IE970224A1

IE970224A1 - N-Phenylpyrazole-based antiparasitic external device for¹cattle, in particular ear-rings

Info

Publication number: IE970224A1
Application number: IE970224A
Authority: IE
Inventors: Philippe Jeannin
Original assignee: Rhone Merieux
Priority date: 1996-03-29
Filing date: 1997-03-21
Publication date: 1997-10-08
Also published as: BR9702178A; FR2746596A1; ITTO970267A1; NL1005671C2; NL1005671A1; CA2222199C; CA2222199A1; WO1997036483A1; FR2746596B1; GR970100096A; MX9708994A; BE1010477A3

Abstract

The external device such as a ring, in particular an ear-ring, intended to eliminate cattle parasites, in particular Haematobia irritans, formed of a matrix including from 0.1 to 40%, preferably from 2.5 to 10%, by weight, relative to the ear-ring, of an active substance which is at least one compound of formula (I) below: <CHEM> this external device being designed to ensure efficacy for more than 30 weeks. <Fig. 2>.

Description

N-Phenylpyrazole-based antiparasitic external device for cattle, in particular ear-rings The present invention relates to external 5 antiparasitic devices for cattle, in particular in the form of a ring and more particularly an ear-ring.

The invention also relates to the use of active compounds for the manufacture of such external devices, as well as to a treatment process relating thereto.

One of the main cattle parasites is a fly known as Haematobia irritans (horn fly), the adult of which is a permanent haematophagic parasite of cattle. This parasite, which is encountered especially in North America, but also in Europe, Australia and Southern Africa, can lead to considerable economic losses, as regards both weight gain and milk production, in particular when the parasite density exceed 50 flies per animal, while, in certain regions, it is not uncommon to exceed 200 flies per animal.

At the present time, it is not known how to control this parasite effectively. The difficulty in controlling it results mainly from the fact that the parasite density is constant, since this is a parasite which possesses wings in its adult form, and can thus pass from one herd to another and thereby permanently reinfest herds for which a procedure to control this parasite has been implemented. Zn addition, in certain regions, the parasite density lasts throughout the year.

Breeders currently have few effective means of control available to them, in particular in the case of rearing in open grazing, even by ensuring constant control of these parasites, that is to say regular and closelytimed supplies of insecticides, all the more so since flies have developed resistance to pyrethroid· and to - 2 organophosphorus compounds.

Ear-rings intended, as their name implies, to be attached to the animal' s ear and to release an active substance over a longer or shorter period have also been proposed. These rings consist of a matrix, usually a plastic matrix, which incorporates the active substance and is able to release it over time. The aim of these rings is thus, theoretically, to ensure longlasting protection.

However, despite the activity claims, in the field rings do not display the efficacy required to ensure that these parasites are actually eliminated. The reason for this may be the low activity of the active substance included in the matrix. Another reason may be the accelerated degradation of these active substances under the effect of climatic factors, such as light, heat and rain. Lastly, the control of the release of the active substance from the matrix is widely overevaluated. The release generally proves to be difficult and variable, and it may depend highly on the manufacturing conditions, which may vary from one batch to another, and on the conditions of use, in particular climatic variations, and especially humidity and teiqperature, etc. In addition, only a relatively small amount of the active substance incorporated is actually released and it proves to be difficult to be able to control and optimize its release.

Only organophosphorus compounds have made it possible to obtain a release over about 4 months, but by means o£ considerable concentrations of active substance, of about 40% by weight.

Patent applications WO-A-87/03781, EP-A-0,295,117, EP-A-0,296, 381 and EP-A-0,500,209 relate to a family of insecticides which are N-phenylpyrazoles. These substances are described as being active against a very large number of parasites encountered in various fields, namely agriculture, public health and human and veterinary medicine.

EP-A-0,500,209 indicates that, in the field of public health, these compounds may be used to combat a large number of insects, in particular flies and among which are mentioned homfly or Haematobia irritans. However, Haematobia irritans is not mentioned in the context of treating the animals.

