Freeze-dried bortezomib powder injection and preparation method thereof

Abstract

The invention provides a freeze-dried bortezomib powder injection and a preparation method thereof. The freeze-dried bortezomib powder injection contains bortezomib and mannitol and does not contain organic solvents. The preparation method of the freeze-dried bortezomib powder injection comprises the following steps of dissolving bortezomib in methanol, adding mannitol, dispersing the mannitol uniformly, drying the mixed solution, and removing the methanol to obtain a mixture of the bortezomib and the mannitol; adding the mixture of the bortezomib and the mannitol into water for injection, stirring to dissolve the mixture completely, and adjusting the pH value of a medicinal solution to 4.0-7.0 by using sodium hydroxide; filtering the prepared solution by using a 0.22Mum microporous filtering membrane to obtain a filtrate; filling the filtrate into an injection bottle, free-drying the injection bottle, corking the injection bottle, pressing the cork of the injection bottle, and packaging the injection bottle to obtain the freeze-dried bortezomib powder injection. Because the mannitol is added into the methanol solution of bortezomib and the bortezomib fully reacts with the mannitol to produce a compound, the solubility of the bortezomib can be improved greatly, and the time spent in preparing the freeze-dried bortezomib powder injection can be shortened. The freeze-dried bortezomib powder injection provided by the invention can be redissolved quickly.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a bortezomib freeze-dried powder injection and a preparation method thereof. Background technique [0002] Bortezomib (PS-341), trade name Velcade, is a new type of anti-tumor drug developed by Millennium Pharmaceutical Company of the United States. The drug leads to the death of tumor cells by blocking the degradation of various proteins that regulate apoptosis and signal transduction in cells. A large number of studies have found that bortezomib has strong anti-tumor activity against a variety of tumors, especially multiple myeloma, mantle cell lymphoma, other B-cell lymphomas, and Hodgkin's lymphoma in hematological tumors. [0003] Yi Wenyuan and others pointed out in "Research Progress of Proteasome Inhibitors Reversing Multidrug Resistance of Tumors" ("Foreign Medicine and Pharmacy Volume", April 2007, Volume 34, Issue 2) that boronic acid peptides include bor...

AI Technical Summary

Problems solved by technology

But adopt trometamol to have following shortcoming as cosolvent: first, trometamol itself is alkalescent, needs to be adjusted to the acceptable pH range of human body again with acid, and bortezomib is in aqueous solution, under acid, alkali condition It is easy to degrade and increase the related substances; secondly, if the pH value exceeds the range of 7.6 to 8.4 during adjustment, bortezomib will be precipitated, and this precipitation is irreversible

This invention increases the solubility of the drug by adding clathrates and surfactants, which has a certain effect on improving the solubility of the drug, but the addition of a large number of excipients greatly increases the volume of the reconstituted solution, causing inconvenient infusion. In addition, the surfactant Toxic and irritating

[0011] Bortezomib can form borate esters with polyols such as mannitol, glucose, polyethylene glycol, etc., but adding bortezomib to the polyol solution cannot react quickly, and methods such as heating and ultrasound are needed to speed up the reaction , and heating will lead to the degradation of bortezomib, the increase of impurities, and the same problem will occur if the ultrasonic time is too long

And because the solubility of bortezomib itself is small, only about 3mg / mL, it takes a long time to dissolve in water

In the production process, in order to dissolve bortezomib faster, methods such as heating and ultrasound are usually used, but these methods will lead to increased impurities and affect the stability of the drug

[0012] None of the existing technologies fundamentally solves the problem of difficult drug reconstitution. Even if the solubility is good before filling, reconstitution takes a long time, which brings inconvenience to clinical application.

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