JP2003081719A - Percutaneous administration agent for controlling animal ectozoon - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a percutaneous administration agent which has excellent safety for animals, has high efficacy, and can sustain the efficacy for a long period, on the control of animal ectozoa, while treating methods each comprising dropping, coating, or the like, an insecticide-containing liquid on the surfaces of animals are known as methods for controlling insect pests parasitizing on the surfaces of the animals, the so-called ectozoa. SOLUTION: This percutaneous administration agent for the control of animal ectozoa comprises 1-methyl-2-nitro-3-[(3-tetrahydrofuryl)methyl]guanidine and a solvent consisting mainly of N-methyl-2-pyrrolidone.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a transdermal preparation for controlling animal ectoparasites.

[0002]

2. Description of the Related Art As a method for controlling pests parasitic on animal body surfaces such as fleas, lice, mites and diptera, so-called ectoparasites, insecticidal ingredients have been contained. A transdermal administration method of treating a liquid agent by dropping, coating, etc. on the surface of an animal body is known, and in particular, a liquid agent containing imidacloprid has a safety point higher than that of a conventional agent applied to the application. It has been used for this purpose because it is excellent in However, the liquid agent containing imidacloprid has a problem that its efficacy is reduced in a relatively short period of time as compared with the conventional agent in the above application. The present inventors have proposed 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine and glycol or glycol monoalkyl as safer and highly potent agents suitable for animal ectoparasite control applications. Agents containing ether have been proposed (JP 2000
-198706). Although this agent is highly safe for animals as described above and has high efficacy, it is comparable to the liquid formulation containing imidacloprid in terms of the persistence of its efficacy, is excellent in safety, and has high efficacy. It has been desired to develop a percutaneous agent for controlling animal ectoparasites, which is more effective in sustaining the effect.

[0003]

Means for Solving the Problems As a result of repeated studies by the present inventors, in a liquid preparation containing 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine as an insecticidal component, N- By using a solvent mainly composed of methyl-2-pyrrolidone, it was found that the excellent ectoparasite control effect is maintained for a long period of time when the administration agent is administered to the surface of an animal body, and the present invention has been completed. . That is, the present invention provides a solvent mainly containing 1.1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine (hereinafter referred to as the present compound) and N-methyl-2-pyrrolidone. 1. A percutaneous administration agent for controlling animal ectoparasites (hereinafter, referred to as the administration agent of the present invention), (A) 1-Methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine, (b) Solvent mainly containing N-methyl-2-pyrrolidone, and (c) Juvenile hormone-like substance, pyrethroid 2. A transdermal administration agent for controlling animal ectoparasites, which comprises at least one selected from a compound, an antioxidant, a coloring agent, a light stabilizer and an adhesive. (A) 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine, (b) a solvent containing N-methyl-2-pyrrolidone as a main component, and (c) a juvenile hormone, if necessary. Substance, (d) if necessary pyrethroid compound and (e) optionally, at least one selected from the group consisting of antioxidants, colorants, light stabilizers and adhesives, for transdermal administration to control animal ectoparasites Agent, 4. 1. The juvenile hormone-like substance is at least one selected from pyriproxyfen, phenoxycarb and methoprene. Or 3. 4. A transdermal agent for controlling animal ectoparasites according to 5. The pyrethroid compound is at least one selected from phenothrin, permethrin, etofenprox, resmethrin, phenpropatrine, cifenotrin and flumethrin.2. Or 3. 5. A transdermal administration agent for controlling animal ectoparasites according to 6. (A) 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine, (b) a solvent mainly containing N-methyl-2-pyrrolidone, (c) pyriproxyfen, phenoxycarb and At least one (d) phenothrin, permethrin selected from methoprene,
6. A transdermal agent for controlling animal ectoparasites, which comprises at least one selected from etofenprox, resmethrin, fenpropatrine, cifenotrin and flumethrin; 7. The transdermal administration agent for controlling animal ectoparasites according to 1, 2, 3, 4, 5 or 6, wherein 95% by weight or more of the solvent is N-methyl-2-pyrrolidone. The present invention provides a transdermal administration agent for controlling animal ectoparasites according to 1, 2, 3, 4, 5 or 6, wherein the solvent consists essentially of N-methyl-2-pyrrolidone.

[0004]

BEST MODE FOR CARRYING OUT THE INVENTION
A solvent mainly containing -methyl-2-pyrrolidone, and optionally other components.

The compound of the present invention usually contains the compound of
The content is 1 to 30% by weight, preferably 1 to 30% by weight.

A solvent containing N-methyl-2-pyrrolidone as a main ingredient is usually 40% by weight to 99.9% by weight in the dosage form of the present invention.
Contained. The solvent mainly containing N-methyl-2-pyrrolidone is a solvent containing 90% by weight or more, and preferably 95% by weight or more of N-methyl-2-pyrrolidone. A solvent consisting essentially of N-methyl-2-pyrrolidone is particularly preferably used.

