JP2003313104A - Spot-on agent for exterminating ectoparasite on animal - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To develop a spot-on agent for ectoparasites on animals having high exterminating effects with a small amount of application to the animals and slight adverse effects. <P>SOLUTION: The spot-on agent for exterminating the ectoparasites on the animals comprises cycloprothrin as an active ingredient in a solvent. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention kills ectoparasites such as fleas and mites that parasitize the body surface of pets such as dogs and cats, or cattle, pigs, chickens, other livestock and poultry. Or an ectoparasite anthelmintic spot-on agent for animals.

[0002]

2. Description of the Related Art Generally, the skin of an animal is often infested with fleas, mites and other arthropods, which are parasitic insects, and especially pet animals such as dogs and cats and other mammal animals. Since the skin of the animal has hairs, sebaceous glands, sweat glands, or both, the surface of such a skin is a habitable environment for fleas and mites. Animals such as mammals and birds in which a large number of parasites propagate on the skin have a weakened immune system and other weakened physical strength, and are more likely to be infected with various pathogenic bacteria and die of illness. In addition, when fleas and daniella parasitize small pet animals that live in the same living environment as humans, it causes a hygiene problem because of the lack of cleanliness. Spot-on agents are used as appropriate.

Conventional ectoparasite control agents for animals are fleas and
When mites and the like ingest host blood or other body fluids or secretions on the surface of the skin, it takes advantage of incorporating insecticidal components into the body. A spot-on agent is a small amount dropped on the body surface of pets such as dogs and cats, or cattle, pigs, chickens, other livestock, and poultry, after which the active ingredient contained therein spreads throughout the body, and fleas, ticks, etc. Kill ectoparasites. Of these ectoparasite spot-on agents for animals, liquid formulations are used by locally dropping them on the body surface, and as a commercial product of the liquid formulation, a fipronil formulation containing a deleterious substance as an active ingredient (trade name) ; Front line), fenthion preparations (trade name; Chiguphone Spot), imidacloprid preparations (trade name; Advantage), etc. However, it is a deleterious substance, and it is sold at animal hospitals because of concern about side effects on animals and humans, and is not generally widely distributed.

Further, there are permethrin preparations [trade name: FleaTrol (sold in the United States)] and star anise preparations (trade name: protect), which contain ordinary substances as active ingredients. However, permethrin preparations have a concern that they may be irritating to humans and are highly toxic to cats and cannot be used.Therefore, star anise preparations have a slow onset of effect against fleas and a sufficient exterminating effect. Absent. Under these circumstances, there are no side effects on the animals and fleas
There is a demand for an anthelmintic agent that exerts a sufficient effect on mites. As external ectoparasite spot-on agents for animals containing various insecticidal components, there are disclosed in Japanese Patent Publication No. H05-505399 and Japanese Patent Laid-Open No.
169644, JP-A-11-5702, JP-A-2000-
103711, JP 2000-327504 A, etc., and the composition thereof is disclosed.

[0005]

[Problems to be Solved by the Invention] In an ectoparasite spot-on agent such as a flea / tick spot-on agent, the onset of the effect is fast, there is a sufficient exterminating effect, and there is no side effect on animals and there is no irritation. It is desired to develop a spot-on agent for exterminating ectoparasites of sexual animals.

[0006]

Therefore, as a result of earnest studies on an ectoparasite spot-on agent with few side effects on animals, the present inventor found that cycloprotoline, namely [(R
S) -α-Cyano-3-phenoxybenzyl- (RS)-
2,2-dichloro-1- (4-ethoxyphenyl) cyclopropanecarboxylate] as a spot-on agent for controlling ectoparasites of animals,
The present inventors have completed the present invention by discovering that ectoparasites can be surely exterminated when they are treated on the body surface of animals and that they have few side effects. That is, the present invention is

