WO2004028502A1 - Cleansing composition containing antifungal agent and antibacterial agent - Google Patents

Cleansing composition containing antifungal agent and antibacterial agent Download PDF

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Publication number
WO2004028502A1
WO2004028502A1 PCT/JP2003/012325 JP0312325W WO2004028502A1 WO 2004028502 A1 WO2004028502 A1 WO 2004028502A1 JP 0312325 W JP0312325 W JP 0312325W WO 2004028502 A1 WO2004028502 A1 WO 2004028502A1
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Prior art keywords
agent
antibacterial
bacteria
antifungal
stone
Prior art date
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PCT/JP2003/012325
Other languages
French (fr)
Japanese (ja)
Inventor
Shigenobu Kitsugi
Noriyuki Komatsu
Original Assignee
Mochida Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Mochida Pharmaceutical Co., Ltd. filed Critical Mochida Pharmaceutical Co., Ltd.
Priority to AU2003266643A priority Critical patent/AU2003266643A1/en
Priority to KR1020057003311A priority patent/KR101045867B1/en
Priority to JP2004539553A priority patent/JPWO2004028502A1/en
Publication of WO2004028502A1 publication Critical patent/WO2004028502A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/501,3-Diazoles; Hydrogenated 1,3-diazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/075Ethers or acetals
    • A61K31/085Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/4174Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/10Washing or bathing preparations

Definitions

  • the present invention relates to a cleaning composition for pharmaceuticals, quasi-drugs or cosmetics, which has a broad antibacterial and antifungal spectrum and is excellent in efficacy and safety.
  • the most common method of daily hand washing is with stones and running water, which is the physical removal of dirt, organic matter and transient microorganisms (bacteria, fungi, viruses, etc.) from the hands. .
  • the bactericidal effect of bacteria that have been artificially attached to hands depends on the time of hand washing, and the amount of bacteria is 1/10 in 15 seconds of hand washing. It has been reported that 1Z100 in 30 seconds and 11000 in more than 1 minute. In other words, by washing with ordinary stone stones and running water for 1 minute or more, the attached bacteria can be sufficiently removed.
  • antibacterial agent-containing stones for increasing the disinfection efficiency during washing are commercially available. Used by workers in food production and medical facilities, where bacterial infection is particularly important, to prevent food poisoning, disinfect and disinfect bacteria from the environment that adhere to soil or pets, etc. In addition, cleaning with antibacterial agent-containing stones in ordinary households is becoming commonplace.
  • an antibacterial agent-containing stone an antibacterial agent-containing stone containing triclosan, triclocarban and an antibacterial agent such as Z or isopropylmethylphenol is commercially available.
  • compositions containing an antifungal agent for preventing dandruff are known.
  • an anti-dandruff agent containing miconazole or its nitrate which has a strong antifungal effect against fungi and ora / e (Japanese Patent Application Laid-Open No. 8-3042).
  • the inhibitor used herein is, for example, shampoo for preventing dandruff caused by P. ovale, but the inhibitor does not contain the antibacterial agent as described above.
  • compositions containing one or more antibacterial and antifungal agents and phospholipids that inhibit the biosynthesis of fungi and mold ergosterol (Table 2) Report).
  • azole which is an antifungal agent is exemplified as an antibacterial and antifungal agent, and a compound known as an antibacterial agent is not exemplified.
  • the bacteria in this document substantially means fungi and do not include antibacterial agents.
  • Some actives along with certain surfactants, disclose foaming cleansing creams for greasy or acne-prone skin that include antiseborrheic actives and Z or antimicrobial agents.
  • Japanese Patent Application Laid-Open No. 2002-14045 736 discloses foaming cleansing creams for greasy or acne-prone skin that include antiseborrheic actives and Z or antimicrobial agents.
  • Japanese Patent Application Laid-Open No. 2002-14045 736 disclose foaming cleansing creams for greasy or acne-prone skin that include antiseborrheic actives and Z or antimicrobial agents.
  • a fungicide composition having a skin-protecting effect containing a complex of a fungicide and a water-swellable viscosity mineral has also been proposed (Japanese Patent Application Laid-Open No. 10-265408).
