DK177400B1 - Solution of and use of 1- [2,6-C12-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole to prepare the solution for direct application to the skin to eliminate parasites from cattle and sheep - Google Patents

Abstract

Solution for direct application to the skin intended for the elimination of parasites, especially Boophilus microplus, from cattle and obtains from 0.05 to 25 preferably from 0.5 to 10%, and more preferably from 0.1 to 2% w / v, in relative to the total solution of a compound of formula (I) in a low volume formulation designed to release compound (I) to the skin and hair to a parasitic contact action.

Description

DK 177400 B1 i

The present invention relates to a solution for direct application to the skin which contains the compound 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole and is intended for topical administration for the elimination of parasites from cattle and sheep.

The invention also relates to the use of the compound 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole in the preparation of this skin solution.

10

Cattle and sheep are affected by a large number of parasites.

The most important are mites of the genus Boophilus, among which are the species microplus (cattle tick), decoloratus and 15 anulatus.

The other major parasites in cattle and sheep are listed in order of decreasing importance: 20 -myiasis such as Dermatobia hominis (named Berne in Brazil) and Cochliomyia hominivorax (gold fly); sheep myiasis such as Lucilia sericata, Lucilia cuprina (known as blowfly strike in Australia, New Zealand and South Africa). These are flies whose larva constitutes the animal's parasite 25 flies in the true sense, namely those whose adults constitute the parasite such as Haematobia irritans (small stick fly) lice such as Linognathus vitulorum etc.

30 mites such as Sarcoptes scabiei and Psoroptes ovis.

Blood mites, especially Boophilus microplus, are very closely associated with the pasture where they live and are particularly difficult to fight.

There is currently no really effective method of combating anemia, and even less an effective way of combating all the parasites listed above.

WO-A-87/3781, EP-A-295,117 and EP-A-500,209 disclose a class of insecticides which are N-phenylpyrazole derivatives. These compounds are said to possess activity against a very large number of parasites including Boophilus microplus in such diverse fields as agriculture, public health and veterinary medicine. The general teachings contained in these documents 10 indicate that these insecticidal compounds can be administered by various routes such as oral, parenteral, percutaneous and topical. Topical administration especially includes oral formulations, baits, supplements, skin solutions (pour-on), solutions for spraying (baths, showers, rays, powders, fats, shampoos, creams, etc.) The skin solutions of pour-on The type is designed for percutaneous administration. Example 9 of EP-A-295,117 and Example 291 of EP-A-500,209 disclose a pour-on skin solution containing 15% insecticide and 85% dimethyl sulfoxide for percutaneous administration of the insecticide.

EP-A-296,381 also discloses pyrazole compounds having insecticidal activity in the agricultural, public health and veterinary fields. Boophilus microplus is one of the many targets mentioned. There are also 25 very many forms of administration here, and these include e.g. solutions, emulsions, suspensions, powders, pastes, granules and aerosols.

The problem that arises is to find an effective agent that is perfectly suitable for controlling the parasites of cattle and sheep, especially blood mites and especially Boophilus microplus in cattle and especially lice and blowfly in sheep, under the conditions under which these animals bred.

35 The applicant has found that it is possible to effectively combat Boophilus microplus in cattle using a specific topical formulation. The applicant has also found that this formulation is effective against sheep lice and sheep flies such as "blowfly".

The object of the present invention is thus to provide a novel composition which is completely effective against Boophilus microplus and also against all the other parasites described above, especially sheep lice and blowfly, this preparation being perfectly suitable for controlling these parasites. under the conditions under which these animals are raised.

Another object of the invention is to provide such a formulation which has a long duration of action, preferably longer than or equal to two months.

Another object of the invention is to provide such a formulation which is quick and easy to use and completely compatible with the application to herds or flocks containing a large number of animals.

Another object of the invention is to provide such a formulation which is particularly suitable for extensive grazing breeding and for use intended for the protection of animals during compaction and the final phase of the work (Feed Lot in the USA), namely the final period of the breeding, in which a large numbers of animals are driven together in a small enclosure for an average of two months before slaughter.

The present invention thus relates to a solution for direct application to the skin and intended for the elimination of parasites from cattle and sheep, and in particular blood mites, in particular 30 Boophilus microplus in cattle, and lice and saliva flies in solution comprising from 0.1 to 2 weight / volume relative to the total solution of 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole in a small volume formulation, which is adapted to release 1- [2,6-Cl2-4-CF3-35 phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole on the skin and hairs for a parasitic contact action, wherein the solution comprises a solvent for 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-DK 177400 B1 4 CF3] -5-NH2-pyrazole, a diluent, and optionally a emollient and wherein the solvent is selected from the group consisting of: acetyl tributyl citrate, fatty acid esters such as the dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol, butyldiglycol, dimethyl acetamide, dimethylformam d, dipropylene glycol-n-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycol, propylene glycol, 2-pyrrolidone, especially N-methylpyrolidone, , or a mixture of at least two of these solvents.

