MXPA06006961A - Topical formulations comprising a 1-n-arylpyrazole derivative and a formamidine - Google Patents

Abstract

The present invention provides for, inter alia, novel topical formulations comprising at least one 1-N-arypyrazole derivative and a formamidine such as amitraz, and to methods for treating, controlling, or preventing parasite infestations on mammals or birds. The inventive formulations include spot-on, pour-on or spray formulations and may include a further ectoparasiticide, such as an IGR compound, an avermectin or milbemycin derivative, or a pyrethroid insecticide, and/or anthelmintics such as benzimidazoles or imidazothiazoles. The inventive formulation provides a 1 arger duration of parasite control a t a faster rate o f control. The inventive formula remains effective up to three months from the first application. Moreover, the inventive formulations prevent tick attachment to the animal, thereby providing protection against tick borne diseases. The ectoparasites which may be controlled, treated or prevented by the present invention includes ticks, fleas, mites, mange, lice, mosquitoes, flies and cattle grubs.

Description

TOPICAL FORMULATIONS COMPRISING A DERIVATIVE OF 1-N-ARILPIRAZOLE AND A FORMAMIDINE FIELD OF THE INVENTION This invention provides, inter alia, novel topical formulations comprising at least one derivative of 1-N-arylpyrazole and at least one formaraidin such as amitraz and methods for treating parasite infestations in mammals and birds when applied topically. the inventive formulations to mammals and birds. The inventive formulations exhibit activity against ectoparasites such as fleas and ticks, which is far superior to formulations comprising a 1-N-arylpyrazole derivative alone, such as fipronil, thus indicating synergy. This result is even more surprising given the fact that amitraz is not recognized in the field as a flea product. BACKGROUND OF THE INVENTION Parasitic diseases can be caused either by endoparasites or ectoparasites. As used in the present endoparasites it refers to those parasites that live inside the body of the host, either within an organ (such as the stomach, lungs, heart, intestines, etc.) or simply under the skin. Ectoparasites are those parasites that live on the outer surface of the host but still remove nutrients from the host. Endoparasitic diseases can also be subdivided based on the kind of parasite involved in the infection. For example, the endoparasitic diseases generally referred to as helminthiasis are due to infection of the host with parasitic worms known as helminths. Helminthiasis is a prevalent and serious economic problem worldwide that involves the infection of domesticated animals such as pigs, sheep, horses, cattle, goats, dogs, cats and poultry. Many of these infections, caused by the group of worms described as nematodes, cause diseases in several species of animals worldwide. These diseases are frequently serious and can result in the death of the infected animal. The most common genus of nematodes that infect the animals referred to above include, but are not limited to, Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, B unostomum, Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichoneraa, Dictyocaulus, Capillaria. , Haterakis, Toxocara, Ascaridia, Oxiyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Many parasites are specific to the species (they infect only one host) and most also have a preferred site of infection within the animal. A) Yes, Haemonchus and Ostertagia mainly infect the stomach while Nematodirus and Cooperia mainly attack the intestines. Other endoparasites reside in the heart, eyes, lungs, blood vessels and the like while still others are subcutaneous parasites. Helminthiasis can lead to weakness, weight loss, anemia, intestinal damage, poor nutrition and damage to other organs. If left untreated, these diseases can result in the death of the animal. Examples of endoparasites that infect animals and man may include but are not limited to gastro-intestinal parasites of the genera Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris, Enterobius and the like. Other endoparasites that infect animals and man are found in the blood or other organs. Examples of such parasites include, but are not limited to, Wuchereria, Brugia, Onchocerca, and the like, as well as extra-intestinal stages of the intestinal worms Strongylides and Trichinella. Ectoparasites that infest man and domestic animals include arthropods, such as ticks, fleas, mites, mosquitoes, lice and the like and infections by these parasites can result in the transmission of serious and even fatal diseases. Infestations by ectoparasitic arthropods include but are not limited to, ticks, mites, lice, barn flies, antenna flies, blow flies, face flies, fleas, mosquitoes and the like are also a serious problem. Infection by these parasites results not only in the loss of blood and skin lesions, but can also interfere with normal eating habits thereby causing weight loss. Ectoparasitic infestations of a host may also result in the transmission of serious diseases including, but not limited to, encephalitis, anaplasmosis, babesiosis, rocky typhus fever, Lyme disease, ehrlichiosis, West Nile virus, postulous eruption of pigs, malaria, yellow fever and the like, many of which can be fatal to the host. Animals can be infected by several species of parasites at the same time since infection by a parasite can weaken the animal and make it more susceptible to infection by a second species of parasite. Many of the compounds used in this invention are also active against household pests including, but not limited to, cockroach, Blatella sp., Clothing moth, Tineola sp., Carpet beetle, Attagenus sp. and the homemade fly Musca domestica and against Solenopsis invicta (imported red ants), termites and the like. These compounds are also useful against agricultural pests such as aphids. { Acyrthiosphon sp) cotton locusts and weevils as well as against "insect pests that attack stored grains such as Tribolium sp. And against immature stages of insects that live in plant tissue." Anthelmintic compounds are also useful as a nematodicide for control. of nematodes of the earth, which may be agriculturally important Antiparasitic agents are also useful for the treatment and / or prevention of helminthiasis in domestic animals such as cattle, sheep, horses, dogs, cats, goats, pigs and poultry. They are also useful in the prevention and treatment of parasitic infections of these animals by ectoparasites such as ticks, mites, lice, fleas, mosquitoes and the like.They are also effective in the treatment of human parasitic infections. formulation of antiparasitic formulations are known in the art. cluyen oral formulations, baits, dietary supplements, powders, shampoos, etc. Formulations for localized topical applications of antiparasitic formulations are also known in the art. For example, settling solutions that comprise 1-N-phenylpyrazole derivatives, such as fipronil, are known in the art and are described in, for example, US Patent No. 6,010,710, US Patent No. 6,413,542, US Patent No. 6,001,384, US Patent No. 6,413,542 as well as copending application 10 / 120,691 filed on April 11, 2002 and now admitted. Other methods for formulating antiparasitic agents include certain placement formulations or sprays. Fixed placement formulations are well-known techniques for topically delivering an antiparasitic agent to a limited area of the host. For example, U.S. Patent No. 5,045,536 describes such formulations for ectoparasites. Other determinate placement formulations include U.S. Patent No. 6,426,333 and U.S. Patent No. 6,482,425 and USSN Application 10 / 155,397, now admitted and published as Publication No. U.S. 2003-0050327A1. Reference is also made to Publication No. U.S. 2003-16688A1. WO 01/957715 discloses a method for controlling ectoparasites in small rodents as well as interrupting or preventing diseases caused by small arthropods or rodents, which comprises applying topical formulations, such as set placement compositions, to the skin, or to the hair of the mouses. 1-N-arylpyrazoles as a class of chemical substances are well known in the art, as well as methods for their use in the control of parasites including insects, such as fleas, ticks, lice or mosquitoes in mammals, such as domesticated livestock. or companion animals or birds, either alone or in combination with other pesticides such as insect growth regulators. See, for example, EP-A-295, 217, EP 295 177, EP-A-840-686, EP-A-352, 944, WO 00/35844, WO 98/39972, US Patent Nos. 5,122,530, 5,236,938 , 5,232,940, 5,576,429, 5,814,652, 5,567,429, 6,090,751 and 6,096,329 as well as Publication No. US 2002-90381-A1. See also the co-pending applications USSN 07 / 719,942; 08 / 933,016, 09 / 174,598; 08 / 863,182 and 08 / 863,692. The compounds of the families defined in these patents are extremely active and one of these compounds, 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethyl-sulfinylpyrazole, or fipronil, is particularly effective, but not exclusively effective, against fleas and ticks. The 1-arylpyrazoles exert their activity to be distributed through the sebaceous glands of the animal. WO-A-87/3781, EP-A-295,117 and EP-A-500,209 describe a class of insecticides which are N-phenyl-pyrazole derivatives. These compounds are given to have activity against a very large number of parasites, including insects and acarines in fields as varied as agriculture, public health and veterinary medicine. The general teaching of these documents indicates that these insecticidal compounds can be administered via different routes: oral, parenteral, percutaneous and topical routes. Topical administration includes, in particular, solutions for the skin (specific casting or specific placement), sprays, soaks, baths, irrigations, jets, powders, fats, shampoos, creams, etc. Skin solutions of the given void type can be designed for percutaneous administration. Example 9 of EP-A-295,117 and Example 291 of EP-A-500,209 disclose a solution for the defined void type skin containing 15% insecticide and 85% dimethyl sulfoxide, for percutaneous administration of the insecticide. The 1-N-arylpyrazole derivatives are known in the art to prevent, treat or control the infestation of ectoparasites in mammals, such as cats, dogs and cattle. Amitraz is known in the art as a pesticide and is used to control red mites, leaf mites, coccus