BR102017023690A2 - VETERINARY COMPOSITIONS FOR SIMULTANEOUS CONTROL OF ENDO AND ECTOPARASITES IN CATTLE, IN ADDITION TO ITS EGGS AND LARVAES PRESENT IN THE FEED OF ANIMALS TREATED, USE OF COMPOSITIONS, USE OF IGR, BENZIMIDAZOLIC AND MICROMINERA I COMPOUNDS AND KIT - Google Patents

Abstract

Veterinary compositions for simultaneous control of endo and ectoparasites in cattle, as well as their eggs and larvae present in the feces of treated animals, use of the compositions, use of igr, benzimidazole and micromineral compounds and kit. The present invention relates to a veterinary composition, preferably in powder form, for addition to food (feed) or nutritional supplementation (salt, mineralized salt, vitamin concentrates, among others) based on igr compounds (insect growth). regulator?), insect growth regulators, or particularly based on substituted benzoyl ureas, in combination with at least one delayed release benzimidazole compound and with micro-minerals for simultaneous control of endo and ectoparasites, preferably for tick control, hornet (ectoparasites) and haemonchus contortus (endoparasite) and their eggs and larvae present in the feces of treated cattle.

Description

VETERINARY COMPOSITIONS FOR SIMULTANEOUS CONTROL OF ENDO AND ECTOPARASITES IN CATTLE, IN ADDITION TO THEIR EGGS AND LARVES PRESENT IN THE TREATMENT OF TREATED ANIMALS, USE OF COMPOSITIONS, USE OF IGR COMPOUNDS, BENZIMIDAZOLIC 00 AND MICROMINERIAL 00] [2] The invention relates to a veterinary composition, preferably in powder form, for addition to food (ration) or nutritional supplementation (salt, mineralized salt, vitamin concentrates, among others) based on IGR compounds (from the English “insect growth regulator” ”), Insect growth regulators, or particularly based on substituted benzoyl urea, in association with benzimidazole compounds, with delayed release and micro minerals, for simultaneous control of endo and ectoparasites, preferably for control of bull ticks and fly doschifres (ectoparasitas), and worms of the species Haemonchus contortus (endoparasite), in cattle, in addition to their eggs and larvae present in the feces of the treated animals.

[003] BACKGROUND OF THE INVENTION [004] TICK:

[005] The ox tick (Rhipicephalus (Boophilus) microplus) is the main bovine ectoparasite present in tropical and subtropical countries.

[006] THE TICK CYCLE:

[007] The life cycle of this arthropod can be divided into two phases: parasitic and free.

[008] The parasitic life stage begins with the arrival of the infesting larva (with three pairs of paws) in the host, which feeds on lymph until it turns into metalarva. The urge metalarva is

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2/42 metamorphosed, as a new individual, the nymph, comes out of its interior, now with four pairs of legs. The nymph feeds on lymph again until it becomes a metamorphosis and undergoes the second metamorphosis, releasing a sexed individual: male or female. The female matures and begins the hematophagism phase. The blood-engulfed female is called a teleogen.

[009] Each teleogenine ingests around 3 ml of blood during its passage in the host and transforms 60% of its body mass into eggs. Thus, a group of 3 grams of teleologists (8 to 10 individuals) produces around 1.8 grams of eggs, and each gram of eggs produces 20,000 larvae (GONZÁLES, JC The control of the ox tick. Porto Alegre: Sulina, 1993. 104 p.). Each female can produce 2,000 to 3,000 eggs.

[010] The free-living phase begins with the teleogen which, after detaching itself from the host's body, falls to the ground, and seeks a favorable environment to lay its eggs, which when hatched will give rise to infesting larvae.

[011] The tick-free life stage varies on average from 28 to 51 days, and can extend to more than 300 days. In addition, the larvae can go for more than 6 months without feeding.

[012] LOSSES CAUSED BY TICK:

[013] The damage caused by the tick is estimated at two billion dollars a year (FURLONG & PRATA, 2004). These losses occur directly and indirectly. Directly, due to the effect of the bite and its consequences: irritability, blood loss, resulting in weight reduction and milk production, secondary myiasis and consequent damage to the leather, impairing its quality, and also by the possibility of transmitting the agents of sadness. bovine parasite. Among the indirect losses, can be

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3/42 cited: the cost of chemical control, labor, environmental damage resulting from the use of these products, the residues left in products of animal origin (ANDREOTTI & GOMES, 2003), since, if not met the grace period, the product must not be destined for human consumption (FURLONG & PRATA, 2006), and the risks of poisoning, which for prolonged periods, can lead to teratogenic and / or carcinogenic effects in man (ROJAS etal., 2000 cited by SILVA, 2001).

[014] Ectoparasite causes numerous damage to livestock, such as the transmission of agents that cause parasitic diseases of a hemolytic nature (anaplasmosis and babesiosis), the inoculation of toxins in meat and anemia, in addition to the low quality for the use of skins in leather industry, due to the injuries caused by the fixation of the parasite.

[015] Also, irritation and blood loss cause the animal to lose weight, to have a reduction in fertility and milk production in the order of 10 to 15% (IBGE data released in 2000).

[016] Based on information gathered from the agricultural departments of the Brazilian states, Horn (Horn SC. Probable damage caused by ticks. Bull. Def. San. Ani .; Brasília: Ministry of Agriculture; 1983.) estimated that the losses caused by the tick, considering aspects related to mortality (1.2%), decreased weight gain (6kg / animal / year), effects on the leather, spending on ticks, decreased milk production (1.5 billion liters ), reached US $ 968 million. Due to the growth of the cattle herd from 76 million head in 1983 to 180 million in 2005, these losses can be estimated at 2 billion dollars.

[017] These Brazilian research data are also confirmed

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4/42 by numerous international entities.

[018] PRODUCTS USED TO CONTROL OX TICKS [019] Currently, the control of ticks is a challenge for livestock, as for the application of products on the market for the control of ticks, it is necessary that the cattle be collected from the field and confined in a corral. This procedure is called management.

[020] Handling is an extremely laborious task, which involves a lot of labor and has a long duration. During management, cattle do not consume food, are subjected to stress, are injured and suffer considerable weight loss, which results in losses for livestock farmers.

[021] In addition to all these losses, the movement of the animals to the corral - handling, to receive the treatment, produces a disorganization in their activities (PARANHOS DA COSTA & NETO, 2003), and this causes the animal to thin until 15kg per handling (ARENALES, 2004). With the stress of the animals during the handling routine, the risks of accidents are exacerbated, leading to an increase in bruises on the carcasses, in addition to the meat becoming harder and darker (PARANHOS DA COSTA etal., 2004).

[022] Nor is it technically and economically feasible to eradicate the parasite in the free-living phase by treating pastures.

[023] Currently existing products for the control of tick can be classified into families or chemical groups. Over the years, new chemical groups have appeared and others have disappeared. Currently, in addition to this classification by families, ticks can be grouped into “contact” or “systemic” (acting through blood circulation),

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5/42 following alternatives (FURLONG, 2005):

[024] a - Contact ticks:

[025] They are applied by spraying, immersion or pour-on, and are divided into five groups or families.

[026] a.1) Organophosphate: it is the oldest group of ticks still being sold to cattle. It has little residual power. Many producers no longer use these products, because they believe there is resistance from ticks to them, and because the younger groups, due to their greater residual power, allow a wider interval between spraying, providing greater savings. Perhaps the most well-known commercial organophosphate product is ASSUNTOL, currently found on the market in association with a bernicidal product. More recently CARBESON and ECTOFÓS appeared. Other organophosphates are available on the market, however, most products in this family are in association with pyrethroids.

[027] a.2) Amidinics: it is the group of ticks that succeeded the organophosphates and was characterized by having a greater residual power, allowing for longer treatment intervals, was widely accepted by producers and continues to be one of the most used in the market, even after more than 20 years of commercialization. There are properties where the group has been used for many years, with no evidence of resistance problems. The most well-known amidine product is TRIATOX.

