Patent Application
20050084553
(a) Field of the Invention
The present invention relates to a composition comprising a Moutan root bark extract as an active ingredient, and more particularly, to a composition for the prevention and treatment of athlete's foot, osmidrosis, or acne, a composition for oral cleansing, a bactericidal/disinfectant composition, and a kitchen detergent composition applicable to medicines, cosmetics or cleansing agents.
(b) Description of the Related Art
Bacteria or fungi exist throughout the world, and there are many various kinds. Bacteria and fungi grow and reproduce under suitable growth conditions, and they may also induce diseases in animals including humans. In particular, candidiasis and athlete's foot due to fungi frequently occur, and microbes cause damage to the quality and performance of foods or industrial products.
Fungi are parasitized in skin and give rise to dermato-mycosis. In particular, dermatophytes parasitized in keratin tissues such as the keratin of skin, hair, fingernails, and toenails may also cause dermato-phytosis, Tinea, or superficial fungal infection. The main source of the superficial fungal infection is microsporum, epidermo-phyton, Trichophyton, candida species, and Malassezia furfur. The bacteria causing the superficial fungal infection mostly induce superficial lesions by proliferating in the keratin tissues of upper epithelial cells, but sometimes they may induce inflammation below the upper part of epithelia and also give rise to Dermatophytid.
As a disease generated by bacteria, Osmidrosis can be mentioned. Osmidrosis is a disease generating a foul odor caused by microbes residing in the axilla, by which substances of the skin surface including apocrinal gland secretion, keratin secretion, sebum, and sweat are degraded.
The bacteria causing osmidrosis include aerobic diptheroid, coaglucoccus negative Staphylococci, etc. (Korean Journal of Dermatology, Vol. 28, No. 5, pp. 559-564, 1990). In order to resolve such osmidrosis, methods of inhibiting the secretion of sweat or inhibiting the degradation of sweat have been attempted, and research on using direct or indirect microbe inhibitors or enzyme inhibitors such as ethyl lactate, octylcrotonate, triethyl citrate, carathane(4,6-dinitro-2-(methylheptyl)phenylcrotonate), etc. has been conducted. In addition, given that the oxidative substances of a large amount of unsaturated compounds contained in sebum contribute to the generation of foul odor, anti-oxidant agents such as BHA (Butylate HydroxyAnizol) or BHT (Butylated HydroxyToluene) have been used. However, such methods showed poor deodorization effects, and they may give rise to serious damage to skin. The use of the inhibitors of sweat secretion may impede normal homostasis, and microbe inhibitors and anti-oxidant agents may cause skin toxicity, and in many cases they can induce skin stimulation by lowering its pH.
Bacteria are divided into useful bacteria that are beneficial to humans, and noxious bacteria that cause damage. The useful bacteria are used in food processing or as antibiotics. As typical noxious bacteria that give rise to diseases, there are clostridium tetati, comma bacillus, C. diphtheriae, and tubercle bacillus. Particularly, pathogenic bacteria cause fever or inflammation reaction by infecting animals including humans.
In prior arts, in order to suppress the activities of the noxious microbes, synthetic organic antibacterial agents or inorganic antibacterial agents have been used. However, the existent synthetic, organic antimicrobial agents have the drawbacks of causing strong stimulation to eyes, skin, or olfactory sense, and of exhibiting weak antibacterial activities against gram-negative bacteria (presence of cellular membrane). Also, the inorganic antibacterial agents generally exhibit weak antibacterial abilities, and in particular, they exhibit little antibacterial activity against fungi and their antibacterial abilities are suddenly reduced when they come into contact with moisture.
As typical natural antibacterial agents, which are currently available, there are polylysines or niacins which are the bacteriocins of Streptomyces sp.
However, a large amount of them is required for antibacterial activities, and they are very expensive. Further, chito acids are more effective against gram-positive bacteria than against gram-negative bacteria, but they show relatively weak antibacterial abilities against fungi, and furthermore, their effects are insignificant against genuses containing chito acids within their cell walls (Riccardo M et al., Antimicrobial Society and Chemotherapy, 1990, 34, 2019-2023).
To prevent and treat infection of bacteria or fungi, Korea Laid-Open Patent No. 90-17490 discloses a composition having dosage forms such as powders, solutions, suspensions, creams, gels, pastes, ointments, or tinctures as a pharmaceutical composition suitable to the treatment of fungal skin diseases by local administration, and a cosmetic composition. However, in the case that the composition of such dosage forms are applied to the affected parts, a large quantity of medicine is required when the parts to be applied are broad, controlling the amount to be applied uniformly is difficult, and semi-solids with high viscosity (ex.: ointments and creams) have a problem of adhering to clothes after being applied to skin.
Further, in the case of antibacterial or antifungal agents for oral administration, the medicines are circulated in the whole body, and thus in order to have an effect from the medicines, an excessive dose must be administered, and side effects due to long-term medication may be generated. Particularly, toxicity in the body from triazole medicines has become problematic: for example, they give rise to side effects in the liver when taken for a long-term period.
The present invention has been made to solve the problems the prior arts as mentioned above, and it is an object of the invention to provide a composition that is harmless to a human body and has excellent antibacterial activity against dermatophytes such as athlete's-foot-causing pathogens and dandruff-causing pathogens.
