JPS63174926A - Anticoccidial agent for domestic fowl - Google Patents

Abstract

PURPOSE:To obtain a safe anticoccidial agent, containing an organic bismuth compound as an active ingredient, having low toxicity to domestic fowls as well as excellent anticoccidial action and effective against even drug-resistant strains due to use of a drug for many years. CONSTITUTION:An anticoccidial agent containing an organic bismuth compound expressed by the formula [A is H, F, Cl, methyl, methoxy or trifluoromethyl; s is 1-3; t is 0-2; t is 1 or 2 when s is 1; Q is -Br2(pyridine)2 or -Br2(dipyridyl) when t is 1 and phenylthio or N,N-dimethylaminothiocarbonylthio when t is 2; t is 1 when s is 2; Q is I, cyano, azide, etc.; t is 0, 1 or 2 when s is 3; Q is -Cl(OH) when t is 1 and F, Cl, etc., when it is 2] as an active ingredient. The blending ratio of the compound expressed by the formula is within the range of 0.01-0.08wt.%, preferably 0.02-0.05wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION Background of the Invention The present invention relates to an anticoccidial agent for poultry containing an organic bismuth compound as an active ingredient.

Prior art and its problems Coccidiosis is an infectious disease caused by microorganisms of the genus Coccidia. Mainly Eimeria tenera (Eimer
It occurs in poultry infected with E. necatrix and E. necatrix, and exhibits various symptoms such as gastrointestinal bleeding, mortality, and stunted growth. Outbreaks of coccidiosis at poultry farms where poultry, including chickens, turkeys, and ducks, are raised for commercial purposes are often serious concerns, as they result in extremely large losses for the operators. This has become a serious problem.

Therefore, there is great interest in anti-coccidial agents that are effective in preventing and treating coccidiosis.

Conventionally, sulfa drugs, nitrofuran drugs, quinoline drugs, antithiamine drugs, benzamides, and the like have been put into practical use as anticoccidial drugs, and currently antibiotics are mainly used. The strength of the main anti-coccidial effect of these drugs is not as strong as that shown in the left, and there are problems with toxicity to the host. Additionally, due to the long-term use of drugs, drug-resistant strains have emerged.
This has resulted in a situation where the efficacy of the drug gradually decreases. In consideration of these circumstances, there is a need for the development of a new type of anti-coccidial agent for poultry that is effective against resistant strains and at the same time does not easily impart resistance.

In order to solve the problems, the present inventors have taken the above-mentioned circumstances into account and have set out to develop an anticoccidial agent that can effectively prevent and treat coccidiosis in poultry and is safe for the host poultry. As a result of repeated research aimed at this purpose, it was discovered that certain types of existing organic bismuth compounds have previously unknown, excellent anti-coccidiosis effects, leading to the completion of the present invention.

That is, the present invention relates to the general formula (■): [wherein A is hydrogen, fluorine, chlorine, methyl, methoxy or trifluoromethyl, S is an integer of 1 to 3, and L is 0 to 2]
is an integer, and when S is 1, t is! or 2,
When L is 1, Q is -I3r, (pyridine)! or -B
rt (dipyridyl), when L is 2, Q represents phenylthio, N,N-dimethylaminothiocarbonylthio, when S is 2, t is l, and Q represents iodine, cyano, azide, -Br (phenylated). (tetramethylammonium halide), or -I3r (tetraethylammonium halide),
halide), and when S is 3, L is 011 or 2
And when L is 1, Q! t-0ff(OH),
When t7><2, Q represents a fluorine, chlorine, acetoxy or nitrate radical, and the present invention provides an anticoccidial agent for poultry containing an organic bismuth compound as an active ingredient.

The compound group represented by the above general formula (I) can be further classified into the following groups. That is, they have the general formula (II
) ~ (■): (R)mBi(Y)3-II, (IV), RBiBr
t・(L)n(V).

