JPH07233053A - Parasiticide - Google Patents

Abstract

PURPOSE:To obtain an endoparasiticide for an oral or endermic administration, containing a natural pyrethroid compound or a synthetic pyrethroid compound as an active component. CONSTITUTION:This parasiticide contains a natural pyrethroid compound or a synthetic pyrethroid compound of formula (R1 is a lower alkyl, a lower alkoxy or a lower haloalkoxy; R2 is a lower alkyl or a lower haloalkoxy; R3 is a lower alkyl or H; A is C or Si; B is O or CH2; X is H or a halogen; Y is H or a halogen) as an active component by 0.01-99wt.%, preferably 0.01-20wt.%. Its dosage is 0.001-10000mg/kg per day for an oral dose, and 0.001-10000mg/kg per day for a parenteral dose. It manifests a parasiticidic efficacy to not only parasites living in bodies of an intermediate host and a final host but also those of a reservoir host.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is characterized by an endoparasiticidal agent containing a natural pyrethroid compound or a synthetic pyrethroid compound as an active ingredient, and the oral or transdermal administration of the endoparasiticidal agent. The present invention relates to a method for exterminating internal parasites.

[0002]

2. Description of the Related Art Conventionally, a natural pyrethroid compound or a synthetic pyrethroid compound according to the present invention is known as a compound having activity against pesticide pests, sanitary pests, wood forest pests and food pests.

[0003]

Generally, parasitosis is caused by parasitic infection of an animal host with parasites, that is, unicellular protozoa (protozoa), multicellular helminths or arthropods. Parasitic diseases are said to have been markedly reduced in Japan due to improved environmental hygiene, but from a global perspective, it is widespread, especially in developing countries.
Has caused a great deal of damage. Also, in recent years, there has been a new increase in infections caused by long and short-term travelers to these foreign countries, infections from imported foods or frozen foods, and infections from eating and drinking of raw meat and fish due to the development of transportation technology, and parasitic diseases from pets. Is beginning to show. Furthermore, opportunistic infections in which parasites that have been non-pathogenic or low-pathogenic in the past acquire pathogenicity have become a problem because they become immunodeficient due to large-scale administration of immunosuppressive agents, anticancer agents and the like, AIDS infection and the like.

Parasitosis is a universal and serious economic problem in domestic animals such as pigs, horses, cows, sheep, goats, dogs, cats and poultry. In other words, parasite infection causes anemia, malnutrition, weakness, weight loss, and serious damage to the intestinal wall and other tissues and organs in infected animals, contributing to reduced feed efficiency and reduced productivity. , Financial loss is large. Therefore, providing a novel antiparasitic agent or antiprotozoal agent is an important issue that is always sought.

Therefore, an object of the present invention is to provide an anthelmintic agent for exterminating these human and animal endoparasites.

[0006]

[Means for Solving the Problems] In order to solve the above problems, natural pyrethroid compounds or synthetic pyrethroid compounds show activity against pesticide pests, sanitary pests, wood forest pests, food pests, but they are extremely harmful to humans and animals. Due to its high safety, we have been repeatedly studying whether it could be applied directly to humans and livestock to control parasites. As a result, they found that parasites can be efficiently exterminated by orally or transdermally administering these compounds, and the present invention has been completed.

[0007] That is, the present invention is an endoparasiticidal agent containing at least one natural pyrethroid compound or synthetic pyrethroid compound as an active ingredient.

The endoparasiticidal agent of the present invention can efficiently exterminate endoparasites parasitic on humans and animals, and thereby prevent or treat parasitosis.

