SK64798A3 - Dry formulations of pesticides for controlling ectoparasites on animals - Google Patents

Abstract

Dry formulations of organophosphate insecticides provide effective and convenient to use treatments for protecting animals from infestation by fleas and other ectoparasites. These dry formulations are effective for periods of up to two weeks because of the controlled release of the insecticide onto the animal, they are convenient to use and most importantly, they do not cause severe adverse reaction in the treated animals.

Description

The invention relates to a method of protecting an animal from infecting fleas and other ectoparasites. Dry organophosphate insecticide formulations control fleas in animals when applied at high concentration. small volume and in a single small application. limited area of animal hair. These formulations have unexpected properties. which favor them over liquid insecticide formulations that are currently used to control animal wounds. ^with

BACKGROUND OF THE INVENTION

Methods of protecting animals from flea flea and other, ectoparasitic agents usually involve the administration of large volumes of pesticidal compositions which comprise the administration of large amounts of pesticidal compositions containing low concentrations of insecticides. These methods include spraying the animal's skin or hair with the composition. immersing the animal in a bath containing the formulation or dusting the animal with an insecticide-containing powder. The application of these liquid or powdered infectious compositions is inconvenient, awkward and bulky. Pets are often traumatized by having their entire body sprayed, immersed in a bath or dusted. In addition, a significant amount of insecticide never reaches the animal and a large amount of this insecticide often falls off the animal very much. This significantly reduces the effectiveness of being so soon after treatment.

Its application, in spite of unused insecticide in an undesirable way of immersion solutions affects the living can be a stressful environment. Use for pets.

especially for cats that often have a natural resistance to water. Submersible solutions are expensive, especially if only one or a few animals are treated and the solutions used must be disposed of in the prescribed manner to avoid environmental contamination. Most importantly, however, it is necessary to repeat all of these pesticidal compositions frequently because their efficacy lasts only for one or two weeks.

Because cats tend to be cleansed by licking the body and hair, they are very susceptible to developing undesirable reactions that occur as a result of ingesting insecticides applied to their body to protect against ectoparasitic infection. For example, foams may appear in the mouth after application of the insecticide or may excessively sinter. In more serious cases, treated animals may vomit. These adverse reactions may be due to the toxicity of the insecticides used in the treatment. Adverse reactions may also occur where problems are not caused by the toxicity of the insecticidal preparation but by the undesirable reaction of the animals to the taste or odor of the preparation.

Insecticide-impregnated collars are used to protect against flea infections. Many pets, especially maClek, protest against wearing collars around their necks and many pet owners do not like to expose animals or themselves to insecticides in collars. In addition, flea collars are generally less effective in preventing flea infestation than previously discussed methods, pet owners often use collars to supplement some other method, including direct application of Insecticide to the animal's body.

It is known that many pesticides commonly used in agriculture and veterinary practice include organophosphate compounds. It can also be applied effectively for the control of ectoparasites, e.g. However, these compounds, when administered at the concentrations and dosages necessary for effective control of spinal fluid. They often produce undesirable responses in domestic animals. It is known to those skilled in the art that the biological efficacy of pesticidal compositions in particular applications is often influenced by the type of formulation used. Formulations which provide pesticides in solution are generally more biologically effective than dry pesticide formulations. However, these liquid formulations are more toxic than formulations that come into contact with the treated and treating subject, especially the animal and the person applying the pesticide to the animal, because they are readily absorbed by the skin.

Application of certain pesticide formulations may cause undesirable reactions in domestic animals. For example, domestic cats may over-salivate and even vomit after application of organophosphate insecticides. Adverse reactions may also occur when the animal does not receive a toxic dose of Insecticide but only responds to the unpleasant taste or odor of the insecticide formulation used. AJ in case. where the insecticide formulation does not present any health risk to the animal being treated. these responses can be stressful for animal keepers, as these farmers often do not realize that the animal responds only to the unpleasant taste or unpleasant odor of the preparation.

Thus, there is a continuing need for effective compositions for controlling fleas in animals, particularly domestic cats. It is therefore an object of the present invention to provide formulations of organophosphate compositions that are effective over the long term, are safe, easy to apply and do not cause undesirable reactions in the animals to which the formulations are applied.