and aphids. In animals, amitraz is used to control ticks, mites and lice. Extoxnet htt_; __ // ace. orst edu / ínfD / extpnet / pi s / amitraz .html. However, amitraz is not known in the art to treat fleas. Amitraz belongs to the chemical group of formamidine, a group that includes clordimeform and clormebuform, both of which are useful in crop protection. Amitraz, described in US Patent Nos. 3,781,355 and 3,864,497 (the contents of which are incorporated herein by reference in their totals) has the following structure: Other compounds that are known in the art to prevent, treat or control the infestation of endo- and ectoparasites include derivatives of milbemycin or avermectin. The avermectin and milbemycin series of compounds are potent anthelmintic and antiparasitic agents against a wide range of internal and external parasites. The compounds belonging to this series are either natural products or are semi-synthetic derivatives thereof. The structures of these two series of compounds are closely related and both share a complex 16-membered macrocyclic lactone ring; however, milbemycin does not contain an aglycone substituent at position 13 of the lactone ring. Natural product avermectins are disclosed in U.S. Patent No. 4,310,519 to Albers-Schonberg et al., And compounds 22, 23-dihydro avermectin are disclosed in Chabala et al., U.S. Patent No. 4,199,569. For a general discussion of avermectins, which include a discussion of their uses in humans and animals, see "Ivermectin and Abamectin," W.C. Campbell, ed., Springer-Verlag, New York (1989). Milbemycins that occur naturally are described in Aoki et al., US Patent No. 3,950,360 as well as in the various references cited in "The Merck Index" 12th ed., S. Budavari, Ed., Merck &Co., Inc. Whitehouse Station, New Jersey (1996) Semi-synthetic derivatives of these classes of compounds are well known in the art and are described, for example, in U.S. Patent No. 5,077,308, U.S. Patent No. 4,859,657, U.S. Patent No. 4,963,582, Patent -North American No. 4,855,317, North American Patent No. 4,871,719, U.S. Patent No. 4,874,749, Patent North American No. 4,427,663, US Patent No. 4,310,519, US Patent No. 4,199,569, US Patent No. 5,055,596, US Patent No. 4,973,711, US Patent No. 4,978,677 and US Patent No. 4,920,148. The avermectins and milbemycins share the same common 16-membered acrocyclic lactone ring; however, milbemycins do not possess the disaccharide substituent at position 13 of the lactone ring. While many avermectin compounds are known in the art, a structure representative of the class of compounds is as follows: where the dashed line indicates a single or double link at positions 22, 23; Ri is hydrogen or hydroxy with the proviso that Ri is present only when the dashed line indicates a single bond; R 2 is alkyl of 1 to 6 carbon atoms or alkenyl of 3 to 6 carbon atoms or cycloalkyl of 3 to 8 carbon atoms; R3 is hydroxy, methoxy- or = NOR5, where R5 is hydrogen or lower alkyl; and R 4 is hydrogen, hydroxy or where Re is -hydroxy, amino, mono- or di-lower alkylamino or lower alkanoylamino. The preferred compounds are avermectin Bla / Blb (abamectin), 22, 23-dihydro avermectin Bla / Blb (ivermectin) and the 4-acetylamino-5-ketoximino derivative of avermectin Bla / Blb. Both abamectin and ivermectin are approved as broad spectrum antiparasitic agents. The structures of abamectin and ivermectin are as follows: wherein for abamectin the dashed line represents a double bond and Ri is not present and for ivermectin the double bond represents a single bond and Ri is hydrogen; and R2 is isopropyl or sec-butyl. The 4"-acetyl amino-5-ketoximino derivatives of avermectin Bla / Blb have the following structural formula: where R2 is isopropyl or sec-butyl. The avermectin products are generally prepared as a mixture of at least 80% of the compound where R2 is sec-butyl and not more than 20% of the compound where R2 is isopropyl. Other preferred avermectins include enamectin, eprinomectin and doramectin. Doramectin is disclosed in U.S. Patent No. 5,089,490 and EP 214 738. This compound has the following structure: In the present formulations, ivermectin and eprinomectin are especially preferred. A representative structure for a milbemicin is that for milbemicin oti: A particularly preferred avermectin is moxidectin, whose structure is as follows: The compound is disclosed in the Patent North American No. 5,089,490. Other classes of compounds are known to treat endo- and ectoparasites. These classes include benzimidazoles, which are effective against tapeworms, roundworms and lung worms, imidazothiazoles that are effective against worms, tapeworms and lung worms, and pyrethroids. Examples of benzimidazoles include albendazole (North American Patent No. 3,915,986); Fenbenzazole Patent North American No. 3,954,791), mebendazole (US Patent No. 3,657,261), oxibenzazole (US Patent No. 3,574,845) and triclabenzazole (US Patent No. 4,197,307). An example of an imidazothiazole is levamisole (U.S. Patent No. 3,529,350). Pyrethroids are a class of naturally occurring insecticides or derivatives synthetically. Synthetic pyrethroids include pyrethrin I and pyrethrin II. Synthetic pyrethroids include permethrin (Patents North American Nos. 4,113,968), resmethrin and sumitrin (U.S. Patent Nos. 3,934,023 and 2,348,930), deltamethrin and fenvalerate. BRIEF DESCRIPTION OF THE INVENTION The present invention provides, inter alia, novel topical formulations comprising at least one derivative of 1-N-arylpyrazole and a formamidine, such as but not limited to amitraz, and methods for treating, controlling or preventing infestations. of parasites in mammals or birds. The inventive formulations include formulations of particular placement, set or spray and may include an additional ectoparasiticide, such as an IGR compound, an avermectin or milbemycin derivative, or pyrethroid insecticides, and anthelmintics, such as benzimidazoles and imidazothiazoles. The inventive formulation provides a longer duration of parasite control at a faster rate of control. The inventive formula remains effective up to three months from the first application. In addition, the inventive formulations prevent binding of the ticks to the animal, thus providing protection against tick-borne diseases. Ectoparasites that can be controlled, treated or prevented by the present invention include ticks, fleas, mites, scabies, lice, mosquitoes, flies and larvae of livestock. More specifically, the present invention provides, inter alia, a certain parasitic positioning formulation, comprising: a) an effective amount of an ectoparasitic combination comprising a 1-N-arylpyrazole derivative and a formamidine; b) a pharmaceutically or veterinarily acceptable liquid carrier vehicle; c) optionally, a crystallization inhibitor. This invention further provides a certain parasitic voiding formulation, comprising: a) an effective amount of an ectoparasitic combination comprising a derivative of 1-N-arylpyrazole and amitraz; b) a pharmaceutically or veterinarily acceptable liquid carrier vehicle; c) optionally, a crystallization inhibitor; and d) optionally, an antioxidant. Also provided in the present invention is a parasitic dew formulation, comprising: a) an effective amount of an ectoparasitic combination comprising a 1-N-arylpyrazole and amitraz derivative; b) a pharmaceutically or veterinarily acceptable liquid carrier vehicle. A further embodiment of the present invention is the formulations of particular placement, set or dewatering which additionally comprise at least one additional anti-parasiticidal or anthelmintic agent, such as an IGR compound, a derivative of milbemycin or avermectin, a pyrethroid, a benzimidazole , such as albendazole, fenbenzazole, mebendazole, oxybendazole or triclobendazole, or an imidazothiazole, such as levamisole. The present invention further provides a method for preventing, eliminating or controlling parasites in a mammal or bird in need thereof or in an environment in which they reside, which comprises applying an effective amount of the formulation for a particular placement, determined emptying or inventive spray to the mammal or bird. The animals include mammals, - such as dogs, cats, zebras and horses, and birds, such as chickens, turkeys and quail. The environments include animal houses, such as dog or cat beds, horse stables and soft chicken straw. DETAILED DESCRIPTION OF THE INVENTION Other objects, features and aspects of the present invention are disclosed in, or are obvious from, the following Detailed Description. It will be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only and is not intended as limiting the broader aspects of the present invention, than the broader aspects that are encompassed in the exemplary construction . In fact, it will be apparent to those skilled in the art that various modifications and variations may be made in the present invention without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one embodiment may be used in another embodiment to provide a still further embodiment. It is proposed that the present invention covers such modifications and variations as fall within the scope of the appended claims and their equivalents. For convenience, certain terms used in the Specification, the Examples and the attached Claims are collected here. Definitions: As used herein, the term "comprising" in this description may mean "including" or may have the meaning commonly given to the term "comprising" in the United States Patent Act. Preferred topical formulations include those formulations wherein 1-arylpyrazole is a compound of the formula: wherein: Ri is a halogen atom, CN or alkyl; R2 is S (0) nR3 or 4,5-dicyanoimidazol-2-yl or haloalkyl; R3 is alkyl, alkenyl, alkynyl, haloalkyl ,. haloalkenyl or haloalkyl; R4 is hydrogen, halogen, NR5Re / SC (0) mR7, 15C (0) 'R7, C (0) OR7, alkyl, haloalkyl, OR8 or substituent -N = C (R9) (Rio); R5 and R6 independently represent a hydrogen atom, alkyl, haloalkyl, C (O) alkyl, S (0) rCF3 or alkoxycarbonyl or Rs and Re together can be combined to form a 5- to 7-membered ring; R7 represents an alkyl or haloalkyl group; R8 represents an alkyl, haloalkyl or a hydrogen; R9 represents an alkyl or a hydrogen; Rio represents an optionally substituted aryl or an optionally substituted heteroaryl group; Ru and Ri2 represent, independently of each other, hydrogen, halogen, CN or N02; R13 represents a halogen atom or a haloalkyl, haloalkoxy, S (0) qCF3 or group SF5; 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 C-R 2, the other three valences of the carbon atom that are part of the aromatic ring optionally with a pharmaceutically acceptable carrier or excipient. A more preferred formulation is one wherein 1-N-arylpyrazole is a compound of the formula: wherein: Ri is a halogen atom, CN or methyl; R2 is S (0) nR3 or 4,5-dicyanoimidazol-2-yl or haloalkyl; R is alkyl, haloalkyl, haloalkenyl • or haloalkynyl; • R4 represents a hydrogen or atom of Halogen or NR5R6, S (0) mR7, C (0) R7 or C (0) 0R7, alkyl, haloalkyl or 0R8 or a group N = C (Rg) (Rio); R5 and R6 independently represent a hydrogen atom or an alkyl group, Haloalkyl, C (O) alkyl, S (O) rCF3 or alkoxycarbonyl or R5 and Re together can form a 5- to 7-membered ring; R7 represents an alkyl substituent or Haloalkyl; R8 represents an alkyl or haloalkyl or a hydrogen; R9 represents an alkyl or a hydrogen atom; Rio represents an optionally substituted aryl or an optionally substituted heteroaryl group; Rn and R12 represent, independently of each other, hydrogen, halogen CN or N02; Ri3 represents a halogen atom or a haloalkyl, haloalkoxy, S (0) qCF3 or group SF5; 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 C-Ri2, the other three valences of the carbon atom that are part of the aromatic ring; with the proviso that, when i is methyl, then either 3 is haloalkyl, R 4 is NH 2, Ru is Cl, R 13 is CF 3 and X is N or R 2 is 4,5-dicyanoimidazol-2-yl, R 4 is Cl , Rn is Cl, 13 is CF3 and X is C-Cl. More preferably, this invention provides a certain parasitic placement formulation wherein the 1-N-arylpyrazole in the ectoparasitic combination is a compound of the formula (I) wherein: Ri is a halogen atom, CN or methyl; R 2 is S (0) nR 3 or 4,5-dicyanoimidazol-2-yl or haloalkyl; R3 is C? -C6 alkyl or C? -C6 haloalkyl; R4 represents a hydrogen atom or halogen; or NR5R6, S (0) raR7, C (0) R7 or C (0) OR7, alkyl, haloalkyl or OR8 or - N = C (R9) (R10); R5 and R6 independently represents a hydrogen atom or Ci-Ce haloalkyl of C? -C6, C (O) Ci-Ce alkyl, S (0) rCF3, C? -C6 acyl or C? - alkoxycarbonyl C6; Rs and Re together may be combined to form a 5- to 7-membered ring, which may include one to two divalent heteroatoms selected from the group consisting of oxygen or sulfur; R7 represents C? -C6 alkyl or C? -C6 haloalkyl; R8 represents a C? -C6 alkyl or C? -C6 haloalkyl or a hydrogen atom; R9 represents a Ci-Cß alkyl or a hydrogen atom; Rio represents an optionally substituted phenyl or optionally substituted heteroaryl group wherein the substituents are selected from the group consisting of halogen OH, -0-, Ci-Cß-S-alkyl-C6-C6 alkyl, cyano or C-alkyl. ? -C6; Rii and R12, independently of one another, represent hydrogen, halogen, CN or N02; Ri3 represents a halogen, a haloalkyl of C? -C6, haloalkoxy of C? -C6, S (0) qCl3 or group SF5; and, m, n, q and r independently of each other are 0, 1, or 2; (b) the liquid carrier vehicle comprises a solvent and a cosolvent wherein the solvent is selected from the group consisting of acetone, acetonitrile, benzyl alcohol, bitildiglicol, dimethylacetamide, dimethylformamide, dipropylene glycol n-butyl ether, ethylene glycol monoethyl ether, monomethylacetamide , dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, 2-pyrrolidone, in particular N-methylpyrrolidone, diethylene glycol monoethyl ether, ethylene glycol, fatty acid esters of diethyl phthalate, such as diethyl ester or diisobutyl adipate, and a mixture of at least two of these solvents and the cosolvent is selected from the group consisting of ethanol, isopropanol or methanol; and (c) a crystallization inhibitor selected from the group consisting of an anionic surfactant, a cationic surfactant, a nonionic surfactant, an amine salt, an amphoteric surfactant or polyvinylpyrrolidone, polyvinyl alcohols, vinyl acetate and vinylpyrrolidone copolymers, polyethylene glycols , benzyl alcohol, mannitol, glycerol, sorbitol, esters of polyoxyethylenated sorbitan; lecithin, sodium carboxymethylcellulose and acrylic derivatives, or a mixture of these crystallization inhibitors. Especially preferred as determined placement formulations are those wherein the 1-N-arylpyrazole derivative in the ectoparasitic combination is a compound wherein the ring formed by the divalent alkylene substituent representing R5 and R6 and the nitrogen atom to which R5 and Re are joined have 5, 6 or 7 members or where Ri is CN, R3 is haloalkyl of C? -C6, R4 is NH2, Rn and R12 are, independently of each other, hydrogen or halogen and R13 is haloalkyl of Ci- The most preferred 1-N-arylpyrazoles, which are used in the determined deposition and pouring formulations, are: (A) 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole; or (B) 1-N-arylpyrazole derivative of the formula: .55" Other 1-N-arylpyrazole derivatives which are used in the formulation of the invention which are preferred are those of the formula (II) wherein: Rioi is cyano, -C (O) alkyl, C (S) NH2, alkyl, haloalkyl, C (= NOH) NH2 or C (= NNH2) NH2; R102 is S (0) n'R? O3 alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl or alkynyl; R103 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl or haloalkynyl; R? O is -N = C (R? O5) ~ ZR? Oe, -N = C (R105) -N (R107) -Rios, or -N (R? 09) -C (R? O5) = NR ? oe; R105 is hydrogen; I rent; or alkyl substituted by halogen, alkoxy, Haloalkoxy or -S (0) mR; R106 and R107 each independently represents hydrogen, alkyl, alkenyl or alkynyl, or alkyl substituted by one or more of halogen, alkoxy, haloalkoxy, Amino, alkylamino, dialkylamino, cyano or -S (0) m'Ru5; or alkyl substituted by phenyl or pyridyl each of which is optionally substituted with one or more groups selected from halogen, Nitro and alkyl group; or R107 and Rios can form together with the nitrogen to which a 3 to 7-membered ring is attached which may additionally contain one or more heteroatoms selected from oxygen, nitrogen or sulfur; Rivers is alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, -C (0) Rn4 or -S (0) t'Rpo; R109 R110 114 are alkyl or haloalkyl; Rui and R112 are independently selected from halogen, hydrogen, CN and N02; R113 is selected from halogen, haloalkyl, haloalkoxy, -S (0) q > CF3, and -SF5; US is alkyl or haloalkyl; X is selected from nitrogen and C-Rn2; Z is O, S (O) a ', - or NR10-7; a ', m /, n' and q 'are independently selected from 0, 1 and 2; and t 'is 0, 1 or 2; and acceptable veterinary salts thereof. Other preferred 1-N-arylpyrazole derivatives that can be included in the inventive formulations are those compounds of the formula (III): Cpn wherein: R 2- 01 is cyano, C (O) alkyl, C (S) NH 2, alkyl, C (= NOH) NH 2 or C (= NH 2) NH 2; R 202 is S (O) hR 203, alkenyl, haloalkenyl, cycloalkyl, halocycloalkyl or alkynyl; R203 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl or haloalkynyl; 10 R2 04 eS -N (R205) C (O) CR205R2O7R208, -N (R205) C (0) aryl, or -N (R205) C (0) OR207; R2 05 is alkyl, haloalkyl, cycloalkyl, halocycloalkyl, cycloalkylalkyl, halocycloalkylalkyl, alkoxyalkyl, Haloalkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl; R? Oe is hydrogen, halogen, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, formyloxy, Alkylcarbonyloxy, haloalkylcarbonyloxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, dialkylamino, Haloalkylamino, di (haloalkyl) amino, cycloalkyloxy, halocycloalkyloxy, alkoxyalkoxy, haloalkoxyalkoxy, alkoxyalkoxyalkoxy, aryloxy or arylalkoxy; R207 and R208 are independently hydrogen, alkyl, haloalkyl, cycloalkyl or halocycloalkyl; or R207 and R208 can form together with the carbon to which a 3 to 7-membered ring is attached which may additionally contain one or more heteroatoms selected from nitrogen, oxygen and sulfur; Xi is selected from nitrogen and C-R2? 2; R211 and R212 are independently selected from halogen, hydrogen, CN and NO ^; R213 is selected from halogen, haloalkyl, haloalkoxy, -S (0) kCF3 and -SF5; and h and k are independently selected from 0, 1 and 2; and an acceptable veterinary carrier, excipients and salts thereof. A preferred class of compounds of the formula (II) for use in the inventive formulation is that wherein: Rioi is cyano or alkyl; R102 is S (0) n '? O3; R103 is alkyl or haloalkyl; R104 is -N = C (R? O5) -Z-R? O6; R105 is hydrogen, alkyl or haloalkyl; Z is 0, S (0) a,; or NR? 07; Rioe and R107 are independently selected from hydrogen and unsubstituted or substituted alkyl; or Riod and R107 may form together with the nitrogen to which a 3 to 7 membered ring is attached which may additionally contain one or more heteroatoms selected from oxygen, nitrogen or sulfur; X is selected from nitrogen and C-R112; Rui and R112 are independently selected from halogen,. hydrogen, CN and N02; R113 is selected from halogen, haloalkyl, haloalkoxy, -S (0) q'CF3, and SF5; Preferably, Rioe is alkyl which is substituted by one or more of halogen, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, sulfide, sulfoxide, sulphone, or pyridyl portions of which the phenyl or pyridyl portion is optionally substituted with one or more groups selected from halo, nitro and alkyl. Preferably, 1-N-arylpyrazole has one or more of the following characteristics: Rioi is cyano; R104 is -N = C (R? 05) -Z-R? O6 and Z is -NR107; X is C-Rn2; Rm and R112 represents a chlorine atom; and n3 is CF3, OCF3 or -SF5; R ??2 is S (0) n'CF3 and n is 0, 1 or 2. A further preferred class of 1-N-arylpyrazoles which may be included in the inventive formulations or processes are those of the formula II wherein: R101 is cyano or alkyl; R104 is -N = C (R105) -Z- Rioe; and R105 is hydrogen or C1-C3 alkyl. The compounds of the formula (II) preferably have one or more of the following characteristics: R101 is cyano or methyl; R103 is halomethyl (preferably CF3); Rui and R112 each independently represents a halogen atom; X is C-Rn2; R113 is haloalkyl (preferably CF3 haloalkoxy (preferably OCF3), or -SF5; or n 'O, 1 or 2 (preferably O or 1). A further preferred class of compounds of the formula (II) for use in the formulations and inventive methods are those wherein: Rioi is cyano; R102 is S (0) n'R? O3; R103 is halo ethyl; R104 is -N = C (R? O5) -Z-R? Oe; Z is NRio; R105 is hydrogen or alkyl; Rioe and R107 each independently represent hydrogen, alkyl, alkenyl or alkynyl; or alkyl substituted by one or more of halogen, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, cyano or -S (0) mRi5; or alkyl substituted by phenyl or pyridyl