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A kind of doxycycline controlled-release quaternary ammonium salt chitosan-liposome composite nanoparticle with pH responsiveness and preparation method thereof

A quaternary ammonium salt chitosan and doxycycline technology, applied in the field of biomedicine, can solve the problems of difficult to completely remove the infected site, increase resistance immune attack, threaten human health, etc., and achieve good development and application potential and manufacturing cost. Inexpensive, release-promoting effect

Active Publication Date: 2020-09-22
THE AFFILIATED HOSPITAL OF QINGDAO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The formation of biofilm increases the resistance of bacteria to antibiotics and helps bacteria escape the immune attack of the host, and it is difficult to completely remove the infection site, and it can also induce drug resistance, which makes biofilm more likely to cause refractory and persistent diseases in clinical practice. Chronic infection, a serious threat to human health

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  • A kind of doxycycline controlled-release quaternary ammonium salt chitosan-liposome composite nanoparticle with pH responsiveness and preparation method thereof

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preparation example Construction

[0026] 2. Preparation of liposomes: Weigh egg yolk lecithin (SPC), add chloroform and absolute ethanol to dissolve, the mass volume ratio of the mass of egg yolk lecithin, the volume of chloroform and the volume of absolute ethanol is 10 :1:1-20:1:1. Heat treatment in a water bath at 35°C for 1 h, so that the lecithin forms a uniform film on the inner wall of the flask. Then add the pH 7.4 PBS buffer solution containing sodium cholate and doxycycline at a mass ratio of 5:1, rotate and stir in a water bath at 55°C for 30 min, and obtain liposome nanoparticles loaded with doxycycline after ultrasonication. particle suspension.

[0027] 3. Preparation of pH-responsive doxycycline controlled-release quaternary ammonium chitosan-liposome composite nanoparticles: prepare 0.5 mg / mL-2 mg / mL of the quaternary ammonium chitosan solution, slowly drop In the liposome nanoparticle suspension of described entrapped doxycycline, stir while adding dropwise, the volume ratio of described quat...

Embodiment 1

[0030] The doxycycline controlled-release quaternary ammonium salt chitosan-liposome composite nanoparticle of the present embodiment is prepared by the following preparation method:

[0031] 1. Weigh 2 g of chitosan powder with a molecular weight of 15 kDa, add 6 mL of 15% (m / v) NaOH, and swell at room temperature for 10 min in a flat-bottomed flask; then add 20 mL of dimethyl sulfoxide and 6 mL of methyl iodide, React at 60°C for 1 h. After 1 h, 3 mL of NaOH and 3 mL of methyl iodide were added respectively, and the reaction was continued for 1 h. After the reaction was completed, absolute ethanol was added to form a white precipitate to terminate the reaction, dialyzed for three days, and freeze-dried. That is, water-soluble quaternary ammonium salt chitosan is obtained.

[0032] 2. Preparation of liposomes: Weigh 70 mg egg yolk lecithin (SPC), add 5 ml chloroform and 5 ml absolute ethanol to dissolve. Heat treatment in a water bath at 35°C for 1 h, so that the lecithin ...

Embodiment 2

[0035] The doxycycline controlled-release quaternary ammonium salt chitosan-liposome composite nanoparticle of the present embodiment is prepared by the following preparation method:

[0036] 1. Weigh 2 g of chitosan powder with a molecular weight of 150 kDa, add 12 mL of 15% NaOH, swell in a flat-bottomed flask at room temperature for 10 min, add 40 mL of dimethyl sulfoxide and 12 mL of methyl iodide, and react at 60 °C for 1 h. After 1 h, 6 mL of NaOH and 6 mL of iodomethane were added, and the reaction was continued for 1 h. After the reaction was completed, absolute ethanol was added to form a white precipitate to terminate the reaction, dialyzed for three days, and freeze-dried. That is, water-soluble quaternary ammonium salt chitosan is obtained.

[0037] 2. The preparation method of the liposome nanoparticle suspension loaded with doxycycline is the same as that in Example 1.

[0038] 3. Prepare 2 mg / mL of the quaternary ammonium chitosan solution, slowly add it into ...

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Abstract

The invention provides a doxycycline controlled-release quaternary-ammonium-salt chitosan-lipidosome composite nanoparticle with pH responsiveness and a preparation method thereof. The doxycycline controlled-release quaternary-ammonium-salt chitosan-lipidosome composite nanoparticle prepared by adopting chitosan, lecithin, doxycycline, iodomethane and the like as raw materials and adopting a thin-film dispersion method and a positive-negative charge adsorption method can be adsorbed on the surface of a pellicle by charge action, and when the composite nanoparticle is in a unique low-pH environment of the pellicle, free amino groups without being quaternized in the quaternary-ammonium-salt chitosan generate protonation reaction, so that a nanoparticle shell carries more positive charges, the stability of the original quaternary-ammonium-salt chitosan-lipidosome nanoparticle is destructed, the release of doxycycline at the pellicle is promoted and finally the effects of destructing the pellicle and killing germs are achieved. The doxycycline controlled-release quaternary-ammonium-salt chitosan-lipidosome composite nanoparticle with pH responsiveness and the preparation method provided by the invention have the advantages that the medicine delivery efficiency and the medical effect of the doxycycline are improved and the prospect of study, development and application in the aspects of medicines and medical materials and the like is good.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a doxycycline controlled-release quaternary ammonium chitosan-liposome composite nanoparticle with pH responsiveness and a preparation method thereof. Background technique [0002] A bacterial biofilm is a colony of microbial cells enclosed in an extracellular polymeric matrix that irreversibly adheres to abiotic or biotic surfaces. Bacteria adhere to solid surfaces through self-synthesized hydrated polymers and grow in a fixed manner to form biofilms. The formation of bacterial biofilms involves several obvious stages, including initial attachment, cell-to-cell There are four stages: adsorption and proliferation, biofilm maturation, and finally bacterial detachment. It has been reported in the literature that almost all bacteria can form biofilms under certain conditions. The biofilm structure is very complex. In addition to different types of bacteria, there are also va...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/65A61K9/127A61K9/51A61K47/36A61P31/04
CPCA61K9/127A61K9/5161A61K9/5192A61K31/65
Inventor 胡芳王蕾吉秋霞徐全臣范春于新波李玮徐烁
Owner THE AFFILIATED HOSPITAL OF QINGDAO UNIV
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