(1) A spot-on agent for combating ectoparasites of animals, which contains cycloprothrin as an active ingredient in a solvent, and (2) an organic solvent and / or vegetable oil as a solvent. A spot-on agent for controlling ectoparasites of animals, (3) the organic solvent is one or more selected from the group consisting of ethylene glycol monoethyl ether, dipropylene glycol monobutyl ether, ethanol, propylene glycol, isopropanol, and dimethoxy sulfoxide. A spot-on agent for controlling ectoparasites of animals according to (2), (4) vegetable oil is soybean oil, coconut oil, palm oil, linseed oil, cottonseed oil, rapeseed oil, tung oil,
A spot-on agent for controlling ectoparasites of animals according to the above item (2) or (3), which is one or more selected from the group consisting of castor oil, mandarin oil, olive oil and rice sugar oil, and (5) in a solvent The above (1), (2), which contains a surfactant,
(3) or a spot-on agent for controlling ectoparasites of animals according to (4).

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The spot-on agent for controlling ectoparasites of animals according to the present invention is a chisel which is spread after a small amount of liquid agent is dripped on the back, shoulder or neck and the active ingredient diffuses on the body surface and comes into contact with it. , Ticks, lice, and other ectoparasites cause death.

The active ingredient contained in the spot-on agent for controlling ectoparasites of animals of the present invention is diluted with a solvent that does not have side effects on animals, such as an organic solvent and / or vegetable oil, and is secreted onto the skin surface. The insecticidal active ingredient mixed with the oil and fat efficiently diffuses and spreads on the body surface of the animal. Therefore, the spot-on agent for controlling ectoparasites of animals of the present invention spreads over a wide area of the skin with a small amount of use, has a high ectoparasite control effect, and is highly efficient in use.

Cycloprotoline contained as an active ingredient in the spot-on agent for controlling animal ectoparasites of the present invention is disclosed in JP-A-52-83354, which shows insecticidal activity against pests. , Can be easily obtained from the market.

The amount of cycloprothrin in the spot-on agent for controlling ectoparasites of animals of the present invention is usually 0.1.
It is from 05 to 99% by weight, preferably from 0.1 to 50% by weight.

The vegetable oils and organic solvents that can be used as the solvent in the present invention are safe without any irritation or other side effects on the skin, and are well-known vegetable oil products that are liquid at room temperature, such as mineral oils. However, those having irritation are not adopted as the spot-on agent component of the present invention.

The organic solvent which can be used as a solvent for the spot-on agent for controlling animal ectoparasites of the present invention includes, for example, diethylene glycol monoethyl ether, diethylene glycol monomethyl ether, dipropylene glycol monobutyl ether, propylene glycol, ethanol,
Propylene carbonate, benzyl alcohol, kerosene (No. 1 kerosene), dimethoxysulfoxide and the like can be mentioned, with preference given to glycol ethers such as diethylene glycol monoethyl ether, diethylene glycol monomethyl ether and dipropylene glycol monobutyl ether, and dimethyl sulfoxide.

As the vegetable oil that can be used as a solvent in the spot-on agent for controlling animal ectoparasites of the present invention, soybean oil,
Examples thereof include coconut oil, palm oil, linseed oil, cottonseed oil, rapeseed oil, tung oil, castor oil, olive oil, rice sugar oil, tangerine oil and the like, and preferably soybean oil, cottonseed oil, rapeseed oil and tung oil.

The amount of the organic solvent and / or vegetable oil used as a solvent in the spot-on agent for controlling animal ectoparasites of the present invention is usually 5 to 99% by weight, preferably 10 to 80%. . If the amount is less than the above range, it is difficult to efficiently diffuse or spread the active ingredient on the body surface, which is not preferable. Further, if it is blended in a large amount exceeding the above-mentioned predetermined range, the amount of the active ingredient in the spot-on agent is relatively reduced and the insecticidal effect is reduced, which is not preferable. The mixing ratio of the organic solvent and the vegetable oil in the solvent is usually 20: 1 to 1:10, preferably 10: 1 to 1: 2.

