Anti-tumor macromolecular prodrug compound, and preparation method and application thereof

Abstract

The invention discloses an anti-tumor macromolecular prodrug compound, and a preparation method and application of the anti-tumor macromolecular prodrug compound. The anti-tumor macromolecular prodrug compound is prepared from heparin or a derivative-a doxorubicin type macromolecular prodrug of the heparin and a hyaluronic acid-natural active component type macromolecular prodrug in a compounding way. The invention also provides the preparation method of the anti-tumor macromolecular prodrug compound and the application of the anti-tumor macromolecular prodrug compound in preparing anti-tumor drugs. Compared with the prior art, by compounding two kinds of macromolecular prodrugs, not only are multiple tumor targeting properties obtained, but also multi-drug resistance of tumor can be effectively reversed; the two kinds of macromolecular prodrugs work together and are in mutual synergy, so that the treating effect is obviously enhanced.

Description

technical field [0001] The invention relates to an anti-tumor macromolecular prodrug complex and a preparation method and application thereof, belonging to the fields of polymer materials and pharmaceutical preparations. Background technique [0002] Doxorubicin (DOX), also known as doxorubicin and 14-hydroxydaunorubicin, is a common anthracycline antitumor antibiotic with a broad antibacterial spectrum and is mainly used in the treatment of breast cancer and ovarian cancer in clinic. , Bronchial lung cancer, malignant lymphoma and other malignant tumors play an important role in tumor treatment. Similar to most antineoplastic drugs, long-term use of doxorubicin has obvious toxic and side effects on normal tissues and organs, such as heart, kidney, and bone marrow. Doxorubicin has many clinical adverse reactions, the most serious being dose-dependent cardiotoxicity. According to reports, the cumulative dose of doxorubicin in clinical use should be controlled at 450-600 mg / ...

AI Technical Summary

Problems solved by technology

However, although these technologies have improved the clinical application of doxorubicin to a certain extent, they still have their own defects: when doxorubicin hydrochloride is used in combination with other drugs or chemotherapy sensitizers, precipitation and flocculation are prone to occur, and flocculent precipitates enter Blood vessels may cause embolism of small arteries; although liposome preparations can reduce the toxicity of doxorubicin, they also have problems such as low encapsulation efficiency, easy leakage, stability, increased bone marrow toxicity, and new skin toxicity; The release rate of micellar preparations is uncontrollable, and there are limitations in reversing tumor multidrug resistance; long-term use of new anticancer drugs still faces problems such as toxic side effects and multidrug resistance

However, antineoplastic drugs and chemosensitizers have disadvantages such as low bioavailability and poor tumor selectivity, and cannot obtain ideal therapeutic effects. At the same time, the accumulation of drugs or chemosensitizers in normal tissues may also lead to increased toxic and side effects

The application of nanotechnology to deliver anti-tumor drugs has become a hot spot in the research of drug delivery systems in recent years, but ordinary nanosystems still have defects such as low targeting efficiency, inability to efficiently overcome tumor multidrug resistance, and uncontrollable drug release rate.

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