rings which are optionally substituted with one or more groups selected from halogen, nitro and alkyl; X is selected from nitrogen and C-Ru2; Rioe and R? I2 are each independently represents a halogen atom; Rn3 is selected from haloalkyl, haloalkoxy and -SF5; us is alkyl or haloalkyl; and n 'and / are independently selected from 0, 1 and 2. A further preferred class of compounds of the formula (II) is that wherein: Rioi is cyano; R102 is S (0) n'CF3; R104 is -N = C (R? O5) -Z-R? Oe or -N = C (Rivers) -N (R107) -R? O8; Z is NR? 07; R105 is hydrogen or alkyl; R106 and R107 each independently represents hydrogen, alkyl, alkenyl or alkynyl; or alkyl substituted by one or more of halogen, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, cyano or S (0) Rn5; or methyl substituted by phenyl or pyridyl, rings that are optionally substituted with one or more groups selected from halogen, nitro and alkyl; R 8 is alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or -S (O) 'Ruo; X is selected from nitrogen and C-Rn2; R109 / u6 and u-i independently represent alkyl or haloalkyl; Rui and R112 each represent a chlorine atom; R113 is CF3 or -SF5; and 'm' and n 'are 0, 1 or 2; and t 'is 0 or 2. An additional preferred class of compounds of formula (II) are those wherein: R101 is cyano; R102 is S (0) mCF3; R104 is -N = C (R? O5) -Z-R? Oe; z is NR? 07; R105 is hydrogen or methyl; Rioe and R107 each independently represent hydrogen, alkyl, alkenyl or alkynyl; or alkyl substituted by one or more of halogen, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, cyano or S (0) m '? i5; or alkyl substituted by phenyl or pyridyl rings which are optionally substituted by one or more groups selected from halogen, nitro and alkyl; X is C-R112 Rui and R112 each represents a "chlorine atom; Rus is CF3 or -SF5; m is zero, one or two; and n 'is 0 or 1. A further preferred class of compounds of the formula (II) is that wherein: Rioi is cyano; R102 is S (0) n'CF3; R? O4 is -N = C (R? O5) -Z-R? Oe; Z is NR? 07; Rivers and R107 each represents a hydrogen atom; Rioe is alkyl or haloalkyl; X is C-R112; R111 and R112 each represents a chlorine atom; R113 is CF3 or -SF5; and n 'is 0. The compounds of the formula (III) which are preferred according to the present invention are those wherein: R201 is cyano; R202 is S (O) hR203; R203 is alkyl or haloalkyl; R204 is -N (R2o5) C (0) CR2oeR2? 7R2? 8; R205 is alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl and halocycloalkylalkyl; R206 is alkoxy, haloalkoxy or hydrogen; R2Q7 and R2o8 are independently hydrogen, alkyl or haloalkyl; or R207 and R208 can form together with the carbon to which they are attached to a 3 to 7 membered ring which may additionally contain one or more heteroatoms selected from nitrogen, oxygen and sulfur; Xi is selected from nitrogen and C-R212; R211 and R212 are independently selected from halogen, hydrogen, CN and N02; '213 is selected from halogen, haloalkyl, haloalkoxy, -S (O-CF3 and -SF5; and h and k are independently selected from 0, 1 and 2. A preferred group of compounds of the formula (III) is that where the ring that is formed by R207 or R208 contain one or more heteroatoms, more preferably an oxygen atom. The compounds of the formula (III) of the present invention preferably have one or more of the following characteristics: R201 is cyano; R203 is halomethyl, preferably CF3; 211 and R212 are independently halogen; Xi is C-R212; R213 is haloalkyl, haloalkoxy or -SF5; Oh is 0 or 1, or 2, preferably 0 or 1. A preferred class of compounds is one wherein R204 is N (R205) C (0) CR206 207R208 • Another preferred class of compounds is that wherein R204 is N ( R205) C (0) aryl. Another preferred class of compounds is, that wherein R204 is N (R205) C (0) OR2o7. Preferably 205 is C 1 -C 4 alkyl, more preferably C 1 -C 2 alkyl, much more preferably methyl. Preferably R2oe is alkoxy, more preferably methoxy, ethoxy or propoxy. Preferably R2Q7 and 208 are both hydrogen. Another especially preferred group of 1-N-arylpyrazole derivatives is 4-thiocarbonylpyrazole of the formula: CV) R301 is H2N-C (S) -, R302 is halogenoalkyl, haloalkenyl or haloalkynyl, R303 is hydrogen, amino or one of the following groups: ^ N -NHFf1 where R304 represents alkyl, haloalkyl, alkoxyalkyl or in each case optionally substituted phenyl or pyridyl, R305 represents hydrogen or alkyl, R30d represents hydrogen, alkyl or in each case optionally substituted phenyl or pyridyl and R307 represents alkyl, alkenyl, alkynyl , formyl, alkylcarbonyl, haloalkylcarbonyl or alkoxycarbonyl; Ar represents in each case optionally substituted phenyl or pyridyl and n represents a number 0, 1 or 2. The especially preferred derivatives of the formula (IV) are those wherein R301 represents H2N-C (S) -; R302 preferably represents halogenoalkyl of (Ci-Ce) having from 1 to 12 halogen atoms; halogenalkenyl of (C-C6) having from 1 to 8 halogen atoms or halogenalkynyl of (C6-6) having 1 to 6 halogen atoms; R303 preferably represents hydrogen, amino or one of the following groups: wherein: R304 represents (C? -Ce) alkyl, (C? -C6) halogenoalkyl having 1 to 3 halogen atoms, (C? ~ Ce) alkoxy (Ci-Ce) alkyl, or represents phenyl or pyridyl, each of which is optionally monosubstituted to trisubstituted with identical or different substituents from the group consisting of cyano, nitro, halogen, C?-C6 alkyl, Ci-Cß alkyl C 1 alco alkyl alkoxy / C 1 -C 4 halogenoalkyl, C 1 -C 4 halogenoalkoxy or C 1 -C 4 haloalkylthio having in each case 1 to 5 halogen atoms, R 305 represents hydrogen or (C 6 -C 6) alkyl, R306 represents hydrogen, (C? -Cd) alkyl, phenyl which is optionally monosubstituted to trisubstituted by identical substituents or different from the group consisting of cyano, nitro, Halogen, C 1 -C 6 alkyl, C 1 -C alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 haloalkyl, C 1 -C 4 halogenoalkoxy or C 1 -C 4 haloalkylthio having in each case 1 to 5 carbon atoms. halogen or hydroxyl, or represents pyridyl which is substituted by cyano, nitro, halogen, C? -C6 alkyl / C? -C6 alkoxy, C? -C6 alkylthio C? -C4 haloalkyl, C1-C haloalkoxy or Halogenalkylthio of C1-C4 having in each case 1 to 5 halogen atoms, and 'R307 represents (C?-C5) alkenyl (C2-C6) alkenyl (C2-C6) alkynyl, formyl, Alkylcarbonyl of (C? -Cd), haloalkylcarbonyl of (Ci-Ce) having from 1 to 6 halogen atoms or (C? -C6) alkoxycarbonyl; Ar preferably represents phenyl or Pyridyl, each of which is optionally monosubstituted to trisubstituted by identical substituents or different groups consisting of halogen-halogen-alkyl of (C? -C6) Halogen-alkylthio of (C? -C6), halogenoalkoxy of (C? -C6), alkoxy of (C? -C6) methoxy, hydrazine, dialkylhydrazino of (C? -C6), amino, alkylamino of (C? C6) / dialkylamino of (C? -C6), alkylimino of (Ci-Ce) rcyano, alkylthio of (C? -C5) or the group Wherein R308 and R309 are identical or different and represent hydrogen or (Ci- C6) alkyl; n111 preferably represents a number 0, 1, 5 or 2; R301 represents H2N-C (S) -; R302 particularly preferably represents halogenalkyl of (C? -C) having 1 or 9 identical or different halogen atoms of the group consisting of fluorine, chlorine and bromine, halogenalkenyl of (C2-C4) having 1 to 5 halogen atoms identical or different from the group consisting of fluorine, chlorine or bromine or halogenalkynyl of (C2-C4) which has from 1 to 5 halogen atoms identical or different from the group consisting of fluorine, chlorine and bromine; R303 especially preferably represents hydrogen, amino or one of the following groups: wherein R 304 represents (C 1 -C 4) alkyl, (C 1 -C 4) halogenoalkyl having 1 to 3 halogen atoms, (C 1 -C 4) alkoxy-(Ci-C 2) alkyl or phenyl which is optionally monosubstituted to trisubstituted- by identical or different substituents from the group consisting of hydroxyl, cyano, nitro, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogenoalkyl (C 1 -C 2), C 2 -C 2 haloalkoxy or haloalkylthio L-C2 having in each case 1 to 3 halogen atoms, R305 represents hydrogen or (C1-C4) alkyl, R30d represents hydrogen, (C1-C4) alkyl or phenyl which is optionally monosubstituted or disubstituted by substituents identical or different from the group consisting of hydroxyl, cyano, nitro, halogen, C1-C4 alkyl, C1-C4 alkoxy, halogenoalkyl, C1-C2-, C1-C2 haloalkoxy or C1-C2 haloalkylthio having in each case 1 to 3 halogen atoms, in particular 4-hydroxy-3-methoxy-phenyl, and R307 represents (C? -C4) alkyl ), (C2-C4) alkenyl, (C2-C4) alkynyl, formyl, (C1-C4) alkylcarbonyl, (C1-C4) haloalkylcarbonyl having 1 to 5 halogen atoms identical or different from the group consists of fluorine, chlorine or bromine or (C 1 -C 4) alkoxycarbonyl; Ar especially preferably represents phenyl or pyridyl, each of which is optionally monosubstituted to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, methoxy, hydrazine, dimethylhydrazino, amino, methylamino, dimethylamino , cyano, methylthio or the group where R308 and R309 are identical or different and represent hydrogen or (C 1 -C 4) alkyl, especially preferably represents a number 0, 1 or 2. The compounds of the formula (IV) which are much more preferably preferred are those where R301 represents H2N-C (S) -; R302 more preferably represent one of the following groups: -CF3, -CHF2-CF2-CH3-CF3-CHF2, -CF2CHFC1, -CH2-CF3, -CH2CF2C1, -CH2- 10 CF2-CHF2, -CF2-CFCI-CF3 , -C (C1) (CF3) -CF2C1, -C (C1) (CF3) -CHC1-CF3, -C (CF3) = CC12 R303 more preferably represents hydrogen, amino or one of the following -NH- CO groups -CH3, -NH-CO-C2H5, -N = CH-NH2, -N = C (CH3) -15 NH2, -N = CH-N (CH3) 2, -N = C (CH3) -N (CH3 ) 2, -NHC2H5 or -NH-CH2-CH = CH2. Most preferably represents • (1) phenyl which is disubstituted or trisubstituted by identical or different substituents, where fluoro or chloro occupies the 2-position, trifluoromethyl in the 4-position and fluorine, chloro, cyano, methoxy, methyl, trifluoromethyl, trifluoromethoxy , trifluoromethylthio or hydrazino, position 6; or (2) a 2-pyridyl substituent that is substituted at the 4 position by trifluoromethyl and at the 6 position by fluoro or chloro. n111 more preferably represents one of the integers 0, 1 or 2. A more especially preferred compound is one in which R302 is-CF3, R303 is amino, Ar is a phenyl that is trisubstituted and the substituents are a chloro group in the position 2, a trifluoromethyl group in the 4 position and a chloro group in the 6-position, and ni11 is 1. Especially preferred compounds are those of the formulas.