These substances may be applied in different ways, namely via the oral, parenteral, percutaneous or topical route. Topical administration itself covers various possibilities, namely sprays, powders, baths, showers, jets, greases, shampoos, creams, waxes, preparations of skin solution type (pour-on) and external devices such as ear-rings and collars to provide local or systemic treatment.

EP-A-0,295,117 and EP-A-0,500,209 also propose a composition for slow release which may be in the form of a collar or ear-rings, to control harmful insects. Such a formulation may comprise from 0.5 to 25% active material, from 75 to 99.5% polyvinyl chloride and a catalytic amount of a plasticizer, dioctyl phthalate.

US-A-5,472,955 illustrates the difficult nature of controlling Haematobia irritans and indicates that it is necessary to make use of a combination of two active compounds, diazinon and chlorpyrifos, in high concen-tration in a slow-release device. That document indicates that the compounds taken alone are not as effective as the synergistic combination of the two compounds. Diazinon simply affords an acceptable level of control of Haemotobia irritans over 3 to 5 months, whereas chlor-pyrifos appears to be incapable of this. The said document specifies at the end that an ear-ring containing a 40% mixture was much more active than two ear-rings applied on the same animal and containing - 4 21.4% diazinon as sole active ingredient. Although the proportion of active principle may range in theory from 8 to 40%, it is preferably between 20 and 40%. In the case of ear-rings, the proportion is from 10 to 50% by weight, preferably from 30 to 45% and optimally 40% by weight.

None of the documents cited either describee or suggests that it is possible to effectively protect cattle against Haematobia irritans, over a long period, using ear-rings comprising a single active compound, for which, in addition, a specialist might expect to encounter conventional problems of release from the rings and thus problems of activity.

As with the other insecticides of the prior art, these N-phenylpyrazoles are, indeed, subject to the same difficulties in the context of external release devices such as ear-rings.

It therefore did not appear to be conceivable to be able thus to effectively control parasites liable to be found on any part of the animal, which is all the more the case for winged parasites which give rise to a parasite density as high and constant as that of Haematobia irritans.

The Applicant has now found, surprisingly, that it is actually possible to effectively eliminate Haematobia irritans from cattle by using an ear-ring using an N-phenylpyrazole under specific concentration conditions. The Applicant has observed with surprise that, despite the problems associated with release by ear-rings, the efficacy extended throughout the animal's body and was very long-lasting and that, for example, with rings loaded to a content of 10%, it was possible to exceed 32 weeks at an efficacy of greater than 90%.

The active substance acts by simple contact, the parasite becoming impregnated with it on contact - 5 with the hairs and the skin.

The subject of the present invention is thus an external device such as a ring, in particular an earring, intended to eliminate cattle parasites, in particular Haematobia irritans, this device being formed of a matrix including from 0.1 to 40% by weight, relative to the ear-ring, of an active substance which is at least one compound of formula (I) below: *13 (I) in which: Rx is CN or methyl or a halogen atom; R2 is S(O)nR3 or 4,5-dicyanoimidazol-2-yl or haloalkyl; R, is alkyl or haloalkyl; R4 represents a hydrogen or halogen atom; or a radical NRsRe, SiO.R,, C(O)R,, C(O)O-R,, alkyl, haloalkyl or OR, or a radical -N»C (R,) (R10) ; Rs and Re independently represent a hydrogen atom or an alkyl, haloalkyl, C(O)alkyl, alkoxycarbonyl or S(O)rCF, radical; or R, and Re may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms, such as oxygen or sulphur; R, represents an alkyl or haloalkyl radical; R, represents an alkyl or haloalkyl radical or a hydrogen atom; R, represents an alkyl radical or a hydrogen atom; - 6 R10 represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; RX1 and Rxa represent, independently of each other, a hydrogen or halogen atom, or optionally CN or NOa; R13 represents a halogen atom or a haloalkyl, haloalkoxy, S(O)CF3 or SFs group; m, n, q and r represent, independently of each other, an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a radical C-Rxa, the other three valency positions of the carbon atom forming part of the aromatic ring; with the proviso that when Rx is methyl, either R3 is haloalkyl, R4 is NHa, Rxx is Cl, R13 is CF3 and X is N; or Ra is 4,5-dicyanoimidazol-2-yl, R4 is Cl, Rxx is Cl, R13 is CF3 and X is -C-Cl, this external device being designed to ensure efficacy for more than 30 weeks.

