Preparation method for bortezomib for injection

Abstract

The invention relates to a preparation method for bortezomib for injection. The preparation method comprises the following steps: (1) polylactic acid and tertiary butanol are weighed, and a certain quantity of injection water is added for dissolving to obtain a polylactic acid and tertiary butanol mixed solution; (2) bortezomib raw materials are weighed, added in the mixed solution, and stirred until the raw materials are dissolved totally; (3) mannitol is weighed, added in the solution with the dissolved raw materials, and the injection water is added to account for 70% of the total amount, then is quickly stirred until the mixture is completely dissolved; (4) 5 g of activated carbon is added and stirred for 20 minutes, then is filtered out; (5) the injection water is added to reach 9.5 L; the pH value is regulated to 4.0-7.0 by using sodium hydroxide or hydrochloric acid; then the injection water is added until the total amount achieves 10 L; (6) the vacuum freeze drying technique is adopted for freeze-drying after filling; the freeze-drying technique is as follows: the pre-freezing temperature is kept for -40 DEG C for 3 hours; the sublimation drying time is 16 hours; the resolve drying time is 4 hours; the total time is 23 hours.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a safe and stable quality bortezomib for injection and a preparation method thereof. Background technique [0002] The English name of Bortezomib is Bortezomib for Injection, and its chemical name is [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazine carboxyl)amino] Propyl]amino]butyl]boronic acid. [0003] Its structural formula: [0004] [0005] Bortezomib (bortezomib) is a dipeptidyl boronic acid compound, a new type of highly efficient and specific protease inhibitor, also known as LDP-341 and PS-341 before, developed by Millennium Pharmaceutical Company of the United States, and in May 2003 Received FDA approval on 19th to The trade name is listed and sold, and it is a freeze-dried powder preparation. It is mainly used for the treatment of relapsed and refractory multiple myeloma. It was approved for marketing in the UK in May 2004 for multiple myeloma t...

AI Technical Summary

Problems solved by technology

Aiming at the problem that the clarity of the bortezomib preparation is poor after reconstitution, and the impurities of the bortezomib preparation increase rapidly as the storage time increases, the present invention provides a bortezomib freeze-dried powder injection, which contains bortezomib, Excipients, antioxidants and pH regulators, the resulting preparation has good resolubility, and the dissolution time is 29 to 36 seconds. At the same time, after the preparation is placed at room temperature for 9 hours, the total impurity content is not higher than 1.27%, and it has good stability. , help to increase drug safety

[0013] The above-mentioned prior art mainly solves the problems of insoluble and unstable bortezomib in the preparation process, but the inventors have found that the reconstitution speed of the bortezomib freeze-dried powder prepared by the above-mentioned method has not been improved, resulting in the need for manipulation during use. It can only be used after repeated dilution and dissolving by personnel. At the same time, the existing injections are irritating to blood vessels to a certain extent, and a solution needs to be found

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