[028] a.3) Synthetic pyrethroids: always looking for products with less toxicity to cattle and with greater residual power, that is, that remain longer on the hair and leather of animals, the chemical industry has developed this new group of ticks, which was widely accepted by producers. There are many

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6/42 subfamilies of synthetic pyrethroids, although the most common products originate from Deltamethrin, Cypermethrin and Alfamethrin. Furthermore, this greater residual power favored the development of the resistance of tick populations to this chemical group. In order to try to prolong the useful life of this chemical group for a longer time, new formulations were developed, in which pyrethroids are being associated with organophosphates, thus increasing efficiency. Perhaps the best known commercial product in this group is BUTOX.

[029] a.4) Phenylpyrazoles: the product acts in a similar way to avermectins, that is, on a certain substance in the nervous system of ticks, paralyzing them. It has the disadvantage that it cannot be used in lactating animals. It is applied in the form of pour-on. A representative product of this group is TOP LINE, whose active ingredient is the substance called Fipronil.

[030] a.5) Cymiazole: old chemical group, little used against ticks in Brazil until the early 70s (Thiazoline), it was relaunched in the market, and has in its formulation an association with synthetic pyrethroid (used in the form spray). It is released for use in lactating animals, with zero deficiency for the consumption of milk from treated animals. As for the use of meat, the grace period is 3 days. As commercial representative of this group there is EKTOBAN.

[031] a.6) Naturalyte: it is the most recent chemical group in the national market and the active component, Spinosad, comes from the fermentation of an actinomycete fungus. Can be used on lactating cows. [032] b - Systemic ticks:

[033] They are ticks applied by means of injections or pour on. Either way, the product's active ingredient is metabolized by

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7/42 organism and distributed to the whole body of the animal, arriving through blood, to ticks.

[034] b.1) Macrocyclic lactones: these products appeared in the early 1980s and produced a major revolution in the world market for antiparasitic drugs. In addition to having greater residual power, they are effective against worms and worms, which is why they are called endectocides. They are derived from products obtained with the fermentation of the fungus Streptomyces avermitiles, and there are four subgroups on the market: Abamectin, Ivermectin, Doramectin and Moxidectin). These ticks also act by blocking the transmission of nerve impulses in ticks, which therefore die paralyzed. They have the great disadvantage that they cannot be used in lactating animals, or in animals 30 days before slaughter, due to the level of residues that remains in milk and meat. The exceptions are Eprinex and Supramec pour on, which are released for use in lactating animals. They are applied in an injectable or pour on form, and after being metabolized by the body, they reach the blood. The first product in this group, and therefore perhaps the best known, is IVOMEC.

[035] b.2) Growth inhibitors: it has the ability to inhibit the production of chitin, the largest component of the tick cuticle. The subfamily used to control the tick is Fluazuron. . Completely different from all the ticks already mentioned, it does not allow the ticks to change phases and grow, besides preventing the larvae from hatching from the eggs, controlling the tick population in the pasture. The representative product of this group is ACATAK, which is prohibited for use in lactating cows.

[036] Another major disadvantage of existing products is that they leave toxic chemical residues in the meat and milk of animals

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8/42 treated, it being necessary to establish grace periods where the meat and milk of the treated animals should not be eaten. Here are some examples:

Product trade name Laboratory Active ingredient (P.A.) P.A. concentration Grace period Beef milk Triatox Intervet Amitraz 12.5% 15 days 24 hours Ectop Vallée Amitraz 12.5% 15 days 24 hours Topline Merial Fipronil 1% 100 days Do not apply to lactating cows. Acatak Novartis Fluazuron 2.5% 42 days Do not apply to lactating cows. Treo Ace Injectable Pfizer Doramectin 3.4% 63 days Do not apply to lactating cows. Dectomax Injectable Pfizer Doramectin 1% 35 days Do not apply to lactating cows. Injectable Cydectin Fort Dodge Moxidectin 1% 28 days Do not apply to lactating cows. Ivomec Gold Injectable Merial Ivermectin 3.15% 122 days Do not apply to lactating cows Avotan THERE Injectable Intervet Abamectin 1% 42 days Do not apply to lactating cows.

[037] Contamination occurs through the absorption of active ingredients used in ticks by the organisms of treated animals.

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9/42 [038] The object of the present invention uses active ingredients of very low toxicity that are poorly absorbed and rapidly excreted by cattle, thus preventing the contamination of treated animals from occurring.

[039] Below is a table with the respective * LD50 oral of the products most commonly used to combat ticks:

PRODUCT CLASS DL50 ORAL Cypermethrin PIRETHROID 250mg / Kg DELTAMETRINA PIRETHROID 130mg / Kg DICLORVÔS ORGANOPHOSPHORATE > 50mg / Kg CLORPIRIFÓS ORGANOPHOSPHORATE 95 to 270mg / Kg ABAMECTIN MACROLACTONES 10mg / kg IVERMECTIN MACROLACTONES 52mg / Kg DORAMECTIN MACROLACTONES 50 to 200mg / kg FIPRONIL PHENYLPIRAZOLE 97mg / Kg

[040] * DL or LD, from English Lethal Dose) is the most commonly used lethality indicator, corresponding to the dose capable of killing 50% of individuals in a test population.

[041] Diflubenzuron, one of the active ingredients of the present invention, has LD50 = 4640mg / Kg, that is, it is dozens of times safer than the other active ingredients currently used.

[042] Some compounds that regulate insect growth are used in oral compositions to combat ectoparasites, however, administered in this single dose form, high amounts of active ingredients are necessary to achieve the necessary efficacy, different from the object of the present invention, which because it is given daily and in small doses, it allows a much more effective and safe action.

[043] ADVANTAGES OF THE PRESENT INVENTION [044] The object of the present invention represents an innovation, since

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10/42 avoids all the above inconveniences, particularly with regard to handling costs or the accumulation of residues in the animal's organism, since it refers to a powdered veterinary composition, suitable to be added to food or nutritional supplementation , highly effective in combating ectoparasite and with very low toxicity, since it has specific and selective action, acting only and exclusively in interrupting the synthesis of chitin, a substance that forms the tick's exoskeleton and does not interfere in any other function of the animal's organism treated.

[045] HORSE FLY [046] The horn fly (Haematobia irritans) is a blood-sucking parasite, that is, it feeds on blood, and is approximately half the size of a house fly.

[047] THE HORN FLY CYCLE [048] The practically exclusive target of its attacks is cattle. Their bites are constant and very painful, causing great irritation in the animal, leaving it stressed, causing consequent weight loss and great losses for the farmer.

[049] In the case of horn flies, both males and females are hematophagous, remaining day and night on the animal's body, where mating occurs.

[050] After fertilization, the females - capable of producing 400 to 700 eggs during their lifetime - move to the lower parts of the cattle, waiting for it or a nearby animal to be defecated.

[051] The eggs are deposited on the sides of the fresh fecal mass, after which the female returns to suck the animal's blood. The larvae penetrate the fecal mass and develop in a period of 4 to 8 days, when they migrate to the drier areas, becoming pupae. After 6 or 8 days adult flies appear, which fly to the

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11/42 cattle and restart the cycle. An adult fly lives for an average of 4 weeks.

[052] LOSSES CAUSED BY THE HORN FLY:

[053] According to EMBRAPA (Brazilian Agricultural Research Corporation), in its Technical Communication η ^θ 25, of May 1985, the horn fly remains 24 hours a day on the animal, perforating its skin 20 to 40 times per each sting lasts up to four minutes.

[054] The prolonged presence of the fly makes the cattle restless, making them walk all the time, the bites are constant and painful, causing discomfort, and with this, the animal eats poorly and cannot sleep peacefully.

[055] The irritation and blood loss causes the animal to lose up to 30 kilos per year, to have a reduction in fertility and milk production of around 20%. Cattle that do not receive any kind of treatment can even die.

