JPS5989627A - Preventive for animal coccidiosis - Google Patents

Abstract

PURPOSE:To provide the titled drug having excellent oocystocidal effect and useful for the prevention of animal coccidiosis, by using a specific quinoxaline compound as an active component. CONSTITUTION:A preventive for animal coccidiosis, containing the quinoxaline compound of formula (R1 and R2 are H, lower alkyl, halogen, etc.; X is O or S) as an essential component. Coccidiosis is a disease of cattle and poultry caused by the infection with protozoal parasite belonging to Eimeria genus, etc., and causes diarrhea and hemorrhage, and resultantly nutrition disorder of the animal, etc. For the remedy and prevention of coccidiosis caused by the protozoa belonging to Eimeria genus, there are two ways in view of the growth cycle of coccidium, i.e. the administration of the drug to the animal and the treatment of feces, etc. excreted from the body; however, the above drug exhibits remarkably excellent effect to kill the oocyst when used as an external agent (e.g. emulsion, powder, etc.) for treating the living environment of the animal, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel preventive agent for coccidiosis in animals. Let me explain in more detail.

A quinoxaline compound represented by the general formula (in the formula, R1 and present represent the same or different hydrogen atom, lower alkyl group, halogen atom, or lower alkoxy group, and X represents an oxygen atom or a sulfur atom) is an essential component. This invention relates to a preventive agent for coccidiosis in animals.

Coccidiosis is a disease of livestock and poultry caused by infection with protozoan parasites such as those of the genus Eimeria, and these diseases cause diarrhea and bleeding, resulting in malnutrition.

In particular, the damage caused by chickens is extremely severe, such as chicken caecal coccidiosis.

Chicken small intestinal coccidiosis is feared by poultry farmers because the symptoms are acute and accompanied by bloody diarrhea, and chicks die within a few days.Also, chicken small intestinal coccidiosis is chronic and rarely causes death of chickens, but it can be caused over a long period of time. Because it parasitizes the small intestine and causes malnutrition, it is a disease that causes great damage, similar to cecal coccidiosis.

The growth cycle of coccidia is shown below.

That is, when a chicken eats an oocyst, sporozoites are released within the gastrointestinal tract, immediately invade the mucosal cells of the gastrointestinal tract, and begin to proliferate. After a day or two, this develops into a group of protozoa called schizonts.

This membrane ruptures and dozens of merozoites escape from inside.
This parasite invades cells again and multiplies through schizonts a few hours later. At this time, chickens show symptoms. Chickens that survive this period recover, and the protozoa also develop into male and female forms. The chickens then fertilize, form countless new oocysts, and are excreted in the feces, waiting for an opportunity to infect other chickens.

Measures for the treatment and prevention of coccidiosis caused by protozoa of the genus Eimeria that have such a cycle include:
Broadly speaking, it can be divided into two methods: one is to give it to a parasitic animal to kill the pathogenic protozoa, and the other is to kill the pathogenic protozoa by disposing of the feces once it is excreted outside the body.

Method 2 to control the outbreak and spread of coccidiosis in animals
There is one.

From this point of view, research has been conducted over a long period of time, and as a result, many drugs have been developed that can be administered internally to parasitic animals.

It is difficult to expect that there will be no percentage of excretion as oocysts, and the current situation is that there is still no perfect product in terms of effectiveness. Furthermore, regarding the above-mentioned latter external treatment method, for example, the main ingredient is an inorganic substance such as ammonia or orthoni-dichlorobenzene, and if necessary, phenol or cresol.

Drugs in combination with halocresol or sulfocresol have been used, but there are problems with their oocysticidal effects, and the development of even better drugs is desired.

Therefore, the present inventors have conducted extensive research on oocysticides for many years, and found that the first general formula (I) (wherein R5 and R2 are the same or different hydrogen atoms, lower alkyl groups, halogen atoms, lower It has surprisingly been found that when a quinoxaline compound represented by the following formula (representing an alkoxy group and X represents an oxygen atom or a sulfur atom) is used as an essential component, the oocysticidal effect is significantly superior.

