CN-122005548-A - Use of Obatoclax mesylate and/or NIGERICIN for the preparation of antibiotic sensitizers

Abstract

The invention relates to the technical field of biological medicine. The present invention provides the use of Obatoclax mesylate and/or NIGERICIN in the preparation of an antibiotic sensitizer, including being colistin. The invention also provides application of the pharmaceutical composition of colistin and Obatoclax mesylate or NIGERICIN in preparing medicines for resisting colistin-resistant gram-negative bacteria. The technical scheme of the invention shows that the combined use of the colistin and Obatoclax mesylate or NIGERICIN has a synergistic effect, can obviously reduce the MIC value of the colistin against colistin resistant gram-negative bacteria and inhibit the growth of the gram-negative bacteria.

Inventors

• WANG HUI
• ZHANG YAWEI

Assignees

• 北京大学人民医院

Dates

Publication Date

20260512

Application Date

20260330

Claims (5)

1. Use of 1.Obatoclax mesylate and/or NIGERICIN for the preparation of an antibiotic sensitizer, characterized in that the antibiotic comprises colistin.
2. 2. Use of a pharmaceutical composition of colistin with Obatoclax mesylate or NIGERICIN as defined in claim 1 for the preparation of an anti-colistin resistant gram negative bacterial medicament.
3. 3. The use according to claim 2, wherein the gram-negative bacteria comprise coliform bacteria and klebsiella pneumoniae resistant to coliform bacteria.
4. 4. The use according to claim 2, wherein the concentration of colistin in the pharmaceutical composition is 4-64 mg/L.
5. 5. The use according to claim 2, wherein the concentration of Obatoclax mesylate in the pharmaceutical composition is 0.032-512 mg/L; the concentration of NIGERICIN in the pharmaceutical composition is 0.032-512 mg/L.

Description

Use of Obatoclax mesylate and/or NIGERICIN for the preparation of antibiotic sensitizers Technical Field The invention relates to the technical field of biological medicines, in particular to application of Obatoclax mesylate and/or NIGERICIN in preparation of an antibiotic sensitizer. Background Colistin is the last line-proof drug for treating multiple drug-resistant klebsiella pneumoniae, and is often clinically used in combination with other antibiotics to treat severe carbapenem-resistant klebsiella pneumoniae (carbapenem-resistance k. Pneumoniae, CRKP) infection. However, as the amount of colistin used increases, the CRKP strain resistant to colistin has appeared and the drug resistance rate is about 4%. More severely, most of the colistin resistant CRKP is a ST11 type high virulent strain, and such "superbacteria" are resistant to almost all antibacterial drugs except tigecycline and ceftazidime/avibactam. A large amount of clinical data shows that tigecycline has poor effects in treating CRKP-caused infections, and that colistin or tigecycline pressure can cause carbapenem-resistant high-virulence klebsiella pneumoniae (CR-hvKP) to rapidly become resistant to colistin in a short period of time. CRKP has been listed by the world health organization as the highest priority for research, discovery and development of novel antibacterial agents. Therefore, overcoming the drug resistance problem of CRKP to colistin has become an urgent need and a core task of current clinical treatment. Along with the increasing severity of the bacterial drug resistance problem, the development period of the novel antibiotics is long, the difficulty is high, the number of batches is greatly reduced, the novel use of the old drugs is excavated, and the high-efficiency antibiotic sensitizer is developed, so that the novel antibiotic has become a key strategy for coping with drug-resistant bacterial infection and breaking the dilemma of clinical treatment. Disclosure of Invention The invention aims to provide an application of Obatoclax mesylate and/or NIGERICIN in preparing antibiotic sensitizer, and Obatoclax mesylate or NIGERICIN can effectively enhance the action of colistin when being combined with colistin, so as to achieve better effect of inhibiting growth of colistin resistant gram-negative bacteria. In order to achieve the above object, the present invention provides the following technical solutions: The invention provides use of Obatoclax mesylate and/or NIGERICIN in the preparation of an antibiotic sensitizer. Preferably, the antibiotic comprises colistin. The invention also provides application of the pharmaceutical composition of colistin and Obatoclax mesylate or NIGERICIN in preparation of anti-colistin drug-resistant gram-negative bacteria drugs. Preferably, the gram-negative bacteria include Escherichia coli and Klebsiella pneumoniae. Preferably, the concentration of colistin in the pharmaceutical composition is 4-64 mg/L. Preferably, the concentration of Obatoclax mesylate in the pharmaceutical composition is 0.032-512 mg/L. Preferably, the concentration of NIGERICIN in the pharmaceutical composition is 0.032-512 mg/L. By adopting the technical scheme, the invention has the following beneficial effects: According to the technical scheme, a plurality of existing ionophores are screened through a chessboard method, so that Obatoclax mesylate or NIGERICIN and colistin are determined to have a synergistic effect when being combined, and a new application of the ionophores serving as a sensitizer of antibiotics to drug-resistant bacteria treatment is excavated. The sterilization curve and the drug sensitivity test also show that Obatoclax mesylate or NIGERICIN can inhibit the growth of colistin resistant gram-negative bacteria by being combined with colistin, and can obviously reduce MIC values of colistin resistant gram-negative bacteria, including Escherichia coli and Klebsiella pneumoniae. That is, obatoclax mesylate or NIGERICIN of the invention can reverse colistin resistance. The Obatoclax mesylate and NIGERICIN in the technical scheme of the invention are anti-tumor drugs, and have better anti-cancer activity on various cancers, especially on tumor stem cells which are highly resistant to chemotherapy and cause tumor recurrence. Drawings FIG. 1 is a graph showing the results of in vitro sterilization curves of different treatment groups (FIG. 1 (a) shows the sterilization effect of NIGERICIN, NIGERICIN in combination with colistin, and (b) shows the sterilization effect of Obatoclax mesylate, obatoclax mesylate in combination with colistin). Detailed Description The invention provides an application of Obatoclax mesylate (product number 010012, beijing Przewald Biotechnology Co., ltd.) and/or NIGERICIN (nigericin) (product number N60011, beijing Przewald Biotechnology Co., ltd.) in preparing antibiotic sensitizer. In the present invention, the antibiotic is preferably Colistin. The invention also provid