Amphiphilic polysaccharide-anti-tumor medicament conjugate capable of releasing medicines specifically at lesion site of living body, as well as preparation method and application of medicinal composition of amphiphilic polysaccharide-anti-tumor medicament conjugate

Abstract

The invention relates an amphiphilic polysaccharide-anti-tumor medicament conjugate capable of releasing medicines specifically at a lesion site of a living body, as well as a preparation method and application of a medicinal composition of the amphiphilic polysaccharide-anti-tumor medicament conjugate. In the conjugates, hydrophobic anti-tumor medicaments are introduced into a polysaccharide skeleton through a connecting arm which contains a disulfide bond, so that the polysaccharide-anti-tumor medicament conjugate has amphipathic characteristics and can be self-assembled into nano-micelles; the nano-micelles can load anti-tumor medicaments additionally and also can be directly used as conjugate pre-drug micelles. The amphiphilic polysaccharide-anti-tumor medicament conjugate is mainly characterized in that 1) after the nano-micelles reach the lesion site, the disulfide bond connecting arm of the conjugate can be specifically degraded by high-concentration reducing substances in lesion cells, so that the micelles are depolymerized and the medicament is released quickly, and therefore, the treatment effect is improved; 2) the anti-tumor medicament is chemically conjugated and physically coated to achieve a common treatment effect. The polysaccharide conjugate and the medicinal composition thereof can be used for injection, oral administration or external use administration; the anti-tumor activity can be improved remarkably; new ideas are provided for the development of anti-tumor medicaments.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an amphiphilic polysaccharide-antitumor drug conjugate that releases drugs specifically at the lesion site of a biological body as a drug carrier, and also relates to a preparation method and application of the conjugate carrier. Background technique [0002] Cancer is one of the major diseases threatening human health. According to a survey report published by the World Health Organization on February 1, 2013, the number of people who died of cancer in the world in 2008 reached 7.6 million, and there were about 13 million new cancer patients every year, and the trend was increasing year by year. [0003] Antineoplastic drugs are one of the main methods of clinical treatment at present. However, most of the existing antineoplastic drugs are insoluble water-soluble small molecular compounds, which have poor oral absorption, low bioavailability, and rapid metabolism in the ...

AI Technical Summary

Problems solved by technology

Some polysaccharide-antineoplastic drug conjugates are currently in the research stage, but these conjugates still have obvious disadvantages: the synthesis conditions are relatively harsh; the bridging groups connecting the drug and the polymer are mostly amide bonds or ester bonds, The high stability of these two chemical bonds in the body makes the hydrophobic anti-tumor drug fall off very slowly, which leads to the inability to release the drug in time after reaching the drug effect site, resulting in insufficient drug dose to achieve anti-cancer effect after sustained release. It is conducive to the exertion of the curative effect; treating tumors in the form of polymer prodrugs alone, the mechanism of action is single, and the therapeutic effect is not optimal, etc.

Specific drug release at the site of biological focus formed by introducing a hydrophobic group through a linker containing a disulfide bond Amphiphilic polysaccharide-antitumor drug conjugates have not yet been reported in any literature or patents

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