The natural pyrethroid compound or the synthetic pyrethroid compound according to the present invention is a known pyrethroid compound, specifically, acrinathrin: (S).
-Α-cyano-3-phenoxybenzyl (Z)-(1
R, 3S) -2,2-Dimethyl-3- [2- (2,2,
2-trifluoro-1-trifluoromethylethoxycarbonyl) vinyl] cyclopropanecarboxylate,
Allethrin: (RS) -3-allyl-2-methyl-4-
Oxocyclopentenyl (1RS) -cis, tran
s-Chrysanthemate, alpha-cypermethrin:
α-Cyano-3-phenoxybenzyl-3- (2,2-
Dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate, cycloprothrin: (RS) -α-cyano-3-phenoxybenzyl (RS) -2,2-dichloro-1- (4-ethoxyphenyl) cyclopropane Carboxylate, cyfluthrin: (RS) -α-cyano-4-fluoro-3-phenoxybenzyl (1RS, 3
RS: 1RS, 3SR) -3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate, cyphenothrin: (RS) -α-cyano-3-phenoxybenzyl (1R) -cis, trans-chrysanthemate, empensulin: (RS) -1-ethyl-2-methyl-2-pentenyl (1R) -cis, tr
ans-chrysanthemate, fenvalerate: (R
S) -α-Cyano-3-phenoxybenzyl (RS)-
2- (4-chlorophenyl) -3-methylbutyrate,
Cadesulin: 5-benzyl-3-furylmethyl (E)-
(1R, 3S) -2,2-Dimethyl-3- (2-oxothiolane-3-ylidenemethyl) -cyclopropanecarboxylate, permethrin: 3-phenoxybenzyl (1RS) -cis, trans-3- (2,2- Dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate, phenothrin: 3-phenoxybenzyl
2,2-Dimethyl-3- (2-methylpropenyl) cyclopropanecarboxylate, Praresulin: (S)-
2-Methyl-4-oxo-3- (2-propynyl) cyclopentenyl (1R) -cis, trans-chrysanthemate, resmethrin: 5-benzyl-3-furylmethyl (1RS) -cis, trans-chrysanthemate , Tetramethrin: cyclohexene-1,2-dicarboximidomethyl (1RS) -cis, trans-
2,2-Dimethyl-3- (2-methylpropenyl) cyclopropanecarboxylate, tralomesulin: (S)
-Α-cyano-3-phenoxybenzyl (1R, 3
S) -2,2-Dimethyl-3-[(RS) tetrabromoethyl] cyclopropanecarboxylate, pyrethrin, and general formula (1)

[0010]

[Chemical 2] (In the formula, R ₁ represents a lower alkyl group, a lower alkoxy group or a lower haloalkoxy group. R ₂ represents a lower alkyl group or a lower haloalkyl group. R ₃ represents a lower alkyl group or a hydrogen atom. A represents a carbon atom. A represents an atom or a silicon atom, B represents an oxygen atom or CH ₂ , X represents a hydrogen atom or a halogen atom, and Y represents a hydrogen atom or a halogen atom.) Is a synthetic pyrethroid compound.

In particular, the synthetic pyrethroid compound represented by the general formula (1) is preferable as the endoparasiticidal agent of the present invention from the viewpoint of safety for humans and animals. The compound represented by the general formula (1) is, for example, flufenprox:
[3- (4-chlorophenoxy) benzyl] (RS)-
2- (4-ethoxyphenyl) -3,3,3-trifluoropropyl ether, SSI-116: dimethyl (4-ethoxyphenyl) silylmethyl-3-phenoxybenzyl ether, HOE-498: (4-ethoxyphenyl) [ 3- (4-fluoro-3-phenoxyphenyl) propyl] (dimethyl) silane, etofenprox: 2- (4-ethoxyphenyl) -2-methylpropyl 3-phenoxybenzyl ether, halphenprox: 2- [4 -(Bromodifluoromethoxy)
Phenyl] -2-methylpropyl 3-phenoxybenzyl ether, MTI-790: 1- (3-phenoxyphenyl) -4- (4-ethoxyphenyl) -4-methylpentane, MTI-800: 1- (3-phenoxy −
4-fluorophenyl) -4- (4-ethoxyphenyl) -4-methylpentane.