Surfactants which can be used in the spot-on agent for controlling animal ectoparasites of the present invention include, for example, nonionic surfactants such as polyoxyethylene octyl ether, polooxyethylene dodecyl ether and polyoxyrennonyl phenyl ether. Dodecylbenzene sulfonic acid metal salt, fatty acid metal salt such as sodium oleate, naphthalene sulfonic acid polycondensation metal salt, certain naphthalene sulfonic acid metal salt, anionic interface such as special polycarboxylic acid type polymer surfactant Activator etc. are mentioned. These may be used alone or in combination of two or more, depending on the active ingredient and solvent used, but are not limited thereto. By containing a surfactant in the spot-on agent for controlling ectoparasites of animals of the present invention, the active ingredient spreads evenly after dropping and then spreads without aggregation. Also,
The content of the surfactant in the spot-on agent is usually 0.01 to 20%, preferably 0.1 to 10%. And when using a surfactant in combination with an organic solvent and / or vegetable oil, the surfactant is usually 1 to 2 with respect to 100 parts by weight of the organic solvent and / or vegetable oil.
About 0 parts by weight is used.

Further, in the present invention, a synergist or a stabilizer may be added together with the above-mentioned active ingredient and solvent to enhance the stability.

Specific examples of synergists which can be used in the spot-on agent for controlling animal ectoparasites of the present invention include N- (2-
Ethylhexyl) -1-isopropyl-4-methylbicyclo [2,2,2] oct-5-ene-2,3-dicarboximide (abbreviated as cinepyrine), isobornyl thiocyanoacetate (abbreviated as IBTA). ), Piperonyl butoxide (abbreviated as PBO), N-.
(2-Ethylhexyl) -bicyclo [2,2,1] -hept-5-ene-2,3-dicarboximide (MGK-
It is abbreviated as H.264. ) And the like.

Specific examples of the stabilizer that can be used include
Butylhydroxytoluene (abbreviated as BHT),
Butyl hydroxyanisole (abbreviated as BHA), 4,4′-thiobis (3-methyl-6-t-butylphenol) (abbreviated as TBMTBP), and the like can be given.

When a synergist and a stabilizer are used in the spot-on agent for controlling ectoparasites of animals of the present invention, the addition amount is usually 0.01 to 10% each, preferably 0.1 to 1%.
Is.

The target animal to which the spot-on agent for controlling ectoparasites of animals of the present invention is applied is a land animal other than human that may parasitize parasites such as fleas and mites on the skin. And humans, including humans and animals that can be bred by humans as livestock, poultry (cows, horses, pigs, chickens, etc.) or pets (dogs, cats, birds, etc.).

The ectoparasites to be exterminated by the spot-on agent for exterminating ectoparasites of animals of the present invention include dog fleas, cat fleas, human fleas, ticks, chiggers, sardines,
Examples include a mite mite, a pistil mite, and a mosquito.

[0023]

EXAMPLES The present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples, but the present invention is not limited to these Examples.

Example 1 10 parts of cycloprothrin was mixed with 90 parts of kerosene (No. 1 kerosene) to obtain a spot-on agent of the present invention.

Example 2 10 parts of cycloprothrin and 90 parts of diethylene glycol monomethyl ether were mixed to obtain a spot-on agent of the present invention.

Example 3 10 parts of cycloprothrin, 75 parts of diethylene glycol monoethyl ether and 15 parts of ethanol were mixed to obtain a spot-on agent of the present invention.

Example 4 50 parts of cycloprothrin, 40 parts of diethylene glycol monoethyl ether and 10 parts of ethanol were mixed to obtain a spot-on agent of the present invention.

Example 5 10 parts of cycloprothrin, 75 parts of dipropylene glycol monobutyl ether and 15 parts of ethanol were mixed,
The spot-on agent of the present invention was obtained.

