KR100507041B1 - Antimicrobial compounds, periconicin A, B and the composition comprising the same - Google Patents

Abstract

The present invention relates to a novel antibiotic and an antimicrobial composition containing the same, and in particular, a novel diterpene-based compound which is an antimicrobial antibiotic produced by Periconia minutissima fungi, which are endogenous fungi of the endothelial tree of yew. Phosphorus periconicin (periconicin) A, B and an antimicrobial composition containing the same.

Description

Antimicrobial compounds, periconicin A, B and the composition comprising the same

The present invention relates to a novel antibiotic and an antimicrobial composition containing the same, and in particular, a novel diterpene-based compound which is an antimicrobial antibiotic produced by Periconia minutissima fungi, which are endogenous fungi of yew endothelium. Phosphoric Perinicin (Periconicin) A, B and an antimicrobial composition containing the same.

The classical meaning of antibiotics is a secondary metabolite produced by microorganisms, which means that they kill or inhibit growth at very low concentrations. The term antibiotic was first used by Waksman in the 1940's and initially used penicillins produced by the synthetic sulfonamides and penicillin sp. Used to distinguish. Since the discovery and synthesis of many substances that exhibit antimicrobial activity, it has become difficult to uniquely define the meaning of antibiotics. Currently, antibiotics generally have a natural, semi-synthetic or It is taken to mean a compound of synthesis.

In the early days, antibiotics were known to be produced mainly by microorganisms, but now, various kinds of antibiotics produced by various higher animals or plants have been reported. Research on the exploration and use of natural products is the exploration and utilization of the biosynthetic ability of the organism, so far, mainly plants and microorganisms have been the target species. Microorganisms, in particular, have produced a unique and interesting bioactive substance with a variety of species, short generation period, easy mass production, and high industrial availability, making it an attractive source of bioactive substances. However, since the opening of the antibiotic era in the mid-1950s the physiological activity of the 10,000 species of microbes known origin until now materials in it was about 70% is released from actinomycetes 20% of the fungi, the remaining 10% of Bacillus (Bacillus) and Isolated from Pseudomonas-derived bacteria (Strohl WR Biotechnology of antibiotics. Marcel Dekker Inc., New York, 1997). Researches on new substances in these fields have often been limited to the re-separation of matrix substances due to the limitations of chemical diversity.Increasing time and cost has led to the need for new resources for the discovery of new substances. It is attempting to isolate the bacteria (Riguera R., J. Mar. Biotechnol . 5 , pp187-193, 1997). Acquiring a variety of microbial resources, both biologically and chemically, such as soil actinomycetes, is critical for the future of the biological industry and human health. For example, in Korean Patent Application No. 1998-0056360, Tetricin-, a novel polyene-based compound having anti-fungal activity against anti-fungus from a strain of Streptomyces sp. A method for preparing tetricine A is disclosed. In addition, patent application No. 2000-0005508 discloses a substance called peptide kryptonin, which is a new antibiotic substance isolated from Cryptotympana dubia from Jeju, and which shows anti-bioactivity against fungi such as gram-positive bacteria, gram-negative bacteria and Candida. have.

Taxus cuspidata SIEB. Et Zuccarini used in the present invention is a plant belonging to the Taxaceae family and has the names of red pine, ginseng, transportation, confession, red-eye, flame tree, fern, hardwood, and tree The varieties are Seoraksan Snow and Snow. The leaves and twigs of this plant are called medicinal leaves (Taxi Folium et Ramulus), and the main ingredients are alkaloid taxine, taxinine and taxane. The alkaloid content reaches 0.22%, and it is known that there is an alkaloid decay with time. Flavonoids contain 0.1% to 0.5% of biflavonoid bisflavopoids (sciadopitysin), and other flavonoids such as ginkgetin, kayakflavone, and sotsutsuflavone. Other monoflavonoids contain quercetin. Biological activity or drug efficacy by the use of these compounds is expected. Other ingredients include diterpenes, 0.14% waxy compounds, and neck-like substances. Isotaxiresinol, isolarisirresinol and isosterone, ponasterone, ecdysterone and taxosterone as steroids, and cyanogen glycosides and proanthotes Cyanidin (proanthocyanidin) derivatives and the like. The Pacific yew, native to the United States, is widely known for its powerful new anticancer substance, taxol, which is very important from a chemical taxonomy point of view because it is a homogenous plant. . The medicinal effect and pharmacological action has been used in the private sector, diuretics, pain economy, kidney disease, diabetes, bark and tree trunks have been used to treat cough medicine and neuralgia. The main alkaloid of this herb is taxine, which lowers blood pressure and slows cardiac movement, but in excess, cardiac movement may stop at the diastolic phase. Today, taxane (diterpene) -based substances have been emphasized in terms of effectiveness represented by taxol, and they are effective for ovarian cancer and breast cancer (Taxus brevifolia), Taxus baccata, etc. Taxol, cephalomannine ), Search, extraction, and quantification, and tissue cultures continue to produce these active substances (Jung Bo-seop and Shin, Min-kyo; Hyang-Yaksa Dictionary, Yeonglimsa, pp113-114, 1998).