SUMMARY OF THE INVENTION

As already mentioned, the invention relates to a method for reducing the adverse reactions in animals caused by the application of insecticides in the treatment of an animal infected with parasites. It has unexpectedly been found that the administration of a dry formulation of an organophosphate insecticide provides an effective and convenient treatment in protecting an animal from infecting fleas and other ectoparasites, while reducing the adverse reactions in animals caused by the insecticide used. Such dry formulations include insecticide-containing microcapsules that can be applied to one or more restricted areas of the animal's body or coat. Controlled release of the insecticide results in a prolongation of the efficacy of the formulations of the invention in inhibiting ectoparasite infection up to two weeks. The formulations of the invention do not cause serious adverse reactions in treated animals.

The invention relates to highly concentrated, low-volume, substantially dry insecticide formulations which are effective in controlling bovine and other ectoparasites in animals. Ectoparaslts are parasites that live on the outer parts of the animal body and that are different from the endoparasites living inside the body of the host animal. Ectoparaslts include fleas, ticks, mites, bumble bees and flies.

The invention further relates to methods of applying these formulations to the animals to be treated. Application of the dry formulations of the invention provides effective protection against Infectious Ectoparasitmil while minimizing the number and severity of adverse reactions that may occur when treated with topical Insecticide formulations.

Adverse reactions may include long-term or delayed toxic effects caused by exposure of the treated animal to insecticides. These undesirable effects include skin irritation or other visible signs of toxicity, such as increased sunlight or vomiting, which may last for several hours and even several days after treatment. In the most severe cases, these adverse reactions result in the death of the animal.

Adverse reactions may include reactions not caused by a toxic dose of Insecticide. These reactions, such as excessive sunlight or even vomiting, are only to the unpleasant taste and odor of the insecticidal composition, which are disgusting to the animal. These undesirable reactions are a problem especially in the treatment of cats whose natural behavior includes the applied substances cleansing the body and hair by licking. The tips are usually licked and then vomited shortly after application to the animals. If the substance is disgusting or unpleasant, the animal will salivate excessively and may vomit in more severe cases. Because these reactions have usually scared the animal owner so much that they do not repeat the oetrenle of animals to control ectoparasites. These reactions can also be considered as undesirable reactions, even if they are not caused by the insecticides present in the applied formulations.

Without being bound to a particular theory, which would explain why the methods of the invention eliminate or reduce unwanted reactions. It will be appreciated that the respective formulations together with the appropriate methods of administration of these formulations of the invention reduce the likelihood that the treated animal will be cleaned upon application of the Insecticide. This phenomenon is most likely due to the nature of the formulation used, which is substantially dry rather than wet.

Pesticides that are useful for the dry formulations of the invention include a group of compounds known as organophosphates. It is known in the art that this class of compounds exhibits beneficial pesticidal properties, particularly in animal flea control. Suitable organophosphate pesticides may be phosphates, phosphotloate or phosphotlonate compounds. Preferred pesticides for use in the formulations of the invention are, for example, the organophosphate compound known as pllinolphos-methyl-O-C2-diethylamino-6-methylpyrimidin-4-yl-10-o-dimethylphosphorotloate). List of specific examples of organophosphate compounds that can be used in the formulations of the invention. It is shown in Table I.

TABLE I

Chloryrlphos Plrlmlphos-methyl Dlazlnone

T etrachlorovlnphos

The term dry formulation, as used herein, means that the insecticide is formulated to contain no more than a negligible amount of water. One of the ways in which a dry formulation can be prepared. It encapsulates the pesticide into microcapsules using organic polyl isocyanate intermediates to form a polymoxic capsule surrounding the water-miscible insecticide. The amount of water in the final formulation will be determined based on the ability of the Inert ingredients surrounding the microcapsules to adhere to the water under the conditions existing in the dry device used to dry the final encapsulated formulation. In most cases, the amount of water adsorbed on the inert solvent is very small, so that the formulation is substantially dry.

