KR20100041258A - Novel use of js-1 thereof - Google Patents

Abstract

PURPOSE: A composition containing JS-1 or Baeckea frutescens L. extract is provided to use in acne treatment with excellent antibacterial activity. CONSTITUTION: An antibacterial composition contains JS-1 compound of chemical formula 1 or its pharmaceutically acceptable salt as an active ingredient. The composition has antibacterial activity to Propionibacterium acnes, Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis or Staphylococcus saprophyticus. The JS-1 of chemical formula 1 is isolated from Baeckea frutescens L. The antibacterial composition contains Baeckea frutescens L. extract as an active ingredient. The Baeckea frutescens L. extract is isolated using water, organic solvent of C1-C6, subcritical water, or supercritical carbon dioxide. A composition for treating acne contains the JS-1 compound of chemical formula 1 or its pharmaceutically acceptable salt as an active ingredient.

Description

New use of JS1 {Novel use of JS-1 approximately}

The present invention relates to a novel use of the JS-1 (JS-1) compound or Bahia Fruitsense extract, more specifically, the antibacterial of the JS-1 (JS-1) compound or Bachia Fruits extract And acne treatment uses.

[Formula 1]

Numerous microorganisms exist in the skin of the human body. Among the microorganisms causing the skin diseases are Propionibacterium acnes, Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus aureus. ), Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus Prophyticus (Staphylococcus saprophyticus), and especially the microorganisms that cause acne and inflammation are Propionibacterium acnes, Staphylococcus epidermidis and Micrococcus luteus Et al. (Raman A. et al., Lett. Appl. Microbiol., 21: 242-245, 1995). They are also present in normal skin, and in particular, Propionibacterium acnes is the main cause of acne. The microorganism first penetrates into the hair follicles through the hair follicle tube, and deeply inoculates the hair follicles while decomposing sebum to generate free fatty acids, and when staphylococcal bacteria are secondaryly infected, reddened swells and pus is formed.

The acne is caused by an inflammatory disease of the fur branch and is a very common skin disease that causes inflammation of facial hair follicles of puberty and young age. However, these days, acne is widening due to air pollution, sex hormone imbalance, drug abuse, stress, and visceral diseases. At puberty, both male and female sex hormones become active, stimulating the sebaceous glands attached to the hair follicles, and as a result, the sebaceous glands become larger and secrete more sebum. At the same time, the stratum corneum of the hair follicles, or pores inlet, becomes thick and the adhesion increases, resulting in narrowing or clogging the pores. As a result, sebum accumulates in the hair follicles, and bacteria living in the hair follicles multiply and develop into inflammation.

Until now, benzoyl peroxide, salicylic acid, benzalkonium chloride, phenol and tetracycline have been used to suppress the bacteria that cause the inflammatory skin diseases of acne and fur branch. Or antibiotics such as erythromycin. However, antibiotics such as tetracycline are known to be effective in treating skin, but are highly likely to cause side effects such as the emergence of strains resistant to propionibacterium and photosensitivity (Gollnick, H. et al., Dermatology., 196: 119-125, 1998). In addition, salicylic acid preparations, whose main effect is the removal of keratin, cannot be used for purulent dermatitis and may cause skin redness and erythema, while benzoyl peroxide preparations that suppress purulent bacteria may cause allergic dermatitis and erythema. It is reported and does not cure acne in terms of efficacy.

In addition, recently, natural acne, such as tea tree oil (royal tree oil), royal jelly extract (gin jelly), ginseng extract (ginseng extract) is used to treat acne, but since most of the natural products are not a single substance external skin preparations or cosmetics Due to the addition of other substances in the formulation, the antimicrobial activity may be drastically reduced, and there is a problem in that the antimicrobial activity spectrum is not wide and the antimicrobial activity is not effectively exhibited against acne-inducing bacteria. In particular, natural-derived antimicrobial material has a problem that it is difficult to formulate because a large portion of the active ingredient is lost by evaporation or weak thermal stability when heated, the antibacterial activity tends to drop sharply (Higaki, S. et al., J. Dermatology., 23: 310-314, 1996).

The present inventors have searched for a long time to find a natural-derived compound having strong antimicrobial activity against skin microorganisms, and as a result, JS-1 (JS-1) or bacia fruitsens extract isolated from Bachia Fruitsense has excellent antimicrobial activity against It was confirmed that the present invention was completed.

The present invention provides a natural compound or a natural extract showing an excellent antimicrobial activity to skin microorganisms and a composition for treating antibacterial or acne containing the same, and a method for inhibiting the growth of skin microorganisms using the compound or extract or treating acne It provides a method for providing a new use for the production of antimicrobial or acne treatment of the compound or extract.

In order to achieve the above technical problem, the present invention is Propionibacterium acnes (Propionibacterium acnes), Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus ( Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus xylosus, Staphylococcus hominista, Staphylococcus hominis JS One (JS-1) represented by the following formula (1) showing antimicrobial activity against a microorganism selected from the group consisting of Staphylococcus saprophyticus (Staphylococcus saprophyticus) containing a pharmaceutically acceptable salt as an active ingredient To provide.