The weight ratio of the present compound to N-methyl-2-pyrrolidone in the administration agent of the present invention is usually 1: 1 to 1:99.
9, and preferably 1: 1 to 1:99.

Other components that are optionally contained in the administration agent of the present invention include insecticidal components other than the present compound, antioxidants, colorants, light stabilizers, adhesives and the like.

As the insecticidal ingredient other than the present compound,
For example, pyrethroid compounds such as phenothrin, permethrin, ethofenprox, resmethrin, fenpropatorin, cifenotrin, flumethrin; organophosphorus compounds such as tetrachlorvinphos, fenthion; carbamate compounds such as propoxar, carbaryl, fenobucarb; lufenuron, novalron , Chlorfluazuron and other chitin formation inhibitors; juvenile hormone-like substances such as pyriproxyfen, phenoxycarb and methoprene;
Examples include neonicotinoid compounds such as nitenpyram and thiamethoxam; N-phenylpyrazole compounds. Among them, pyriproxyfen, phenoxycarb,
It is more effective in controlling animal ectoparasites to contain one or more selected from methoprene, phenothrin, permethrin, etofenprox, resmethrin, phenpropatrine, cifenotrin and flumethrin. When the agent of the present invention contains an insecticidal component other than the present compound, such as a juvenile hormone-like substance, the total content is usually 0.05 to 50% by weight.

Antioxidants such as BHT and BHA, and colorants such as yellow No. 4 (tartrazine), green No. 3 (fast green FCF), blue No. 1 (brilliant blue FCF), etc. Examples of the stabilizer include benzophenone compounds and benzotriazole compounds, and examples of the adhesive include cellulose derivatives, starch derivatives, polyacrylates, natural polymers, alginates, gelatin and the like. When the administration agent of the present invention contains these antioxidants, colorants, light stabilizers, adhesives, etc., the total content is usually 0.0001 to 1% by weight.

Examples of components other than N-methyl-2-pyrrolidone that can be contained in a solvent mainly containing N-methyl-2-pyrrolidone include alcohols such as ethyl alcohol, isopropyl alcohol and benzyl alcohol, and propylene glycol. , Hexylene glycol,
Diethylene glycol, dipropylene glycol, tripropylene glycol, diethylene glycol monoalkyl ether, propylene glycol monoalkyl ether, dipropylene glycol monoalkyl ether,
Examples thereof include glycols such as ethylene glycol monophenyl ether, propylene carbonate, γ-butyrolactone, and water.

When water is contained in the solvent containing N-methyl-2-pyrrolidone as a main component, a pH adjusting agent is contained, if necessary. Examples of the pH adjuster include citric acid, sodium dihydrogen citrate, disodium hydrogen citrate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, ammonium dihydrogen phosphate, ammonium benzoate, sodium benzoate, boric acid. , Tartaric acid, succinic acid, lactic acid and the like. These pH adjusting agents may be contained in the dosage form of the present invention in a proportion of usually 0.01 to 1% by weight based on the total weight of water.

Further, as specific examples of the administration agent of the present invention,
(A) 0.1 to 30% by weight of 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine,
(B) 40% solvent mainly consisting of N-methyl-2-pyrrolidone
~ 99.9% by weight, (c) juvenile hormone-like substance (pyriproxyfen, phenoxycarb, methoprene, etc.), pyrethroid compound (phenothrin, permethrin, etofenprox, resmethrin, fenpropatrine, cifenotrin, flumethrin) 0.05 to 50% by weight of an insecticidal component other than the present compound such as) and (d) 0.0001 of at least one selected from an antioxidant, a colorant, a light stabilizer, an adhesive, etc., if necessary. Examples of the agent include 1 to 1% by weight.

As a further specific example, (a) 1-
0.1-30% by weight of methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine, (b) N-
40-99.9% by weight of a solvent mainly containing methyl-2-pyrrolidone, (c) 0.5% of juvenile hormone-like substances (pyriproxyfen, phenoxycarb, methoprene, etc.) as necessary
~ 5.0% by weight, (d) if necessary, pyrethroid compound (phenothrin, permethrin, etofenprox,
Resmethrin, fenpropatorin, cifenotrin,
Flumethrin, etc.) in an amount of 5.0 to 45% by weight and (e) 0.0001 to 1% by weight of at least one selected from antioxidants, colorants, light stabilizers, pressure sensitive adhesives, etc. be able to.

The administration agent of the present invention is usually used in the form of a liquid agent such as a so-called spot-on treatment liquid agent and a pour-on treatment liquid agent.