Preferably, the compound of formula (I) is such that: Rx is CN or methyl; Ra is S(O)nR3; Rj is alkyl or haloalkyl; R4 represents a hydrogen or halogen atom; or a radical NR5RS, SfOl.R,, CCOJR,, alkyl, haloalkyl or OR, or a radical -N-C(R,) (R10); Rs and Re independently represent a hydrogen atom or an alkyl, haloalkyl, C(O) alkyl or S(O)rCF3 radical; or Rs and Rs may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms, such as oxygen or sulphur; R, represents an alkyl or haloalkyl radical; R, represents an alkyl or haloalkyl radical or a hydrogen atom; - 7 Rg represents an alkyl radical or a hydrogen atom; R10 represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; R1X and R12 represent, independently of each other, a hydrogen or halogen atom; R13 represents a halogen atom or a haloalkyl, haloalkoxy, S(O)qCF3 or SFs group; m, n, q and r represent, independently of each other, an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a radical C-R12, the other three valency positions of the carbon atom forming part of the aromatic ring; with the proviso that when Rx is methyl, then R3 is haloalkyl, R4 is NH2, R1X is Cl, R13 is CF3 and X is N.

The compounds of formula (I) in which Rx is CN will be selected most particularly. The compounds in which Ra is S(O)nR3, preferably with n 1, R3 preferably being CF3 or alkyl, for example methyl or ethyl, or alternatively n - 0, R3 preferably being CF3, as well as those in which X C-R12, R12 being a halogen atom, will also be selected. The compounds in which Rtl is a halogen atom and those in which Rx3 is haloalkyl, preferably CF3, are also preferred. In the context of the present invention, the compounds which combine two or more of these characteristics will advantageously be selected. λ preferred class of compounds of formula (I) consists of confounds such that Ηχ is CN, R3 is haloalkyl, preferably CF3, or ethyl, R4 is NH2, R1X and R12 are, independently of each other, a halogen atom, and/or RX3 is haloalkyl.

The alkyl radicals in the definition of the compounds of formula (I) generally comprise from 1 to 6 - 8 carbon atoms. The ring formed by the divalent alkylene radical representing Rs and R6, as well as the nitrogen atom to which Rs and Rs are attached, is generally a 5-, 6- or 7-membered ring.

A compound of formula (X) which is most particularly preferred in the invention is 1- [2,6-Cl24-CF3phenyl ] 3-CN4- [SO-CF3] 5NH2pyrazole, referred to hereinbelow as compound A.

Mention may also be made of two compounds which differ from the above A by the following characteristics: 1- n 0, R3 CF3 2- n « 1, r3 as ethyl.

Compounds of formula (X) may be prepared according to one or other of the processes described in patent applications WO-A-87/3781, 93/6089, 94/21606 or European patent application EP-A-0,295, 117, or any other process falling within the competence of a specialist skilled in the art of chemical synthesis. For the chemical preparation of the products of the invention, a person skilled in the art is considered as having at his disposal, inter alia, all the contents of Chemical Abstracts and the documents which are cited therein.

However, low concentrations of from 1 to 15% by weight and more particularly, especially for compound A, from 2.5 to 10% are preferred. Under optimum conditions, the rings according to the invention comprise from 5 to 10% by weight of active substance, in particular of compound A.

Within the context of the present invention, the external devices obviously include any device intended to be attached to the animal's body and which allows the active substance to be released under the efficacy conditions of the invention. - 9 By acting on the concentration of active substance and/or on the composition, ear-rings can be made with an efficacy towards Haematobia irritans which can exceed 90% and even 95% for more than 30 weeks, in particular for 32 weeks.

