JP2001288013A - Raticide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a raticide which can exhibit a high fatal potency against raticide-sensitive rats by the intake of the raticide for a short period and can also similarly show a high fatal potency against raticide-resistant rats. SOLUTION: This raticide is characterized by containing a cytochrome P-450 derivative and a blood anticoagulant.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a rodenticide which has a high lethality against rats and is effective against rats which have acquired drug resistance to conventional rodenticides.

[0002]

2. Description of the Related Art Hitherto, anticoagulants such as warfarin have been known to have a lethal effect on rats, and rodenticides containing this type of anticoagulant have been widely used.

[0003] Usually, the above-mentioned rodenticide can obtain a high lethal effect by ingesting a rodent having drug sensitivity (hereinafter referred to as "sensitive rat") every day for about 4 to 5 days. When a rodenticide is administered to a susceptible rat, the bleeding gradually starts in the living body of the susceptible rat from 2 to 3 days after the administration, and the animal dies quietly about one week after the start of the administration. It has the advantage that it does not give other rats an unusual vigilance.
In addition, the content of the anticoagulant in the rodenticide is far lower than the lethal dose to humans, and it is very unlikely that humans will ingest this, making it an extremely safe formulation for use. There is an advantage.

[0004] However, there is a problem that susceptible rats must continuously ingest the rodenticide in order to exert its lethal effect. In other words, if a susceptible rat ingests a lethal dose before taking a dead day, the number of days until lethality tends to be prolonged, such as taking it every other day or taking two days and taking a day off Repeated intake patterns tended to reduce efficacy by half.

[0005] In addition, among the susceptible rats continuing to discontinuously ingest the rodenticide, those having a gene resistant to the rodenticide by mutation appear, and as a result of selection by the rodenticide, drug resistance is obtained. Of rats (hereinafter referred to as resistant mice) are currently proliferating mainly in urban areas. The efficacy of conventional rodenticides against such resistant rats is extremely low, and among resistant mice, there are individuals that do not die even if they are ingested continuously for more than one year. Has been confirmed.

[0006]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and is a rodenticide capable of obtaining a high lethal efficacy in a short period of time for susceptible rats without requiring long-term continuous ingestion. And even for resistant mice,
It is another object of the present invention to provide a rodenticide capable of obtaining a high lethal effect.

[0007]

This problem is solved by combining an anticoagulant with a cytochrome P-450 inducer.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. The present invention is based on the finding that a blood coagulation inhibitor is metabolized to a compound having a rodenticidal action by a reaction catalyzed by cytochrome P-450, which is a drug metabolizing enzyme present in liver microsomes and the like. It was done. That is, in order for the anticoagulant to exert a rodenticidal action, activation by cytochrome P-450 is necessary, and the anticoagulant and cytochrome P-450 are required.
When used in combination with the inducer, the metabolism of the anticoagulant is promoted, and the lethal effect is enhanced. Therefore, the rodenticide of the present invention comprises an anticoagulant and cytochrome P-450.
It consists of an inducer and a rat diet.

[0009] The anticoagulant used in the present invention includes coumarin-based drugs such as warfarin, coumatetralyl, fumarin, brodifacom, bromadiolone,
Examples include difenacum, flocumafen, indandione drugs such as difanosine, chlorophanosine, pindon, or a mixture thereof.

The cytochrome P-45 used in the present invention
0-inducing agents include dexamethasone, betamethasone, triamcilone, halopredone, fluorinated corticosteroids such as paramethasone, cortisone corticosteroids such as hydrocortisone, pregnenolone-16α-carbonitrile, triacetyloleandmycin or a derivative thereof, erythromycin or Derivatives, chlordane, phenobarbital, rifampicin, or mixtures thereof, and the like can be given. Examples of the derivative of triacetyl oleandomicin include monobenzoyl oleandomicin and the like, and examples of the derivative of erythromycin include diacetoxyerythralosamine. Due to the above drugs, cytochrome P-450
Is induced to increase cytochrome P-450 content in liver microsomes.

[0011] The rat food used in the present invention includes:
Flour, bread crumbs, starch, rice bran, sunflower seeds, canary seeds and the like. One or two of these
A mixture of more than one species in any proportion is used.

The content of the anticoagulant in the rodenticide is about 0.001 to 0.5% by weight, preferably about 0.005 to 0.025% by weight. When the content is less than 0.001% by weight, sufficient lethal effect cannot be obtained. When the content is more than 0.5% by weight, rats are tastefully repelled and do not eat. The content of the cytochrome P-450 inducer in the rodenticide was 0.0%.
About 01 to 0.25% by weight, preferably 0.005 to
It is about 0.2% by weight. If the content is less than 0.001% by weight, cytochrome P-450 cannot be sufficiently induced, so that a sufficient lethal effect on resistant mice cannot be obtained. Beyond that, the rat tastefully repels and does not eat it.

