Liposome lyophilized composition of carfilzomib drug and preparation method thereof

Abstract

Belonging to the technical field of drug synthesis, the invention in particular relates to a liposome lyophilized composition of carfilzomib drug and a preparation method thereof. The liposome lyophilized composition of carfilzomib drug comprises the following components by weight: 5-20 parts of carfilzomib; 0.1-1 part of an antioxidant; 1-5 pars of a pH value regulator; 40-100 parts of phospholipids; 5-20 parts of cholesterol; and 5-25 parts of a lyophilization protective agent. The preparation method provided by the invention comprises the steps of: 1) preparation of a multilamelar liposome suspension; 2) preparation of a unilamelar liposome; and 3) preparation of carfilzomib liposome lyophilized powder. The carfilzomib liposome lyophilized composition obtained by the method provided by the invention has stable pH value and particle size variation before and after lyophilization, maintains stable encapsulation rate, and has good water re-dissolution after lyophilization, water redissolved particles have uniform size, the particles are spherical or sphere-like, and the appearance is round and even.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a liposome freeze-dried composition of carfilzomib and a preparation method thereof. Background technique [0002] Multiple myeloma is a cancer of the blood that occurs in blood cells that usually grow in the bone marrow, the spongy soft tissue that makes up most bones, where blood cells are produced. According to the American Cancer Society, 21,700 people will be diagnosed with multiple myeloma in 2012 and 10,710 will die from the disease. [0003] The U.S. Food and Drug Administration approved Kyprolis (carfilzomib, also known as Carfilzomib) on July 20 for multiple myeloma patients who have previously been treated with at least two priority therapies, including Velcade (bortezomib) and immunomodulators Treatment. The safety and efficacy of Kyprolis were evaluated in a clinical study of 266 patients with relapsed multiple myeloma who had previously received bortezomib ...

AI Technical Summary

Problems solved by technology

Kyprolis currently on the market is a sterile injection powder consisting of 60mg carfilzomib, 3000mg sulfobutyl ether-β-cyclodextrin and 57.7mg citric acid, although the package formed by sulfobutyl ether-β-cyclodextrin The compound improves the solubility of the drug to a certain extent, but the drug is very unstable in the solution, and can only be stable for 4 hours at room temperature (15-30 ° C), which requires the best infusion at low temperature. The safety of the drug cannot be fully guaranteed

In addition, because the prescription includes sulfobutyl-β-cyclodextrin, for patients who take continuous medication for a long time, there is a potential safety hazard because a large amount of sulfobutyl-β-cyclodextrin enters the human blood

The pH value of the sterile injection powder is 3.5, first dissolve it with 29ml sterile water for injection, take the dosage and then dilute it with 50ml 5% glucose injection to complete the intravenous infusion in 2 to 10 minutes, because the pH value of the infusion is low, The infusion speed is too fast, which not only brings stimulation and pain to the patient, but also causes vasospasm and phlebitis

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