Microscopic encapsulation of selected pesticides can be accomplished by polymerizing the monomer units present in the emulsion droplets that are formed.

if the water-miscible pesticide vigorously mixes with the polymerizing monomers and Seaman et al., Trends ln an aqueous solution containing an additional heat as described by the Formulatlon of Pestlddes - An

Overvleu, Pesticide Science 29 C1990) p. 437 to 449, said polymerization being carried out at the interface. The monomers react to form a polymer coating that encapsulates the pesticide and controls its release. Encapsulation can reduce the oral toxicity of the pesticide 100-fold compared to treatment with non-encapsulated water-based formulations, and can reduce skin toxicity by 10-fold.

A preferred method of encapsulating pesticides. useful in the treatment of ectoparasltml infections in animals. It is described in US Patent 4,295,720. The water-miscible insecticide which is encapsulated is dispersed in an aqueous solution containing suitable surfactants and a protective collagen. Useful surfactants include non-lunar, anilone, or cationic surfactants having a hydrophilic-III (CHLB) balance of from about 12 to about 16. Suitable surfactants include, for example, sodium isopropyl isophthalenesulfonate, polyoxyethylene sorphenol phthololeateol and polyethylene glycol ethers of linear alcohols. Preferred surfactants are polyethylene glycol ethers of linear alcohols.

an emulsifier

Linear alcohol ethoxylate based tergitol 15-S-20. Suitably, a wide variety of these protective colloids can be selected from materials including polyactylates, methylcelluloses. polyvinyl alcohol, polyacrylamide and polymethyl vinyl ether and maleic anhydride. Protective colloid It is possible to add to the microscopically encapsulated formulation either before or after the organic dispersion.

Dry microscopically encapsulated formulations of the invention contain about 20 to 80 wt. % of active pesticide. One preferred embodiment is a dry microscopically encapsulated formulation comprising about 55-75% of Pl-mlphos-methyl.

The dry composition of the invention can be advantageously applied to one restricted area on the animal to be treated. Alternatively, the formulation can be applied to two or more specific sites of restricted areas on an animal. Preferably, the composition is applied as a single spot to a restricted area on the back of the animal between the shoulder blades at a point where the animal is unable to reach the tongue so that the applied pesticide cannot lick out of its hair. This is particularly important when the composition is used in the treatment of cats, since the cats have a taste or odor when exposed to substances which are considered disgusting or unpleasant. often drool or need to vomit. When applied topically to another part of the body of the animal, shortly after application of the composition to cats, due to the natural habit of the cat to cleanse its body by licking, licking it or swallowing it.

The amount of dry composition to be applied to the animal is determined from the animal's weight and the pesticide concentration in the formulation. Compositions It is usually possible to administer about 0.1 g to 1.0 g of active compound per kilogram of animal weight. Animals (weighing about 2.2 to 4.5 kg) may be treated in a single application at a dose of about 0. 3-4 g of a dry formulation containing 20 to 90% organophosphate. A preferred treatment involves the administration of 0.3 g dry formulation containing about 70 to 75% plmiphos-methyl per kilogram animal weight.

The dry pesticidal formulations of the invention are useful in controlling bovine and other ectoparasites in animals, particularly in smaller animals. which are kept as pets, including dogs, cats, rabbits and rodents. The disclosed compositions and methods are particularly advantageous in the control of cats on cats. Cats are unable to digest pesticides effectively and are therefore very susceptible to their toxic effects. Owing to the natural habit of cats to cleanse the body by licking, especially in cats, the reactions are detrimental due to the unpleasant taste or odor of the preparations applied to the animal's coat. The application of the disclosed compositions by the method of the invention is substantially non-toxic to cats and the application of the compositions does not appear to dampen immediately after application of the animal to clean the fur.

The disclosed compositions and methods of their application are also useful in controlling other species of insects, including beasts, lice, ticks and flies, on animals living in herds, such as bovine, sheep, goat, horse, camel, pig, reindeer, North American reindeer and buffaloes.