Etofenprox, MTI-790,
MTI-800, SSI-116, HOE-498
It is particularly preferable in terms of activity against endoparasites and safety for humans and animals.

Human animals to which the present invention is applied include humans and pigs, horses, cows, sheep, goats, rabbits, camels, buffalos, deers, minks, chinchillas and other livestock, chickens, ducks, geese, turkeys and the like. Pets such as poultry, dogs, cats, small birds and monkeys, and experimental animals such as rats, mice, golden hamsters and guinea pigs.

The general endoparasites parasitic on humans for which the compounds of the present invention are effective are roughly classified into protozoa and helminths. The protozoa are amoebas such as Entamoeba histolytica (Rhizop
oda), Leishmania, Trichomonas and other flagellates (Z
oomastigophora), toxoplasma, sporozoites such as malaria parasite (Telosporidea), and ciliates (Ciliata) such as large intestine Valantidium. Nematoda are worms, nematoda, dog worms, anisakis, pinworms, hookworms, ciliated nematodes, schistosome nematodes, Malay filamentous insects, onchocerca, loa filamentous insects, Manson filamentous insects, dog filamentous nematodes, etc. , Acrothocephala, such as giant hookworm, schistosomiasis, liver fluke, liver fluke, Thai liver fluke, pancreas fluke, lung fluke, Yokokawa fluke, heteromorphous fluke,
Trematodas such as hypertrophic flukes and stab flukes (Trematoda), cestodes of cranial tapeworms, no hookworms, echinococcus and other tapeworms (Cestoda)
Etc.

Common endoparasites parasitic on animals for which the compounds of the present invention are effective include Ascaris and Toxocara ( Tox ).
ocara ), small dog worm ( Toxascaris ), horse worm ( Parascari )
s ), chicken worm ( Ascaridia ), chicken cecal worm ( Heterakis ),
Pinworm ( Oxyuris ), Capillaria ( Capillaria ), Trichinella ( Tr
ichinella ), roundworm ( Strongylus , Triodontophorus ),
Caterpillars ( Trichonema ), swine nematodes ( Stephanurus ), intestinal tuberculosis ( Desophagostomum ), large intestine nematodes ( Chabertia ),
Beetle bug ( Syngamus ), hookworm ( Ancylostoma , Uncinaria ,
Necator , Bunostomum ), Ciliary nematode ( Trichostrongylu)
s ), Coober's hairy nematode ( Cooperia ), Fine hairy nematode ( N)
ematodirus ), stomach worm ( Haemonchus ), stomach worm ( Ostertagia ), pneumonia ( Dictyocaulus ), Metastro
ngylus ), canine tapeworm ( Dirofilaria ), polychaete tapeworm ( P
arafilaria ), horse threadworm ( Setaria ), onchocerca ( O
nchocerca ), stomach bug ( Habronema , Arduenna , Acuaria )
And other nematodes, Diphyllobothrium , Anoplocephara , Moniezi
a ), tapeworms ( Dipylidium ), hookless tapeworms and tapeworms ( T
aenia), measles (Dithyridium), Rerichina genus (Railli
etina ), Echinococcus and other tapeworms, Schistosoma , Schistosoma , Paraphistomum , Fasciola and other flukes, and various other parasites.

The endoparasiticidal agent of the present invention exerts an effect not only on the parasites inhabiting the body of the intermediate host and the final host, but also on the parasites in the living body of the insect host. Further, the endoparasiticidal agent of the present invention exerts an effect at all stages of parasite development. For example, in protozoa, cysts, precapsular types, vegetative or asexual divisions, amoebic bodies,
It is a sexual reproductive maternal body, reproductive body, fusion body, spore, or the like. Among nematodes, eggs, larvae, and adults. Furthermore, the compound of the present invention can prevent parasite infection not only by exterminating parasites in the body but also by prophylactically applying the compound in an environment which is an infection route. For example, soil-borne infections from soils such as fields and parks, percutaneous infections from rivers, lakes, wetlands, water systems such as paddy fields, oral infections from feces of animals such as dogs and cats, saltwater fish, freshwater fish, It is possible to prevent oral infection from crustaceans, shellfish, raw meat of livestock, infection from mosquitoes, flies, flies, cockroaches, mites, fleas, lice, turtles, and chiggers.