However, low concentrations which are optimally between 0.25 and 1.5% are preferred and especially in the range of 1%.

By a solution for application to the skin (in English pour-on solution) is meant a ready-to-use solution intended for topical and local administration to the animal, preferably on the animal's back and at several points or along the line of the spine and administered in low volume, preferably 5. to 20 ml per 100 kg, preferably approx. 10 ml per 100 kg with a total volume of 10 to 150 ml per animal and preferably limited to 50 ml.

25

The compounds act by simple contact, the parasites being impregnated with the compound by contact with the hair or with the skin.

30 This, in a remarkable way, provides both perfect compatibility with the application restrictions of extensive grazing, in particular ease of use and a spectrum of activity and effect as well as a duration of action suitable for this type of breeding.

In the case of the concentration of compound A, 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole, solutions are obtained with noteworthy activities, especially two months of action against Boophilus microplus, the result of which has never been achieved. Furthermore, the solution of the invention allows Boophilus microplus to be completely eliminated from an infected 5 animal in less than 2 days.

As indicated above, the solution of the present invention is administered topically in a small volume on the animal's back. The compound of formula 1- [2,6-Cl 2 -4-CF 3-10 phenyl] -3-CN-4- [SO-CF 3] -5-NH 2 pyrazole is then spread in a remarkable manner, as reflected by a distribution of the compound. all over the body of the animal. It has also been observed that the animals remained protected in case of passage through water or by exposure to rain.

15

The dose of the compound of formula 1- [2,6-Cl 2 -4-CF 3 -phenyl] -3-CN-4- [SO-CF 3] -5-NH 2 -pyrazole is preferably between 0.1 and 2 mg / kg ( animal weight), preferably between 0.25 and 1.5 mg / kg, and more preferably about. 1 mg / kg.

20

Compound of Formula 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole will hereinafter be referred to as Compound A. This compound In particular, A will be used in a ratio of from 0.1 to 2% by weight, and more preferably about 1% by weight, relative to the total solution.

DK 177400 B1 6

Compound A can be prepared according to one of the methods described in patent application WO-A-87/3781, 93/6089, 94/21606 or European patent application EP-A-0,295,117 or any other method falling within for the expertise of a person skilled in chemical synthesis. For the chemical preparation of the solutions according to the invention, the person skilled in the art is considered to have, among other things, the complete content of "Chemical Abstracts" and the documents cited therein.

10

Other insecticides are incorporated into the solution of the present invention.

The solutions of the invention, which are advantageously oily, comprise a diluent, diluent, or vehicle and also a solvent (organic solvent) for compound A if the latter is not soluble in the diluent.

The organic solvent used in the invention is: acetyl tributyl citrate, fatty acid esters such as the dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol, butyldiglycol, dimethylacetamide, dimethylformamide, dipropylglycol-n-butyl ether, ethanol, ethanol, monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, 2-pyrrolidone, especially N-methylpyrrolidone, diethylene glycol monoethyl ether, ethylene glycol and diethylphenylsulfate of one or more mixtures of one or more

Particularly mentioned as vehicle or diluent are: plant oils such as soybean oil, peanut oil, castor oil, 35 corn oil, cotton seed oil, olive oil, grape seed oil, sunflower oil etc./ mineral oils such as petroleum jelly, paraffin, silicone etc .; aliphatic or cyclic hydrocarbons or alternatively e.g. average chain length triglycerides (especially C8 to C12).

