Composition used for killing drug-resistant aspergillus fumigatus and prepared from sodium houttuyfonate and application of composition

A kind of Houttuyniacin sodium, drug-resistant Aspergillus fumigatus technology, applied in the field of microorganisms

Inactive Publication Date: 2017-10-20
GUANGXI MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that houttuyfonate sodium (chemical structure: capricoyl acetaldehyde sodium bisulfite), one of the main active ingredients of the Chinese herbal medicine Houttuynia cordata in the family Tribaumaceae, has a significant antifungal effect, with few side effects and a wide range of sources , low price, and not easy to induce drug resistance, but whether it has the same inhibitory effect on AMB drug-resistant Aspergillus fumigatus and the effect of combining with AMB has not been reported

Method used

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  • Composition used for killing drug-resistant aspergillus fumigatus and prepared from sodium houttuyfonate and application of composition
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  • Composition used for killing drug-resistant aspergillus fumigatus and prepared from sodium houttuyfonate and application of composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Drug-resistant Aspergillus fumigatus pharmaceutical composition test

[0023] 1.1 Sources of strains The experimental strains were 7 strains of Aspergillus fumigatus (numbered as AF 5, AF 14, AF 15, AF 17, AF 18, AF 26, AF 32; Among them, 5 strains of sputum samples, 1 strain of alveolar lavage fluid, and 1 strain of wound secretion) were identified as classic Aspergillus fumigatus by lactic acid phenol cotton blue staining morphology and 48°C temperature test. It was confirmed to be AMB drug-resistant strain after sex test. The quality control strain was Candida parapsilosis ATCC22019 specified by CLSI M38-A2 guidelines.

[0024] 1.2 Main reagents and instruments Houttuyfonate Sodium (National Institute for Food and Drug Control, batch number 100247-199601); AMB (Amresco Company, batch number 1397893); RPMI-1640 powder (Gibco Company); 3-(N-morpholino ) propanesulfonic acid-4-morpholine propanesulfonic acid (MOPS, Sigma Company); potato dextros...

Embodiment 2

[0032] Embodiment 2 pharmaceutical composition test result

[0033] 2.1 Quality control standards The MIC value of the quality control strain ATCC 22019 for AMB measured in each independent experiment was 1 μg / mL, which was within the reference range specified in the CLSI M38-A2 guideline, and the strains in the growth control wells grew well, and the drug susceptibility test results reliable.

[0034] 2.2 MIC of houttuyfonate sodium and AMB used alone or in combination According to the ECVs standard recommended by CLSI, the sensitivity of the tested Aspergillus fumigatus to AMB was judged, and the MIC of AMB was ≤1 μg / mL as sensitive, and >1 μg / mL as resistant . The MICs of the two drugs alone and in combination are shown in Table 1.

[0035] Table 1 MIC of Houttuyfonate Sodium and AMB alone or in combination

[0036]

[0037] Note: R Indicates that the strain is resistant to AMB

[0038] 2.3 Evaluation of the combined effect of Houttuyfonate Sodium and AMB For the co...

Embodiment 3

[0041] Example 3 Cytotoxicity Experiment

[0042] Take 1-3ml of heparin anticoagulant blood from healthy adults, wash it with PBS buffer at pH=7.0 for 3 times, and centrifuge at 20-25°C and 2500rpm for 10min, remove the centrifuged supernatant, add PBS buffer, and prepare 10% erythrocyte-PBS suspension, and then dilute the suspension 1:10 with PBS, take 500 μL and place it in an EP tube, add 500 μL houttuyfonate sodium or positive control AMB serially diluted twice with PBS. Incubate the EP tube at 37°C for 1 h, centrifuge at 20-25°C and 2500 rpm for 10 min, transfer 150 μL of the supernatant to a 96-well plate, and measure the absorbance A540 at a wavelength of 540 nm with a microplate reader. Red blood cells treated with 0.1% Triton X-100 in Triton X-100 wells were regarded as 100% complete hemolysis, and negative control wells were treated with red blood cells-PBS suspension containing 1% DMSO as 0% hemolysis, see Table 3 for details. Hemolysis percentage (%) = (houttuyfon...

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Abstract

The invention discloses a composition used for killing drug-resistant aspergillus fumigatus and prepared from sodium houttuyfonate and application of the composition and belongs to the technical field of microorganisms. The composition comprises sodium houttuyfonate and antifungal drug, and the antifungal drug comprises AMB, voriconazole and itraconazole. Concentration of sodium houttuyfonate is 1 / 32XMIC-4XMIC while that of the antifungal drug is 1 / 32XMIC-4XMIC when the composition is in use. Synergistic effect generated by the composition improves antibacterial effect of drug to a drug-resistant aspergillus fumigatus strain and lowers using dosage of the antifungal drug, thereby lowering toxic and side effect, so that the composition is an ideal drug composition for treating infection of aspergillus fumigatus resistant to the antifungal drug.

Description

technical field [0001] The invention belongs to the technical field of microbes, and in particular relates to a composition for preparing and killing drug-resistant Aspergillus fumigatus with houttuyfonate sodium and its application. Background technique [0002] With the acceleration of the aging population, the increase of patients with malignant tumors, AIDS, and organ transplantation, the extensive development of interventional diagnosis and treatment technology, and the extensive use of broad-spectrum antibiotics and glucocorticoids, the current clinically acquired deep fungal infection is showing a rapid development trend, and has It is one of the leading causes of death in immunocompromised patients. Among them, the infection rate of Aspergillus fumigatus is second only to Candida albicans, and the mortality rate of invasive aspergillosis (IA) caused by it is as high as 80%. The results of global microbial resistance surveillance show that nearly 28.6% of Aspergillus...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/185A61K31/7048A61P31/10
CPCA61K31/185A61K31/7048A61K45/06A61K2300/00
Inventor 陈一强罗劲孔晋亮
Owner GUANGXI MEDICAL UNIVERSITY
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