CN111420026B - Application of capsaicin and colistin in preparation of medicines for inhibiting acinetobacter baumannii infection - Google Patents
Application of capsaicin and colistin in preparation of medicines for inhibiting acinetobacter baumannii infection Download PDFInfo
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- CN111420026B CN111420026B CN202010466197.3A CN202010466197A CN111420026B CN 111420026 B CN111420026 B CN 111420026B CN 202010466197 A CN202010466197 A CN 202010466197A CN 111420026 B CN111420026 B CN 111420026B
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Abstract
The invention provides an application of capsaicin and colistin in preparation of a medicine for inhibiting acinetobacter baumannii infection, belonging to the technical field of biological medicines, wherein the acinetobacter baumannii comprises colistin-resistant acinetobacter baumannii; the capsaicin can cooperate with colistin to play a role in resisting acinetobacter baumannii, so that the infection caused by colistin-resistant acinetobacter baumannii is treated. When capsaicin was used in combination with colistin, more than 50% of colistin-resistant A.baumannii was killed within 12h, with a reduction of more than 2log10 after 12h per ml CFU, demonstrating a synergistic effect of capsaicin and colistin.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to application of capsaicin and colistin in preparation of a medicine for inhibiting acinetobacter baumannii infection.
Background
Acinetobacter baumannii (Ab) is an obligate aerobic non-fermentative gram-negative bacillus, and is very easy to infect patients with serious basic diseases or low autoimmunity, so that ventilator-associated pneumonia (VAP), bacteremia, skin and soft tissue infection, endocarditis, urinary tract infection and meningitis are caused. Therefore, it is important to find new strategies for the treatment of acinetobacter baumannii infection.
Due to the scarcity of effective therapeutic drugs and newly developed antibiotics, some of the traditional antibiotics that have been abandoned, such as polymyxins (colistin, polymyxin B), are forced to be re-used to treat serious infections caused by multidrug resistant gram-negative bacteria. Colistin is highly sensitive to drug-resistant gram-negative bacteria and is the ultimate hope for the treatment of severe infections caused by multi-drug resistant gram-negative bacteria. However, it is feared that as the frequency of use and the dosage thereof increase, colistin-resistant (heterogeneous drug-resistant) strains are sequentially detected. In order to protect this last barrier against multi-drug resistant gram-negative pathogens from being breached, it is important to seek an appropriate treatment regimen to delay the onset of colistin resistance or to restore its antibacterial activity.
Disclosure of Invention
The invention aims to provide application of capsaicin and colistin in preparation of a medicine for inhibiting acinetobacter baumannii infection, wherein the capsaicin can inhibit infection caused by colistin-resistant acinetobacter baumannii.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides application of capsaicin and colistin in preparation of a medicine for inhibiting acinetobacter baumannii infection.
Preferably, the acinetobacter baumannii comprises colistin-resistant acinetobacter baumannii.
The invention provides a medicament for inhibiting acinetobacter baumannii infection, which comprises capsaicine and colistin which are packaged independently.
Preferably, the mass concentration of capsaicin in the medicine is 8-256 mg/L; the mass concentration of colistin in the medicine is 0.5-16 mg/L.
Preferably, the dosage form of the medicament comprises an injection.
The invention has the beneficial effects that: the invention provides an application of capsaicin and colistin in preparing a medicament for inhibiting acinetobacter baumannii infection, wherein the medicament comprises colistin-resistant acinetobacter baumannii; the capsaicin can cooperate with colistin to play a role in resisting acinetobacter baumannii, so that the infection caused by colistin-resistant acinetobacter baumannii is treated. When capsaicin was used in combination with colistin, more than 50% of colistin-resistant A.baumannii was killed within 12h, with a reduction of more than 2log10 after 12h per ml CFU, demonstrating a synergistic effect of capsaicin and colistin.
Drawings
FIG. 1 is a time sterilization curve of capsaicin and/or colistin against colistin-resistant A.baumannii, wherein A in FIG. 1 is the change trend of the bacterial number of a strain Ab13-R within 12h after 4 different medicaments are treated; b in FIG. 1 is the trend of the bacterial count of the strain Ab156-R within 12h after 4 different drug treatments; FIG. 1C shows the trend of the number of bacteria in ATCC19606-R after 4 different treatments for 12 hours;
FIG. 2 is a graph showing the effect of capsaicin and/or colistin on the bacterial load in different organs of mice after Acinetobacter baumannii infection; wherein A in FIG. 2 is the Acinetobacter baumannii loading in the liver for 4 different drug treatment modes; b in FIG. 2 is the Acinetobacter baumannii loading in lungs for 4 different drug treatment modes; c in FIG. 2 is the Acinetobacter baumannii loading in the kidneys of 4 different drug treatment modes; d in FIG. 2 is the Acinetobacter baumannii loading in the spleens for 4 different drug treatment modes;
FIG. 3 is a graph showing the effect of capsaicin and/or colistin on the blood content of mice infected with Acinetobacter baumannii.
Detailed Description
The invention provides application of capsaicin and colistin in preparation of a medicine for inhibiting acinetobacter baumannii infection.
In the present invention, the acinetobacter baumannii is preferably colistin-resistant acinetobacter baumannii. Capsaicin is available from selelck, and colistin is available from selelck. Through research on the influence of capsaicin on the Acinetobacter baumannii biofilm, the capsaicin is found to be capable of obviously inhibiting the formation of the Acinetobacter baumannii biofilm, so that the aggregation of the Acinetobacter baumannii can be reduced, the obstacle of medicine diffusion is relieved, and the antibacterial effect of colistin is finally enhanced.
The invention provides a medicament for inhibiting acinetobacter baumannii infection, which comprises capsaicine and colistin which are packaged independently. The capsaicin can obviously reduce the MIC value of the colistin-resistant acinetobacter baumannii to colistin, so that the MIC value of colistin of most strains is lower than a sensitive value. Therefore, the capsaicin can cooperate with colistin to play a role in resisting acinetobacter baumannii, so that the infection caused by colistin-resistant acinetobacter baumannii can be treated.
In the invention, the mass concentration of capsaicin in the medicine is preferably 8-256 mg/L, more preferably 32-128 mg/L, and most preferably 64-90 mg/L; the mass concentration of colistin in the medicine is preferably 0.5-16 mg/L, and the optimal concentration in clinic is 2mg/L in consideration of neurotoxicity and nephrotoxicity of colistin.
In the present invention, the solvent of capsaicin is preferably dimethyl sulfoxide (DMSO); the solvent of the colistin is preferably ddH 2 O。
In the present invention, the dosage form of the drug includes an injection.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1 checkerboard test for the synergistic Effect of capsaicin and colistin
The clinical isolates of different sources, acinetobacter baumannii Ab13, acinetobacter baumannii Ab156 and the standard strain acinetobacter baumannii ATCC19606, induced drug resistance, and the resulting drug resistant strains were named: acinetobacter baumannii Ab13-R, Acinetobacter baumannii Ab156-R and Acinetobacter baumannii ATCC 19606-R. Wherein Ab13, Ab156, Ab13-R, Ab156-R and ATCC19606-R are deposited at the university of Yangzhou pathogenic microbiology laboratory. The capsaicin solvent is DMSO, the colistin solvent is ddH 2 O, make up mother liquor and dilute to the desired concentration (27g/1000mL distilled water) with MH broth.
Firstly, singly treating drug-resistant and non-drug-resistant Acinetobacter baumannii strains by capsaicin with the concentrations of 256mg/L, 128mg/L, 64mg/L, 32mg/L and 16mg/L, and the result shows that the MIC of the capsaicin singly used for all tested strains is more than 512mg/L, and no antibacterial activity is found;
and then, detecting the synergistic effect of capsaicin and colistin by using a chessboard test, wherein the concentration of each row of the multiplicable capsaicin (0-256 mg/L) and the concentration of each row of the multiplicable colistin (0-64 mg/L) are in a 96-well plate. Each well was inoculated with 100. mu.l of test strain suspension (5X 10) 5 CFU/mL) with a final volume of 200. mu.l, and then incubating at 37 ℃ for 24h, the results are shown in Table 1, and it can be seen that capsaicin reduced the Ab13-R MIC value by 8-128 times, the Ab156-R MIC value by 16-128 times, and the A19606-R1 MIC value by 128-2048 times. Therefore, different concentrations of capsaicin significantly reduce the MIC value of colistin to colistin of colistin-resistant Acinetobacter baumannii, so that the MIC value of colistin of most strains is lower than the sensitive value (2 mg/L). The capsaicin is prompted to cooperate with colistin to play an antibacterial role, so that the infection caused by colistin-resistant acinetobacter baumannii is treated.
TABLE 1 Effect of different concentrations of capsaicin on the MIC values of colistin-resistant A.baumannii colistin
Example 2 time sterilization Curve to examine the synergistic Effect of capsaicin and colistin
To further demonstrate the synergistic effect of capsaicin and colistin, the 3 colistin-resistant A.baumannii strains that demonstrated efficacy as described above were subjected to a time sterilization curve test. Respectively to 5 × 10 9 Ab13-R and 5X 10 of CFU/mL 6 CFU/mL Ab156-R, ATCC19606-R inoculum with different drugs was shake-cultured at 37 ℃ and plates were counted with samples taken every 2 h. The colistin concentration in this test is the clinical sensitivity threshold: 2mg/L, capsaicin concentration Ab13-R of 256mg/L, Ab156-R and ATCC19606-R of 32 mg/L. The results are shown in fig. 1, and it can be seen that the bacterial growth of the single drug group is not significantly different from that of the control group within 12 h; however, when capsaicin was used in combination with colistin, more than 50% of the bacteria were killed within 12h, with a greater than 2log10 reduction per ml of CFU after 12h, demonstrating a synergistic effect of capsaicin and colistin.
Example 3 synergistic Effect of capsaicin and colistin in vivo
First using 2X 10 7 Mice were injected intraperitoneally with CFU/A13-R strain suspension, and no death was observed after 24h, indicating that the separated and induced colistin-resistant strain A13-R is relatively weak in toxicity. Injecting A13-R strain suspension into abdominal cavity of mouse, and injecting sterile PBS into control group; the drug treatment group received treatment 24h after infection of the mice, and the colistin group received 5mg/kg colistin; the capsaicin group is treated by 200 mu mol/L capsaicin solution; in the combination group, 1mg/kg colistin and 100. mu. mol/L capsaicin solution were injected and the administration was performed in two divided portions at 2h intervals. After the treatment lasts for 3 days, blood is taken from eyeballs, lungs, kidneys, spleens and livers are collected, the bacterial load of the eyeballs is detected, the results are shown in the table 2, the figure 2 and the figure 3, the acinetobacter baumannii exists in the blood and different organs, and the bacterial load of the blood, the lungs, the livers, the spleens and the kidneys is remarkably reduced by combining capsaicin and colistin.
TABLE 2 determination of the bacterial content of capsaicin and/or colistin in mice after Acinetobacter baumannii infection
**P<0.01。
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (3)
1. Use of capsaicin and colistin for inhibiting the formation of a biofilm of acinetobacter baumannii; the use is not for the treatment of disease.
2. The use according to claim 1, wherein said acinetobacter baumannii comprises colistin-resistant acinetobacter baumannii.
3. The use as claimed in claim 1, wherein the concentration of capsaicin is 8-256 mg/L; the mass concentration of the colistin is 0.5-16 mg/L.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010466197.3A CN111420026B (en) | 2020-05-28 | 2020-05-28 | Application of capsaicin and colistin in preparation of medicines for inhibiting acinetobacter baumannii infection |
| AU2021101008A AU2021101008A4 (en) | 2020-05-28 | 2021-02-23 | Use of capsaicin and colistin in preparing a medicament for inhibiting acinetobacter baumannii infection |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010466197.3A CN111420026B (en) | 2020-05-28 | 2020-05-28 | Application of capsaicin and colistin in preparation of medicines for inhibiting acinetobacter baumannii infection |
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| Publication Number | Publication Date |
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| CN111420026A CN111420026A (en) | 2020-07-17 |
| CN111420026B true CN111420026B (en) | 2022-08-05 |
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| CN202010466197.3A Active CN111420026B (en) | 2020-05-28 | 2020-05-28 | Application of capsaicin and colistin in preparation of medicines for inhibiting acinetobacter baumannii infection |
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| CN (1) | CN111420026B (en) |
| AU (1) | AU2021101008A4 (en) |
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2020
- 2020-05-28 CN CN202010466197.3A patent/CN111420026B/en active Active
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- 2021-02-23 AU AU2021101008A patent/AU2021101008A4/en not_active Ceased
Non-Patent Citations (9)
| Title |
|---|
| Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids;Berrin Ozçelik等;《Pharm Biol》;20110430;第49卷(第4期);表2 * |
| Inhibiting Bacterial Drug Efflux Pumps via Phyto-Therapeutics to Combat Threatening Antimicrobial Resistance;Varsha Shriram等;《Front Microbiol》;20181210;摘要和第2页右栏第3段 * |
| Synergistic Activity of Capsaicin and Colistin Against Colistin-Resistant Acinetobacter baumannii: In Vitro/Vivo Efficacy and Mode of Action;Tingting Guo等;《Front Pharmacol》;20210917;第1-14页 * |
| 外排泵抑制剂研究进展;顾觉奋;《国外医药（抗生素分册）》;20200115;第41卷(第1期);第1-10页 * |
| 粘菌素等抗菌药物对临床分离鲍曼不动杆菌的抗菌活性;李然等;《中国临床药理学与治疗学》;20090326(第03期);第287页右栏第2段、第289页左栏第1段和第290页左栏第2段 * |
| 辣椒素抑菌作用的初步研究;张祖姣等;《辣椒杂志》;20121220(第04期);第37-39页 * |
| 辣椒素的抑菌活性研究现状;刘营营等;《粮食科技与经济》;20100915(第05期);第18-22页 * |
| 辣椒素类物质抑菌作用的研究与评价;陈世化;《中国优秀硕士学位论文全文数据库 工程科技I辑》;20090915;B024-51 * |
| 鲍曼不动杆菌CRISPR相关蛋白Csy1抑制耐药性及辣椒素联合粘菌素的抗菌作用与机制研究;李梦影;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20210815;E079-70 * |
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| AU2021101008A4 (en) | 2021-04-29 |
| CN111420026A (en) | 2020-07-17 |
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