It is another object of the invention to provide a composition for the prevention of osmidrosis and for the treatment of Osmidrosis.
It is a further object of the invention to provide a composition for the prevention and treatment of acne.
It is a still further object of the invention to provide an antimicrobial spray composition that can be easily and simply applied to affected parts, and that can enable antibacterial and antifungal substances to readily permeate into skin.
Further, it is an object of the invention to provide an antimicrobial spray composition that can prevent and treat diseases due to bacteria or fungi and that is harmless to human body.
Still further, it is an object of the invention to provide a composition capable of effectively sterilizing and/or disinfecting noxious microbes distributed in nature.
Still further, it is an object of the invention to provide a composition for the inhibition of halitosis and the prevention of tooth decay having an antibacterial activity against noxious oral microbes.
Further, it is an object of the invention to provide a kitchen detergent composition capable of effectively inhibiting noxious microbes that can be seen in ordinary life.
In order to achieve the aforementioned objects, the present invention provides a composition for the prevention and treatment of athlete's foot comprising a Moutan root bark extract as an active ingredient.
Also, the invention provides a composition for the prevention of osmidrosis comprising a Moutan root bark extract as an active ingredient.
Also, the invention provides an anti-acne composition comprising a Moutan root bark extract as an active ingredient.
Also, the invention provides an antimicrobial composition comprising a Moutan root bark extract, and one or more compounds selected from the group consisting of Ketoconazole, Itraconazole, Fluconazole, Miconazole, Clotrimazole, Fenticonazole, Econazole, Bifonazole, Oxiconazole, Cloconazole, Rolcyclate, Amphotericin B, Flucytosine, Griceofulvin, Terbinafine, Nystatin, Tolnaftate, Naftifine, Haloprogin, Ciclopirox, and Triclosan.
Also, the invention provides a bactericidal disinfectant composition comprising a Moutan root bark extract, and one or more compounds selected from the group consisting of norfloxacin, ciprofloxacin, ciprofloxacin salt, itraconazole nitrate, mitoconazole nitrate, and ketoconazole.
Also, the invention provides a composition for oral cleansing comprising a Moutan root bark extract, and one or more compounds selected from the group consisting of xylitol, propolis, triclosan, chlorohexidine gluconate (XII), cetyl pyridinium chloride (XIII), isopropylmethylphenol, hitokitiol, glytylitylic acid, and allantoin.
Also, the invention provide a kitchen detergent composition comprising a Moutan root bark extract, and one or more compounds selected from the group consisting of Ketoconazole, Itraconazole, Fluconazole, Miconazole, Clotrimazole, Fenticonazole, Econazole, Bifonazole, Oxiconazole, Cloconazole, Rolcyclate, Amphotericin B, Flucytosine, Griceofulvin, Terbinafine, Nystatin, Tolnaftate, Naftifine, Haloprogin, Ciclopirox, and Triclosan.
The inventors found that the Moutan root bark extract effectively functions against athlete's foot, osmidrosis, halitosis, tooth decay, and acne, and thereby completed the subject invention.
The Moutan root bark extract of the invention is prepared by extracting Moutan root bark according to conventional extraction methods.
Moutan root bark, the root bark of Paeonia Suffruticosa Andrews, is a substance that has been used medicinally in oriental medicine, and it is harmless to a human body.
Moutan root bark extract, for example, can be prepared by dipping dried plant roots into an extraction solution to prepare an extract, and concentrating it under a reduced pressure, or it can be obtained by separating layers with an extraction solution. The extraction solution may be one or more compounds selected from the group consisting of water, ethyl acetate, butyl acetate, ethyl alcohol, isopropyl alcohol, butyl alcohol, hexane, chloroform, ethyleneglycol, propyleneglycol, propanol, acetone, benzene, ethanol, methanol, and butanol.
The present invention provides a composition for the prevention and treatment of athlete's foot comprising a Moutan root bark extract as an active ingredient.
The composition for the prevention and treatment of athlete's foot of the invention may comprise the Moutan root bark extract alone, or it may comprise 0.001 to 40% by weight of Moutan root bark extract and the remaining amount as pharmacologically acceptable substances.
Further, the composition for the prevention and treatment of athlete's foot of the invention may further comprise one or more compounds selected from the group consisting of Ketoconazole, Itraconazole, Fluconazole, Miconazole, Clotrimazole, Fenticonazole, Econazole, Bifonazole, Oxiconazole, Cloconazole, Rolcyclate, Amphotericin B, Flucytosine, Griceofulvin, Terbinafine, Nystatin, Tolnaftate, Naftifine, Haloprogin, Triclosan, and Ciclopirox, and the content of these compounds may be 0.001 to 30% by weight with regard to the total composition. If the content of such compounds is less than 0.001% by weight, the antibacterial effect may be insignificant, and if it exceeds 30% by weight, the compounds may be precipitated or the economic efficiency may be low in comparison with the effect obtained. The preferred content of the compounds is 0.05 to 10% by weight.
The composition for the prevention and treatment of athlete's foot of the invention can be manufactured in an oral or parenteral form, and its dosage form may be plasters, granules, lotions, liniments, lemonades, aromatic waters, powders, syrups, liquids and solutions, aerosols, sprays, extracts, elixirs, ointments, fluidextracts, emulsions, suspensions, decoctions, infusions, tablets, injections, capsules, creams, tinctures, pastes, or pills. Preferably, the composition for the prevention and treatment of athlete's foot is manufactured in the form of aerosols or sprays.