Fungus belongs to the fungus of lower plants with simple nutritional structure that does not differentiate into roots, stems, leaves, etc., it does not have chlorophyll and is characterized by parasitics, also called fungus. . Mold is widely used not only for fermented foods, but also for the production of antibiotics, pharmaceuticals, and food enzymes. The size varies from single-cell yeast, which can only be seen under a microscope, to what can be seen by eyes, and there are tens of thousands of fungi, but there are about 100 types of diseases that cause diseases in humans or animals among fungi and yeasts. Some of them are pathogenic to the human body from the beginning, and some of them coexist with the human body. This also causes disease when the human body (host) gets worse.

Endogenous fungi currently living in 270,000 species of related plants are estimated to be about 1.5 million, and its importance is recognized as abundant resources of bioactive new substances for the development of new medicines. As an example, the fact that the taxol produced by the yeast is produced by the fungus Taxomyces andreanae , which is present in the yeast, and the fact that substances believed to exist only in plants are now found in various microorganisms, even at low concentrations. At some point in the past, the biosynthetic genes of this secondary metabolite were shared. Pseudomycin, also found in Pseudomonas syringae, has entered preclinical stages with potent antifungal activity (Harrison L., et al., J. Gen. Microbiol . 137 , pp2857-2865, 1991). In Korea, research has been carried out sporadically from the point of view of toxins, focusing on plant pathologists.

The present inventors have recognized the importance of such a new search source of bioactive substances, and have been conducting new antibiotic development research from plant endogenous fungi. As a result, two antibiotics were isolated from the culture solution of the fungus Periconia minutissima OBW-15 isolated from the endothelium of Taxus cuspidata from Korea. fusicoccane) was identified as a diterpene-based compound with a skeleton (El Sayed KA Microbial transformation of hypoestenone. J. Nat. Prod. 64 , 373-375, 2001), and in its novelty periconicin A, B (Periconicin A, B The present invention was completed by confirming the anti-bioactivity of these compounds.

SUMMARY OF THE INVENTION An object of the present invention is to isolate and cultivate periconia minutishima fungi from yew trees, and to provide a new antibiotic antibiotic pertericin A, B, and an antimicrobial composition containing the same. have.

In order to achieve the above object, the present invention is to isolate and manufacture periconia minutishima fungi from the yew tree to isolate and manufacture the periconicin A and B, which is a novel diterpene-based compound produced by periconia minutishima fungi Provide a method.

The present invention also provides a periconicin derivative compound represented by the following general formula (I), which is a novel compound isolated above.

(Ⅰ)

R ₁ and R ₂ are each independently a methyl group or a hydroxy methylene group.

Preferred compounds of the general formula (I) include periconicin A and B compounds represented by the following formulas (2) and (3), respectively.

The present invention also provides an antimicrobial composition containing the compound of the general formula (I), preferably a periconicin A or B compound as an active ingredient.

The antimicrobial composition may include Bacillus subtilis , Staphylococcus aureus , Staphylococcus epidermis , Micrococcus leuteus , Krebsiella pneumoniae Klebsiella pneumoniae), Proteus vulgaris (Proteus vulgaris), is effective for Salmonella typhimurium infectious diseases caused by microorganisms such as (Salmonella typhimurium), Escherichia coli in Sheridan (Escherichia coli).

Infectious diseases caused by the microorganism include staphylococcal food poisoning, cellulitis, urinary tract infections, meningitis, peritonitis, cystitis, lymphangitis, seizures, otitis media, respiratory disease, pneumonia, purulent inflammation, sepsis, and the like. .

Hereinafter, the present invention will be described in detail.

The general formula (I) compound of the present invention can be prepared as a separation or a simple manufacturing process well known in the art through the following process.

The present invention is a manufacturing process for producing periconicin A and B, the first step of separating the periconia minutishima fungus from yew tree, the second step of culturing the isolated fungi, the fungal culture of the second step And separating and removing the fungi from the fungus, followed by a third step of extracting and concentrating the culture and a fourth step of separating and obtaining the compound of the present invention by a chromatography method from the concentrate.

The yew tree used in the first step may be used above ground, stems, underground roots, leaves, fruits, seeds and the like, preferably to use the yeast bark. The plant may be used as it is, but is preferably a plant sample collected for cutting and harvesting the bark to a suitable size, and separating the Periconia fungus, preferably Periconia Minutishima OBW-15, from the yew tree. Is immersed in C ₁ to C ₄ lower alcohols, such as methanol and ethanol, preferably ethanol for 1 to 15 minutes, more preferably 3 to 5 minutes, surface sterilization and rinsed with sterile water and dried. The sample is cut back to an appropriate size, the outer shell is removed, and the endothelial is abraded into the agar medium.

The fungus isolated from the first step is to be cultured in the fermenter for 2 to 4 weeks, preferably 3 weeks, more preferably S-7 medium (Stierle, A. et al., Science , 260 , pp214-216 , 1993) for 3 weeks.

The fungi culture was isolated and removed from the fungus by using a cotton cloth, and the organic solvent was selected from the group consisting of dichloromethane, ethyl acetate, chloroform and one or more mixtures thereof. Pear, preferably 1 to 3 folds, more preferably according to Kuchan scheme, Tillekeratne, LM V, et al., J. Nat. Prod , 52 , pp1143-1145, 1989 After repeating this operation 2 to 3 times, the organic solvent layer formed was concentrated under vacuum at a temperature of less than 35 ° C., and then the concentrated solution was dissolved in an organic solvent such as chloroform, hexane, and ethyl acetate. Separate layers. Preferably, 0.5 to 4 times the amount of chloroform is added to the organic solvent using chloroform, and the layers are separated two to three times. The water layer is discarded and the chloroform layer is concentrated under reduced pressure under vacuum. The concentrate is dissolved in 5-20 times, preferably 10-15 times, ethanol: butanol = 1: 1 of the concentrate, and the insoluble suspension is filtered and hexane: ethyl acetate = 1: 1-1: 3, preferably Hexane = ethyl acetate = 1: 1 is added 1 to 5 times, preferably 1 to 3 times the amount of ethanol: butanol = 1: 1, and the layers are separated 2-3 times. Discard the hexane layer and use the ethyl acetate layer as a sample to purify the compound. At this time, the ethyl acetate layer may be used as it is or in the form of a dried product by vacuum drying.

The concentrate obtained in the third step is subjected to open-column chromatography to separate the compounds. In this case, two fractions may be separated according to the degree of anti-biological activity by using a chloroform: hexane: methanol mixed solvent as a developing solvent. Collect these fractions and use acetonitrile: water: methanol mixed solvent again as a developing solvent, perform thin-layer chromatography filled with silica gel, and carefully watch the silica gel in the plate portion containing the active substance. Make a good collection. The recovered silica gel is extracted completely with an organic solvent such as chloromethane, chloroform, ethyl acetate, hexane, acetonitrile, preferably using acetonitrile, the solvent is evaporated, and the obtained residue is recrystallized to obtain periconisin A of the present invention. And B can be obtained.

The antimicrobial properties of periconicin A and B obtained by the above manufacturing process were evaluated using a liquid medium. Activity evaluation is to dissolve the test sample in dimethyl sulfoxide (dimethyl sulfoxide) to make a two-fold dilution series with the above liquid medium and then to distribute in 96-well plate (96-well plate) and inoculate the test solution to room temperature to 40 Evaluation was carried out at 12 to 48 hours, preferably 24 hours at 37 ℃, preferably 37 ℃ (Wu, M. & Hancocks, REW J. Biol. Chem. , 274 , pp 29-35, 1999).

Pericolicin A or Periconicin B, which is a novel antimicrobial agent of the present invention obtained by the above method, is Bacillus cilialis, Staphylococcus oreus, Staphylococcus epidermis, Microcoke Luteus, Klebsiella It showed antimicrobial activity against various kinds of bacteria such as pneumoniae, proteus vulgaris, Salmonella typhimurium and Escherichia coli.

The composition comprising an antimicrobial substance of the present invention, periconicin A or B is staphylococcal food poisoning caused by the microorganism, cellulitis (蜂窩織炎), lymphadenitis, bottoms, urinary tract infections, meningitis, peritonitis, cystitis, respiratory tract It can be used as a pharmaceutical composition for the treatment of infectious diseases such as purulent inflammation and sepsis, such as disease, otitis media, pneumonia.

Compositions comprising an antimicrobial agent 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 antimicrobial agents of the 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.

The composition containing the antimicrobial agent according to the present invention may be prepared in the form of powder, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like, external preparation, suppository and sterile injectable solution, respectively, according to a conventional method. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the antimicrobial agent 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 include at least one excipient such as starch, calcium carbonate, sucrose ( It is prepared by mixing sucrose or lactose and gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use may include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to water and liquid paraffin, which are commonly used to include suspensions, solutions, emulsions, and syrups. have. 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 antimicrobial agents 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 antimicrobial material of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 100 mg / kg. Administration may be administered once a day or may be divided several times.

The antimicrobial agent of the present invention can be administered to mammals such as rats, mice, livestock, humans and the like by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

 The present invention is described in more detail based on the following examples and experimental examples, but the present invention is not limited thereto.

Example 1 Periconia Minutishima from Yew Trees Isolation of OBW-15 Fungi

The bark of the yew tree (1.5m above the ground) was cut to a size of 1 × 10 cm and sterilized by immersion in 70% ethanol for 5 minutes and rinsed with sterile water. This sample was again sterilely cut (1 × 1 cm) to a suitable size, the outer skin was removed and the endothelial was placed on 1.5% water agar and incubated at 27 ° C. for 3 to 7 days. The mycelial tips of the fungal colonies grown from the sections are cut out and transferred to PDA (potato dextrose agar, Difco) agar medium and cultured at 27 ° C. for 1-2 weeks to form spores. Preserved at -80 ° C in% glycerol solution and used if necessary (Strobel, G. et al., Microbiology , 142, pp435-440, 1996).

Example 2 Periconia Minutishima  Preparation of OBW-15 Media

The culture of Periconia minutishima OBW-15 was carried out at 25 ° C. with 500 ml of S-7 medium (Stierle, A. & Strobel, D. Science , 260, pp241-216, 1993). 21 days in a small culture bottle was incubated in the dark. 15 l of the culture was taken to remove mycelia (fungal mycelium) with a cotton cloth, and the remaining filtrate was concentrated in vacuo. The filtrate obtained was fractionated by a modified method (Kupchan scheme, Tillekeratne, LM V, et al., J. Nat. Prod , 52 , pp1143-1145, 1989), and layered by ethyl acetate: methanol = 9: 1. An ethyl acetate soluble fraction layer was obtained. The ethyl acetate layer obtained by repeating this operation once more was vacuum dried at 35 deg.

Example 3 Isolation of Periconicin A and B

The dried product prepared in Example 2 was subjected to open-column chromatography filled with silica gel using a mixed solvent of chloroform: hexane: methanol = 7: 6: 1 as an eluting solvent. Two fractions were separated. This fraction was again eluted with thin layer chromatography (RP-18 F254S, 20 × 20) packed with 1 mm silica gel plate using a mixed solvent of acetonitrile: water: methanol = 2: 1: 1. Cm, Merck), and carefully cut and recovered the silica gel of the portion of the plate containing the active substance (periconicin A, R _f = 0.32, periconicin B, R _f = 0.67). The recovered silica gel was completely extracted with acetonitrile, the solvent was evaporated, and the obtained residue was recrystallized with ethyl acetate to prepare periconicin A and B in the form of white solid having the following physical properties. 1 is shown.

Periconicin A ; Melting Point: 81.5 ℃

[α] _D = +63.1 ( c 0.45, CHCl ₃ ); UV (MeCN) λ _max 276 log ε (0.623), 226 (1.636), 198 (1.868) nm).

Molecular Formula: C ₂₀ H ₂₈ O ₃ (found m / z 316.2046 (M +)

IR: 3430, 1630, 1750 cm ^-1 .

Periconicin B ; Melting Point: 71.4 ℃

[α] _D = +93.3 (c. 120, CHCl ₃ ); UV (MeCN) λ _max 274 log ε (0.089), 224 (0.260), 200 (0.354)).

Molecular Formula: C ₂₀ H ₂₈ O ₄ (found m / z 332.2008 (M +).