Another preferred 1-N-arylpyrazoles include the following compounds: The especially preferred 1-N-arylpyrazole derivative in addition to fipronil include fipronil thio and fipronil sulfone In addition to patents discussing derivatives of 1-N-arylpyrazoles discussed previously, one skilled in the art could make these compounds by adopting the procedures described in DE 19928155, DE 19853560, WO 2000031043, DE 19650197, WO 9824769, US 6265430, US Pat. 2001007876, all of which are incorporated herein by reference. The alkyl groups of the definition of the compounds (1) of the formula (1) generally comprise from 1 to 6 carbon atoms. The ring formed by R5 and R6 and the nitrogen atom to which they are attached and generally a ring of 5, 6 or 7 members. Unless otherwise specified, the alkyl and alkoxy groups are generally lower alkyl and alkoxy groups, i.e. having from one to six carbon atoms, preferably one to four carbon atoms. Generally, haloalkyl, haloalkoxy and alkylamino groups have from one to four carbon atoms. The haloalkyl and haloalkoxy groups can carry one or more halogen atoms; Preferred groups of this type include -CF3 and -0CF3. Cycloalkyl groups generally have from 3 to 6 carbon atoms, preferably from 3 to 5 carbon atoms, and can be substituted by one or more halogen atoms. The alkenyl, haloalkenyl, alkynyl and haloalkynyl groups generally contain from 3 to 5 carbon atoms. By the term aryl phenyl, pyridyl, furyl and thiophenyl are generally proposed, each of which is optionally substituted by one or more halogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, hydroxy, amino, alkylamino or dialkylamino. In the compounds of formulas (1) to (III), by the term "substituted alkyl" is meant alkyl which is substituted by, for example, one or more of halogen, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, cyano or -S (0) mR ?? s; or alkyl substituted by phenyl or pyridyl each of which is optionally substituted with one or more groups selected from halogen, nitro and alkyl; where Rus is alkyl or haloalkyl and m is zero, one or two. Preferably, in the compounds of the formula (I), the alkyl groups are generally substituted by one to five halogen atoms, preferably one to three halogen atoms. The chlorine and fluorine atoms are preferred. The compounds of the formula wherein R? O4 is -N = C (Rios) -Z-Rioe »-Z is NR107 and Rioe represents a hydrogen atom may exist as the form of the double tautomeric isomer -NH-C ( R105) = R? O7. It is to be understood that both of such forms are encompassed by the present invention. In the compounds of the formula (III) the following examples of substituent are provided: An example of cycloalkylalkyl is cyclopropylmethyl; an example of cycloalkoxy is cyclopropyloxy; An example of alkoxyalkyl is CH3OCH2-; An example of alkoxyalkoxy is CH3OCH20-; An example of alkoxyalkoxyalkoxy is CH3OCH2OCH20-; An example of aryloxy is the phenoxy group; and An example of the arylalkoxy group is benzyloxy or 2-phenylethoxy. Generally, in the dialkylamino or di (haloalkyl) amino groups), the alkyl and haloalkyl or nitrogen groups can be independently selected from each other. A preferred class of compounds of the formula (I) comprises the compounds such that Ri is CN, R3 is haloalkyl, R4 is NH2, Ru and Ru are, independently of each other, a halogen atom and R3 is haloalkyl. Preferably still, X is C-R12. A compound of the formula (I) is very particularly preferred in the invention is 6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole or fipronil .. The compounds of the formulas (I) - (III) can be prepared according to one or other of the processes described in Patent Applications WO 87/3781, 93/6089 and 94/21606, and 00/59862 or European Patent Application 295, 117 or any other process falling within the competence of a person skilled in the art who is an expert in chemical synthesis. For the chemical preparation of the products of the invention, a person skilled in the art is considered to have at his disposal, inter alia, the complete contents of "Chemical Abstracts" and of the documents that are cited therein. As discussed in the above, amitraz is well known in the art and can be obtained commercially. Amitraz belongs to a chemical group known as formamidines. Thus, the invention comprises the use in the inventive compositions and methods of at least one formamidine, such as amitraz. Formamidines are insecticides having the structure -N = CH-N, such as amitraz, chlorordimeform, chlorodebuform, formetanate and 1-dimethyl-2- (2'-methyl-4'-chlorophenyl) -formamidine (Chlorphenamidin) which, without Desire to be related by some particular theory are useful as insecticides in inhibiting the monoamine oxidase and / or interfering with the insect nervous system (for example the voltage sensitive steps in the nerve membranes) and are especially useful against all stages of mites and ticks. The amounts for the application in animals of these insecticides can be determined from their known insecticides, without undue experimentation. (For example, MITABAN is a commercially available amitraz product approved for cattle, pigs and dogs, in the US, typically used as a collar for dogs, but also available in liquid forms such as liquid concentrate, amitraz has an oral LD50 in rats of 800 mg / kg, a dermal LD50 in rabbits of> 200 mg / kg, when applied to the dog's skin in a 0.025% solution of amitraz produces transient sedation, depression of the rectal temperature and increase in blood glucose , and amitraz is well tolerated when fed at 0.25 mg / kg / dx 90A days with, in doses of 1-4 mg / kg hyperglycemia constantly observed, but sedation, which is the most frequent adverse effect). Accordingly, in the inventive compositions and methods, a formamidine, advantageously amitraz, can be employed, that is, amitraz is exemplary of a formamidine that can be used in the invention. The parasiticidal compounds useful in the present invention also include those with ovicidal and / or larvicidal effect in the immature stages of several ectoparasites. Many of these are already known, for example from U.S. Patent No. 5,439,924. Among these compounds, insect growth regulator compounds (IGRs) are characterized that act either by blocking the development of the immature stages (eggs and larvae) in adult stages, or by inhibiting the synthesis of chitin. Patent FR-A-2, 713, 889 is also known, which generally describes the combination of at least one compound of type IGR (insect growth regulator), which comprises compounds with juvenile hormone activity and synthesis inhibitors of chitin, with at least one of the three compounds of N-aryldiazole, in particular fipronil, to control many harmful insects belonging to very varied orders. See also US Patents No. 6,797,724 6,685,954, 6,413,542 6,096,329, each of which, together with each document cited in and about each of these patents, is incorporated herein by reference, such as IGRs therein and formulations of the same. same, which additionally contains one or more formamidines such as amitraz or clordimeform can be used in the practice of this invention. The IGR compounds are another class of insecticides or acaricides, which are provided in the bait formulations in this invention. The compounds belonging to this group are well known to the professional and represent a wide range of different chemical classes. These compounds all act by interfering with the development or growth of insect pests. Compounds with an ovicidal and / or larvicidal effect in the immature stages of several ectoparasites are already known, for example from U.S. Patent No. 5,439,924. Among these described compounds are those IGR compounds that act either by blocking the development of the immature stages (eggs and larvae) in adult stages, or by inhibiting the synthesis of chitin. The regulators of. Insect growth are described, for example, in U.S. Patent No. 3,748,356; U.S. Patent No. 3,818,047; U.S. Patent No. 4,225,598; U.S. Patent No. 4,798,837; and U.S. Patent No. 4,751,225, as well as EP 179,022 or U.K. 2,140,010. French Patent No. 2,713,889 generally describes a combination of IGR comprising at least one compound with juvenile hormone activity and chitin synthesis inhibitors, with at least one of the three N-arylpyrazole compounds, in particular fipronil, for control many harmful insects that belong to very varied orders. Examples of IGR compounds that can be used in this invention include compounds that mimic juvenile hormones, in particular: azadirctin (Agridyne) diofenolan (Novartis) phenoxycarb (Novartis) hydroprene (Novartis) quinoprene (Novartis) methoprene (Novartis) pyriproxyfen (Sumitomo / Mgk) tetrahydroazadiractin (Agridyne) 4-chloro-2- (2-chloro-2-methylpropyl) -5- (6-iodo-3-pyridylmethoxy) pyridizin-3 (2H) -one and inhibitors of chitin synthesis, in particular : chlorfluazuron (Ishihara Sangyo) cyromazine (Novartis) diflubenzuron (Solvay Duphar) fluazuron (Novartis) flucycloxuron (Solvay Duphar) flufenoxuron (Cyanamid) hexaflumuron (Dow Elanco) lufenuron (Novartis) tebufenozide (Rohn &Haas) teflubenzuron (Cyanamid) triflumuron ( Bayer). These compounds are defined by their international common name ((The Pesticide Manual, edition, 1994, Ed. Clive Tomlin, Great Britain) Chitin synthesis inhibitors also include compounds such as 1- (2,6-difluorobenzyl) -3 - (2-fluoro-4- ((trifluoromethyl)) phenylurea, 1- (2,6-difluorobenzoyl) -3- (2-fluoro-4- (1,1,2,2-tetrafluoroethoxy)) phenylurea and 1- (2,6-difluorobenzoyl) -3- (2-fluoro-4- ((trifluoromethyl)) phenylurea Novaluron (Isagro, Italian company) is also an example of an IGR compound.

