MXPA98003838A - Dry formulations of pesticides for controlling parts in anima - Google Patents

Abstract

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

Description

DRY FORMULATIONS OF PEST1C1DES TO CONTROL ECTOPARASITES IN ANIMALS This invention relates to a method for protecting an animal from infestation by fleas and other ectoparasites. Dry formulations of organophosphate insecticides control fleas in animals when applied to a small, limited area of the animal's liner in a single application of high concentration, low volume. These formulations have unexpected properties which makes their use advantageous in comparison with liquid insecticide formulations that are currently used for the control of fleas in animals.

BACKGROUND OF THE INVENTION Methods for protecting animals from infestation by fleas and other ectoparasites typically involve the application of large volumes of pesticide compositions containing low concentrations of the insecticide. These methods include spraying the composition into the lining or skin of the animal, immersing the animal in a bath containing the pesticidal formulation, or powdering the animal with a powder containing the insecticide. The application of these compositions of liquid or powder insecticides is inconvenient, problematic and uncomfortable. Domestic animals are often traumatized by having their bodies sprayed, submerged or powdered. Significant amounts of the insecticide never reach the animal, and much of what is applied often falls shortly after the treatment is applied, which greatly reduces the effectiveness of the treatment and can adversely affect the environment. The use of immersion solutions can be disturbing for pets, particularly for cats, who often have a natural aversion to water. Immersion solutions are expensive, particularly when only one or a few animals are treated, and solutions must be disposed of properly after use to avoid contamination to the environment. More importantly, all these applications of pesticide compositions should be repeated frequently, as they are only effective for periods of one to two weeks. Because cats tend to groom themselves by licking their bodies and skin, they are particularly susceptible to adverse reactions that arise from the ingestion of insecticides applied to their bodies to prevent insect infestation. For example, cats can foam in the mouth or make excess saliva after the application of certain insecticides. In more severe cases, treated animals may vomit. These adverse reactions can be due to the toxicity of the insecticides used for the treatment. They can also occur under circumstances where the insecticide preparation does not pose a problem due to its toxicity, but the animal reacts to the unpleasant taste or odor of the insecticide in an adverse way.

Collars impregnated with insecticide have been used to prevent the infestation of domestic animals with fleas. Many pets, particularly cats, refuse to wear necklaces around their necks, and many of the animal owners do not like to expose the animal or themselves to the insecticides on the collar. In addition, flea collars are usually less effective in preventing flea infestation than the methods previously described. Pet owners often use the collars to supplement other methods that involve direct application of the insecticide to the animal's body. Many of the pesticides commonly used in agricultural and veterinary applications, including organophosphate compounds, are known to be effective in the control of ectoparasites such as fleas. However, these compounds often produce unwanted responses in domestic animals when applied in concentrations and in dosage forms necessary to effectively control flea infestation. It is well known to those who formulate pesticide compositions that their biological functioning in specific applications is frequently affected by the formulation that is used in particular. The formulations that make the pesticides available in solution are commonly more biologically active than the dry pesticide formulations. Nevertheless, these liquid formulations are more toxic for those who have contact with them, particularly the animal being treated and the person who applies the pesticide to the animal, since they are absorbed more quickly throughout the skin. The applications of certain pesticide formulations can cause adverse reactions in domestic animals. For example, domestic cats may respond to the application of organophosphate insecticides by producing excess saliva and even vomiting. Adverse reactions can also occur even where the animal does not receive a toxic dose of the insecticide, but reacts simply to the unpleasant taste or odor of the insecticide formulation used. Although the insecticide formulation does not pose any health risk to the animal, these responses can be very disturbing to the owner of the animal, particularly since the owners often do not realize that the animal is simply reacting to the unpleasant taste or smell of the preparation. In this way, effective compositions for controlling fleas in animals, in particular domestic cats, are still needed. Accordingly, an object of this invention is to develop formulations of organophosphate compositions which are effective for substantial periods and which are safe, simple and convenient to use and which do not cause adverse reactions in the animals to which the formulations are applied.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to a method for reducing adverse reactions to an insecticide by an animal in need of administration of an insecticide to treat an infestation of parasites. It has been unexpectedly discovered that the application of a dried formulation of an organophosphate insecticide provides an effective and convenient treatment to protect an animal against infestation by fleas and other ectoparasites, at the same time reducing adverse reactions by the animal to the insecticide. These dry formulations include microcapsules containing insecticide, which can be applied to one or more limited areas of an animal's body or skin. The formulations are effective in inhibiting ectoparasite infestation for periods of up to two weeks as a result of controlled release of the insecticide, and do not cause severe adverse reactions in the treated animals.