The administration agent of the present invention generally contains the compound, if necessary, an insecticidal component other than the compound, and if necessary, an antioxidant, a coloring agent, a light stabilizer, an adhesive, etc., in N-methyl-2.
It can be obtained by mixing pyrrolidone with a solvent mainly.

The animals to which the agent of the present invention is administered include animals that can be hosts for ectoparasites such as fleas, lice, mites and diptera, and are usually fed as livestock or pets. The animals that are being used are listed. Specifically, for example, as mammals, dogs, cats, carnivora such as ferrets, cattle, sheep, goats, artiodactyla such as pigs,
Rodents such as mice, rats, hamsters and squirrels, rabbits such as rabbits, primates such as monkeys; as birds, animals such as ducks and other ducks, pigeons and others, parrots and other parrots Is mentioned.

The agent of the present invention can be treated by methods such as spot-on treatment and pour-on treatment. Spot-on treatment is usually a method of dropping or applying a liquid preparation onto the skin of the scapula dorsum of the host animal, and pour-on treatment is usually pouring the liquid preparation along the back line of the host animal body. Is the way.

The amount of the administration agent of the present invention to be treated on an animal may vary depending on the type of the target animal or the ectoparasite to be controlled, etc., but converted to the amount of this compound per 1 kg of fresh weight of the target animal. And usually 0.05-1000m
g / kg, preferably 0.1-200 mg / kg.

As the ectoparasites which can be controlled by the administration agent of the present invention, various arthropod pests known as ectoparasites of the above-mentioned host animals (in the present specification, arthropod pests are referred to as pests). In some cases, specifically, the housefly (Musca domestica) and the housefly (Musca).
hervei), Musca bezzii, Haematobia irritans, Simulium iw
atens), Utsunukaka (Culicoides oxystoma), Ushiabu (Tabanus chrysurus), Culex pipiens (Culexpipien)
s), Aedes albopictus and other dipterous pests, cattle lice (Haematopinus eurysternus), lice (Damalinia ovis) and other lice pests, Haemaphyxalis longicornis, and ticks (Boophilus mites). Ctenocephalides felis), dog flea (Ctenocephalid)
es canis), Keopsunezuminomi (Xenopsylla cheopi)
flea pests such as s) and the like.

[0021]

The present invention will be described in more detail with reference to the following examples.

Formulation Example 1 Formulation 1 was obtained by adding 9 g of N-methyl-2-pyrrolidone to 1 g of this compound and mixing.

Formulation Example 2 To 1 g of this compound, 8.6 g of N-methyl-2-pyrrolidone and 0.4 g of tripropylene glycol were added and mixed,
Formulation 2 was obtained.

Formulation Example 3 To 10 g of the present compound, 40 g of d-phenothrin, 1.0 g of pyriproxyfen, and N-methyl-2-pyrrolidone were added to bring the total to 100 g, and mixed to obtain Formulation 3.

Formulation Example 4 To 10 g of the present compound, 30 g of etofenprox, 1.0 g of pyriproxyfen and N-methyl-2-pyrrolidone were added to bring the total to 100 g, and a formulation 4 was obtained.

Formulation Example 5 To 10 g of this compound, 0.5 g of pyriproxyfen and N-methyl-2-pyrrolidone were added to bring the total to 100 g, and mixed to obtain a formulation.

Formulation Example 6 To 10 g of the present compound, 10 g of phenpropatrine, 1.0 g of pyriproxyfen, and N-methyl-2-pyrrolidone were added to make 100 g, and the mixture was obtained.

Formulation Example 7 To 10 g of the present compound, 10 g of flumethrin, 1.0 g of pyriproxyfen and N-methyl-2-pyrrolidone were added to make 100 g, and the mixture was obtained.

Comparative Example 1 To 1 g of this compound, 3 g of N-methyl-2-pyrrolidone and 6 g of propylene glycol were added and mixed to obtain Comparative Preparation 1.

Comparative Example 2 Polyethylene glycol 300 was added to propylene glycol.
Comparative Preparation 2 was prepared in the same manner as in Comparative Example 1 except that
Got

Comparative Example 3 To 1 g of this compound, 2.4 g of N-methyl-2-pyrrolidone and 6.6 g of tripropylene glycol were added and mixed,
Comparative formulation 3 was obtained.

Comparative Example 4 To 1 g of this compound, 9.0 g of tripropylene glycol was added and mixed to obtain Comparative Preparation 4.

Comparative Example 5 To 1 g of this compound, 6.6 g of tripropylene glycol and 2.4 g of isopropyl alcohol were added and mixed to obtain Comparative Preparation 5.

