Pharmaceutical composition of aminopyrimidine compounds and preparation method thereof

Abstract

The invention relates to a pharmaceutical composition of aminopyrimidine compounds and a preparation method thereof. Specifically, the pharmaceutical composition comprises 4-[(4-methyl-1-piperazinyl)methyl]-N-[6-methyl-5-[(4-(3-pyridyl)-2-pyrimidinyl)amino]pyridine-3-yl]-3-(trifluoromethyl)-benzamide, a polymorph, a solvate, a hydrate,pharmaceutically acceptable salt or a combination thereof whichare used as the active components, and at least a pharmaceutically acceptable accessory. The composition has good stability and drug dissolution; product quality is controllable; and the preparationmethod has simple process and strong operationality, and is suitable for industrial mass production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a pharmaceutical composition of aminopyrimidine compounds and a preparation method thereof. Background technique [0002] Chronic myeloid leukemia (CML) is a hematological malignancy originating from hematopoietic stem cells. The annual incidence in my country is about 0.36 / 100,000, and the median age of onset is 40-50 years old. CML manifests as unrestricted massive proliferation and aggregation of myeloid cells in the patient's bone marrow, which inhibits normal hematopoiesis in the bone marrow, and malignant granulocytes spread to the whole body through the blood, resulting in anemia, hemorrhage, infection and organ infiltration in the patient, thus seriously endangering the patient's body Health can even lead to death. About 95% of CML patients have a characteristic t(9:22) chromosomal translocation, which forms the Bcr / abl fusion gene, and the encoded ...

AI Technical Summary

Problems solved by technology

The development and application of imatinib and second-generation and third-generation drugs have extended the survival time of patients with chronic myelogenous leukemia from 4-5 years to 10-20 years, but the application of tyrosine kinase inhibitors has not yet cure CML

[0004] Since imatinib does not really act on CML stem cells, CML patients must take the drug for a long time or even for life. Once the drug is stopped, the probability of disease recurrence or disease progression increases; Imatinib is mainly aimed at patients with early CML, and the complete remission rate for patients with middle and late stages is less than 30%, and a series of toxic reactions will occur after long-term use; especially some patients may develop imatinib resistance and the proportion is increasing year by year, a large number of reports show that this It is mainly related to the decreased sensitivity to imatinib caused by Bcr / abl mutation; in addition, the increased expression of the fusion protein caused by Bcr / abl gene amplification is also an important mechanism of its drug resistance

To address these problems, some new tyrosine kinase inhibitors such as Nilotinib and Dasatinib have been continuously developed and applied, but they still cannot successfully treat CML patients with T315I mutation

[0005] Before the discovery of imatinib, drugs active against Philadelphia chromosome (Ph)-positive myeloid leukemia (CML) were IFN-, cytarabine, and homoharringtonine (HHT), which could be used alone or in combination , but these already used drugs still have unsatisfactory effects

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