DETAILED DESCRIPTION OF THE INVENTION The invention of the present application relates to substantially dry formulations of high concentration, low volume, of insecticides that are effective for the control of fleas and other ectoparasites in animals. Ectoparasites are parasites that live in the outer parts of an animal's body, unlike the endoparasites that live inside the body of a host animal. Common ectoparasites include fleas, ticks, lice, mites and flies. The present invention also relates to methods by which these formulations are applied to the animal being treated. The application of the dry formulations of the invention provides effective protection against infestation by ectoparasites at the same time reducing to the minimum the number and severity of adverse reactions that may occur after treatment with topical formulations of insecticides. Adverse reactions include reactions that can produce prolonged or long-lasting toxic effects due to exposure of the animal to an insecticide treatment. Such adverse effects include skin irritation or other exhibited signs of toxicity, such as excessive salivation or vomiting, which may last for hours or even days after the treatment is applied. In the most severe cases, such adverse reactions can result in the death of the animal. In addition, adverse reactions include reactions that can occur even when the animal does not receive a toxic dose of the insecticide, but reacts when exposed to the treatment. These adverse reactions include excessive salivation and even vomiting, which occurs in response to the smell of the insecticide where the preparation is offensive to the animal. Such adverse reactions are particularly a problem when treating cats because of their natural grooming behavior. The substances applied topically will be almost licked and ingested shortly after being applied to the animal. When the substance is bad or unpleasant, the animal will often salivate immediately and, in more severe cases, may vomit. Since such reactions generally alarm pet owners and lead to their repetitive treatments to control ectoparasites, these reactions are also considered as adverse reactions, although they do not result from the toxic effects of the insecticides present in the formulations. Without wishing to be limited to any particular theory as to why the methods of the present invention prevent or reduce adverse reactions, it appears that the particular formulations, together with the particular methods of the present invention for applying the formulations, reduce the likelihood that the treated animal will be cleaned after the application of insecticide. This effect is largely due to the treatment being a substantially dry formulation instead of a wet formulation. Pesticides that are useful for the dry formulations of the present invention include compounds of the group known as organophosphates.This group of compounds is known in the art to possess useful pesticidal properties., in particular in the control of fleas in animals. Suitable organophosphate pesticides may include phosphate, phosphothioate or phosphothionate compounds. Preferred preferred pesticides for use in the formulations include the organophosphate compound known as pirimiphos-methyl O- (2-diethylamino-6-methylpyrimidin-4-yl) or, o-dimethyl phosphorothioate). Specific examples of organophosphate compounds that can be used in the formulation are listed in Table I.