(R)t[3iI3r-M (Vl) [wherein R is a phenyl group optionally substituted with fluorine, chlorine, methyl, methoxy or trifluoromethyl; X is a fluorine, chlorine, acetoxy or nitrate radical; m is an integer from 1 to 3; when mh<1, Y is phenylthio or N,N-dimethylaminothiocarbonylthio; when m is 2, Y is iodine, cyano or azide; n is 1 or 2; Te, n
When is 1, L is pyridine; when n is 2, L is pyridine; M is phenyltrimethylammonium halide, tetramethylammonium halide or tetraethylammonium halide;

All of the above organic bismuth compounds are known compounds and can be produced according to methods known to those skilled in the art [Friedman (I7, D, Freedma
n) and Poak (C;, O, Poak), chemical
Reviews (Chemical Reviews) l
982.82.15-57, Gilman () I, Q
ilman) and Yale (I(.

Yale) Chemical Reviews, 1942.30.2
81-320].

All compounds of formula (1) can be derived from Rs B i when S is 3 and t is 0, ie m is 3 in formula C'N). The compound of Ra13i has the reaction formula (1),
According to (2), it can be produced by reacting a bismuth halide with a Grignard reagent or a lithium reagent in an ether solvent, hot or cold.

(1) BiX's+3nMgX'=RsBi1,0003MgX
'*(2) BiX's+3RLi -4RsBi+3
LiX' (wherein, Xo represents CI2 or Br, and R is the same QFA as above.) Compounds of formulas (n) and (III) are prepared by reacting fl, Bi and halogen with chloroform, or Reaction in carbon tetrachloride or hydrocarbon solvent at 10°C or lower 11
When 3BiCf2 or rtsI3i13rt is produced and then reacted with various sodium or potassium salts or silver salts in alcohol or acetone at room temperature or hot according to reaction formula (4), the compound of formula (■) can be produced. ,
On the other hand, the compound of formula (III) can be produced by reacting with ammonia water in an aromatic hydrocarbon solvent at room temperature according to reaction formula (5).

(3) RaB i+ X' t → Ra B I
X' t(4)R3B iX' t+ X M' →
I't 3B iX 1+? , M'X'(5)R
iB iX' t + N H40H → (In the formula, Xo represents CQ or Br5X represents Fl-OCOCII3 or a nitrate group, and Mo represents Na, K or Ag.) In formula (IV), m force (the compound of 2 is a reaction formula According to (6), R, l3i1
3r, and then react with various sodium or potassium salts in a hydrous or non-aqueous alcohol or a hydrous or non-aqueous acetone at room temperature according to reaction formula (7).

(6) 2RsBi+B1Br3→3RtB+Br(7)
11tI3inr+YM"→RtBiY+M'Br(
(wherein R and Y are according to the above definitions, and M'' does not represent Na or K.) In the formula (IV), the compound where m is 1 is formed by combining ns[3i and bismuth tribromide] according to the reaction formula (8). to produce RB iB rt in a 1:2 molar ratio in an ether solvent (preferably ether) at room temperature, and then acetone or alcohol etc. according to reaction formula (9) or (10). It can be prepared by reacting with a sodium or potassium salt of a dialkyldithiocarpermate at room temperature in a solvent of 1-IBr, or with a mercaptan using a base as a catch agent for I-IBr.

(8) RsBi+213iBrs→3RBfBrt(9
) nBiBrt+M”ss CN(F), -.

RB i(S S CN (R')z) *+ 2 M
oB "(In the formula, R, M" have the same meanings as above, R' is Me + (base) (HBr) (R has the same Q definition as above.) The compound of formula (V) has the reaction formula It can be produced by reacting at room temperature in an aromatic hydrocarbon solvent or a hydrocarbon solvent according to (11) or (12).

(11) flI3 iBr, +nL-+IIB 1Br
t ・(L)n(12)2 rttI3iBr+ 2
L'→nBiBrt・(L')t+ RzB i (In the formula, "represents 1 or 2," represents pyridine or dipyridyl, and "Lo" represents pyridine.) The compound of formula (VI) is converted into an alcoholic solvent according to reaction formula (13). Alternatively, it can be produced by thermally reacting RtBiBr and a quaternary ammonium salt in acetone.

(13) RtBiI3r+M −' [RtBIBr]
[M] (In the formula, R and M have the same meanings as above.) All of the above manufactured compounds can be purified by recrystallization or precipitation method. In addition, the compound was identified by measuring infrared rays, proton nuclear magnetic resonance, halogen content, melting point, and bismuth content.

