Preparation method of imidocarb dipropionate sterile APIs (active pharmaceutical ingredients)

Abstract

The invention discloses a preparation method of imidocarb dipropionate sterile APIs (active pharmaceutical ingredients), and belongs to the field of veterinary drugs. The method comprises the following steps: 1) mixing imidocarb with purified water in a weight ratio of 1:3-10, stirring the obtained product so as to obtain suspension liquid, heating the suspension liquid to 30-40 DEG C, dropwise adding propionic acid, and stirring for reacting the obtained mixture, so that an initial liquid medicine is obtained; 2) treating the initial liquid medicine by using a sterilizing and filtrating system, so that a sterile liquid medicine is obtained; and 3) carrying out spray drying on the sterile liquid medicine in a sterile environment, so that sterile APIs disclosed by the invention are obtained. According to the invention, by taking the purified water as a solvent, imidocarb and propionic acid are reacted so as to form a salt, then the salt is dissolved, and after sterile filtrating is performed, the obtained product is directly sprayed for preparation. Compared with traditional processes, firstly, a prepared product is a sterile API, so that the convenience and security of the prepared product are increased; and secondly, water is taken as a solvent and directly subjected to spray drying, the yield is above 95%, and the solvent is cheap, therefore, the preparation method is low in cost, simple and convenient in operation, and suitable for large-scale industrial production.

Description

technical field

[0001] The technical field of veterinary drug raw materials of the present invention, in particular to a preparation method of imidazolidin dipropionate aseptic raw materials. Background technique

[0002] Imidazuron dipropionate is a kind of propionate of imidazuron, which is a new type of anti-protozoal chemical drug specially used for animals. It is usually made into preparations of dipropionate or bishydrochloride in clinical practice. Or subcutaneous injection, for the treatment and prevention of various diseases caused by babesiosis, piroplasma, trypanosoma, eperythrocytic cells, borderworms and Theileria.

[0003] In the prior art, imidazolium dipropionate is a non-sterile raw material drug, and the preparation method is recrystallization after synthesis of imidazuron and propionic acid in different organic solvents. This method requires a large amount of organic solvents, and a large amount of The recrystallization mother liquor causes a large loss o...

Examples

Embodiment 1

[0017] A kind of preparation method of imidazolone dipropionate aseptic crude drug, the steps are as follows:

[0018] 1) Add 34.8kg of imidazolium to 104.4kg of purified water, mix well 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 to react (reaction solution dissolved) to obtain the initial drug solution.

[0019] 2) Pass the initial liquid medicine through the diaphragm pump and the third-stage filter respectively, and pressurize the pump to control the delivery speed of the liquid to 1.0kg / min; in the third-stage filter, the pore size of the first-stage filter element is 0.5um , the pressure is 4bar; the pore diameter of the second stage filter element is 0.2um, the pressure is 4bar, the pore diameter of the third stage filter element is 0.2um, and the pressure is 1.5bar; the sterile medicinal solution is obtained after filtration.

[0020] 3) Spray and dry the sterile ...

Embodiment 2

[0022] A preparation method of imidazuron dipropionate aseptic bulk drug, the steps are as follows:

[0023] 1) Add 34.8kg of imidazolium to 208.8kg of purified water, mix well and stir to form a suspension; heat the suspension to 35°C, control the temperature to maintain 35°C, add 17.0kg of propionic acid dropwise, and stir to react (reaction solution dissolved) to obtain the initial drug solution.

[0024] 2) Pass the initial liquid medicine through the diaphragm pump and the third-stage filter respectively, and pressurize the delivery speed of the liquid to be 1.5kg / min when passing through the diaphragm pump; the pore size of the first-stage filter element in the three-stage filter filtration is 0.5 microns , the pressure is 5.1bar; the pore size of the second-stage filter element is 0.2 micron, the pressure is 5.1bar, the pore size of the third-stage filter element is 0.2 micron, and the pressure is 1.8bar; the sterile medicinal solution is obtained after filtration.

[...

Embodiment 3

[0027] A preparation method of imidazuron dipropionate aseptic bulk drug, the steps are as follows:

[0028] 1) Add 34.8kg of imidazolium to 348kg of purified water, mix well and stir to form a suspension; heat the suspension to 40°C, control the temperature to maintain 40°C, add 14.8kg of propionic acid dropwise, and stir to react (the reaction solution dissolves ) to get the initial drug solution.

[0029] 2) Pass the initial liquid medicine through the diaphragm pump and the third-stage filter respectively, and pressurize the pump to control the delivery speed of the liquid to 2.0kg / min; in the third-stage filter, the pore size of the first-stage filter element is 0.5um , the pressure is 6bar; the pore diameter of the second-stage filter element is 0.2um, the pressure is 6bar, the pore diameter of the third-stage filter element is 0.2um, and the pressure is 2bar; the sterile medicinal solution is obtained after filtration.

[0030] 3) Spray and dry the sterile medicinal li...

technical field

[0001] The technical field of veterinary drug raw materials of the present invention, in particular to a preparation method of imidazolidin dipropionate aseptic raw materials. Background technique

[0002] Imidazuron dipropionate is a kind of propionate of imidazuron, which is a new type of anti-protozoal chemical drug specially used for animals. It is usually made into preparations of dipropionate or bishydrochloride in clinical practice. Or subcutaneous injection, for the treatment and prevention of various diseases caused by babesiosis, piroplasma, trypanosoma, eperythrocytic cells, borderworms and Theileria.

[0003] In the prior art, imidazolium dipropionate is a non-sterile raw material drug, and the preparation method is recrystallization after synthesis of imidazuron and propionic acid in different organic solvents. This method requires a large amount of organic solvents, and a large amount of The recrystallization mother liquor causes a large loss o...

Examples

Embodiment 1

[0017] A kind of preparation method of imidazolone dipropionate aseptic crude drug, the steps are as follows:

[0018] 1) Add 34.8kg of imidazolium to 104.4kg of purified water, mix well 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 to react (reaction solution dissolved) to obtain the initial drug solution.

[0019] 2) Pass the initial liquid medicine through the diaphragm pump and the third-stage filter respectively, and pressurize the pump to control the delivery speed of the liquid to 1.0kg / min; in the third-stage filter, the pore size of the first-stage filter element is 0.5um , the pressure is 4bar; the pore diameter of the second stage filter element is 0.2um, the pressure is 4bar, the pore diameter of the third stage filter element is 0.2um, and the pressure is 1.5bar; the sterile medicinal solution is obtained after filtration.

[0020] 3) Spray and dry the sterile ...

Embodiment 2

[0022] A preparation method of imidazuron dipropionate aseptic bulk drug, the steps are as follows:

[0023] 1) Add 34.8kg of imidazolium to 208.8kg of purified water, mix well and stir to form a suspension; heat the suspension to 35°C, control the temperature to maintain 35°C, add 17.0kg of propionic acid dropwise, and stir to react (reaction solution dissolved) to obtain the initial drug solution.

[0024] 2) Pass the initial liquid medicine through the diaphragm pump and the third-stage filter respectively, and pressurize the delivery speed of the liquid to be 1.5kg / min when passing through the diaphragm pump; the pore size of the first-stage filter element in the three-stage filter filtration is 0.5 microns , the pressure is 5.1bar; the pore size of the second-stage filter element is 0.2 micron, the pressure is 5.1bar, the pore size of the third-stage filter element is 0.2 micron, and the pressure is 1.8bar; the sterile medicinal solution is obtained after filtration.

[...

Embodiment 3

[0027] A preparation method of imidazuron dipropionate aseptic bulk drug, the steps are as follows:

[0028] 1) Add 34.8kg of imidazolium to 348kg of purified water, mix well and stir to form a suspension; heat the suspension to 40°C, control the temperature to maintain 40°C, add 14.8kg of propionic acid dropwise, and stir to react (the reaction solution dissolves ) to get the initial drug solution.

[0029] 2) Pass the initial liquid medicine through the diaphragm pump and the third-stage filter respectively, and pressurize the pump to control the delivery speed of the liquid to 2.0kg / min; in the third-stage filter, the pore size of the first-stage filter element is 0.5um , the pressure is 6bar; the pore diameter of the second-stage filter element is 0.2um, the pressure is 6bar, the pore diameter of the third-stage filter element is 0.2um, and the pressure is 2bar; the sterile medicinal solution is obtained after filtration.

[0030] 3) Spray and dry the sterile medicinal li...