The composition for the prevention of athlete's foot of the present invention may be medicines, cleansing agents, or cosmetics. In the case of medicines, they may be directly applied to the affected parts, and the cleansing agents may be soaps. The cosmetics may be in the form of lotions or massage creams.
Also, the present invention provides a composition for the prevention of osmidrosis comprising a Moutan root bark extract as an active ingredient. The composition for the prevention of osmidrosis of the invention may comprise the Moutan root bark extract alone, or it may comprise 0.001 to 40% by weight of Moutan root bark extract and the remaining amount as pharmacologically acceptable substances. As said substances that may be further included, there are Triclosan and aluminium hydroxychloride.
The composition for the prevention of osmidrosis of the invention can be manufactured in a parenteral form, and its dosage form may be lotions, powders, syrups, liquids and solutions, sticks, gels, aerosols, sprays, ointments, emulsions, suspensions, or creams. The preferred dosage forms are aerosols or sprays.
Also, the present invention provides an anti-acne composition comprising a Moutan root bark extract as an active ingredient. The anti-acne composition of the invention may comprise the Moutan root bark extract alone, or it may comprise 0.001 to 40% by weight of Moutan root bark extract and the remaining amount as pharmacologically acceptable substances. As such substances, there are Triclosan or aluminium hydroxychloride.
The anti-acne composition of the invention can be manufactured in a parenteral form, and its dosage form may be lotions, powders, syrups, liquids and solutions, aerosols, sprays, ointments, emulsions, suspensions, or creams. The anti-acne composition of the invention can be applied to cosmetics, cleansing agents, or medicines, and the cosmetics or cleansing agents may be all kinds of forms applicable to human skin. For example, the cosmetics may be lotions, creams, emulsion solutions, gels, or packs, and the cleansing agents may be soaps.
The present invention also provides an anti-microbial composition comprising a Moutan root bark extract and anti-microbial compounds. The anti-microbial activity as referred to herein means a bactericidal activity against noxious microbes such as algae, bacteria, protozoa, mold, yeasts, or viruses, and as noxious microbes, there are germs causing athlete's foot, dermatomycosis-causing pathogens, skin flora, noxious bacteria, and superficial fungal infection-causing bacteria.
The anti-microbial compounds may be one or more compounds selected from the group consisting of Ketoconazole, Itraconazole, Fluconazole, Miconazole, Clotrimazole, Fenticonazole, Econazole, Bifonazole, Oxiconazole, Cloconazole, Rolcyclate, Amphotericin B, Flucytosine, Griceofulvin, Terbinafine, Nystatin, Tolnaftate, Naftifine, Haloprogin, and Ciclopirox. The preferred compound is Ketoconazole.
The anti-microbial composition of the invention may comprise the Moutan root bark extract and the anti-microbial compounds in a ratio of 1:5 to 5:1 by weight, and may further comprise other pharmacologically acceptable substances. In the case that the anti-microbial composition comprises substances other than the Moutan root bark extract and antimicrobial compounds, the Moutan root bark extract can be contained in the anti-microbial composition in an amount of 0.001 to 20% by weight and the anti-microbial compounds can be contained in the anti-microbial composition in an amount of 0.001 to 20% by weight. If the content of the Moutan root bark extract and the anti-microbial compounds is less than 0.001% by weight, anti-microbial activity may be insignificant, and if it exceeds 20% by weight, the economic efficiency may be low as their activity does not increase in proportion to the amount added. The preferred content of each of the Moutan root bark extract and the anti-microbial compounds is 1 to 10% by weight.
Further, the anti-microbial composition of the invention may further comprise conventional pharmacologically acceptable substances, in addition to the Moutan root bark extract and the anti-microbial compounds. As such substances, there are skin moisturizers, skin permeation enhancers, fragrances, fragrance encapsulation carriers, organic solvents, or fillers.
The skin moisturizers can be one or more compounds selected from the group consisting of ethylene glycol, propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol (PEG) 200 to 600, polypropylene glycol (PPG), glycol ester and ether, alkyl ester of PEG or PPG, carboxylic ester of PEG or PPG, sorbitol, trihydroxy stearine, and polyhydric alcohol derivatives. The content of the skin moisturizers in the anti-microbial composition is preferably 0.05 to 5% by weight. If the content of the skin moisturizers is less than 0.05% by weight, sufficient moisturizing effects are not obtained, and if it, exceeds 5% by weight, the properties of the anti-microbial composition may be changed. More preferably, the content of the skin moisturizers is 0.1 to 3% by weight.
The skin permeation enhancers are used to facilitate the penetration into skin keratin and permeation into corium of the anti-microbial substances, and examples thereof include polyethylene glycol monolaurate (PEGML), glycerol monolaurate, propylene glycol monolaurate, eucalyptol, lecithin, 1-substituted azacycloheptane-2-one, 1-n-dodecyl cycleazacyclohepta-2-one (Trademark: IZON), cetyl alcohol, stearyl alcohol, myrist alcohol, polyethylene sorbitan fatty acid ester (ex.: Tween 20, 40, 60, 80, etc.), sorbitan fatty acid ester (ex: SPAN 60, 80, etc.), dodecyl amine or lanolin.