The JS-1 (JS-1) compound represented by Formula 1 of the present invention or Bachia fruitsens extract is propionibacterium acnes, Staphylococcus epidermidis, Micrococcus luteus ( Micrococcus luteus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylalos, Staphyusocsta xylos It is effective in inhibiting the growth of microorganisms selected from the group consisting of Staphylococcus hominis and Staphylococcus saprophyticus and inhibiting the growth of microorganisms, and thus, it is effective in antimicrobial compositions or compositions for treating acne. Can be used.

[Formula 1]

The present invention is propionibacterium acnes (Propionibacterium acnes), Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus warne Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus saproticocus saphyticus It provides an antimicrobial composition containing as an active ingredient the Bachia fruit extract extract showing antimicrobial activity to the microorganism selected from the group consisting of.

In addition, the present invention provides a composition for treating acne, which contains the JS One (JS-1) compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

In another aspect, the present invention provides a composition for treating acne containing Bachia fruit extract as an active ingredient.

In addition, the present invention by administering an effective amount of the JS One (JS-1) compound represented by the formula (1) to Propionibacterium acnes (Propionibacterium acnes), Staphylococcus epidermidis, Micro Micrococcus luteus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xyloccus xylosus), Staphylococcus hominis, Staphylococcus saprophyticus, and a method for inhibiting the growth of microorganisms selected from the group consisting of.

In addition, the present invention is administered to an individual in need of an effective amount of Bacteria fruitsens extract, Propionibacterium acnes (Propionibacterium acnes), Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus luteus Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus homini Staphylococcus hominis), Staphylococcus saprophyticus (Staphylococcus saprophyticus) provides a method for inhibiting the growth of microorganisms selected from the group consisting of.

In addition, the present invention provides a method for treating acne by administering an effective amount of the JS One (JS-1) compound represented by Formula 1 to a subject.

The present invention also provides a method of treating acne by administering to a subject in need thereof an effective amount of a Bacillus fruitsens extract.

In addition, the present invention is Propionibacterium acnes (Staphylococcus epidermidis), Micrococcus luteus (Jes-1) compound represented by Formula 1 (JS-1) Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus xylosus Provided for the preparation of antimicrobial agents against microorganisms selected from the group consisting of Staphylococcus hominis, Staphylococcus saprophyticus.

In addition, the present invention is Propionibacterium acnes (Propionibacterium acnes), Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus of Bachia fruitsens extract aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus hominis, Staphylococcus warneri Provided are uses for the preparation of antimicrobial agents against a microorganism selected from the group consisting of Staphylococcus saprophyticus.

In addition, the present invention provides a use for the preparation of the acne treatment of the JS One (JS-1) compound represented by the formula (1).

The present invention also provides a use for the preparation of an acne therapeutic agent of Bachia Fruits extract.

Hereinafter, the present invention will be described in detail.

In the present invention, the effective amount refers to an amount that is effective in treating antibacterial or acne against the skin microorganisms in vitro or in vivo.

In the present invention, an individual means an animal, including a mammal, especially a human. The subject may be a patient in need of treatment.

In the present invention, the skin microorganism is propionibacterium acnes (Propionibacterium acnes), Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus Refers to a microorganism selected from the group consisting of Staphylococcus saprophyticus.

The present invention is characterized by providing a novel use of the JS One (JS-1) compound represented by the following formula (1).

[Formula 1]

In addition, the present invention is characterized by providing a novel use of the Bachia fruit extract extract.

 The compounds according to the invention can be used in the form of salts, preferably pharmaceutically acceptable salts. As such salts, acid addition salts formed with pharmaceutically acceptable free acids are preferred. Organic acids and inorganic acids may be used as the free acid. The organic acid is not limited thereto, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, Glutamic acid and aspartic acid. In addition, the inorganic acid includes, but is not limited to, hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid.

The JS-1 (JS-1) compound represented by Chemical Formula 1 of the present invention may be obtained from a plant or a part of a plant using a method of extracting and separating conventional materials, and preferably from Bachia fruitsens. And most preferably from the leaves of Bachia fruitsens. Stems, roots or leaves are dehydrated or dehydrated as appropriate to obtain the desired extracts, and the desired extracts are purified using purification methods known to those skilled in the art. In addition, the JS-one (JS-1) compound represented by the formula (1) derived from a plant is generally a commercially available material, or may be prepared using a known synthesis method. Specifically, it may be extracted from herbal resources such as Bakia fruitsens, and may be prepared by synthesis by conventional chemical synthesis.

In addition, as a preferred compound of the present invention, the JS One (JS-1) compound represented by the formula (1) is separated and purified from water or oil obtained by compressing the leaves of Bachia Fruitsense or organic solvent extracts or Bachia Fruitsense of C1 to C6. can do.

