Azacitidine preparation and method for preparing same

Abstract

The invention belongs to the technical field of medicines, and provides azacitidine injection. The azacitidine injection comprises azacitidine, glycerin, poloxamer 188, sodium metabisulfite, pH (potential of hydrogen) regulators and water for injection. A method for preparing the azacitidine injection includes adding the sodium metabisulfite and the azacitidine into the water for injection, uniformly stirring the sodium metabisulfite, the azacitidine and the water for injection to obtain medicine liquid and then regulating the pH of the medicine liquid by the pH regulators until a pH value ofthe medicine liquid reaches 5.6-6.7; adding the glycerin and the poloxamer 188 into the medicine liquid, replenishing the water for injection until the quantity of liquid reaches the total preparationquantity, uniformly stirring and mixing the liquid until a pH value of the liquid reaches 5.5-6.5, and carrying out stirring, filtering, filling, sealing, lamp inspection and packaging to obtain theazacitidine injection. The azacitidine injection and the method have the advantages that ampoule bottles are filled with the azacitidine injection, and accordingly risks of turbidity of the azacitidine injection due to the high temperatures can be prevented; the solubility of the azacitidine injection which is a product is preferably improved by flow agents and antioxidants, the azacitidine injection which is a preparation is stable in quality, processes for the azacitidine injection are simple, various detected indexes are free of obvious change after the azacitidine injection which is the preparation is stored for a long term, and the clinical use safety of the medicinal preparation can be improved.

Description

technical field [0001] The invention relates to the field of pharmaceutical synthesis technology, in particular to a preparation of azacitidine and a preparation method thereof. Background technique [0002] Myelodysplastic syndrome (MDS) is a group of diseases characterized by clonal abnormalities of hematopoietic stem cells, which can lead to hematopoietic failure and a high risk of progression to 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-transition (RAEB) -T) and chronic myelomonocytic leukemia (CMML). [0003] Azacitidine (Azacitidine), the chemical name is 1-(β-D-ribofuranosyl)-4-amino-1,3,5-triazin-2(1H)-one, is a DNA developed by Pharmion Company of the United States. Methyltransferase inhibitors, first listed in the United States in July 2004, trade name Vidaza (Vidaza). Its mechanism of action i...

AI Technical Summary

Problems solved by technology

[0010] 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.

[0011] In the experiment, the inventor found that the appearance of azacitidine injection will change from a colorless 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

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