  • fungicides Antibacterial agents such as triclosan and isopropylmethylphenol, azolic antifungal agents and the like are described.
  • the document states that when a fungicide is used in a complex with the above viscous mineral, the antibacterial activity is persistent, and that one or more fungicides are arbitrarily selected.
  • the examples exemplified for each application show the sustained effect when one kind of drug corresponding to each application is formed into a complex with the above-mentioned viscous mineral.
  • fungi attached to the hands can enter the body orally, causing fungal infections in various organs.
  • Fungi are also considered as one of the causes (allergens) of allergic diseases, and C. albicans is regarded as important in relation to atopic dermatitis as an allergic skin disease. .
  • the present inventors have recognized the need for a cleaning composition having a broad antibacterial and antifungal spectrum.
  • the inventor of the present invention in the process of variously examining a cleaning composition containing an antifungal agent and an antibacterial agent, found that among the antifungal agents, this was used as a normal antibacterial stone. It was found that there is a problem that even if it is blended as it is, its solubility, effect, stability, and the like vary greatly, and it is difficult to obtain a stable cleaning composition.
  • antifungals, antibacterials, and cleaning ingredients have a skin irritating effect, and their effects (antifungal, antibacterial, cleaning, It is also necessary to balance the balance between antibacterial agents and residual effects of antifungal agents) and safety (less skin irritation). Disclosure of the invention
  • the present invention solves these problems and provides a cleaning composition containing an antifungal agent and an antibacterial agent, particularly a cleaning composition that can be used for pharmaceuticals, quasi-drugs, or cosmetics. It has a wide spectrum of antibacterial and antifungal properties, is stable and has excellent usability, has excellent detergency, has little skin irritation, and has the effect of preventing itching and deodorizing of the scalp and body.
  • An object of the present invention is to provide a cleaning composition capable of preventing infectious diseases caused by shampoo.
  • the present inventors have conducted intensive studies on a cleaning composition containing an antifungal agent and an antibacterial agent, and found that a cleaning composition containing an azole-based antifungal agent and an antibacterial agent has a strong and broad It has an antibacterial and antifungal spectrum, the product itself is stable, it has excellent usability, it has excellent detergency, it does not cause skin irritation or other adverse events, and it can prevent itching and deodorant effects on the scalp and body.
  • the present inventors have found that at least one of the above-mentioned problems can be solved, such as an effect of preventing infectious diseases caused by indigenous bacteria and passing bacteria, and thus completed the present invention.
  • a cleaning composition for a pharmaceutical, a quasi-drug, or a cosmetic which contains an azole antifungal agent and an antibacterial agent.
  • the antifungal agent is preferably miconazole and / or a salt thereof.
  • the antibacterial agent is preferably at least one selected from triclosan, triclocarban and isopropylmethylphenol.
  • a cleaning composition in which the antifungal agent is miconazole nitrate and the antibacterial agent is Tricsan is a preferred embodiment of the present invention.
  • the content of the antifungal agent is 0.1 to 2.0 wt%, and the content of the antibacterial agent is 0.01 to 1.5 wt%. It is.
  • the cleaning composition of the present invention may contain a mild surfactant as a cleaning component.
  • the washing and cleaning composition of the present invention is provided, for example, in the form of stone.
  • FIG. 1 is a graph showing the results of a bacterial test in Example 5, showing the cleaning effect of the stone of the present invention in comparison with a control stone.
  • FIG. 2 is a graph showing the results of a fungal test in Example 5, showing the cleaning effect of the stone of the present invention in comparison with a control stone.
  • the present invention is an antifungal 'antibacterial cleaning composition for pharmaceuticals, quasi-drugs or cosmetics, having a broad antifungal and antibacterial spectrum.
  • the cleaning composition of the present invention contains an antifungal agent and an antibacterial agent as essential components, and is characterized by containing an azole antifungal agent as the antifungal agent.
  • Examples of the azolic antifungal agent in the present invention include miconazole, clotrimazole, econazole, choconazole, oxiconazole, fluconazole, itraconazole, ketoconazole, croconazole, neticonconazole, and isoconazole.
  • Examples of the salt include nitrate and hydrochloride, and preferably nitrate. In the present invention, two or more of these may be included in the cleaning composition.
