Azacitidine preparation and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and provides an azacitidine injection and a preparation method thereof. Injection is prepared from azacitidine, glycerol, poloxamer 188, sodium pyrosulfite, a pH regulator and injection water. The preparation method comprises the following steps: adding sodium pyrosulfite and azacitidine into injection water, regulating pH value to 5.6-6.7after uniformly stirring, adding glycerol and poloxamer 188, supplementing injection water to total preparation amount, uniformly stirring and mixing to regulate the pH value to 5.5-6.5, stirring, filtering, filling, heat-sealing, performing lamp inspection and packaging. The azacitidine preparation is filled through an ampoule bottle, so that the risk that azacitidine injection has turbidity ata high temperature is avoided, and solubility of the product is preferably improved by a flow aid and an anti-oxidant. The preparation is stable in mass, is simple in process; after injection preparation is stored for a long time, various indexes are detected to not generate obvious changes, so that safety of clinical application of a pharmaceutical preparation is improved.

Description

[0001] This application is a divisional application, the original patent number is: 201810058694.2, the application date is January 22, 2018, and the title of the invention is: a preparation of azacitidine and a preparation method thereof. Technical field [0002] The invention relates to the field of drug synthesis technology, in particular to a preparation of azacitidine and a preparation method thereof. Background technique [0003] Myelodysplastic syndrome (MDS) is a group of diseases characterized by clonal abnormalities of hematopoietic stem cells, which can lead to hematopoietic failure and have a high risk of developing acute myeloid leukemia (AML). The disease is divided into 5 types, namely refractory anemia (RA), ring sideroblastic anemia, refractory anemia with increased blasts (REAB), refractory anemia with increased blasts-conversion (RAEB) -T) and chronic myelomonocytic leukemia (CMML). [0004] Azacitidine, whose chemical name is 1-(β-D-ribofuranosyl)-4-amino-1,3,5-...

AI Technical Summary

Problems solved by technology

[0011] Patent CN201310727931.7 discloses azacitidine for injection and its preparation method. The prescription amount of azacitidine and mannitol is mixed and added to water for injection, stirred until completely dissolved, filtered, sub-packaged, freeze-dried, and freeze-dried. The temperature in the drying process is difficult to control, and the control of temperature leads to the increase of impurities, which brings certain safety factors to clinical medicine.

[0012] The inventor found in the test that the appearance of azacitidine injection will change from a colorless and clear liquid to a milky white liquid with flocs under the influence of 20°C. Furthermore, the azacitidine injection uses Filling with pre-filled syringes, but the cost of packaging materials for pre-filled syringes is high, the production cycle is long, and the requirements for filling and stoppering of equipment are high. The injection is filled in ampoules, but the process of melting and sealing the ampoules at high temperature will also cause the appearance of azacitidine injection to change from a colorless clear liquid to a milky white liquid with flocs. The inventor has done a lot of experiments It was found that none of the current technologies can solve this problem

Images