Amphiphilic block copolymer and preparation method thereof, micelle drug delivery system formed by copolymer and anti-tumor drug

Abstract

The invention relates to an amphiphilic block copolymer and a preparation method thereof, and a micelle drug delivery system formed by the copolymer and an anti-tumor drug. The amphiphilic block copolymer comprises a hydrophilic chain segment and a hydrophobic chain segment, and the end of the hydrophobic chain segment is sealed by hydrophobic radicals. According to the amphiphilic block copolymer disclosed by the invention, methoxy polyethylene glycol (or polyethylene glycol)-polyester segmented copolymer with generally recognized safety is taken as a base material, and terminated hydroxyl hydrophobic radicals of the polyester chain segment are modified, thus the compatibility of hydrophobic chain segments in drug molecules and segmented copolymers is improved, and mutual acting force is increased; through a self-assembling method, the drug can be solubilized in micelle hydrophobic cores of the amphiphilic block copolymer, and the drug molecules are limited in the micelle cores so as not to be likely to be dissolved out, thus drug delivery micelle with high stability is obtained.

Description

technical field [0001] The invention relates to an amphiphilic block copolymer, a preparation method thereof, and a stable micelle drug-carrying system formed by the copolymer and antineoplastic drugs, belonging to the field of nanomedicine preparations. Background technique [0002] Tumor is a kind of disease that seriously threatens the safety of human life. The study of safe and effective anti-tumor drugs is of great significance to improve the quality of human life. [0003] Taxanes (mainly including paclitaxel (PTX), docetaxel (DTX), cabazitaxel, and larotaxel) are very effective and broad-spectrum antitumor agents. The drug, whose mechanism of action is mainly to polymerize and stabilize microtubules, can cause fast-dividing tumor cells to be fixed in the mitotic stage, so that the replication of cancer cells is blocked and they die. In vitro experiments have shown that taxanes have a significant radiosensitizing effect and can stop cells in the G2 and M phases that a...

AI Technical Summary

Problems solved by technology

However, there are many shortcomings in this type of solubilization method: (1) whether the solubilizer polyoxyethylene castor oil (polyoxyethylene castor oil) used in paclitaxel (trade name Taxol) EL), or the solubilizer Tween 80 used in docetaxel (trade name Taxotere) and cabazitaxel (trade name JEVTANA), are prone to cause allergic reactions, so patients need anti-allergic treatment before medication (2) Poor drug stability and low availability for injection: the above-mentioned preparations are prone to precipitation after dilution, and special filtering devices are required when administering the drug, and the injection dilution process needs to be carried out slowly, often due to different operators. As a result, the degree of drug precipitation is inconsistent, which leads to inaccurate dosage of the drug entering the body, and then produces differences in curative effect; (3) Higher hematological toxicity: Both EL and Tween 80 can cause hematological toxicity, which is the main factor limiting the increase of therapeutic dose

For example, patent 201010001047 discloses a method of adding amino acids to micellar solution to improve its stability. Amino acids are added during the formation of micelles, and the position of amino acids in micelles (only as a physical barrier for micelles) It is not mentioned whether the amino acid as an auxiliary additive can still maintain the stability of the micelles after being diluted with the blood after entering the body, so it is used in vivo It is still unclear; in addition, it has been reported that embedding paclitaxel and docetaxel in copolymer micelles can significantly improve the drug loading and stability of micelles, but this compound drug micelles have not been used clinically. It has been recognized (Shao Chengwei et al. In vitro stability study of paclitaxel and docetaxel double-drug micelles, Journal of Shenyang Pharmaceutical University, 2010, 41: 428-434); Huh et al. synthesized a PDENA-PEG block copolymer glue The micelles show long-term stability after embedding paclitaxel, but there is still insufficient data support for the safety of the polymer excipients, and the safety challenges of clinical use are relatively large (Huh KM, et al. Hydmtropic polymer micelle system for delivery of paclitaxel.Journal of Controlled Release, 2005, 101(1-3):59-68)

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