Preferred IGR compounds include metoprenes, pyriproxyphenes, hydroprene, cyromazine, lufenuron, l- (2,6-difluorobenzoyl) -3- (2-fluoro-4- (trifluoromethyl) phenylurea and novaluron.) Another class of compounds that can be combined with the inventive ectoparasitic combination includes derivatives of avermectin and milbemycin, pyrethroids, benzamidazoles and imidazoles Preferred avermectins or milbemycins include doramectin, enamectin, abamectin, eprinomectin, ivermectin, selamectin, moxidectin and milbemycin Preferred pyrethroids include pyrethrins, permethrin and its itrin. Preferred benzimidazoles include albendazole, fenbenacezole, mebendazole, oxybendazole and triclabendazole A preferred imidazoleothiazole is levamisole The amount of these compounds that are included with the inventive ectoparasitic combination depends on the type of animal and degree of infestation. easy to determine by a person skilled in the art. presents include 0.001 mg / kg, 100 mg / kg, with avermectins having the preferred range of 0.001 mg / kg to 10 mg / kg and the other classes of 0.1 mg / kg to 100 mg / kg. The administration of the inventive formulation may be intermittent over time and may be administered daily, weekly, biweekly, monthly, bi-monthly, quarterly, or even with longer time durations. The period of time between treatments depends on factors such as the parasite (s) being treated, the degree of infestation, the type of animal, mammal or bird and the environment where it resides. It is well within the skill level of the professional to determine a specific management period for a particular situation. This invention contemplates a method for permanently fighting a parasite in an environment in which the animal is subjected to a strong parasitic pressure where the administration is at a frequency well below a daily administration in this case. For example, it is preferred for the treatment according to the invention to be carried out monthly in mammals, such as in dogs and cats. Fixed placement formulations can be prepared by dissolving the active ingredients in the pharmaceutically or veterinarily acceptable vehicle. Alternatively, the given positioning formulation can be prepared by encapsulating the active ingredient to leave a residue of the therapeutic agent on the surface of the animal. These formulations will vary with respect to the weight of the therapeutic agent in the combination depending on the species of the host animal being treated, the severity and type of infection and the weight of the host body. The compounds can be administered continuously, particularly for prophylaxis, by known methods. Generally, a dose of about 0.001 to about 10 mg per kg of body weight given as an individual dose or in divided doses for a period of 1 to 5 days will be satisfactory but, of course, there may be a case where ranges of Higher or lower dosages and such are within the scope of this specific administration period for a particular situation. This invention contemplates a method for combating mosquitoes in an environment in which the animal is subjected to strong mosquito pressure where the administration is at a frequency well below a daily administration in this case. For example, it is preferable for the treatment according to the invention that has been carried out monthly in dogs and in cats and / or birds. The determinate set and pour formulations can be prepared by dissolving the active ingredients in the pharmaceutically or veterinarily acceptable vehicle. Alternatively, the given positioning formulation can be prepared by encapsulating the active ingredient to leave a residue of the therapeutic agent on the surface of the animal. These formulations will vary with respect to the weight of the therapeutic agent in the combination depending on the host animal species being treated, the severity and type of infection and the body weight of the host. The compounds can be administered continuously, particularly for prophylaxis, by known methods. Generally, a dose of about 0.001 to about 100 mg per kg of body weight of 1-N-arylpyrazole and 0.01 about 100 mg / kg of amitraz given as a single dose or in divided doses for a period of 1 to 5 days will be satisfactory but, of course, there may be the case where higher or lower dosage ranges have been indicated and are within the scope of this invention. They are well within the routine skill of the professional to determine a particular dosage regimen for a specific and parasitic host. Preferably, an individual formulation containing the 1-N-arylpyrazole derivative is in a substantially liquid carrier and is in a form that makes a single application or repeated application possible a small number of times. The formulation will be administered to the animal on a highly localized region of the animal, preferably between the two shoulders. It is well within the routine skill of the professional to determine a particular dosage regimen for a specific host and parasite. More preferably, this localized region has a surface area of minus 10 cm2, especially between 5 and 10 cm.sup.-area. Notably, it has been found that such a formulation is highly effective against both of the targeted parasites. The preferred treatment is carried out for administering to the host, on an individual occasion, a dose containing between about 0.001 and about 100 mg / kg of a compound of the formula (II). The amount of the 1-N-arylpyrazole compounds for animals that are small in size is preferably greater than about 0.01 mg and particularly preferably between about 1 and about 50 mg / kg of animal weight. It may also be preferable to use controlled release formulations. This invention also provides a method for cleaning the coats and skin of animals by removing the parasites that are present in their debris and excretations. The animals treated in this way exhibit a coat that is more pleasing to the eye and more pleasant to the touch. The invention also relates to a method with a therapeutic objective proposed for the treatment and prevention of parasites that have pathogenic consequences. In another preferred embodiment this provides a flea-fighting composition in small mammals, in particular dogs and cats, characterized in that it contains at least one of the formula (II) as defined above. The formulations of the present invention provide topical administration of a concentrated solution, suspension, microemulsion or emulsion for intermittent application to a given location of the animal, generally between the two shoulders (settlement type solution determined). It has been discovered that the inventive formulations are especially active against parasites when the formulations are applied to animals, such as mammals, especially dogs, cats, sheep, pigs, cattle and horses and birds, especially chickens, turkeys and quail. The ectoparasitic combination may advantageously be present in this formulation in a ratio of about 1 to about 20%, preferably about 5 to about 15% (percentages as weight in volume = P / V). The vehicle "Liquid carrier comprises a pharmaceutically or veterinarily acceptable organic solvent and optionally an organic cosolvent Also contemplated are pharmaceutically or veterinarily acceptable acid or base salts, where applicable, of the active compounds provided herein." The term "acid" it includes all inorganic or organic acids that are pharmaceutically or veterinarily acceptable Inorganic acids include mineral acids such as hydrochloric acids, such as hydrobromic and hydrochloric acids, sulfuric acids, phosphoric acids and nitric acids Organic acids include all aliphatic, alicyclic carboxylic acids and pharmaceutically or veterinarily acceptable aromatics, tricarboxylic acids of dicarboxylic acids and fatty acids The preferred acids are straight or branched chain carboxylic acids, saturated or unsaturated, aliphatic C? -C2o / which are optionally substituted by halogen or by hydroxyl groups, or aromatic C6-Ci2 carboxylic acids. Examples of such acids are carbonic acid, formic acid, fumaric acid, acetic acid, propionic acid, isopropionic acid, valeric acid, a-hydroxy acids, such as glycolic acid and lactic acid, chloroacetic acid, benzoic acid, methanesulfonic acid and acid salicylic. Examples of dicarboxylic acids include oxalic acid, malic acid, succinic acid, tartaric acid and maleic acid. An example of tricarboxylic acid is citric acid. The fatty acids include all pharmaceutically or veterinarily acceptable saturated or unsaturated aliphatic or aromatic carboxylic acids having 4 to 24 carbon atoms. Examples include butyric acid, isobutyric acid, sec-butyric acid, lauric acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid and phenylsteric acid. Other acids include gluconic acid, glycoheptonic acid and lactobionic acid. The term "base" contemplates all pharmaceutically or veterinarily acceptable inorganic or organic bases. Such bases include, for example, the alkali metal and alkaline earth metal salts, such as the lithium, sodium, potassium, magnesium or calcium salts. Organic bases include the common hydrocarbyl amine and heterocyclic salts including, for example, the morpholine and piperidine salts. The organic solvent for the liquid carrier vehicle preferably a dielectric constant of between about 10 and about 35, preferably between about 20 and about 30, the content of this solvent and the total composition preferably representing the remainder of 100% of the composition. It is well within the skill level of the professional to select an adequate solvent based on these parameters. The organic co-solvent for the liquid carrier vehicle will preferably have a boiling point of less than about 100 ° C, preferably of less than about 80 ° C and will have a dielectric constant of between about 10 and about 40, preferably between about 20 and about 30; this cosolvent can advantageously be present in the composition according to the weight / weight ratio (W / W) with respect to the solvent of between about 1/15 and about 1/2; the cosolvent is volatile in order to act in particular as a drying promoter and is miscible with water and / or with the solvent. Again, it is well within the skill level of the professional to select an adequate solvent based on these parameters. The organic solvent for the liquid carrier includes the commonly acceptable organic solvents known in the art of formulation. These solvents can be found, for example, in Remington Pharmaceutical Science, 16th Edition (1986). These solvents include, for example, ketone, ethyl acetate, methanol, ethanol, isopropanol, dimethylformamide, dichloromethane, diethylene glycol monoethyl ether (Trancutol). These solvents can be supplemented by various excipients according to the nature of the desired phases, such as caprylic / capric triglyceride of C8-C? 0 (Estasan or Miglyol 812), of oleic acid or propylene glycol. The liquid carrier may also comprise a microemulsion. The microemulsions are also well suited as the liquid carrier vehicle. Microemulsions are quaternary systems comprising an aqueous phase, an oily phase, a surfactant and a cosurfactant. They are translucent and isotropic liquids. The microemulsions are composed of stable dispersions of microdroplets of the aqueous phase in the oily phase or the reverse of microdroplets of the oily phase in the aqueous phase. The size of these microdroplets is less than 200 nm (1000 to 100,000 nm for emulsions). The interfacial film is composed of an alternation of active molecules on the surface (SA) and co-active on the surface (Co-SA) which, by lowering the surface tension, allows the microemulsion to be formed spontaneously. The oily phase can be formed in particular from mineral or vegetable oils, from unsaturated polyglycosylated glycerides or triglycerides, or alternatively from mixtures of such compounds. The oily phase preferably comprises triglycerides and more preferably medium chain triglycerides, for example caprylic / capric triglyceride of C8-C? Or. The oily phase will represent, in particular, from about 2 to about 15%, more particularly from about 7 to about 10%, preferably from about 8 to about 9%, V / V of the microemulsion. The aqueous phase includes, for example, water or glycol derivatives, such as propylene glycol, glycol ethers, polyethylene glycols or glycerol. Propylene glycol, diethylene glycol monoethyl ether and dipropylene glycol monoethyl ether are especially preferred. Generally, the aqueous phase will represent a ratio of about 1 to about 4% V / V in the microemulsion. Surfactants for the microemulsion include diethylene glycol monoethyl ether, dipropylene glycol monomethyl ether, polyglycolized C 8 -C 12 glycerides or polyglyceryl 6 dioleate. In addition to these surfactants, the cosurfactants include costa chain alcohols, such as ethanol and propanol. Some compounds are common to the three components discussed in the above, namely, aqueous phase, surfactant and cosurfactant. However, it is well within the skill level of the professional to use different compounds for each component of the same formulation. The ratio of cosurfactant or surfactant will preferably be from about 1/7 to about 1/2. Preferably it will be from about 25 to about 75% V / V of surfactant and from about 10 to about 55% V / V of cosurfactant in the microemulsion. Likewise, co-solvents are also well known to a person skilled in the art of formulation. Preferred co-solvents are those which are a drying promoter and include, for example, pure ethanol, isopropanol (2-propanol) or methanol.

