Combretastatin derivative freeze-dried powder injection and preparation method thereof

Abstract

The invention discloses Combretastatin derivative freeze-dried powder injection and a preparation method thereof. The freeze-dried powder injection is prepared from a Combretastatin derivative phospholipid complex, a stabilizer and a freeze-drying protecting agent. The preparation method comprises the following steps of: preparing the Combretastatin derivative phospholipid complex; homogenizing ina high pressure; and freeze-drying. The freeze-dried powder injection is dissolved in 5% of glucose or 0.9% of a normal saline injection solution for using, and can be used for intravenous injection,instillation or direct oral administration so as to treat non-small cell lung cancer, liver cancer and colon cancer. The prepared freeze-dried powder injection has the advantages of being high in ratio of drug to lipid, small in toxic and side effect, good in solubility, and capable of improving hydrophilicity and lipotropy of a Combretastatin derivative, improving oral administration bioavailability, reducing an intravenous administration dosage, and reducing toxicity and enhancing efficacy, and has a certain slow release effect and passive targeting. In addition, the preparation method is simple in technological process, and easy in industrial production.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations and preparation thereof, in particular to a freeze-dried powder injection of compretidine derivatives and a preparation method thereof. Background technique [0002] Combretastatin is a cis-stilbene natural product isolated from the bark of the African shrub willow, among which Combretastatin A4 (hereinafter referred to as CA4) is the most cytotoxic and structurally most A simple compound, which has the basic structure of 3,4,5-trimethoxy substituted benzene ring and 3-hydroxyl-4-methoxy substituted benzene ring connected by cis carbon-carbon double bond connecting arm. The anti-tumor mechanism of CA4 is mainly to inhibit tubulin polymerization, induce cell apoptosis and anti-tumor blood vessels. [0003] However, CA4 has poor water-solubility and fat-solubility, and its cis-stilbene structure is more active but unstable. Therefore, three aspects of structural modification are...

AI Technical Summary

Problems solved by technology

Although CA4P improves the water solubility of CA4, it cannot be stored stably in an aqueous solution, so it needs to be prepared as a freeze-dried powder for storage. The freeze-dried powder has the following defects: ① CA4P freeze-dried powder is easy to produce Degradation, poor stability; ② The phosphate form has poor fat solubility, is not easy to enter the cells to exert the drug effect, and the effective dose is high; ③ The toxic and side effects in the body are large, and it will be degraded and released quickly after intravenous administration, and it will be eliminated quickly, without sustained release. Effect; ④Limited to intravenous administration, does not have the convenience and compliance of oral administration

[0007] In addition, although the method of directly making drugs into new preparations such as liposomes, solid-dispersed nanoparticles, and polymeric micelles can improve the drugs themselves, there are problems such as low drug loading and unstable encapsulation efficiency. Powder injections have similar problems, and there are also deficiencies in the preparation process, dosage of excipients, safety and storage of excipients

[0008] In the existing patents, there is no invention related to compretin derivatives and phospholipid complexes

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