to any one of claims 18 to 26, characterized in that it is applied in quantities ranging from 0.1 to 2 mg / kg, preferably from 0.25 to 1.5 mg / kg, in particular to approximately 0.1 mg / kg. 28. Use in accordance with any one of claims 18 to 26, characterized in that it is applied topically locally on the skin of the animal, <"> the solution is designed to ensure protection of at least two months, in particular against the Boophilus microplus tick. 29. Use in accordance with any of claims 18 to 28, characterized in that the solution is designed to ensure total elimination of the Boophilus microplus tick in less than two days. 30. Use in accordance with any one of claims 18 to 29, characterized by the act which aims at the preparation of such cutaneous solution for an allocation on the animal before its entry into the "Feed Lot". 31. Use in accordance with claim 30, for the preparation of this cutaneous solution intended to be applied to the animal every month, preferably every two months, preferably with interruption of applications in the period from 1 to 3 months prior to slaughter. 32. Process for the treatment of cattle and sheep essentially against the Boophilus microplus tick for cattle and blowfly and lice for sheep, by means of a cutaneous solution for direct application such as that described, and under the conditions indicated in any one of the preceding claims.