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Preparation of hyaluronic-acid-based double-targeting nano-composite medicament and application of double-targeting nano-composite medicament

A nano-composite, hyaluronic acid technology, applied in the direction of drug combination, medical preparations with inactive ingredients, medical preparations containing active ingredients, etc., can solve the problem that the physical and chemical properties such as tumor targeting are difficult to effectively control and the preparation process is complicated. , fast degradation speed and other problems, to achieve high-efficiency and low-toxicity treatment, simple equipment requirements, and reduce the effect of retention

Inactive Publication Date: 2013-06-12
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, HA is sensitive to strong acid, strong alkali, heat, free radicals and hyaluronidase, and its fast degradation rate limits its application in tissue engineering and medicine.
The preparation process of the HA drug delivery system prepared by the prior art is complicated, and the physical and chemical properties such as tumor targeting are difficult to effectively control

Method used

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  • Preparation of hyaluronic-acid-based double-targeting nano-composite medicament and application of double-targeting nano-composite medicament
  • Preparation of hyaluronic-acid-based double-targeting nano-composite medicament and application of double-targeting nano-composite medicament
  • Preparation of hyaluronic-acid-based double-targeting nano-composite medicament and application of double-targeting nano-composite medicament

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Embodiment 1

[0039] 1. Preparation method 1 of HA-CA amphiphilic hyaluronic acid copolymer ( figure 1 ):

[0040] Sodium hyaluronate was dialyzed against deionized water for 24 hours. After lyophilization, hyaluronic acid (5 mg, 1 mmol carboxyl) was dissolved in 1 mL deionized water.

[0041] Dissolve 10g of 5β-cholanic acid (CA) in 50mL of methanol, add 1.80mL of concentrated hydrochloric acid, seal the container with a film, and react at a constant temperature of 60°C for 6 hours under magnetic stirring, add excess distilled water to form a white precipitate, wash 3 times with water, and dry in vacuum to obtain Methyl cholanoate in white powder form.

[0042] Dissolve 9g of methyl cholanoate in 50mL of DMF (dimethylformamide), slowly add EDA (0.9μmol), ethylenediamine), and react with magnetic stirring for 6 hours. Excessive distilled water produces a white precipitate, which is washed three times with water and dried in vacuum to obtain white powder CA-NH 2 .

[0043] HA (120mg, 0....

Embodiment 2

[0056] Characterization and Performance Test of Taxane Nanocomposites

[0057] 1. NMR detection proved the successful synthesis of HA-CA copolymer.

[0058] Dissolve 1 mg of hyaluronic acid (HA), cholanic acid (EtCA) and cholanic acid-modified hyaluronic acid (HA-CA) in D 2 O in the corresponding solution, and then carried out nuclear magnetic resonance spectrum detection analysis, the results are as follows Figure 4 As shown, HA-CA was successfully synthesized.

[0059] 2. Electron microscopy and atomic force microscopy were used to characterize the morphology of the drug-loaded nanocomposite HA-CA / PTX constructed from modified hyaluronic acid.

[0060] HA-CA / PTX was dissolved in deionized water and then modified into mica flakes for atomic force microscopy analysis.

[0061] Such as Figure 5 As shown by the atomic force microscope, the HA-CA / PTX nanocomposite particles dispersed in pure water indicate that the prepared nanocomposite particles can be monodispersed in th...

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Abstract

The invention relates to a hyaluronic-acid-based double-targeting nano-composite medicament and a preparation method thereof. Hydrophobic group ursodeoxycholic acid is included in a hyaluronic acid nano-polymer structure and can form an amphipathic polymer and automatically generate micelles in an aqueous solution, and polyethylene glycol can be introduced into the micelles to improve the dispersity and stability of a composite. An anti-tumor medicament can enter a nano-carrier through electrostatic adsorption or physical inclusion to generate a nano-medicament composite, wherein the nano-medicament composite is selectively concentrated in a tumor cell under an active targeting effect of hyaluronic acid and a surface CD44 receptor of a tumor cell, and promotes a tumor tissue to absorb the nano medicament-carrying composite by using a passive osmotic accumulation effect (EPR) at the same time. After an anti-tumor medicament is wrapped by a modified hyaluronic acid polymer, the anti-tumor medicament has the advantages of improving the bioavailability of the medicament, improving the targeting property, reducing the toxic and side effects, prolonging the half-life period of the medicament, being stably stored and the like, so that the tumor targeting therapy efficiency is improved in many ways.

Description

technical field [0001] The invention discloses a novel dual-target nanocomposite capable of carrying antitumor drugs, and the nanocomposite is composed of hyaluronic acid and cholanic acid modified with different molecular weights. The invention also discloses a preparation method of the novel nanocomposite and its application as a tumor targeting drug, belonging to the fields of biomedical materials and pharmaceutical preparations. Background technique [0002] The "World Cancer Report" recently published by the World Health Organization shows that the incidence of cancer worldwide will increase by 50% in 2020, and the number of new cancer patients worldwide will reach 15 million each year. Current investigations show that the incidence of malignant tumors has increased year by year, from 1‰ in 1993 to 3‰ in 2011. Aging, urbanization, industrialization and changes in living habits are the main reasons for the incidence. In 2010, the proportion of malignant tumor deaths in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K45/00A61K31/337A61K31/4745C08B37/08A61P35/00
Inventor 朱雷崔起荣陈小元刘刚
Owner XIAMEN UNIV
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