The skin permeation enhancers can be used alone or in a mixture of two or more kinds, and they are preferably selected from the group consisting of a Tween compound, which is a polyethylene sorbitan fatty acid ester; a SPAN compound, which is a sorbitan fatty acid ester; lanolin; and a mixture thereof. More preferably, lanolin is used. The content of the skin permeation enhancers in the anti-microbial composition is preferably 0.1 to 10% by weight. If the content of the skin permeation enhancers is less than 0.1% by weight, skin permeating effects may not be effectively attained, and if it exceeds 10% by weight, economic efficiency is low in comparison with the effects to be obtained. More preferably, the amount of the skin permeation enhancers is 0.5 to 5% by weight.
The fragrances are used for masking purposes to eliminate odor, and all kinds of fragrance that are added to conventional cosmetics or medicines and are applicable to humans or animals can be used. Examples of the fragrances include lavender, lemon, floral, herb, apple, strawberry, lily, frisia, lilac, rose, acacia, Chinese quince, musk, pheromones, and pine flavor, and they can be used alone or in a mixture of two or more kinds. It is preferred that the content of the fragrances in the anti-microbial composition is 0.05 to 2% by weight. If the content of the fragrances is less than 0.05% by weight, the masking effects may be insignificant, and if it exceeds 2% by weight, the strong odor may cause reverse effects. More preferably, the content of the fragrances is 0.5 to 1.5% by weight.
Fragrance encapsulation carriers are used to maintain odor-masking functions. The carriers can be conventional substances, and they are preferably dextrines or cyclodextrines. The content of the carriers in the anti-microbial composition is preferably 0.1 to 10% by weight, and more preferably 1.0 to 5% by weight. If the content of the carriers is less than 0.1% by weight, the encapsulating effects of the fragrances may be insignificant, and if it exceeds 10% by weight, this may be uneconomical.
The solvents are used to effectively dissolve or disperse each substance contained in the anti-microbial composition, and any solvents that are harmless to animals can be used. Preferred solvents include ethanol, isopropanol, or mixture thereof, and they can be contained in the spray composition in the remaining amounts.
As the fillers, any filler that are used in spray products can be used. As the typical fillers, liquefied petroleum gas (LPG) can be mentioned. Also, the fillers can be contained in a sufficient amount so that the anti-microbial composition can be applied in the form of sprays. The preferred content is 0.01 to 50% by weight.
The anti-microbial composition of the invention preferably has a pH of 3.0 to 9.0, and more preferably a pH of 4.0 to 7.5. If the pH is less than 3.0 or higher than 9.0, side effects with respect to the stability of the dosage form or application may occur.
The anti-microbial composition of the invention can be manufactured in the form of liquids, gels, solids, aerosols, or sprays, and according to the dosage form, conventional substances known to a skilled person in the pertinent art can be added.
In the case that the anti-microbial composition of the invention is manufactured in the form of sprays, the composition can be manufactured in the form of powder sprays or liquid sprays, and preferably liquid sprays are used. The spray composition can be used by spraying it onto either the skin of animals including humans, things that contact the skin, or the living environment of the animals, that is, it can be used by spraying it directly onto feet or on foul smelling shoes or socks. The anti-microbial spray composition can be filled into conventional spray containers such as plastic, aluminum, or tin containers with spray apparatuses.
The spray composition of the invention can be evenly applied to the affected parts in a constant amount, and it does not adhere to clothing, and thus its usability is superior and its hygienic and antibacterial and antifungal effects are excellent. In particular, the antimicrobial spray composition is effective on foot-and-mouth disease, skin itching, Tinea, dandruff, or athlete's foot.
The antimicrobial composition of the invention may be a detergent composition, a composition for controlling dandruff-causing pathogens, and odor, a bactericidal disinfectant composition, a composition for the sterilization and disinfection of animals and animal breeding farms, or an anti-foot-and-mouth disease composition.
The present invention also provides a composition for oral cleansing comprising a Moutan root bark extract and one or more compounds selected from the group consisting of xylitol, propolis, triclosan, chlorohexidine gluconate (XII), cetyl pyridinium chloride (XIII), isopropylmethylphenol, hitokitiol, glytylitylic acid, and allantoin.
The composition for oral cleansing of the invention may comprise the Moutan root bark extract and the above-mentioned compounds in a ratio of 1:5 to 5:1 by weight, and it my further comprise other pharmacologically acceptable substances. In the case that the composition for oral cleansing further comprises substances other than the Moutan root bark extract and antimicrobial compounds, the Moutan root bark extract can be contained in the composition for oral cleansing in an amount of 0.001 to 20% by weight and the antimicrobial compounds can be contained in the composition for oral cleansing in an amount of 0.001 to 20% by weight. If the respective contents of the Moutan root bark extract and the antimicrobial compounds are less than 0.001% by weight, the antimicrobial activity may be insignificant, and if they exceed 20% by weight, economic efficiency may be low as their activity does not increase in proportion to the amounts added. The preferred content of each of the Moutan root bark and the antimicrobial compounds is 0.1 to 10% by weight.
The composition for oral cleansing of the invention may further comprise substances that are used in conventional toothpaste compositions, gargling compositions, or compositions for the inhibition of halitosis and the prevention and treatment of decayed teeth, or otherwise the composition for oral cleansing can be used as an additive and be contained in toothpastes, mouthwashes, or agents for the inhibition of halitosis and the prevention of decayed teeth.
The composition for oral cleansing of the invention may be the dosage forms of plasters, granules, powders, syrups, liquids and solutions, aerosols, sprays, ointments, fluidextracts, emulsions, suspensions, tablets, capsules, creams, or pills.
Also, the present invention provides a kitchen detergent composition comprising a Moutan root bark extract and one or more compounds selected from the group consisting of Ketoconazole, Itraconazole, Fluconazole, Miconazole, Clotrimazole, Fenticonazole, Econazole, Bifonazole, Oxiconazole, Cloconazole, Rolcyclate, Amphotericin B, Flucytosine, Griceofulvin, Terbinafine, Nystatin, Tolnaftate, Naftifine, Haloprogin, Ciclopirox, Triclosan, norfloxacin, cifloxacin, and salts thereof.
The kitchen detergent of the invention may comprise the Moutan root bark extract and the above-mentioned compounds in a ratio of 1:5 to 5:1 by weight, and it may further comprise other pharmacologically acceptable substances. In the case that the kitchen detergent composition further comprises substances other than the Moutan root bark extract and antimicrobial compounds, the Moutan root bark extract can be contained in the kitchen detergent composition in an amount of 0.001 to 20% by weight and the antimicrobial compounds can be contained in kitchen detergent composition in an amount of 0.001 to 20% by weight. If the respective contents of the Moutan root bark extract and the antimicrobial compounds are less than 0.001% by weight, the antimicrobial activity may be insignificant, and if they exceed 20% by weight, economic efficiency may be low as their activity does not increase in proportion to the amounts added. The preferred content of each of the Moutan root bark and the antimicrobial compounds is 0.1 to 10% by weight.
The kitchen detergent composition of the present invention can comprise conventional compositions for the detergent of dishes and cooking utensils.
The dosage form of the kitchen detergent composition of the invention may be liquids and solutions, aerosols, or sprays.
Hereafter, examples of the present invention will be described. The following examples are provided solely to illustrate the subject invention: the subject invention should not be construed to be limited thereto.
Moutan root bark, the root bark of Paeoniaceae (Paeonia suffruticosa Andrews), which is sold for medical purpose, was purchased. The Moutan root bark was completely dried and crushed, and then passed through 1.18-mm mesh. 10 kg of each solvent of Table 1 below were individually added to 1 kg of the crushed Moutan root bark, which was then placed at a room temperature for 8 hours. Thereafter, it was extracted at 45° C. for 12 hours, and then filtered with a Wattman #6 filter to yield a filtrate. The filtrate was concentrated in a distillation apparatus with a cooling condenser under a reduced pressure at 60° C. to yield extracts.
The yield of Moutan root bark extracts according to each solvent is exhibited in Table 1 below.
1. Patch Test
The skin stimulation of the Moutan root bark extracts was investigated by patch tests.
Each plant extract was applied to a chamber (stiff aluminum) with a diameter of 8 mm and a depth of 0.5 mm, and five chambers were adhered to each of 2 rectangular tape lines. The tapes were adhered to 100 adults for two days, then the patches were removed and skin stimulation was evaluated according to ICDRG standards. As a result, there was no skin stimulation as shown in Table 2 below.
ICDRG Standards
?: doubtful reaction, +: weak positive, ++: strong positive, +++: ultra positive, −: negative, IR: stimulated
2. Verification of Antimicrobial Activity
As bacteria, E. coli 0-157:H7 (KCTC1682), Staphylococcus aureus (KCTC1621), Salmonella typhimutium (KCTC1925), and Listeria monocytogenes (ATCC 19111) were used; and as fungi, Candida albicans (KCTC7729), T. mentagrophytes (KCTC6085), T. rubrum (KCTC6352), A. niger (KCTC6985) P. citrinum (KCTC6990), and A. flavans (KCTC 6081) were used.
Antifungal activities were tested according to ASTM G21, which is the standard of the American Society for Testing and Material, and antibacterial activities were tested by the shake flask method. To determine the antibacterial activity, each strain was cultured while shaking at 25° C. for 24 hours (shaking rate: 150 times/min.), and then the number of strains was measured by harvesting a portion of the culture solutions from the experimental groups that were cultured by addition of 20 μl of Moutan root bark extract and the control groups that were cultured with no addition. Antibacterial activity was converted according to the following equation 1, and the results are exhibited in Table 3 below.
Antibacterial Activity=((Number of Strains in Control Group−Number of Strains in Experimental Group)/Number of Strain in Control Group)×100 (Equation 1)
Antifungal activity was tested according to ASTM G21, which is the standard of the American Society for Testing and Material. The grade of antifungal activity was determined by the following criteria, and the results are exhibited in Table 3 below.
Criteria
grade 0: No strain was grown on specimen
grade 1: Strain within 10% was grown on specimen
grade 2: Strains of about 10%˜30% were grown on specimen
grade 3: Strains of about 30%˜60% were grown on specimen
grade 4: Strains more than 60% were grown on specimen
From Table 3 above, it can be seen that the Moutan root bark extracts of the present invention were excellent in antibacterial and antifungal activities.
