Prednisolone refining technology

Abstract

The invention discloses a prednisolone refining technology, and belongs to the field of chemical pharmacy. The refining technology adopting finished prednisolone as a raw material and a dichloromethane, methanol and water mixed solution as a refining solvent system comprises the following steps: adding a Girard's reagent T and glacial acetic acid to the refining solvent system, adding the raw material prednisolone, carrying out stirring heating to realize refluxing dissolving, then refluxing for a period of time, cooling the obtained solution, and adding water to the above obtained system in a dropwise manner at a proper temperature under a controlled speed to slowly precipitate prednisolone in dropwise addition process in order to obtain refined prednisolone. The technology is in favor of improving the product quality and increasing the enterprise benefit.

Description

Technical field [0001] The invention relates to a manufacturing process of prednisolone, in particular to a refining process of prednisolone, and belongs to the field of chemical pharmacy. Background technique [0002] The chemical name of prednisolone is: 11β, 17α, 21-trihydroxypregna-1,4-diene-3,20-dione, which is an adrenal cortex hormone drug. It has anti-inflammatory and immunosuppressive, anti-toxic and anti-shock effects. [0003] The chemical structural formula is: [0004] [0005] Prednisolone is based on prednisone acetate as the starting material. The ketone groups at C3 and C20 are protected by semicarbazone, and the ketone group at C11 is reduced with potassium borohydride to make β-OH, and then C3 is removed. , C20 protecting group and hydrolyzing C21 acetyl group to get prednisolone. The starting material, prednisone acetate, is obtained by biological dehydrogenation of cortisone acetate. Prednisone acetate contains a certain amount of cortisone acetate impurities....

AI Technical Summary

Problems solved by technology

And starting material prednisolone acetate is obtained through biological dehydrogenation by cortisone acetate, can contain a certain amount of cortisone acetate impurity in the prednisolone acetate, in the prednisolone process, the cortisone acetate impurity also During the process, the ketone groups at the C3 and C20 positions are protected by semicarbazone, and the ketone groups at the C11 position are reduced with potassium borohydride to become β-OH, and then the protecting groups at the C3 and C20 positions are removed and the C21 positions are hydrolyzed. The acetyl group of the hydrocortisone is converted into hydrocortisone. The structure of prednisolone and hydrocortisone only differs by a 1,2 double bond, and the polarity is very similar. The traditional refining process adopts the method of methanol system recrystallization. Generally, the content of impurity hydrocortisone in the finished product of prednisolone obtained by recrystallization and refining twice is between 0.5-1.0%, while high-quality standard prednisolone generally requires the content of impurity hydrocortisone to be 0.5% within 0.3% or 0.1%, because the structures of prednisolone and hydrocortisone only differ by a 1,2 double bond, and the polarities are very similar, the traditional method of methanol recrystallization refines The impurity content of hydrocortisone in the product obtained by prednisolone is not good, generally need multiple recrystallizations to make the content of hydrocortisone in prednisolone reach within 0.5% or 0.3%, and the content of hydrocortisone within 0.1% The method of methanol recrystallization is impossible to reach at all, so prepare high-standard prednisolone with methanol recrystallization process, can make product yield lower, so just increased production cost greatly