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Lactose acidized glycyrrhetinic chitosan material and preparation method and application thereof

A technology of glycyrrhetinic acid and chitosan, which is applied in the direction of pharmaceutical formulations, medical preparations of non-active ingredients, etc., to achieve the effects of reducing distribution, strengthening liver targeting, and improving reliability

Active Publication Date: 2013-01-09
THE FIFTH PEOPLES HOSPITAL OF SHANGHAI FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, not all target receptors are only overexpressed on target cells, which will lead to insufficient binding of single-ligand modified nanoparticles to target receptors. Negishi et al. found that rat liver contains the highest glycyrrhetinic acid receptors, and the kidney also contains a small amount of glycyrrhetinic acid receptors

Method used

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  • Lactose acidized glycyrrhetinic chitosan material and preparation method and application thereof
  • Lactose acidized glycyrrhetinic chitosan material and preparation method and application thereof
  • Lactose acidized glycyrrhetinic chitosan material and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Synthesis and structural characterization of lactose acidified glycyrrhetinic acid chitosan

[0047] In this example, chitosan (CTS) was selected as the matrix material, glycyrrhetinic acid (GA) and lactobionic acid (LA) were used as liver targeting ligands, and glycyrrhetinic acid and Lactobionic acid was grafted onto chitosan to achieve active targeting of liver cancer cells. In order to optimize the reaction conditions and obtain a suitable grafting rate, this experiment designed four factors and three levels of L 9 (3 4 ) Orthogonal experiment to investigate the ratio of the amount of EDC·HCl to NHS substance, the ratio of the amount of EDC·HCl to GA substance, the ratio of the amount of GA to CTS substance and the influence of reaction time on the grafting rate, using Fourier infrared test (IR) and H NMR spectroscopy ( 1 H-NMR) to verify whether the double-ligand modified chitosan material was successfully synthesized, and to calculate its degree of ...

Embodiment 2

[0099] Example 2 In vitro cell experiment and distribution research in rats

[0100] In order to investigate the targeting of lactose-acidified glycyrrhetinic acid chitosan (GCGA) as a drug carrier and its uptake by liver cancer cells after being made into nanoparticles. In this example, the toxicity of the carrier material to L929 cells was evaluated by the MTT method. Then FITC was grafted onto chitosan (CTS), glycyrrhetinic acid chitosan (GA-CTS) and GCGA, respectively, and FITC-labeled CTS, GA-CTS and GCGA were synthesized and prepared by ion cross-linking FITC-labeled non-ligand-modified CTS nanoparticles, single-ligand-modified GA-CTS nanoparticles and double-ligand-modified GCGA nanoparticles. The uptake of FITC-labeled CTS, GA-CTS and GCGA nanoparticles by BEL-7402 human hepatoma cells was studied by flow cytometry and confocal laser microscopy, and the uptake of GCGA nanoparticles by LO2 human normal hepatocytes was compared , and studied the distribution of three...

Embodiment 3

[0146] Example 3 Optimization of preparation conditions, physicochemical properties and in vitro release of drug-loaded nanoparticles

[0147] 1. Experimental method

[0148] 1.1 Experimental reagents and instruments

[0149] Main drugs: pentafluorouracil (5-Fu), chitosan (CTS), glycyrrhetinic acid chitosan (GA-CTS), lactose acidified glycyrrhetinic acid chitosan (GCGA), sodium polyphosphate (TPP), PBS buffer, acetic acid (HAc), hydrochloric acid (HCl), sodium hydroxide (NaOH), dialysis bag.

[0150] Main instruments: full-temperature shaking incubator, field emission scanning electron microscope, ultraviolet-visible spectrophotometer, dynamic light scattering laser particle size and zeta potential analyzer, biomedical freezer, biochemical incubator, magnetic heating stirrer, intelligent magnetic stirrer , freeze dryer, pH meter, physical and chemical drying oven, analytical balance.

[0151] 1.2 Preparation of CTS, GA-CTS and GCGA loaded 5-Fu nanoparticles

[0152] The ...

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Abstract

The invention relates to a lactose acidized glycyrrhetinic chitosan material and a preparation method and the application thereof. The lactose acidized glycyrrhetinic chitosan material is a glycyrrhetinic acid and lactobionic acid jointly modified chitosan material which is synthesized through N-acylation reaction with chitosan serving as carrier and glycyrrhetinic acid and lactobionic acid serving as ligands. The invention further provides a lactose acidized glycyrrhetinic chitosan / 5-fluorouracil medicine carrying nano particle. The lactose acidized glycyrrhetinic chitosan material and the preparation method and the application thereof have the advantages that the dual-ligand co-modified chitosan material is synthesized for the first time, and the nano particle is prepared for target research; and the lactose acidized glycyrrhetinic chitosan which is prepared into the nano particle has higher liver targeting performance and hepatoma cell receptor mediate initiative targeting performance as compared with GA (glycyrrhetinic acid )-CTS (chitosan) and CTS, distribution in other visceral organs can be evidently reduced, reliability in hepatoma targeting is improved, and the lactose acidized glycyrrhetinic chitosan material can be used as a carrier material which has wide application prospect in clinical hepatoma targeted treatment.

Description

technical field [0001] The invention relates to the field of polymer drug carriers, in particular to a lactose acidified glycyrrhetinic acid chitosan material and its preparation method and application. Background technique [0002] At present, domestic and foreign research on liver cancer is mainly focused on the preparation of drug-loaded (or gene) nanoparticles by single-ligand modified polymers. For example, studies on liver-targeting nanoparticles mediated by asialoglycoprotein receptor (ASGP-R) have shown that they have hepatotropism and have certain inhibitory effects on liver cancer. Glycyrrhetinic acid receptor-mediated Active targeting of the liver has the same effect. However, such single-ligand-modified nanoparticles are susceptible to changes in many pathological and physiological conditions during receptor-ligand interactions, resulting in partial failure of receptor-mediated effects and affecting the effect of targeted therapy. For example, for patients with...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/08A61K47/36
Inventor 程明荣何秉洪洋黄陶承顾勇
Owner THE FIFTH PEOPLES HOSPITAL OF SHANGHAI FUDAN UNIV
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