An emollient and / or spreading and / or film forming agent will preferably be added, this agent being particularly selected from -polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, glycerol ; lecithin, sodium carboxymethylcellulose, silicone oils, polydiorganosiloxanols especially polydimethylsiloxanols (PDMS), e.g. those containing silanol functionalities, or a 45V2 oil, anionic surfactants such as alkali metal stearates, especially sodium, potassium or ammonium stearates; calcium stearate, triethanolamine stearate; natriumabietat; alkyl sulfates, especially sodium lauryl sulfate and sodium cetyl sulfate; Sodium dodecylbenzenesulfonate, sodium dioctylsulfosuccinate; fatty acids, in particular 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 the halide, sulfate and sulfonate anions; cetyltrimethylammonium bromide is among the cationic surfactants which can be used, 30-amine salts of the formula N + R, R ,, R", wherein the groups R are octadecylamine hydrochloride is among the cationic surfactants which can be used, 35 nonionic surfactants such as sorbitan esters optionally polyoxyethylenated, especially polysorbate 80, polyoxyethylated alkyl ethers; polyoxypropylated fatty alcohols DK 177400 such as polyoxypropylene-15-stearyl ether; polyethylene glycol stearate, polyoxyethylenated derivatives of castor oil, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylene fatty acids, copolymers of ethylene oxide 5 and pro pylene oxide, amphoteric surfactants such as the substituted betaine lauryl compounds; 10 or a mixture of at least two of these agents.

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

15

For example, compound A has a solubility of 4.3% m / V in acetyl tributyl citrate. It will be tried to have the lowest possible volume.

20 The vehicle makes the difference to 100%.

The plasticizer is preferably used in a ratio of 0.1 to 10%, especially from 0.25 to 5%, based on the volume.

The present invention also relates to the use of 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole for the elimination of parasites, especially Boophilus microplus , from cattle and sheep, using a solution according to the invention for direct application to the skin, so as to obtain a long-lasting and widespread effect, which solution is applied to the animal's back, preferably along the line of the back, in one or more points.

According to a first embodiment, the use consists of administering the solution to the animals on grass and / or before arriving at the pasture, the administration being preferably repeated every month, preferably every two months.

DK 177400 B1 9

According to another embodiment, the use consists in administering the solution to the animals before arriving at said "Feed Lot", as it is possible that this administration is the final one before the animals are slaughtered.

Obviously, the application may also consist in combining these two embodiments, the first followed by the second.

In all cases, the effect makes it advantageous to halt any administration 1 to 3 months before slaughter, especially between 1.5 and 2.5 months, and more preferably approx. 2 months before slaughter.

The solutions of the invention can be administered using any means known per se, preferably using an application gun or a dosing bottle.

The aim of the application is non-therapeutic and is in particular to cleanse the skin and hair of the animals by eliminating the parasites present there as well as their remnants and excrement. The result is that the animals are no longer stressed by the parasites and their bites, which has positive consequences, e.g. for their growth and the application of their federation.

The present invention also relates to the use of a compound of formula 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole to prepare a solution for 30 a direct application to the skin in a small volume, comprising from 0.1 to 2% w / v, relative to the total solution, of 1- [2,6-Cl2-4-CF3-phenyl] -3- CN-4- [SO-CF3] -5-NH2-pyrazole and is adapted to release 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5 -NH2 pyrazole on the skin and hair 35 to contact the parasites in cattle and sheep, especially blood mites such as Boophilus microplus in cattle, and saliva flies and lice in sheep.

DK 177400 B1 10

The use according to the invention is directed to the preparation of skin solutions as described above.

The present invention will now be described in more detail by way of example, and the activity of the solutions of the present invention will be demonstrated with reference to the drawing, in which: 1 is a diagram showing the action against Boophilus microplus of skin solutions according to the invention having a content of 0.25%, 0.5% and 1% relative to a control, which diagram on the x-axis comprises the time in days after administering the solution to the skin and to the y-axis to the left the number of 15 blood mites counted in animals to which the skin solutions of the invention are administered, and to the y-axis to the right the number of blood mites counted in the controls; FIG. 2 is a diagram showing the population of anemia in 20 animals that received the blank of Example 2 over time for days on the x axis and on the y axis the number of anemia; and FIG. 3 compares the effect of a skin solution of the invention containing 1% compound A (filled circles) with a skin solution containing 1% flumethrin (circles) with time in days on the x axis and the number of blood mites on the y axis.

Example 17: Preparation of solutions according to the invention

Ingredient Function Quantity 5

Compound A Active substance xg polyoxypropylene-15 stearyl ether soften 5 g of 10 acetyl tributyl citrate solvent 30 g 15 soybean oil diluent qs in 100 ml x = 0.25 g to 0.25% solution x = 0.5 g to 0.5% solution 20 x = 1 g to 1% solution

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

EXAMPLE 2:

Examination of the effect of the skin solutions of the invention containing 0.25, 0.50 and 1% compound A respectively to control Boophilus microplus.

30

The study was conducted on 16 young castrated Hereford bulls (weighing in the range of 114 to 172 kg).