It is noteworthy that this total and very long-lasting efficacy is obtained by the compound according to the invention alone, without addition of another insecticide.

The active substance can however comprise, in addition to the compound of formula (1), another insecticide, for example pyrethroids (in particular permethrin, cypermethrin, etc.), organophosphorus compounds (for example diazinon), imidacloprid and IGRs (insect growth regulators).

These active substances may be combined in different ways. The active substances are either combined within the same ear-ring, including a composite ear-ring, namely one made of two parts, each part including one of the active substances, or use may be made of two separate ear-rings, each comprising one of the active substances and each preferably intended to be placed on a different ear of the animal. In the latter case, the subject of the invention is a kit comprising these two ear-rings.

The matrix of the external devices according to the invention may be based on polyvinyl chloride (PVC) (see US-A-3,318,769, 3,852,416, 4,150,109, 5,437,869) and other vinyl polymers, to which additives such as plasticizers, pigments, etc. are optionally added. Zn general, the matrices usually used in the common external devices of ear-ring and collar type can be used.

The plasticizers may be chosen in particular from adipates, phthalates, phosphates and citrates. - 10 One or more plasticizers will preferably be added to the PVC, these plasticizers being chosen, in particular, from the following compounds: - diethyl phthalate - dioctyl sebacate - dioctyl adipate - diisodecyl phthalate - acetyl tributyl citrate - diethyl hexyl phthalate - di-n-butyl phthalate -benzyl butyl phthalate - acetyl tributyl citrate - tricresyl phosphate - 2-ethylhexyl diphenyl phosphate.

Even more peferably, a PVC matrix will be used in the presence of a first remanent plasticizer as described above and of a second plasticizer, in particular according to EP-A-0,539,295 and EP-A0,537,998.

Among the secondary plasticizers, mention may be made of the following products: - acetyl triethyl citrate - triethyl citrate - triacetin - diethylene glycol monoethyl ether - triphenyl phosphate.

A common stabilizer may also be added thereto.

Another subject of the present invention is a process for the elimination of external parasites, in particular Haematobia irritans, from cattle, in particular cattle reared in the open air and more particularly in open grazing, which consists in attaching to the animal the ear-ring or -rings according to the present invention, which ensure(s) the effective and longIE 970224 - 11 lasting protection described above.

This process generally consists in attaching to the animal 1 or 2 ear-rings or the like loaded with compound according to the invention, preferably with compound A. These rings have the specifications mentioned above.

The process may also comprise the combined use of other insecticides, by the use of rings, composite rings or separate rings as described above.

In general, the process according to the invention envisages the animal wearing the ring or rings throughout the year.

The aim of the method is non-therapeutic and is in particular to cleanse the animals' skin and hairs by eliminating the parasites which are present thereon, as well as their residues and dejections. The result of this is that the animals are no longer stressed by the parasites and their bites, this having positive consequences, for example on their growth and on the use of their food ration.

Another subject of the invention is a therapeutic method using the external device according to the invention, intended for treating and preventing parasit-oses having pathogenic consequences.

The subject of the present invention is also the use of a compound corresponding to formula (I) above, for the preparation of external devices such as rings, in particular ear-rings, intended to be attached to cattle in order to ensure elimination of Haemotobia irritans to a high degree of efficacy and over a period exceeding 30 weeks. The devices as above are concerned. The use according to the invention preferably includes the incorporation of 0.1 to 40¾ by weight, preferably from 1 to 15¾ by weight, of the compound of formula (I) in a matrix intended to form the external device. Even - 12 more preferably, the incorporation is made in a proportion of 2.5 to 10% by weight, and even from 5 to 10%.

Preferably, the use according to the invention is directed towards the manufacture of earrings .

Preferably, the use according to the invention is directed towards the production of external devices or ear-rings having an efficacy of greater than 90% or 95%.