Bacteria fruitsens is a Myrtaceae family, the leaves are used for colds, fever, abdominal pain, and headaches. Essential oils contained in Bahia Fruitsense have been reported to protect liver and inhibit inflammation (Z, X, Xiang et al., Chemical Abstracts, 100, 17644, 1995). It may also be used. However, the JS One (JS-1) compound represented by Formula 1 has not been reported so far for antimicrobial activity against skin microorganisms, especially acne-inducing bacteria.

The JS-1 compound (JS-1) of the present invention can be separated and purified from water obtained by compressing water of Bahia Fruitsense, organic solvent extract of C1-C6, subcritical water or supercritical carbon dioxide or Bachia Fruitsense. Extraction solvents include purified water, methanol, ethanol, propanol, isopropanol, butanol, butanol, acetone, ether, benzene, chloroform Various solvents such as chloroform, ethyl acetate, methylene chloride, hexane, cyclohexane and petroleum ether may be used alone or in combination. The separation and purification of JS-1 from the extracts of Baquia fruitsens is performed by column chromatography and high performance liquid chromatography filled with various synthetic resins such as silica gel or activated alumina. HPLC) and the like can be used alone or in combination. However, the extraction and separation and purification method of the active ingredient is not necessarily limited to the above method.

The JS-1 compound represented by Chemical Formula 1 of the present invention exhibits excellent antimicrobial activity with respect to acne-inducing bacteria such as Propionibacterium acnes, and has excellent thermal stability and thus antibacterial activity. Is maintained.

The JS-1 compound (JS-1) represented by Chemical Formula 1 has a minimum inhibitory concentration for Propionibacterium acnes (1/500), which is a minimum inhibitory concentration of benzoyl peroxide, which is widely used as an acne treatment agent, respectively. Much lower than 1000 / (Decker, LC. Et al., Antimicro.Agents. Chemother., 33 (3): 326-330, 1989), and the minimum inhibitory concentration of benzalkonium chloride 200-300 / (Gloor, M. et al., Arch.Dermatol.Res., 265 (2): 207-212, 1979) or the minimum inhibitory concentration of terpinen-4-ol, the oil component of the tea tree, 300-500 / (Raman, A. et al. , Lett.Appl.Microbiol., 21 (4): 242-245, 1995), showed about 150 times lower antimicrobial activity. Therefore, the JS One (JS-1) compound represented by Chemical Formula 1 of the present invention can be effectively used as a composition for treating acne.

In addition, the JS One (JS-1) compound represented by Formula 1 may be Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus The minimum inhibitory concentration for the selected microorganisms from the group consisting of Staphylococcus saprophyticus shows strong antimicrobial activity at 8-16 μg / ml. Therefore, the JS One (JS-1) compound represented by Chemical Formula 1 of the present invention can be effectively used as an antimicrobial composition.

The Bachia Fruits extract of the present invention may be prepared using extraction methods known to those skilled in the art, and may be prepared by water, organic solvents of C1 to C6, subcritical water and supercritical carbon dioxide. The organic solvent is C1 ~ C6 alcohol, acetone (acetone), ether (ether), benzene (benzene), chloroform (chloroform), ethyl acetate (ethyl acetate), methylene chloride (hexane), hexane (hexane), Various solvents, such as cyclohexane and a petroleum ether, can be used individually or in mixture. Preferably, the hexane extract may be prepared by extracting Bachia Fruitssen with hexane.

In one embodiment of the present invention, the Bachia fruitsensane hexane extract was found to exhibit excellent antimicrobial activity with a minimum blocking concentration of 8 μg / ml for Propionibacterium acnes. Therefore, the Bachia Fruits extract of the present invention can be effectively used as a composition for treating acne and a composition for antibacterial treatment.

Therefore, the JS-1 (JS-1) compound represented by Chemical Formula 1 of the present invention may be used as a pharmaceutically acceptable salt thereof as an antimicrobial composition or an acne treatment composition, but the composition is not limited thereto. Can be used as

In addition, the Bachia Fruits extract may be used as an antimicrobial composition or a composition for treating acne, and the composition may be used as a pharmaceutical preparation, although not limited thereto.

When formulated in the form of the drug, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which solid formulations may comprise at least one excipient, for example, in the JS-1 (JS-1) compound or bacia fruitsens extract. Starch, calcium carbonate, sucrose or lactose, gelatin and the like are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral administration include suspensions, solutions, 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. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, ointments, creams. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.

The parenteral administration is by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection. In order to formulate into a parenteral formulation, the JS-1 (JS-1) compound represented by Formula 1 or Bachia fruitsen extract is mixed with a stabilizer or a buffer in water to prepare a solution or suspension, which is used as an ampoule or vial. Formulated in unit dosage form. Dosage units may contain, for example, one, two, three or four times, or 1/2, 1/3 or 1/4 times the individual dosage. The individual dosage preferably contains an amount in which the effective drug is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dose.

