Medicinal composition and application of bendamustine

Abstract

The invention discloses a bendamustine pharmaceutical composition comprising: 1.5%-5% bendamustine or a pharmaceutically acceptable salt or ester or solvate thereof, 0%-20% stabilizer, 0.05%-2 % antioxidant, 0%‑0.008% pH regulator, and the rest exclusive solvent. In clinical use, according to the dosage of the patient, 10-100mL injection can be used to dilute the bendamustine hydrochloride with a final concentration of 0.1mg / mL-10mg / mL for use, and the preliminary stability test shows that the present invention can be used after dilution At 25°C or 5°C, it is stable for 48 hours. Compared with commercially available lyophilized preparations, the volume of diluent used is reduced (the existing lyophilized preparations require 500mL injection to be reconstituted), and the stability of the diluted drug solution Improvement, patient compliance is good, and existing clinical problems are solved.

Description

technical field [0001] The present invention relates to the field of pharmaceutical compositions for neoplastic diseases and autoimmune diseases, especially nitrogen mustard bendamustine, such as bendamustine hydrochloride or a pharmaceutically acceptable ester, salt or solvate thereof combination. Background technique [0002] Bendamustine, chemical name: 4-{5-[di(2-chloroethyl)amino]-1-methyl-2-benzimidazolyl}butanoic acid, structural formula: [0003] [0004] Bendamustine was originally synthesized in the German Democratic Republic (GDR) in 1963, and was developed between 1971 and 1992. The trade name is produced by the Jena pharmaceutical company, and since 1993, it has been used by ribosepharm GmbH as marketed under the trade name. In 2008, the injection bendamustine hydrochloride (Bendamustine Hydrochloride) produced by U.S. Cephalon Company was listed in the U.S. under the trade name For the treatment of relapsed and refractory B-cell non-Hodgkin's lymphoma...

AI Technical Summary

Problems solved by technology

The problem in clinical use is that it is difficult to reconstitute the existing freeze-dried powder of bendamustine. According to clinical reports, reconstitution takes at least 15 minutes and may take up to 30 minutes

In addition to being cumbersome and time consuming for the health care professional reconstituting the product, prolonged exposure of bendamustine to water during reconstitution increases failure and impurity formation due to the hydrolysis of the product by water possibility of

Secondly, in order to avoid hydrolysis, once the preparation of this product is completed, it needs to be injected intravenously within 30-60 minutes, resulting in poor adaptability of patients

Furthermore, high infusion volume and longer infusion time are associated with many side effects, for example: when currently using bendamustine therapy, large doses of sodium-containing injections need to be infused, for heart diseases (congestive heart failure and / or or renal failure) is contraindicated in patients who would have benefited from treatment with bendamustine, or in the absence of alternative therapy, where patients are forced to accept significant sodium-containing injections physical damage

Also, high infusion volumes place unhealthy stress on the patient's diseased organs, including the heart and kidneys

Images