Test Example 1 30 cat flea adults per cat (living weight of about 3 kg)
The head was parasitized, and one day later (this day is taken as the drug administration day), Formulation 1, Comparative Formulation 1, Comparative Formulation 2 and a liquid formulation for spot-on treatment containing imidacloprid 10% w / v (Reference Formulation 1. Brand name: Advantage spot 40 for cats,
Bayer, main solvent is benzyl alcohol. ) 0.4 ml of each was applied by spot-on treatment to the skin of the back of the scapula using a pipette to each of the cats infested with the above-mentioned cat fleas. Each cat after administration of the drug was transferred into a cage and fed with water and water. The number of parasitic fleas was counted on the third day from the drug administration day using a flea picking comb.
The flea parasitic rate was calculated based on the number of fleas initially parasitized.
The cats used for the test were fed with water and then fed.
Thirty adult feline fleas were reparasitized to the cat on the 14th day from the drug administration day, and on the 17th day from the drug administration day, the number of parasitic fleas was counted again using a flea comb to determine the flea infestation rate. Also, as a blank, the same test was performed on cats without drug treatment, and the number of parasitic fleas was counted in the same manner as when the drug was administered,
The flea parasitic rate was calculated. The test was performed using two cats for each preparation and blank, the average thereof was calculated, and the flea control rate was calculated by the following formula. The results are shown in Tables 1 and 2.

Flea control rate (%) = (C−T) ÷ C × 100 C: flea parasitic rate in blank, T: flea parasitic rate in formulation treatment group

[0035]

[Table 1] * 1 Imidacloprid 10% w / v

[Table 2] * 1 Imidacloprid 10% w / v

Test Example 2 The same experiment as in Test Example 1 was carried out except that Formulation 1, Formulation 2, Comparative Formulation 3, Comparative Formulation 4 and Comparative Formulation 5 were used as the formulations. The flea control rate was calculated by the above formula. The results are shown in Tables 3 and 4.

[0037]

[Table 3]

[Table 4]

Test Example 3 The same experiment as in Test Example 1 was carried out except that Formulation 3 and Formulation 4 were used as the formulations. The flea control rate was calculated by the above formula. The results are shown in Tables 5 and 6.

[0039]

[Table 5]

[Table 6]

[0040]

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a transdermal preparation which is excellent in animal safety in controlling ectoparasites of animals, has high efficacy, and can maintain the efficacy for a long period of time.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A01N 47/12 A01N 47/12 B 53/04 53/00 508A 53/08 504A 508Z 508D F term (reference) 4H011 AC01 BA01 BA06 BB06 BB09 BB11 BB13 BB15 BC03 BC09 DA13 DD07

Claims (8)

[Claims] 1. A transdermal administration for the control of ectoparasites of animals containing a solvent mainly containing 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine and N-methyl-2-pyrrolidone. Agent. 2. (a) 1-Methyl-2-nitro-3-
[(3-tetrahydrofuryl) methyl] guanidine,
(B) A solvent mainly containing N-methyl-2-pyrrolidone and (c) at least one selected from juvenile hormone-like substances, pyrethroid compounds, antioxidants, colorants, light stabilizers and adhesives Transdermal agent for controlling animal ectoparasites. (A) 1-Methyl-2-nitro-3-
[(3-tetrahydrofuryl) methyl] guanidine,
(B) a solvent mainly containing N-methyl-2-pyrrolidone,
(C) if necessary, a juvenile hormone-like substance, (d) if necessary, a pyrethroid compound, and (e) if necessary, at least one selected from an antioxidant, a colorant, a light stabilizer and an adhesive, A transdermal drug for controlling animal ectoparasites. 4. The transdermal administration agent for controlling animal ectoparasites according to claim 2 or 3, wherein the juvenile hormone-like substance is at least one selected from pyriproxyfen, phenoxycarb and methoprene. 5. The transdermal administration for controlling animal ectoparasites according to claim 2 or 3, wherein the pyrethroid compound is at least one selected from phenothrin, permethrin, ethofenprox, resmethrin, phenpropatrine, cifenotrin and flumethrin. Agent. 6. (a) 1-Methyl-2-nitro-3-
[(3-tetrahydrofuryl) methyl] guanidine,
(B) a solvent mainly containing N-methyl-2-pyrrolidone,
(C) at least one selected from pyriproxyfen, phenoxycarb and methoprene, and (d) at least one selected from phenothrin, permethrin, etofenprox, resmethrin, phenpropatrine, cifenotrin and flumethrin, an animal ectoparasite Transdermal drug for control. 7. 95% by weight or more of the solvent is N-methyl-2-
The transdermal agent for controlling animal ectoparasites according to claim 1, which is pyrrolidone. 8. The solvent according to claim 1, 2, 3, 4, 5 or 6, wherein the solvent consists essentially of N-methyl-2-pyrrolidone.
The transdermal administration agent for controlling animal ectoparasites according to 1.