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Preparation method and application of controlled-release antibiotic composite hydrogel

A composite hydrogel and antibiotic technology, which is applied in the fields of polymer chemistry and biomaterials, can solve the problems of affecting aesthetics and limited therapeutic effect of mixed anaerobic infection, and achieves high antibacterial efficiency, good tissue adhesion performance, and simple synthesis Effect

Active Publication Date: 2019-10-11
SHANGHAI CHANGZHENG HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

(4) In daily life, although the trauma on the body surface does not affect life, it often causes obvious scar healing due to local infection and affects the appearance
[0004] However, this type of gel has limited therapeutic effect on mixed anaerobic infection. Therefore, in clinical application, aminoglycoside antibiotics-oxidized polysaccharide hydrogel still has certain defects for the combined infection of mixed anaerobic infection.

Method used

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  • Preparation method and application of controlled-release antibiotic composite hydrogel
  • Preparation method and application of controlled-release antibiotic composite hydrogel
  • Preparation method and application of controlled-release antibiotic composite hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Embodiment 1: the preparation of G1-ornidazole

[0058] 250mg G1 and 153.6mg ornidazole were formulated into 100mg / mL and 50mg / mL DMSO solutions respectively, and the DMSO solution of ornidazole was added dropwise to G1, followed by the addition of 115.8mg potassium carbonate. Afterwards, it was stirred at a constant speed at 60° C. for two days, and the solvent was removed by lyophilization. Subsequently, the lyophilized product was dissolved in 2 mL of methanol, unreacted small molecule drugs were removed by ether precipitation, further filtered and vacuum-dried to obtain a brownish yellow powder product, which was a dendrimer prodrug of ornidazole. The synthetic route of G1-ornidazole is as follows figure 1 shown.

Embodiment 2

[0059] Example 2: Preparation of oxidized dextran-tobramycin-G1 ornidazole antibacterial hydrogel

[0060] The oxidized polysaccharide in this example is mainly represented by oxidized dextran as the polysaccharide polymer, and the aminoglycoside antibiotic is mainly represented by tobramycin. Mix aminoglycoside antibiotics, G1 ornidazole, and oxidized dextran. synthetic route such as figure 2 shown.

[0061] Mix 25 μL of oxidized dextran solution (30% oxidation degree, 75 mg / mL), 12.5 μL of tobramycin solution (20 mg / mL) and 12.5 μL of L1-ornidazole solution (50 mg / mL), and form at room temperature for about 5 minutes. Gel, defined in the present invention as oxidized dextran-tobramycin-G1 ornidazole composite hydrogel A.

[0062] Mix 25 μL of oxidized dextran solution (oxidation degree 30%, 50 mg / mL), 12.5 μL of tobramycin solution (50 mg / mL) and 12.5 μL of L1-ornidazole solution (100 mg / mL), and form at room temperature for about 5 minutes. Gel, defined in the present ...

Embodiment 3

[0068] Example 3: Schematic diagram of the thixotropic properties of oxidized dextran-tobramycin-G1 ornidazole hydrogel

[0069] Preparation of oxidized dextran-tobramycin-G1 ornidazole hydrogel:

[0070] Mix 300 μL of oxidized dextran solution (oxidation degree 50%, 50 mg / mL), 50 μL of tobramycin solution (20 mg / mL) and 150 μL of LG1-orni solution (200 mg / mL), and form a gel at room temperature for about 5 minutes. Transfer the gel to the plate of the multifunctional rheometer at 37°C, set the strain rate to 1% and 200%, alternately perform time-dependent modulus measurement, and repeat 3 times to detect the thixotropy of the gel performance. Such as image 3 As shown, it can be seen that the composite gel still maintains a high storage modulus after three damage-recovery experiments, indicating that the gel has good thixotropic properties.

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Abstract

The invention provides composite antibiotic hydrogel based on controlled release of aminoglycoside antibiotics and ornidazole. The composite antibiotic hydrogel is obtained by crosslinking an oxidizednatural polysaccharide polymer, the aminoglycoside antibiotics and the ornidazole through an acid-sensitive Schiff base bond, wherein the ornidazole is modified by a first-generation polyamidoamine dendrimer with an amino terminal. The Schiff base bond is broken in an acidic environment caused by bacterial infection, so that gel degradation is caused, and the on-demand release of the antibioticsis realized. The composite antibiotic hydrogel is easy to prepare and low in cost. According to the prepared controlled-release composite antibiotic hydrogel, the strength, morphology and degradationof the gel, the release rate of drugs and the like can be controlled based on the content of antibiotics, the composite antibiotic hydrogel has broad-spectrum high-efficiency antibacterial properties,and the bacteriostatic effect is superior to that of various kinds of commercial antibacterial gel on the market. The hydrogel is expected to be prepared into external dressings, ointment preparations, implants, coatings on medical apparatuses and instruments and the like and used for resisting infection caused by Gram-negative bacteria, Gram-positive bacteria, anaerobic bacteria and the like.

Description

technical field [0001] The invention relates to the technical fields of polymer chemistry and biomaterials. It specifically relates to a medical antibiotic composite hydrogel, in particular, its linker is aminoglycoside antibiotic drug and ornidazole itself modified by a first-generation dendrimer polyamide amine with an amino terminal, and the linker is an acid-sensitive chemical bond . The hydrogel can be degraded in the acidic environment produced by bacterial proliferation, thereby releasing drugs for broad-spectrum sterilization, and at the same time realizing the on-demand release of aminoglycoside antibiotics and ornidazole, and the drug release rate can be self-regulated. Background technique [0002] Despite the rapid development of medicine in recent years, human beings still face many difficulties in the prevention and treatment of bacterial infections. For example: (1) Military aspects: High-energy weapons in modern warfare often cause a variety of compound inj...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/55A61K31/4164A61K31/702A61K31/7036A61K31/7048A61P31/04
CPCA61K47/6903A61K47/552A61K31/4164A61K31/7048A61K31/7036A61K31/702A61P31/04A61K2300/00Y02A50/30
Inventor 肖建如胡婧婧蔡小攀程义云赵越超
Owner SHANGHAI CHANGZHENG HOSPITAL
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