MXPA06005025A - High concentration topical insecticide containing insect growth regulator - Google Patents

Abstract

A topical insecticide is provided which can be safe to use and avoids many common deleterious side effects of conventional topical insecticides. The insecticide contains an insecticide and an insect growth regulator effective for killing fleas, flea larvae and flea eggs. The insecticide is formulated by dissolving an insecticidal (tetrahydro-3-furanyl) methylamine derivative or a chloronicotinyl insecticide and an insect growth regulator (IGR) in a solvent containing a quaternary ammonium salt to increase the solvency of the IGR component, thereby providing an insecticide having high insecticidal activity.

Description

HIGH CONCENTRATION LOCAL INSECTICIDE CONTAINS INSECT GROWTH REGULATOR REFERENCE TO RELATED REQUESTS This application is a continuation in part of the US.

Serial No. 1 0 / 700,013, filed November 1, 2003. Priority is claimed to the above-listed application, which is incorporated herein by reference.

BACKGROUND OF THE INVENTION The invention relates generally to insecticides and more particularly to a local insecticide, such as one suitable for use in domestic pets such as dogs and cats. Infestation of animals with fleas is highly undesirable. In accordance with the above, it has become common to administer both local and internal insecticides to livestock and pets. Local applications may be desirable, since several insecticides are acceptably safe when used locally, but not when used internally. Several local insecticides have deficiencies. Some require a large volume to be applied to the animal. This can cause a considerable problem and can lead to an unpleasant odor. Also, when the animal is a domestic pet, there is an additional complication that the insecticide must be safe for human contact. It should also not lead to coloring of furniture, folders and the like. Finally, even if it is safe, local insecticides for domestic pets should not be irritating or lead to rashes, hair loss or other unpleasant side effects. Accordingly, it is desirable to provide an improved local insecticide, which overcomes the disadvantages of the prior art.