The crystallization inhibitor may be present in particular as a ratio of from about 1 to about 20% (W / V), preferably from about 5 to about 15%. The inhibitor preferably corresponds to the test in which 0.3 ml of a solution comprising 10% (P / V) of the compound of the formula (I) in the liquid carrier and 10% of the inhibitor is deposited on a glass slide to 20 ° C and let stand for 24 hours. The stage is then seen with the naked eye. Acceptable inhibitors are those whose addition provides little or no crystals, and in particular less than 10 crystals, preferably 0 crystals. Although this is not preferred, the formulation may optionally comprise water, in particular a proportion of from 0 to about 30% (volume by volume V / V) in particular from 0 to about 5%. The formulation may also comprise an antioxidant agent proposed to inhibit oxidation in air, this agent being present in particular in a ratio of about 0.005 to about 1% (W / V), preferably from about 0.01 to about 0.05%. Crystallization inhibitors that can be used in the invention include: polyvinyl pyrrolidone, polyvinyl alcohols, vinyl acetate and vinyl pyrrolidone copolymers, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol or polyoxyethylene sorbitan posters; Sodium carboxymethylcellulose or lecithin; or acrylic derivatives, such as methacrylates and others, - Andoni x surfactants such as alkali stearates, in particular sodium, potassium or ammonium stearate, calcium stearate or triethanolamine stearate, sodium abietate, alkyl sulfates, in particular laurel sulfate sodium and sodium cetyl sulfate; sodium dodecylbenzenesulfonate or sodium dioctyl sulfosuccinate; or 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 '~, in which the radicals R are identical or different optionally hydroxylated hydrocarbon radicals and Y ~ is an anion of a strong acid, such as halide, sulfate and sulfonate anions; cetyltrimethylammonium bromide; is one of the cationic surfactants that can be used, - salts of the amine of the formula N + R'R "R" ', in which the R radicals are identical or different hydrocarbon radicals ally hydroxylated; Octadecylamine hydrochloride is one of the cationic surfactants that can be used, non-ionic surfactants, such as optionally polyoxyethylenated sorbitan esters, in particular Polysorbate 80, or polyoxyethylenated alkyl ethers; polyethylene glycol stearate, polyoxyethylene derivatives of castor oil, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids or copolymers of ethylene oxide and propylene oxide, amphoteric surfactants, such as substituted lauryl betaine compounds, - or preferably a mixture of at least two of the compounds listed in the foregoing. In a particularly preferred embodiment, a pair of crystallization inhibitors will be used. Such pairs include, for example, the combination of a film forming agent of the polymeric type and of an active agent on the surface. These agents will be selected in particular mentioned in the above as crystallization inhibitor. Particularly preferred film forming agents of the polymeric type include: the various grades of polyvinyl pyrrolidone, polyvinyl alcohols, and copolymers of vinyl acetate and vinyl pyrrolidone. Especially preferred surface active agents include those made of nonionic surfactants, preferably polyoxyethylenated sorbitan esters, and in particular the various grades of polysorbate, for example Polysorbate 80. The film forming agent and the active agent on the surface can be incorporated, in particular, in similar or identical amounts within the limit of the total amounts of the crystallization inhibitor mentioned elsewhere. The pair thus constituted ensures, in a remarkable manner, the objectives of the absence of crystallization on the coating and of the maintenance of the cosmetic appearance of the coat, that is without a tendency towards stickiness or towards a sticky appearance, in spite of the high concentration of active material. Particularly preferred antioxidants are those conventional in the art and include, for example, butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, sodium metabisulfite, propyl gallate, sodium thiosulfate or a mixture of no more than two of these. The formulation adjuvants discussed in the above are well known to the practitioner in this art and can be obtained commercially or by known techniques. These concentrated compositions are generally prepared by simple mixing of the constituents as defined above.; Advantageously, the starting point is to mix the active material in the main solvent and then it is added to the other ingredients or adjuvants. The volume applied can be of the order of about 0.3 to about 1 ml, preferably of the order of about 0.5 ml, for cats and of the order of about 0.3 to about 5 ml for dogs, depending on the weight of the animal. The pouring solutions determined in accordance with the invention, which are advantageously oily, generally comprise a diluent or carrier and also a solvent (organic solvent) for the compound of the formula (II) if the latter is not soluble in the diluent. Low concentrations of from about 0.05 to about 10% w / v, more particularly from about 0.1 to about 2%, are preferred. Optimally, the value is between about 0.25 and about 1.5, particularly in the region of about 1%. The organic solvents which can be used in the inventive determined pouring solutions can be mentioned in particular: acetyl tributyl citrate, fatty acid esters such as dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol, butyl diglycol , dimethylacetamide, dimethylformamide, dipropylene glycol n-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyethylene glycols, propylene glycol, 2-pyrrolidone, in particular n-methylpyrrolidone, diethylene glycol monoethyl ether, ethylene glycol and diethyl phthalate, or a mixture of at least two of these solvents. As a vehicle or diluent for the inventive determined pouring solutions, particular mention may be made of: plant oils such as soybean oil, walnut oil, castor oil, corn oil, cottonseed oil, olive oil, olive oil, grape seed, sunflower oil, etc .; mineral oils such as petrolatum, paraffin, silicone, etc .; aliphatic or cyclic hydrocarbons or alternatively, for example, medium chain triglycerides (in particular from C8 to Ci2). An emollient and / or dispersing agent and / or film former preferably will be added to this agent which is selected in particular from: polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol esters of polyoxyethylenated sorbitan; lecithin, sodium carboxymethylcellulose, silicone oils, polydiorganosiloxane oils, in particular polydimethylsiloxane oils (PDMS), for example those containing silanol functionalities, or a 45V2 oil, anionic surfactants such as alkali stearates, in particular sodium stearates, potassium or ammonium; calcium stearate, tetranolaraine stearate; sodium abietate; alkyl sulfates, in particular sodium lauryl sulfate and sodium cetyl sulfate; sodium dodecylbenzenesulfonate, sodium dioctyl sulfosuccinate; 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 "", and "in which the radicals R are radicals and optionally hydroxylated hydrocarbons and Y- is an anion of a strong acid such as the halide, sulfate and sulfonate anions; cetyltrimethylammonium bromide is among the cationic surfactants that may be used, salts of the amine of the formula N + R'R "R "wherein the R radicals are optionally hydroxylated hydrocarbon radicals, the octadecylamine hydrochloride is among the cationic surfactants that may be used, nonionic surfactants such as sorbitan esters, which are optionally polyoxyethylenated, in particular Polysorbate 80, polyoxyethylenated alkyl ethers; polyoxypropylated fatty alcohols such as polyoxypropylene-styryl ether; polyethylene glycol stearate, polyoxyethylene derivatives of castor oil, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids, copolymers of ethylene oxide and propylene oxide, amphoteric surfactants such as lauryl or substituted betaine compounds; or a mixture of at least two of these agents. The solvent will be used in proportion to the concentration of compound II and its solubility in this solvent. The emollient is preferably used in a proportion of from about 0.1 to about 10%, in particular from about 0.25 to about 5% by volume. This invention further provides parasitic dew formulations comprising: a) an effective amount of an ectoparasitic combination comprising 1-N-arylpyrazole and amitraz derivative; and b) a pharmaceutically or veterinarily acceptable liquid carrier vehicle. Preferred carriers include isopropanol, ethanol, methanol, acetone, ether (s), propylene glycol, polyethylene glycol, formal glycol, DGME, and DMSO. Examples: The following non-limiting examples illustrate the invention: Example 1 The following formulation according to the present invention was prepared by conventional techniques: Ingredient Amount (% w / v) fipronil 10.0 amitraz 5.0 ethanol 10 0 polyvidone 5 0 polysorbate 80 5 0 butylated hydroxyanisole 0. 02 butylated hydroxytoluene 0 01 diethylene glycol monoethyl ether QS 100 Example 2 The following formulation according to the present invention was prepared by conventional techniques: Ingredient Quantity (% w / v) fipronil 10.0 amitraz 15.0 ethanol 10.0 polividone 5.0 polysorbate 80 5.0 butylated hydroxyanisole 0.02 butylated hydroxytoluene 0.01 diethylene glycol monoethyl ether QS 100 Example 3 The following formulation according to the present invention was prepared by conventional techniques: Ingredient Quantity (% w / v) fipronil 10.0 amitraz 12.0 ethanol 10.0 polyvidone 5.0 polysorbate 80 5.0 butylated hydroxyanisole 0.02 hydroxytoluene butylated 0.01 diethylene glycol monoethyl ether QS 100 Comparative Example 4 The following formulation not according to the present invention was prepared by conventional techniques: Ingredient Quantity (% w / v) fipronil 10.0 ethanol 10.0 polyvidone 5.0 polysorbate 80 5.0 hydroxyanisole butyl 0.02 butylated hydroxytoluene 0.01 diethylene glycol monoethyl ether QS 100 Example 5 The duration of efficacy of the formulation of Example 3 (according to the present invention) was compared to the formulation of Comparative Example 4 against ticks in dogs. The results are presented below: Duration of effectiveness against Rhipicephalus sanguineus ticks in dogs. (% efficiency in 48-hour counts) As can be seen, the formulation according to the present invention remained effective for a much longer period than fipronil alone.

Example 6 The speed of efficacy of the formulation of Example 3 (according to the present invention) was compared with the formulation of Comparative Example 4 against ticks in dogs. The results are presented below: Effectiveness rate against Rhipicephalus sanguineus tick in dogs. (The effectiveness counts were performed 6 hours after each weekly infestation) As can be seen, the formulation according to the present invention exhibits a faster rate of effectiveness than a formulation comprising fipronil alone.

Example 7 The duration of the efficacy of the formulation of the Example 3 (according to the present invention) was compared with the formulation of Comparative Example 4 against fleas in dogs. The results are presented below: Duration of effectiveness against fleas (% effectiveness against fleas measured 24 hours after each weekly infestation) As can be seen the formulation according to the present invention remained effective for a much longer period of time than a formulation comprising fipronil alone. This increased efficacy is surprising since amitraz is not known in the art to be used in the treatment of flea infestations in mammals and birds. The above description is proposed to be illustrative and not limiting. Various changes or modifications in the embodiments described herein may occur to those skilled in the art. These changes can be made without departing from the scope or spirit of the invention.

