Coccidian_Kain Industrial Additives

[Background and Overview]^[1][2][3]

Coccidiosis is caused by one or more of the nine types of coccidia (the nine types of coccidiosis are: heap type, Brucella type, Hardi type, giant type, metamorphic type, slow type, poisonous type Type, precocious type, tender type) is an acute epidemic disease caused by parasitizing the epithelial cells of the intestinal mucosa of poultry. Poultry eats infectious oocysts, and the oocyst sporozoites invade the poultry intestinal mucosal epithelial cells and reproduce asexually, causing intestinal wall rupture and bleeding. Then the coccidia enter the sexual reproduction stage, produce oocysts, and are excreted in the chicken feces. . After chickens are infected with coccidiosis, they become depressed, have inverted feathers, drooped wings, loss of appetite, and feces stained around the cloaca, and then develop ataxia (ataxia refers to neurological symptoms of unsteady gait), drink a lot of water, and have distended crops. , watery feces or blood in the stool, anemia, weight loss, a large number of chicks will die, and adult chickens will have intermittent diarrhea, resulting in reduced meat and egg production, reduced quality, and huge losses. In addition, ducks, geese, turkeys, rabbits, etc. will also suffer from coccidiosis to varying degrees, so coccidiosis is a major threat to the breeding industry. In order to prevent the outbreak of coccidiosis in chickens, in addition to using hot steam to disinfest the poultry houses, the most effective way is to regularly add drugs to prevent coccidiosis in the feed. As early as 1936, someone discovered that adding 1.5% sulfur to feed could effectively reduce the mortality rate of Eimeria tenella. However, sulfur was highly toxic and was not widely used. By 1939, it was discovered that sulfonamide drugs could inhibit six species of coccidia, and drugs such as sulfaquexalin and sulfamethazine were developed, but they had side effects. Since the 1960s, a variety of new drugs have been developed, mainly antibiotics, quinolines, pyridines, thiamine derivatives and benzoic acid drugs. Coccidia quickly develop resistance to these drugs,

Ethopabate is also called Ethopabate. Its main chemical component is 4-acetamido-2-ethoxybenzoic acid methyl ester. When mixed with other coccidial drugs, it can not only inhibit the excretion of infected Eimeria giant oocysts in chickens, block the synthesis of tetrahydrofolate in the para-aminobenzoic acid-folic acid metabolism pathway to exert anti-coccidial effects, but also be effective Delay resistance.

[Physical and chemical properties]^[2]

Pure coccidian is white to pink crystal, soluble in methanol, ethanol, acetone, ethyl ester, insoluble in isopropenol, methyl chloride, and insoluble in water and isooctane. Its melting point is 148-149°C.

[Pharmacological effects]^[3]

The combined use of coccidiostrobin with other drugs can not only inhibit the excretion of infected Eimeria giant oocysts in chickens, but also block the synthesis of tetrahydrofolate in the para-aminobenzoic acid-folic acid metabolism pathway to exert anti-coccidial effects It can also effectively delay drug resistance, is highly efficient, non-toxic, non-mutagenic, non-carcinogenic, and has no accumulation in the poultry body.

[Application]^[1][2]

Coccidiostrobin is used as a feed additive to prevent and treat coccidiosis in chickens. Chickens should start taking medicine from 12 or 15 days after birth and continue to use until 60 days of age. Rabbits should be treated within four months of age. Add 1 gram of original drug to every 2 kilograms of feed and mix it evenly into the feed. After consumption, it can reduce mortality and increase weight by about 20%. Coccidiostrobin can be used alone (mix 40 grams of the original drug per ton of feed and mix evenly in the feed), or it can be mixed with other agents to form a variety of broad-spectrum anti-coccidial drugs, such as coccidiostrobin 4%. Used in combination with 25% amproline, its trade name is compound amproline; fortified amproline composed of 20% amproline, 1% coccidiolin, and 12% sulfaquinoline. Experiments have shown that after feeding 6-week-old chicks with compound amproline for 2 weeks and inoculating them with 30,000 units of Eimeria brucei oocysts, the survival rate of the drug group was 100%, and the survival rate of the control group was 80%. Using amprolin 113.5g/T, coccidian 3.6g/T, and clindamycin 2-4g/T, mixed into the feed can also effectively prevent and treat coccidiosis and increase body weight growth. Tolerance experiments on coccidian show that the concentration in the feed is below 80 to 100 mg/L, which will not have a significant negative effect on the growth of chickens.

【Preparation】^[3]

A: Grind 8.0g of the industrial crude product p-aminosalicylic acid into fine particles, mix with anhydrous methanol, heat until p-aminosalicylic acid is completely dissolved, and cool. Add 8 ml of concentrated sulfuric acid dropwise, and reflux for 8 to 10 hours. After the reaction is completed, evaporate the methanol. When about 10 m of liquid remains, cool, add saturated sodium carbonate solution until neutral, and a small gray solid will precipitate. Filter with suction. . The solid was recrystallized from a 3:2 solution of methanol:water to obtain a pink-purple product. The yield is 40~55%, and the melting point is 117~121℃.

B: Add 20 ml of chloroform, 1.0 ml of ester anhydride, and 1.7 g of the product from the previous step into the reaction bottle. Heat and reflux for 2 hours. The reaction solution will be homogeneous black. Steam off the chloroform. When a solid precipitates, add 1:1 ethanol aqueous solution, heat to dissolve and recrystallize, a light-colored solid will be generated, filter and dry to obtain a silvery white soft solid. The yield is 80%, and the melting point is 148~151℃.

C: Put 4.0g of acylation product and 2.5ml of ethyl iodide into a three-necked flask, add 12ml of DMF and 2.1g of potassium carbonate, stir, reflux at 50-60°C for 6 hours, and immediately pour the reactant into ice water. , a brown solid is produced. Dissolve the solid with n-hexane and toluene (1:1), heat to reflux, and recrystallize. After many experiences�After recrystallization, the product is a silver-white solid. The yield is 80%, and the melting point is 149~151℃.

[Main reference materials]

[1] Si Zongxing. Research on the synthesis of coccidioidal synergist-coccidiostrobin [J]. Chinese Chemical Bulletin, 1998 (5): 57-59.

[2] Jiang Zuopei, Sun Yuqin, Lou Guiqi. Feed additive—coccidyl[J]. Shanghai Chemical Industry, 1987, 1: 18-19.

[3] Zhang Heng, Yang Jianshe. Research on the synthesis of coccidian[J]. Feed Industry, 2002, 23(6): 37-38.