Paclitaxel micelle drug load system and preparation method thereof

Abstract

The invention relates to a novel micelle drug load system formed by an amphiphilic segmented copolymer and paclitaxel. The amphiphilic segmented copolymer comprises a hydrophilic chain segment and a hydrophobic chain segment, the hydrophilic chain segment is polyethylene glycol monomethyl ether, the hydrophobic chain segment is polycaprolactone, and the end group of the hydrophobic chain segment is terminated by a hydrophobic group. The hydrophobic group is tertbutyloxycarbonyl phenylalanine, so the compatibility of a drug molecule with the hydrophobic chain segment in the segmented copolymer is improved, the interaction between the drug molecule and the segmented copolymer is increased, a large space is provided for accommodating the drug molecule, and a prepared micelle can effectively restrict the drug molecule in the core of the micelle, thereby a drug loaded micelle with high stability is obtained.

Description

technical field [0001] The invention relates to a drug-carrying system formed by an amphiphilic block copolymer and paclitaxel and a preparation method thereof, belonging to the field of nano-medicine 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] Paclitaxel (PTX) is a very effective and broad-spectrum anti-tumor drug. Its mechanism of action is mainly to polymerize and stabilize microtubules, which can cause fast-dividing tumor cells to fix in the mitotic stage and block the replication of cancer cells. die. [0004] [0005] In vitro experiments have shown that paclitaxel has a significant radiosensitizing effect and can stop tumor cells in the G2 and M phases that are sensitive to radiotherapy. However, because it is almost insoluble in water and has poor oral absorption, it...

AI Technical Summary

Problems solved by technology

However, because it is almost insoluble in water and has poor oral absorption, it can only be administered by injection at present. The listed preparation (trade name Taxol) is obtained by adding polyoxyethylene castor oil ( EL) to increase drug solubility

Experiments have shown that there are many shortcomings in Taxol: (1) due to the use of EL is easy to cause allergic reactions, so patients need anti-allergic treatment before medication; (2) Poor drug stability and low injection availability: the above-mentioned preparations are easy to precipitate after dilution, and need to pass through a special filter device during administration. Moreover, the injection dilution process needs to be carried out slowly, and the degree of drug precipitation is often inconsistent due to different operators, resulting in inaccurate drug doses entering the body, resulting in differences in curative effect; (3) Hematological toxicity is high: EL can cause hematological toxicity, a major factor limiting therapeutic dose escalation

[0010] How to improve the stability of micellar preparations in vivo is the key to the study of taxane micellar drug delivery system. Chinese patent CN01809632.8 introduces capping of acetoxy or benzoyloxy in the hydrophobic block, thereby improving the polymer The affinity or absorption of excipients to drugs can improve the ability of excipients to capture drugs and improve the stability of drugs in vivo and in vitro. Although the selected acetoxy or benzoyloxy can improve the in vitro stability of micelles, but in the simulation In the body fluid environment, the ability to improve the stability of the drug is limited, and the related preparations are not yet up to the standard of a finished drug

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