Example 6 10 parts of cycloprothrin and 60 parts of dipropylene glycol monobutyl ether, 20 parts of dimethyl sulfoxide,
5 parts of Newcalgen-900 (trade name, surfactant, Takemoto Yushi Co., Ltd.) and 5 parts of ethanol were mixed to obtain a spot-on agent of the present invention. (In addition, New Kalgen-900
Is a mixture of polyoxyalkylene allyl phenyl ether, polyoxyethylene allyl phenyl ether formaldehyde condensing agent, alkylbenzene sulfone metal salt and xylene. )

Example 7 Cycloprothrin 10 parts and dipropylene glycol monobutyl ether 70 parts, Newkalgen-9005
And 15 parts of ethanol were mixed to obtain the spot-on agent of the present invention.

Example 8 10 parts of cycloprothrin, 0.1 part of BHT and 89.9 parts of diethylene glycol monoethyl ether were mixed to obtain a spot-on agent of the present invention.

Example 9 10 parts of cycloprotoline, 10 parts of soybean oil and 80 parts of diethylene glycol monoethyl ether were mixed to obtain a spot-on agent of the present invention.

Example 10 10 parts of cycloprothrin, 10 parts of cottonseed oil and 80 parts of diethylene glycol monoethyl ether were mixed to obtain a spot-on agent of the present invention.

Example 11 10 parts of cycloprothrin, 10 parts of rapeseed oil and 80 parts of diethylene glycol monoethyl ether were mixed to obtain a spot-on agent of the present invention.

Example 12 10 parts of cycloprotoline, 10 parts of tung oil, and 80 parts of diethylene glycol monoethyl ether were mixed to obtain a spot-on agent of the present invention.

Example 13 Cycloprothrin 10 parts, d-limonene (mandarin orange oil) 1
0 part and 80 parts of diethylene glycol monoethyl ether were mixed to obtain the spot-on agent of the present invention.

Example 14 50 parts of cycloprothrin, 20 parts of dipropylene glycol monobutyl ether, 20 parts of dimethyl sulfoxide,
Ethanol 5 parts and Newcalgen-900 5 parts were mixed to obtain the spot-on agent of the present invention.

Example 15 10 parts of cycloprothrin, 10 parts of MGK-264 and 80 parts of diethylene glycol monoethyl ether were mixed to obtain a spot-on agent of the present invention.

Comparative Example 1 Permethrin preparation (FleaTrol: 45% permethrin + 2.9% methoprene, ZODIA)

Comparative Example 2 10 parts of phenothrin, 75 parts of diethylene glycol monoethyl ether and 15 parts of ethanol were mixed to obtain a spot-on agent for comparison.

Comparative Example 3 Permethrin (50 parts), diethylene glycol monoethyl ether (40 parts) and ethanol (10 parts) were mixed to obtain a comparative spot-on agent.

Test Example 1: <Effect confirmation test for cat fleas> Using the obtained spot-on external agent for ectoparasite control of animals, the following effect confirmation test was conducted for the anthelmintic effect on the fleas and the side effect on the test animals. I looked it up.

The test animal was a cat (American short hair, 2-3 years old, female, weight 3 kg), and 20 adult cat fleas were inoculated in advance per cat, and the animals were acclimated for 24 hours. The spot-on agents for controlling ectoparasites of Examples 3 and 9 and Comparative Example were directly dropped onto the skin by scraping off the fur on the back of the cat. Using a dropper, 3 mL of the liquid amount shown below was applied around the neck. The control plot was untreated. The results of the above tests are shown in Tables 1 and 2 below.

Table 1 Used formulation 7 days after dropping Formulation Example 3 − Formulation Example 9- Comparative Example 1- Control ++

Number of parasites: Seven days after the addition of the ectoparasite control agent, the hair was combed using a flea comb and the number of fleas taken off was counted and evaluated according to the evaluation criteria in the table below.

Number of parasitic fleas and evaluation criteria Evaluation criteria Number of parasitic fleas / head ― 0 ~ 2 + 3 to 10 ++ 11 ~ 16 +++ 17 ~ 20

[0047] Table 2 Formulation used Side effects               After 3 hours After 1 day After 2 days After 3 days After 7 days Formulation Example 3 − − − − − Formulation Example 9 − − − − − Comparative Example 1 +++++++++++

Side effects: Side effects on cats were observed 5 hours after the dropping, once a day after the dropping, and once a day according to the evaluation criteria in the table below.