The present invention will now be described in greater detail by means of a non-limiting embodiment example which refers to the drawing in which: - Figure 1 is a graph showing the population of Haematobia irritans in a control group, with the time (weeks) on the X-axis and the arithmetic mean on the Y-axis; and - Figure 2 is a graph with the time (weeks) on the X-axis and the arithmetic mean of the Haematobia irritans count on the Y-axis.

The following groups were prepared: Group A: controls: 10 heifers Group B: 10 heifers which have received earrings containing 2.5% compound A. Each animal receives one ring.

Group C: 10 heifers which have received earrings containing 10% compound A. Each animal receives one ring.

Group D: 10 heifers which have received earrings containing 10% compound A. Each animal receives two ring, one per ear.

The ear-rings are made based on polyvinyl chloride (PVC), to which a stabilizer (Mark 152S), a plasticizer (acetyl tributyl citrate) and a pigment (titanium dioxide) are added. They are manufactured by - 13 20 inj ection-moulding.

Each group of animals is placed in a pasture of about 100 to 150 acres (40 to 60 hectares).

The infestation with Haematobia irritans is 5 of natural origin.

The chronology of events is as follows: the ear-rings are inserted on day 0. The Haematobia irritans parasites are then counted every 6, 7 or 8 days.

An efficacy of greater than 90% and even greater than 95%, which can be up to 100%, over long periods was obtained with all of the formulations according to the invention. The 2.5% composition proved to be greater than 90% effective for 18 weeks. When inserted in only one ear or in both ears, the 10% composition also affords greater than 90% protection, over a much longer period of up to 32 weeks. The use of two ear-rings per animal affords greater protection, which is close to 100% over the entire 32-week period.

The results are reported in Figures 1 and 2.

Claims

1. External device such as a ring, in particular an ear-ring, intended to eliminate Haematobia irritans in cattle, this device being formed of a matrix including from 0.1 to 40% by weight, relative to the ear-ring, of an active substance which is at least one in which: is CN or methyl or a halogen atom; R, is S(O) m R3 or 4,5-dicyanoimidazol-2-yl or haloalkyl; R 3 is alkyl or haloalkyl; R 4 represents a hydrogen or halogen atom; or a radical NR S R C , S(O).R,, C(O)R 7 , C(O)O-R,, alkyl, haloalkyl or OR, or a radical -N»C(R 9 ) (R 10 ); R, and R 6 independently represent a hydrogen atom or an alkyl, haloalkyl, C(O)alkyl, alkoxycarbonyl or S(O) r CF 3 radical; or R s and R e may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms, such as oxygen or sulphur; R, represents an alkyl or haloalkyl radical; R, represents an alkyl or haloalkyl radical or a hydrogen atom; R, represents an alkyl radical or a hydrogen - 15 atom; R 10 represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; R lx and R 12 represent, independently of each other, a hydrogen or halogen atom or optionally CN or NO a ; R 13 represents a halogen atom or a haloalkyl, haloalkoxy, S(O) q CF 3 or SF s group; m, n, q and r represent, independently of each other, an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a radical C-R 13 , the other three valency positions of the carbon atom forming part of the aromatic ring; with the proviso that when R t is methyl, either R 3 is haloalkyl, R 4 is NH a , R tl is Cl, R 13 is CF 3 and X is N; or R, is 4,5-dicyanoimidazol-2-yl, R t is Cl, R X1 is Cl, R 13 is CF 3 and X is C-Cl; this external device being designed to ensure efficacy for more than 30 weeks.

