Freeze-drying process of asparaginase for injection

Abstract

The invention relates to a freeze-drying process of asparaginase for injection. The freeze-drying process comprises the following steps: S1: placing bottles for separately containing medicinal liquid in a freeze dryer in a form of square matrixes, wherein the square matrixes has a length of 210-420 mm and a width of 210-420 mm, and a distance between the square matrixes is 30-60 mm; S2: cooling a shelf of the freeze dryer to be -40 DEG C or lower at a rate of 30-35 DEG C per hour, performing heat preservation for 1-2 hours after cooling a product to be -40 DEG C or lower, heating the shelf to -15 to -20 DEG C, performing heat preservation for 1-2 hours, and then cooling the shelf to -45 DEG C and performing heat preservation for 1-2 hours; S3: evacuating, starting to rise the temperature when the vacuum degree reaches 20 Pa or lower, heating the shelf to 23 DEG C at a heating rate of 8 DEG C per hour, performing heat preservation for 2-4 hours; S4: corking, breaking and discharging to obtain a finished product of asparaginase for injection. The freeze-drying process provided by the invention can be carried out to obtain the asparaginase with good appearance, good compound solubility and stable quality by researching a pre-freezing process of asparaginase.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a freeze-drying process of asparaginase for injection. Background technique [0002] Asparaginase is an antitumor drug derived from an enzyme preparation from Erwinia, which has certain curative effects on acute lymphoblastic leukemia (ALL), acute myeloid leukemia, acute monocytic leukemia, and malignant lymphoma, and has a certain effect on Acute lymphoblastic leukemia works best. [0003] At present, asparaginase for injection in domestic clinical use is in the form of freeze-dried powder injection, mainly produced by Kyowa Hakko Industry Co., Ltd. of Japan and Merck of the United States, with specifications of 5,000 units or 10,000 units each. The asparaginase freeze-dried powder for injection consists of asparaginase and mannitol. The existing freeze-drying process of asparaginase usually needs two processes of sublimation drying and analytical drying, the drying ...

AI Technical Summary

Problems solved by technology

The existing freeze-drying process of asparaginase usually needs two processes of sublimation drying and analytical drying, the drying time is long, and the asparaginase for injection obtained by freeze-drying often has poor resolubility, appearance defects and poor quality. stability problem

Chinese patent 201110081387.4 discloses a freeze-dried powder injection of asparaginase and its preparation method. The freeze-drying process disclosed in the patent is: pre-freezing the product to -25°C, keeping it for 120 minutes, vacuuming, and sublimating to 0°C, keep warm for 270min, and raise the temperature to 25°C within 150min, keep warm for 240min, so as to complete the freeze-drying process. The drying stage of this freeze-drying process takes about 22 hours, the drying time is long, and the quality of the product is poor