[056] These data from Brazilian surveys, confirmed by international entities, are for cattle treated with the products currently available.

[057] PRODUCTS USED FOR THE CONTROL OF HORN FLY:

[058] It is known, in the control of the horn fly, the application of insecticides, mainly of the class of pyrethroids and organophosphates.

[059] These insecticides are for external use and applied to the hair of cattle, or even as a bolus, for internal use, administered orally.

[060] To apply these insecticides, it is necessary to carry out the management, which consists of collecting the cattle from the field, confining them in a

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12/42 corral, to then apply the products. The management, as discussed above, is a source of great expenses for the rancher, and whenever it can be avoided it will bring gains.

[061] The currently existing products for the control of the hornbill can be divided into the following groups, according to the mode of application:

[062] a) spraying: the insecticide, usually liquid in the form of an emulsifiable concentrate, is previously diluted in water in the proportion recommended by the manufacturer, and the obtained syrup is sprayed over the entire body of the animal, usually with the aid of a spraying, until the bovine hair is completely wet with this syrup. Some commercial products for this application are Ectoplus, Ektoban, Bovec, among others.

[063] b) pour-on: a small amount of insecticide, usually liquid, is applied over the animal's dorsal line, usually 20 to 100 mL per animal, according to the manufacturer's recommendation, without previous dilution. Some commercial products for this application are Ciperallvet, Bayofly, Bayticol, among others.

[064] c) earring: insecticide presented in the form of plastic pieces that are attached to the bovine ear region. The earring remains on the animal for about 6 months, after which it must be replaced by another one. Some commercial products for this application are Top Tag, Neocidol, among others.

[065] d) sprinkling: self-sealing bags containing insecticide in the form of powder are placed in places frequented by cattle, which, when they come into contact with the bags, receive the insecticide powder on their backs. The product on the market known for this application is Butox Fly.

[066] e) bolus: insecticide in solid form, cylindrical in shape,

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13/42 administered orally with the aid of an applicator, which directs the bolus into the esophagus, preventing diversion into the trachea, which would cause the animal to die. A commercial product with this application is Vigilante. The bolus, although it has the same active principles and indication as the present invention, has another pharmaceutical form and has very different dosage, dosage, mode of administration, etc.

[067] The products currently in use (except bolus, mentioned on the previous page) are not very efficient, since they can only reach adult forms of flies, since they are applied only externally to animals.

[068] The horn fly does not lay its eggs in the animals' bodies, only in their feces, therefore, the products have no preventive effect, they only minimize the damage that the fly in its adult stage can cause.

[069] It is not feasible, technically and economically, to treat all the feces that are scattered in the pastures with these products, consequently it is impossible to reach the larval stage of insects.

[070] The only exception is the product in the form of a bolus, administered orally. Administration requires the use of specific utensils and experience, otherwise the bolus may reach the trachea, causing the animal to die. In addition, opening the animal's mouth, introducing the applicator and administering the bolus, for each animal, is an extremely difficult and expensive task.

[071] ADVANTAGES OF THE PRESENT INVENTION [072] For the application of the products described above, it is necessary that the cattle be collected from the field and confined in a corral, a procedure called handling.

[073] Management is an extremely laborious task, involving

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14/42 a lot of labor and has a long duration. During management, cattle do not consume food, are subjected to stress, are injured and suffer considerable weight loss, which results in losses for livestock farmers.

[074] The object of the present invention avoids such inconveniences, mainly with regard to the direct costs of handling, since it is a powder or granulated composition, suitable to be added to the feed or nutritional supplement provided to animals.

[075] US patent 4,166,107 refers to bolus compositions for insect control in cattle, which comprises all the above mentioned drawbacks, while the present invention refers to a powder or granular composition for incorporation into the feed or nutritional supplementation provided by the animals.

[076] Throughout the text there are quotes of pure IGR compounds (and not compositions containing IGR) added to the ground feed, expressing that it is an inefficient means to treat cattle. The addition of pure IGR compounds impairs the efficiency of insect control. In contrast, the product of the present invention makes use of several pharmacotechnical resources to make the active ingredient more effective, such as: smaller particle size, facilitating mixing in the feed or nutritional supplement, presence of surfactants, which provide greater and better incorporation of the active ingredient in the bolus and in the fecal mass, accentuating the action of the active principle, etc.

[077] US patent 4,281,003 cites oral administration (which includes boluses and other means of orally inserting medication into the animal's body, unlike spontaneous ingestion by the animal) of insecticides in the control of insects that breed in cattle feces. .

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It mentions diflubenzuron, without suggesting or referring in any way to the advantages or components of the composition of the present invention.

[078] HAEMONCHUS CONTORTUS [079] Haemonchus contortus is a blood-sucking worm that is very resistant to traditional wormers.

[080] HEMQNCQSE CYCLE [081] Animals are contaminated by worms infected with worms. The overcrowding in this area contributes significantly to the intensification of worms. The cohabitation of young people with adults increases the rates of worms in the former, whose organisms are not yet endowed with adequate protection against worms, which install themselves there easily (SPROVIERI, 1980).

[082] As described by FORTES (1997), the life cycle of gastrointestinal worms involves a free and a parasitic phase. The free phase is characterized by the development of eggs to contaminating larvae (L3) and occurs in pastures. The parasitic phase occurs during the evolution of the infective larvae ingested by the animals until they become adults and produce eggs.

[083] The free-living phase begins with the elimination of eggs in the feces of parasitized animals. In the environment, a larva develops inside the egg and is released after hatching. The larva grows and changes twice before becoming infectious when it then migrates from the interior of the faeces to the pasture.

[084] From egg development to contaminating larva, it usually takes five to seven days, in environmental conditions with high temperature and humidity. The larvae actively leave the grass leaves using the moisture film that in the morning hours

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16/42 lines.

[085] After being ingested with pasture, the contaminating larva continues its development in animals, reaching the adult stage in about 21 to 28 days after the egg hatches, in most species.

[086] During development, the larvae change to the fourth stage or immature adult, increase in size, differentiate the organs and become adults.

[087] It is important to note that each contaminating larva when ingested generates only one adult, male or female. Adult worms copulate and females start laying. The number of eggs produced varies from hundreds to thousands each day, depending on the species. Thus, each female produces a large amount of eggs. Each egg, finding favorable environmental conditions, creates a contaminating larva. Each female of Haemonchus contortus can produce between 5 and 10,000 eggs per day during adulthood (FORTES, 1997).

[088] LOSSES CAUSED BY HEMONCOSIS:

[089] Hemmoncosis is caused by Haemonchus contortus (worms 10 to 30 mm long) and Haemonchus similis (8 to 17 mm). They parasitize the abomasum (or coagulator, the real stomach of ruminants). Signs of the disease appear when animals (especially young ones) suffer from severe nutritional deficiencies. When well fed, the infection takes a subclinical form. A drop in pasture protein levels (in the dry season) can cause a drop in resistance that causes the disease. Adult parasites live in the true stomach of cattle, and those that have already acquired immunity can be sources of contamination of pastures.

[090] PRODUCTS USED TO CONTROL THE

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HAEMONCHUS:

[091] Existing wormers intervene by killing adult worms and immature species through their toxic effect, however, they do not have a residual effect to eliminate the reinfestation cycle, and after 28 to 35 days it is estimated that 70% of the worm infestation has turned. In addition, they leave toxic residues in the meat and milk of the treated animals.

[092] There are works by EMBRAPA (Brazilian Agricultural Research Corporation) that indicate 12 treatments against worms per year as the most effective and cost-effective.

[093] For HOSSETTO (2000), the dairy herd that has a high incidence of worms can represent a substantial drop in milk production, reaching 25% of the total. An increase of 5% to 10% (Marques, 2003) in annual mortality can be expected, mainly of young animals and a decrease of up to 12% in the birth of calves per year (FADIL, s / d.).