The organic bismuth compound represented by the general formula (1) produced as described above is effective in preventing and treating coccidiosis in poultry, as described below.

In addition, it has low toxicity to the host poultry, and resistant strains do not easily appear, so it can be said to be the main component of an extremely useful anticoccidial agent.

The coccidia preventive and therapeutic agent for poultry of the present invention containing the compound of general formula (1) as an active ingredient may be used alone or together with a suitable carrier normally used for this type of drug, optionally an excipient, a disintegrant, It can be prepared and used in dosage forms such as powders, granules, solutions, suspensions, premixes, capsules, emulsions, and tablets using lubricants, coating agents, and the like.

When administering, the compound of the present invention may generally be mixed into poultry feed at a ratio of at least 0.0°C by weight; O1 to about 0.
08% by weight, preferably about 0.02~0.05% by weight. Solutions, suspensions, emulsions, etc. can be added to drinking water11, and capsules, tablets, etc. can be administered orally as they are. good.

Here, the carrier is not particularly limited as long as it can be added to poultry feed or drinking water, but water, lactose, sucrose,
Examples include talc, colloidal silica, pectin, wheat flour, rice bran, corn flour, soybean, oil cake, ground flour, and other commercially available poultry feeds.

In addition, it can also be used in combination with veterinary drugs containing known poultry coccidial agents, antiparasitic agents, infectious disease preventive agents, or growth promoters.

The method for producing the compound of general formula (1), which is the active ingredient of the preparation of the present invention, will be explained in detail below with reference to production examples.

Production Example 1 Tri(metatrifluoromethylphenyl)bismuth (Compound 12) 13.3 g (0.54 mol) of Mg was placed in a LF2 four-bottle flask equipped with a cooling tube, a thermometer, and a stirring funnel, and the mixture was replaced with nitrogen and heated. did.

A mixture of 121.5 g (0.54 mol) of metatrifluoromethylphenyl bromide and 230 g of tetrahydrofuran was placed in the dropping funnel, and the mixture was dropped into the reaction flask. After confirming the start of the reaction, reduce the remaining liquid to 50-60%
The mixture was added dropwise over a period of about 2 hours at a temperature of .degree. 3 at temperature after dropping
Heat for an hour and cool. In another dropping funnel, add 49.69 (0.16 mol) of bismuth trichloride and 2.2 mol of tetrahydrofuran.
00g of the mixed solution was added dropwise at a temperature of 30°C or lower. The reaction was completed by refluxing for 2 hours. Cool to 30℃
Hydrolysis was carried out by adding 200zQ of a saturated ammonium chloride aqueous solution at the following temperature.

If you decant the layer, take it out, filter it, and concentrate it, it will be 84.
．． 9g of solid was obtained. This was distilled under reduced pressure, bp, 17
0~! Colorless solid tri(
51 g of bismuth (metatrifluoromethylphenyl) was obtained. Melting point 35-36℃, gas chromatography purity 9
8.7%, Bi content 132.1% (theoretical value 32.4%
).

Production Example 2 Tri(methachlorophenyl)bismuth dichloride (compound 26) rθ 1) Tri(methachlorophenyl)bismuth (103.4 g (0.54 mol) of methachlorophenyl bromide instead of the compound metatrifluoromethylphenyl bromide)
By reacting in the same manner as in Production Example 1 using
I got it. Bi content 37.9% (theoretical value 38.4%), gas chromatography purity 99.9%.

2) Tri(methachlorophenyl) bismuth dichloride This tri(methachlorophenyl) bismuth 209C0,
037 mol) was dissolved in 100 ml of chloroform and placed in a reaction flask. 100 ml of a chloroform solution containing 39 (0,042 mol) of chlorine was added dropwise at 0°C.

After filtration, the chloroform in the filtrate was partially concentrated under pressure to drive it out, and methanol was added to precipitate crystals. This was taken out by filtration under reduced pressure and dried to obtain 13.39 of tri(methachlorophenyl)bismuth dichloride as a colorless solid. Melting point 83-85℃, chlorine content ff1l 1;6% (
Theoretical value 11.5%), bismuth content fTh34, 1%
(Theoretical value 3/i, 0%).