Three skin solutions of Example 1 were prepared: 35

1. 1% compound A

2. 0.5% compound A

3. 0.25% compound A

40 A blank was prepared which deviated from the skin solutions of the invention in that it contained no compound A.

In the studies, 1 ml of skin solution or blank was used per 10 kg of animal weight.

5

The dose volume was placed along 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 attacked on 10 11 occasions with 2,500 Boophilus microplus larvae. The target of exposure to attack for 24 days is to ensure that all Boophilus microplus stages are present on the animal (eggs, larvae, adults).

On day 0, the animals receive one of the skin solutions or blind sample.

Before administering the skin solutions or blank samples, the number of blood mites present on the various animals in the different groups is counted.

20

The following table lists the recorded values, the weight of the animals and the dose of skin solution or a blank sample that will be administered to each of these animals.

DK 177400 B1 13

Group Animal No. Number Weight Dose of blood mites (in kg) (ml) 5 _ 1.00% 94 588 134 13.4 43 470 140 14.0 47 300 154 15.4 39 254 160 16.0 10 0.50% 34 706 145 14.5 99 452 143 14.3 48 375 114 11.4 45 201 153 15.3 15 0.25% 40 510 148 14.8 92 453 144 14.4 41 432 155 15.5 36 236 171 17.1 20

Blind sample 96 627 150 15, 0 44 482 144 14.4 93 315 140 14.0 97 292 172 17.2 25 _

The blood-filled female blood mites that become detached are also included in the count. The results are given in FIG. First

A dose-dependent effect is obtained with 100% efficacy for the skin solution of the invention containing 1% compound A.

The less concentrated solutions nevertheless produce remarkable results.

The high rate of action of the solutions of the invention is also noted as the 1% solution allows complete elimination of Boophilus microplus in less than 2 days.

EXAMPLE 3:

Comparison of the effect between a skin solution of the invention containing 1% compound A and a skin solution 5 containing 1% flumethrin.

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

On day 0, the groups are treated with: 10

skin solution containing 1% compound A

skin solution containing 1% flumethrin (mineral oil and ethylhexyl alcohol excipient) 15 blank (excipient identical to the solution of the invention) Table 2 below lists for each group the weight of the animals, 20 dose of the receiving skin solution and dose of the administered active substance. fabric.

DK 177400 B1 15

Group Animal No. Weight Dose Dose (in ml) (ml / kg) 5 _ 1% 719 141 14.1 1

Compound A 709 125 12.5 1 713 150 15.0 1 710 136 13.6 1 10 703 138 13.8 1 1% 706 145 14.5 1 flumethrin 711 136 13.6 1 715 132 13.2 1 15 702 142 14.2 1 701 127 12.7 1

Blind sample 717 133 13.3 0 707 133 13.3 0 20 704 134 13.4 0 718 132 13.2 0 708 143 14.3 0 25 From day 2 to day 32, animals receive 5,000 Boophilus microplus larvae three times per week . From days 18 to 64, the blood-filled female blood mites are collected, which become detached and counted.

The results are given in FIG. 2 and 3, demonstrating the overall effect of the skin solution of the invention.

EXAMPLE 4:

Investigation of the effect in relation to time.

Skin solutions of the invention containing 0.25, 0.5 or 1% compound A were used in this example.

35 DK 177400 B1 16

The composition of these solutions is the same as in the examples above.

The cattle were pre-attacked to have all Boophilus 5 microplus stages present (exposure to attacks with 5,000 larvae 22 days, 15 days and 8 days before the administration of the skin solution).

After administering the skin solutions, the cattle are again subjected to larval attacks weekly for 13 weeks to determine the effect of the three concentrations.

The results are given in Table 3 below: 17 DK 177400 B1

Weeks of attack Effect index of after treatment each concentration 5 _ 0.25% 0.5% 1.0% 1 97.6 100 100 10 _ 2 98.8 100 100 15 3 99.7 100 100 4 99.3 100 100 20 5 96.7 92.9 100 6 98.6 93.2 100 25 _ 7 92.4 88.6 99.7 30 8 85.8 83.4 100 9 28.0 37.9 79.8 35 10 23.0 41.4 65.3 11 18.9 55.2 61.5 40 _ 12 1.7 37.3 32.2 45 13 8.4 48.5 46.4

It is thus observed that remarkable effect, which can last for two months or more, is obtained.