[094] Parasite control over the years has been accomplished through the use of drugs, and the use of these drugs has been partly responsible for increasing the productivity of herds. However, its indiscriminate use resulted in the selection of populations of helminths with resistance to the different chemical groups used in the treatment of animals (AMARANTE et al., 1992).

[095] Parasitic resistance is a phenomenon by which some organisms in a population are selected and become dominant after constant use of a chemical compound. The diagnosis will be positive for “resistance” when a specific drug that showed a reduction of more than 99% in the parasitic load obtains a reduction of less than 95% against a given organism after

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18/42 a certain period of time (MOLENTO, 2004).

[096] Resistance has three components: establishment, development and dispersion. The establishment of resistance is largely influenced by the size and diversity of the population and the rate of mutation of the gene involved (SUTHERST & COMINS, 1979). The development of resistance is due to the use of the selective agent, in this case, the anthelmintic (SUTHERST & COMINS, 1979). The high frequency of treatments selects for resistance, decreasing the drug's useful life (BARNES & DOBSON, 1990). Finally, the process of dispersing genes in the population is carried out by migration and gene flow (HUMBERT et al., 2001). Therefore, the development and dispersion processes are influenced by the biology and management of the parasites responsible for resistance. It usually happens within five to eight generations after the introduction of the new class of compound (GRANT, 2001), with approximately one year being the maximum interval of one generation of gastrointestinal nematodes in ruminants (PRICHARD et al., 1980). The process of developing resistance can be fast, given the record made by SHOOP (1993), of the occurrence of resistance to ivermectin in just five years after its introduction in South Africa.

[097] Since the first descriptions of nematodes resistant to anthelmintics, three decades ago, this phenomenon is no longer just a curiosity in parasitology to give rise to a state of crisis in some sectors of livestock (Chart 1). This situation has become particularly serious in small ruminant farms in the tropical and subtropical regions of South America, where resistance to all groups of broad spectrum anthelmintics occurs (Waller, 1997).

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19/42 [098] The literature establishes as criteria for qualifying nematode strains as resistant, the survival of more than 1000 helminths to a treatment and / or effectiveness of a certain active principle (calculated using geometric means) less than 90% (PRESIDENT, 1985).

[099] Haemonchus spp. and Ostertagia spp. have already developed resistance to ivermectin and moxidectin in sheep, respectively. In the case of Haemonchus contortus, if 100 females survive a certain treatment, soon after this, they will be able to eliminate more than half a million eggs through the feces per day (MOLENTO, 2004).

[0100] In addition to genetic factors, others can influence the greater or lesser spread of resistance, which are operational, biological and ecological (HENNON, 1993). With underdosing, the drug will only reach sensitive individuals in the parasitic population and resistant individuals survive giving rise to new generations (CRAIG, 1993). The rapid rotation of the active principle selects nematodes resistant to all drugs used in this rotation (BARNES & DOBSON, 1990).

[0101] The bioecological factor that influences the development of resistance is the amount of nematode population in refuge, that is, the pre-parasitic stages of free life that are found in the pasture and escape the exposure of the anthelmintic. Therefore, the larger the size of the population in refuge, the lower the selection pressure and consequently the development of resistance will be delayed (PRICHARD, 1990; JACKSON, 1993).

[0102] The first report of resistance to anthelmintics used against gastrointestinal nematodes in sheep was with thiabendazole (DRUDGE ET AL., 1964). This problem has spread throughout the world

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20/42 entire (WALLER ET AL. 1995; WALLER ET AL., 1996; CHARTIER et al., 1998). However, it usually occurs in areas with rainy summers and where the parasite Haemonchus contortus is endemic, mainly Australia, South Africa and South America (WALLER et al., 1995).

[0103] The resistance to levamisole is widely distributed and is a serious problem that limits the treatment of different helminth parasites (SANGSTER and GILL, 1999), and was determined in 1976 (MOLENTO, 2004).

[0104] At the end of the following decade, SANTIAGO & COSTA (1979) reported the appearance of strains of Haemonchus contortus, T. colubriformis and Ostertagia resistant to Imidothiazole levamisole. In Australia, one of the countries that suffers most from parasitic resistance, a study of 900 properties detected the problem in 91% of them and found 85% resistance to Benzimidazoles and 65% to Levamisol (OVEREND et al., 1994).

[0105] At the same time, the fungus that originated another great miracle was discovered. Streptomices avermitilis was discovered on a golf course in Japan and originated from avermectins. Much was researched and from various combinations the commercial ectmectin of endectocidal action was launched in 1981 in France. However, due to its enormous use, H. contortus developed resistance mechanisms against the new molecule.

[0106] Table 4. Parasitic resistance to macrocyclic lactones in Brazil.

Author Place Helminths (Genres) Active principle Paiva, 2001 SP Cooperia Haemonchus Ivermectin1% Cardoso, 2002 RJ Cooperia Ivermectin1%

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Doramectin1% Rangel, 2004 MG Haemonchus Cooperia Ivermectin1% Doramectin1% Borges, 2004 MG and SP Cooperia Haemonchus Ivermectin 3.15% Borges, 2006 MG, RS, SP Cooperia Haemonchus Ivermectin 3.15%

[0107] To apply the existing dewormer it is necessary that the cattle be collected from the field and confined in a corral, a procedure called handling. The damages and inconveniences of handling have already been described in the topics above.

[0108] Existing wormers leave residues in the meat and milk of the treated animals, requiring periods of grace.

[0109] Below are some examples of these grace periods:

Product trade name Laboratory Active ingredient (P.A.) P.A. concentration Grace period Car milk Dysophenol 20% for injection Ibasa Dysophenol 20% 21 days 2 days Pradoverme Injectable Meadow Dysophenol + Tetramisole 10% + 8% 14 days 3 days Treo Ace Injectable Pfizer Doramectin 3.4% 63 days Do not apply to lactating cows. Dectomax Injectable Pfizer Doramectin 1% 35 days Do not apply to lactating cows. Cydectin Fort Dodge Moxidectin 1% 28 days Do not apply

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Injectable in lactating cows. Ivomec Gold Injectable Merial Ivermectin 3.15% 122 days Do not apply to lactating cows Avotan L.A Injectable Intervet Abamectin 1% 42 days Do not apply to lactating cows. Bullmec Gold Clarion Ivermectin 3.25% 125 days Do not apply to lactating cows. Ranger LA Vallée Ivermectin 3.5% 122 days Do not apply to lactating cows. Abamectin Bayer Bayer Abamectin 1% 35 days Do not apply to lactating cows.

Source: Veterinary Compendium (2009).

[0110] ADVANTAGES OF THE PRESENT INVENTION [0111] Knowing that iron is the oxygen-carrying element par excellence in biology, and that all nematode larvae have respiratory equipment of the aerobic type, it was found that the elimination of worms is the consequence of the increase in oxygen tension in the intestinal habitat, of an anaerobic nature. Such an increase in oxidative tension gives these nematodes a sense of security and unnecessary attachment to mucous membranes, canceling tropism

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23/42 respiratory, due to the usual low oxygen tension in this habitat. The food of the worm is the cells of the gastrointestinal wall.

[0112] The environments in which the worm lives, stomach and intestine, are anaerobic. When in contact with the gastrointestinal environment, our invention releases oxygen.

[0113] If there is oxygen, in the stomach and intestine, the worm comes off the walls and becomes loose in the gastrointestinal content. Staying loose, the worm is surrounded by the stomach and intestinal bolus and is gradually eliminated.

[0114] This unique mechanism of action does not promote the emergence of resistance, which is one of the major problems of the products currently used.

[0115] The object of the present invention avoids the inconveniences related to handling costs, accumulation of residues in the animal's organism and constant reinfestation, since it refers to a powdered veterinary composition, suitable to be added to the food or nutritional supplementation , highly effective in combating blood-sucking endoparasites, and with low toxicity.