The rodenticide obtained by mixing the anticoagulant, the cytochrome P-450 inducer, and the rat's bait so as to satisfy the above-mentioned content may contain, if necessary, a red No. 3 aluminum lake. Additives such as coloring agents and fragrances can be appropriately compounded. Further, the dosage form of the rodenticide can be arbitrarily set such as powder, tablet, solvent and the like.

[0014] Since such a rodenticide contains a cytochrome P-450 inducer, a rat taking the same contains a cytochrome P-450 inducer. The induced cytochrome P-450 promotes the metabolism of the anticoagulant contained in the rodenticide, and increases the production of metabolites exhibiting rodenticidal action. For this reason, a rodenticide containing a cytochrome P-450 inducer can obtain a high lethal effect even by short-term drug intake. In addition, an effective lethal effect can be obtained for resistant rats that have acquired resistance to conventional rodenticides that do not contain a cytochrome P-450 inducer.

[0015]

The present invention will be described below more specifically with reference to examples. These examples show one embodiment of the present invention, and do not limit the present invention, and can be arbitrarily changed within the scope of the present invention. (Example 1) Warfarin which is an anticoagulant, dexamethasone which is a cytochrome P-450 inducer,
Rat flour, which is a rat feed, was blended to obtain a rodenticide having a warfarin content of 0.025% by weight and a dexamethasone content of 0.2% by weight. When the obtained rodenticide was freely fed (eating) to a susceptible mouse, the rat lost 256 ± 70 g (mean ± standard deviation) per kg of body weight and died. In addition, FIG. 1 shows the number of surviving days of rats from the start of rodenticide administration to death, and the cumulative mortality was calculated. The average number of surviving days is shown in FIG.
4.8 ± 1.1 days (mean ± standard deviation).

Example 2 A rodenticide was obtained in the same manner as in Example 1. When the obtained rodenticide was freely fed (eating) to resistant mice, 273 ± 10 per kg of body weight was obtained.
He ingested 5 g (mean ± standard deviation) and died. In addition, FIG. 2 shows the number of surviving days of rats from the start of rodenticide administration to death, and the cumulative mortality was calculated. The average number of surviving days is 7.4 ± 2.4 days (average ± 2.4 days). Standard deviation).

Example 3 A rodenticide was obtained in the same manner as in Example 1, except that the dexamethasone content was 0.1% by weight. When the obtained rodenticide was freely fed (eating) to resistant rats, 401 ± 184 g (mean ± standard deviation) per kg of body weight was consumed and the rats died. In addition, FIG. 2 shows the number of surviving days of rats from the start of rodenticide administration to death, and the calculated total mortality is shown in FIG. 2. The average surviving days was 7.9 ± 2.5 days (average ± 2.5 days). Standard deviation).

Example 4 A rodenticide was obtained in the same manner as in Example 1, except that the dexamethasone content was 0.01% by weight. When the resulting rodenticide was freely fed (eating) to resistant mice, the body weight was 1 kg.
He ingested 413 ± 153 g (mean ± standard deviation) and died. In addition, FIG. 2 shows the number of surviving days of rats from the start of rodenticide administration to death, and the total mortality was calculated. The average number of surviving days is 7.4 ± 3.6.
Days (mean ± standard deviation).

Example 5 Bromadiolone was used as an anticoagulant, and the bromadiolone content was 0.0
A rodenticide was obtained in the same manner as in Example 1 except that the dexamethasone was added so as to have a content of 05% by weight and dexamethasone to be 0.1% by weight. When the obtained rodenticide was freely fed (eating) to resistant mice, 458 ± 1 per kg of body weight was obtained.
He ingested 33 g (mean ± standard deviation) and died. In addition, FIG. 2 shows the results obtained by measuring the number of days a mouse survived from the start of rodenticide administration to death and calculating the cumulative mortality.
The average number of surviving days was 6.3 ± 1.5 days (mean ± standard deviation).

Example 6 Chlorofacinone was used as an anticoagulant, and the content of chlorofacinone was 0.0
A rodenticide was obtained in the same manner as in Example 1 except that the dexamethasone was added so as to have a content of 05% by weight and dexamethasone to be 0.1% by weight. When the obtained rodenticide was freely fed (eating) to resistant mice, 376 ± 6 per kg of body weight was obtained.
He ingested 7 g (mean ± standard deviation) and died. In addition, FIG. 2 shows the number of surviving days of rats from the start of rodenticide administration to death, and the calculated total mortality is shown in FIG. 2. The average number of surviving days was 5.7 ± 0.6 days (mean ± 0.6 days). Standard deviation).