Periconicin A Periconicin B 13C (75 MHz) 1H (300 MHz) HMBC NOESY 13C (75 MHz) 1H (300 MHz) One 50.66 (C) H-2, H-3, H-10β, H-13, H-15 50.85 (C) 2β 45.54 (CH ₂ ) 1.84 (d, 15.1) H-3, H-7, H-14, H-15 H-4, H-15, H-16 45.31 (CH ₂ ) 1.86 (d, 15.0) 2α 1.70 (dd, 9.9, 15.2) H-7, H-10α, H-15, H-16 3 37.54 (CH) 2.00 (ddq, 6.2, 9.5) H-2α, H-7, H-16 H-4, H-5, H-14β 37.59 (CH) 1.98 (ddd, 6.3, 9.6, 9.6) 4 39.04 (CH) 2.43 (ddq, 6.9, 6.9) H-2α, H-5, H-16 H-2β, H-3, H-5 39.02 (CH) 2.42 (ddq, 6.9, 6.9, 7.2) 5 72.29 (CH) 4.81 (d, 7.8) H-4, H-16 H-3, H-4 79.27 (CH) 4.78 (d, 7.8) 6 216.67 (C) H-4, H-16 216.66 (C) 7 48.00 (CH) 2.65 (d, 9.3) H-2, H-4, H-9, H-17 H-2α, H-16 47.97 (CH) 2.63 (d, 9.3) 8 141.28 (C) H-3, H-10, H-17 141.14 (C) 9 156.27 (CH) 7.01 (dt, 0.8, 8.8) H-10 H-17, H-19, H-20 156.62 (CH ₂ ) 7.14 (dt, 0.9, 8.7) 10β 24.56 (CH ₂ ) 2.66 (dd, 9.2, 13.0) H-19, H-20 24.41 (CH ₂ ) 10α 3.05 (dd, 8.4, 12.5) H-2α 3.07 (dd, 8.4, 12.3) 11 137.83 (C) H-2α, H-10, H-13, H-14α, H-15 139.49 (C) 12 144.21 (C) H-13, H-14α, H-18, H-19, H-20 142.92 (C) 13β 26.32 (CH ₂ ) 2.08 (m) H-14, H-18 H-14β, H-19, H-20 26.64 (CH ₂ ) 2.04 (m) 13α 2.19 (m) H-19, H-20 14α 36.21 (CH ₂ ) 1.52 (m) H-2β, H-15 H-15 36.02 (CH ₂ ) 1.53 (m) 14β 1.58 (m) H-3, H-13β 15 26.50 (CH ₃ ) 0.98 (s) H-2, H-14 H-2, H-14α 26.36 (CH ₃ ) 1.00 (s) 16 217.32 (CH ₃ ) 0.76 (d, 7.2) H-15 H-2, H-7 7.32 (CH ₃ ) 0.75 (d, 7.2) 17 192.18 (CH) 9.16 (s) H-7, H-9 H-9 192.61 (CH) 9.15 (s) 18 28.41 (CH) 2.61 (heptet, 6.8) H-19, H-20 36.90 (CH) 2.69 (m) 19 21.87 (CH ₃ ) 0.96 (d, 6.8) H-18, H-20 H-9, H-10β, H-13 65.82 (CH ₂ ) 3.50 (m) 20 20.89 (CH ₃ ) 0.95 (d, 6.7) H-18, H-19 H-9, H-10β, H-13 15.23 (CH ₃ ) 0.94 (d, 6.7)

Experimental Example 1. Determination of antimicrobial activity of periconicin A and B

The antimicrobial test was carried out using a liquid medium dilution method (Wu, M. & Hancocks, REW J. Biol. Chem. , Using m-plate count broth, manufactured by Difco) 274 , pp 29-35, 1999). Dissolve the test sample in dimethyl sulfoxide (dimethyl sulfoxide), make a 2-fold dilution series with the above liquid medium and distribute to 96-well plate, inoculate the test solution (about 10 ⁴ CFU / ml) at 37 ℃ Incubated for 24 hours. The antimicrobial activity was determined by the minimum inhibitory concentration (MIC), which completely inhibited the growth of bacteria in the 2-fold dilution series. The assay strains used were Bacillus sertilis (ATCC 6633) and Staphylococcus oreus. (ATCC 6538p), Staphylococcus Epidermis (ATCC 12228), Microcoke Luteus (IFO 12708), Klebsiella pneumoniae (IFO 13541), Proteus vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028) ), Escherichia coli (ATCC 25922) was used. Minimum growth inhibition concentrations (MIC, μg / ml) of periconicin A and B were measured and shown in Table 2 below. Periconicin A exhibited antimicrobial activity in the range of 3.12 to 12.5 μg / ml of minimum growth inhibition for the assay strain, and ferricinicin B showed 25-50 μg / ml of minimum growth inhibition for the assay strain. It showed a range of antimicrobial activity.

microbe Antimicrobial Minimum Growth Concentration (MIC, ㎍ / ㎖) One 2 Gentamicin Bacillus stills 3.12 25 3.12 Staphylococcus Oreus 12.5 50 3.12 Staphylococcus Epidermis 12.5 100 3.12 Microcoke Luteus 25 > 100 6.25 Krebssiela Pneumonia 3.12 25 12.5 Proteus Bulgari 6.25 50 6.25 Salmonella typhimurium 6.25 50 3.12 Eshericia collie 100 > 100 1.56

Although the formulation examples of the pharmaceutical composition comprising the periconicin A or periconicin B of the present invention will be described, the present invention is not intended to limit this but only to be described in detail.

Formulation Example 1 Preparation of Powder

Dry powder of Periconicin A compound · 500 mg

Corn starch · · · · · · · · · · · · 100mg

Lactose · · · · · · · · · · 100mg

Talc · · · · · · · · · 10 mg

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

Formulation Example 2 Preparation of Tablet

Dry Powder of Periconicin A Compound · · · · · · 100mg

Corn starch · · · · · · · · · · · · · 100mg

Lactose · · · · · · · · · 100 mg

Magnesium Stearate · · · · · · · · · · 2mg

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

Formulation Example 3 Preparation of Capsule

Dry powder of Periconicin A compound · 50 mg

Lactose · · · · · · · · 50mg

Magnesium stearate · · · · · · · · · 1 mg

The above ingredients are mixed and compressed into tablets according to a conventional method for preparing capsules to fill gelatin capsules.

Formulation Example 4 Preparation of Injection

Dry powder of periconicin A compound · · · · · 10 mg

Sterile distilled water for injection · · · · · · · · · · ·

pH regulator · · · · · · · · · · · ·

According to the conventional method for preparing an injectable drug, the active ingredient is dissolved in distilled water for injection, the pH is adjusted to about 7.5, and the whole is filled with 2 ml of ampoule with distilled water for injection to sterilize it.

Formulation Example 5 Preparation of Liquid

Dry powder of Periconicin A compound · · · · · · · 1g

Isomerized sugar · · · · · · · · · · · · · · 10g

Per stand · · · · · · · · · · · · · · · 10g

Lemon zest · · · · · · · · · · · · ·

Purified water · · · · · · · · · · · · · ·

According to the conventional method for preparing a liquid solution, each component is added to the purified water, dissolved, and lemon flavor is added, and then purified water is added to adjust the total amount to 100 ml, and then filled into a brown bottle to prepare a liquid solution.

Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be modified according to regional and ethnic preferences such as demand hierarchy, demand country, and use purpose.

As described above, the present invention provides an antimicrobial composition containing a new antibiotic substance, periconicin A, B, which is produced by Periconia minutishima fungus isolated from yew tree, and an active ingredient thereof.

In addition, the present invention is an active ingredient with periconicin A and B, staphylococcal food poisoning, cellulitis (림프), lymphangitis, basal tract, urinary tract infection, meningitis, peritonitis, cystitis, respiratory disease It provides a pharmaceutical composition for the treatment of infectious diseases such as purulent inflammation and sepsis, such as otitis media, pneumonia.

1 is a diagram of the coupling of ¹ H- ¹³ C obtained through the HMBC experiment of periconicin A,

2 is a diagram showing a NOESY analysis of periconicin A.

Claims (5)

Periconicin derivatives of a novel structure represented by the following general formula (I) (Ⅰ) R ₁ and R ₂ are each independently a methyl group or a hydroxy methylene group. The compound of claim 1, wherein the periconicin A or B compound. Bacillus certilis, Staphylococcus oreus, Staphylococcus epidermis, Microcoke Luteus, Krebsciella pneumoniae, Proteus, containing the compound of formula (I) of claim 1 and a pharmaceutically acceptable carrier. An antimicrobial composition for the treatment of infectious diseases caused by microorganisms selected from Bulgari, Salmonella typhimurium and Escherichia coli. delete delete