[0116] In addition, by presenting a Benzimidazolic compound with delayed release technology in its composition, it makes the present invention act against the eggs and larvae present in the feces of the treated animals. These compounds are broad-spectrum agents, which form one of the main groups of anthelmintics used in veterinary clinic, as well as in humans.

[0117] Benzimidazoles act by binding to free beta-tubulin, inhibiting its polymerization and thus interfering with the uptake of glucose dependent on microtubules. They have a selective inhibitory action on the microtubular function of helminths, 250 to 400 times

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24/42 more potent in helminths than in mammalian tissues.

[0118] Through a specially developed formulation, the present invention allows the release of these benzimidazole compounds only after their complete excretion in the feces, which occurs between 10 and 72 hours after ingestion, depending on the treated ruminant species. Thus, there will be no absorption of the active compounds by the treated animals, because between 10 and 72 hours after ingestion, the composition containing the benzimidazole compounds will have been completely eliminated from the ruminants' organism through feces.

[0119] Thus, it is ensured that the action of the product will occur only in the feces, protecting animals from exposure to benzimidazole compounds, which despite being chemical compounds of low toxicity for mammals and poorly absorbed, could generate unwanted residues in the meat and in the milk of the treated animals.

[0120] The faeces are treated with the composition of the present invention, and the faeces are practically the only place of growth of the worms' eggs and larvae, particularly of the genus Haemonchus spp. larvae of worms, the reproductive cycle of this parasite will be broken.

[0121] The benzimidazolic compound will only be released in the faeces, thanks to the delayed release technology, thus avoiding the undesired metabolism of the compound and the subsequent accumulation of residues in the animal's body.

[0122] By having its action concentrated in the fecal cake, the benzimidazolic compound will have 100% of its potency used against the immature forms (eggs and larvae) of the helminths present in the feces,

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25/42 with an unprecedented ovicidal and larvicidal action, interrupting the reproductive cycle of worms, since with the elimination of eggs and larvae, the adult worms population decreases, since there is no more emergence of new worms, this makes future reinfestations to be reduced or avoided.

[0123] DESCRIPTION OF THE INVENTION [0124] Unlike the previous art, including commercial uses and available in the literature, the present invention relates to a veterinary composition, preferably in powder form, to be added to the feed or nutritional supplement consumed by animals, particularly cattle, which is effective in combating endo and ectoparasites, mainly Haemonchus contortus and its eggs and larvae present in the feces of treated animals, Rhipicephalus (Boophilus) microplus and Haematobia irritans.

[0125] The veterinary composition according to the present invention comprises in a first embodiment:

[0126] a) insect growth regulating compounds, IGR, which are selected from at least one among diflubenzuron, cyromazine, triflumuron, metoprene, S-methoprene, hydroprene, S-hydroprene, fluazuron, dicyclanyl, azadiraquitine, lufenuron, flufenoxuron, nitenpiram, imidacloprid, teflubenzuron, noviflumuron, methoxyfenozide, pyriproxifen, tebufenozide, phenoxycarb, buprofezin, hexaflumuron, and / or one of its derivatives;

[0127] b) benzimidazole compounds which are preferably selected from at least one of: thiabendazole, fenbendazole, albendazole, triclabendazole, cambendazole, parbendazole, mebendazole, flubendazole, oxfendazole, carbendazin, fuberidazole, triazole, riazole, riazole, rendezol, and rizobazole its derivatives.

[0128] c) a mixture of micro minerals composed of iron, copper,

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26/42 cobalt, manganese, zinc, iodine, selenium and chromium, among others, in the form of their biologically absorbable salts;

[0129] d) at least one vehicle acceptable for veterinary use.

[0130] The composition of the present invention may further comprise stabilizers, surfactants, flavors, flavors, preservatives, antioxidants and / or other adjuvants known in the art.

[0131] The veterinary composition according to the present invention comprises in a second embodiment:

[0132] one or more compounds selected from the benzoyl urea substituted, defined in formula I below:

[0133] where:

[0134] - Rí and R ₂ can be the same or different, selected from halogen atoms or a methyl group, preferably fluorine atoms.

[0135] - R ₃ can be selected from halogen atoms or alkyl groups containing 1 to 15 carbon atoms, optionally halogenated, more particularly R ₃ represents a chlorine atom.

[0136] b) one or more benzimidazole compounds, characterized by having in their chemical structure a bicyclic group formed by the fusion of a benzene ring and an imidazole ring, as shown in the following figure:

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[0137] c) in particular the salts that make up the mixture of micro minerals are one or more among iron sulphate, copper sulphate, cobalt sulphate, manganese sulphate, calcium iodate, zinc oxide and sodium selenite.

[0138] d) at least one vehicle acceptable for veterinary use, such as surfactants, thickeners, flavorings, stabilizers, preservatives, dye, inert vehicles, etc.

[0139] Preferably, the composition of the present invention comprises the compound IGR 1- (4-chlorophenyl) -3- (2,6-difluorobenzoyl) urea, also called diflubenzuron, at least one of the benzimidazole compounds: thiabendazole and / or fenbendazole and / or albendazole, and the micro minerals: iron sulphate, copper sulphate, cobalt sulphate, manganese sulphate, calcium iodate, zinc oxide.

[0140] The compositions according to the invention have the advantage of eliminating endo and ectoparasites, in addition to their eggs and larvae present in the faeces of the treated animals, simultaneously, effectively, without accumulating substantially in the animals' organisms and, consequently, without leaving residues in meat and milk that could be harmful to human health.

[0141] The effective fight against endo and ectoparasites, in particular ox ticks, horn fly and the worm Haemonchus spp and their eggs and larvae present in the feces of the treated animals, is

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28/42 achieved in a particular way with a dosage of active ingredients in the composition of the present invention, which varies according to the selected compounds. In particular, the present invention comprises about 1 to 10% by weight, more particularly about 5 to 7% by weight of at least one IGR compound or a substituted benzoyl urea of formula I, and about 0.01 to 95% of a mixture of micro minerals, selected from iron, copper, cobalt, manganese, zinc, iodine, selenium and chromium, among others. In particular, salts are one or more of iron, copper, cobalt and manganese sulfates, calcium iodate, zinc oxide and sodium selenite.

[0142] The vehicles acceptable for veterinary use according to the present invention include all those known in the art, for example: - surfactants such as ethoxylated nonyl phenol, sodium lignosulfonate, dodecyl benzene sulfonate, ethoxylated octyl phenol, sodium polysorbate, polysorbate potassium, citric pectin or sodium lauryl sulfate, [0143] - particulate solid vehicles such as micronized silica, kaolin, talc, or mixtures thereof, microcrystalline cellulose, calcium phosphate, calcium sulfate, mannitol, calcium carbonate [0144] - polymers such as ethyl cellulose, zein, polymethacrylate copolymers, hypromellose, polyvinylpyrrolidone, carrageenan, hydroxypropylmethylcellulose, starch. The composition of the present invention may further comprise thickeners, stabilizers, flavors, flavors, anticoagulants, pH correction agents or vehicles that can be added to adjust and stabilize the pH to the desired value, preservatives and / or other adjuvants known in the art.

[0145] Within another aspect, the present invention deals with the use of benzoyl urea substituted in association with at least one benzimidazole compound and with a mixture of micro minerals,

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29/42 as described above, in the preparation of veterinary compositions to combat ectoparasites, particularly ticks and horn flies and endoparasites, particularly Haemonchus contortus and its eggs and larvae present in the feces of treated animals, in cattle.

[0146] In yet another aspect, the present invention deals with a composition for the control of endo and ectoparasites, to be made available via diet or nutritional supplement, in an effective daily amount of about 20 to about 40 mg, preferably 30 mg, at least one IGR compound or a substituted benzoyl urea of formula I, 5 to 10 mg of at least one benzimidazole compound, 60 to 90 mg of iron, 3 to 7 mg of copper, 0.5 to 4.5 mg of cobalt, 1 to 5 mg of manganese, 2 to 6 mg of iodine, 0.1 to 0.5 mg of selenium, 01 to 0.5 mg of chromium.