Production Example 3 Tri(methachlorophenyl)bismuth difluoride (compound 35) ρθ 5 g (0,008 mol) of tri(methachlorophenyl)bismuth dichloride obtained in Production Example 2 and 3.89 mol of potassium fluoride were placed in a reaction flask. 0,032 mol), acetone 50
The mixture was incubated for 2 days at room temperature.

When the solvent was partially concentrated under pressure and water was added, a pale brown solid precipitated. Remove the solid by vacuum filtration,
After washing with water, drying and recrystallizing with acetone, the melting point was 194.
Tri(methachlorophenyl)bismuth difluoride 2°19 was obtained as a colorless solid at ~197°C. Contains bismuth
136.4% (theoretical value 35°9%).

Production Example 4 Tri(methachlorophenyl)(hydroxy)bismuth chloride (compound 42) Place tri(methachlorophenyl)bismuth dichloride 59 (0,008 mol) synthesized in Production Example 2 and benzene 50xQ in an Erlenmeyer flask and dissolve. After that, add 28% ammonia water 29
was added and shaken vigorously for 2 to 3 minutes.

When the mixture was filtered and petroleum ether was added to the filtrate, a slightly yellow solid precipitated out. It was filtered under reduced pressure, taken out, and dried to obtain 3.4 g of tri(methchlorophenyl)(hydroxy)bismuth chloride as a pale yellow solid with a melting point (decomposition) of 139 to 143°C. Chlorine content, 6.1% (theoretical value 6.0
%), Bi-containing nail, 34.7% (theoretical value 35.1%).

Production Example 5 Tri(methachlorophenyl)bismuth diacetate (compound 49-1) In a reaction flask, tri(methachlorophenyl)bismuth dichloride)'5Li (0,008 mol) synthesized in Production Example 2, sodium acetate 2 .69 (0,032 mol)
, acetone 50 was added, and after reacting at room temperature for 4 hours, water was added to precipitate a yellow solid.

After filtering under reduced pressure, washing with water, drying, and recrystallizing with acetone, 2.8 g of tri(methchlorophenyl)bismuth diacetate was obtained as a pale yellow solid with a melting point of 158 to 160'C. 13i content f1131.0% (theoretical value 31.6%), chlorine content 0.1% or less.

Production Example 6 Triphenylbismuth dinitrate (Compound 51) l) Triphenylbismuth (Compound I) React in the same manner as in Production Example 1 using phenyl chloride 599 (0.52 mol) in place of metatrifluoromethylphenyl bromide. By recrystallizing with chloroform:methanol, colorless solid triphenyl bismuth 229 was obtained.

Melting point: 75-76°C, gas chromatography purity: 98.
3%, Bi content 147.1% (theoretical value 47.5%).

2) Triphenylbismuth dichloride (compound 1G) Using triphenylbismuth 16.39 (0,037 mol) in place of tri(methachlorophenyl)bismuth,
The reaction and treatment were carried out in the same manner as in Production Example 2.2) to obtain 13.8y of triphenyl bismuth dichloride as a pale yellow solid.

Melting point: 132-136°C, I3i content: 140.5% (theoretical value: 40.9%), chlorine content! 3°6% (theoretical value 13.
9%).

3) Triphenyl bismuth dinitrate In a reaction flask, dissolve triphenyl bismuth dichloride 59 (0.01 mol) synthesized as above in acetone 50112,
In this solution, 3.49 (0.02 mol) of nitrate radical was added to 50%
A solution dissolved in 50 g of ethanol water was added dropwise at room temperature. Insoluble materials were removed by filtration under reduced pressure, dried, extracted with acetone while hot, and allowed to cool to precipitate 2.1 g of triphenyl bismuth dinitrate as a colorless solid. Melting point (decomposition) 127-13
0℃, Bi-free! 37.3% (theory (a37, 0
%).