The endoparasiticidal agent of the present invention can be administered as an animal drug or a human drug for the purpose of treating or preventing parasitic disease. The administration method may be either oral administration or parenteral administration. For oral administration, capsules, tablets, pills, powders, granules, fine granules,
It can be administered by blending it in a powder, syrup, enteric solution, suspension, paste, or liquid beverage or feed for animals. For parenteral administration,
Injectable solution, drops, suppositories, emulsions, suspensions, drops, ointments, creams, solutions, lotions, sprays, aerosols, poultices, tapes to maintain mucosal or transdermal absorption Administered in various dosage forms.

The endoparasiticidal agent of the present invention is effective against endoparasites when administered alone, but it can also be used in combination with existing parasite drugs for humans and animals, resulting in a synergistic effect. It can be expected, and it is possible to reduce the mutual dosage.

When the endoparasiticidal agent according to the present invention is used as a drug for animals or humans, the optimum amount to be used varies depending on the treatment or prevention, the type of infectious parasite, the type and degree of infection, the financial form, etc. However, when administered orally, it is generally about 0.001 to 10000 mg per day.
/ Kg body weight range. In the case of parenteral administration, it is in the range of about 0.001 to 10000 mg / kg body weight per day, which is administered in single or divided doses.

The concentration of the natural pyrethroid compound or the synthetic pyrethroid compound in the endoparasiticidal agent according to the present invention is generally 0.01 to 99% by weight, preferably 0.01 to 20% by weight. The endoparasiticidal agent according to the present invention can be provided as a high-concentration composition which is used by diluting it with an appropriate diluent at an appropriate concentration.

[0021]

EXAMPLES Next, examples of actual internal parasite control agents will be given.
The following examples and test examples exemplify the effects of the present invention, and do not limit the scope thereof. The synthetic pyrethroid compounds used in this example (formulation and test example) are as follows.

Compound 1: Etofenprox: 2-
(4-Ethoxyphenyl) -2-methylpropyl 3-
Phenoxybenzyl ether compound 2: MTI-790: 1- (3-phenoxyphenyl) -4- (4-ethoxyphenyl) -4-methylpentane compound 3: MTI-800: 1- (3-phenoxy-4)
-Fluorophenyl) -4- (4-ethoxyphenyl)
-4-Methylpentane Compound 4: HOE-498: (4-ethoxyphenyl)
[3- (4-Fluoro-3-phenoxyphenyl) propyl] (dimethyl) silane

Example 1 Emulsion Emulsion was obtained by dissolving 10 parts of compound 1 or compound 2 or compound 3 or compound 4 and 6 parts of emulsifier (Sorpol 355F: manufactured by Toho Kagaku) in 84 parts of xylene.

Example 2 Ointment Compound 1 (1 part), white beeswax (50 parts) and white petrolatum (49 parts) were thoroughly mixed to obtain an ointment.

Example 3 Tablets Compound 1 2 parts, vegetable oil (olive oil) 10 parts, crystalline cellulose 3 parts white carbon 20 parts and kaolin 65 parts were thoroughly mixed and tableted to give tablets.

Example 4 Injection Solution An injection solution was prepared by mixing 10 parts of Compound 1, 10 parts of propylene glycol for food additives and 80 parts of vegetable oil (corn oil).

Example 5 Aqueous agent An aqueous agent was obtained by thoroughly mixing 5 parts of compound 1, compound 2 or compound 3, 20 parts of a surfactant (Tween 80) and 75 parts of deionized water.

