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A drug-resistant Staphylococcus aureus combination drug and its application

A staphylococcus, golden yellow technology, applied in the field of pharmacy, can solve the problems of reduced antibiotic concentration, inability to play an antibacterial effect, serious bacterial drug resistance, etc., and achieve the effect of reducing the inhibitory concentration

Active Publication Date: 2017-11-17
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Bacterial cells pump most of the commonly used antibiotics out of the cells through efflux pumps, reducing the concentration of antibiotics in the cells and failing to play an antibacterial role
[0005] Norfloxacin is a fluoroquinolone antibiotic that has been used clinically since 1986; it is widely used because of its strong inhibitory effect on Gram-positive and Gram-negative bacteria, especially Staphylococcus aureus For the anti-infection treatment of urinary tract, respiratory tract, etc.; with the wide application of norfloxacin in clinical and animal husbandry, bacteria have developed serious drug resistance to it, thus limiting the application of norfloxacin

Method used

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  • A drug-resistant Staphylococcus aureus combination drug and its application
  • A drug-resistant Staphylococcus aureus combination drug and its application
  • A drug-resistant Staphylococcus aureus combination drug and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1. Isolation of synergistic compound soybean isoflavones (genistein) from plants

[0037] Sophora japonica (( Sophora moorcroftiana ) aboveground part 1.0 kg, dried and pulverized with 95% ethanol 45 o Extracted three times at C, combined the extracts, concentrated under reduced pressure to obtain 124 g of extract, extracted with petroleum ether and water in turn, and the remaining part weighed 35 g after the solvent was evaporated. The 35 g extract was mixed with 200-300 mesh silica gel, and gradient eluted with petroleum ether and ethyl acetate (the initial ratio was 8:2, and finally washed with pure ethyl acetate), and each 60 mL was used as one split. The 21st-34th fractions were combined and recorded as fractions Fr 03-21 after recovering the solvent, with a total of 1.7 g. Fraction 21 was mixed, first washed with chloroform for two column volumes, and then eluted with chloroform-acetone (9:1), each 20 mL was a fraction. Fractions 32-40 were collected an...

Embodiment 2

[0038] Example 2. Isolation of soy isoflavones from soybean products commercial food raw material Bioisogen®

[0039] Food raw material Bioisogen® was purchased from Jichun Factory, Amorepacific Co. Ltd., Korea. 100 g of Bioisogen® raw material was extracted three times with 1 liter of acetone or chloroform-methanol (1:1) solvent, and the solvent was evaporated to dryness to obtain about 23 grams of light yellow amorphous solid. Get 1 gram of it and use silica gel column chromatography, elute with chloroform-methanol (95:5) mobile phase, every 8 mL is a flow fraction, combine the 8th-25th flow fraction, evaporate to dryness to obtain 300 mg soybean isoflavones (genistein ).

Embodiment 3

[0040] Example 3. Determining the optimal ratio of compound soybean isoflavone (genistein) and norfloxacin in combination

[0041] Soy isoflavones and norfloxacin were respectively prepared mother liquors, and the mother liquors were pipetted and mixed according to the ratios shown in the table below to obtain 12 compositions numbered 1-12, and the volume of each composition was 120 µL. Pipette 100 µL of the composition numbered 1 and add it to 1.5 mL broth to obtain the stock solution of composition 1. Treat compositions 2-11 in the same way. Composition 12 does not contain genistein and norfloxacin, and it is negative control. Each composition was subjected to an antibacterial test and the MIC value of each composition was recorded (as shown in Table 2).

[0042] Table 2. Compositions of Compositions 1-12 and their MIC values ​​against drug-resistant Staphylococcus aureus

[0043] Composition number

[0044] G: genistein; N: norfloxacin. MIC: minimum inhibitory c...

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Abstract

Belonging to the field of pharmacy, the invention relates to a drug resistant Staphylococcus aureus combined drug and application. The drug resistant Staphylococcus aureus combined drug involved in the invention is composed of isoflavone and norfloxacin, wherein the natural compound isoflavone can be separated from plants, is especially high in content in leguminous plants, and has no obvious toxic or side effect. The result of bacteriostatic experiments shows that for norA gene containing fluoroquinolone resistant methicillin-resistant Staphylococcus aureus SA1199B, the isoflavone itself has no bacterial growth inhibiting effect, but after compatibility of the isoflavone and the antibiotic norfloxacin in a ratio of 1:1, the formed combined drug can reduce the minimum bacteriostatic concentration value of norfloxacin by 4 times, and has the same synergistic ability to that of the positive reference substance reserpine. The combined drug provided by the invention can lower the minimum bacteriostatic concentration of norfloxacin, generate an drug-resistant Staphylococcus aureus synergistic effect for norfloxacin, and can be further prepared into drug-resistant Staphylococcus aureus drugs or pharmaceutical preparations for external use.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a drug-resistant Staphylococcus aureus combination drug and its application. Specifically relate to a compound with synergistic resistance to drug-resistant Staphylococcus aureus, especially compound 3-(4-hydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one and its Use in the preparation of drugs against fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus (drug resistant MRSA). Background technique [0002] Methicillin-resistant Staphylococcus aureus Staphylococcus aureus , MRSA) is one of the most common infectious bacteria in hospitals. In addition to superficial skin infections, it can also cause deep infections in the human body. Studies have shown that MRSA, which is resistant to all lactam antibiotics such as penicillin, has also developed resistance to antibiotics such as macrolides, fluoroquinolones, and tetracyclines, making the infection more difficult to treat ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/496A61P31/04A61K31/352
CPCA61K31/352A61K31/496A61K2300/00
Inventor 王双英穆青孙仲琳西蒙·吉本斯
Owner FUDAN UNIV
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