Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof

Abstract

The invention relates to preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof with anti-tumor activity and biodegradability. The conjugate has amphiphilicity by using alkylenediamine as a connecting arm and introducing hydrophobic segmer, namely a carboxyl-containing anti-tumor medicament, on a polysaccharide framework, and are formed into nanometer micelles by self-assembly in water. The invention is characterized in that 1) the anti-tumor medicament is physically coated by a hydrophobic inner core consisting of hydrophobic groups so as to remarkably improve the solubility of the anti-tumor medicament; and 2) the anti-tumor medicament obtained by chemical conjugation and physical coating can jointly achieve treatment effect and improve medicament action. The polysaccharide conjugate and the medicinal compositions thereof can be used for injection, oral administration, external use or mucosa administration. The invention has the advantages of simple preparation method, mature technology, high yield, and suitability for large-scale continuous production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an amphiphilic polysaccharide conjugate having both antitumor activity and biodegradability as a drug carrier, and also relates to a preparation method and application of the conjugate. Background technique [0002] Cancer is one of the major diseases threatening human health. According to the statistics of the World Health Organization, there are currently 24.6 million cancer patients in the world, and almost 7 million people die of cancer every year, and the trend is 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 body. The time to maintain blood drug concentration is relatively short. In order to improve the curativ...

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Problems solved by technology

Some polysaccharide-antineoplastic drug conjugates are currently in the research stage, but these conjugates still have the following defects: the synthesis conditions are relatively harsh; the bridging group connecting the drug and the polymer is not easy to find. When such functional groups are directly condensed, the linking arms used are relatively complex, such as amino acids or polypeptides; the prodrug itself does not show pharmacological activity, and only the original drug has curative effect, but the grafting rate of anti-tumor drugs is low, resulting in slow The amount of drug after release is not enough to achieve anti-cancer effect, affecting the therapeutic effect; treating tumors in the form of polymer prodrug alone, the mechanism of action is single, and the therapeutic effect is not optimal, etc.

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