Test Example 1 Anti-Microfilaria Action Test Microfilaria collected from the peritoneal cavity of peritoneally infected gerbils was cultured in a culture medium containing Compound 1, and after a certain period of time, its insecticidal effect was investigated. The results are shown in Table 1 (Table 1).

[0029]

[Table 1]

From the above results, it was revealed that Compound 1 has an insecticidal action on Microfilaria.

Test Example 2 Test against Malaria Protozoa Compound 1, Compound 2, Compound 3 and Compound 4 were dissolved in corn oil to infect mice with malaria (5 in 1 group).
Oral or percutaneous administration to the head), and the life and death of the mice were observed over time. The results are shown in Table 2 (Table 2) and Table 3 (Table 3).
Respectively shown.

[0032]

[Table 2]

[0033]

[Table 3]

As is clear from Tables 2 and 3, Compound 1, Compound 2, Compound 3 and Compound 4 all contributed to prolonging the life of mice infected with malaria by oral administration or transdermal administration.

Test Example 3 Effect on dog worms and hookworms Prior to the anthelmintic experiment, the feces of the test dogs were formalin-
An ether method was used to check the presence of parasites in the digestive tract (helminths and hookworms). Dogs infected with the target parasites shown in Table 4 (Table 4) were selected, and Compound 1 was suspended in a predetermined amount of corn oil and orally administered. After administration, the excreted feces in the feces are examined every day, and on the 7th day of administration, the excreted feces are inspected again by the formalin-ether method to check for the presence of eggs (worms) and insects (hookworms). did. As a result of the fecal test, the number of dogs and the types of parasites that were positive for eggs were determined as the fourth.
The results are shown in the table (Table 4). The effects of Compound 1 on dog worm are shown in Table 5 (Table 5). The effects of Compound 1 on Hookworm are shown in Table 6 (Table 6).

[0036]

[Table 4]

[0037]

[Table 5]

[0038]

[Table 6]

Compound 1 in dogs at 50 mg / kg, 250 m
By administration at a rate of g / kg, dog worms and hookworms could be completely repelled.

Test Example 4 Effect on heartworm From the 5th day after infection of gerbils previously infected with heartworm ( Brugia pahangi ), Compound 1 dissolved in corn oil was administered transdermally at a dose of 20 mg / kg daily for 5 consecutive days. Was administered. Rat blood was collected at regular intervals, and the number of microfilariae therein was counted. The results are shown in Table 7 (Table 7).

[0041]

[Table 7]

From the above results, it is clear that Compound 1 is effective in exterminating filaria ( Brugia pahangi ) infected with gerbils and that the effect continues. From the above test examples, it is understood that oral or transdermal administration of the preparation containing the compound according to the present invention has an excellent effect on various parasites.

[0043]

INDUSTRIAL APPLICABILITY The endoparasiticidal agent of the present invention can efficiently exterminate endoparasites parasitic on humans and animals, and thereby prevent or treat parasitosis.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Kazutomi Onuma 1144, Togo, Mobara-shi, Chiba Mitsui Toatsu Chemical Co., Ltd.

Claims (2)

[Claims] 1. An endoparasiticidal agent containing at least one natural pyrethroid compound or synthetic pyrethroid compound as an active ingredient. 2. A synthetic pyrethroid compound is represented by the general formula (1) (In the formula, R ₁ represents a lower alkyl group, a lower alkoxy group or a lower haloalkoxy group, R ₂ represents a lower alkyl group or a lower haloalkyl group, R ₃ represents a lower alkyl group or a hydrogen atom, A represents a carbon atom or A silicon atom, B is an oxygen atom or a CH ₂ group, X is a hydrogen atom or a halogen atom, and Y is a hydrogen atom or a halogen atom.)
The endoparasiticidal agent according to claim 1, which is a compound represented by: