KR101008480B1 - A composition containing a gall bladder extract having an antimicrobial activity or a compound separated therefrom as an active ingredient - Google Patents

Abstract

The present invention relates to a composition having an antimicrobial activity, and in particular, the composition of the present invention containing an extract of Galla Rhois or a compound separated therefrom as an active ingredient exhibits excellent antimicrobial effect against common infectious disease strains. Therefore, it can be usefully used as an antimicrobial composition and antimicrobial adjuvant for the prevention and treatment of common infectious diseases.

Gall bladder, antibacterial, antiviral

Description

A composition comprising the extract of Galla Rhois or the compounds isolated therefrom showing antibacterial activity}

The present invention relates to an antimicrobial composition and an antimicrobial adjuvant for the prevention and treatment of a common infectious disease containing a gall extract or a compound isolated therefrom as an active ingredient.

[Document 1] Jung-seop Jung et al., Hyangjadae Dictionary , pp.380-384, Younglimsa, 1998

Harborne JB, Phytochemical methods: A guide to modern techniques of plant analysis, 3 rd Ed . , pp. 6-7, 1998

3 Cha et al., Kor . J. Pharmacogn . , 31 , pp.185-189, 2000

[4] Nishizawa et al., J. Chem . Soc . Perkin Trans . I , pp. 2963-2968, 1982

[5] Khanbabaee and Lotzerich, Tetrahedron , 53 , pp. 10725-10732, 1997

[6] Redwane et al., J. Ethnopharmacol ., 79 , pp. 261-263, 2002

8, Kim O, Chae C. Journal of Comparative Pathology. 129 , pp.55-60, 2003

Document 9 Veterinary Microbiology, 20, pp. 131-142, 1989

[Reference 10] Yang et al., Yaoxue Xuebao , 34 , pp.457-462, 1999

It is urgent to develop new antimicrobial drugs to cope with 15% market share of medicines and 1.5 trillion won antibiotic market. In addition, in Korea, economic and cultural international exchanges are active, foreign pathogenic bacteria are more likely to be introduced, and livestock imports are increasing. Currently, most of the bacteria present in domestic livestock are resistant to conventional antibiotics, and the treatment is becoming increasingly difficult. These therapeutic problems will be severely transmitted to the human body through livestock products infected with these bacteria. According to a recent report, more than 50% of the infectious diseases in the human body appear to be common infectious diseases, so the safe supply of livestock products is the most important problem to be solved in public health. Antibiotic resistance of bacteria is expressed in almost all drugs currently in use, rather than in some localized antibiotics, and bacterial physiological and genetic characterization is expected to have the ability to resist any drug. Among the many antibiotic-resistant bacteria, methicillin-resistant S. aureus ( MRSA), vancomycin-resistant enterococci (VRE), vancomycin-mediated Staphylococcus aureus vancomycin intermediate S. aureus; VISA), and Escherichia coli (E. coli) with the antibiotic resistance of at least 6 kinds of O157: H7 including a. In Korea alone, MRSA is a nosocomial infection agent in hospitals, and it is located almost 80% in large general hospitals. VRE and VISA have also been rampant since the 1990s and have spread throughout the country. Escherichia coli O157: H7 is also resistant to multiple antibiotics due to multiple agent resistance and there is no complete therapeutic antibiotic yet. E. coli has already been a frequent social problem in the United States, Europe, and nearby Japan, and has occurred sporadically in humans and livestock in Korea. And since the import of cattle has been liberalized since 2001, it is certain that E. coli will prevail in Korea when importing livestock or livestock from the E. coli Sangje region. These resistant bacteria do not have special antibiotic selection system in Korea, and the factor of rapid increase in resistance is much larger than in other countries. Increasing antibiotic resistance is a vicious cycle of increasing use of new expensive antibiotics, increasing treatment duration, and mortality, which in turn increases economic and social problems. Therefore, in order to solve this problem, it is urgently necessary to understand the mechanism of resistance that is occurring and to develop a new antibiotic having a structure that does not cause resistance.

In order to cope with the rapidly increasing bacterial drug resistance and effectively treat various bacteria, new drugs different from the existing antibiotics (molecular structure, efficacy of drugs, etc.) are urgently needed. In particular, due to the emergence of super bacteria that are resistant to antibiotics, the development of new antibiotics is urgently required. In addition, the condition of the new drug should be a safe drug with no side effects on human and animal cells as well as bactericidal effect. No matter how good the antibiotic is, the resistance develops over time, and natural medicines are expected to solve this problem. The reason for this is that natural products are new components that are not known until now, and since individual actions are mixtures of various single components, it is thought that the side effects such as resistance may be reduced by the pharmacological action between complexes.

Many antibiotics currently used for livestock are at severe levels of resistance and some are close to 100%. In livestock, antibiotics are mainly used as feed additives or for cleaning purposes regularly between 7 and 10 days for broilers. According to the report, the antibiotic resistance rates of Salmonella and enterococci, such as Salmonella and Enterococci isolated from bovine pigs from all over the country, were found to be higher than 57% against quinolones. As such, currently used for livestock raising, most antibiotics are resistant to bacteria, so it is urgent to develop new antibiotics that can be effectively used for livestock raising.

Recently, the research trend of medicines are getting serious side effects, toxicity and resistance, so the research on the development of medicines from natural products is actively being carried out worldwide. On the other hand, in the East, including Korea, it has a background that has promoted the steady development of traditional medicine, which is one of natural medicines, through long periods of time. Antibiotics have been discovered since 1941 when penicillin was clinically used, and more than 5,500 species have been discovered, of which only 100 are fermented and mostly chemically synthesized. In order to be effectively used for the treatment of diseases, the therapeutic dose should not be toxic to the host and the antibacterial effect to the infectious agent should be very large, but it has poisoning or unusual side effects. to be. Therefore, research and development of new antibiotics having low toxicity and effective against resistant bacteria, and research to reduce the appearance and toxicity of resistant bacteria in the same way as combined administration is required.

The most common incidence of bacterial diseases in Korea is Salmonellosis, which is especially mediated in food for humans. More than 2,300 serotypes have been reported, and their symptoms are similar. Salmonella (Salmonella) can cause a variety of clinical symptoms and there is a variety of toxins such as endotoxins, cell toxin, enterotoxin cells exist. In particular, the pathogen can be transmitted through the intestinal epithelial cells invade host cells, and almost all mammals are susceptible to a representative strains of the most common strains of pathogens that cause food poisoning in people causing zoonotic epidemic Salmonella typhimurium (Salmonella typhimurium ) . It is spread to humans mainly through contaminated meat and usually causes symptoms such as acute enteritis, high fever and sepsis.

Antibiotics have been continuously used everywhere for the control of bacteria, and antibiotic-resistant bacteria have recently emerged due to the misuse and abuse of such antibiotics and antimicrobial substances, which has become a big problem in society. As awareness of these problems spreads, societal atmospheres that prevent the use of antibiotics or antimicrobial agents are being created. In addition, research on substances that can replace antibiotics has been actively conducted, and plants and probiotics (which have been used as folk remedies for a long time) ( Probiotics have been actively used to obtain antimicrobial and immune enhancing effects.

Rhus is a Rhus tree belonging to the family Anacardiaceae. It is a worm house in which the Aphis chinensis J. Bell gives a stab to the leaves of javanica L.). It is distributed all over Korea. In terms of the shape of the gall, the outer surface is grayish brown with light hairs, 3-7cm long, 2-5cm wide and 2mm thick, and hard and easily broken. The inside is usually empty or grayish white with dead bugs and secretions, sometimes with a disgusting smell. Gathered gall dry or boil or steam in the sun. Its main ingredient is 50 ~ 70% of pyrogallol tannin, and it contains malic acid and gallic acid. A drug is used in a converging, branch, hemostatic diarrhea, sputum, diabetes, bleeding, anemia, or the like (jeongboseop et al., Hyangyak Dictionary, pp. 380 ~ 384, Younglim Inc., 1998).

Accordingly, the inventors of the present invention completed the present invention by identifying a substance having an antimicrobial effect from a natural drug source or the compound of the gall bladder extract of the present invention or the antimicrobial effect against a common infectious disease strain.

In order to achieve the above object, the present invention is antimicrobial for the prevention and treatment of common infectious diseases containing Galla Rhois extract or a compound isolated therefrom as an active ingredient is less toxic and resistant to the living body and exhibits antimicrobial activity To provide a composition.

In addition, the present invention is a compound isolated from the Galla Rhois extract is gallic acid (gallic acid; 1) represented by the following structural formulas (1) to (5), a mixture of paradigal acid and metadigal acid (a mixture of methyl p -digallic acid and methyl m -digallic acid; 2), penta- O -galloyl glucose (3), ethyl gallate (4) or ethyl paradigalate and ethyl metadigal A mixture of ethyl p -digallate and ethyl m -digallate; 5, preferably a mixture of p -digallic acid and m -digallic acid or ethyl paradi A mixture of ethyl p -digallate and ethyl m -digallate, more preferably a 1 to 2: 1 weight ratio thereof, most preferably a 1: 1 weight ratio For the common infectious disease strain containing the complex as an active ingredient It provides a bacterial composition.

(1)

(One)

(2)

(2)

(3)

(3)

(4)

(4)

(5)

(5)

In addition, the extract is a solvent selected from water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water, ethanol or a mixed solvent thereof, more preferably a 50 to 90% ethanol mixed solvent, even more preferred. Preferably 70-80% extracted with ethanol mixed solvent.

Animals of the acquired common infectious diseases include mammals such as pigs, cattle and goats; Fish such as carp and goldfish; And poultry such as pheasants, chickens, ducks, turkeys and the like.

In addition, the acquired common infectious disease strain is Mycobacterium tuberculosis ), Mycobacterium bovis , Bacillus anthracis ), Brucella genus abortus, B. melitensis, B. suis, B. canis), Leptospira disease isolates (Leptospira canicola , L. pomona , L. icterohaemorrhagiae , L. ballum ), Pseudomonas mallei ), Pseudomonas strain Pseudomallei ), Erysipelothrix rhusiopathiae (E. insidiosa), Shigella disenteriae, S. flexneri, S. boydii, S. sonnei, Yersinea pestis, Francicella tularensis, Yersinia pseudotuberculosis, Yersina enterocoretics Yersinia enterocolitis, Listeria monocytogenes, Pasteurella multocida, Streptobacillus moniliformis, Spirilium minor (Spirillum minus) Borrelia recurrentis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus equimyris, Streptococcus faecalis (S. faecalis), Clostridium tetani, Clostridium perfringens, Clostridium novi (Cl.novyi), Clostridium septicum, Clostridium Historiticum, Clostridium sporogenes, Fusobacterium necrophorum, Salmonella typhi, Salmonella paratyphi, Salmonella gallinarium (Salmonella gallinarium), Salmonella typhimurium, Salmonella enteritidis, Champylobacter fetus (subsp.fetus, venerealis), Champilobacter jejuni (C. jejuni, C. coli, Actinomyces bovis, Actinomyces isralii, Nocardia asterioides, Nocar N. madurae, N. farcinica, Rabies virus, Hantan virus, Seoul virus, Pumara virus, Herpesvirus simiae (herpesvirus B), Filoviridae (Marburg virus), Newcastle virus in Paramyxovirus, and Cowfox virus in Orthopoxvirus. ), Pseudocowpoxvirus in the Parapoxvirus, Contagious pustular dermatitis virus in the Parapoxvirus, and Foot-and-mouth disease virus (Fo) ot and mouth disease virus, Vesicular stomatitis virus, Lymphocytic choriomeningitis virus, Arena virus, Lassa fever virus, Arena virus fever virus, Influenza virus of Orthomyxoviridae, Japanese B encephalitis virus of the genus Flavivirus, Aspergillus fumigata ), Cryptococcus neoformans, Candida albicans, Sportoricum scheckii, Coccidioides immitis, Blastomas dermatitis (Blastomyces dermatitidis), Histoplasma capsulatum, Haplosporangium parvum, Haplos What a sense Clear Kress (H. crescens, Trichphyton schoenleini, Richettia typhi (R. mooseri), Ricketta prowazekii, Rickettsia tsutsugamusi (R. orientali), R. akari, Coxiella burnetii, Chlamydia psittaci, Entamoeba histolytica, Toxoplasna gondii, Barantidium colli (Balantidium coli), Fasciola hepatica, Fasciola gigantica, Clonorchis sinensis, Paragonimos westermanii, Dibotherio cephalas latum (Dibothriocephalus latum), Taenia saginatus, Taenia solium, Echinococcus glanulosus, Ascaris lumbricoides, Ascaris Ascaris suum, Vibrio cholerae, Escherichia coli, Neospora caninum ), Anaplasma last ( Anaplasma) marginale), Tay Trang Le palba (Theileria parva), Tay Trang Le ahnyu Rata (Theileria annulata ), Thereeria Sergenti sergenti ), Cryptosporidium muris ), Cryptosporidium palmum ( C. parvum ), Tritrichomonas foetus ), Fusobacterium Necro Forum necrophorum ), Campylobacter fetus ), Bovine ephemeral fever virus, Ibaraki virus, Linderest virus, Bovine Viral Diarrhea virus, Bovine Rotavirus Rotavirus), Infectious bovine rhinotracheitis virus (IBRV), Bovine respiratory syncytial virus (BRSV), Polkaine reductive derivatives and respira Tory syndrome virus (Porcine reproductive and respiratory syndrome virus) , the kinase ski disease (Aujeszky's disease), Hog cholera (Hog cholera), a polka-les Spira storage corona virus (Porcine respiratory coronavirus), bolde telra beuroki counts Mathematica (Bordetella bronchiseptica ), Actinobacillus pleureopneumoniae , Swine influenza virus, Haemophilus parasuis ), Erysipelothrix rhusiopathiae ), Chicken infectious anemia virus, Avian leukosis / sarcoma virus, Mareck virus, Newcastle virus, Haemophilus para Galinarum ( Haemophilus paragallinarum ), African horse sickeness virus, Equine Infectious Anemia, Pseudomonas mallei ), Streptococcus equi ), Duck hepatitis virus, Salmonella gallinarum ), Transmissible gastroenteritis virus, Clostridium botulinum, Canine parvovirus, Canine distemper, Canine Infectious Canine Infectious hepatitis virus, Canine herpesvirus, Rabbit Viral Haemorrhage Disease, Canine Parainfluenza virus, Dirophyllaria Dirofilaria immitis, Feline leukemia virus, Feline panleukokemia virus, Feline infectious peritonitis virus or Methicillin-resistant yellow grapes aureus (methicillin-resistant S. aureus; MRSA ), preferably Salmonella Galina Solarium (Salmonella gallinarium), live Includes; Nella typhimurium (Salmonella typhimurium), Salmonella Entebbe utility disk (Salmonella enteritidis), Vibrio cholera (Vibrio cholerae), E. coli (Escherichia coli) or methicillin-resistant Staphylococcus aureus (MRSA methicillin-resistant S. aureus) .

The present invention provides an antimicrobial adjuvant for the prevention and treatment of common infectious diseases containing Galla Rhois extract or a compound isolated therefrom as an active ingredient.

In addition, the present invention is a compound isolated from the Galla Rhois extract is gallic acid (gallic acid), a mixture of paradigal acid and metadigal acid (a mixture of methyl p -digallic acid and methyl m -digallic acid), panta- galloyl glucose (penta- O - galloyl glucose), ethyl gallate (ethyl gallate) or a composite of ethyl di-p-gallate and ethyl gallate meta-di (a mixture of ethyl p -digallate and ethyl m -digallate), preferably Is a mixture of paradigal acid and metadigal acid (a mixture of p -digallic acid and m -digallic acid) or a mixture of ethyl paradigallate and ethyl metadigalate (a mixture of ethyl p -digallate and ethyl m- digallate), more preferably a 1 to 2: 1 weight ratio complex, most preferably a 1: 1 weight ratio complex thereof, to provide an antimicrobial adjuvant for the prevention and treatment of common infectious diseases. .

Hereinafter, a method of obtaining the extract and the compound of the present invention will be described in detail.

The gall bladder extract of the present invention may be dried by cutting dried gall bladder into about 1 to 30 times water, preferably about 10 to 20 times dry weight, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water. , Ethanol or a mixed solvent thereof, more preferably a 50 to 90% ethanol mixed solvent, even more preferably a 70 to 80% ethanol mixed solvent, at an extraction temperature of 20 to 100 ° C., preferably 80 to 100 ° C. 1 to 10 days, preferably about 2 to 5 hours extraction method such as cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, preferably 1 to 5 times obtained using a reflux cooling extraction method, Preferably repeated extraction 2 to 3 times and then concentrated under reduced pressure to obtain the five gall extract of the present invention.

     Therefore, the present invention is obtained from the above production method and the above production method, gallic acid (1) as described in Fig. 1 (HPLC) herein, a complex of paradigal acid and metadigal acid (2), ethyl gallate (4) and a quinine 70% ethanol extract (hereinafter referred to as "GR") consisting of the content ratio (4.3: 1: 7.2: 16.3) of the complex of ethyl paradigalate and ethyl metadigallate (5) do.

Compound of the present invention, the first step to obtain the gallastula extract; A second step of dissolving the crude extract in distilled water and then eluting with distilled water, 50% aqueous ethanol and ethanol on an Amberlite XAD-2 resin column; A third step of subjecting the 50% aqueous ethanol eluting fraction obtained in the second step to chromatography and dividing into seven fractions; A fourth step of dividing the first fraction from the third fraction into three fractions by chromatography; A fifth step of separating the first fraction from the fourth step fraction by silica gel column chromatography to obtain gallic acid; A sixth step of subjecting the second fraction of the fourth step fraction to column chromatography to obtain a complex of paradigal acid and metadigal acid; A seventh step of subjecting the third fraction of the fourth step fraction to column chromatography to obtain pantao-galloyl glucose; An eighth step of column chromatography of the fourth fraction of the fractions of the fourth step to obtain ethyl gallate; The sixth fraction of the fraction of the fourth step was purified by column chromatography to obtain a complex of ethyl paradigalate and ethyl metadigalate. Compounds can be obtained.

In addition, conventional fractionation processes can also be carried out (Harborne JB, Phytochemical methods: A guide to modern techniques of plant analysis , 3 rd Ed . , pp. 6-7, 1998).

The present invention is a complex of gallic acid, paradigalic acid and metadigalic acid, which is isolated from the gallolae extract obtained by the above method, a complex of panta-galloyl glucose, ethyl gallate and ethyl paradigallate and ethyl metadigallate It provides an antimicrobial composition for preventing and treating common infectious diseases containing as an active ingredient.

The gall bladder extract of the present invention and the compound isolated therefrom are characterized by low toxicity and resistance and antibacterial activity against common infectious disease strains.

The antimicrobial composition of the present invention comprises 0.1 to 50% by weight of the extract or compound based on the total weight of the composition.

The antimicrobial composition containing the extract or compound of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

Pharmaceutical dosage forms of the extracts or compounds of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.

Compositions containing extracts or compounds according to the invention are in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Carriers, excipients and diluents which may be contained in the composition containing the compound include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose, or the like. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the extracts or compounds of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract or compound of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 10 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The extracts or compounds of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

As mentioned above, the gall bladder extract of the present invention and the compound isolated therefrom can be used as an antimicrobial composition by showing an excellent antimicrobial effect against the common infectious disease strains.

Below, The invention is illustrated in detail by the following examples and experimental examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Example  1. The Governor Crude extract  Produce

1-1. Preparation of Gallia Water Extract

After drying the dried gall from the University of Korea, Iksan, using a grinder to obtain a gall powder, the particle size is less than 30 mesh (mesh), 10 of the mass of dried gall (30 g) obtained above Distilled water corresponding to the pear was added, reflux cooled extraction at 100 ° C. for 2 hours, filtration and lyophilization to obtain 20.0 g of Gallja water extract (hereinafter referred to as “G”; extraction rate of 66.7%).

1-2. Preparation of Methanol Ethanol Extract

1-2-1. Preparation of 70% Ethanol Extract

After drying the dried gall from the University of Korea, Iksan, using a grinder to obtain a powder by pulverizing to a particle size of 30 mesh or less, which is equivalent to 10 times the mass of the dried gall (30 g) obtained above. 70% aqueous ethanol was added, followed by reflux cooling for 2 hours at 100 ° C, filtration and concentration under reduced pressure (EYELA, N-1000, Japan) to give 22.4 g of gall ethanol extract (hereinafter referred to as "GR"; extraction rate 74.7%). Obtained.

1-2-2. Preparation of 30% Ethanol Extract

Only 30% ethanol extraction solvent was used as the extraction solvent, and extraction was carried out in the same manner as in the manufacturing process to obtain a quintet 30% ethanol extract (extraction rate 67.9%).

1-2-3. Preparation of 50% Ethanol Extract

Only 50% ethanol extraction solvent was used as the extraction solvent, except that 50% ethanol extract (extraction rate 69.7%) was obtained by performing extraction in the same manner as in the above production process.

1-2-4. Preparation of 100% Ethanol Extract

Only 100% ethanol extraction solvent was used as the extraction solvent, and extraction was carried out in the same manner as in the manufacturing process to obtain a 5-fold ethanol extract (extraction rate 53.3%).

Example  2. Isolation of the Compound from the Methanol Ethanol Extract

2-1. By resin GR of Fraction  Produce

37.3 g of GR obtained in the above Example 1-2-1 was placed on an Amberlite XAD-2 resin column and chromatographed using 1 L of distilled water, 50% ethanol and 100% ethanol as elution solvent, respectively. Elution fractions of 50% ethanol and 100% ethanol were obtained.

2-2. Gallic  detach( Compound 1 )

Take 2.5 g of the 50% ethanol elution fraction obtained in Example 2-1, place it on a reversed phase YMC column and chromatograph using methanol: distilled water (3: 7 → 5: 5 → 10: 0, v / v) as the eluent. The chromatography was combined, concentrated and divided into seven fractions (AG). The first fraction, A (0.9 g), was placed on a Sephadex LH-20 column, followed by chloroform and methanol (6). Chromatography was carried out using: 1 → 3: 1 → 1: 1, v / v) as the elution solvent, and small fractions (A1 to A3) were separated into three secondary fractions. The first fraction of the second fraction, A1 (30 mg), was subjected to silica gel column chromatography using chloroform: methanol: distilled water (6: 1: 0.1, v / v) using an eluting solvent to give compound 1 (7 mg). It was confirmed that the result of the instrumental analysis is gallic acid (gallic acid) having the following physical properties (Cha et al., Kor . J. Pharmacogn . , 31 , pp. 185-189, 2000).

Colorless powder: (−)-ESI-MS m / z 169 [M ⁻ H] ⁻ ;

¹ H-NMR (acetone- d ₆ , 500 MHz): 7.06 (2H, s, galloyl-2, 6).

2-3. Paradi Galsan Meta  D Gallic  detach( Compound 2 )

Compound A2 (80 mg), which is the second fraction of the second fraction obtained in Example 2-2, was subjected to silica gel column chromatography using chloroform: methanol: distilled water (4.5: 1: 0.1, v / v). 2 (50 mg) was obtained, and the results of the instrument analysis confirmed that it was a complex of paradigal acid and its isomer metadigallic acid ( p -and m -digallic acid) having the following physical properties (Nishizawa et al., J . Chem. Soc. Perkin Trans . I , pp. 2963-2968, 1982).

Colorless powder: (-)-ESI-MS m / z 321 [M ⁻ H] ⁻ ;

¹ H-NMR (acetone- d ₆ , 500 MHz): ( p -digallic acid) 7.20 (2H, s, galloyl-2 ', 6'), 7.11 (2H, s, galloyl-2, 6); ( m -digallic acid) 7.40 (1H, d, J = 1.8 Hz, galloyl-2), 7.23 (1H, d, J = 1.8 Hz, galloyl-6), 7.20 (2H, s, galloyl-2 ', 6 ');

¹³ C-NMR (acetone- d ₆ , 125 MHz): ( p -digallic acid) 128.5 (C-1), 108.8 (C-2, 6), 150.4 (C-3,5), 131.3 (C-4 ), 168.0 (C = O), 119.4 (C-1 '), 109.7 (C-2', 6 '), 145.3 (C-3', 5 '), 138.8 (C-4'), 164.7 (C '= O); ( m -digallic acid) 121.0 (C-1), 114.0 (C-2), 146.1 (C-3), 142.7 (C-4), 138.8 (C-5), 116.4 (C-6), 167.7 ( C = O), 119.5 (C-1 '), 109.8 (C-2', 6 '), 145.4 (C-3', 5 '), 139.0 (C-4'), 164.22 (C '= O) .

2-4. Panta  Five- Galloyl Glucose  detach( Compound 3 )

A3 (460 mg), the third fraction of the second fraction obtained in Example 2-2, was placed on a Sephadex LH-20 column and chromatographed using methanol as the elution solvent to give one fraction (A31). Purified. Chromatography using A31 on a reverse phase YMC column with methanol: distilled water (4: 6, v / v) as the eluent, combining and concentrating those fractions showing the same behavior in thin layer chromatography (A311-A314). The third fraction A313 (146 mg) was subjected to Sephadex LH-20 column chromatography using methanol: distilled water (8: 2 → 9: 1 → 10: 0, v / v). (42 mg) was obtained, and the results of the instrument analysis confirmed that it is penta - O- galloyl- β-D- glucopyranose having the following physical properties (Khanbabaee and Lotzerich, Tetrahedron , 53 , pp.10725 ~ 10732, 1997).

Colorless powder: (-)-ESI-MS m / z 939 [M ⁻ H] ⁻ ;

¹ H-NMR (CD ₃ OD, 500 MHz): 7.10, 7.04, 6.97, 6.94, 6.89 (each 2H, s, galloyl-2, 6), 6.23 (1H, d, J = 8.2 Hz, H-1) , 5.90 (1H, t, J = 9.6 Hz, H-3), 5.61 (1H, t, J = 9.6 Hz, H-4), 5.58 (1H, t, J = 9.6 Hz, H-2), 4.35 -4.51 (3H, m, H-5, 6);

¹³ C-NMR (CD ₃ OD, 125 MHz): 92.5 (C-1), 70.8 (C-2), 72.7 (C-3), 68.4 (C-4), 73.1 (C-5), 61.8 ( C-6), 118.4, 118.8, 118.9, 119.0, 119.6 (galloyl-1), 109.0, 109.1, 109.3 (galloy-2, 6), 144.8, 144.9, 145.0, 145.1, 145.2 (galloy-3, 5), 138.7, 138.8, 139.0, 139.1, 139.4 (galloy-4), 164.9, 165.6, 165.7, 165.9, 166.6 (C = O).

2-5. ethyl Gallate  detach( Compound 4 )

Compound 4 (D) (430 mg), the fourth fraction of the fraction obtained in Example 2-2, was subjected to silica gel column chromatography using chloroform: methanol: distilled water (9: 1: 0.1, v / v). 240 mg) was obtained, and the results of the instrument analysis confirmed that it was ethyl gallate (ethyl gallate) having the following physical properties (Redwane et al., J. Ethnopharmacol., 79 , pp. 261 to 263, 2002).

Colorless powder: (−)-ESI-MS m / z 197 [M ⁻ H] ⁻ ;

¹ H-NMR (acetone- d ₆ , 500 MHz): 7.11 (2H, s, galloyl-2, 6), 4.23 (2H, q, J = 7.3 Hz, OCH ₂ ), 1.30 (3H, t, J = 7.3 Hz, CH ₃ );

¹³ C-NMR (acetone- d ₆ , 125 MHz): 121.3 (C-1), 108.9 (C-2, 6), 145.2 (C-3, 5), 137.8 (C-4), 60.0 (OCH ₂ ), 13.8 (CH ₃ ), 165.9 (C = O).

2-6. Ethyl paradi Gallate  ethyl Meta  D Gallate  detach( Compound 5 )

F (190 mg), the sixth fraction of the fraction obtained in the step 2-2, was placed on a reversed phase YMC column, and the chromatography was repeatedly performed using methanol: distilled water (4: 6, v / v) as the elution solvent. Compound 5 (15.6 mg) was obtained, and the results of the instrument analysis confirmed that the mixture of ethyl paradigalate having isomers and isomer ethyl ethyl digallate (ethyl p -and m -digallate) having the following physical properties (Nishizawa et al., J. Chem . Soc.Perkin Trans . I , pp. 2963-2968, 1982; Yang et al., Yaoxue Xuebao , 34 , pp. 457-462, 1999).

Colorless powder: (−)-ESI-MS m / z 349 [M ⁻ H] ⁻ ;

¹ H-NMR (acetone- d ₆ , 500 MHz): (ethyl p -digallate) 7.25 (2H, s, galloyl-2 ', 6'), 7.17 (2H, s, galloyl-2, 6), 4.29 ( 2H, q, J = 7.3 Hz, OCH ₂ ), 1.33 (3H, t, J = 7.3 Hz, CH ₃ ); (ethyl m -digallate) 7.44 (1H, d, J = 1.8 Hz, galloyl-2), 7.33 (1H, d, J = 1.8 Hz, galloyl-6), 7.26 (2H, s, galloyl-2 ', 6 '), 4.27 (2H, q, J = 7.3 Hz, OCH ₂ ), 1.31 (3H, t, J = 7.3 Hz, CH ₃ );

¹³ C-NMR (acetone- d ₆ , 125 MHz): (ethyl p -digallate) 128.3 (C-1), 108.8 (C-2, 6), 150.4 (C-3,5), 131.5 (C-4 ), 165.5 (C = O), 119.9 (C-1 '), 109.8 (C-2', 6 '), 145.3 (C-3', 5 '), 139.0 (C-4'), 60.4 (OCH ₂ ), 13.8 (CH ₃ ), 164.1 (C ′ = O); (ethyl m -digallate) 121.1 (C-1), 113.6 (C-2), 146.1 (C-3), 142.5 (C-4), 138.5 (C-5), 116.4 (C-6), 165.3 ( C = O), 120.0 (C-1 '), 109.9 (C-2', 6 '), 145.2 (C-3', 5 '), 138.7 (C-4'), 60.6 (OCH ₂ ), 13.7 (CH ₃ ), 163.4 (C '= 0).

Experimental Example  1. Composition Analysis HPLC Chromatogram )

The GR obtained in Example 1-2-1 was analyzed for components according to the following HPLC conditions (see Table 1).

device Analysis condition HPLC pump Sykam S2100 (Germany) Detector Sykam S3205 UV / VIS detector (Germany) column Inertsil ODS-3,4.6 I.D.x150mm (GL Sciences Inc., Japan) Elution solvent 0.2% aqueous acetonitrile → 10% aqueous acetonitrile (30 minutes) Sample injection volume 10 μl Flow rate 1.5 ml / min detection UV (254 nm)

As a result, the retention time (R _t ) of the compounds was shown in Table 2, and the content ratio was shown to be Compound 1: Compound 2: Compound 4: Compound 5 = 4.3: 1: 7.2: 16.3. Could be (see FIG. 1).

compound Retention time (R _t ) Compound 1 1.633 minutes Compound 2 11.666 minutes Compound 4 18.5 minutes Compound 5 15.483 minutes

Experimental Example 2. Antibacterial test ( in vitro )

2-1. Disclosure strains and medium and strain culture

Strains used for the determination of antibacterial activity are isolated outdoor strains and ATCC standard strains in humans or animals, and the list of strains is shown in Table 3. Strains were inoculated in TSB (Tryptic Soy broth; Difco, USA) medium and incubated for 24 hours in a 37 ° C thermostat and used for the experiment. It was.

Name origin Vibrio cholerae O1 JOL375 Vibrio cholerae O139 JOL376 E. coli O157 Animal isolate MRSA ATCC 700698 Shigella dysenteriae ATCC 49557 Salmonella gallinarium Water-based Standard Strains E. coli O157 ATCC 35150 Salmonella typhimurium Water-based Standard Strains (Sal-13) Salmonella enteritidis Water-based Standard Strains (Sal-36) E. coli K99 Water-based Standard Strains (E-125) E. coli K88 Water-based Standard Strains (E-126)

2-2. Minimum inhibitory concentration (MIC) measurement

Muller-Hinton agar medium was used to determine the minimum inhibitory concentration for the 11 test strains shown in Table 3. The bacteria grown on TSB (Tryptic Soy broth; Difco, USA) were re-sterilized using the same medium, the absorbance was measured at 590 nm, and the CFU (dog / ml) was calculated.Then, 1X 10 ⁵ using 0.85% saline solution Dilute to / ml.

The measured concentrate was dissolved in Muller-Hinton broth at 55-60 ° C., incubated with diluted bacteria, and incubated in a 37 ° C. thermostat for 24 hours. The cultured bacteria were diluted 100-fold with sterilized distilled water, and then 100 μl diluted solution was added to Muller-Hinton agar medium and incubated at 37 ° C for 18 hours, followed by visual observation to minimize the concentration of less than 100 colonies. It was determined as the inhibitory concentration.

2-2-1. Antimicrobial activity of G and GR

As a result of investigating the antimicrobial activity of G and GR obtained in Examples 1-1 to 1-2-1, as shown in Table 4, GR was 2 to 10 times with respect to 11 kinds of causative bacteria causing the common infectious disease compared to G. It showed that the above strong antibacterial activity was shown.

Name origin Antimicrobial Activity (Minimum Growth Concentration: μg / ml) G GR Penicillin ga ^a Kanamycin ^a Vibrio cholerae O1 JOL375 100 50 10 10 Vibrio cholerae O139 JOL376 200 100 10 10 E. coli O157 Animal isolate > 500 200 25 100 MRSA ATCC 700698 > 500 > 500 25 500 Shigella dysenteriae ATCC 49557 > 500 50 10 10 Salmonella gallinarium Water-based Standard Strains 100 50 10 10 E. coli O157 ATCC 35150 100 50 10 10 Salmonella  typhimurium Water-based Standard Strains (Sal-13) 100 50 10 10 Salmonella  enteritidis Water-based Standard Strains (Sal-36) 100 50 10 10 E. coli K99 Water-based Standard Strains (E-125) 100 50 10 10 E. coli K88 Water-based Standard Strains (E-126) > 500 100 10 10 ^a : positive counterpart

2-2-2. Determination of Antimicrobial Activity of Compounds Isolated from GR

As a result of examining the antimicrobial activity of the five compounds (Compounds 1 to 5) obtained in Example 2, as shown in Table 5, all compounds exhibited antimicrobial activity against 11 kinds of causative agents causing common infectious diseases. Compounds 3, 4, and 5 showed excellent antimicrobial activity.

Name origin Antimicrobial Activity (Minimum Growth Concentration: μg / ml) Compound 1 Compound 2 Compound 3 Compound 4 Compound 5 Penicillin ga ^a Kanamycin ^a Vibrio cholerae O1 JOL375 > 200 > 200 100 50 > 200 10 10 Vibrio cholerae O139 JOL376 200 200 200 25 50 10 10 E. coli O157 Animal isolate > 200 > 200 > 200 200 > 200 25 100 MRSA ATCC 700698 > 200 > 200 > 200 > 200 > 200 25 500 Shigella dysenteriae ATCC 49557 > 200 > 200 > 200 > 200 > 200 10 10 Salmonella gallinarium Water-based Standard Strains > 200 > 200 100 100 200 10 10 E. coli O157 ATCC 35150 > 200 > 200 100 200 200 10 10 Salmonella typhimurium Water-based Standard Strains (Sal-13) > 200 > 200 100 200 200 10 10 Salmonella  enteritidis Water-based Standard Strains (Sal-36) > 200 > 200 100 100 200 10 10 E. coli K99 Water-based Standard Strains (E-125) > 200 > 200 100 100 200 10 10 E. coli K88 Water-based Standard Strains (E-126) > 200 > 200 200 200 200 10 10 ^a : positive counterpart

Experimental Example 2. Antibacterial Experiment ( in vivo )

2-1. Experiment preparation

In the present invention, a 10-year-old Landrace hybrid male pig was purchased and used in Jeolla Livestock (Jeonbuk, Iksan), and the weight average was similarly classified in the group consisting of healthy pigs with no disease. The diet was fed milk powder for weaning pigs without antibiotics.

Pathogenic E. coli F44 strain ( E. coli F44 strain, wild type) was inoculated intragastrically with a catheter at 2x10 ¹⁰ CFU, as shown in Table 6 negative control group not inoculated with E. coli, positive control group inoculated with E. coli, GR The extract was divided into high concentration and low concentration groups.

group Treatment Head Head E. coli matter term I Voice Control Group X - 7 days II Positive control group O - 7 days III High concentration O GR 0.5% 7 days IV Low concentration O GR 0.25% 7 days

2-2. Weight change and mortality observation

As described in Experimental Example 2-1, the weight change and mortality of the four groups were observed.

The mean weights of the groups were similar at the time of introduction, but the animals of group II positive control group showed weight loss 3 days after E. coli inoculation compared to animals of group I negative control group, showing significant difference from negative control group. (p <0.01). Animals of group IV that received 0.25% blastula ethanol extract also lost weight three days after colon colon administration (p <0.01). On the other hand, animals of group III, which were 0.5% of the offspring, had a high weight value. On the 5th day after E. coli inoculation, only body weight of the positive control group II was significantly lower than that of the negative control group (p <0.01). Mortality was observed during the course of the test and no mortality was observed in all groups of test animals.

group Day 0 3rd day Day 5 I 4.0 ± 0.20b 4.2 ± 0.25 4.3 ± 0.31 II 4.0 ± 0.21 3.4 ± 0.25 * 2.2 ± 0.26 * III 4.1 ± 0.39 3.6 ± 0.41 3.8 ± 0.30 IV 3.9 ± 0.33 3.6 ± 0.26 * 3.5 ± 0.35 a: 1 day after E. coli inoculation
b: mean weight ± standard deviation of animals in the group
* Significant difference compared to control group (p <0.01)

2-3. Visual observation

As described in Experimental Example 2-1, the visual status was observed daily during the course of the test for the four groups, the visual scores of each individual were recorded, and the mean and standard deviation of each group were obtained. The visual score is “0; Health, 1; Reduced motor status and rough skin, 2; Down and premature, 3; Death ”.

After the inoculation of E. coli, the subjects of group II showed gross diarrhea, locomotion, depression and weakness, and showed higher visual score than those of group I, III and IV. On the other hand, GR 0.5% animals and 0.25% group was found to have a low gross score compared to animals of group II, a positive control group.

group Day 0 Day 1 Day 2 3rd day Day 4 Day 5 Day 6 I 0 ± 0 0 ± 0 * 0 ± 0 * 0 ± 0 * 0 ± 0 * 0 ± 0 * 0 ± 0 * II 0 ± 0 1.0 ± 0b 1.7 ± 0.58 2.0 ± 0 1.3 ± 0.38 1.0 ± 0 1.0 ± 0 III 0 ± 0 1.0 ± 0 0.8 ± 0.50 0.5 ± 0.58 * 0.3 ± 0.50 * 0.3 ± 0.50 * 0 ± 0 * IV 0 ± 0 1.0 ± 0 1.3 ± 0.50 1.0 ± 0.00 * 1.0 ± 0.00 0.8 ± 0.50 0.5 ± 0.58 a: 1 day after E. coli inoculation
* Significant differences were shown in comparison with the positive control group (group II) (p <0.01)

2-4. Fecal state  observe

As described in Experiment 3-1, fecal status was observed daily during the course of the test for the four groups, the fecal score of each individual was recorded, and the mean and standard deviation of each group were obtained. Fecal score is “0; Normal, 1; Yanbian, 2; Diarrhea, 3; Death ”. The average and standard deviation of the fecal score of each group after inoculation of the E. coli F44 strain was shown in Table 8.

Group II subjects showed severe diarrhea after E. coli vaccination. On the other hand, the fecal status of animals in group III and IV of the extract-administered group showed a stool level on day 1 after inoculation, but gradually recovered, indicating that fecal status was getting closer to normal and that fecal score was low. Could be (see FIG. 2). From day 2 to day 5 after E. coli inoculation, the fecal scores of group III and IV, which were GR-treated, were significantly lower than those of positive control group II (p <0.01).

group Day 0 Day 1 Day 2 3rd day Day 4 Day 5 Day 6 I 0 ± 0 0 ± 0 * 0.3 ± 0.58 * 0.3 ± 0.58 * 0.0 ± 0.00 * 0.0 ± 0 * 0.0 ± 0 * II 0 ± 0 2.0 ± 0.00 3.0 ± 0.00 3.0 ± 0.00 2.0 ± 0.00 2.0 ± 0 1.3 ± 0.58 III 0 ± 0 1.8 ± 0.50 1.0 ± 0 * 0.3 ± 0.50 * 0.3 ± 0.50 * 0.3 ± 0.50 * 0.0 ± 0 * IV 0 ± 0 2.0 ± 0 1.5 ± 0.58 * 0.8 ± 0.50 * 0.3 ± 0.50 * 0.3 ± 0.50 * 0.5 ± 0.58 a: 1 day after E. coli inoculation
* Significant differences were shown in comparison with the positive control group (group II) (p <0.01)

2-5. Blood test

As described in Experiment 3-1, the subjects of each group were anesthetized with xylzin (xylazin, Bayer Animal, Korea) at 1 week after E. coli inoculation of the 4 groups, and blood was collected by collecting blood cells. The results of calculating the mean and standard deviation of each group are shown in Table 10.

WBC levels were higher in E. coli-administered positive controls than in the other groups.

Blood test group I II III IV WBC (10 ³ / μl) 9.6 ± 0.45 * 16.3 ± 2.0 9.55 ± 0.45 * 10.2 ± 0.00 * RBC (10 ⁶ / μl) 6.1 ± 0.66 6.7 ± 0.76 6.6 ± 0.52 6.5 ± 0.29 HGB (g / dL) 12.1 ± 0.73 12.6 ± 0.88 13.1 ± 1.00 12.5 ± 0.43 HCT (%) 40.7 ± 2.83 43.4 ± 3.59 45.8 ± 4.29 43.7 ± 1.20 MCV (fL) 66.7 ± 2.41 65.2 ± 3.09 69.3 ± 2.35 67.8 ± 3.11 MCH (pg) 19.8 ± 0.86 19.0 ± 0.91 19.8 ± 0.40 19.4 ± 0.57 MCHC (g / dL) 29.7 ± 0.26 29.2 ± 0.58 28.6 ± 0.57 28.6 ± 0.52 PLT (10 ³ / μl) 483.3 ± 96.55 432.7 ± 210.12 477.5 ± 235.98 509.5 ± 57.89

2-6. Histopathology

As described in Experiment 3-1, each individual of the four groups was euthanized, autopsied, small intestine collected, dissected, fixed in 10% formalin, and subjected to the normal procedure for the preparation of pathological tissue. Histopathological examinations were performed with matoxylin and eosin stained slides. Histopathological examination was performed by making 9 small intestine sites per individual to reduce the variable according to the sample position. The histopathologic findings were scored according to the status of each lesion, and scored by the scores of six tissues. The mean and standard deviation of each group were calculated. Histopathological score was “0; Normal, 1; Inflammatory cell infiltration into the intestinal epithelium, 2; Small intestinal villi epithelial necrosis and ulcer, 3; Death ”.

E. coli At one week after the inoculation, the small intestine was collected from each group to perform a pathological examination. The group scored the sum of the pathological tissue scores of six tissues for each individual, and then the mean and standard deviation of each group were measured. The calculated values are shown in Table 11.

The pathologic scores of the III and IV animals treated with 0.5% and 0.25% GR were lower than those of the positive control group II animals (p <0.01). Histopathologically, the animals of the positive control group II showed damage to the small intestine mucosal epithelial cells and proliferation of the lymphoid follicles due to E. coli infection (see FIGS. 3 and 4). On the other hand, histopathologic examination of group III and IV animals treated with 0.5% and 0.25% GR showed that the lesion scores were reduced and the lesion score was low.

group Pathological score I 0.7 ± 0.58 * II 11.0 ± 1.0 III 4.5 ± 0.58 * IV 6.8 ± 0.96 * * Significant differences were shown in comparison with the positive control group (group II) (p <0.01)

Examples of the preparation of the pharmaceutical composition containing the extract or compound of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.

Formulation example  One. Powder  Produce

20 mg of GR extract (Example 1-2-1)

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation example  2. Preparation of Tablets

10 mg of compound 2 (Example 2-3)

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation example  3. Preparation of Capsule

10 mg of compound 5 (Examples 2-6)

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

10 mg of compound 2 (Example 2-3)

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO ₄ 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation example  5. Liquid  Produce

10 mg of compound 5 (Examples 2-6)

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added, the above ingredients are mixed, and then, purified water is added to adjust the total amount to 100 ml, and then sterilized by filling into a brown bottle. Manufacture.

1 is a diagram showing the HPLC chromatogram of the gall bladder 70% ethanol extract,

Figure 2 is a diagram showing the feces of Group II (A) and Group III (B) after 3 days of inoculation,

3 is a view showing the small intestine of group II (A) and group III (B),

4 is a diagram showing pathological examination (H & E stain, x200) of small intestine of group I (A), group II (B), group III (C) and group IV (D).

Claims (7)

The dried gallnut is chopped and dried with cold solvent extraction, hot water extraction, ultrasonic extraction or reflux cooling for 2 to 5 hours at an extraction temperature of 20 to 100 times with 70 to 80% ethanol mixed solvent of 10 to 20 times the dry weight. Gallic acid (1), a mixture of paradigalic acid and metadigalic acid (2), ethyl gallate (4) and ethyl 70 to 80% ethanol mixed solvent extracts consisting of the content ratio (4.3: 1: 7.2: 16.3) of the complex of paradigallate and ethyl metadigallate (5) or the pantao-galloyl glucose isolated therefrom ( Siegel containing penta- O -galloyl glucose, ethyl gallate or a mixture of ethyl paradigallate and ethyl metadigallate (a mixture of ethyl p -digallate and ethyl m -digallate) as an active ingredient La descenterie (Shigella disenteriae), S. flexneri, S. boydii, S. sonnei, Salmonella typhi, Salmonella paratyphi , Salmonella gallinarium, Salmonella typhimurium, Salmonella enteritidis, Vibrio cholerae, Salmonella gallinarum ( Salmonella gallinarum ), or methicillin Antimicrobial composition against the acquired common infectious disease strain selected from methicillin-resistant S. aureus ( MRSA) and antimicrobial composition for the prevention and treatment of the acquired common infectious disease. The method of claim 1, wherein the nut gall (Galla Rhois) separated from the extract compound is ethyl gallate (ethyl gallate) or a composite of ethyl di-p-gallate and ethyl gallate meta-di (a mixture of ethyl p -digallate and ethyl m Antimicrobial composition against a common infectious disease strain containing a compound selected from -digallate) as an active ingredient. delete The method of claim 1 wherein the common infectious disease strains are Shigella disenteriae, S. flexneri, S. boydii, S. sonnei. Salmonella typhi, Salmonella paratyphi, Salmonella gallinarium, Salmonella typhimurium, Salmonella enteritidis, Rabies virus , Hantan virus, Seoul virus, Pumara virus, Herpesvirus simiae (herpesvirus B), Filoviridae (Marburg virus), Paramyxovirus ( Newcastle virus in Paramyxovirus, Cowpox virus in Orthopoxvirus, Pseudocowpoxvirus, Parapavirus Contagious pustular dermatitis virus, Foot and mouth disease virus, Vesicular stomatitis virus, Arenavirus of the genus Parapoxvirus Lymphocytic choriomeningitis virus, Lassa fever virus, Orthomyxoviridae, Influenza virus, Flavivirus of the genus Lymphocytic choriomeningitis virus Japanese B encephalitis virus, Vibrio cholerae, Escherichia coli or methicillin resistant Staphylococcus aureus; MRSA) antimicrobial composition characterized in that the strain selected from. delete The dried gallnut is chopped and dried with cold solvent extraction, hot water extraction, ultrasonic extraction or reflux cooling for 2 to 5 hours at an extraction temperature of 20 to 100 times with 70 to 80% ethanol mixed solvent of 10 to 20 times the dry weight. Gallic acid (1), a mixture of paradigalic acid and metadigalic acid (2), ethyl gallate (4) and ethyl 70 to 80% ethanol mixed solvent extracts consisting of the content ratio (4.3: 1: 7.2: 16.3) of the complex of paradigallate and ethyl metadigallate (5) or the pantao-galloyl glucose isolated therefrom ( Siegel containing penta- O -galloyl glucose, ethyl gallate or a mixture of ethyl paradigallate and ethyl metadigallate (a mixture of ethyl p -digallate and ethyl m -digallate) as an active ingredient La descenterie (Shigella disenteriae), S. flexneri, S. boydii, S. sonnei, Salmonella typhi, Salmonella paratyphi , Salmonella gallinarium, Salmonella typhimurium, Salmonella enteritidis, Vibrio cholerae, Salmonella gallinarum ( Salmonella gallinarum ), or methicillin Antimicrobial adjuvant for the prevention and treatment of common infectious diseases selected from methicillin-resistant S. aureus ( MRSA). delete

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