The following examples are illustrative only and are not intended to limit the scope of the invention as set forth in the appended claims.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

Preparation of dry encapsulated plmiphos-methyl

The dry encapsulated p-mlphos-methyl was prepared by mixing

770 g of water with 47.0 g of 40% Reax product, 100-1 of sodium gnosulfonate solution (polymer protective collagen) and 76.0 g of 20% aqueous Tergltol XD emulsifier with stirring in an open reaction vessel. In a separate vessel, 2000 g of technical grade (methylphenylmethyl C at least 90% purity) was mixed with 32.0 g of polymethylene polyphenyl isocyanate and 130.0 g of tolylene diisocyanate, and the resulting mixture was then added to the aqueous solution in the reaction vessel. A suitable catalyst, for example a basic tertiary organic amine, may also be added to the water-miscible mixture. The mixture was vigorously stirred using a high friction stirrer to form an oil-in-water emulsion. After the emulsion had formed and the desired particle size was obtained, stirring was continued until the reaction was complete. The temperature of the emulsion was raised to 60 ° ^C and the pH of the dispersion was maintained for 3 hours with continuous stirring to 6.5 by creating conditions to complete the polymerization at the interface. The resulting aqueous microcapsule suspension was cooled to room temperature. To the aqueous microcapsule suspension was added 1.1 g of Ultconate ΑΩΚ soap, 15.5 g of Collold 225 dispersant and 5.9 g of Kaolin RC-32 disintegrant and the resulting suspension was spray dried. The dry encapsulated product in the form of microcapsules contained 72.5 wt. % plmmlphos-methyl.

The use of the formulations can be made more pleasant by the addition of free, for example, Alplne Mask, which is added to the formulation after encapsulation and in an amount of about 0.9%.

Example 2

Evaluation of the effectiveness of dry formulations of organophosphate insecticides in cattle control

The efficacy of microscopically encapsulated dry pesticide formulations is demonstrated by a dose filtration study using a microscopically encapsulated 74X plmmlphos-methyl dry formulation applied to cats selected from a random population of mixed breeds of domestic animals. The animals were placed in

Individual cages, which were located in rooms with controlled environment and were provided with normal cat food and water. For the objectives of the dose titration study, animals were divided into four groups, with three cats in each group. The first group of cats was not treated; the second group was treated with 0.2 g of a dry formulation of a microscopically encapsulated 74% plmlphos-methyl preparation prepared as described in Example 1; a third group of cats was treated with 0.3 g of the preparation; and a fourth group of 0.4 g preparation. Each cat was infected with 100 Cat fleas Cspenocephalidejs One day prior to application of the microscopically encapsulated preparation. The preparation was applied to the animal hair so as to form a single area on the back of each animal in a tangle near the shoulder blades.

The effects of the preparation in reducing, i.e., flea control, were determined by monitoring the number of whites that remained on the bodies of both treated and untreated animals. The number of beasts remaining on the animals was determined by daily counting the dead beasts found on the trays that covered the bottom of each cage and performing a direct calculation of the flea individuals remaining - on each animal being monitored. The data obtained was used to calculate the percent reduction of the whiteness in each group using the formula given in Table II.

Table II

Tested day treatment ** 0.2 g ^B 0.3 g ^B 0.4 g ^B 3 100X 100% 100% 7 95% 97% 90% 9 94% 94% 94%

The paws were infected with 100 fleas one day prior to treatment and again

Sixth day. On the third, seventh and ninth day, all fleas that remained on the body of each animal were counted.

^B Data are expressed as the total number of fleas total number on control cats per treatment% reduction of bitches on cats cat cats = x 100 total number of balls on control cats

WITH

The results of the efficacy study show that microscopically encapsulated dry formulations reduce 100% infection on treated cats three days after treatment, as compared to control animals. In addition, a single treatment, applied on day 1, protected the animals from recurrence for more than nine days under the conditions used in the test.

Example 3

The responses of cats to the dry formulation of microscopically encapsulated organophosphate cat and cat insecticides were randomly divided into four treatment groups, with the result of their response to the dry formulation treatment of microscopically encapsulated microspheryl methyl. The first group C1) was treated with 0.3 g 722 dry microscopically encapsulated pllmlphos-methyl, the second group C 2) was treated with 0.6 g 722 dry plrlmlphos-methyl and the third group C3) was treated with 1 ml 212 pllmlphos-methyl in 792 methylcarbltole . Treatment of the third group served as a positive control for the study.

The animals were housed in separate cages and equipped with normal cat food and water according to the vol. All treatments were administered on a single day 0 study on a cat back, at the dorsal torax site near the shoulder blades. The liquid composition, intended for the control oetrenle (C3), was applied by sealing 1 ml of the all-tissue moieties directly onto the animal's skin.