Therefore, one object of the present invention is to provide a novel preventive agent for coccidiosis in animals that has an excellent oocysticidal effect.

A further object of the present invention is to provide a pharmaceutical composition that can be used externally to treat the living environment of animals to reliably kill pathogenic protozoa of the genus Eimeria in order to suppress the occurrence of coccidiosis in animals. There is something to do.

Representative compounds of the quinoxaline compound (I) used in the present invention are as follows.

06-Methyl-1,3-dithiolo(4,5-b)-quinoxalin-2-one (morestan) 06-Methyl-1,3-dithiolo(4,5-b)-quinoxalin-2-thione 01.3- Dithiolo(4,5-b)-quinoxaline-2
-thione (eladitone) 06-chloro-1,3-dithiolo(4,5-b)-quinoxaline-2-thione Ol, 3-dithiolo(4,5-b)-quinoxaline-2
-one 05-methyl-1,3-dithiolo(4,5-b)-quinoxalin-2-one 05.7-dimethyl-1,3-dithiolo[4,5-b)
-Quinoxalin-2-one When carrying out the present invention, there are nine different dosage forms, such as powders.

Any dosage form may be used, such as granules, wettable powders, emulsions, oils, and smoking agents, but emulsions are the most preferred dosage form because they exhibit the best effects.

If this is to be made into an emulsion, a main solvent is added and dissolved, and a surfactant suitable for making a stable emulsion in water is added, and if necessary, co-solvents, penetration aids, etc.
Stabilizers, ultraviolet absorbers, fixing agents, etc. can be added. In addition, substituted phenol compounds such as phenol, cresol, and xylenol, and di-chlorobenzene can also be used as oocysticidal synergists and as the main solvent for the quinoxaline compound.

As the surfactant, one is selected that has good emulsion stability, does not reduce the oocysticidal effect, and has high adhesiveness.

For example, as anionic substances, carboxylates,
Cationic salts such as sulfonates, sulfate ester salts, phosphate ester salts, quaternary ammonium salts, birimidium salts.

Imidazolium salts, etc., as well as zwitterionic types, aminocarboxylic acid salts, imidazolium betaine type,
Examples include carboxybetaine type. However, using only the above-mentioned ionic surfactant may sometimes lack emulsion stability in water.

Specifically, metal ions such as alkali metal ions in animal feces and soil, or mixed organic matter, destroy the emulsification and not only prevent the desired effect from being achieved.

The quinoxaline compound, which is an essential component of the present invention, locally coalesces and concentrates in the object to be sprayed.

In particular, when the object to be sprayed is animal excrement such as chicken manure, and when this is applied to agricultural crops as fertilizer, there is also concern about secondary chemical damage to the crops. In order to avoid this, such a phenomenon can be prevented by selecting an optimal nonionic surfactant and using it in combination with the above-mentioned ionic surfactant. Here is an example of a nonionic surfactant.

Polyoxyethylene alkyl ether, polyoxyethylene alkyl allyl ether and their formalin condensates, ether ester type nonionic surfactants such as polyoxyethylene glycerin fatty acid ester, polyoxyethylene fatty acid ester type nonionic surfactants, polyoxy Examples include nitrogen-containing nonionic surfactants such as ethylene fatty acid amide.

Examples of co-solvents include ketones such as cyclohexanone and isophorone, ethers of ethylene glycol monophenyl ether, sulfolane, ethylene carbonate, and tetrahydrofuran.

Examples include hexamethylphosphoric triamide, dimethylsulfoxide, dimethylformamide, and N-methylpyrrolidone.

Examples of penetration aids include alkyl sulfosuccinates, and stabilizers include acidic substances such as alkyl acid phosphates and polyhydric phenols.

Examples include epoxy compounds such as epichlorohydrin and butylgrindyl ether, and alkali compounds such as alkanolamines, alkylamines, and alkylanilines.

Further, as a fixing agent, for example, various oil-soluble resins can be used.

Higher fatty acids, high molecular weight hydrocarbons, etc. are used as UV inhibitors, such as benzophenone, salicylic acid such as ethylene glycol salicylate, etc.

