Application of isoquinoline alkaloid in preparation of staphylococcus haemolyticus drug resistant to drug resistance

A technology of staphylococcus and isoquinoline, applied in the field of medicine, can solve the problems of drug resistance, time-consuming and labor-intensive new drugs, etc., and achieve the effects of good drug resistance inhibition, improved sensitivity, and good efflux inhibition.

Active Publication Date: 2020-11-06
CHONGQING BULL ANIMAL PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the development of new drugs is time-consuming and labor-intensive, and the developed drugs may quickly ...

Method used

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  • Application of isoquinoline alkaloid in preparation of staphylococcus haemolyticus drug resistant to drug resistance
  • Application of isoquinoline alkaloid in preparation of staphylococcus haemolyticus drug resistant to drug resistance
  • Application of isoquinoline alkaloid in preparation of staphylococcus haemolyticus drug resistant to drug resistance

Examples

Experimental program
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Effect test

Embodiment 1

[0024] Embodiment 1, the influence of isoquinoline alkaloids combined with oxytetracycline hydrochloride on drug resistance of hemolytic staphylococcus

[0025] 1) Determination of minimum inhibitory concentration (MIC) of tetrandrine, berberine hydrochloride, oxytetracycline hydrochloride and m-chlorophenylhydrazone to hemolytic staphylococcus

[0026] The MICs of tetrandrine (TET), berberine hydrochloride (BBR) and oxytetracycline hydrochloride (OTC) against hemolytic Staphylococcus were determined by broth microdilution method. In a 96-well plate, use MH broth to sequentially dilute the drug solution from wells 1 to 9 to a final concentration of 1280-5 μg / mL. Only the bacterial solution was added to the 10th well as a control, and the 11th well Only broth was added as a blank control, and only medicinal solution was added to the 12th well as a medicinal solution control. At this time, the volume of each well is 60 μL, and the prepared bacterial suspension of 0.5 McFarland ...

Embodiment 2

[0056] Example 2, the influence of isoquinoline alkaloids on OTC accumulation in the body of hemolytic staphylococcus

[0057] Due to the overexpression of efflux pumps, antibacterial drugs are excreted from the bacteria, showing multi-drug resistance. Aiming at the characteristic of active efflux of bacteria, active efflux inhibitors (EPIs) such as verapamil, reserpine, and cyanochlorophenylhydrazone (CCCP) have been developed. Discharge, restore the sensitivity of bacteria to drugs, but because of its high toxicity and side effects, it is not suitable for clinical use. In this example, isoquinoline alkaloids are selected as the test drug, and its effect on the OTC intake in the hemolytic staphylococcus is detected by high-performance liquid chromatography, in order to confirm whether the test drug increases by affecting the efflux of bacteria. Susceptibility of haemolytic staphylococci to OTC. The result is as Figure 4 shown. The results showed that the OTC intake of th...

Embodiment 3

[0058] Embodiment 3, the influence of isoquinoline alkaloids on hemolytic staphylococcus tet K and tet L gene transcription levels

[0059] The active efflux system refers to the protein transport system for bacteria to expel toxic and harmful substances or drugs from the body. The genes encoding efflux pumps are generally located in chromosomes or plasmids. Under the induction of the substrate, the efflux pump genes in drug-resistant bacteria can be overexpressed, and even some efflux genes can only be expressed under the induction of the substrate. Efflux is one of the main resistance mechanisms of staphylococci to oxytetracycline. The tet L and tet K efflux pumps of the major facilitator superfamily (MFS) are tetracycline-specific efflux pumps that mainly exist in Gram-positive bacteria. drain pump. The transmembrane region of these efflux pumps is helical, with six hydrophilic channels wrapped by transmembrane helices, and drugs are mainly effluxed through these channels....

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Abstract

The invention discloses an application of isoquinoline alkaloid in preparation of a staphylococcus haemolyticus drug resistant to drug resistance. The isoquinoline alkaloid has lower minimum inhibitory concentration, and the sensitivity of staphylococcus haemolyticus to OTC can be improved after the isoquinoline alkaloid is combined with OTC; the isoquinoline alkaloid can also increase the accumulation amount of the OTC in the staphylococcus hemolyticus, has a certain inhibition effect on the gene transcription level of an efflux pump, and shows a good efflux inhibition effect; and therefore,the isoquinoline alkaloid can be prepared into the staphylococcus haemolyticus drug resistant to drug resistance independently or in combination with antibiotics.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of isoquinoline alkaloids in the preparation of drugs against drug-resistant hemolytic staphylococci. Background technique [0002] In recent years, the problem of bacterial drug resistance has become increasingly prominent, and the level of bacterial drug resistance has been increasing, showing the development from single-drug resistance to multi-drug resistance. However, the development of new drugs is time-consuming and labor-intensive, and the developed drugs may quickly develop drug resistance, so it is difficult to solve the current problem of bacterial drug resistance in a timely manner. [0003] Traditional Chinese medicine is a unique natural resource in my country, and it has shown its unique role in the treatment of infections. According to reports, research on traditional Chinese medicine to reverse bacterial drug resistance has already begun in the 1990s. St...

Claims

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Application Information

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IPC IPC(8): A61K31/4375A61K31/4748A61K31/65A61P31/04
CPCA61K31/4375A61K31/4748A61K31/65A61P31/04A61K2300/00
Inventor 吴俊伟金顺鑫曾杨梅姜波杨锦涛程希邓茂雨
Owner CHONGQING BULL ANIMAL PHARMA
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