Production Example 7 Di(balachlorphenyl) bismuth iodide (compound 58) l) Tri(parachlorophenyl) bismuth (103.4 g (0.54 mol) of parachlorophenyl bromide instead of the compound metatrifluoromethylphenyl bromide)
The reaction was carried out in the same manner as in Production Example 1 using the following methods, followed by recrystallization with hexane to obtain tri(parachlorophenyl) bismuth 459 as a colorless solid with a melting point of 104 to 106°C. Gas chromatography pure [99.6%, Bi content 38.
8% (theoretical value 38°4%).

2) Di(parachlorophenyl)bismuth iodide In a reaction flask, tri(parachlorophenyl)bismuth 4y (0,0074 mol) synthesized as above, bismuth tribromide 1.7f (0,0037 mol), and tetrahydrofuran 50JIQ was added and refluxed for 4 hours.

After cooling, a methanol solution of 3.3 g of sodium iodide (50xQ) was added at room temperature, and the mixture was reacted at the same temperature for 6 hours. The solvent was partially removed under reduced pressure and water was added to precipitate a solid.

It is filtered under reduced pressure, dried, extracted with 50 ml of ethyl acetate while hot, concentrated, and washed with n-hexane to give red crystals of di(parachlorophenyl) bismuth iodide.4.
I got 39. Melting point (decomposition) 142-145°C, Bi content 37.0% (theoretical value 37.4%).

? J Preparation Example 8 Di(parafluorophenyl) bismuth cyanide (Compound 66) l) Tri(parafluorophenyl) bismuth (Compound 1
0) React in the same manner as in Production Example 1 using 94.59 (0.54 mol) of parafluorophenyl bromide instead of metatrifluoromethylphenyl bromide, recrystallize from methanol, and obtain a colorless product with a melting point of 92-93°C. 55.39 g of solid tri(barafluorophenyl)bismuth was obtained. Gas chromatography purity 99.9%, Bi-containing fj142,
1% (theoretical value 42.3%).

, 2) Di(parafluorophenyl)bismuth cyanide 59 (o, o + mol), bismuth tribromide 2.29 < 0.005 mol) synthesized as above were placed in a di(barafluorophenyl)bismuth cyanide reaction flask. , 50xQ of tetrahydrofuran was added and refluxed for 4 hours. After cooling, 1.5 g (0.03 mol) of sodium cyanide and 50xQ of methanol were added at room temperature, and the mixture was further stirred at room temperature for 4 hours. Some of the solvent was driven off and water was added to precipitate an oil. Extracted with chloroform and concentrated. When lSS condensed petroleum ether was added, a white solid precipitated. A white solid was taken out by filtration under reduced pressure, dissolved in acetone, and purified by adding petroleum ether to precipitate crystals again. Colorless solid of di(parafluorophenyl) bismuth cyanide 2.09
I got it. Melting point: 155°C (decomposition), Bi content: 149°6
% (theoretical value 49.2%).

? aP+9 Triphenyl bismuth 59 (0,
0,114 mol), bismuth tribromide 2, 6 g (0,00
57 mol) and tetrahydrofuran and 50 husks of rice were placed in a reaction flask and refluxed for 4 hours. Cool and add 2.2 g (0,034 mol) of sodium azide and 50 g of methanol at room temperature.
J! 12 was added thereto, and the mixture was further stirred at the same temperature for 4 hours. After partially expelling the solvent under reduced pressure, water was added to obtain a pale yellow solid. Recrystallization from a mixed solvent of acetone 20-hexane gave 1.4 g of a colorless solid of diphenyl bismuth azide. Melting point 164°C, Bi content 51.4% (theoretical value 5
1.6%).

Production Example 10 Methalyl bismuth di(phenyl sulfide) (Compound 93) 1) Tri(methlyl) bismuth (Compound 3) Methalyl bromide 92.49 (Q, 54 mol) was used instead of methatrifluoromethylphenyl bromide The reaction mixture was reacted in the same manner as in Production Example 1, and recrystallized from chloroform:methanol to obtain 54.0 g of tri(methacryl)bismuth, a colorless solid with a melting point of 48 to 49°C. Gas chromatography purity 99.9%, Bi content 43.2
% (theoretical value 43°3%).