Criteria for evaluating side effects on test animals Findings-No abnormalities + Abnormal activity, slight abnormalities ++ Abnormalities such as leg wobbling ++ + Abnormalities such as tremor and spasm a Violent intoxication was observed and the patient was moribund, so shampooing was performed and the drug was removed. as a result,
Two days after shampoo, it recovered normally.

As shown in Tables 1 and 2, in the cats to which the spot-on agents of Examples 3 and 9 and Comparative Example 1 were dropped,
After the day, almost no fleas were found on the body, showing a high anthelmintic effect. On the other hand, no side effect was observed in Examples 3 and 9, but in Comparative Example 1, severe symptoms were observed,
Three days after the dropping, the body became moribund. This was considered to be due to the fact that the cat licked the drug and took it orally, and the side effects of the drug appeared.

Test Example 2: <Effect confirmation test against Phytophthora infestans> Next, using the spot-on agents for controlling ectoparasites obtained in Examples 3 and 4 and Comparative Example 3, the antiparasitic effect against Phytophthora infestans and The skin irritation, which is a side effect on the test animals, was examined by the following effect confirmation test.

The test animal was a rabbit, and the hatched larvae of Haemaphysalis longicornis larvae were ingested using a cloth bag and parasitically sucked. Two
After 4 hours, the number of parasites was counted, and 0.1 mL of each preparation was dropped into the center of the ear. The control plot was untreated. In addition, the skin irritation was observed by observing the ear drip site 1 day after the drip, and the number of ticks on the rabbit ear was counted 5 days after the drip, and the control rate (%) was calculated. . The results are shown in Table 3 below.

[0053]

From Table 3, the rabbits to which the spot-on agents of Examples 3 and 4 and Comparative Example 3 were dripped showed almost no ticks on the body after 5 days and showed a high anthelmintic effect. The irritation to the skin was also observed and is shown in Table 4 below.

Table 4 Preparations used Irritation findings (1 day after dropping) Example 3- Example 4- Comparative Example 3 + Control-

Evaluation Criteria Findings-No abnormalities + Slight erythema ++ Clearly discernible erythema ++ + Clearly discernible erythema over the ear

From Table 4 above, slight erythema was observed in Comparative Example 3 and weak irritation was observed, but no irritation was observed in Examples 3 and 4.

[0058]

EFFECTS OF THE INVENTION A spot-on agent for combating ectoparasites of animals, which contains cycloprotoline as an active ingredient, is easy to apply and has side effects such as acute toxicity and skin irritation on animals such as cats and rabbits. However, it showed anthelmintic effect at low application rates.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 47/10 A61K 47/20 47/20 47/44 47/44 A61P 33/14 A61P 33/14 A01N 53 / 00 508D

Claims (5)

[Claims] 1. A spot-on agent for combating ectoparasites of animals, which comprises cycloprothrin as an active ingredient in a solvent. 2. The spot-on agent for controlling ectoparasites of animals according to claim 1, which contains an organic solvent and / or a vegetable oil as the solvent. 3. The ectoparasite of an animal according to claim 2, wherein the organic solvent is one or more selected from the group consisting of ethylene glycol monoethyl ether, dipropylene glycol monobutyl ether, ethanol, propylene glycol, isopropanol and dimethoxy sulfoxide. A spot-on agent for insect control. 4. The vegetable oil is one or more selected from the group consisting of soybean oil, coconut oil, palm oil, linseed oil, cottonseed oil, rapeseed oil, tung oil, castor oil, tangerine oil, olive oil and rice sugar oil. Item 2. A spot-on agent for controlling ectoparasites of animals according to item 2 or 3. 5. The method according to claim 1, wherein the solvent contains a surfactant.
The spot-on agent for controlling ectoparasites of animals according to 2, 3, or 4.