[0147] The feed or nutritional supplement available to the animal can be, for example, in the form of powder, ground or pelleted. As a person skilled in the art knows, nutritional supplements can be one or more, without any limitation, between salt, mineralized salt, vitamin concentrates, protein supplements, etc.

[0148] The amount of composition applied to the feed or nutritional supplement is established based on the expected consumption of the feed or supplement in use, which in livestock is well known, for example:

[0149] - the average consumption of sodium chloride by cattle is 30g / head / day. In this case it would be necessary to add the present invention in the proportion of 600.0 grams for each 25 kg of sodium chloride.

[0150] Within yet another aspect, the present invention deals with a kit, characterized by the fact that it comprises a container

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30/42 containing a composition according to the present invention, a dosing device for quantities and instructions for its use in the simultaneous treatment of endo and ectoparasitic infestations, particularly ticks, horn flies and Haemonchus contortus and their eggs and larvae present in the feces of treated cattle.

[0151] The following are merely illustrative examples of particular embodiments of the invention, without creating any limitations to its scope other than those contained in the appended claims.

[0152] EXAMPLES OF COMPOSITION ACCORDING TO THE PRESENT INVENTION [0153] EXAMPLE 1

Formula 1 Kg Iron Sulfate 409.53 Copper sulphate 41.15 Cobalt sulfate 20.57 Manganese sulphate 20.57 potassium lodate 15.43 Zinc oxide 5.14 Sodium selenite 1.13 Chromium oxide 0.82 Technical diflubenzuron 45.78 Micronized Silica 91.36 Ethoxylated nonylphenol 1.28 Sodium lignosulfonate 8.42 Kaolin 61.04 Thiabendazole 111.11 Ethylcellulose 138.89 Hypromellosis 27.78

[0154] EXAMPLE 2

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Formula 1 Kg Iron Sulfate 410.00 Copper sulphate 40.00 Cobalt sulfate 20.00 Manganese sulphate 20.00 potassium lodate 15.00 Zinc oxide 5.00 Sodium selenite 1.00 Chromium oxide 1.00 Technical diflubenzuron 46.00 Micronized Silica 92.00 Ethoxylated nonylphenol 1.50 Sodium lignosulfonate 8.50 Kaolin 60.00 Thiabendazole 110.00 Ethylcellulose 140.00 Hypromellosis 30.00

[0155] EXAMPLE 3

Formula 1 Kg Iron Sulfate 410.00 Copper sulphate 40.00 Cobalt sulfate 20.00 Manganese sulphate 20.00 potassium lodate 15.00 Zinc oxide 5.00 Sodium selenite 1.00 Chromium oxide 1.00 Technical diflubenzuron 46.00 Micronized Silica 92.00 Ethoxylated nonylphenol 1.50 Sodium lignosulfonate 8.50 Kaolin 20.00

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Fenbendazole 200.00 Ethylcellulose 100.00 Hypromellosis 20.00

[0156] EXAMPLE 4

Formula 1 Kg Iron Sulfate 400.00 Copper sulphate 40.00 Cobalt sulfate 20.00 Manganese sulphate 20.00 potassium lodate 15.00 Zinc oxide 5.00 Sodium selenite 1.00 Chromium oxide 1.00 Technical diflubenzuron 46.00 Micronized Silica 92.00 Ethoxylated nonylphenol 1.50 Sodium lignosulfonate 8.50 Kaolin 20.00 Albendazole 200.00 Ethylcellulose 110.00 Hypromellosis 20.00

[0157] EXAMPLE 5

Formula 1 Kg Iron Sulfate 410.00 Copper sulphate 42.00 Cobalt sulfate 21.00 Manganese sulphate 21.00 potassium lodate 16.00 Zinc oxide 6.00 Sodium selenite 2.00 Chromium oxide 1.00 Technical diflubenzuron 46.00

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Micronized Silica 92.00 Ethoxylated nonylphenol 2.00 Sodium lignosulfonate 9.00 Kaolin 50.00 Thiabendazole 112.00 Ethylcellulose 140.00 Hypromellosis 30.00

[0158] EXAMPLE 6

Formula 1 Kg Iron Sulfate 380.00 Copper sulphate 41.20 Cobalt sulfate 21.00 Manganese sulphate 21.00 potassium lodate 15.50 Zinc oxide 5.20 Sodium selenite 1.20 Chromium oxide 0.85 Technical diflubenzuron 45.80 Micronized Silica 91.40 Ethoxylated nonylphenol 1.30 Sodium lignosulfonate 8.50 Kaolin 89.15 Thiabendazole 111.20 Ethylcellulose 138.90 Hypromellosis 27.80

[0159] TEST 1 [0160] USE OF MICROMINERALS AND INSECT DEVELOPMENT INHIBITORS IN INTEGRATED CONTROL

OF PARASITES.

[0161] Abraão Garcia Gomes ¹ , Roberta de Souza Santos da Mata ² , Antônio Sérgio Fidelis de Souza ² , Rosália Meireles de Souza Rocha ² .

[0162] ¹ Federal University of Goiás, Institute of Tropical Pathology

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34/42 and Public Health - Rua 235 - s / n - Setor Universitário - CEP: 74605050 - Goiânia, GO, Brazil. E-mail: gomesag@uol.com.br. ² Champion Farmoquímico LTDA.

[0163] The experiment was carried out at Fazenda Santo Amaro in the municipality of Ouro Verde de Goiás - GO, from October 2011 to January 2012, using 20 male steers aged 12 to 16 months and weighing between 147 and 305 kg, divided into a control group (TO) and a treated group (T1).

[0164] The animals were weighed, identified and kept in Brachiaría brizantha pasture containing drinking fountains with water "ad libitum". The control group (TO) received mineral salt at will, while the animals in the treated group received a mixture of micro minerals containing iron, copper, manganese, iodine, cobalt, zinc, selenium and chromium mixed with white salt. To this mixture, Diflubenzuron was added in the proportion of 1.1 grams per kilogram of mixture. The source of macrominerals was supplied separately in the trough.

[0165] To determine the number of horn flies, ticks and helminth eggs per gram of feces (OPG), in addition to monitoring live weight, the animals were handled every 30 days.

[0166] CHALLENGE FOR Haematobia irritans [0167] TEST IN VITRO [0168] In order to evaluate the effectiveness of Diflubenzuron on the larval development of H. irritans, without possible influence of climate changes, an experiment was carried out under controlled conditions.

[0169] Adult horn flies were harvested with plugs from animals not treated with the drug in question and were sent to

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Institute of Tropical Pathology and Public Health (IPTSP / GO) to obtain eggs. The flies were placed in cages with moistened filter paper to serve as a substrate for oviposition. The paper was examined every three hours to obtain the eggs. The eggs obtained were then evaluated for viability and transferred to containers containing feces from 4 animals chosen at random from untreated animals and treated with Diflubenzuron, each containing 50 viable eggs. These flasks with feces and eggs were kept in a B.O.D. with constant temperature, at 25 ° C and a 12-hour photoperiod, for a period of 20 days, at the end of which the emergence of adults emerged.

[0170] Efficacy was determined by the relationship between the number of adults obtained from each bottle and the initial number of eggs. The TO and T1 groups were statistically compared using the MannWhitney test, with P adjusted at 0.05, due to the impossibility of testing the normal distribution, given the low number of repetitions (n = 4).

[0171] CAMP TEST [0172] The animals were passed through a hose for initial counting of the total number of H. irritans in the cervico-dorsal-lumbar region, from the nape to the tips of the hips. The experimental groups, core (TO) and treated with Diflubenzuron (T1), had statistically similar mean parasitic intensity (C = 474.5 ± 123.8; T = 465.0 ± 125.2; t = 0.2425 and P = 0 , 8097), as recommended by Ordinance No. ^Q 48 of the Ministry of Agriculture, Livestock and Supply (MAPA, 1997).