2. Device according to claim 1, characterized in that the compound of formula (I) is such that: Ri is CN or methyl; Rj is S(O) a R 3 ; R 3 is alkyl or haloalkyl; R 4 represents a hydrogen or halogen atom; or a radical NR,R C , S(0).R,, C(O)R ? , alkyl, haloalkyl or OR, or a radical -N-C (R 9 ) (R 10 ) ; R, and R e independently represent a hydrogen atom or an alkyl, haloalkyl, C(0)alkyl or S(O) r CF 3 radical; or R, and r 6 may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms, such as oxygen or sulphur; R, represents an alkyl or haloalkyl radical; R, represents an alkyl or haloalkyl radical - 16 or a hydrogen atom; R, represents an alkyl radical or a hydrogen atom; R lo represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; R tl and R 12 represent, independently o£ each other, a hydrogen or halogen atom; R 13 represents a halogen atom or a haloalkyl, haloalkoxy, S(O),jCF 3 or SF s group; m, n, q and r represent, independently of each other, an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a radical C-R ia , the other three valency positions of the carbon atom forming part of the aromatic ring; with the proviso that when R a is methyl, then R 3 is N. 3. haloalkyl, R, is NH a , R 1X is Cl, Rl3 is CF 3 and X is Device according to claim 1 or 2, characterized in that the compound of formula (I) is such that R t is CN. 4. Device according to one of claims 1 to 3, characterized in that the compound of formula (I) is such that R 13 is haloalkyl, preferably CF 3 .

3. 5. Device according to one of claims 1 to 4, characterized in that the compound of formula (I) is such that 1½ is S(O) a R 3 , preferably with n 1, R 3 preferably being CF 3 or alkyl, in particular methyl or ethyl, or n - 0, R 3 preferably being CF 3 .

4. 6. Device according to one of claims 1 to 5, characterized in that the compound of formula (I) is such that X is C-R ia , R ia being a halogen atom.

5. 7. Device according to one of claims 1 to 6, characterised in that the aompound (I) is chosen from those for which R a is CN, R 3 is haloalkyl, R< is NH a , R 1X - 17 and R 12 are, independently of each other, a halogen atom, and/or R 13 is haloalkyl.

6. 8. Device according to claim 2, characterized in that the compound of formula (I) is 1- [2,6-Cl a 4-CF 3 phenyl ] 3-CN4- [SO-CF 3 ] 5NH 2 pyrazole.

7. 9. Device according to any one of claims 1 to 8, characterized in that the compound of formula (I) is present in a proportion of from 1 to 15% by weight.

8. 10. Device according to any one of claims 1 to 9, characterized in that the compound of formula (I) is present in a proportion of from 2.5 to 10%, preferably from 5 to 10%, by weight.

9. 11. Device according to any one of claims 1 to 10, characterized in that it is in the form of an earring.

10. 12. Device according to any one of claims 1 to 11, characterized in that it comprises a concentration of active substance which affords a greater than 90%, and even greater than 95%, efficacy over a long period of time exceeding 30 weeks.

11. 13. Use of a compound corresponding to formula (I) below: (I) in which: R x is CN or methyl or a halogen atom; R 2 is S(O) n R 3 or 4,5-dicyanoimidazol-2-yl or - 18 haloalkyl; R 3 is alkyl or haloalkyl; R 4 represents a hydrogen or halogen atom; or a radical NR S R S , S(O) m R 7 , C(O)R,, CtOjO-R,, alkyl, haloalkyl or OR, or a radical -N=C (R,) (R 10 ) ; R 5 and R s independently represent a hydrogen atom or an alkyl, haloalkyl, C(O)alkyl, alkoxycarbonyl or S(O) r CF 3 radical; or R s and R e may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms, such as oxygen or sulphur; R, represents an alkyl or haloalkyl radical; R 8 represents an alkyl or haloalkyl radical or a hydrogen atom; R, represents an alkyl radical or a hydrogen atom; R 10 represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; R X1 and R 13 represent, independently of each other, a hydrogen or halogen atom or optionally CN or NO a ; R 13 represents a halogen atom or a haloalkyl, haloalkoxy, S(O),CF 3 or SF s group; m, n, q and r represent, independently of each other, an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a radical C-R ia , the other three valency positions of the carbon atom forming part of the aromatic ring; with the proviso that when R x is methyl, either R 3 is haloalkyl, R 4 is NH a , R 1X is Cl, R X3 is CF 3 and X is N, or R a is 4,5-dicyanoimidazol-2-yl, R 4 is Cl, R xx is Cl, R XJ is CF 3 and X is -C-Cl; for the production of an external device such as a ring, in particular an ear-ring, intended to - 19 be attached to cattle in order to ensure the elimination of Haematobia irritans to a high degree of efficacy and over a period exceeding 30 weeks.

