Crystal form of rosustat and preparation method thereof

Abstract

The invention discloses a crystal form of rosustat, a preparation method of the crystal form, a pharmaceutical composition of rosustat and an application of rosustat in treating diseases such as chronic renal anemia. The structure of rosustat is as follows in the specification.

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, the English name is Roxadustat, the Chinese name is: Trade name: The chemical name is [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, and the structural formula is as 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. Globally, this drug was first clinically studied in China, and was launched in December 2018. It was first launched in China in August 2019 for the treatment of anemia in dialysis patients with chronic kidney disease (CKD), including hemodialysis and peritoneal dialysis. Renal (NDD-CKD) anemia. This drug has four characteristics: First, its curative effect is not affected by ...

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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