BRIEF DESCRIPTION OF THE INVENTION Generally speaking, according to the invention, a local insecticide is provided which includes an insecticide plus an insect growth regulator. These ingredients are advantageously dissolved in a high concentration in a solution containing a quaternary ammonium salt, such as cetyltrimethylammonium chloride, tallowalkyltrimethylammonium chloride, or oleyldimethylammonium chloride. The insecticidal formulation of the invention can be safe to use and avoids several common side effects of conventional local insecticides. In accordance with the foregoing, an improved local insecticide is provided which overcomes the deficiencies of the prior art, a method for preparing such an insecticide and a method for controlling infestation with the insecticide. The invention provides a local insecticide containing an insecticide and an insect growth regulator, which is advantageously effective for killing fleas, flea eggs and flea larvae. The insecticide component preferably contains an insecticide derived from (tetrahydro-3-furanyl) methylamine or a chloronicotinyl insecticide. Advantageously, it also includes an insect growth regulator (IGR) in a solvent component. Advantageous solvent solutions include those containing water, ethyl lactate and / or quaternary ammonium salt. The quaternary ammonium salt is preferably a hydrophobic ammonium salt such as oleyldimethylammonium chloride, tallowalkyltrimethylammonium chloride, and oleyldimethylammonium chloride. It has been determined that an "ammonium chloride with large numbers of carbon atoms, preferably about 16 or more, results in a more favorable solvent system In a preferred embodiment of the invention, the solvent component advantageously contains a sufficient amount of the salt to increase the solvency of the IGR compared to the solvency of the IGR in the solvent without the salt.The selection of components in the solvent system is allowed for the increased solubility of the insecticide and the insect growth regulator thereby providing an insecticide which has high insecticidal activity The active ingredients and the insecticides according to the preferred embodiments of the invention are generally available as crystals and solids It has been determined that it is advantageous to dissolve or otherwise place these active in a liquid form for use as products of local spot on animals. Locals are more advantageous if the amount of liquid applied can be minimized. This should be balanced with the need for adequate dosage to achieve the desired insecticidal effect. ThusIt is desirable to use a solvent that will allow the solubilization of a high concentration of insecticide. In a preferred embodiment of the invention, the insecticide contains 1 - [(tetrahydro-3-furanyl) methyl} -2-nitro-3-methyIguanidine (dinotefuran) and the IGR comprises piriproxifen and / or metroprene. In another preferred embodiment of the invention, the insecticide comprises a chloronicotinil insecticide, preferably acetamiprid, imidacloprid, nitenpyram or clothianidin, and the IGR comprises pyriproxfen and / or methoprene. Dinotefuran is an insecticide that kills adult fleas, and piriproxifen and metropreno are insect growth regulators that kill flea larvae and prevent flea eggs from hatching. Accordingly, the combination of an insecticide, such as acetamiprid or dinotefuran and an IGR, such as pyriproxyfen or methoprene, is provided for an effective flea control system since only about 5% of the fleas existing in an animal they are adults and another 95% are in a young state (eggs and larvae). Dinotefuran and piriproxifen are hydrophilic and lipophilic, respectively. A solvent system that is provided for solubilization of a high concentration of dinotefuran will typically not allow pyriproxygen to solubilize. However, it has been determined that the addition of a quaternary ammonium salt such as cetyltrimethylammonium chloride, tallow alkyltrimethylammonium chloride, and oleyldimethylammonium chloride is allowed for an effective amount of pyriproxyfen to be solubilized. In addition, salt can help prevent emulsification of the formulation. This advantageously produces an insecticide with high insecticidal activity. Accordingly, an object of the invention is to provide an improved local insecticide. Another object of the invention is to provide a method for controlling insect infestation. Another object of the invention is to provide a local insecticide that works more quickly and / or more permanently different from other insecticides and / or may include a lower total volume of applied insecticide. Another object of the invention is to provide an improved method for making an insecticide. Other objects and characteristics will be partly apparent and partly pointed out.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES According to the invention, local insecticide formulations, containing an insecticide and an insect growth regulator effective for killing fleas, flea eggs and flea larvae, are provided. The combination of an effective insecticide against adult fleas with an insect growth regulator effective against flea eggs and larvae results in a highly effective insecticidal formulation. In a preferred embodiment of the invention, the insecticide is formulated by dissolving an insecticidal derivative (tetrahydro-3-furanyl) methylamine and an insect growth regulator (IGR) in a solvent component comprising water, ethyl lactate and quaternary ammonium salt. The solvent component contains a sufficient amount of quaternary ammonium salt to increase the solvency of the IGR compared to the solvency of the IGR in the solvent without the quaternary ammonium salt and to increase the effectiveness of the insecticide compared to its effectiveness without the quaternary ammonium salt. In a preferred embodiment of the invention, the active ingredient of the insecticide formulation is an amine derivative, which has a nitro-methylene group, a nitroamino group or a cyanoamino group, which can be formulated by having low toxicity and excellent insecticidal activity. The active ingredients of insecticides and their method of formation according to the preferred embodiments of the invention are discussed in U.S. Patent Nos. 5,532,365 and 5,434,181, the contents of which are incorporated herein by reference. In another preferred embodiment of the invention, the insecticide comprises an insecticidal (tetrahydro-3-furanyl) methylamine derivative of the following formula (1). The (tetrahydro-3-furanyl) methylamine derivatives of the formula (1) have an excellent insecticidal activity even in the absence of pyridylmethyl group or a thiazolylmethyl group in their molecular structure. where Xi, X2, X3, X4, X5, Xß. and X7. each represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; Rt represents a hydrogen atom, an alkyl group having from 1 to 5 carbon atoms, an alkenyl group having 3 carbon atoms, a benzyl group, a. alkoxyalkyl group having from 2 to 4 carbon atoms (in its total group), an alkyloxycarbonyl group having from 1 to 3 carbon atoms, a carbonyl phenoxy group, an alkylcarbonyl group having from 1 to 6 carbon atoms, alkenylcarbonyl group having from 2 to 3 carbon atoms, a cycloalkylcarbonyl group having from 3 to 6 carbon atoms, a benzoyl group, a benzoyl group substituted by alkyl group (s) having from 1 to 4 carbon atoms, a benzoyl group substituted by halogen atom (s), a 2-furanylcarbonyl group or a N, N-dimethylcarbamoyl group; R2 represents a hydrogen atom, an amino group, a methyl