2) Methatolyl bismuth di(phenyl sulfide) Tri(methatrile) synthesized as above in the reaction flask
Bismuth 1.99 (0,004 mol), bismuth tribromide 3.6 g (0,008 mol) and diethyl ether 5
1. Add 0 shochu and stir at room temperature for 1 hour. Ta.

Concentrate under reduced pressure to drive off diethyl ether, add acetone 5011ρ, filter, and dilute the filtrate with diophenol 2.
．． 69 (0,024 mol), triethylamine 2.4 g
(0,024 mol) and acetone (0,024 mol) at room temperature or below. After the dropwise addition, the mixture was further stirred at room temperature for 1 hour, water was added, and the mixture was filtered under reduced pressure to obtain a yellow solid. Recrystallization from acetonitrile yielded 1.5 g of a yellow solid of methalyl bismuth di(phenyl sulfide). Melting point 127-131'C (decomposed), Bi-containing fn41
, 8% (theoretical value 40.3%).

Production Example 11 Metachlorophenyl bismuth bis(dimedyl didiocarbamate) (Compound 107) 5.4 g of tri(methachlorophenyl) bismuth synthesized in Production Example 2 (
0.01 mol), 9.09 (0.02 mol) of bismuth tribromide, and 70zQ of jediyl ether were placed in a reaction flask and stirred at room temperature for 1 hour.

After concentrating under reduced pressure to drive off diethyl ether, 11.2 g of sodium dimedyl dithiocarbamate dihydrate (
0,063 mol) and 100xQ of acetone were added, and the mixture was stirred at room temperature for 2 hours. Part of the acetone was expelled under reduced pressure, water was added, and the mixture was filtered under reduced pressure to obtain 16.0 g of a yellow solid.

When recrystallized with acetonitrile, yellow crystals of methachlorophenyl bismuth bis(nomedyl didiocarbame) 1
1.8g was obtained.

Melting point>145°C (decomposition), Bi content 39.3% (theoretical value 38.8%).

Production Example 12 Metafluorophenyl bismuth dibromide/dipyridine adduct (Compound 110) 1) Tri(metafluorophenyl) bismuth (Compound 9) Metafluorophenyl bromide 94.5 g (0,54 mol) in the same manner as in Preparation Example I and recrystallized from methanol to obtain 48.59 mol of tri(metafluorophenyl) bismuth, a colorless solid having a melting point of 67-68'C. Gas chromatography purity 98.0%, Bi-containing ffk42.
6% (theoretical value 42.3%).

2) Metafluorophenyl bismuth dibromide/dipyridine adduct 3 g (0,006 mol) of tri(metafluorophenyl) bismuth synthesized as above, 5.4 g (0,012 mol) of bismuth tribromide, and diethyl ether were placed in a reaction flask. 50xQ was added thereto, and the mixture was stirred at room temperature for 1 hour. Under reduced pressure
The diethyl ether was expelled, and A7Tone 50xQ was added and filtered. The filtrate was added dropwise to a mixed solution of 50 pieces of acetone and 2.8 g (0,018 mol) of pyridine at room temperature. After the dropwise addition, the mixture was filtered, and the filtrate was partially concentrated under reduced pressure, and petroleum ether was added to precipitate a metafluorophenyl bismuth dibromide/dipyridine adduct (3.59 g) as pale yellow crystals.

Melting point>140°C (decomposed), Bi content 34.3% (theoretical value 33.6%).

Production Example I3 Di(methachlorophenyl)bismuth bromide/tetramedylammonium chloride adduct (compound 75) Cθ 4 g (0,007 mol) of tri(methachlorophenyl)bismuth obtained in Production Example 2.1), tri-odor Bismuth! .

7 g (0,0037 mol) and tetrahydrofuran 5
0 mg was placed in a reaction flask and heated under reflux for 4 hours. Concentrate under reduced pressure to drive off tetrahydrofuran, add 50x methanol and filter.The filtrate was added to a mixture of 1.29 (o, ot t mol) of tetramethylammonium chloride and 50 ml of methanol at room temperature. added.