Claims (20)

1. CLAIMS 1. A parasitic topical formulation, characterized in that it comprises: a) an effective amount of an ectoparasitic combination comprising a derivative of 1-N-arylpyrazole and a formamidine; b) a pharmaceutically or veterinarily acceptable liquid carrier vehicle; and c) optionally, a crystallization inhibitor.
2. 2. The parasitic topical formulation according to claim 1, characterized in that - the liquid carrier vehicle comprises a solvent and a cosolvent wherein the solvent is selected from the group consisting of acetone, acetonitrile, benzyl alcohol, butyl diglycol, dimethylacetamide, dimethylformamide , dipropylene glycol n-butyl ether, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, mono-ethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propoylene glycol, 2-pyrrolidone, diethylene glycol monoethyl ether, ethylene glycol, fatty acid esters of diethyl phthalate , and a mixture of at least two of these solvents and the cosolvent selected from the group consisting of ethanol, isopropanol and methanol; the crystallization inhibitor is present and is selected from the group consisting of an anionic surfactant, a cationic surfactant, a nonionic surfactant, an amine salt, an amphoteric surfactant or polyvinylpyrrolidone, polyvinyl alcohols, vinyl acetate copolymers and vinyl pyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylenated sorbitan esters, lecithin, sodium carboxymethylcellulose and acrylic derivatives, and a mixture of these crystallization inhibitors.
3. 3. The topical parasitic composition according to claim 2, characterized in that the formulation further comprises an antioxidant.
4. 4. The topical parasitic composition according to claim 3, characterized in that the antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, sodium metabisulfite, propyl gallate and sodium thiosulfate.
5. 5. The parasitic topical formulation according to claim 2, characterized in that the water is present in a proportion of 0 to about 30% v / v.
6. 6. The parasitic topical formulation according to claim 2, characterized in that the crystallization inhibitor is present in an amount of about 1 to about 20% w / v.
7. 7. The parasitic topical formulation according to claim 1, characterized in that the formulation is a specific voiding formulation.
8. 8. The parasitic topical formulation according to claim 1, characterized in that the formulation is a specific placement formulation.
9. 9. The parasitic topical formulation according to claim 1, characterized in that the formulation is a spray formulation.
10. 10. The parasitic topical formulation according to claim 2, characterized in that the anionic surfactant is alkaline stearates, sodium abietate, alkyl sulfates, sodium dodecylbenzenesulfate, sodium dioctylsulfosuccinate and fatty acids; - the cationic surfactant, is water-soluble quaternary ammonium salts of the formula N + R'R "R" 'R "" Y ~ ", in which the radicals R independently are optionally hydroxylated hydrocarbon radicals and Y" is an anion of a strong acid; - the amine salt is an amine salt of N + R 'R "R"', in which the R radicals independently are optionally hydroxylated hydrocarbon radicals; the nonionic surfactant is esters of optionally polyoxyethylenated sorbitan, polyoxyethylenated alkyl ethers, polyethylene glycol stearate, polyoxyethylenated castor oil derivatives, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids, copolymers of ethylene oxide and propylene oxide; and - the amphoteric surfactant, is betaine compounds substituted in lauryl.
11. 11. The parasitic topical formulation according to claim 1, characterized in that the 1-N-pyrazole of the formula ? wherein: Ri is a halogen atom, CN or alkyl; R 2 is S (0) nR 3 or 4,5-dicyanoimidazol-2-yl or haloalkyl; R3 is alkyl, alkenyl, alkynyl ', haloalkyl, haloalkenyl or haloalkyl; R represents a hydrogen or halogen atom or an NR5R6, S (0) mR7, C (0) R7, C (0) 0R7, alkyl, haloalkyl, 0R8 or a group -N = C (R9) (Rio); R5 and Re independently represent a hydrogen atom or an alkyl, haloalkyl, C (O) alkyl, S (O) rCF3 or alkoxycarbonyl radical or R5 and R6 together can form a divalent alkylene radical which is optionally interrupted by one or two divalent heteroatoms; R7 represents an alkyl or haloalkyl group; R8 represents an alkyl, haloalkyl or a hydrogen atom; Rg represents an alkyl group or a hydrogen atom; Rio represents an optionally substituted aryl or an optionally substituted heteroaryl group; Ru and R12 represent, independently of each other, hydrogen, halogen, CN or N02; Ri3 represents a halogen atom or a haloalkyl, haloalkoxy, S (0) qCF3 or group SF5; 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 C-R radical? , the other three valences of the carbon atom that are part of the aromatic ring; with the proviso that, when Ri is methyl, then either R3 is haloalkyl, R4 is NH2 / Rp is Cl, R13 is CF3 and X is N or also R2 is 4,5-dicyanimidazol-2-yl, R4 is Cl , Rn Cl, Ri3 is CF3 and X is C-Cl, or an acceptable salt thereof.
12. 12. The parasitic topical formulation according to claim 1, characterized in that 1-N-pyrazole • is a compound of the formula wherein: R201 is cyano, C (O) alkyl, C (S) NH2, alkyl, C (= NOH) NH2 or C (= NH2) NH2; R202 is S (O) hR203 / C2-C3 alkenyl, C2-C3 haloalkenyl, cycloalkyl, halocycloalkyl or C2-C3 alkynyl; R203 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl or haloalkynyl; R204 eS -N (R205) C (O) CR205R207R208, N (R205) C (0) aryl, or -N (R205) C (O) OR207; R205 is alkyl, haloalkyl, cycloalkyl, halocycloalkyl, cycloalkylalkyl, halocycloalkylalkyl, alkoxyalkyl, haloalkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl; R206 is hydrogen, halogen, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, formyloxy, alkylcarbonyloxy, haloalkylcarbonyloxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, dialkylamino, haloalkylamino, di (haloalkyl) amino, cycloalkyloxy, halocycloalkyloxy, alkoxyalkoxy, haloalkoxyalkoxy, alkoxyalkoxyalkoxy, aryloxy or arylalkoxy; R207 and 08 are independently hydrogen, alkyl, haloalkyl, cycloalkyl or halocycloalkyl; or R07 and R2o8 can form together with the carbon to which a 3 to 7-membered ring is attached which can additionally contain one or more heteroatoms selected from nitrogen, oxygen and sulfur; Xi is selected from nitrogen and C-R212; R211 and R212 are independently selected from halogen, hydrogen, CN and N02; R213 is selected from halogen, haloalkyl, haloalkoxy, -S (0) kCF3 and -SF5; and h and k are independently selected from 0, 1 and 2; or an acceptable salt thereof.
13. 13. The parasitic topical formulation according to claim 1, characterized in that the 1-N-arylpyrazole derivative is a compound of the formula where: R2o? is cyano, C (0) alkyl? / C (S) NH2, alkyl, C (= NOH) NH2 or C (= NH2) NH2; R202 is S (O) h 203 / C-C3 alkenyl, C2-C3 haloalkenyl, cycloalkyl, halocycloalkyl or C2-C3 alkynyl; R203 is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl or haloalkynyl; R204 eS ~ N (R205) C (O) CR205R207R208, N (R205) C (O) aryl, or -N (R2os) C (0) OR207; R205 is alkyl, haloalkyl, cycloalkyl, halocycloalkyl, cycloalkylalkyl, halocycloalkylalkyl, alkoxyalkyl, haloalkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl; R206 is hydrogen, halogen, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, formyloxy, alkylcarbonyloxy, haloalkylcarbonyloxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkylamino, dialkylamino, haloalkylamino, di (haloalkyl) amino, cycloalkyloxy, halocycloalkyloxy, alkoxyalkoxy, haloalkoxyalkoxy, alkoxyalkoxyalkoxy, aryloxy or arylalkoxy; R207 and R208 are independently hydrogen, alkyl, haloalkyl, cycloalkyl or halocycloalkyl; or R207 and 08 can form together with the carbon to which a 3 to 7 membered ring is attached which may additionally contain one or more heteroatoms selected from nitrogen, oxygen and sulfur; Xi is selected from nitrogen and C-R2? 2; R211 and R212 are independently selected from halogen, hydrogen, CN and N02; R2i3 is selected from halogen, haloalkyl, haloalkoxy, -S (0) kCF3 and -SF5; and h and k are independently selected from 0, 1 and 2; or an acceptable salt thereof.
14. 14. The parasitic topical formulation according to claim 1, characterized in that the 1-N-arylpyrazole derivative is a compound of the formula: wherein R302 is halogenoalkyl, haloalkenyl or haloalkynyl, R303 is hydrogen, amino or one of the following groups: -NHRJl wherein R304 represents alkyl, haloalkyl, alkoxyalkyl or in each case phenyl or optionally substituted pyridyl, R305 represents hydrogen or alkyl, R306 represents hydrogen, alkyl or in each case optionally substituted phenyl or pyridyl and R307 represents alkyl, alkenyl, alkynyl, formyl, alkylcarbonyl , halogenoalkylcarbonyl or alkoxycarbonyl; Ar represents in each case phenyl or optionally substituted pyridyl, and a represents a number 0, 1 or 2, or an acceptable salt thereof.
15. 15. The parasitic topical formulation according to claim 1, characterized in that the formulation further comprises an insect growth regulator.
16. 16. The parasitic topical formulation according to claim 1, characterized in that the 1-N-arylphenyl pyrazole is fipronil, the formamidine is amitraz, the pharmaceutically or veterinarily acceptable carrier is diethylene glycol monoethyl ether, the crystallization inhibitor is polyvidone, the Surfactant is Polysorbate 80 and the antioxidant is butylated hydroxyanisole and butylated hydroxytoluene.
17. 17. The topical parasitic formulation according to claim 1, characterized in that it further comprises at least one derivative of milbemycin or avermectin, anthelmintic of imidazothiazide, anthelmintic of benzimidazole or a pyrethroid.
18. 18. A method for providing antiparasiticidal activity for preventing, controlling or eliminating parasites in a mammal or bird in need thereof, characterized in that it comprises applying an effective amount of the topical formulation according to claim 1 to the mammal or bird.
19. 19. The method according to claim 18, characterized in that the antiparasitic activity lasts for an extended duration of about one month to about three months. The method according to claim 18, characterized in that the 1-aryl-pyrazole is fipronil, the formamidine is amitraz, the mammal is a cat or a dog and the parasites are fleas, ticks or both.