12. 14. Use according to claim 13, characterized in that the compound of formula (I) is such that: R a is CN or methyl; R a is S(O) n R 3 ; R 3 is alkyl or haloalkyl; R 4 represents a hydrogen or halogen atom; or a radical NR S R,, S(O) m R 7 , CfOlR,, alkyl, haloalkyl or OR, or a radical -N-C(R 9 ) (R 10 ) ; R, and R, independently represent a hydrogen atom or an alkyl, haloalkyl, C(O)alkyl or S(O) r CF 3 radical; or R s and R, may together form a divalent alkylene radical which may be interrupted by one or two divalent hetero atoms, such as oxygen or sulphur; R, represents an alkyl or haloalkyl radical; R, represents an alkyl or haloalkyl radical or a hydrogen atom; R, represents an alkyl radical or a hydrogen atom; R 10 represents a phenyl or heteroaryl group optionally substituted with one or more halogen atoms or groups such as OH, -O-alkyl, -S-alkyl, cyano or alkyl; R X1 and R ia represent, independently of each other, a hydrogen or halogen atom; R 13 represents a halogen atom or a haloalkyl, haloalkoxy, S(O) q CF 3 or SF, group; m, n, g and r represent, independently of each other, an integer equal to 0, 1 or 2; X represents a trivalent nitrogen atom or a radical C-R la , the other three valency positions of the carbon atom forming part of the aromatic ring; with the proviso that when R x is methyl, then R 3 is haloalkyl, R 4 is NH a , R lt ia Cl, R 13 ie CF 3 and X is - 20 N.

13. 15. Use according to claim 13 or 14, characterized in that the compound of formula (I) is such that R x is CN.

14. 16. Use according to one of claims 13 to 15, characterized in that the compound of formula (I) is such that R 13 is a haloalkyl, preferably CF 3 .

15. 17. Use according to one of claims 13 to 16, characterized in that the compound of formula (I) is such that R 3 is S(O) n R 3 , preferably with n = 1, R 3 preferably being CF 3 or alkyl, especially methyl or ethyl, or n - 0, R 3 preferably being CF 3 .

16. 18. Use according to one of claims 13 to 17, characterized in that the compound of formula (I) is such that X is C-R 13 with R 13 being a halogen atom.

17. 19. Use according to one of claims 13 to 18, characterized in that the compound of formula (I) is such that R t is CN, R 3 is haloalkyl, R< is NH a , R X1 and R 13 are, independently of each other, a halogen atom, and/or R 13 is haloalkyl.

18. 20. Use according to claim 14, characterized in that formula (I) is 1- [2,6-Cl 3 4-CF 3 phenyl] 3-CN4- [SO-CF 3 ] 5-NH 3 pyrazole.

19. 21. Use according to one of claims 13 to 20, characterized in that the compound of formula (X) is incorporated in a proportion of 0.1 to 40% by weight, preferably from 1 to 15% by weight, in a matrix intended to form the collar or other external device.

20. 22. Use according to one of claims 13 to 21, characterized in that the compound of formula (X) is incorporated in a proportion of 2.5 to 10% by weight, preferably from 5 to 10%, in a matrix intended to form the external device.

21. 23. Use according to one of claims 13 to 22, characterized in that it is directed towards the μ > f 7 (f - 21 manufacture of ear-rings. 24. Use according to one of claims 13 to 23, characterized in . that the efficacy is greater than 90% or 9 5%. 5 25. Use according to one of claims 13 to 24, characterized in that the efficacy is maintained over a long period of time exceeding 30 weeks.

22. 26. Process for the treatment of cattle against Haematobia irritans, which consists in attaching to the 10 animal at least one external device as described, and under the conditions indicated, in any one of the preceding claims.

23. 27 . External device substantially as described herein