After heating under reflux for 20 minutes, methanol was expelled under reduced pressure, dissolved in acetone 50112, and n-hexano was added to give 2.6 g of di(methchlorophenyl) bismuth bromide tetramedylammonium chloride adduct as colorless crystals. Obtained. Melting point 155°C (decomposition), BrCQ,
Contains 219.0% (theoretical value 18.6%), Bi-contains fn33
．． 6% (theoretical value 33°6%).

Other compounds according to the present invention were synthesized in the same manner as in the above production examples. Table 1 below shows those compounds.

person-upper 2)! =3, t=2 4) s=3, t=2 5) s-2, t=1 6)! 1=2- t=1 8) s=I, L=1 Note: In the above table, φ represents a phenyl group.

Examples are given below to explain the preparation method of the preparation of the present invention containing the above-mentioned compound as a main component.

Example 1 10% by weight of the compound of the present invention is thoroughly mixed with 90% by weight of lactose to form a 10-fold powder. At the time of administration, 0.0% of this was administered as feed. O1
Use diluted to an active substance concentration of ~0.05%.

Example 2 10% by weight of the compound of the present invention is thoroughly mixed with 90% by weight of starch to form a 10-fold powder. At the time of administration, 0.0% of this was administered as feed. O1
Use diluted to an active substance concentration of ~0.05%.

Example 3 25 parts by weight of the compound of the present invention and 75 parts by weight of wheat flour are uniformly mixed to form a powder. At the time of administration, 0.0% of this was administered as feed. O1
Use diluted to an active substance concentration of ~0.05%.

Effects The preparation of the present invention has low toxicity to poultry to which it is administered, but is effective in preventing and treating coccidiosis in poultry.

Table 2 below shows some of the results of the toxicity tests.

The in vivo anticoccidial effect of the formulation of the present invention was investigated as shown in the following test example.

Test Example 1) Test Method A group of five white Regpon chicks aged 7 to 10 were infected with 50,000 spore-forming oocysts of Eimeria tenella per bird.

The sample was added to the feed from the day before infection and administered continuously for 9 days.
Necropsy was performed on the 8th day after infection, cecal lesions were observed, and the extent of bloody stool excretion, survival rate, relative weight gain, and cecal lesion values were calculated.

2) Test results Coccidiosis in chicken chicks (Eimeria tenella)
Table 3 shows the results of in-vivo tests for.

In the table, the following words have the following meanings:

Relative weight gain: The weight gain of the test group is expressed as a ratio to the weight gain of the uninfected control group.

Excretion of bloody stool: The results of evaluating the degree of bloody stool excreted per 5 birds during the test period on a 4-grade scale from - to +++ are shown.

1: No bloody stool excretion is observed.

+: Mild bloody stool excretion ++: Moderate bloody stool excretion +++: Same as the infection-free control group Frequent hematochezia Cecal lesion value: Based on Merck's test method.

Surviving chicks were sacrificed 8 days after infection. and visually observe the cecal lesions. The degree of the lesion was divided into 0 to 4. (severe is rated 4, disease is (If there is no change, it is set as 0) Determine the strength of It is expressed as the average value.

13 Coccidiosis in chicken chicks (Eimeria
Preventive effect against (Tenella)

Claims (1)

[Claims] 1. General formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, A is hydrogen, fluorine, chlorine, methyl, methoxy or trifluoromethyl, and s is 1 An integer of ~3, t is 0 to 2
is an integer of , and when s is 1, t is 1 or 2,
When t is 1, Q is -Br_2 (pyridine)_2 or -
Br_2 (dipyridyl), when t is 2, Q represents phenylthio, N,N-dimethylaminothiocarbonylthio, when s is 2, t is 1, and Q is iodine, cyano,
represents azide, -Br (phenyltrimethylammonium halide), -Br (tetramethylammonium halide), or -Br (tetraethylammonium halide), and when s is 3, t is 0, 1 or 2, When t is 1, Q represents -Cl(OH), and when t is 2, Q represents fluorine, chlorine, acetoxy or nitrate. 2. 0.01% by weight of the compound represented by general formula (I)
The poultry anticoccidial agent according to item 1, containing the poultry anticoccidial agent in a proportion of ~0.08% by weight.