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Application of tryptophan to enhancement of bactericidal effect on gram-negative bacteria

A Gram-negative bacteria, tryptophan technology, applied in antibacterial drugs, organic active ingredients, resistance to vector-borne diseases, etc. The emergence of drug-resistant bacteria, the effect of good therapeutic effect

Inactive Publication Date: 2020-01-21
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the research and development cycle of new antibiotics is also relatively long, and bacteria have more adaptation mechanisms as the environment changes, so safe and effective bactericidal enhancers are very promising and effective ways to treat bacterial infections

Method used

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  • Application of tryptophan to enhancement of bactericidal effect on gram-negative bacteria
  • Application of tryptophan to enhancement of bactericidal effect on gram-negative bacteria
  • Application of tryptophan to enhancement of bactericidal effect on gram-negative bacteria

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1: Determination of the minimum inhibitory concentration of the sensitive strain MG1655 and the resistant strain EY1

[0036] Gentamicin and kanamycin were selected as the representative drugs of antibiotics in this experiment. The antibiotics were serially diluted by adding physiological saline, and the diluted antibacterial solution was added to a sterilized 96-well plate, and then added after freeze-drying. For the bacterial suspension cultured in broth, determine the smallest concentration MIC that inhibits the growth of the bacteria. The results are shown in the table below

[0037] Table 1. Minimum inhibitory concentration MIC determination (mg / L):

[0038] Strain Gentamicin Kanamycin MG165543.5 EY1 240220

Embodiment 2

[0039] Example 2: Sterilization effect experiment

[0040] Select E. coli MG1655 in logarithmic growth phase and stable phase, and add the same concentration of gentamicin (0mg / L, 1mg / L, 2mg / L, 3mg / L, 4mg / L) and kanamycin to the medium (0mg / L, 1mg / L, 2mg / L, 3 mg / L, 4mg / L) and gentamicin and kanamycin after adding 5mM tryptophan for 24h, calculated by the method of viable bacteria count The number of surviving bacteria in each experimental group after treatment was used to determine the bactericidal effect of each group of drugs. The experimental results are as figure 1 As shown in (a)(b)(d): when combined with gentamicin, the bactericidal effect of tryptophan at 3mg / L and minimum inhibitory concentration of 4mg / L is higher than that of the experimental group without tryptophan 100 times, when combined with kanamycin, tryptophan at 1.5mg / L to the minimum inhibitory concentration of 3.5mg / L can increase the sterilization by 10-100 times. For stable MG1655, 5mM tryptophan and genta...

Embodiment 3

[0041] Example 3: Determination of the rate of production of resistant bacteria

[0042] Transfer the overnight culture to fresh medium according to the transfer amount of 1%, and cultivate MG1655 for different time (from 3 hours to 9 hours) after 60mg / L gentamicin and 40mg / L calorie After 5 hours of natamycin treatment, different concentrations of tryptophan were added for 30 minutes, and the ratio of bacteria before and after treatment was compared by the method of viable bacteria count to determine the rate of drug-resistant bacteria. The experimental results are as figure 2 As shown in (a) and (b), tryptophan concentration-dependently reduces the production of resistant bacteria. The reduced efficiency can reach 10-1000 times.

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Abstract

The invention discloses that tryptophan has the effect of enhancing the bactericidal effect on gram-negative bacteria, and particularly relates to application of tryptophan to preparation of bactericidal medicines for gram-negative bacteria. The design experiment proves that tryptophan can be added to gentamicin and kanamycin to increase the intracellular reactive oxygen species level of bacteriaand further increase the absorption of antibiotics by the bacteria, thereby improving the sensitivity of the bacteria to drugs. The trapping effect of tryptophan on the gram-negative bacteria and theimprovement of the bactericidal effect on drug-resistance bacteria are fully proved. Based on the above findings, secondary medical use of tryptophan, a bactericidal composition, a bactericidal drug and a bactericidal method are correspondingly disclosed.

Description

Technical field [0001] The invention relates to the technical field of killing gram-negative bacteria, and in particular to the application of tryptophan to enhance antibiotics to kill gram-negative bacteria. Background technique [0002] With the widespread use of antibiotics, more and more resistant bacteria and resistant bacteria appear. This brings great difficulties to the treatment of bacterial infections in the future. Drug-resistant bacteria are also an important cause of chronic and recurrent infections, such as urinary tract infections. The existing research results indicate that 90% of chronic urinary tract infections are caused by E. coli. However, the research and development cycle of new antibiotics is relatively long, and bacteria have more adaptive mechanisms with environmental changes, so safe and effective bactericidal enhancers are a very promising and effective way to treat bacterial infections. It is very promising for clinical application if it can have a...

Claims

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Application Information

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IPC IPC(8): A61K31/405A61K31/7036A61P31/04
CPCA61K31/405A61K31/7036A61P31/04A61K2300/00Y02A50/30
Inventor 李艳张利宁刘巍峰丛华郭晶晶孙夏慧
Owner SHANDONG UNIV
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