Crystallizing method of erythromycin
The present invention provides an erythromycin crystallizing method, which comprises using dichloromethane containing solvent as a preparation solvent, and the dichloromethane solution of erythromycin received was gradiently cooled from high temperature down to low temperature, and thus making erythromycin crystallize. According to the method of the present invention, the content of erythromycin A is high, the content of erythromycin A in the erythromycin crystalline is more than 94.5% (HPLC detection method), the content of dichloromethane in the erythromycin crystalline is less than 600 ppm, the content of water in the erythromycin crystalline is less than 2.5%, the microbiological titre of the erythromycin crystalline is more than 940 μ/mg.
1. A method for recrystallizing erythromycin, comprising the steps:
(1) first dissolving erythromycin or an erythromycin salt in dichloromethane or a solvent mixture comprising dichloromethane under alkaline condition to form an erythromycin solution, wherein the pH of the erythromycin solution is from 8.6 to 12;
(2) then cooling the erythromycin solution gradiently from 37° C. to −5° C. to form a suspension of erythromycin crystals, wherein a temperature is gradiently cooled from 37° C. to −5° C. at a cooling rate of 1° C. to 10° C. per hour for a recrystallization time period from 2 hours to 36 hours;
(3) then separating the erythromycin crystals from the suspension; and
(4) finally washing and drying the crystals.
2. The method of claim 1 , wherein the solvent mixture comprising dichloromethane further comprises a solvent selected from the group consisting of ethanol, acetone, ethyl acetate and butyl acetate; and the volume content of dichloromethane in the solvent mixture is from 60 to 100%.
3. The method of claim 1 , wherein the amount of erythromycin A in the erythromycin solution is from 4 to 20%.
4. The method of claim 1 , wherein the temperature of the erythromycin solution is kept at 23-28° C. for 1 to 10 hours during the gradient cooling.
5. The method of claim 1 , wherein an organic solvent or pure water is used for washing.
6. The method of claim 5 , wherein the organic solvent comprises more than 90% of dichloromethane and another organic solvent component, wherein the organic solvent component is an alcohol, ketone or ester.
7. The method of claim 2 , wherein the amount of erythromycin A in the erythromycin solution is from 4% to 20%.
8. The method of claim 2 , wherein an organic solvent or pure water is used for washing.
9. The method of claim 3 , wherein an organic solvent or pure water is used for washing.
10. The method of claim 4 , wherein an organic solvent or pure water is used for washing.