CN-122005563-A - Application of chelerythrine in preparing medicines or antibiotic synergists for treating bacterial infectious diseases

Abstract

The invention discloses an application of chelerythrine in preparing medicines or antibiotic synergists for treating bacterial infectious diseases, wherein the bacteria are carbapenem antibiotics-resistant bacteria, and the antibiotics are carbapenem antibiotics. The invention discloses that chelerythrine can restore the sensibility of carbapenem resistant bacteria for the first time, can reduce the minimum antibacterial concentration of meropenem to bacteria producing metal beta-lactamase by 16 times, and provides a new strategy for solving the drug resistance of bacteria.

Inventors

• GUO YUSHUO
• XIAO XIA
• WANG ZHIQIANG
• LI TENGFEI
• HUANG YANHU

Assignees

• 扬州大学

Dates

Publication Date

20260512

Application Date

20260327

Claims (10)

1. 1. The application of chelerythrine in preparing medicines or antibiotic synergists for treating bacterial infectious diseases is characterized in that the bacteria are carbapenem antibiotic-resistant bacteria, and the antibiotics are carbapenem antibiotics.
2. 2. The use according to claim 1, wherein the antibiotic is meropenem.
3. 3. The use according to claim 1, wherein the carbapenem antibiotic-resistant bacteria are bacteria producing metallo-beta-lactamase.
4. 4. The use according to claim 1, wherein the bacteria comprise e.coli B2 (bla NDM-5 )、E.coliM593(bla NDM-1 ) or e.coli HH194 (bla NDM-9 ).
5. 5. The use according to claim 1, characterized in that the chelerythrine concentration is 16-240 μg/ml.
6. 6. The use according to claim 1, wherein the concentration of the antibiotic is 4-64 μg/ml.
7. 7. An antibacterial agent, which is characterized in that, comprises chelerythrine and meropenem.
8. 8. The antibacterial agent according to claim 7, wherein the chelerythrine is at a concentration of 16 to 240 μg/ml and the meropenem is at a concentration of 64 μg/ml.
9. 9. A carbapenem antibiotic synergist is characterized by comprising chelerythrine.
10. 10. The carbapenem antibiotic potentiator of claim 9, it is characterized in that the method comprises the steps of, the antibiotic is meropenem.

Description

Application of chelerythrine in preparing medicines or antibiotic synergists for treating bacterial infectious diseases Technical Field The invention relates to application of chelerythrine in preparing a medicament or an antibiotic synergist for treating bacterial infectious diseases, belonging to the field of antibacterial medicaments. Background With the massive use of antibiotics, the problem of bacterial resistance worldwide is increasing. Among the last antibiotics used, carbapenems are considered as "last line of defense" drugs for eradicating multi-drug resistant (MDR) bacteria, treating multi-drug resistant gram-negative bacterial infections. However, in recent years, drug resistance genes resistant to carbapenems are produced and widely spread, and antibacterial activity of carbapenem drugs such as meropenem is seriously impaired, and the drug resistance mechanism of carbapenems is mainly by producing carbapenemases such as class a serine carbapenemases, class B metallo beta-lactamases (NDM) and class D OXA-48 serine carbapenemases, among which NDM enzymes are the most popular, and therefore development of carbapenem potentiators against NDM enzyme inhibitors has great significance for restoring carbapenem antibacterial activity. Herba Chelidonii (Chelidonium majus) is fresh or dried whole plant with root of herba Chelidonii belonging to Papaveraceae perennial herb, and is named as rhizoma Coptidis and mountain watermelon. From the "salvage Ben Cao", belongs to the whole grass category. Herba Chelidonii is produced in northeast China, north China and northwest China, and has rich resources. The shanxi Chinese medicine is recorded in Shanxi Zhi, and has the efficacies of reducing heart fire, reducing fever, diminishing inflammation, sterilizing, easing pain and calming. The Chinese herbal medicines commonly used in north are recorded with the actions of easing pain, relieving cough, sterilizing, promoting urination and relieving sore toxin. The main active ingredients of the herba celandiae are alkaloids, the whole herb contains 0.97-1.87% of alkaloids, the root contains 1.9-4.14% of alkaloids, and the main alkaloids comprise chelidonine (Chelidonine), chelerythrine (CHELERYTHRINE), sanguinarine (Sanguinarine) and the like. Wherein chelerythrine has various pharmacological activities such as disinsection, pain relieving, antibacterial, antiinflammatory, antitumor, and anti-fibrosis. And researches show that the antibacterial agent has strong antibacterial activity on gram positive bacteria, staphylococcus Aureus (SA), methicillin-resistant staphylococcus aureus (MRSA) and broad-spectrum beta-lactamase staphylococcus aureus (ESBLs-SA), and the main antibacterial mechanism is likely to destroy channels on bacterial membranes, so that proteins leak out of cells and inhibit biosynthesis of the proteins. In addition, studies have shown that chelerythrine in combination with Oxacillin (OXA) and Ampicillin (AMP) have a synergistic effect on staphylococcus aureus ATCC43300 and ESBLs escherichia coli ATCC 35218. These results indicate that chelerythrine is a promising natural antimicrobial ingredient, however the specific effect of the combination of chelerythrine and the carbapenem antibiotic meropenem on its resistant bacteria is not yet known. Disclosure of Invention The invention aims to provide a synergistic agent which can improve the sterilization effect of carbapenem antibiotics on bacteria producing metallo beta-lactamase. According to the technical scheme, the chelerythrine is applied to the preparation of medicines for treating bacterial infectious diseases or antibiotic synergists, wherein the bacteria are carbapenem antibiotics resistant bacteria, and the antibiotics are carbapenem antibiotics. Further, the antibiotic is meropenem. Further, the carbapenem antibiotic-resistant bacterium is a bacterium producing metallo beta-lactamase. Further, the bacteria include e.coll B2 (bla NDM-5)、E.coli M593(blaNDM-1) or e.collhh194 (bla NDM-9). Further, the concentration of chelerythrine is 16-240 mug/ml. Further, the concentration of the antibiotics is 4-64 mug/ml. An antibacterial agent contains chelerythrine and meropenem. Further, the concentration of chelerythrine is 16-240 mug/ml, and the concentration of meropenem is 4-64 mug/ml. Carbapenems an antibiotic synergistic agent, which is used for preparing the antibiotic synergistic agent, contains chelerythrine. Further, the antibiotic is meropenem. Compared with the prior art, the invention has the following remarkable advantages that the invention discloses that chelerythrine can restore the sensibility of carbapenem resistant bacteria for the first time, can reduce the minimum antibacterial concentration of meropenem to bacteria producing metal beta-lactamase by 16 times, and provides a new strategy for solving the drug resistance of bacteria. Drawings FIG. 1 is a graph showing the in vitro synergistic activity of chelerythrine and meropenem against