The bactericidal disinfectant compositions containing the Moutan root bark of Examples 1 to 11 and natural herb substances to confer an odor masking function, with which purified water and ethanol were mixed, were prepared as shown in Table 4 below (units: wt. %).
The determination of bactericidal ability was conducted according to the strain reduction rate determination method (Shaking flask method), by observing bacteria reduction rate after 24 hours from the time E. coli (KCTC1682), Staphylococcus aureus (KCTC 1621), and Salmonella typhimurium (KCTC1925), which are readily found in daily life, were inoculated, and the results are as shown in Table 4 below.
From Table 4, it can be seen that the Moutan root bark extracts of the invention still maintained excellent antibacterial activities even when they were liquids and solutions comprising the fragrances.
With the compositional ratios of Table 5 below, antimicrobial agents were prepared and their antibacterial activities were verified.
From Table 5 above, it can be seen that the antimicrobial agents comprising the Moutan root bark ethyl acetate extract and antimicrobial compounds had excellent antibacterial and antifungal activities.
With the compositional ratios of Table 6 below (units: wt. %), the bactericidal disinfectant agents were prepared by mixing the Moutan root bark ethyl acetate extract, antimicrobial compounds, fragrances, and solvents. Thereafter, antibacterial, antifungal and anti-foot-and-mouth disease activities were tested.
Anti-foot-and-mouth disease activity was measured by the following method.
1. Antimicrobial agent and foot-and-mouth disease virus were contacted at 4° C. for 30 minutes.
2. BHK21 (cell for investigating the presence of virus) was inoculated thereto and then cultured at 37° C. for 1 hour.
3. The culture was inoculated on agar media and then incubated at 37° C. for 48 hours.
4. After dyeing it with methylene blue, whether or not plaque was formed was observed under the presence of natural light.
From Table 6, it can be seen that the bactericidal disinfectant agents of Examples 22 to 25 were excellent in antibacterial and antifungal activities, and they were also efficient as foot-and-mouth disease inhibitors.
With the compositional ratios of Table 7 below, the compositions of Examples 26 to 28 were prepared. Thereafter, their antifungal activities were determined.
From Table 7 above, it can be seen that the compositions of Examples 26 to 28 had excellent antifungal activities. Therefore, the above compositions can be used for the treatment and prevention of skin itching, Tinea, dandruff, or athlete's foot.
The compositions of Examples 26 to 28 were charged into hand-operated sprayers. These antimicrobial agents were sprayed onto the affected parts of 20 adults whose feet were infected three times a day for 3 seconds each time, and then the treatment effects of athlete's-foot-causing pathogens and Trichophyton were investigated over the time. As the result of treatment, in the case of persons suffering from severe athlete's foot, the following symptoms were observed over the usage time.
In the case of persons whose athlete's feet were not severe, treatment 6 times over 3 days induced sufficient formation of keratin and thus the complete recovery of athlete's-foot-causing pathogens and Candida species, which are itch-inducing pathogens, was possible. A skin stimulation test was not separately conducted, but special lesions or side effects on the skin of the patients were not observed.
Therefore, the antimicrobial agents of Examples 26 to 28 were very effective in the prevention and treatment of athlete's foot, by causing keratinization of the tissues containing athlete's foot and thereby inducing the change in growth conditions of Trichophyton.
The antimicrobial agents of Examples 26 to 28 were treated to strains residing in skin and inducing acne and various skin diseases, and the antibacterial activities were determined. The results are as shown in Table 8 below.
From Table 8 above, it is revealed that the antimicrobial agents of Examples 26 to 28 of the present invention had excellent antibacterial activities against skin flora, and thus they can be used in cosmetics or cleansing detergents for the prevention and treatment of skin diseases.
The antimicrobial agents of Examples 26 to 28 were applied to acne-infected skin, and clinical experiments were conducted.
22 eruptive acne patients and 14 inflamed acne patients were constituted in a male to female ratio of 11:25, and they used the agents 2 to 3 times a day for 15 days. Acne treatment effects were evaluated by being observed by the naked eye. The results are exhibited in Table 9 below. As a control, EJ oriental medicine soap composition was used.
From Table 9 above, it can be seen that the antimicrobial agents of Examples 26 to 28 of the present invention had excellent treatment effects with regard to acne, with no skin stimulation, but the control, which was used as conventional treatment agent of acne, in some cases, even deteriorated acne.
250 ml of each of cyclodextrine and water were charged into a mixing container and sufficiently stirred at 750 rpm, then 75 g of natural flavor or synthetic flavor oil were slowly added thereto and stirred, and thereafter, moisture was completely eliminated therefrom and the resultant was micro-powdered to prepare the fragrance encapsulator. Also, the Moutan root bark extract used herein was a mixed extract of ethyl acetate and water, and spray compositions of Examples 29 to 65 were prepared with the compositional ratios of Table 10a and 10b below (units: wt. %).
Encapsulator: Artificially Synthetic/Natural Fragrance of Bolak (Co., Ltd.) + Cyclodextrine, IPA: isopropyl alcohol, PEG: polyethylene glycol 400, EG: ethylene glycol, PG: propylene glycol
The determination of skin permeation enhancement effects of Ketoconazole, Fluconazole, Terbinafine, and Moutan root bark was conducted using a percutaneous absorption apparatus (Franz-type diffusion cell, Hason Co., Ltd.) with regard to the skin of Guinea pigs.
With the compositional ratios of Table 11 below, compositions 1 to 8 were prepared as experimental groups, and compositions 9 and 10 were used as control groups.
1 cm2 of the abdominal skin of Guinea pigs was gathered, placed in permeation cells whose diameter was 0.9 cm, and then fixed with a clamp. 0.5 ml of each of the experimental groups and control groups was applied to one side of the skin and placed at 32° C. for 24 hours. Thereafter, the permeated samples were collected from the applied skin and analyzed with HPLC to determine the degree of absorption into the skin. The results are exhibited in Table 12 below.
From Table 12 above, it can be seen that the experimental groups using the skin permeation enhancers had significantly better skin permeation rate as compared with the control groups that did not use the skin permeation enhancers.
Antibacterial and antifungal activities were determined with regard to the compositions of Examples 29 to 65.
The antibacterial test was conducted according to ASTM G22, which is the standard of the American Society for Testing and Materials, and the antifungal test was conducted according to ASTM G21.
The antibacterial and antifungal activities were observed and classified into the following grades, and the results are exhibited in Table 13 below.
(Grade)
Criteria
grade 0: No strain was grown on specimen
grade 1: Strain within 10% was grown on specimen
grade 2: Strains of about 10%˜30% were grown on specimen
grade 3: Strains of about 30%˜60% were grown on specimen
grade 4: Strains more than 60% were grown on specimen
From Table 13 above, it is reveled that the antimicrobial spray compositions of the present invention had excellent antifungal and antibacterial activities against Trichophyton mentgrophytes and Trichophyton rubrum, which are athlete's-foot-causing bacteria; Candida albicans and Epidermophyton floccosum, which are skin eczema and itching-causing bacteria; A. niger, and P. citrinum. Also, the compositions of Examples 42 to 43 and 59 to 65, which used the antimicrobial substances in a mixture form, exhibited the same results.
In order to verify the antibacterial activities of Moutan root bark extracts when they were used alone or in a mixture form, the antibacterial activities were tested with regard to the compositions of Examples 55 and 65.
The antibacterial activity was converted according to the following Equation 1, and the results are exhibited in Table 14 below.
Antibacterial Activity=((Number of Strains in Control Group−Number of Strains in Experimental Group)/Number of Strains in Control Group)×100 (Equation 1)
From Table 14 above, it can be seen that the spray composition comprising the Moutan root bark extract had bactericidal effects against skin flora. Also, Example 59, in which the Moutan root bark extract and Ketoconazole were mixed, also exhibited antibacterial activities against skin flora. Therefore, it is expected that the Moutan root bark extract can substantially prevent foul odor from a human body by exhibiting antibacterial effects against skin flora.
The skin stimulation degree of the antimicrobial spray compositions of the present invention was tested according to the same method as in Experiment 1.
The test was applied to 10 subjects of 19 to 34 year-old males and females of 22 years on average, and Psoriasis, Eczema, other skin lesion holders, pregnant women, nursing women, or persons who take contraceptive agents, antihistamines, etc. were excluded from this experiment. The results are exhibited in Table 15 below.
From Table 15 above, it can be seen that the antimicrobial spray compositions of the invention were harmless, inducing no stimulation to skin.
The spray compositions of Examples 66 to 82 were prepared with the compositional ratios of Table 16 (units: wt. %).
According to ASTM G21 (the standard of American Society for Testing and Materials), the spray compositions of Examples 66 to 82 were tested.
As a result, the spray compositions of Examples 66 to 82 exhibited bactericidal activities against fungi. A portion of the results is exhibited in Table 17 below.
From Table 17 above, it is revealed that the compositions comprising 0.1 to 1.0% by weight of Ketoconazole exhibited excellent antifungal effects against athlete's-foot-causing pathogens (Trichophyton mentgrophytes, rubrum), and skin eczema-causing pathogens (Candida albicans, Epidermophyton floccosum), and Example 76 in which Itraconazole was mixed exhibited particularly excellent antifungal effects.
With the compositional ratios of Table 18 below (units: wt. %), the compositions for the prevention of osmidrosis of Examples 83 to 85 were prepared.
1. Verification of Antibacterial Activity against osmidrosis-inducing pathogens
According to strain reduction rate determination (Shaking Flask Method), the compositions for the prevention of osmidrosis of Examples 83 to 85 were tested against Staphylococcus aureus, (KCTC1621), Stenotrophomonas maltophilia, (KCTC 2437), and Candida albicans, (KCTC 7729), which are typical Osmidrosis-inducing pathogens, and the results are exhibited in Table 19.
From Table 19, it can be seen that the compositions of Examples 83 to 85 had superior bactericidal effects against osmidrosis —inducing pathogens.
2. Comparison of Deodorization Effect against Osmidrosis and Foul Odor.
The test was conducted with regard to 30 females and 30 males of 20˜45 years who perceived unpleasant osmidrosis from themselves and believed that the osmidrosis become a source of annoyance to other people. The compositions of Examples 83 to 85 were sprayed onto them three times (morning, afternoon, evening) a day for 4 weeks, the deodorizing effects against osmidrosis were evaluated by panels according to the criteria as shown in Table 20 below, and their averages are exhibited in Table 21.
Furthermore, to evaluate skin stimulation, skin stimulation was tested according to the same method as in Experiment 1, and the results are exhibited in Table 22.
From Tables 21 and 22, it can be seen that when the compositions for the prevention of osmidrosis of the present invention were used in the form of powder spray aerosols, they exhibited excellent deodorizing effects against unpleasant osmidrosis and foul odor, and induced no skin stimulation.
With the compositional ratios of Table 23 below (units: wt. %), the compositions for oral cleansing were prepared.
1. Antibacterial Test against Oral Microorganism
According to the strain reduction rate method (Shaking Flask Method), antibacterial test was conducted. As strains, Streptococcus mutans (KCTC 3065) and Streptococcus mitis (KCTC 3556) were used, and the results are exhibited in Table 24 below.
2. Verification of Durability of Antibacterial Effect
The compositions of Examples 86 to 88 were added to Streptococcus mutans, and strain reduction rate was measured over time. The results are exhibited in Table 25 below.
3. Verification of Pain Relief Effect
After the compositions of Examples 86 to 88 were applied, the number of subjects who did not feel pain any more was counted, and the results are exhibited in Table 26 below.
4. Verification of Halitosis Inhibition Effect
It was tested whether the elimination efficacy of halitosis actually occurs when the compositions for oral cleansing of Examples 86 to 88 are applied to humans.
The halitosis-detecting component contained in garlic was defined to methyl mercaptan, and its elimination rate was measured in terms of deodorization rate. For the test, a halitosis-detector was used (Dr. Etiquette DE-160 (Winners Japan Co., Ltd.), which is a device to measure the amount of methyl mercaptan, and five people was tested.
The subjects were forced not to ingest anything within 2 hours of the test, and they chewed 0.5 g of garlic for 2 minutes and then sprayed their mouths with the compositions of Examples 86 to 88 for 1 minute. Thereafter, the concentration of methyl mercaptan within each mouth was measured six times at ten minute intervals. Also, as a control, subjects chewed 0.5 g of garlic for 2 minutes, and then the concentration of methyl mercaptan within their mouth was measured six times at ten minute intervals.
The deodorization rate was calculated according to the following Equation 2.
Deodorization Rate (%)=((S−H)/S)×100 (Equation 2)
The deodorization rate results, as shown in Table 27, show that the compositions for oral cleansing of the present invention had durable inhibition effects against halitosis.
As revealed in the above, the compositions for oral cleansing of Examples 86 to 88 had excellent durable deodorization effects against halitosis, and Example 88, in which the Moutan root bark extract and the compounds were used together, showed particularly excellent results.
With the compositional ratios of Table 28 below (units: wt. %), the detergent compositions were prepared.
1. Evaluation of Bactericidal Ability of Dish Towel
To a solution prepared by mixing E. coli(KCTC 1682), S. aureus (KCTC 1621), and P. aeruginosa (KCTC 2004) and diluting them (2.0×106/ml) were added pieces of test cotton (white cotton pieces sterilized at 121° C. for 15 minutes) to thereby contaminate them, and they were then washed with the compositions of Examples 89 to 91 for 1 minute and mounted on media for bacterial culture and left at 37° C. Thereafter, the proliferation degree of bacteria was evaluated according to the following criteria, and the results are exhibited in Table 29 below.
Bacteria Proliferation Degree
2. Evaluation of Bactericidal Ability
With regard to Salomella typhimurium (KCTC1925) and Shigella flexneri (KCTC 2008), the same experiment as above was conducted. The bacteria culture was carried out at 40° C. for 24 hours.
3. Evaluation of Deodorization Ability
The compositions of Examples 89 to 91 were charged into the sealed containers and equal amounts of foul odor sources (3 kinds), were respectively added thereto, and after a predetermined time the remaining portion of foul odor that was not deodorized was absorbed to detector tubes to thereby determine the concentration of the remaining gas (Use of Gastec Detector Tubes).
Source of Foul Odor
Evaluation (Evaluated by the Detected Concentration in the Detector Tubes)
The following Table 29 exhibits bactericidal and deodorizing ability of the compositions of Examples 89 to 91.
With the compositional ratios of Table 30 below (units: wt. %), soap compositions were prepared.
1. Antibacterial Activity
The antibacterial activities of the compositions of Examples 92 to 94 were investigated through the formation of inhibition zones, and the results are exhibited in Table 31 below.
From Table 31 above, it can be seen that in cases comprising both the Moutan root bark extract and the compounds, they exhibited broad antibacterial effects throughout gram positive bacteria, gram negative bacteria, and fungi.
2. Deodorization Effect
The deodorization effects of the compositions of Examples 92 to 94 were measured, and the results are exhibited in Table 32.
As described above, the Moutan root bark extract of the present invention has excellent antimicrobial activity. Therefore, the Moutan root bark extract can be applied to medicines, food additives, cosmetics, bactericidal/disinfectant agents, and detergents to effectively prevent foot-and-mouth disease viruses, skin-itching, Tinea, dandruff, osmidrosis, halitosis, decayed teeth, or athlete's feet.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2002-4660 | Jan 2002 | KR | national |
| 2002-45033 | Jul 2002 | KR | national |
| 2003-4683 | Jan 2003 | KR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/KR03/00160 | 1/24/2003 | WO |
