KR102251577B1 - ANTIMICROBIAL COMPOSITION COMPRISING Evernia mesomorpha extracts - Google Patents

Abstract

The present invention relates to an antibacterial composition comprising an extract of Evernia mesomorpha , and more particularly, has excellent antimicrobial activity against methicillin-resistant Staphylococcus aureus, Enterococcus faecium, and Candida albicans. And it relates to an antibacterial composition comprising an extract of Evernia mesomorpha , which has excellent stability because there is no side effect on the human body.

Description

Antimicrobial composition containing Evernia mesomorpha extract {ANTIMICROBIAL COMPOSITION COMPRISING Evernia mesomorpha extracts}

The present invention relates to an antibacterial composition comprising a lichen Evernia mesomorpha extract having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus, Enterococcus faecium and Candida albicans.

Staphylococcus aureus is a Gram-positive bacterium found on the surface of the skin and mucous membranes, and is also commonly found in healthy human bodies. However, in some people, such as patients with weakened immunity, Staphylococcus aureus ( S. aureus ) may have pathogenic characteristics and may cause minor skin infections as well as life-threatening diseases such as pneumonia, endocarditis, and sepsis. . Moreover, Staphylococcus aureus ( S. aureus ) is associated with nosocomial infections, and methicillin-resistant Staphylococcus aureus , MRSA) has become a major health problem. Recently, new kinds of antibiotic compounds having activity against methicillin-resistant Staphylococcus aureus have been developed by two-step synthesis or easy synthesis. Antibiotics against Staphylococcus aureus target cell membranes, ribosomes, and nucleic acids. Vancomycin has been proven to be effective in treating methicillin-resistant Staphylococcus aureus infection, and in other ways, vancoaicin is administered in cases of failure in the treatment of methicillin-resistant Staphylococcus aureus infection. However, vancomycin is a type of antibiotic and may exhibit side effects such as vomiting or diarrhea in some patients, so its use is limited, and the stability problem for the human body remains a task to be solved. In addition, Enterococcus faecium is a Gram-positive bacterium found in human gastrointestinal tract, is known to cause diseases such as neonatal meningitis and endocarditis, and is known as a difficult pathogen.

On the other hand, lichens are complex organisms composed of algae and fungi or cyanobacteria (bacteria), and produce various biologically active secondary metabolites having antiviral, antibiotic, antitumor, or antiallergic effects. Numerous secondary metabolites obtained from more than 20,000 lichens have been studied as potential scaffolds for drug development. Among these metabolites, the most studied compound, usinic acid, has antibiotic activity and is used in drug and cosmetic development. Recently, usinine derivatives have been synthesized to enhance the antimicrobial activity of usinic acid.

Therefore, while searching for an extract with antibacterial activity, the researchers studied divaricatic acid, which was isolated as a major component of the acetone extract of Evernia mesomorpha , a lichen, especially methicillin-resistant Staphylococcus. aureus , MRSA), Enterococcus faecium , and Candida albicans .

Marijana, K.; Branislav, R.; Slobodan, S. Antimicrobial activity of the lichen Lecanora frustulosa and Parmeliopsis hyperopta and their divaricatic acid and zeorin constituents. Afr. J. Microbiol. Res. 2010, 4, 885-890.

In order to solve the above problems, the present invention is to provide an antibacterial composition comprising divaricatic acid having excellent antibacterial activity against methicillin resistance 　 yellow Staphylococcus aureus, Enterococcus faecium, and Candida albicans. do.

In addition, it is an object of the present invention to provide an antibacterial health functional food comprising divaricatic acid as an active ingredient.

The object of the present invention is not limited to the object mentioned above. Objects of the present invention will become more apparent from the following description, and will be realized by means described in the claims and combinations thereof.

The antimicrobial composition according to the present invention has an advantage of excellent antibacterial activity against methicillin resistance 　 yellow Staphylococcus aureus, Enterococcus faecium, and Candida albicans by including davaricatic acid as an active ingredient. In addition, the antimicrobial composition has excellent stability because there is no side effect on the human body, and thus it can be variously applied to pharmaceutical compositions, quasi-drug compositions, or preservative compositions using the same. In particular, the antibacterial composition can be used to treat methicillin-resistant Staphylococcus aureus infection. In addition, it can be applied to health functional foods for preventing or improving infectious diseases by including the dabaric acid as an active ingredient.

In the present specification, "extract" refers to a resultant product such as a liquid component obtained by immersing a target substance in various solvents and then extracting it for a certain period of time at room temperature or warming state, and a solid component obtained by removing the solvent from the liquid component. do. In addition, in addition to the resulting product, it can be comprehensively interpreted as including all of the diluted solution of the resultant, the concentrated solution thereof, the preparation thereof, and the purified product.

In the present specification, the term "active ingredient" refers to an ingredient capable of exhibiting a desired activity by itself, or capable of exhibiting activity together with a carrier that is not itself active.

Specifically, the present invention relates to an antimicrobial composition comprising divaricatic acid represented by the following formula (1) or a pharmaceutically acceptable salt thereof.

[Formula 1]

The divaricatic acid may be a compound isolated from one selected from the group consisting of plant extracts, chemical compounds, microorganisms, or lichens. Preferably, the dibaric acid may be a compound isolated from lichens. As a specific example, the divaricatic acid may be a compound isolated from Evernia mesomorpha extract.

The structure of divaricatic acid is different from previously known antibiotics, so it may have antimicrobial activity by inhibiting nucleotide synthesis rather than destroying the cell wall. In addition, the divaricatic acid may have high activity against E. coli RecA inhibition associated with SOS reaction in bacteria.

Preferably, the antimicrobial composition is methicillin-resistant Staphylococcus aureus , MRSA), Enterococcus faecium , and Candida albicans may have antibacterial activity against at least one selected from the group consisting of.

The antimicrobial composition is methicillin-resistant Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA), Enterococcus faecium , and Candida albicans The minimum inhibitory concentration (MIC) for at least one selected from the group consisting of 7-64 μg/ml, preferably May be 16 to 64 μg/ml, more preferably 16 to 32 μg/ml. At this time, if the minimum inhibitory concentration of the antimicrobial composition is less than 7 μg/ml, the antimicrobial activity may hardly occur, and if it exceeds 64 μg/ml, it may be inefficient because it does not show any more improved antimicrobial activity.

The antibacterial composition contains 0.001 to 30% by weight, preferably 0.01 to 20% by weight, more preferably 0.1 to 10% by weight, most preferably 5% by weight of the divaricatic acid based on the total weight of the composition can do. At this time, if the content of divaricatic acid is less than 0.001, the antimicrobial activity may be insignificant, and if it is more than 30% by weight, the antimicrobial activity effect may no longer be improved, which may be inefficient, and the stability of the formulation may not be secured.

The antibacterial composition may be one selected from the group consisting of a pharmaceutical composition, an antiseptic composition, and a quasi-drug composition.

When the antimicrobial composition is used as the pharmaceutical composition, the pharmaceutical composition may be used in oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories according to a conventional method. And it may be formulated and used in the form of a sterile injectable solution. Carriers, excipients and diluents that may be included in the composition containing the compound include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate. , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils.

In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient, such as starch, calcium carbonate, and sucrose ( sucrose), lactose, or gelatin. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. .

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 60, cacao butter, laurin paper, glycerogelatin, and the like may be used.

When the antibacterial composition is used as an antiseptic composition, the antiseptic composition includes a food preservative, a cosmetic preservative, or a pharmaceutical preservative. The food preservatives, cosmetic preservatives and pharmaceutical preservatives are additives used to prevent deterioration, spoilage, discoloration, and chemical change of pharmaceuticals. These include fungicides and antioxidants, and inhibit the growth of microorganisms such as bacteria, mold, and yeast. And functional antibiotics such as inhibiting the growth of decaying microorganisms or sterilizing in medicines are also included. Ideal conditions for such an antiseptic composition should be non-toxic, and should be effective even in trace amounts.

When the antibacterial composition is used as a quasi-drug composition, the quasi-drug composition may be a disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment, patch, or filter filler.

On the other hand, the present invention can provide a health functional food for preventing or improving infectious diseases including divaricatic acid represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

The infectious disease may be selected from the group consisting of pneumonia, sepsis, tuberculosis, endocarditis, meningitis, methicillin-resistant Staphylococcus aureus (MRSA) infection, candidiasis, and colitis.

The health functional foods include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickeners (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like may further be included. In addition, the health functional food may further include flesh for the manufacture of natural fruit juice and fruit juice beverages and vegetable beverages. These components may be used independently or in combination.

The antimicrobial composition according to the present invention contains davaricatic acid or a pharmaceutically acceptable salt thereof as an active ingredient, thereby having excellent antibacterial activity against methicillin resistance 　 yellow Staphylococcus aureus, Enterococcus faecium, and Candida albicans. have.

In addition, the antibacterial composition according to the present invention is excellent in stability because there is no side effect on the human body, and thus can be applied to a pharmaceutical composition, quasi-drug composition, or an antiseptic composition using the same.

In addition, the health functional food according to the present invention has the advantage of preventing or improving infectious diseases by including the dabaric acid as an active ingredient.

The effects of the present invention are not limited to the above-mentioned effects. It should be understood that the effects of the present invention include all effects that can be inferred from the following description.

1 is a photograph showing the results of measuring the antimicrobial activity of 29 samples of Example 2 according to the present invention by the disk diffusion method.
2 is a high-performance liquid chromatography chromatogram graph performed on sample 458 (Evernia mesomorpha ) of Example 2 according to the present invention.

The above objects, other objects, features, and advantages of the present invention will be easily understood through the following preferred embodiments related to the accompanying drawings. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the embodiments introduced herein are provided so that the disclosed content may be thorough and complete, and the spirit of the present invention may be sufficiently conveyed to those skilled in the art.

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited by the following examples.

Material selection

[Material ingredients]

(1) badge

Dimethyl sulfoxide (DMSO), ethyl acetate (EA), methanol (methanol, MeOH), chloroform, toluene, dioxane, dichloromethylene (DCM), acetic acid, and vancomycin are Sigma Aldrich (Sigma-Aldrich) (St. Louis, Missouri, USA). The seawater liquid medium was purchased from MB Cell (Seoul, Korea). Nutrient liquid medium, brain heart infusion (BHI), peptone, yeast extract, and agar were purchased from Becton, Dickinson and Company (Spark, Maryland, USA). Glucose was purchased from Junsei (Tokyo, Japan), and was used to prepare a glucose-peptone-yeast extract-agar (GPYA) medium.

(2) Lichen extract and lichen-forming fungus culture extract

Acetone extract (177 samples) of lichens and EA extracts (258 samples, 100 mg/ml) of cultured lichen-forming fungi (LFF) were obtained from the Korean Lichen Research Institute (KLRI) (Korea Lichen Research Institute, KoLRI) (Korea Lichen Research Institute, KoLRI). , Sunchon National University). The samples were collected from several regions including Korea, China, Chile, Cameroon, Philippines, Romania, Vietnam, and the Arctic. After drying the acetone extract of the lichen, it was dissolved in dimethyl sulfoxide (DMSO) (100 mg/ml).

(3) microbial strain

Staphylococcus aureus (S. aureus ) CCARM 3A048 and Enterococcus faecium (E. faecium) CCARM 5202, which are methicillin-resistant S. aureus (MRSA), were used for screening. (Culture Collection of Antimicrobial Resistant Microbes, CCARM) (Korea). To evaluate antimicrobial activity, five Gram-positive bacterial strains ( Bacillus subtilis KCTC 2189, Micrococcus luteus ) CCARM 0022, Staphylococcus aureus CCARM 0027, Staphylococcus aureus CCARM 0027, Staphylococcus aureus CCARM 0027, Staphylococcus aureus S. epidermidis CCARM 3709, and Streptococcus mutans CCARM 0079); Five Gram-negative bacterial strains ( Escherichia coli KCTC 2441, Pseudomonas aeruginosa ) CCARM 0057, Klebsiella pneumoniae CCARM 0015, Salmonella typhimurium CCARM 0240 , And Vibrio vulnificus KCTC 2959); And the fungal strain Candida albicans ( C. albicans ) KCTC 27242 was used.

Example 1: Antimicrobial activity analysis

Staphylococcus aureus ( S. aureus ) CCARM 3A048 and Enterococcus faecium (E. faecium) CCARM 5202 in BHI liquid medium (calf brain 7.7 g, bovine heart 9.8 g, protease peptone 10.0 g, dextrose 2.0 g, sodium chloride) 5.0 g, disodium phosphate 2.5 g/L, pH 7.2 to 7.4) at 37° C. for 24 hours with shaking at a speed of 150 rpm. After incubation, 0.1 ml of the culture solution was evenly applied to the BHI agar plate, and a paper disk spotted with the extract was placed on the plate so that the paper disk and the medium in which the culture solution was absorbed were brought into contact with each other. In this case, the paper disc spotted with the extract is a paper disc (8 mm) sterilized with UV for 10 minutes (Advantec, Toyo Roshi Kaisha. Ltd., Tokyo, Japan) on a 0.1 extract 0.1 After spotting ㎖, it was prepared by drying for 2-3 days. When performing the primary screening, aliquots of 5 extracts (1.0 mg each) were placed on the plate. Control of 10% EA or 10% dimethylsulfoxide (DMSO), vancomycin (20 or 40 ppm for each of Enterococcus faecium CCARM 5202 and S. aureus CCARM 3A048) Became. The plate was incubated at 37° C. for 12 hours, and the diameter of a halo formed around the disk was measured. Secondary screening (duplicate experiments) using 0.5 mg of extract was performed on the samples showing the effect.

[Measurement result]

For acetone extract of lichens (177 samples) and EA extracts of cultured lichen-forming fungi (LFF) (258 samples, 100 mg/ml), 1.0 mg of each extract was added onto a paper disk. Spotting was performed to measure the antibacterial activity of the extract. Based on the halo size, the tested samples were classified into three groups, namely, low, medium, and effective groups. Of these, extracts of 258 cultured lichen-forming fungi (LFF) were active against any of the tested bacteria, Staphylococcus aureus ( S. aureus ), and Enterococcus faecium (E. faecium). Did not look. On the other hand, among the acetone extracts of the remaining 177 species of lichens, 9 extract samples showed activity against Staphylococcus aureus (S. aureus ), and 28 extract samples were active against Enterococcus faecium (E. faecium). Was shown, and 8 extract samples showed activity against both strains. Among them, additional analysis was performed on 29 samples.

Example 2: Analysis of antibacterial activity

Antimicrobial activity was measured by the disk diffusion method for 29 samples in Example 1, and the results are shown in FIG. 1 and Table 1. At this time, 0.5 mg of lichen extract was dropped on the disk during each experiment, and the degree of diffusion was measured in millimeters.

1 is a photograph showing the results of measuring the antimicrobial activity of 29 samples of Example 2 by the disk diffusion method. In FIG. 1, (A) represents Staphylococcus aureus ( S. aureus ), and (B) represents Enterococcus faecium (E. faecium).

According to the results of Fig. 1 and Table 1, when analyzing the antimicrobial activity of the prepared samples, the size of the halo for Staphylococcus aureus (S. aureus ) is for Enterococcus faecium (E. faecium). It was confirmed that it was smaller than the halo size. When measuring the size of the halo, the diameter of the halo including the disk (8 mm) was measured. In the case of Staphylococcus aureus ( S. aureus ), sample 419 exhibited a larger halo size than sample 407, and samples 407 and 431 exhibited the same halo size (ie, 419> 407 = 431). .

On the other hand, in the case of E. faecium , the halo size was reduced in the order of sample 449, sample 407, and sample 458, and samples 458 and 517 showed the same halo size. (I.e., 449>407> 458 = 517).

Example 3: Analysis of Selected Extracts by High Performance Liquid Chromatography

Before selecting the extracts for further study, information on the components and biological activities of the eight extracts in Example 1 above was investigated with reference to the literature. Based on halo size and literature information, eight extracts were analyzed by high performance liquid chromatography. The results are shown in Fig. 2 and Tables 2 and 3.

[How to measure]

The compounds contained in the extract showing high antimicrobial activity are high-performance liquid chromatography (LC-10AT, YMC-Pack ODS-A) equipped with a YMC-Pack ODS-A column at the Korean Lichen Research Institute (KOLRI). Shimadzu, Japan). In this case, a solvent containing methanol, water, and phosphoric acid (H ₃ PO ₄ ) (80:20:1 by volume) was used as the eluent, and presumptive identification was performed by comparing the retention time of the compound with the database. .

[Measurement result]

2 is a high-performance liquid chromatography chromatogram graph performed on sample 458 of Example 1-2 ( Evernia mesomorpha).

According to the results of FIG. 2 and Tables 2 and 3 , 6 peaks were observed in sample 458 (Evernia mesomorpha ), and 4 to 7 peaks were also observed in other samples. The retention time of each peak was compared with standard data to confirm the constituent components corresponding to each peak. Among the above-identified compounds, divaricatic acid and usinic acid, excluding organic solvents, occupied the most proportions. In particular, the content of divaricatic acid was 17.8 times higher than that of usinic acid, which is well known to have antibacterial activity, and divaricatic acid exhibited high antibacterial activity in a screening experiment. Through this, divaricatic acid isolated from the extract of Everia mesomorpha having excellent antibacterial activity was selected.

Example 4: Structural analysis of major active compounds for divaricatic acid isolated from Everia mesomorpha extract

The structure of the main active compound was analyzed for divaricatic acid isolated from the Everia mesomorpha extract selected in Example 3 above. The measurement method is as follows.

[How to measure]

The compounds contained in the Lichen Everia mesomorpha extract selected in Example 3 were separated using thin layer chromatography (TLC). The acetone extract was dissolved in 1 ml of acetone contained in a 1.5 ml EP tube. For preliminary experiments, the solution was spotted on a plate (Merck Millipore, Darmstadt, Germany) previously coated with silica gel 60 F254. According to the method described by Culberson, after spotting the sample on the thin-layer chromatography plate, the plate was subjected to a solvent containing toluene, dioxane and acetic acid (180:45:5 by volume). It was loaded into a twin trough chamber. When the front surface of the solvent absorbed and moved by the plate reached a height of 15 cm from the baseline and observed in light of 254 and 365 nm, the plate was taken out of the chamber. A 10% sulfuric acid aqueous solution was applied to the removed plate, followed by heating at 50° C. for 5 minutes.

For purification of the compound, the lichen extract was prepared by preparative thin layer chromatography (preparative TLC, PTLC) (silica gel 60 F254, 0.5 mm) using toluene, dioxane, and acetic acid (90:25:4 by volume) mobile phase. Separated. The spot was visualized at 254 nm, and the main spot was separated. Subsequently, the obtained silica gel was washed with methanol and dichloromethylene (DCM) (a volume ratio of 5:95) to obtain a filtrate. The obtained filtrate was evaporated to dryness. Analysis of the compound was carried out by liquid chromatography equipped with a reversed-phase column (Shim-pack VP-ODS/-C8/-Phenyl, 250 Х 4.6 mm, Shimadzu). -Analysis was performed using a liquid chromatography-mass spectrometer (LC-MS) (LCMS-2020, Shimadzu, Tokyo, Japan). The compound was eluted by combining two solvents containing 1% formic acid in water (A) or acetonitrile (B). Linear gradient elution was carried out according to the following procedure: for 0-5 minutes in 5% B solvent; 5 to 30% B solvent for 5 to 10 minutes; For 10 to 15 minutes in 30% B solvent; In 30 to 70% B solvent for 15 to 20 minutes; And in 70% B solvent for 20-25 minutes. The structure of the compound was determined using ¹ H-NMR (JNM-ECZ400s/L1, JEOL, Japan, Tokyo).

[Measurement result]

The major MS peaks of m / z ratio detected by the anionic mode mass analysis [MH] ^- ion ^{_{(C 21 H 23 O 7 -}} , m / z = 387) showed the formation of. ^{The 1} H-NMR data indicated that one carboxyl group, two benzene ring protons, one methoxy group, and two propyl groups were present. ^Based on 21 carbon peaks in 13 C-NMR and protonated carbon transfer from DEPT-NMR (DEPT: distortionless enhancement by polarization transfer (Distortionless enhancement by polarization transfer)), the compound is represented by the following Formula 1 It was confirmed that it was a divaricatic acid represented by.

[Formula 1]

The purity of divaricatic acid measured by liquid chromatography (LC) was 97.1%, and the peak was the acetone extract of sample 458 (E. mesomorpha) under the same analysis conditions. It corresponds to the third peak of.

Example 5: minimum inhibitory concentration (MIC)

The concentration of inhibition of antimicrobial activity against Staphylococcus aureus (S. aureus ) and Enterococcus faecium (E. faecium) was analyzed for divaricatic acid isolated from the Evernia mesomorpha extract of Example 4. The results are shown in Table 4.

[How to measure]

The strain was incubated with shaking at 150 rpm for 24 hours at 37°C. For Bacillus subtilis (B. subtilis ) KCTC 2189 and E. coli ( E. coli ) KCTC 2441, agar medium was used; Seawater medium was used for V. vulnificus KCTC 2959; And Candida albicans ( C. albicans ) For KCTC 27242, GPYA medium was used. Other strains were cultured in BHI medium. The cell density was adjusted to have an OD value of 1.0 at 600 nm, and the cells were diluted 500 times. The isolated compound was dissolved in dimethyl sulfoxide to prepare a stock solution having a concentration of 10 mg/ml, and the stock solution was diluted with BHI medium and adjusted to a concentration of 256 μg/ml. The obtained solution was serially diluted to prepare dilutions diluted step by step, and 50 µl of each of the prepared dilutions was added to a 96 well plate according to the diluted concentration sequence from the first well to the tenth well. . At this time, in the same manner, another set of dilutions was added to the 96 well plate (ie, repeated experiments twice). Thereafter, 50 μl of the diluted cells were added to each well (the first to tenth wells) and the 11th well (the solution was not contained), and incubated at 37° C. for 12 hours. At this time, the total volume of each well was 100 μl; The 11th well did not contain compound or vancomycin; And the 12th well contained only medium without cells. The minimum inhibitory concentration was determined by comparing the degree of turbidity of the wells, and the obtained result was confirmed by a duplicate experiment. The resulting minimum inhibitory concentration value was expressed as "mean ± standard error".

According to the results of Table 4, in the case of divaricatic acid , the minimum inhibitory concentrations against Staphylococcus aureus (S. aureus ) and Enterococcus faecium (E. faecium) were 64 µg/ml and 16 µg/ml, respectively. . The above results were consistent with the results of the disk diffusion experiment. Through this, it was confirmed that the divaricatic acid exhibited an antibacterial effect against Staphylococcus aureus (S. aureus ) (32 μg/ml) and Enterococcus faecium (16 μg/ml).

In addition, Bacillus subtilis (B. subtilis ), Staphylococcus epidermidis (S. epidermidis ), Str. mutans , and Enterococcus faecium (E. faecium) (5202) For Gram-positive bacteria including, the divaricatic acid showed a minimum inhibitory concentration of 7.0 to 64.0 µg/ml, while vancomycin showed a minimum inhibitory concentration of 0.78 to 25.0 µg/ml.

In particular, the antimicrobial activity of divaricatic acid against Staphylococcus epidermidis and E. faecium (5202) was higher than that of vancomycin. In addition, divaricatic acid also showed activity against Candida albicans (C. albicans). In contrast, vancomycin did not show antifungal activity against C. albicans. In addition, compared to vancomycin, divaricatic acid was less effective against Gram bacteria, but against Enterococcus faecium and methicillin-resistant Staphylococcus aureus ( S. aureus ), divaricatic acid was a broad-spectrum antibiotic, cellular, cellular It was more effective than Taksim.

As described above, divaricatic acid isolated from the Everia mesomorpha lichen is particularly methicillin-resistant Staphylococcus aureus , MRSA), Enterococcus faecium , and Candida albicans showed excellent antibacterial activity. In addition, it was found that the divaricatic acid was derived from lichens, a natural component, and had excellent stability to the human body, and was more effective in reducing side effects caused by it by replacing vancomycin or cetotaxime, which are conventional antibiotics.

Claims (5)

Lichen Everia mesomorpha (Evernia mesomorpha) antibacterial composition comprising the extract as an active ingredient.
The method of claim 1,
The antimicrobial composition is methicillin-resistant Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA), Enterococcus faecium (Enterococcus faecium), and Candida albicans ( Candida albicans ) to one or more selected from the group consisting of an antimicrobial composition that has antibacterial activity.
A preservative composition comprising the Lichen Evernia mesomorpha extract as an active ingredient.
A health functional food for the prevention or improvement of infectious diseases, including the Lichen Evernia mesomorpha extract as an active ingredient.
The method of claim 4,
The infectious disease is selected from the group consisting of pneumonia, sepsis, tuberculosis, endocarditis, meningitis, methicillin-resistant Staphylococcus aureus (MRSA) infection, candidiasis, and colitis.

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