group, an alkylamino group having from 1 to 5 carbon atoms, a di-substituted alkylamino group having from 2 to 5 carbon atoms (in its total group), a 1-pyrrolidinyl group, an alkenylamino group having 3 carbon atoms, an alkynylamino group having 3 to 6 carbon atoms, a benzoyl group, a benzoyl group substituted by alkyl group (s) having from 1 to 4 carbon atoms, carbon, a benzoyl group substituted by halogen atom (s), a 2-furanylcarbonyl group, a N, N-dimethylcarbamoyl group, a (tetrahydro-3-furanyl) methyl group or a benzyl group, and Y2 represents a hydrogen atom or an alkyl group having from 1 to 5 carbon atoms); and Z represents = N-NO2, = CH-NO2 or = N-CN. The intermediates for producing the compounds of the formula (1) are represented by a formula (2): where Xi, X2, X3, X, X5. Xß, and X7, each represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R10 represents. an alkyl group having from 1 to 5 carbon atoms or a benzyl group; and R ^ represents an alkyl group having from 1 to 5 carbon atoms or a benzyl group. The derivatives (tetrahydro-3-furanyl) methylamine of the formula (1) and formula (2) according to the invention are excellent compounds having high insecticidal activity and broad insecticidal spectrum. In addition, agricultural chemicals containing the derivatives (tetrahydro-3-furanyl) methylamine of the formula (1) and (2) according to the invention have outstanding characteristics as insecticides and are hence useful. Specific examples of the alkyl group for Xi, X2, X3, X4, X5, X6, and X7, in the above formulas (1) and (2) include a methyl group, an ethyl group, an n-propyl group, a group So-propyl, a tert-butyl group, and the like, preferably a methyl group. Specific examples of the alkyl group for R include a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, an n-butyl group, an iso-butyl group, a sec-butyl group, a tertiary group -butyl, an n-pentyl group, and the like. Specific examples of the alkenyl group for R ^ include a 1-propenyl group, a 2-propenyl group, and the like. • Specific examples of the alkoxyalkyl group for R ^ include a methoxymethyl group, an ethoxymethyl group, an n-propoxymethyl group, an iso-propoxymethyl group, a methoxyethyl group, an ethoxyethyl group, and the like. Specific examples of the alkyloxycarbonyl group for R-incluyen include a methyloxycarbonyl group, an ethyloxycarbonyl group, an n-propyloxycarbonyl group, an iso-propyloxycarbonyl group, and the like. Specific examples of the alkylcarbonyl group for R1 include a methylcarbonyl group, an ethylcarbonyl group, an n-propylcarbonyl group, an iso-propylcarbonyl group, an n-butylcarbonyl group, an iso-butylcarbonyl group, a sec-butylcarbonyl group, a tertiary group -butylcarbonyl, an n-pentylcarbonyl group, an n-hexylcarbonyl group, and the like. Specific examples of the alkenylcarbonyl group for R1 include a vinylcarbonyl group, an l-methylvinylcarbonyl group, and the like. Specific examples of the cycloalkylcarbonyl group for include a cyclopropylcarbonyl group, a cyclobutylcarbonyl group, a cyclopentylcarbonyl group, a cyclohexylcarbonyl group, and the like. Specific examples of the benzoyl group substituted by alkyl group (s) for Ri include a 2-methylbenzoyl group, a 3-methylbenzoyl group, a 4-methylbenzoyl group, a 4-tert-butylbenzoyl group, and the like. Specific examples of the benzoyl group substituted by halogen atom (s) for Ri include a 2-chlorobenzoyl group, a 3-chlorobenzoyl group, a 4-chlorobenzoyl group, a 3,4-dicioro-benzoyl group, a 4-fIuorobenzoyl group , and the similar. Although R-i may take several substituents as described above, it is preferably a hydrogen atom, an alkylcarbonyl group having 1 to 4 carbon atoms or a cyclopropylcarbonyl group. Specific examples of the alkylamino group for R2 include a methylamino group, an ethylamine group, an n-propylamino group, an iso-propylamino group, an n-butylamino group, an iso-butylamino group, a sec-butylamino group, an tert-butylamino group, an n-pentylamino group, and the like, preferably a methylamino group. Specific examples of the di-substituted alkylamino group for R 2 include a dimethylamino group, a diethylamino group, a N-methyl-N-ethylamino group, a N-methyl-N-propylamino group, a N-methyl-Nn-butylamino group, and the like, preferably a dimethylamino group. Specific examples of the alkenylamino group for R 2 include a 1-propenylamino group, a 2-propenylamino group, and the like. Specific examples of the alkynylamino group for R2 include a propargylamine group, and the like. Specific examples of the alkoxyalkylamino group for R 2 include a methoxymethylamino group, an ethoxymethylamino group, an n-propoxymethylamino group, an iso-propoxymethylamino group, a methoxyethylamino group, an ethoxyethylamino group. and the similar. Specific examples of the alkyloxycarbonyl group designated by Y1 for R2 include a methyloxycarbonyl group, a thioxycarbonyl group, an n-propyloxycarbonyl group, an iso-propyloxycarbonyl group, and the like. Specific examples of the alkylcarbonyl group denoted by Y ^ for R2 include a methylcarbonyl group, an ethylcarbonyl group, an n-propylcarbonyl group, an iso-propylcarbonyl group, an n-butylcarbonyl group, an isobutylcarbonyl group, a sec-butylcarbonyl group, a group tert-butylcarbonyl, an n-pentylcarbonyl group, an n-hexylcarbonyl group, and the like, preferably a methylcarbonyl group, an ethylcarbonyl group, an n-propylcarbonyl, an iso-propylcarbonyl group, an n-butylcarbonyl group, an iso-butylcarbonyl group, a sec-butylcarbonyl group and a tert-butylcarbonyl group. Specific examples of the alkenylcarbonyl group denoted by Y i for R2 include a vinylcarbonyl group, a 1-methylvinylcarbonyl group, and the like. Specific examples of the cycloalkylcarbonyl group denoted by Y ^ for R2 include a cyclopropylcarbonyl group, a cyclobutylcarbonyl group, a cyclopentylcarbonyl group, a cyclohexylcarbonyl group, and the like, preferably a cyclopropylcarbonyl group. Specific examples of the benzoyl group substituted by alkyl group (s) denoted by Y ^ for R2 include a 2-methylbenzoyl group, a 3-methylbenzoyl group, a 4-methylbenzoyl group, a 4-tert-butylbenzoyl group, and the like. Specific examples of the benzoyl group substituted by halogen atom (s) denoted by Y, for R2 include a 2-chlorobenzoyl group, a 3-chlorobenzoyl group, a 4-chlorobenzoyl group, a 3,4-dichlorobenzoyl group, a 4-group -fluoro benzoyl, and the like. The specific examples of the alkyl group indicated by Y2 for R2 include a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, an n-butyl group, an iso-butyl group, a sec-butyl group, a tert-butyl group, a group n-pentyl, and the like, preferably a methyl group. In formula (1), compounds in which R-, and Yi are concurrently an alkylcarbonyl group having 1 to 4 carbon atoms or a cyclopropylcarbonyl group are preferred from the viewpoint of both insecticidal activity and production method . In a preferred embodiment of the invention, the derivative (tetrahydro-3-furanyl) methylamine dissolved in the solvent component is dinotefuran. Dinotefuran is an insecticide that will kill adult fleas. Preferably, dinotefuran is dissolved in the formulation at a concentration range of about 5 to 20%, more preferably about 10 to 15% and more preferably about 12 to 15%. All percentages, unless it is otherwise evident, they are on a weight basis. In another preferred embodiment of the invention, the insecticide is formulated by dissolving an insecticidal-effective amount of a chloronicotinyl insecticide and an insect growth regulator.

