Background and overview[1]
Imidocal dipropionate is a propionate salt of imidazole urea and is a new antiprotozoal chemical drug specifically for animals. In clinical practice, it is generally made of its dipropionate or bishydrochloride. Preparations, by intramuscular or subcutaneous injection, are used for the treatment and prevention of various diseases caused by babesiosis, piroplasmosis, trypanosomatosis, epierythrozoon, anaplasma marginale and theileria. In the prior art, imidazole dipropionate is a non-sterile raw material drug, and the preparation method is to synthesize imidazole and propionic acid in different organic solvents and then recrystallize. This method requires a large amount of organic solvents, and a large amount of The recrystallization mother liquor causes a large loss of product, and the recovery of the solvent consumes high energy. With the discovery of new clinical uses of imidocal dipropionate, such as the disclosed preparation method of imidocal dipropionate long-acting preparation for veterinary use and the disclosed method of imidocal dipropionate for veterinary use in epierythrozoonosis Compound preparations and preparation methods, etc. It is more difficult to produce compound preparations using non-sterile imidazole dipropionate raw materials.
Apply[2]
Imidocal dipropionate is effective against Babesia bibudae, Babesia bovis, Babesia ovatus, Babesia crossbow, Babesia equi, Babesia gibsoni, Babesia moselii and sheep Both Theileria and Anaplasmosis have specific effects. And it is not metabolized by the body in the body and is eliminated slowly, so the plasma concentration can be maintained for a long time. It can be injected intravenously or intramuscularly. This drug is excreted slowly and can directly act on the insect body, causing nuclear expansion and disintegration. Its toxicity, dosage, safety range, and efficacy are better than quinolin urea sulfate, triazine, yellow pigment, trypan blue, primaquinoline phosphate, oxydiphenylurea, m-phenylurea, and neoplastamine , and has a good preventive effect. It is currently the best diphenylurea anti-piroplasm drug and has good social value and application value. The drug is also the only drug approved for anti-piroplasmosis treatment in the United States.
Preparation[1]
A method for preparing sterile raw material of imidazole dipropionate, the steps are as follows:
1) Add 34.8kg of imidazole to 104.4kg of purified water, mix evenly and stir to form a suspension; heat the suspension to 30°C, control the temperature to maintain 30°C, add 14.8kg of propionic acid dropwise, and stir for reaction (The reaction solution dissolves) to obtain the initial solution.
2) Pass the initial liquid through the diaphragm pump and the third-stage filter respectively. When passing through the diaphragm pump, the speed of the liquid is pressurized and controlled to be 1.0kg/min; the pore size of the first-stage filter element in the three-stage filter filtration The pore size of the second-stage filter element is 0.2um and the pressure is 4bar; the pore size of the third-stage filter element is 0.2um and the pressure is 1.5bar; the sterile liquid is obtained after filtration.
3) Spray dry the sterile liquid in the sterile area. The spray conditions are: inlet air temperature 130-135℃, outlet air temperature 60-65℃, feeding speed 1.0kg/min, hot air flow 12m3/ min; the spray-dried product was packaged under aseptic conditions; a total of 47.6kg of sterile imidazole dipropionate raw material was obtained, with a molar yield of 96.0%.
Main reference materials
[1]CN201410806993.1 Preparation method of sterile raw material of imidocarb dipropionate
[2] Research on the synthesis of an anti-piroplasm drug imidazole and its salt
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