A preparation method and application of hyaluronic acid nitrate deoxycholic acid polymer micelles capable of providing nitric oxide

Abstract

The invention relates to a preparation method and an application of a hyaluronic acid nitrate deoxycholic acid polymer micelle capable of providing a nitric oxide, and aims at effectively solving the medication problems of preparation of the hyaluronic acid nitrate deoxycholic acid polymer micelle capable of providing the nitric oxide and achievement of comprehensive treatment on cancers. The method comprises the following steps: putting 15-20ml of concentrated nitric acid into a beaker; adding 150-200mg of hyaluronic acid, controlling the temperature to be 0 DEG C, and reacting for 3-6 hours; adding 400-500ml of ice water, participating, and carrying out suction filtration; washing a sediment by virtue of distilled water until the pH is 6.8-7.0; freezing and drying to obtain hyaluronic acid nitrate; dissolving 10-15mg of deoxycholic acid into 5-7ml of organic solvent, adding 60-80mg of 1-ethyl-(3-dimethyl amino propyl) carbodiimide and 36-45mg of H-hydroxy succinimide; carrying out activating reaction at room temperature for 15 minutes, and dissolving 100-150mg of hyaluronic acid nitrate into 20-25ml of organic solvent; and adding the solution to a deoxycholic acid solution, stirring and reacting at room temperature for 24-48 hours, dialyzing for 48 hours, freezing and drying to obtain the hyaluronic acid nitrate deoxycholic acid polymer micelle. According to the preparation method, the problem of absorption of insoluble drugs is effectively overcome; the targeting property is high; and comprehensive treatment on cancers is achieved.

Description

technical field [0001] The invention relates to medicine, in particular to a preparation method and application of hyaluronic acid nitrate deoxycholic acid polymer micelles capable of providing nitric oxide. Background technique [0002] So far, the treatment of tumors mainly relies on chemical drug therapy, surgery, radiotherapy, immunotherapy and comprehensive therapy. Most of the commonly used anti-tumor drugs in clinical practice are cytotoxic drugs targeting traditional nucleic acids and proteins. It has poor selectivity, strong toxic and side effects, single mechanism of action, and is prone to drug resistance. Nitric oxide (NO) is an important messenger substance and effector molecule in the body, participates in a variety of physiological and pathological reactions, and has a wide range of physiological functions. NO can enhance the toxicity of macrophages to tumor cells, inhibit the proliferation of tumor cells, inhibit angiogenesis and metastasis, and accelerate t...

AI Technical Summary

Problems solved by technology

[0005] Select hyaluronic acid, a natural polysaccharide with good biocompatibility and tumor cell targeting, and introduce nitro groups into HA molecules through concentrated nitric acid nitration method to form hyaluronic acid nitrate, and then esterify the nitrate through amide reaction The HA and deoxycholic acid are covalently connected to form an amphiphilic diblock copolymer, which can self-assemble in water to form nanoscale micelles, thereby constructing a new type of NO donor and tumor cell active Targeted hyaluronic acid nitrate-deoxycholic acid polymer micelles, combined with an effective NO donor, powerful micelle-loaded drug properties, unique tumor cell targeting of hyaluronic acid, auxiliary The organic integration of anti-tumor activity and good biocompatibility can not only overcome the absorption of insoluble drugs, the non-targeting problems of traditional chemotherapy techniques, and the short half-life of NO in vivo, but also realize the combination of NO and chemotherapy drugs. The purpose of synergistic treatment of tumors is to achieve comprehensive treatment of cancer, but so far there is no public report on the preparation method and application of hyaluronic acid nitrate-deoxycholic acid polymer micelles that can provide nitric oxide

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