50

Claims (13)

A solution for direct application to the skin intended for the elimination of parasites from cattle and sheep, and in particular 5 blood mites, in particular Boophilus microplus in cattle and lice and saliva fly in sheep, characterized in that it comprises from 0.1 to 2% wt / volume relative to the total solution of 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole in a small volume formulation which is adapted to release 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole on the skin and hairs for a parasitic contact action, wherein the solution comprises a solvent for 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole, a diluent, and optionally a plasticizer, and wherein the solvent is selected from the group consisting of: acetyl tributyl citrate, fatty acid esters such as the dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol, butyldiglycol, dimethylacetamide, dimethylformamide, dipropylene glycol-n-butyl ether, ethanol, isopro panol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, 2-pyrrolidone, especially N-methylpyrrolidone, diethylene glycol monoethyl ether, ethylene glycol and ethylene glycol, ethylene glycol and ethylene glycol solvents. A solution according to claim 1, characterized in that it comprises from 0.25 to 1.5% w / v, relative to the total solution, of 1- [2,6-Cl2-4-CF3-phenyl] -3 -CN-4- [SO-CF3] - 5-NH2-pyrazole. A solution according to claim 2, characterized in that it comprises 1% w / v, relative to the total solution, of 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO -CF3] -5-NH2-pyrazole. A solution according to any one of claims 1-3, characterized in that the solution is arranged to be capable of being administered in a volume of 5 to 20 ml, preferably approx. 10 ml, per 100 kg of animal. A solution according to claim 1, characterized in that the diluent is selected from the group consisting of: plant oils such as soybean oil, peanut oil, castor oil, corn oil, cotton seed oil, olive oil, grape seed oil, sunflower oil; mineral oils such as vaseline, paraffin, silicone; 10 aliphatic or cyclic hydrocarbons or alternatively the medium chain length triglycerides, especially C8 to C12. A solution according to any one of claims 1-5, characterized in that the plasticizer is selected from the group consisting of: -polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, mannitol, mannitol, mannitol, mannitol sorbitan esters; lecithin, sodium carboxymethyl cellulose, silicone oils, anionic surfactants such as alkali metal stearates, especially sodium, potassium or ammonium stearates; calcium stearate, triethanolamine stearate; 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 is an anion of a strong acid such as the halide, sulfate and sulfonate anions; cetyltrimethylammonium bromide is among the cationic surfactants, amine salts of the formula N + R'R''R '' wherein the R groups are optionally hydroxylated hydrocarbon groups; octadecylamine hydrochloride is among the cationic surfactants, nonionic surfactants such as sorbitan esters optionally polyoxyethylenated, especially polysorbate 80, polyoxyethylenated DK 177400 B1 alkyl ethers; polyoxypropylated fatty alcohols such as polyoxypropylene-15 stearyl ether; polyethylene glycol stearate, polyoxyethylenated castor oil derivatives, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids, copolymers of ethylene oxide and propylene oxide, amphoteric surfactants such as the substituted betaine lauryl compounds; or a mixture of at least two of these agents. 10 A solution according to any one of claims 1-6, characterized in that it is an oily solution. Use of a Compound of Formula 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2-pyrazole to prepare a solution for direct application to the skin in a small volume, comprising from 0.1 to 2% w / v, relative to the total solution, of 1- [2,6-Cl2-4-CF3-phenyl] -20 3-CN-4 - [SO-CF3] -5-NH2-pyrazole and is adapted to release 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2- pyrazole on the skin and hair to interact with the parasites of cattle and sheep, especially blood mites such as Boophilus microplus in cattle, and saliva flies and lice in sheep. 25 Use according to claim 8, characterized in that the solution comprises from 0.25 to 1.5% w / v, relative to the total solution, of 1- [2,6-Cl2-4-CF3-phenyl] -3 -CN-4- [SO-CF3] -5-NH2-pyrazole. 30 Use according to claim 9, characterized in that the solution comprises 1% w / v, relative to the total solution, of 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO CF 3] -5-NH 2 pyrazole. 35 Use according to any one of claims 8-10, k characterized in that the solution is adapted to be administered in a volume of 5 to 20 ml, preferably 10 ml, per 100 kg of animal with a total volume from 10 to 150 ml per animal, preferably limited to 50 ml. Use according to any one of claims 8-11, characterized in that 1- [2,6-Cl2-4-CF3-phenyl] -3-CN-4- [SO-CF3] -5-NH2- pyrazole is administered at a ratio of 0.1 to 2 mg / kg, preferably 0.25 to 1.5 mg / kg, in particular 0.1 mg / kg. Use according to any one of claims 8-12 for the preparation of such a skin solution intended for administration monthly, preferably every two months, to the animal, the administrations terminating preferably 1 to 3 months before slaughter. 15