Roxadustat crystal form and preparation method thereof

Abstract

The invention discloses a crystal form of roxadustat and a preparation method thereof, as well as a pharmaceutical composition and use thereof in the treatment of chronic renal anemia and other diseases. Roxadustat is structured as follows:

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a crystal form of roxadustat and a preparation method and application thereof. Background technique [0002] Roxadustat, English name is Roxadustat, Chinese name: Trade name: The chemical name is [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, and the structural formula is shown in formula (1): [0003] [0004] Roxadustat is the world's first oral hypoxia-inducible factor prolyl hydroxylase inhibitor jointly developed by FibroGen and AstraZeneca. The drug was firstly clinically studied in China worldwide, and was launched in December 2018. In August 2019, it was first launched in China for the treatment of anemia in chronic kidney disease (CKD) dialysis patients, including hemodialysis and peritoneal dialysis patients. Renal (NDD-CKD) anemia. This drug has four major characteristics: first, its curative effect is not affected by in...

AI Technical Summary

Problems solved by technology

Patent CN109369524A discloses four crystal forms of roxadustat, namely Form A, Form B, Form C and Form D, wherein Form A is a pure crystal form, and Form B is a hydrate crystal form, which can Spontaneously converted to Form A, Form C is a solvate containing hexafluoropropan-2-ol, and Form D is a solvate containing DMSO and water; patent WO2013013069 discloses seven crystal forms of roxadustat, which are Form I, Form II, FormIII, Form IV, Form V, Form VI and Form VII, most of these crystal forms are solvates and are not suitable for development as pharmaceutical crystal forms; patent CN109369525A discloses 12 crystal forms of roxadustat, They are crystalline form ARE-A, crystalline form ARE-B, crystalline form ARE-C, crystalline form ARE-D, crystalline form ARE-E, crystalline form ARE-F, crystalline form ARE-G, crystalline form ARE-H, Crystal form ARE-I, crystal form ARE-J, crystal form ARE-K and crystal form ARE-L, these crystal forms are solvate crystal forms and metastable crystal forms, which have poor stability and cannot be developed as drug crystal forms and cannot be industrialized

Therefore, among the many crystal forms of roxadustat, crystal form A is the most thermodynamically stable crystal form, which is suitable for development as a pharmaceutical crystal form. Dissolution, which directly leads to low solubility in the human body, which affects absorption and makes it difficult to exert the drug effect

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