Treatments C1) and C2) were first observed for the formulations tested.

it gashed into the maCacle's back. MaCky continuously One hour after application for another four hours per hour

Intervals and then twice a day for the next two days.

Five of the nine macrophages that were subjected to control treatment (C12 ml (21% (mlmphos-methyl in 79% methylcarbol)) showed an undesirable sintering of the pesticide one hour after application, with one macaque sintering slightly. that is, she had clear drops of saliva on her paw. Three cats had strong sunshine within an hour after treatment and one cat had profound sunshine. All of these reactions persisted 10 to 20 minutes after application of the pesticide formulation and were marked as non-transient. One of the cats continued to overheat for four hours after the application of the liquid plmphos-methyl formulation. Six patients vomited twice during the first hour after dosing and vomited again the following day.

Unlike animals subjected to control treatment (C3), none of the first group C1) treated with a 0.3 sec microscopically encapsulated dry composition of 72% plmphosmethyl did not last more than two minutes. In addition, none of this group reversed the pesticide in response to the application of the microscopically encapsulated dry formulation. Only two cats showed a weak sintering response during the first hour after treatment and two cats showed a strong saliva. One cat showed a mild sintering response three hours after application of the microscopically encapsulated formulation.

Animals from the second group C2), which were treated with 0.6 g of a microscopically encapsulated dry formulation of 72% plmlphosmethyl, showed only very short transient responses that did not last longer than two minutes. None of this group vomited in response to dry formulation application.

Claims (12)

PATENT CLAIMS 1. A method for reducing adverse reactions to an insecticide in an animal requiring the administration of an insecticide in the treatment of parasite infections, characterized in that it comprises topically applying the organophosphate insecticide in a dry formulation to the animal. Method according to claim 1 1 v y z on the No. at J ú C 1 with and T ý m. that Insecticide Is provided within a mlkrokapsullek :. A method according to claim 2 v y z on the No. at J ú C 1 with and Λ ý m. that The insecticide contains plmphos-methyl. The method of claim 2 v y z on the No. at J ú C and with and T ý m. wherein the insecticide comprises a microscopically encapsulated dry formulation of about 20 to about 0 X organophosphate. 5. The method of claim 2, wherein the insecticide comprises a microscopically encapsulated dry formulation of about 70-75% organophosphate. The method of claim 1, wherein the dry formulation is applied only to a single limited area of animal hair or skin. 7. The method of claim 6, wherein about 0.1 g to 1.0 g of dry formulation per kilogram of body weight of the animal is applied to the animal. Θ. The method of claim 1 wherein the parasites comprise fleas, ticks or lice. 9. The method of claim 1 wherein the animals to be treated are selected from the group consisting of cattle, sheep, goats, horses, donkeys, pigs, dogs, cats and rabbits. A method according to claim 1, characterized in that. that the animal to be treated. She's a cat. 11. Method according to claim 10, characterized by by dry phos-methyl. It is microscopically encapsulated by plrlmi- 12th to an insecticide in reducing adverse reactions of animals. A method which involves infusions requiring ectoparasites, topically administering a formulation of about 20 doses at about treatment by: 0.1 g to up 1.0 administration of the insecticide indicated microscopically encapsulated dry 80X plmphml-methyl per animal in g per kilogram animal weight. protection of accounts 1 p 13. The method of indicating a dry organophosphate formulation needs such protection. an animal prior to infection with ectoparasltml, and comprising topically applying the insecticide to the animal, 14. The method of claim 13, wherein the insecticide is provided in the form of microcapsules. 15. A method according to claim 14, wherein the insecticide comprises pirimiphos-methyl. 16. The method of claim 14, wherein the insecticide comprises a microscopically encapsulated dry formulation of about 20-90% organophosphate. 17. The method of claim 14, wherein the insecticide comprises a microscopically encapsulated dry formulation of about 70-75% organophosphate. 19. The method of claim 14, wherein the animal to be treated. Je maôka. 19. The method of claim 13, wherein about 0.1 g to 1.0 g dry formulation is applied to the animal. kg of animal body weight.