The effective dose of the JS 1 compound (JS-1) compound or Bachia fruit extract extract represented by Formula 1 of the present invention is a single dose of 0.1-50 mg / kg, preferably 1-10 mg / kg, It may be administered 1-3 times. Dosage levels for a particular patient may vary depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of the disease, and the like.

Toxicity of oral administration of the JS-1 compound (JS-1) compound represented by the formula (1) of the present invention and Bahia Fruitsense extract to the mouse as a result, 50% lethal dose (LD ₅₀ ) by oral toxicity test was 2,000 It was found to be more than mg / kg.

In particular, the antimicrobial composition and acne treatment composition of the present invention may be formulated in the form of a medicament for skin application, ie, ointment, cream, and 0.001-10.0% by weight, preferably 0.001-5.0% by weight, based on the total weight of the formulation. It can be suitably formulated according to the formulation within the range of. If the amount is less than 0.001% by weight, the antimicrobial activity is lowered. If the amount is added more than 10.0% by weight, only the amount is increased.

In addition, the antimicrobial composition or the acne treatment composition of the present invention can be used in the form of cosmetic preparations for acne skin. The cosmetics include, but are not limited to, detergents, creams, lotions, essences and lotions. The composition of the present invention may be formulated in various forms such as cream, lotion, gel, water soluble liquid, essence, oil-in-water type and water-in-oil type, but it may be used in cosmetics, which formulation is used in the technical field to which the present invention belongs. It can be determined very easily by those skilled in the art. For example, in the case of preparing the detergent, in order to add the composition of the present invention to a conventional detergent base and to improve the acne treatment effect, salicylic acid, alpha-hydroxy acid, and beta-hydroxy acid (Keratolytic or Exfoliating agents) such as (beta-hydroxy acid) or sulfur (Sulfur) can be added, fragrances, pigments, fungicides, antioxidants, preservatives, moisturizers, etc. can be used, and to improve physical properties Thickeners, inorganic salts, synthetic polymers and the like can be used.

The antimicrobial composition and acne treatment composition of the present invention may be suitably formulated according to the formulation within the range of 0.001-10.0% by weight, preferably 0.001-5.0% by weight, based on the total weight of the cosmetic preparation. If the amount is less than%, the antimicrobial activity is lowered, and if it is added in excess of 10.0% by weight, only the amount of the addition is increased.

In addition, the JS 1 (JS-1) compound or Bachia fruitsens extract represented by the formula (1) of the present invention can be used in a method of inhibiting the growth of microorganisms or a method of treating acne.

Specifically, the compound may be used in a method of inhibiting the growth of microorganisms or treating acne by administering an effective amount to a subject in need thereof, and the microorganism may be propionibacterium acnes or Staphylococcus epidermis. Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus haemolyticus Skin microorganisms such as Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus saprophyticus, and the like.

The effective amount is a single dose of 0.1-50 mg / kg, preferably 1-10 mg / kg, and may be administered 1-3 times a day. Dosage levels for a particular patient may vary depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of the disease, and the like. The administration method may be oral or parenteral, and the parenteral method is by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection injection.

In addition, the JS 1 compound (JS-1) or Bachia fruitsens extract of the present invention can be used to prepare an antimicrobial or acne treatment of microorganisms, the microorganism is propionibacterium acnes (Propionibacterium acnes) , Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemoraiti Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus saprophyticus, and the like. The antimicrobial agent or acne treatment agent is not limited thereto, but refers to medicines or cosmetics using the compound of the present invention as an active ingredient.

In addition, the JS One (JS-1) compound represented by the formula (1) of the present invention or Bachia fruit extract extract may be used for the preparation of the acne treatment and the acne treatment agent is not limited to this compound or extract of the present invention It refers to a cosmetic comprising a detergent, cream, lotion, essence and lotion containing the active ingredient.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples. However, the following Examples and Experimental Examples illustrate the present invention and do not limit the scope of the present invention.

In addition, in the following Examples and Experimental examples, the% not specifically indicated as% by weight indicates weight%.

<Example 1>

Isolation and Structure Determination of JS-1 Compound

<1-1> Isolation and Structural Determination of JS-1 (JS-1) Compound from Bakia Fruitsense

To 100 g (dry weight) of dry pulverized Bahia Fruitsense was added 100 vol% hexane 400 and left at room temperature for 2 days, the solution was filtered using Whatman filter paper # 2. After repeating the above procedure twice, the hexane filtrate was concentrated in vacuo and lyophilized, and then eluted with a solvent in which dichloromethane and methanol were mixed at a ratio of 10: 0.1 by silica gel column chromatography. Completely removed to prepare a crude extract of Bachia Fruitsen.

The crude extract of Bakia fruitsen was separated on a TLC plate using a solvent system in which dichloromethane and methanol were mixed at 10: 0.1 and confirmed by TLC plate analysis. By using a solvent system in which dichloromethane and methanol were mixed at 10: 0.1 with the antimicrobial active material of the extract identified by TLC plate analysis, the ratio of the distance at which the solvent was developed and the distance at which the antimicrobial active material was developed was adjusted to 0.2. A single compound having a value of Rf = 0.2 and having a strong absorption band in ultraviolet (254, 365 nm, VL-6-LC, Vilber lourmat) was isolated.

¹ H-NMR spectra and ¹³ C-NMR spectra were measured at 400 MHz and 100 MHz (solvent: CDCl ₃ ) for the structure determination of the separated single material, respectively, and are shown in FIGS. 1 and 2, respectively. ¹³ C-DEPT spectrum that can recognize the hydrogen attached to the carbon is shown in FIG.

In addition, the results of EI / MS measured for mass spectrometry of the separated single material are shown in FIG. 4. The compound was found to have a molecular weight of 406 in EI / MS, and the molecular formula was C ₁₄ H ₂₀ O ₅ .

The results of the above ¹ H-NMR, ¹³ C-NMR, ¹³ C-DEPT, and EI / MS were compared with previous published research reports (Tsui WY, Tetrahedron, 52: 9735-9742, 1996). , The single material isolated in Example 1-1 was (1-hydroxy-9-methoxy-4,4,8,10,10-pentamethyl-2,3-dioxabicyclo [4.4.0] dec-5,8-diene -7-one) was identified as a JS-1 (JS-1) compound represented by the formula (1).

[Formula 1]

<Example 2>

Evaluation of Antimicrobial Activity of Microorganisms of JS-1 (JS-1)

<2-1> Bactericidal Activity of the Compound of JS-1 (JS-1)

The JS-1 (JS-1) compound prepared in Example <1-1> was dissolved in dimethyl sulfoxide to 0.00005%. Samples were prepared at concentrations of 0.0001%, 0.0002%, 0.0004%, and 0.0008%. After diluting Propionibacterium acnes to 2 × 10 ⁵ CFU / ml in the prepared sample, 100 ml were added to each test tube and 4, 8, 12, 16, After reacting for 20 hours, 24 hours, and 28 hours, the number of viable cells of propionibacterium acnes, a representative acne-inducing bacterium, was measured for each sample.

As can be seen in the graph of FIG. 5, when the 4 μg / ml JS One (JS-1) compound was added, the bacteria were almost killed within 48 hours. The result is that taking medicines is usually taken once every 8 hours, and ointments or applied drugs are used in about 2-4 hours. When used as a treatment for acne, it represents a very effective bactericidal activity against the typical acne causing bacterium, Propionibacterium acnes.

Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus warneri of J. S. in the same manner as above. Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, and Staphylococcus saprophyticus, indicating staphylococcus saprophyticus Minimum concentrations were measured and the results are shown in Table 1.

Minimum concentration (unit: μg / ml) showing bactericidal activity against microorganisms of JS One Concentration of JS One Compound Propionibacterium Acnes 4 Staphylococcus Epidermis 32 Micrococos Luteus 20 Staphylococcus aureus 125 Staphylococcus Warneri 125 Staphylococcus Haemoraiticus 500 Staphylococcus Xylose 32 Staphylococcus Hominis 32 Staphylococcus sapropicus 32

As a result, it was found that JS-1 (JS-1) exhibited very effective bactericidal activity against the microorganisms as well as propionibacterium acnes, an acne-causing bacterium, and thus could be used as a useful antimicrobial composition. .

<2-2> Minimum Inhibitory Concentration (MIC) Measurement of JS-1 Compound

The JS-one (JS-1) compound prepared in Example <1-1> was dissolved in 0.5% methanol, and 100 ul of each of the platelets of blood was added to the prepared 96-well plate, and the JS-one (JS- 1) The compounds were added 100 ul each at a concentration of 0.1%, and then diluted 2 times sequentially. To this dilution, Propionibacterium acnes 100 was added to each test tube to be 2 × 10 ⁵ CFU / ml, and after culturing at 37 or more for 24 hours, the minimum concentration without turbidity was measured. . Also in the same manner as above, Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Staphylococcus warne of JS-1 (JS-1) Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis, and Staphylococcus saproticocus saphyticus The minimum inhibitory concentration for was measured and the results are shown in Table 2.

Minimum concentration for microorganisms of JS-1 (JS-1) (unit: μg / ml) Concentration of JS-1 Compound Propionibacterium Acnes One Staphylococcus Epidermis 16 Micrococos Luteus 16 Staphylococcus aureus 16 Staphylococcus Warneri 16 Staphylococcus Haemoraiticus 500 Staphylococcus Xylose 16 Staphylococcus Hominis 16 Staphylococcus sapropicus 16

<Example 3>

Confirmation of acne treatment effect using JS-1 compound

Clinical experiments on the prevention and treatment of acne were carried out using JS-1 (JS-1) prepared in Example <1-1>. The test subjects were 30 males and females in their mid teens to mid 30s who suffered from acne, and then administered 600 mg twice a day for 4 weeks. The results are shown in Table 3. The number of lesions decreased significantly after 4 weeks compared to the number of lesions before the start of the study, which was statistically significant (p-value <0.05).

Average number before the start of the study Average number after 4 weeks of study P-value Cotton cloth 19.12 6.82 0.0065 papule 13.86 5.57 0.011 pustule 5.78 2.41 0.033 nodule 0.84 0.21 0.0208

<Example 4>

Thermal Stability of JS-1 Compound

<4-1> Thermal Stability of JS-1 Compound

The JS-1 compound (JS-1) prepared in Example <1-1> was dissolved in dimethyl sulfoxide to prepare a 0.1% sample, and then 60 ° C, 70 ° C, 80 ° C, 90 ° C, and 100%, respectively. After the heat treatment for 30 minutes at ℃ and 121 ℃, respectively, the results of measuring the antimicrobial activity to the minimum concentration showing the bactericidal activity are shown in Table 4 below.

Table 4

Result of Antibacterial Activity According to the Temperature of JS One Compound 60 80 100 121 Treatment temperature (℃) Minimum blocking concentration added with JS1 (μg / ml) One One One One

As can be seen from the results of Table 4, even after the heat treatment from 60 ℃ to 121 ℃ hardly reduced the antimicrobial activity. Therefore, it was confirmed that the JS One (JS-1) compound of the present invention was stable even at high temperature.

Example 5

Evaluation of Antimicrobial Activity against Bacteria Fruit Extract of Hexane Extract

Sterilization of propionibacterium acnes, which is an acne-inducing bacterium of Bacillus fruitsen 100% hexane crude extract prepared in the process of separating JS-1 (JS-1) in Example <1-1> Activity was measured in the same manner as in Example <2-1>. As a result, when the hexane extract of 64 μg / ml was added, the acne-causing bacteria were almost killed. In addition, the minimum inhibitory concentrations for the acne-inducing bacteria of the hexane extract are propionibacterium acnes, Staphylococcus epidermidis, and Micrococcus luteus. As measured in the same manner as 2>, it was confirmed that 8 μg / ml, 250 μg / ml, 64 μg / ml, respectively.

As a result of measuring the minimum inhibitory concentration for the acne-inducing bacterium Propionibacterium acnes of the extract in the same manner as in Example <2-2>, it was confirmed to be 8 μg / ml.

Therefore, the bacterium extract extract can be used as a very effective antimicrobial composition with excellent bactericidal activity against the microorganism in a relatively small amount. It was found that it can be used as an excellent acne treatment composition.

<Example 6>

Evaluation of the Antimicrobial Activity of Bacteria Fruit Sense Ethanol Extracts against Microorganisms

400 ml of 100 vol% ethanol was added to 100 g (dry weight) of dry pulverized Baquia fruitsen leaves, and left at room temperature for two days. The solution was then filtered using Whatman filter paper No. 2. After repeating the above procedure twice, the ethanol filtrate was concentrated in vacuo and lyophilized. The minimum inhibitory concentrations for the acne-inducing bacteria of the ethanol extract, Propionibacterium acnes, Staphylococcus epidermidis, and Micrococcus luteus, are shown in Example <2-2. As measured in the same manner as>, it was confirmed that the 16 μg / ml, 500 μg / ml, 64 μg / ml, respectively.

<Example 7>

Evaluation of Antimicrobial Activity against Bacteria Fruit Extract of Chloroform

To 100 g (dry weight) of dry pulverized Baquia fruitsens were added 100 vol% chloroform 400 and left at room temperature for two days, after which the solution was filtered using Whatman filter paper No. 2. After repeating the above procedure twice, the chloroform filtrate was concentrated in vacuo and lyophilized. The minimum inhibitory concentration of propionibacterium acnes, Staphylococcus epidermidis, and Micrococcus luteus, which are acne-inducing bacteria of the chloroform extract, are shown in Examples <2-2. As measured in the same manner as>, it was confirmed that 8 μg / ml, 125 μg / ml, 128 μg / ml, respectively.

<Example 8>

Evaluation of Antimicrobial Activity against Bacteria Fruit Extract Supercritical Extracts

The antimicrobial material was extracted from Bachia Fruits using a supercritical fluid extractor using carbon dioxide (CO ₂ ) as the supercritical fluid. As extraction conditions, extraction temperature was extracted at 50 ° C and extraction pressure at 200 bar, and then solvent was removed from the extract to obtain supercritical extract. Minimal low concentrations for the acne-inducing bacteria of the supercritical extract, Propionibacterium acnes, Staphylococcus epidermidis, Micrococcus luteus As measured in the same manner as 2>, it was confirmed that 64 μg / ml, 500 μg / ml, 128 μg / ml, respectively.

<Manufacture example 1-4>

Preparation of lotion containing JS-1 (JS-1) compound

Using the JS-one (JS-1) compound of the present invention to prepare a lotion having the following composition. The JS-1 (JS-1) compound isolated in Example <1-1> was dissolved in a predetermined amount of water at four concentrations of 1.0, 0.1, 0.01, and 0.001%, and then mixed with an aqueous solution of phosphoric acid. Ethanol, glycerin, and propylene glycol were mixed and mixed into the mixture prepared above, flavoring and preservatives were added, the weight was adjusted with purified water, and mixed evenly.

Preparation Example 1 Production Example 2 Production Example 3 Preparation Example 4 Main Components JS One 1.0% JS 0.1% JS 0.01% JS 0.001% Glycerin 2.0% Glycerin 2.0% Glycerin 2.0% Glycerin 2.0% Propylene Glycol 2.0% Propylene Glycol 2.0% Propylene Glycol 2.0% Propylene Glycol 2.0% Potassium Phosphate 0.1% Potassium Phosphate 0.1% Potassium Phosphate 0.1% Potassium Phosphate 0.1% Sodium Diphosphate0.05% Sodium Diphosphate 0.05% Sodium Diphosphate 0.05% Sodium Diphosphate0.05% Fragrance 0.02% Fragrance 0.02% Fragrance 0.02% Fragrance 0.02% Ethanol (96%) 50% Ethanol (96%) 50% Ethanol (96%) 50% Ethanol (96%) 50% Purified water balance Purified water balance Purified water balance Purified water balance 0.1% preservative 0.1% preservative 0.1% preservative 0.1% preservative

Experimental Example 1

Determination of antimicrobial activity of lotion containing JS-1 (JS-1) compound

To the test tube containing 4 ml of each of the prepared cosmetics containing JS-1), each concentration was added 1 ml of acne-inducing bacteria, such as propionibacterium acnes, and shake the tube. After 24 hours of incubation, measuring the number of viable cells to measure the antimicrobial activity is shown in Table 6 below.

Acne pathogenic bacteria Test solution Viable Count (Bacterial / ml) 0 hours 24 hours Propionibacterium Acnes Preparation Example 1 2.5 × 10 ⁵ <1 Production Example 2 2.5 × 10 ⁵ <10 Staphylococcus Epidermis Preparation Example 1 5.5 × 10 ⁵ <1 Production Example 2 5.5 × 10 ⁵ <1 Microcaucus Luteus Preparation Example 1 6.0 × 10 ⁵ <1 Production Example 2 6.0 × 10 ⁵ <2

As can be seen from the results of Table 6, the medicinal cosmetics according to the present invention is antibacterial against acne-inducing bacteria such as Propionibacterium acnes when compared to the component except the JS-1 (JS-1) compound The activity was very high.

<Manufacture example 5-8>

Preparation of cream containing JS-1 (JS-1) compound

Using the JS One (JS-1) compound of the present invention to prepare a cream having the following composition. First, substances labeled B were dissolved at 75 to 80 ° C., and cetyl alcohol and preservatives were dissolved at the same temperature. C was emulsified in B, and then mixed with one of the JS One (JS-1) compounds represented by A at concentrations of 3.0, 0.1, 0.01, and 0.001%, respectively, and finally mixed with perfume and quantified with purified water.

Production Example Preparation Example 5 Preparation Example 6 Preparation Example 7 Preparation Example 8 Main Components A JS One 3.0% JS 0.1% JS 0.01% JS 0.001% B Glycerin 2.0% Glycerin 2.0% Glycerin 2.0% Glycerin 2.0% Propylene Glycol 2.0% Propylene Glycol 2.0% Propylene Glycol 2.0% Propylene Glycol 2.0% Lauryl chloride sulfide 8.0% Lauryl chloride sulfide 8.0% Lauryl chloride sulfide 8.0% Lauryl chloride sulfide 8.0% Stearin 5.4% Stearin 5.4% Stearin 5.4% Stearin 5.4% Mineral oil 4.5% Mineral oil 4.5% Mineral oil 4.5% Mineral oil 4.5% C Fragrance 0.02% Fragrance 0.02% Fragrance 0.02% Fragrance 0.02% Cetyl alcohol 6.5% Cetyl alcohol 6.5% Cetyl alcohol 6.5% Cetyl alcohol 6.5% Purified water balance Purified water balance Purified water balance Purified water balance 0.1% preservative 0.1% preservative 0.1% preservative 0.1% preservative

Experimental Example 3

Determination of the Antimicrobial Activity of Creams Containing JS-1 Compound

1 ml of a solution containing acne-producing bacteria, such as propionibacterium acnes, was added to a test tube containing 4 ml of each of the prepared CS1 (JS-1) compounds at each concentration. After incubation with shaking the tube and after 24 hours to measure the number of viable cells to measure the antimicrobial activity is shown in Table 8 below.

Acne pathogenic bacteria Test solution Viable Count (Bacterial / ml) 0 hours 24 hours Propionibacterium Acnes Preparation Example 5 2.5 × 10 ⁵ <1 Preparation Example 6 2.5 × 10 ⁵ <1 Preparation Example 7 2.5 × 10 ⁵ <20 Preparation Example 8 2.5 × 10 ⁵ 1.2 × 10 ³ Cream without JS One 2.5 × 10 ⁵ 3.9 × 10 ³ Staphylococcus Epidermis Preparation Example 5 5.5 × 10 ⁵ <1 Preparation Example 6 5.5 × 10 ⁵ <2 Preparation Example 7 5.5 × 10 ⁵ <50 Preparation Example 8 5.5 × 10 ⁵ 3.8 × 10 ² Cream without JS One 5.5 × 10 ⁵ 5.6 × 10 ³ Microcaucus Luteus Preparation Example 5 6.0 × 10 ⁵ <1 Preparation Example 6 6.0 × 10 ⁵ <4 Preparation Example 7 6.0 × 10 ⁵ <15 Preparation Example 8 6.0 × 10 ⁵ 3.3 × 10 ² Cream without JS One 6.0 × 10 ⁵ 2.8 × 10 ³

As can be seen from the results of Table 8, the cream of the embodiment according to the present invention is antibacterial against acne-inducing bacteria such as Propionibacterium acnes (Propionibacterium acnes) when compared to the ingredients minus JS-1 (JS-1) The activity was very high.

Experimental Example 5

Skin application of creams containing JS-1 compounds

Clinical experiment on the prevention and treatment of acne was carried out using the cream containing JS-1 (JS-1) prepared in <Production Example 9>. Subjects were 30 males and females in their mid teens to mid 30s who suffered from acne, and the results were shown in Table 9 after applying the skin twice a day for 4 weeks. The number of lesions decreased significantly after 4 weeks compared to the number of lesions before the start of the study, which was statistically significant (p-value <0.05).

Acne lesion count measurement Average number before study Average number after 4 weeks of study P-value Cotton cloth 24.52 7.89 0.067 papule 20.43 6.12 0.018 pustule 6.23 2.18 0.024 nodule 0.82 0.36 0.043

1 is a ¹³ C-NMR spectrum of the isolated purified JS One of the present invention (JS-1).

Figure 2 is a ¹ H-NMR spectrum of the isolated purified JS One of the present invention (JS-1).

Figure 3 is a ¹³ C-DEPT spectrum of the isolated purified JS One (JS-1) of the present invention

4 is an EI-Mass spectrum of the separated and purified JS One (JS-1) of the present invention.

Figure 5 is a graph showing the results of measuring the antimicrobial activity of Propionibacterium acnes (Propionibacterium acnes) of the isolated and purified JS-1 of the present invention by viable count.

◆: Dimethyl sulfoxide, a control

■: JS-1 sample with 0.00005% concentration

▲: Sample of JS-1 (0.0001%)

×: Sample of JS-1 (JS-1) at 0.0002% concentration

*: Sample of JS-1 (0.001%)

●: JS-1 sample with 0.00008% concentration

Claims (7)

The antimicrobial composition containing any one selected from the group consisting of a JS One (JS-1) compound represented by the following Chemical Formula 1 and a pharmaceutically acceptable salt thereof as an active ingredient. [Formula 1]

According to claim 1, wherein the composition is Propionibacterium acnes (Propionibacterium acnes), Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus (Staphylococcus aureus) Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylosus, Staphylococcus hominis and Staphylococcus hominis Antimicrobial composition, characterized in that exhibits antimicrobial activity against a microorganism selected from the group consisting of phyticus (Staphylococcus saprophyticus). Propionibacterium acnes, Staphylococcus epidermidis, containing water from Bachia Fruits, organic solvents from C1 to C6, subcritical water or supercritical carbon dioxide as active ingredients , Micrococcus luteus, Staphylococcus aureus, Staphylococcus warneri, Staphylococcus haemolyticus, Staphylococcus xylose (Staphylococcus xylosus), Staphylococcus hominis (Staphylococcus hominis) and Staphylococcus saprophyticus (Staphylococcus saprophyticus) Antimicrobial composition characterized in that it exhibits antimicrobial activity against at least one microorganism selected from the group consisting of. According to claim 3, wherein the organic solvent of C1 ~ C6 is C1 ~ C6 alcohol, acetone (acetone), ether (ether), benzene (benzene), chloroform (chloroform), ethyl acetate (ethyl acetate), methylene chloride ( methylene chloride), hexane (hexane), cyclohexane (cyclohexane), petroleum ether (petroleum ether) composition for antibacterial, characterized in that selected from the group consisting of. A composition for treating acne, containing any one selected from the group consisting of JS-1 (JS-1) compounds represented by Chemical Formula 1 and pharmaceutically acceptable salts thereof as an active ingredient. A composition for treating acne, comprising an extract of Bachia Fruitsen water, an organic solvent of C1-C6, subcritical water, or supercritical carbon dioxide as an active ingredient. According to claim 7, wherein the C1 ~ C6 organic solvent is C1 ~ C6 alcohol, acetone (acetone), ether (ether), benzene (benzene), chloroform (chloroform), ethyl acetate (ethyl acetate), methylene Chloride (methylene chloride), hexane (hexane), cyclohexane (cyclohexane), petroleum ether (petroleum ether) composition for treating acne, characterized in that selected from the group consisting of.

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