Examples include cyanoacrylic compounds.

Next, to explain the effects of the present invention in more detail.

Examples of formulations and experimental examples are shown in Examples.

It goes without saying that the formulation examples are merely examples, and the present invention is not limited thereto. In addition, the percentage (%) in the prescription example of the combination is.

All parts are by weight.

Example i Combination Prescription Example 06-Methyl-1,3-dithiolo(4,5-b)-quinoxalin-one (Molestan)
・・・・3 圀0 pheasant roll・・・・・・・・・・・・・
・・・・・・・・・・・・・・・・・・・・・・・・
・80Ko surfactant・・・・・・・・・・・・・・・
・・・・・・・・・・・・・・・・・・・・・・・・1
2. Total amount: 100 (up to) Make an emulsion using the above recipe using a conventional method.

Example 2 1,3-dithiolo[4°5-b]-quinoxaline-2-thione (eladitone) instead of 6-methyl-1,3-dithiolo(4,5-b)-quinoxaline-2-one An emulsion was prepared using exactly the same recipe.

Next, the effects of the present invention will be illustrated by test examples.

Test Example Anti-volatility effect on Eimeria tenella oocysts 11. Test method (1) Regarding the samples of the combination formulations shown in Examples 1 and 2,
The oocysticidal effect on Eimeria teneua immature oocysts was tested. Ortho agent [prescription], which is commonly used as an oocysticide, is used as a control drug.

90% orthodichlorobenzene and 10% emulsifier] were used.

(2) 50.0% per bird for white Leghorn male chicks (Goto 360) raised coccidia-free.
00 Eimeria tenella ossis)
Orally inoculated.

Eight days later, the chicks were killed and the caecum was collected. Oocysts were collected from the cecal contents, suspended in distilled water, and used in the test.

The number of oocysts used in the test was 107-108.

(3) The sample was diluted 200 times with distilled water, and 3 d of this and 3 d of the oocyst suspension were added to a petri dish, and after stirring, the mixture was left at 24 to 26°C.

By the above operation, the sample was made to act on the oocysts at 400 times the amount. After 2 hours, transfer these liquids to a centrifuge tube.
Add 0.596 Lybon (manufactured by Lypon Nilion Oil Co., Ltd.) solution, stir well, centrifuge at 400g for 5 minutes, remove the supernatant, suspend the precipitate in Lybon solution again, and repeat the centrifugation process. The specimen was removed. In each test, centrifugation was repeated five times to remove the specimen. After washing and removing the specimen, the number of oocysts was determined, transferred to a petri dish, and cultured at about 25 to 28°C.

(4) Observation and Judgment After 4 to 5 days of culture, a small amount of the test body fluid was placed on a slide glass, covered with a cover glass, and observed under a microscope. A total of 200 or more immature oocysts and mature oocysts were counted.

The sporulation rate was expressed as the percentage of mature oocysts to the total number of oocysts counted, and it was judged that the lower the sporulation rate, the better the effect of the sample.

A significant difference test was performed on the voloration rate of the sample compared to the control ortho-drug.

2. Test results The results are shown in Table 1.

Table 1 As is clear from Table 1, all of the nine samples of the present invention have a significantly superior svolvation rate compared to the control orthodrug, and therefore have excellent oocysticidal effects and can be used as a preventive agent for coccidiosis in animals. It can be put to practical use.

patent applicant Ko-zai Co., Ltd.

Claims (1)

[Claims] (1) General formula (in the formula, R and R7 represent the same or different hydrogen atom, lower alkyl group, halogen atom, or lower alkoxy group, and X represents an oxygen atom or a sulfur atom). An agent for preventing coccidiosis in animals, which contains a quinoxaline compound represented by the following as an essential ingredient. (21ki/+ sarin-based compounds are 6-methyl-1,3-
The agent for preventing coccidiosis in animals according to claim 1, which is dithiolo(4,5-b)-quinoxalin-2-one. (3) The quinoxaline compound is 1,3-dithiolo[4
, 5-b)-quinoxaline-2-thione, the coccidiosis preventive agent according to claim 1.