"(IGR) in a solvent component The solvent component contains a sufficient amount of quaternary ammonium salt to increase the solvency of the IGR compared to the solvency of the IGR in the solvent without the quaternary ammonium salt and increase the effectiveness of the insecticide compared to its effectiveness without the quaternary ammonium salt. In a preferred embodiment of the invention, the The solvent component comprises ethanol and quaternary ammonium salt. In another preferred embodiment of the invention, the solvent component comprises water, ethyl lactate and a quaternary ammonium salt. In a preferred embodiment of the invention, the chloronicotinyl insecticide in the formulation is N - ((6-chloro-3-pyridinyl) methyl) -N'-25 cyano-N-methyl-ethanimidamide (acetamiprid) and the growth regulator of Insect is piriproxifen or methoprene. Acetamiprid is an insecticide that mainly kills adult fleas. Acetamiprid is described in international applications PCT / JP90 / 01282 and PCT / EP93 / 01286, the contents of which are described herein for reference. In another preferred embodiment of the invention, the insect growth regulator is pyriproxyfen. In a preferred embodiment of the invention, pyriproxyfen is dissolved in the formulation in a concentration range of about 0.1 to 3%, more preferably about 0.5 to 3% and more preferably about 0.9 to 1.1%. In another preferred embodiment of the invention, the formulation comprises a dosage of at least about 10 mg of pyriproxyfen to an animal. Therefore, if the formulation contains 1% pyriproxyfen, an acceptable dose could be about 10 mg or more in a 1 ml application. In yet another preferred embodiment of the invention, the insect growth regulator is methoprene. In a preferred embodiment of the invention, methoprene is dissolved in the formulation at a concentration range of about 0.1 to 5%, more preferably about 0.5 to 5%, and more preferably about 3.0 to 5.0%. In another preferred embodiment of the invention, the dose comprises at least about 30 mg of methoprene administered to the animal. In a preferred embodiment of the invention, the insecticide is formulated by dissolving dinotefuran and pyriproxyfen in a solvent comprising water, ethyl lactate and a quaternary ammonium salt, preferably oleyldimethylammonium chloride. In another preferred embodiment of the invention, the insecticide is formulated by dissolving dinotefuran and pyriproxyfen in a solvent comprising ethanol and a quaternary ammonium salt, preferably oleyldimethylammonium chloride. Dinotefuran is an insecticide that kills adult fleas, acetamiprid is an insecticide that mainly kills adult fleas, and piriproxifen is an insecticide when you kill flea larvae and flea eggs. By killing fleas in adult and young settings, the insecticide formulation of the invention is useful in improving the rate of result and reducing the reoccurrence of pest infestation compared to other insecticide formulations. In another preferred embodiment of the invention, the insecticide is formulated by dissolving acetamiprid and pyriproxyfen in a solvent preferably comprising water, ethyl lactate and a quaternary ammonium salt, preferably oleyldimethylammonium chloride. In yet another preferred embodiment of the invention, the insecticide is formulated by dissolving acetamiprid and pyriproxyfen in a solvent preferably comprising ethanol and a quaternary ammonium salt, preferably oleyldimethylammonium chloride. Acetamiprid is an insecticide that kills mainly adult fleas, and piriproxifen is an insecticide that kills flea larvae and flea eggs. By killing fleas in adult and juvenile settings, the insecticidal formulation of the invention is useful for improving the rate of result and reducing the reoccurrence of flea infestation compared to other insecticide formulations. The high concentrations of dinotefuran and acetamiprid can be solubilized in a combination of water and ethyl lactate or ethanol. However, because dinotefuran is hydrophilic and piriproxifen is lipophilic, a solvent system that is provided for solubilization of a high concentration of dinotefuran will not allow pyriproxygen to be adequately solubilized. It has been determined that the addition of a quaternary ammonium salt such as an ammonium chloride, preferably with one or more carbon atoms, for example, cetyltrimethylammonium chloride, ammonium chloride tallowalkyltrimethyl and an oleyl dimethyl ammonium chloride, to the solvent component allows for an effective amount of pyriproxyfen to be solubilized in the formulation without emulsification, thereby allowing the delivery of high concentrations of hydrophilic and lipophilic insecticides in a highly effective local insecticide solution. Because pyriproxyfen is hydrophobic, it is preferable to select a quaternary ammonium salt in such a way that it is also hydrophobic in order to dissolve an effective amount of pyriproxyfen in the insecticidal formulation. The quaternary ammonium salts having a high number of carbon atoms in the alkyl chains such as cetyltrimethylammonium chloride, tallow alkyl ammonium chloride and oleodimethylammonium chloride are preferably selected for use in the solvent component. Preferably, the insecticidally effective amounts of dinotefurn and pyriproxyfen are incorporated in relatively low volumes. Such insecticide formulations are advantageously stable under various conditions of high and low temperature. In another preferred embodiment of the invention, the preferred solvent component comprises a mixture comprising water, ethyl lactate and oleyldimethylammonium chloride, wherein the final concentration of oleyldimethylammonium chloride ranges from 0.5 to 20%, more preferably 0.5 to 5%, of oleyldimethylammonium chloride, and more preferably a final concentration of 1.0% oleyldimethylammonium chloride. When the solvent contains oleyl dimethyl ammonium chloride, the proportion of water for ethyl lactate in the solvent is preferably about 1: 1 to 1: 2. Ethanol can also be added to the solvent component to improve solubility and to prevent high concentrations of dinotefuran or acetamiprid from crystallizing over time at low temperatures. In another preferred embodiment of the invention, the preferred solvent component comprises a mixture comprising water, ethyl lactate, ethanol and oleyldimethylammonium chloride, wherein the final concentration of oleyldimethylammonium chloride ranges from 0.5 to 20%, more preferably 0.5 to 5% chloride oleyldimethylammonium, and more preferably a final concentration of 1.0% oleyldimethylammonium chloride. When the solvent contains oleyl dimethyl ammonium chloride, the ratio of water in ethyl lactate to ethanol in the solvent is preferably about 1: 1: 1 to about 3: 4: 3, and all ratios therebetween. All proportions, unless otherwise evident, are on a weight basis. In a preferred embodiment of the invention, the insecticide is formulated by dissolving dinotefuran and pyriproxyfen in a solvent comprising water, ethyl lactate and one of the above salts, such as oleyl dimethyl ammonium chloride. Dinotefuran is dissolved in the formulation at a concentration range of about 5 to 20%, pyriproxyfen is dissolved in the formulation at a concentration range of about 0.5 to 3%, the concentration of oleyldimethylammonium chloride ranges from about 1 to 20%, and the concentration of ethyl lactate varies from approximately 50 to 67%. Preferably, dinotefuran is dissolved in the formulation at a concentration of about 15%, pyriproxyfen is dissolved in the formulation at a concentration of about 1%, and the concentration of oleyldimethylammonium chloride is about 1%. When the insecticide is formulated by dissolving dinotefuran and pyriproxyfen in a solvent comprising water, ethyl lactate and oleyldimethylammonium chloride, the ratio of dinotefuran to pyriproxyfen to oleyldimethylammonium chloride is preferably about 15: 1: 1, and the concentration of dinotefuran in the formulation of insecticide does not exceed 15%. In other preferred embodiments, the ratio of dinotefuran to pyriproxyfen to oleyldimethylammonium chloride is preferably about 10: 1: 1, 20: 1: 1, or 30: 1: 1 and all ratios therebetween, and the dinotefuran concentration preferably does not exceed fifteen%. For the application of approximately 0.5 to 1.33 ml of the insecticide to a companion animal weighing 9 pounds or less, it is preferable that the insecticide be formulated by dissolving approximately 150-200 mg of dinotefuran and approximately 10 mg of pyriproxyfen in a solvent comprising water, ethyl lacatate and oleyl dimethyl ammonium chloride to achieve a 90% death rate for fleas. In still another embodiment of the invention, the preferred solvent component comprises a mixture comprising water, ethyl lactate and oleyldimethylammonium chloride, wherein the final concentration of oleyldimethylammonium chloride is about 1.9 to 20%, and more preferably, the final chloride concentration Oleyldimethylammonium is approximately 20%. Ethanol can also be added to the solvent component to improve solubility. Preferably, when the insecticide is formulated by dissolving dinotefuran and pyriproxyfen in a solvent comprising water, ethyl lactate and oleyldimethylammonium chloride, dinotefuran is dissolved in the formulation at a concentration range of about 14 to 15%, pyriproxygen is dissolved in the formulation at a concentration range of about 1 to 3%, the concentration of oleyl dimethyl ammonium chloride ranges from about 19 to 20%, and the concentration of ethyl lactate ranges from about 40 to 75%. In still another embodiment of the invention, the preferred solvent component comprises a mixture comprising water, ethyl lactate and tallowalkyltrimethyl ammonium chloride, wherein the final concentration of ammonium chloride seboalkyltrimethyl ranges from about 1 9 to 20%, and more preferably, the concentration end of ammonium chloride tallowalkyltrimethyl is approximately 20%. Ethanol can also be added to the solvent component to improve solubility. Preferably, when the insecticide is formulated by dissolving dinotefuran and pyriproxyfen in a solvent comprising water, ethyl lactate and ammonium chloride seboalkyltrimethyl, dinotefuran is dissolved in the formulation at a concentration range of about 14 to 15%, pyriproxygen is dissolved in the formulation at a concentration range of approximately 1 to 3%, the concentration of ammonium chloride tallow alkyltrimethyl varies from approximately 19 to 20%, and the concentration of ethyl lactate ranges from approximately 40 to 75%. In another embodiment of the invention, the insecticide is formulated by dissolving acetamiprid pyriproxyfen in a solvent comprising water, ethyl lactate and a quaternary ammonium salt such as cetyltrimethylammonium chloride, tallowalumomethyltrimethyl ammonium chloride and oleyldimethylammonium chloride. Acetamiprid is dissolved in the formulation at a concentration range of approximately 5 to 50%, pyriproxyfen is dissolved in the formulation at a concentration range of approximately 0.5 to 3%, the concentration of the quaternary ammonium salt varies from approximately 1 to 20% , and the concentration of ethyl lactate ranges from approximately 50 to 67%. For the application of approximately 0.4 to 1.33 ml of the insecticide to a companion animal weighing 9 pounds or less, it is preferable that the insecticide is formulated by dissolving approximately 100 mg / ml of acetamiprid and approximately 10 mg / ml of chloride oleildimethylammonium to achieve a 90% death rate for fleas. In the preparation of a formulation according to the invention for use in companion animals, there are various parameters that should be considered. These are: (a) sufficient high concentration to minimize the volume of the room applied to the animal (one could not wish to place 20 ml, for example, on a small cat). (b) the formulation should be stable for one month at 54.4 ° C, 43.3 ° C, 4.44 ° C, room temperature and 0 ° C. This helps to ensure that the formulation remains stable under conditions that could be met in commerce. (c) Safe to be used on the animal - particularly non-irritating since the product is applied to the skin. It is also safe if swallowed by the animal; Ingestion can occur when cats choke on their own. (d) Insurance to be used by the consumer. (e) Effective in use - you must kill more than 80% or even 90% of the fleas up to 28 days. (f) The efficacy could be reduced if the crystallization was presented in the package. (g) It needs to be aesthetically pleasing - "no oily drop" on the animal when applied, (h) Fast Drying to reduce the opportunity for animal agitation of the liquid thereby reducing efficiency. (i) Microbiologically stable. Other additives to the insecticidal formulation may include, but are not limited to, fragrances for better odor and surfactants such as myristate isopropyl and sorbitan derivatives such as polysorbate 20 and spreading agents to increase performance. The polymers can also be used to provide the insecticide safety and adhesion for skin and hair. Examples of polymers that can be used include cationic cellulose, cationic guar, cationic acrylate polymers, agar, gelatin, and alginate. In practice, an effective amount of the insecticidal formulation as described herein may be applied to a companion animal, preferably a dog or cat, or a foaming shampoo, dye, aerosol spray, pump sprayer, lotion, emulsifiable concentrate, suspension concentrate, liquid or aqueous fluid, and by any other suitable methods for administering the local compositions to animals. In a preferred embodiment of the invention, the insecticidal formulation can be applied as a local drop about once a month, preferably in the area between the protruding blades and the base of the hide to kill fleas, flea larvae and flea eggs. during a period of one month. The following examples are given for the purposes of illustration only and are not intended to be construed in a limiting manner.

EXAMPLES Example 1: Preparation of 1 -. { (tetrahydro-3-furanyl) methyl) -2-nitro-3-methylquanidine (dinotefuran) A mixture comprising 10.0 g of (tetrahydro-3-furanyl) methanol, 29.5 of trifluoromethanesulfonate anhydride, 10.0 g of pyridine and 200 ml of dichloromethane it was stirred for one hour at room temperature. The water was poured into the reaction solution to separate the organic layer, which was washed with 1 N hydrochloric acid, water and a saturated saline solution, dried, and concentrated to obtain 20 g of 3-tetrahydro-furnamethyltriflate, 3.25 g of 60% sodium hydride were added to 12.5 g of 1, 5-dimeti! -2-nitroiminohexahydro-1, 3,5-triazine and 60 ml of DMF at room temperature, followed by stirring for one hour, 20.0 g of 3-tetrahydrofuranylmethyl triflate were added thereto, and the mixture was stirred at 50 ° C for 2 hours. After the mixture was cooled to room temperature, 50 ml of 2N hydrochloric acid were added thereto, followed by stirring at 50 ° C for 2 hours. The resulting mixture was neutralized with sodium bicarbonate and extracted with dichloromethane, and the extract was dried and concentrated. The residue obtained in this way was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1/1) to obtain 7.8 g of 1 -. { (tetrahydro-3-furanyl) methyl} -2-nitro-3-methylguanidine (dinotefuran).

Example 2: Preparation of Insecticide Formulation Containing Dinotefuran. Pyriproxyfen and Chloride Oxyldimethylammonium 0.5 g of oleyldimethylammonium chloride was added to 0.5 g of pyriproxyfen with heat (50 degrees C) and dissolved. 20.75 g of water followed by 20.75 g of ethyl lactate was added as well. 2.1 g of t-octylphenoxypolyethoxyethanol containing 9 moles of ethylene oxide (OP 9) was added. 7.8 g of dinotefuran was dissolved in the solution upon stirring to produce a clear homogenous solution followed by cooling to room temperature. The pH was adjusted with sodium carbonate solution to between 5.5 and 7.

Example 3: Stability of Dinotefuran / Pyriproxyfen Formulations Few solvent systems will be allowed for dinotefuran to remain in solution for one month at low temperatures. In addition, the solvent systems that are allowed for high concentrations of dinotefuran to dissolve are typically allowed for the solubilization of pyriproxyfen. As shown in Table 1, it has been determined that the inclusion of a quaternary ammonium salt in the solvent is allowed for an effective amount of pyriproxyfen to become and remain solubilized, thereby producing a stable formulation. The stability of the formulation is based on the criterion of non-crystal formation at 0 ° C during 1 month period.

Table 1: Formulation Stability Studies (% are p / p) It has been determined that the solubility of pyriproxyfen in a solution containing dinotefuran can be increased by adding a quaternary amine such as ammonium chloride salt, for example, cetyltrimethylammonium chloride, tallow alkyl ammonium chloride and oleyldimethylammonium chloride in comparison to a similar formulation without the ammonium salt Quaternary The inclusion of a quaternary ammonium salt to about 20% results in the formulation being stable.

Example 4 Formulations containing variant proportions of solvent components were prepared using the procedure discussed in Example 2. Table 2 contains the composition of the various formulations and demonstrates that the inclusion of a quaternary ammonium salt yields a stable solution containing dinotefuran and piriproxifen. The stability of the formulation is based on the criterion of no crystal formation at 0 ° C for a period of 1 month.

Table 2 In this way it will be observed that the previously established objects, among those apparent facts of the preceding description, are effectively achieved and, since certain changes can be made by carrying out the above method and in the established formulations without departing from the spirit and scope of the invention, it is intended that all the matter contained in the above description should be construed as illustrative and not in a limiting sense. It will also be understood that the following claims are intended to cover all the generic and specific features of the invention described herein and all statements of the scope of the invention which, as a matter of language, should be said to fall between them. Particularly it will be understood that in said claims, the ingredients or compounds recited in the singular are intended to include a mixture of such ingredients as long as the sense permits.

Claims (36)

1. CLAIMS 1. An insecticide formulated by combining (i) an insecticidally effective amount of an insecticide derived from (tetrahiro-3-furanyl) methylamine or a chloronicotinyl insecticide and (ii) an insect growth inhibitory effective amount of an insect growth regulator. (IGR) in an effective amount of a solvent component comprising water, ethyl lactate and a quaternary ammonium salt, said solvent component comprising an effective amount of quaternary ammonium salt to increase the solvency of the IGR in the solvent component without the quaternary ammonium salt and to increase the effectiveness of the insecticide compared to its effectiveness without the quaternary ammonium salt.
2. 2. The insecticide according to claim 1, wherein the insecticide-derived component comprises dinotefuran.
3. 3. The insecticide according to claim 2, wherein the IGR component comprises pyriproxyfen or methoprene.
4. 4. The insecticide according to claim 3, wherein the IGR component comprises pyriproxyfen.
5. The insecticide according to claim 4, wherein the quaternary ammonium salt component comprises oleyl dimethyl ammonium chloride, cetyltrimethylammonium chloride, or segoalkyltrimethyl ammonium chloride.
6. 6. The insecticide according to claim 1, wherein the chloronictinyl insecticide component comprises acetamiprid.
7. 7. The insecticide according to claim 6, wherein the IGR component comprises pyriproxyfen or methoprene.
8. 8. The insecticide according to claim 7, wherein the IGR component comprises pyriproxyfen.
9. 9. The insecticide according to claim 8, wherein the quaternary ammonium salt component comprises oleyl dimethyl ammonium chloride, cetyltrimethylammonium chloride or tallow alkyl ammonium chloride.
10. The insecticide according to claim 1, wherein the solvent component further comprises ethanol. eleven .
11. The insecticide according to claim 5, wherein said insecticide derivative is dissolved in the formulation at a concentration of about 5 to 20%.
12. 12. The insecticide according to claim 1, wherein said IGR component is dissolved in the formulation at a concentration of about 0.5 to 3%.
13. The insecticide according to claim 12, wherein the concentration of quaternary ammonium salt is about 1 to 20%.
14. The insecticide according to claim 5, wherein said chloronicotinyl insecticide component is dissolved in the formulation at a concentration of about 5 to 50%.
15. 15. The insecticide according to claim 1, wherein said IGR component is dissolved in the formulation at a concentration of about 0.5 to 3%.
16. 16. The insecticide according to claim 12, wherein the concentration of quaternary ammonium salt is about 1 to 20%.
17. The insecticide according to claim 1, wherein the formulation is non-irritating to dogs or cats and is effective in killing fleas with applications of less than 10 ml to a dog or cat.
18. 18. The insecticide according to claim 13, wherein the formulation is non-irritating to dogs or cats and is effective for killing fleas with applications of less than 10 ml to a dog or cat.
19. 19. The insecticide according to claim 16, wherein the formulation is non-irritating to dogs or cats and is effective in killing fleas with applications of less than 10 ml to a dog or cat.
20. 20. A method for controlling insect infestation in animals, comprising dissolving dinotefuran and pyriproxyfen in a solvent mixture comprising water, ethyl lactate, ethanol and a quaternary ammonium salt, and applying an insecticidally effective amount of the solution to an animal . twenty-one .
21. The method according to claim 20, wherein the quaternary ammonium salt is oleyldimethylammonium chloride, cetyltrimethylammonium chloride or ammonium chloride tallow alkyltrimethyl.
22. 22. The method according to claim 21, wherein the animal is a dog or a cat.
23. 23. The method according to claim 21, wherein the insect is a flea.
24. 24. A method for controlling insect infestation in animals, comprising dissolving acetamiprid and pyriproxyfen in a solvent mixture comprising water, ethyl lactate, ethanol and a quaternary ammonium salt, and applying an effectively nonsecticidal amount of the solution to an animal.
25. 25. The method according to claim 24, wherein the quaternary ammonium salt is oleyldimethylammonium chloride, cetyltrimethylammonium chloride or tallow alkyl ammonium chloride.
26. 26. The method according to claim 25, wherein the animal is a cat or a dog.
27. 27. The method according to claim 26, wherein the insect is a fly.
28. 28. A method for preparing an insecticide formulation, said method comprising dissolving an insecticide in a composition comprising oleyl dimethyl ammonium chloride, wherein the at least part of the insecticide is dissolved by the oleyldimethylammonium chloride.
29. 29. An insecticide composition comprising an insecticidally effective amount of dinotefuran and an amount of insect growth regulating pyriproxyfen.
30. 30. The insecticidal composition according to claim 29, further comprising a solution comprising a quaternary ammonium salt.
31. 31. The insecticidal composition according to claim 30, wherein the quaternary ammonium salt component comprises oleyldimethylammonium chloride, cetyltrimethylammonium chloride, ammonium chloride, ceboalkyltrimethyl.
32. 32. The insecticidal composition according to claim 31, wherein the solution further comprises ethyl lactate, ethanol and water.
33. 33. An insecticidal composition comprising an insecticidally effective amount of acetamiprid and an amount of insect growth regulating pyriproxyfen.
34. 34. The insecticidal composition according to claim 33, further comprising a solution comprising a quaternary ammonium salt.
35. 35. The insecticidal composition according to the claim 30, wherein the quaternary ammonium salt component comprises oleyl dimethyl ammonium chloride, cetyltrimethylammonium chloride, ammonium chloride, ceboalkyltrimethyloyl.
36. 36. The insecticidal composition according to the claim 31, wherein the solution further comprises ethyl lactate, ethanol and water.