[0173] CHALLENGE FOR Rhipicephalus (Boophilus) microplus [0174] For this challenge 5 animals were chosen at random

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36/42 of each group. The animals from the control group (TO) and the treated group (T1) were transferred to individual tick-free stalls with slatted floors, where they remained for twenty-one days until the engorgged females fell. These were collected daily for a period of five days, and packed in common plastics, washed and dried on paper towels, weighed, checking the average weight of each of the teleologists, and then placed in disposable plastic Petri dishes and kept in an oven BOD, at 270C temperature, relative humidity above 85% for two weeks (SANTOS and FURLONG, 2002; PEREIRA, 2006).

[0175] After this period, the postures of each plate were weighed and transferred to test tubes (15 cm high by 15 mm in diameter) closed by cotton. The duly identified tubes returned to the B.O.D greenhouse, under the same humidity and temperature conditions as before, until the larvae hatched.

[0176] CHALLENGE FOR GASTROINTESTINAL VERMES [0177] The animals had fecal samples taken directly from the rectal ampoule to count eggs per gram of feces (OPG). The samples were kept in the collection glove, identified, stored on ice and sent to the laboratory of the Parasitology Department of the Institute of Tropical Pathology and Public Health (IPTSP) - Federal University of Goiás, for the examination by the method of GORDON & WITHLOCK (1939) modified.

[0178] For the determination of the number of eggs per gram of feces (OPG) and monitoring of live weight, the animals were handled every 30 days.

[0179] On the penultimate day of the experiment, feces were collected for OPG examination and weighing. On the last day and after a 12-hour fast, the steers were slaughtered in the Goiás slaughterhouse, in Anápolis Petição 870170084595, from 11/01/2017, p. 39/52

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GO.

[0180] After opening the thoracic and abdominal cavities, double ligatures were made with the aid of a string between: posterior end of the reticulum and anterior of the abomasum; posterior end of the abomasum and anterior of the small intestine, and finally between the posterior end of the small intestine and anterior of the large intestine (UENO & GONÇALVES, 1998). The organs were placed separately in plastic bags, identified with the numbers of the respective animals, packed in a polystyrene box containing ice, and sent to the laboratory for post-mortem examination.

[0181] Statistical analyzes of the results obtained were performed with the aid of the GraphPad Prism v. 5.04, with P adjusted to 0.05.

[0182] DISCUSSION OF RESULTS [0183] Haematobia irritans [0184] The in vitro evaluation ended after 20 days of development. The control group had an average emergence of 43 ± 4.1633, while the group cultivated in feces of cattle treated with Diflubenzuron had an average emergence rate of only 0.5 ± 0.1. The calculated efficacy, based on the control group, was 98.83%, according to the methodology proposed by HOLDSWORTH et al., 2006. By the Mann-Whitney analysis, a clear statistical difference was found between the groups (U = 0.0; P = 0.0265).

[0185] FIELD TEST [0186] The field experiment was developed during the summer, which represents the most critical period for horn flies in cattle in Brazil (BIANCHIN et al., 2004). At the beginning of the experiment, no statistical difference was found between the experimental groups,

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38/42 who had equivalent average infestations (C1 = 474.5 ± 123.8 and T1 = 465.0 ± 125.2). During the experimental period, the caretakers reported an apparent reduction in infestation in the animals in the treated group, while the animals in the control group remained infested and even exhibited signs of discomfort.

[0187] At the end of the experimental period, the animals were again contained in the trunk for counting the flies. There was no significant reduction in the fly count in the control group (t = 07307, P = 0.4469). Regarding the treated group, there was a clear reduction in H. irritans infestation (t = 16.46, P <0.0001). There was also a statistical difference between the final times of the two experimental groups (t = 15.75; P <0.0001). The effectiveness of the product, under field conditions, was 99.20%.

[0188] According to GROSSCURT (1978), Diflubenzuron acts commonly in all larval stages of insects, but in some species, the first and the last stages may be more or less susceptible. KUNZ et al. (1976), in turn, observed that this molecule could also be absorbed by the females of the arthropods, interfering in the reproductive processes in order to affect the embryos and preventing the birth of most of the larvae. The in vitro test, in the present work, clearly demonstrated the action of this presentation of the molecule on the development of immature forms, showing the elimination of the molecule still active in the feces of the animal treated with this formulation, in addition to its good effectiveness in the field challenge, in a reduction in the fly count in the treated group of over 99% was observed.

[0189] In 2002, SILVA & MENDES found that in addition to the 3 ^Q larval stage of H. irritans being more sensitive to the action of Diflubenzuron when compared to previous stages, adult progenies

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39/42 collected from the field and treated with different concentrations of this drug showed pupal malformation. According to EISLER (1992), by acting on the chitin synthesis, Diflubenzuron develops in cuticle insects that do not support the muscles during molting, being unable to release their exuvia, resulting in death due to starvation or rupture of the new, delicate and malformed cuticle (GROSSCURT et al., 1988), resulting in a decrease in the adult population in the environment.

[0190] Diflubenzuron efficacy results have also been proven in the control of insects of public health importance, such as Aedes aegypti (BORGES et al., 2004; MARTINS and SILVA, 2004), Culex quinquefasciatus and pipiens (SELF et al., 1978 ; HAJJAR, 1979), Musca domestica (MILLER et al., 1975; ABLES, 1975) and Anopheles darlingi (COSTA, 2007).

[0191] Rhipicephalus (Boophilus) microplus [0192] The weight of the teleogins harvested from the bovines of the control group when they fell on the floor, was between 260 to 295mg, which, according to the literature, is the normal weight of healthy teleogins.

[0193] The teleogins of the bovines of the group treated with Diflubenzuron when they fell on the floor, reached a weight of 145 to 165mg, being well below normal.

[0194] The average weight of the teleologists in the treated and control group was 153mg, 278mg respectively, indicating that there was a statistically significant difference (p <0.005) between the groups.

[0195] The result of the average oviposition of females of Rhipicephalus (Boophilus) microplus from the control and treated groups, was 2,600 and 900 eggs, respectively.

[0196] With the results of this work, even though it is not the product of knock-down effect, the decrease in the weight of teleologists and

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40/42 its ovicidal action found with the use of Diflubenzuron, showed its effectiveness in controlling Rhipicephalus (Boophilus) microplus.

[0197] According to the authors (SILVA and MENDES, 2002; KUNZ et al., 1976; COSTA 2007; MARTINS and SILVA, 2004) studying Diflubenzuron in several species, there is an action of this active principle as ovicidal in several phases or instar in the biological cycle of these parasites.

[0198] GASTROINTESTINAL WERMES [0199] Regarding the weight of the animals, the statistical analysis revealed a strong difference between the weights of the group treated with the mixture of micro minerals (F = 8.732; P = 0.0002) in contrast to the control group, which did not show a significant difference for this parameter over the experimental period (F = 2.821; P = 0.525). Although the comparison between the initial (Pi) and final (Pf) weight averages of the experimental groups by the t test does not reveal a relevant difference (Pi - t = 0.4038; GL = 18; P = 0.6911; Pf - t = 1.590; GL = 18; P = 0.1292), there was a numerical difference of 15 kg. Regarding the egg count per gram of feces, a statistical difference was found by the ANOVA test with Tukey posterior throughout the experimental period for both the group treated with the mixture of micro minerals (F = 56.95; P <0.0001) and for the control group (F = 3.087; P = 0.0393), although in the latter, the test indicated a difference only between the initial count and the count at 60 days. The comparison of the mean of the initial and final count of the groups using the t test revealed that at the beginning of the experimental period, the groups had equivalent means (t = 0.5695; GL = 18; P = 0.5761), while the final means of this parameter were clearly different (t = 7.609; GL = 18; P <0.0001).