Example 7 Difacinone was used as an anticoagulant, and the content of difacinone was 0.005.
A rodenticide was obtained in the same manner as in Example 1 except that the dexamethasone content was 0.1% by weight, and the dexamethasone content was 0.1% by weight. When the obtained rodenticide was freely fed (eating) to resistant mice, 416 ± 29 per kg of body weight was obtained.
g (mean ± SD) and died. In addition, FIG. 2 shows the number of surviving days of rats from the start of rodenticide administration to death, and the calculated total mortality is shown in FIG. )Met.

Example 8 Coumatetralyl was used as an anticoagulant, and the content of coumatetralyl was 0.025.
A rodenticide was obtained in the same manner as in Example 1 except that the content was adjusted to be 0.1% by weight and the content of dexamethasone was 0.1% by weight. When the obtained rodenticide was freely fed (eating) to resistant mice, 251 ± 11 per kg of body weight was obtained.
He ingested 8 g (mean ± standard deviation) and died. The average number of surviving days was 5.3 ± 1.2 days (mean ± standard deviation) after the start of rodenticide administration.

COMPARATIVE EXAMPLE 1 Warfarin, a blood coagulation inhibitor, was mixed with wheat flour, a rat feed, to obtain a rodenticide having a warfarin content of 0.025% by weight. When the obtained rodenticide was freely fed (eating) to susceptible rats, 428 ± 182 g / kg of body weight was obtained.
(Mean ± standard deviation) and died. In addition, the number of days a rat survived from the start of rodenticide administration to death was measured.
The calculated total mortality is shown in FIG. 1, and the average survival time was 8.1 ± 2.7 days (mean ± standard deviation).

Comparative Example 2 A rodenticide was obtained in the same manner as in Comparative Example 1. When the obtained rodenticide was freely fed (eating) to resistant rats, 14,81 / kg body weight was obtained.
He ingested 5 ± 2,618 g (mean ± standard deviation) and died. In addition, FIG. 2 shows the survival days of rats from the start of rodenticide administration to death, and the cumulative mortality was calculated. The average survival days were 160.1 ± 13.
8.3 days (mean ± SD).

[0025]

[Table 1]

From the results shown in Table 1 and FIGS.
It can be seen that the rodenticide used in Example 1 containing a cytochrome P-450 inducer can obtain a higher lethal efficacy against susceptible rats in a short period of time than the rodenticide used in Comparative Example 1 containing no cytochrome P-450 inducer. . In addition, cytochrome P-
The rodenticides used in Examples 2 to 8 containing a 450 inducer showed sufficient lethal efficacy against resistant mice, whereas the rodenticides used in Comparative Example 2 without cytochrome P-450 showed And the lethal efficacy against resistant mice was extremely low. Thus, cytochrome P-45
It can be seen that the rodenticide containing the 0 inducer not only can shorten the number of days until lethality of a susceptible mouse, but also can exert a sufficient lethal effect on a resistant mouse.

[0027]

As described above, since the rodenticide of the present invention is a combination of an anticoagulant and a cytochrome P-450 inducer, the lethal effect is enhanced, and a high lethal effect is obtained in a short period of time. Thus, it is possible to obtain a high lethal effect on resistant mice which have acquired resistance to conventional rodenticides.

[Brief description of the drawings]

FIG. 1 is a graph showing the cumulative mortality in Example 1 and Comparative Example 1.

FIG. 2 is a graph showing the cumulative mortality in Examples 2 to 7 and Comparative Example 2.

Claims (4)

[Claims] 1. A rodenticide comprising a cytochrome P-450 inducer and an anticoagulant. 2. The cytochrome P-450 inducer is at least one selected from pregnenolone-16α-carbonitrile, triacetyloleandomycin or a derivative thereof, erythromycin or a derivative thereof, chlordane, phenobarbital, and rifampicin. The rodenticide according to claim 1, characterized in that: 3. The rodenticide according to claim 1, wherein the cytochrome P-450 inducer is at least one selected from fluorinated corticosteroids and cortisone corticosteroids. 4. The blood coagulation inhibitor is a group of coumarins consisting of warfarin, coumatetralyl, fumarin, brodifacom, bromadiolone, difenacum, flocumafen, or an indandione consisting of diphanosin, chlorofacinone and pindon The rodenticide according to any one of claims 1 to 3, wherein the rodenticide is at least one selected from the group consisting of: