CN111803476A - Use of fingolimod for inhibiting the activity of gram-positive bacteria - Google Patents

Abstract

The present invention provides the use of fingolimod for inhibiting the activity of Gram-positive bacteria, and the fingolimod is used for inhibiting the growth of Gram-positive bacteria. The technical scheme of the present invention discloses a new application of fingolimod, which has bacteriostatic activity and lower gram-positive bacteria, such as Staphylococcus aureus, Enterococcus and Streptococcus agalactiae, etc. The MIC value, especially in the environment of Staphylococcus aureus, fingolimod has a strong bactericidal effect on Staphylococcus aureus, and the MIC value is generally 3.125μg/mL; it can significantly inhibit grape aureus at 1/2 MIC. Formation of coccus biofilms; in addition, fingolimod has demonstrated the ability to clear Staphylococcus aureus biofilms at a concentration of 2×MIC, and can significantly remove Staphylococcus aureus biofilms at concentrations ≥4×MIC membrane. Fingolimod also induced a significant decrease in the ability of Staphylococcus aureus to form biofilms.

Description

Use of fingolimod for inhibiting the activity of gram-positive bacteria

technical field

The invention belongs to the technical field of medicine, and particularly relates to the use of fingolimod for inhibiting the activity of gram-positive bacteria.

Background technique

Staphylococcus aureus, referred to as Staphylococcus aureus, is one of the common pathogens of hospital and community-acquired infections, and one of the most common life-threatening bacterial infections. It can cause a series of purulent infections, food poisoning, and even cause Serious life-threatening diseases such as sepsis and toxic shock syndrome. With the widespread use of antibacterial drugs, the detection rate of drug resistance of Staphylococcus aureus continues to increase, especially methicillin-resistant Staphylococcus aureus (MRSA), and even vancomycin-resistant Staphylococcus aureus (VRSA) With the continuous increase, Staphylococcus aureus may break through the last line of defense of human antibiotics and directly threaten human life and health. It is urgent to develop new anti-Staphylococcus aureus drugs. In addition, either MRSA or MSSA Staphylococcus aureus can form biofilms on the surface of human tissue cells or medical implant materials, thereby reducing the sensitivity to antimicrobial drugs and evading host immune cell attacks. Bacterial biofilms It will also lead to the formation of persistent bacteria, which will eventually lead to chronic infection and prolonged unhealing of patients, seriously affecting the quality of life of patients. At present, there are only a few antibacterial drugs that have inhibitory activity on the formation of Staphylococcus aureus biofilms. Therefore, there is an urgent need to research and develop drugs that can effectively inhibit the formation of Staphylococcus aureus biofilms.

At present, the clinical anti-Staphylococcus aureus drugs are oxacillin, vancomycin and linezolid. Among them, oxacillin is the first choice for MSSA, and vancomycin is the only choice for MRSA. Vancomycin has strong toxic and side effects on the kidneys and ear nerves, while linezolid is a bacteriostatic drug, and its bactericidal effect is not strong.

Fingolimod is a new type of immunosuppressant obtained by chemical modification of the immune-related component myriocin-1 (ISP-1) isolated from Cordyceps sinensis. Studies have found that in addition to its immunosuppressive effect, it also has a certain improvement effect on stroke and neurological damage. It acts as a non-selective agonist of sphingosine 1-phosphate receptor (S1PR) and a selective functional antagonist of S1P1 subtype by inducing receptor downregulation to exert its physiological activity. A review of the literature found that no studies on the antibacterial activity of the drug have been found so far.

SUMMARY OF THE INVENTION

In view of the above technical problems, the present invention discloses a use of fingolimod for inhibiting the activity of gram-positive bacteria, which is a new use of fingolimod. For example, Staphylococcus aureus, Enterococcus and Streptococcus agalactiae have good bacteriostatic and bactericidal effects, and can significantly inhibit the formation of gram-positive bacterial biofilms, especially the formation of Staphylococcus aureus biofilms.

To this, the technical scheme adopted in the present invention is:

Use of fingolimod for inhibiting the activity of Gram-positive bacteria, said fingolimod for inhibiting the growth of Gram-positive bacteria. The gram-positive bacteria are Staphylococcus aureus, Enterococcus, Streptococcus agalactiae and the like.

Fingolimod is a sphingosine 1-phosphate receptor modulator drug, which is mostly used clinically for multiple sclerosis, as well as for neurological diseases such as stroke. Although fingolimod has been used clinically for many years, there is no research report on its anti-infection. It is found in the present invention that fingolimod has a good effect on inhibiting the activity of Gram-positive bacteria, especially Staphylococcus aureus. Fingolimod has bacteriostatic activity and low MIC (minimum inhibitory concentration, the lowest) in various bacterial infections related antibiotics caused by a variety of gram-positive bacteria (such as Staphylococcus aureus, Enterococcus, and Streptococcus agalactiae, etc.). Inhibitory concentration) value.

As a further improvement of the present invention, the concentration of fingolimod is not less than 1.5625 μg/mL. Preferably, the MIC of fingolimod for inhibiting Gram-positive bacteria is 1.5625-12.5 μg/mL. Wherein, the gram-positive bacteria are Staphylococcus aureus, Enterococcus, Streptococcus agalactiae and the like.

As a further improvement of the present invention, the concentration of fingolimod is not less than 3.125 μg/mL.

As a further improvement of the present invention, the concentration of fingolimod is not less than 6.25 μg/mL.

As a further improvement of the present invention, the concentration of fingolimod is not less than 12.5 μg/mL.

As a further improvement of the present invention, fingolimod is used as a relevant antibiotic for various bacterial infections caused by gram-positive bacteria (Staphylococcus aureus, Enterococcus, Streptococcus agalactiae, etc.).

The invention discloses the use of fingolimod for anti-Staphylococcus aureus biofilm activity, and the fingolimod has biofilm removal activity at a concentration of 4×MIC. After research, it was found that the MIC value of fingolimod is generally 3.125 μg/mL, and it has a strong bactericidal effect. The concentration of fingolimod can significantly inhibit the formation of Staphylococcus aureus biofilm at 1/2 MIC, that is, 1.5625 μg/mL; in addition, when the concentration of fingolimod is 2×MIC, that is, 6.25 μg/mL, it has been shown The ability to remove Staphylococcus aureus biofilm, and when the concentration is greater than 4 × MIC or 12.5μg/mL, it can significantly remove Staphylococcus aureus biofilm.

The invention discloses the application of fingolimod in the preparation of a medicament against gram-positive bacterial infection, and the medicament against gram-positive bacterial infection includes fingolimod. Wherein, the gram-positive bacteria are Staphylococcus aureus, Enterococcus, Streptococcus agalactiae and the like.

As a further improvement of the present invention, the concentration of fingolimod is not less than 1.5625 μg/mL.

As a further improvement of the present invention, the concentration of fingolimod is not less than 3.125 μg/mL.

As a further improvement of the present invention, the concentration of fingolimod is not less than 6.25 μg/mL.

As a further improvement of the present invention, the concentration of fingolimod is not less than 12.5 μg/mL.

Preferably, the concentration of fingolimod is 1.5625-12.5 μg/mL.

Preferably, the drug can be in the form of spray, oral granules, oral tablets or injection.

As a further improvement of the present invention, the drug against Gram-positive bacterial infection includes other drugs, such as other antibiotics. Preferably, the drug against gram-positive bacterial infection comprises oxacillin. The combined use of fingolimod and oxacillin has better anti-gram-positive bacteria, especially Staphylococcus aureus infection.

As a further improvement of the present invention, in the drug against gram-positive bacterial infection, the concentration of fingolimod is not less than 3.125 μg/mL, and the concentration of oxacillin is not less than 0.25 μg/mL. Preferably, the concentration of the oxacillin is not less than 0.5 μg/mL. Preferably, the concentration of the oxacillin is not less than 16 μg/mL.

The invention discloses the application of fingolimod in the preparation of coatings for the surface of medical devices, the fingolimod is used for inhibiting the formation of gram-positive bacteria biofilm and the adhesion of gram-positive bacteria.

As a further improvement of the present invention, in the coating for the surface of a medical device, the concentration of fingolimod is not less than 1.5625 μg/mL. Preferably, the concentration of fingolimod is 1.5625-12.5 μg/mL. The fingolimod concentration of 1.5625-12.5 μg/mL has the ability to inhibit biofilm formation, so if the compound is directly adhered to the surface of the medical material, the adhesion of Gram-positive bacteria on the surface of the medical material can be reduced.

The invention discloses a coating for the surface of medical equipment, which comprises fingolimod. Preferably, the concentration of fingolimod is not less than 1.5625 μg/mL. Preferably, the concentration of fingolimod is not less than 3.125 μg/mL. Preferably, the concentration of fingolimod is not less than 6.25 μg/mL. Preferably, the concentration of fingolimod is not less than 12.5 μg/mL.

The invention discloses the application of fingolimod in the preparation of a disinfectant against Gram-positive bacteria, and the disinfectant against Gram-positive bacteria comprises fingolimod. The fingolimod can inhibit gram-positive bacterial biofilm formation and gram-positive bacterial adhesion. Fingolimod has good activity for inhibiting or killing a variety of Gram-positive bacteria (such as Staphylococcus aureus, Enterococcus and Streptococcus agalactiae, etc.).

Wherein, the MIC value of the fingolimod for inhibiting or killing Gram-positive bacteria is lower than 6.25 μg/mL. Preferably, in the anti-Gram-positive bacteria disinfectant, the concentration of fingolimod is not less than 1.5625 μg/mL. Preferably, the concentration of fingolimod is not less than 3.125 μg/mL. Preferably, the concentration of fingolimod is not less than 6.25 μg/mL. Preferably, the concentration of fingolimod is not less than 12.5 μg/mL.

The invention discloses a disinfectant against Gram-positive bacteria, which comprises fingolimod. Preferably, in the anti-Gram-positive bacteria disinfectant, the concentration of fingolimod is not less than 1.5625 μg/mL. Preferably, the concentration of fingolimod is not less than 3.125 μg/mL. Preferably, the concentration of fingolimod is not less than 6.25 μg/mL. Preferably, the concentration of fingolimod is not less than 12.5 μg/mL.

Compared with the prior art, the beneficial effects of the present invention are:

The technical scheme of the present invention discloses a new application of fingolimod, which is used for inhibiting the activity of gram-positive bacteria, and the gram-positive bacteria are Staphylococcus aureus, Enterococcus, Streptococcus agalactiae, etc., The drug has bacteriostatic activity and low MIC value. Especially in the environment of Staphylococcus aureus, fingolimod has a strong bactericidal effect on Staphylococcus aureus, and the MIC value is generally 3.125 μg/mL. It can significantly inhibit the formation of Staphylococcus aureus biofilm at 1/2 MIC; in addition, at the concentration of fingolimod at 2 × MIC, it has shown the ability to clear Staphylococcus aureus biofilm, while at concentrations ≥ 4 When ×MIC, it can significantly remove Staphylococcus aureus biofilm. Fingolimod also induced a significant decrease in the ability of Staphylococcus aureus to form biofilms. Preferably, fingolimod can be combined with oxacillin to have a better synergistic inhibitory effect on the bacterial growth of Staphylococcus aureus.

Description of drawings

Fig. 1 is the growth curve diagram of eight strains of Staphylococcus aureus of the embodiment of the present invention under the action of different concentrations of fingolimod, wherein a) is SE13 Staphylococcus aureus, b) is SE16 Staphylococcus aureus, and c) is CHS350 Staphylococcus aureus, d) is SA113 Staphylococcus aureus, e) is YUSA10 Staphylococcus aureus, f) is CHS655 Staphylococcus aureus, g) is CHS101 Staphylococcus aureus, h) is YUSA16 Staphylococcus aureus.

Fig. 2 is the growth curve of different Enterococcus faecalis under the action of different concentrations of fingolimod in the embodiment of the present invention; wherein, a) is Enterococcus faecalis EF16C112, b) is Enterococcus faecalis EF16C118, c) is Enterococcus faecalis EF16C123 , d) is Enterococcus faecalis EF16C129.

3 is the growth curve of different Streptococcus agalactiae under the action of different concentrations of fingolimod in the embodiment of the present invention; wherein, a) is Streptococcus agalactiae NSGC64, and b) is Streptococcus agalactiae NSGC116.

FIG. 4 is a bactericidal curve diagram of fingolimod against SE13 and CHS350 under the drug concentration of 4×MIC according to the embodiment of the present invention; wherein, a) is SE113 Staphylococcus aureus, and b) is CHS350 Staphylococcus aureus.

FIG. 5 is a graph showing the results of inhibiting the formation of crystal violet by fingolimod in the biofilm of Staphylococcus aureus according to an embodiment of the present invention.

FIG. 6 is the results of the inhibition ability of fingolimod at different concentrations on Staphylococcus aureus biofilm formation according to the embodiment of the present invention. After culturing 6 clinical S. aureus strains (4 strains MSSA, 2 strains MRSA) with or without fingolimod, biofilms were stained with 1% crystal violet and detected by optical density at 570 nm (OD570). *P<0.01 compared to control; **P<0.001 compared to control (t-test).

Fig. 7 is the antibacterial activity results of fingolimod, linezolid, vancomycin single drug and combination drug on different Staphylococcus aureus of the embodiment of the present invention, wherein a) is CHS350 Staphylococcus aureus, b) is CHS655 Staphylococcus aureus, c) is YUSA10 Staphylococcus aureus, d) is YUSA16 Staphylococcus aureus.

Fig. 8 is the antibacterial activity result of fingolimod, oxacillin single drug and combination drug of the embodiment of the present invention to different Staphylococcus aureus, a) is YUSA10 Staphylococcus aureus, b) is YUSA16 Staphylococcus aureus, c) is CHS350 Staphylococcus aureus.

Fig. 9 is the result of clearing crystal violet of Staphylococcus aureus biofilm by fingolimod in the embodiment of the present invention.

FIG. 10 is a graph showing the results of clearing Staphylococcus aureus biofilm with different concentrations of fingolimod and three antibiotics in the embodiment of the present invention. *P<0.01 compared to control; **P<0.001 compared to control (t-test).

FIG. 11 is the test result of biofilm formation ability of fingolimod-induced strains according to the embodiment of the present invention. *P<0.001 compared to control group.

Detailed ways

The preferred embodiments of the present invention will be further described in detail below.

A variety of gram-positive bacteria (including Staphylococcus aureus, Enterococcus faecalis, and Streptococcus agalactiae, etc.) are common opportunistic pathogens in nosocomial and community-acquired infections. The infection rate of MRSA is rising in various places, which seriously threatens human life and health. The emergence of vancomycin-resistant Staphylococcus aureus has exacerbated this form. There is an urgent need to develop new anti-Staphylococcus aureus drugs.

Fingolimod is mostly used clinically for multiple sclerosis and also for neurological diseases such as stroke. Although it has been used clinically for many years, there is no research report on its anti-infection. The present invention finds the new application of fingolimod for anti-a variety of gram-positive bacteria activity (including Staphylococcus aureus, Enterococcus faecalis and Streptococcus agalactiae, etc.), the following is the experimental process:

1.1 strain information

Seven strains of Staphylococcus aureus (2 strains of MRSA and 5 strains of MSSA) were selected from the clinical strains collected in our hospital in the early stage as the experimental strains in this study. The resuscitated strains were preliminarily identified and analyzed using the Phoenix 100 automatic analysis and identification instrument from BD Company in the United States, and the strains were re-identified using a flight mass spectrometer (IVD MALDI Biotyper, Germany) after inoculation and stable passage for two generations. The drug-susceptible quality control strain used in this study was Staphylococcus aureus ATCC29213, and SA113 was the biofilm positive control strain. The clinical strains of Enterococcus faecalis and Streptococcus agalactiae were collected from the clinical microbiology laboratory of Huazhong University of Science and Technology Union Shenzhen Hospital.

1.2 The minimum inhibitory concentration (MIC) of fingolimod against Staphylococcus aureus was measured by broth dilution method

Bacteria were cultured overnight in TSB medium at 37°C and 220rpm/min for 10-12h; the above bacterial solution was adjusted with sterile saline to reach turbidity of 0.5 McFarland (the bacterial volume was about 1.0×10 ⁸ cfu /ml), and then diluted 1:100 with medicated CAMHB medium, the drug was serially diluted with CAMHB medium, and the drug was 8 gradients (100 μg/mL times decreased to 0.78 μg/mL), and the bacterial liquid was added In a 96-well plate, set 3 duplicate wells, and place them in a 37°C incubator for 20-24 hours to observe the minimum concentration at which bacterial growth in each well is completely inhibited.

1.3 Determination of fingolimod killing curve of Staphylococcus aureus

The strains were incubated overnight at 37°C and 220rpm/min in MHB medium for 12h, and then diluted with CAMHB medium at 1:100 and continued to be shaken at 37°C and 220rpm/min for 2 hours. Draw 1 mL of bacterial solution 0.9% NaCl diluted plate (TSA plate) for counting, at the same time divide the bacterial solution and add 4 × MIC drug concentration, when the drug acts for 3 hours and 24 hours, draw 1 mL of bacterial solution 0.9% NaCl for centrifugation and washing 1 Resuspend the diluted plate and count after 2 times.

1.4 Biofilm assay after fingolimod inhibited Staphylococcus aureus

A 96-well plate (Costar 3599, 200 μL/well) was used to establish a Staphylococcus aureus biofilm model, the biofilm was stained with crystal violet, and the OD570 absorbance value was measured by a microplate reader. Briefly, strains were diluted 1:200 and activated in TSB medium at 37°C at 200rpm/min overnight for 10-12 hours, then treated with fingolimod-containing TSBG medium (TSB containing 0.25% glucose) 1:200 After dilution, it was added to a 96-well plate, and three wells were set; after standing for 24 hours, the supernatant was removed, the plate was washed three times with 0.9% NaCl solution, stained with 1% crystal violet solution for 20 minutes, and the free crystal violet was washed with ddH2O; Use a microplate reader to detect the absorbance of OD570 to determine the biofilm content of the strain.

1.5 Biofilm assay after fingolimod eradication of Staphylococcus aureus

After the strain was recovered for 10-12 hours according to the above method, it was diluted with TSBG medium at 1:200 and added to a 96-well plate, and three duplicate wells were set; The 0.9% NaCl solution was gently washed three times, and the drug-containing TSBG solution was added to incubate for 48 hours, and the dressing was changed at 24 hours. Stain and measure absorbance as described above.

1.6 Determination of growth curve of planktonic bacteria of experimental strains

Use the Finnish Bioscreen automatic growth curve analyzer to detect the growth curve of bacteria: take the strain at 1:200 dilution, activate it in TSB medium at 37°C, 200rpm/min overnight for 10-12 hours, and add the pre-prepared strain at 1:200. In TSB medium containing different concentrations of drugs, and three duplicate wells were added to the special well plate of the automatic growth curve instrument, the drug concentration was prepared according to the multi-dilution method; the program was set according to the instrument manual, and the OD600 absorbance was measured every hour. Measure the growth activity of planktonic bacteria, record for 24 hours, repeat the experiment three times, and the final result is the average value of detection.

1.7 Statistical processing

GraphPad prism 8.0 software was used for statistical processing of data, measurement data were expressed as x ± s, and t-test was used for the mean of two independent samples.

Through the above experiments, the experimental results after statistical analysis are as follows:

(1) Fingolimod has good bacteriostatic effect on Staphylococcus aureus, Enterococcus faecalis and Streptococcus agalactiae

In the experiment, we selected eight Staphylococcus aureus strains SE13, SE16, CHS350, SA113, YUSA10, CHS655, CHS101 and YUSA16, four strains of Enterococcus faecalis EF16C112, EF16C118, EF16C123 and EF16C128, and two strains of Streptococcus agalactiae NSGC116 and NSGC64. Under the action of different concentrations of fingolimod, their OD values were measured every 1 hour, and a 24-hour growth curve was drawn, as shown in Figures 1 to 3. It can be seen from the results that when the concentration of fingolimod is 3.125μg/mL, the effect of inhibiting the growth of Staphylococcus aureus and Enterococcus faecalis has appeared, and when the concentration is ≥6.25μg/mL, all Staphylococcus aureus and Enterococcus faecalis can hardly grow, and 50 clinical Enterococcus faecalis strains were selected to further confirm that their MIC≤6.25μg/mL; while for Streptococcus agalactiae, the obvious inhibitory effect appeared at the concentration of 1.56μg/mL, when Concentration ≥3.125μg/mL almost completely inhibited the growth, and 60 clinical strains of Streptococcus agalactiae were selected to further confirm their MIC≤3.125μg/mL. The above results show that fingolimod has a good ability to inhibit the growth of Gram-positive bacteria, and it has a bacteriostatic effect at a very low concentration. As shown in Figure 1, Figure 2, and Figure 3.

(2) Fingolimod has a good bactericidal effect on Staphylococcus aureus

The MIC values of 8 strains of Staphylococcus aureus were all 3.125 μg/mL measured by the broth dilution method. We selected two strains of SA113 (MSSA) and CHS350 (MRSA) (Fingolimod and the antibiotics used in the experiment). The MIC values are shown in the table. 1), the bactericidal effect of fingolimod was detected under the action of 4×MIC, and the bactericidal effect of vancomycin, cefazolin (only acting on SA113), and linezolid was detected. The results are shown in Table 1. Select 0 hours and drug effects for 3 hours and 24 hours to take 1 mL of bacterial solution to dilute and plate for counting. As shown in Figure 4, the results show that fingolimod has a good killing effect on Staphylococcus aureus, especially on MSSA.

Table 1 MIC values of fingolimod and four antibiotics

(3) Fingolimod significantly inhibited the formation of Staphylococcus aureus biofilm

In our experiment, 6 biofilm-positive strains were selected from the above-mentioned strains, among which SE13, SE16, SA113, YUSA10 were MSSA, CHS350, CHS655 were MRSA, at 1/2MIC, 1/4MIC, 1/8MIC fingolimod The ability of strains to form biofilms was tested under the action. The results are shown in Figure 5 and Figure 6, indicating that fingolimod can significantly inhibit the formation of Staphylococcus aureus biofilm at 1/2 MIC concentration, and fingolimod inhibits biofilm formation at 1/4 MIC concentration. The ability was significantly decreased, and the ability to inhibit biofilm formation was no longer at 1/8MIC. The 1×MIC strain did not grow.

(4) Inhibitory effect of fingolimod combined with linezolid, oxacillin and vancomycin on bacterial growth of Staphylococcus aureus

In the experiment, two strains of MRSA (CHS350, CHS655) and two strains of MSSA (YUSA10, YUSA16) were selected to study the effect of fingolimod combined with linezolid, oxacillin and vancomycin in inhibiting the growth of Staphylococcus aureus. As shown in Figure 7, the results show that fingolimod, linezolid and vancomycin have no obvious combined antibacterial effect, only a slight difference; as shown in Figure 8, while fingolimod and cefazolin It showed obvious synergistic effect. It can be seen from the figure that under the action of 3.125 μg/mL fingolimod combined with 16 μg/mL oxacillin, the growth of strain CHS350 basically stopped; 0.25μg/mL oxacillin and 3.125μg/mL fingolimod combined with 0.5μg/mL oxacillin stopped the growth of strains YUSA16 and YUSA10, respectively. The above experimental results show that fingolimod has no obvious synergistic anti-infective effect with vancomycin and linezolid, but has a more significant synergistic anti-infective effect with oxacillin.

(5) Fingolimod significantly removed Staphylococcus aureus biofilm

The strong biofilm positive strain SA113 was selected, and the biofilm removal ability of S. aureus was observed under the action of different concentrations of fingolimod, vancomycin, linezolid and daptomycin. As shown in Figure 9 and Figure 10, the results show that fingolimod has demonstrated the ability to clear Staphylococcus aureus biofilm at a concentration of 2 × MIC, while at a concentration of ≥ 4 × MIC, it can significantly clear Staphylococcus aureus biofilm.

(6) Changes in fingolimod-induced biofilm formation in Staphylococcus aureus

In the experiment, we induced drug-resistant SA113 and CHS101 strains, and detected their MIC values when fingolimod was induced for 30 generations, and found that they did not change. The induced strains were inoculated on TSA plates, and monoclonal strains were selected to measure their biofilm forming ability. As shown in Figure 11, the results showed that the biofilm formation ability of the induced strain was significantly decreased.

In summary, the experimental results show that fingolimod has good anti-Staphylococcus aureus activity, whether it is bacteriostatic, bactericidal, biofilm inhibition or removal of biofilm, and may have a synergistic antibacterial effect with oxacillin, which is expected to become a Alternative medicines for commonly used antibiotics against Staphylococcus aureus, and its antibacterial-related mechanism of action needs to be further studied.

The embodiment of the present invention discloses the application of fingolimod in the preparation of a medicament against gram-positive bacterial infection, and the medicament against gram-positive bacterial infection includes fingolimod. Preferably, the drug against gram-positive bacterial infection includes oxacillin.

The embodiment of the present invention discloses the application of fingolimod in preparing a coating for the surface of a medical device, and the coating on the surface of the medical device includes fingolimod. Preferably, in the coating for the surface of a medical device, the concentration of fingolimod is not less than 1.5625 μg/mL.

The embodiment of the present invention discloses a coating for the surface of a medical device, which comprises fingolimod.

The embodiment of the present invention discloses the application of fingolimod in the preparation of a disinfectant against gram-positive bacteria, and the disinfectant against gram-positive bacteria comprises fingolimod.

The embodiment of the present invention discloses a disinfectant against Gram-positive bacteria, which comprises fingolimod.

The above content is a further detailed description of the present invention in combination with specific preferred embodiments, and it cannot be considered that the specific implementation of the present invention is limited to these descriptions. For those of ordinary skill in the technical field of the present invention, without departing from the concept of the present invention, some simple deductions or substitutions can be made, which should be regarded as belonging to the protection scope of the present invention.

Claims (10)

1. Use of fingolimod for inhibiting the activity of gram-positive bacteria, characterized in that: the fingolimod is used for inhibiting the growth activity of gram-positive bacteria.

2. Use of fingolimod according to claim 1 for inhibiting gram positive bacterial activity, characterized in that: the MIC of the fingolimod for inhibiting gram-positive bacteria is 1.5625-12.5 mu g/mL.

3. Use of fingolimod for anti-staphylococcus aureus biofilm activity, characterised in that: the fingolimod has the function of eliminating the activity of a biological membrane at the concentration of 4 multiplied by MIC.

4. The application of fingolimod in preparing a medicament for resisting gram-positive bacterial infection is characterized in that: the medicament against gram-positive bacterial infection comprises fingolimod.

5. Use of fingolimod according to claim 4 for the preparation of a medicament against gram positive bacterial infection characterized in that: the drug for resisting gram-positive bacterial infection comprises oxacillin.

6. The application of fingolimod in preparing a coating for the surface of a medical device is characterized in that: the coating on the surface of the medical device comprises fingolimod.

7. Use of fingolimod according to claim 6 in the preparation of a coating for the surface of a medical device, characterized in that: in the coating for the surface of the medical device, the concentration of the fingolimod is not less than 1.5625 mu g/mL.

8. A coating for a medical device surface, characterized by: which includes fingolimod.

9. The application of fingolimod in preparing a disinfectant for resisting gram-positive bacteria is characterized in that: the disinfectant against gram-positive bacteria comprises fingolimod.

10. A disinfectant against gram-positive bacteria, characterized by: which includes fingolimod.

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