[0200] Comparison of the averages of helminths obtained at necropsy

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41/42 revealed strong differences for the three diagnosed genders, showing the effect of treatment on this parameter (Haemonchus U = 0.0000; P = 0.0002; Trichostrongylus U = 5,000;

P = 0.0007; Oesophagostomum U = 3,000; P = 0.0004).

[0201] When comparing the results of various drug combinations, ROCHA (1951) concluded that the synergistic action of iron, copper and other minerals when administered in the usual sodium chloride diet, combined two advantages: that of promoting the elimination of nematodes and to fight anemia.

[0202] The increase in weight of 15 kg seen in treated cattle is within expectations. Such an effect had previously been observed by (FIGUEIREDO et al. (1972), VIEIRA (1973), PINHEIRO, 1985; SOUTELLO, 2001; CABRAL (2007).

[0203] The results obtained in the present experiment, once again demonstrated the controlling action of the compound of microminerals on the population of gastrointestinal trichrostrongylids, especially those of hematophagic habits (FERRARI, 1972; FIGUEREDO et al., 1972; VIEIRA, 1973; GONÇALVES , 1976; SILVA and QUINTANA, 1976; CABRAL, 2007; DELL'PORTO et al., 2009; VILELA, 2011), and that the reduction in the population of these nematodes also depends directly on the improvement in the general state of the host.

[0204] CONCLUSION [0205] In addition to its easy administration and effectiveness, it was also proven that the mixture of micro minerals and Diflubenzuron did not present chemical residues in the final product according to TFOUNI et al. (2007), there is no grace period for the use of final products such as meat and milk, an important fact for public health.

[0206] An integrated parasite control program with a mineral supplementation rich in iron and copper, mainly

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42/42 together with the addition of IGRs to this mixture, it is a rational and less stressful way of treating herds, aiming above all, greater weight gain in less time.

[0207] In experimental conditions, the addition of a mixture of micro minerals and Diflubenzuron to the white salt, proved to be effective for controlling the main parasites of the Brazilian herd.

[0208] Based on the results obtained, it appears that the composition of the present invention, as well as the treatment method, are highly effective in combating ticks in cattle, in addition to presenting numerous technical and economic advantages.

[0209] From the data and information presented here, a technician in the subject can use the invention in various ways, in a manner not identical to the one exposed here, but with the function and result taught here, thus being within the scope of the attached claims.

Claims (21)

1 - VETERINARY COMPOSITION FOR ENDO AND ECTOPARASITES CONTROL IN ANIMALS, characterized by the fact that it comprises at least one IGR compound, at least one benzimidazole compound, a mixture of micro minerals and at least one vehicle acceptable for veterinary use. 2 - USE OF THE COMPOSITION defined in claim 1, characterized by the fact that it is in the preparation of a veterinary medicine to combat endo and ectoparasites. 3 - COMPOSITION, according to claims 1 to 2, characterized in that it is administered to the animals orally, through feeding and / or nutritional supplementation, in an effective amount; 4 - COMPOSITION, according to claims 1, 2 and 3, characterized by the fact that the feed is preferably ground or pelleted. 5 - COMPOSITION, according to claims 1, 2, 3 and 4, characterized by the fact that nutritional supplementation is preferably selected from sodium chloride, mineralized salt, calcium phosphate, vitamin concentrates and protein supplements. 6 - COMPOSITION, according to claims 1, 2, 3, 4 and 5, characterized by the fact that the compound IGR is selected from diflubenzuron, cyromazine, triflumuron, metoprene, S-metoprene, hydroprene, S-hydroprene, fluazuron, dicyclanil, azadiraquitine, lufenuron, flufenoxuron, nitenpiram, imidacloprid, teflubenzuron, noviflumuron, methoxyfenozide, pyriproxifen, tebufenozide, fenoxicarb, buprofezin, hexaflumuron, and / or one of its derivatives. 7 - COMPOSITION, according to one of claims 1, 2, 3, 4, 5 and 6, characterized by the fact that the compound IGR is Petition 870170084595, of 11/01/2017, p. 46/52 preferably diflubenzuron. 8. COMPOSITION according to claim 1, 2, 3, 4, 5, 6 and 7, characterized by the fact that it comprises about 3 to 7% by weight of the IGR compound or a substituted benzoyl urea of formula I. 9 - COMPOSITION, according to claim 1, 2, 3, 4, 5, 6, 7 and 8, characterized by the fact that it comprises one or more benzimidazole compounds, characterized by having in their chemical structure a bicyclic group formed by the fusion of a benzene ring and an imidazolic ring, as shown below: 10 - COMPOSITION, according to claims 1, 2, 3, 4, 5, 6, 7, 8 and 9, characterized by the fact that the benzimidazole compound is selected from: thiabendazole, fenbendazole, albendazole, triclabendazole, cambendazole, parbendazole , mebendazole, flubendazole, oxfendazole, carbendazin, fuberidazole, triazoxide, ricobendazole, oxylbendazole, and / or one of its derivatives. 11 - COMPOSITION according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, characterized by the fact that the benzimidazyl compound preferably comprises thiabendazole and / or fenbendazole and / or albendazole. 12. COMPOSITION according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11, characterized by the fact that it comprises about 5 to 25% by weight of the benzimidazolic compound. 13 - COMPOSITION according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12, characterized by the fact that the compound Petition 870170084595, of 11/01/2017, p. 47/52 3/4 benzimidazole presents delayed release, due to the formulation specially developed for this. 14 - COMPOSITION, according to claims 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13, capable of controlling eggs and helminth larvae that develop in the animals' feces treated. 15 - COMPOSITION, according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, characterized by the fact that the vehicle can contain one or more among : surfactants such as ethoxylated nonyl phenol, sodium lignosulfonate, dodecyl benzene sulfonate, ethoxylated octyl phenol, sodium polysorbate, potassium polysorbate, citric pectin or sodium lauryl sulfate, - particulate solid vehicles such as micronized silica, kaolin, talc, or mixtures thereof, microcrystalline cellulose, calcium phosphate, calcium sulfate, mannitol, calcium carbonate - polymers such as ethylcellulose, zein, polymethacrylate copolymers, hypromellose, polyvinylpyrrolidone, carrageenan, hydroxypropylmethylcellulose, starch. 16 - COMPOSITION, according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, characterized by the fact that it can additionally comprise thickeners, stabilizers, flavoring, flavoring, anticoagulants, pH correction agents or vehicles that can be added to adjust and stabilize the pH to the desired value, preservatives and / or other adjuvants known in the art. 17 - COMPOSITION, according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16, characterized by the fact that ectoparasite is the tick and / or horn fly, the endoparasite is Haemonchus contortus, and the animal is bovine. 18 - VETERINARY COMPOSITION FOR ENDO CONTROL AND Petition 870170084595, of 11/01/2017, p. 48/52 4/4 ECTOPARASITES IN ANIMALS, according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17 characterized by the fact that it contains a mixture of micro minerals made up of iron, copper, cobalt, manganese, zinc, iodine, selenium, chromium and molybdenum, among others, and their salts. 19 - COMPOSITION, according to claims 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 and 18, characterized by the fact of providing an effective daily amount of about 20 to about 40 mg, preferably 30 mg, of at least one IGR compound or a substituted benzoyl urea of formula I, 50 mg to 200 mg of at least one benzimidazole compound, 60 to 90 mg of iron, 3 to 7 mg of copper, 0.5 to 4.5 mg of cobalt, 1 to 5 mg of manganese, 2 to 6 mg of iodine, 0.1 to 0.5 mg of selenium, 01 to 0.5 mg of chrome. 20 - COMPOSITION, according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and 19 characterized by the fact that supply ectoparasite with blood containing at least one IGR compound. 21 - AUXILIARY KIT IN THE ECTOPARASITES CONTROL METHOD characterized by the fact that it comprises a container containing at least the composition of one of the claims 1,2,3, 4, 5, 6,7,8,9,10,11,12 , 13,14,15,16,17,18, 19 and 20, a metering device for quantities and optionally instructions for use.