TABLE I Chlorifos Pirimifos-methyl Diazinon Tetrachlorovinfos In the present application the term "dry formulation" is used to indicate that the insecticide is prepared so that it contains no more than insignificant or negligible amounts of water. One way in which said dry formulation can be prepared is to micro-encapsulate the pesticide by using organic polyisocyanate intermediates to form a polyurea capsule around the water-immiscible insecticide. The amount of water in the final preparation will be determined by the ability of the inert ingredients that surround the microcapsules to maintain water under the conditions in the drying apparatus used to dry the final microencapsulated preparation. In most cases the amount of water adsorbed on the inert material is very small, so that the formulation is substantially dry. The microencapsulation of selected pesticides can be achieved by the interfacial polymerization of monomer units present in emulsion droplets, which are formed when the water immiscible pesticide is vigorously mixed with an aqueous solution containing additional and heated polymerization monomers as discussed in Seaman. and others, "Trends in the Formulation of Pesticides - An Overview," Pesticide Science 29 (1990) p. 437-449. The monomers react to form a polymer skin that encapsulates the pesticide and controls its release. The encapsulation can reduce the oral toxicity of the pesticide as much as 100 times that of the non-microencapsulated water-based treatments and reduces the toxicity of the skin by 10 times that of the non-microencapsulated water-based treatments. A preferred method of encapsulating pesticides for use in the treatment of ectoparasite infestation in animals is that described in the U.S. Patent. No. 4,285,720, the description of which is incorporated herein by reference. The water-immiscible insecticide being encapsulated is dispersed in an aqueous solution containing suitable surfactants and a protective colloid. Useful surfactants include nonionic, anionic or cationic surfactants having a hydrophilic to lipophilic balance scale (HLB) of about 12 to about 16. Examples of suitable surfactants are sodium isopropyl naphthalene sulfonate, polyoxyethylene sorbitol isopropyl laurate, ethoxylated nonylphenols, and polyethylene glycol ethers. Preferred surfactants are polyethylene glycol ethers of linear alcohols such as the linear alcohol ethoxylate emulsifier Tergitol 15-A-20. Suitable protective colloids can be selected from a wide range of such materials, including polyacrylates, methylcelluloses, polyvinyl alcohol, polyacrylamide and polymethylvinyl ether / maleic anhydride. The protective colloid can be added to the microencapsulation system either before or after the organic dispersion is made. The dried microencapsulated formulations of the invention contain from about 20 to 80% by weight of the active pesticide. A preferred embodiment is a dry microencapsulated formulation containing from about 55 to 75% pirimiphos-methyl. Advantageously, the dry composition of the present application can be applied to a single limited area in the animal to be treated. Alternatively, the treatment can be applied to two or more specific sites of limited area of the animal. Preferably, the composition is applied as a single spot to a limited area on the back of the animal between its shoulder blades in a location that the animal is unable to reach with its tongue, so that it can not lick or clean the pesticide composition of its skin. This is important in particular when the composition is used to treat cats, since cats will often produce saliva or nausea after being exposed to substances they consider unpleasant or tasteless., either orally or by smell. Since the composition is applied topically, it will probably be licked or ingested shortly after it is applied to cats due to its grooming behavior. The amount of the dry formulation to be applied to an animal is determined by the size of the animal and by the concentration of pesticide in the formulation. Generally, the compositions can be applied at a dose within a range of about 0.1 gram (g) to about 1.0 gram of active compound per kilogram (kg) of animal weight. Animals weighing between about 2.2 to 4.5 kg can be treated with a single application of about 0.3 to about 4 g of the dry formulation, which contains 20 to 90% organophosphate. A preferred treatment comprises applying 0.3 g of a dry formulation containing about 70-75% pirimiphos-methyl per kg of animal weight. The dry pesticide formulations of the present invention are useful for controlling fleas and other ectoparasites in animals, in particular smaller animals that are kept as pets, including dogs, cats, rabbits and rodents. The compositions and methods described are particularly advantageous for controlling fleas in cats. Cats are very ineffective in metabolizing pesticides and, therefore, are particularly susceptible to their toxic effects. In addition, due to their natural grooming behavior, cats are particularly susceptible to reactions due to the unpleasant taste or odor of the preparations that are applied to the lining or skin of animals. The application of the compositions described by the method of the present invention is essentially non-toxic to cats, and the application of the preparations does not appear to stimulate the animal to groom itself immediately after application. The methods and compositions described are also useful for the control of other insect pests, including fleas, lice, ticks and flies, in herd animals such as cows, sheep, goats, horses, donkeys, camels, pigs, deer, caribou and buffalo EXAMPLE 1 PREPARATION OF PIRIMIFOS-DRY ENCAPSULATED METHYL Dry encapsulated pirimiphos-methyl was prepared by mixing 1770 g of water with 47.0 g of 40% Reax, 100 mg sodium lignosulfonate (a poly-protective colloid) and 76.0 g of 20% aqueous Tergitol XD emulsifier in a reaction vessel open with agitation. In a separate container, 2000 g of technical grade pirimiphos-methyl (at least 90% purity) was mixed with 32.0 g of polymethylene polyphenylisocyanate and 130.0 g of toluene diisocyanate, then added to the aqueous solution in the vessel. reaction. It also owes to create an aorooiado catalyst. such EXAMPLE 2 EVALUATION OF THE EFFECTIVENESS OF THE APPLICATIONS OF DRY FORMULATIONS OF ORGANOPHOSPHATE INSECTICIDES TO CONTROL FLEAS IN CATS The efficacy of dry microencapsulated formulations of pesticides was shown in a volumetric dose analysis using a dry microencapsulated formulation of 74% pirimiphos-methyl, which was applied to cats selected from a random population of mixed-breed domestic animals. The animals were housed in individual cages in environmentally controlled rooms and provided with commercial cat food and water ad libitum. For volumetric dose analysis, the animals were divided into four groups of three cats each. Each group received either 1) no treatment; 2) 0.2 grams of the 74% dry formulation of microencapsulated pirimiphos-methyl preparation prepared in accordance with the procedures of Example 1; 3) 0.3 grams of the preparation or 4) 0.4 grams of the preparation. Each cat was infected with 100 cat fleas, (species Ctenocephalides felis) one day before applying the microencapsulated preparation. The preparation was applied to the skin or lining of the animal as a single application of spot to the area of the dorsal neck of each animal, near the shoulder.

The effect of the preparation to reduce or control infestation by fleas was determined by controlling the number of fleas that remain in the bodies of treated and untreated animals. The number of fleas that remain in the animals was determined by counting the number of dead fleas found in the trays that covered the bottom of each cage each day and by making direct body counts on each animal to determine the number of fleas that remain the animal. The data obtained was used to calculate the percent reduction of fleas in each group by using the formula given in Table I I.

TABLE II Treatments Test Day 0.20 '0.30' 0.4g '3 100% 100% 100% 7 95% 97% 90% 9 94% 94% 94% a Cats were infested with 100 fleas a day before treatment and once again on day 6. Full body counts were made of fleas that remain on each animal on days 3, 7 and 9. The data are expressed as per percent reduction Total fleas in - Total fleas in fleas in cats Control cats Cats treated x 100 Total fleas in Control Cats The results of the efficacy study indicate that the microencapsulated dry formulations reduced the infestation in animals treated three days after treatment for 100% compared to controls. In addition, the treatment, applied on day 1, protected the animals against reinfestation for more than nine days under the conditions used in the test.

EXAMPLE 3 CATS RESPONSE TO A DRY FORMULATION OF MICROENCAPULATED ORGANOPHOSPHATE INSECTICIDES Thirty-six female and male cats were randomly placed in one of the four treatment groups to evaluate their response to treatment with a dry formulation of microencapsulated pirimiphos-methyl. Each group received one of the following four treatments: 1) 0.3 grams of 72% dry pirimiphos-microencapsulated methyl, 2) 0.6 grams of 72% dry pirimiphos-microencapsulated methyl and 3) 1 ml (milliliter) of 21% pirimiphos -method in 79% of methyl carbitol. Treatment 3 served as a positive control for the study. The cats were housed individually and were provided with a commercial cat food and water ad libitum. All treatments were applied to the back of the cat, in the thorax dorsal near the shoulder blades, once on day 0 of the study. The liquid composition of control treatment 3 was applied by pipette of 1 ml aliquots directly into the skin of the animal. Treatments 1 and 2 were rubbed briefly on the cat's skin. The cats were observed continuously for the first hour after the application of the test formulation, at intervals of one hour for the next four hours after treatment, then twice a day for the next two days. Five of the nine cats that received control treatment 3 (1 ml of 2% pirimiphos-methyl in 79% methyl carbitol) showed an adverse salivation response within one hour after pesticide application. One of these responses was light, with the animal having clear drops of saliva on its lips. Three of the cats had a strong salivation response in one hour of treatment and one cat had a deep salivation response. All of these responses lasted 10 to 20 minutes after the pesticide application and were determined as non-transient responses. A cat continued to produce saliva abnormally for four hours after the application of the liquid pirimiphos-methyl formulation. A sixth cat vomited twice in the first hour after treatment and once again the next day. Unlike the animals receiving the control treatment 3, none of the cats in group 1 of treatment, the group treated with 0.3 grams of dried microencapsulated formulation of 72% pirimiphos-methyl, had episodes of salivation that lasted more than two minutes. Additionally, none of the cats in this group vomited in response to the application of the microencapsulated dry formulation of pesticide. Only two of the cats showed a mild salivation response during the first hour after treatment, and two showed a strong response. A cat exhibited a strong salivation response 3 hours after the application of the microencapsulated formulation. The animals in treatment group 2, the group treated with 0.6 grams of the dried microencapsulated formulation of 72% pirimiphos-methyl, showed extremely short transient responses that lasted no more than two minutes. None of the cats in this group vomited in response to the application of the dry formulation.

Claims (17)

1 .- A method for reducing adverse reactions to an insecticide by an animal in need of administration of insecticide to treat an infestation of parasites that comprises applying topically to the animal a dry formulation of a microencapsulated organophosphate prepared by the combination of the organophosphate and a polyisocyanate with an aqueous solution of a surfactant and a protective colloid to form a dispersion so as to microencapsulate the organophosphate and then dry the resulting microcapsules.

2. The method according to claim 1, wherein the insecticide comprises pirimiphos-methyl.

3. The method according to claim 1, wherein the insecticide comprises a dry microencapsulated formulation of about 20 to 80% organophosphate.

4. The method according to claim 1, wherein the insecticide comprises a dry microencapsulated formulation of about 70 to 75% organophosphate.

5. The method according to claim 1, wherein the dry formulation is applied only to a single limited area of the lining or skin of the animal.

6. The method according to claim 5, wherein from about 0. 1 gram to about 1.0 gram of the dry formulation per kilogram of body weight is applied to the animal.

7. The method according to claim 1, wherein the parasites comprise fleas, ticks and lice.

8. The method according to 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.

9. The method according to claim 1, wherein the animal to be treated is a cat.

10. The method according to claim 9, wherein the dry formulation is microencapsulated pirimiphos-methyl.

11. A method for reducing adverse reactions to an insecticide by an animal in need of administration of insecticide to treat an ectoparasite infestation comprising treating the animal by topical application to the animal of a microencapsulated dry formulation of from about 20 to about 80% of pirimiphos-methyl at a dose of about 0.1 gram to about 1.0 gram per kilogram of animal weight.

12. A method for protecting an animal from infestation with ectoparasites comprising topically applying a dry formulation of a microencapsulated organophosphate insecticide to an animal in need of such protection, wherein said microencapsulated formulation is prepared by combining the organophosphate and a polyisocyanate with an aqueous solution of a surfactant and a protective colloid to form a dispersion so as to microencapsulate the organophosphate and subsequently dry the resulting microcapsules.

13. The method according to claim 12, wherein the insecticide comprises pirimiphos-methyl.

14. The method according to claim 12, wherein the insecticide comprises a dry microencapsulated formulation of about 20 to 90% organophosphate.

15. The method according to claim 12, wherein the insecticide comprises a microencapsulated dry formulation of about 70 to 75% organophosphate.

16. The method according to claim 12, wherein the animal to be treated is a cat.

17. The method according to claim 12, wherein from about 0.1 gram to about 1.0 gram of the dry formulation per kilogram body weight is applied to the animal.