  • miconazole clotrimazole, econazole, choconazole, oxyconazole, sulconazole, bifonazole and their salts are preferred, and miconazole nitrate is more preferred. It is.
  • the above-mentioned miconazole and miconazole nitrate mean a compound having a structure represented by the following (I) and ( ⁇ ).
  • the above azole antifungal agent is available as a commercial product.
  • the antibacterial agent used in the present invention is not particularly limited as long as it has a growth inhibitory effect on bacteria, but a diphenyl ether compound, a carbanilide compound or a phenol compound is preferable, and specifically, triclosan, triclocarban And isopropylmethylphenol. Among them, Trik mouth sun is preferred.
  • antibacterial agents are available as commercial products.
  • a particularly preferred embodiment of the present invention is the combination, wherein the antifungal agent is miconazole nitrate and the antibacterial agent is Tricsan.
  • the amount of the antifungal agent and the antibacterial agent in the composition is not particularly limited, but is usually
  • the compounding amount of the antifungal agent is 0.1 to 2.0%, and the compounding amount of the antibacterial agent is 0.0 :! ⁇ 1.5 wt%.
  • the amount is preferably 0.1 to 1.0 wt%, and when the antibacterial agent is triclosan, the amount is 0.05 to 0.5 wt%. 1.0% is preferred.
  • the cleaning component to be added to the cleaning composition is not particularly limited as long as the cleaning component does not impair the efficacy of the antifungal agent and the antibacterial agent, and may include an anionic surfactant.
  • anionic surfactants such as alkyl sulfate sodium salt, amphoteric surfactants such as alkyl dimethyl ammonium betaine, and nonionic surfactants such as polyoxyethylene alkyl ether Surfactants and the like can be used in appropriate combination.
  • These surfactants are preferably low irritants, and examples of low irritant anionic surfactants include monoalkyl phosphates, acyl glutamates, acyl methyl taurates, cocoyl isethionates, Lauroyl-methyl
  • Examples of the low-irritating amphoteric surfactant include betaine-type amphoteric surfactants such as 2-alkyl-1-N-carboxymethyl_N-hydroxy. And ethyl imidazolidine betaine.
  • a combination of a mildly anionic surfactant and a mildly amphoteric surfactant is preferred.
  • the cleaning composition of the present invention further includes components used in ordinary cleaning compositions, for example, humectants such as propylene glycol and glycerin, conditioning components such as cationic polymers, coloring agents such as pigments and pigments, Viscosity modifiers such as methylcellulose and polyethylene glycol, pH regulators such as citric acid and potassium oxide, salts such as sodium chloride, plant extracts, preservatives, vitamins, fragrances, ultraviolet absorbers, antioxidants , Water and the like can be appropriately added.
  • humectants such as propylene glycol and glycerin
  • conditioning components such as cationic polymers
  • coloring agents such as pigments and pigments
  • Viscosity modifiers such as methylcellulose and polyethylene glycol
  • pH regulators such as citric acid and potassium oxide
  • salts such as sodium chloride
  • plant extracts such as preservatives
  • vitamins, fragrances, ultraviolet absorbers, antioxidants , Water and the like can be appropriately added.
  • cleaning composition refers to a composition in which a cleaning component is blended, and after use, is washed away with running water or the like.
  • the form is not particularly limited, stone (solid stone, liquid stone, foamed stone, body soap, hand soap, etc.), cleansing foam, shampoo (hair shampoo, dry shampoo, etc.) And the like. Of these, stones are preferred, and liquid stones and body soaps are particularly preferred. Examples of the cleaning composition of the present invention are shown below, but the present invention is not limited thereto.
  • test drug was dissolved in DMSO, and miconazole was adjusted to 102,400 Mg / mL (titer) and triclosan was adjusted to 409,600 ⁇ g / mL (titer).
  • the miconazole solution prepared at 102, 400 / mL (titer) was further prepared in a two-fold dilution series using DMS0 to prepare 102, 400 to 50 wgZmL (titer).
  • Triclosan drug solution adjusted to 409, 600 M g / mL (titer) was further prepared in a 2-fold dilution series using DMSO, and adjusted to 409, 600 to 6.00 g / mL (titer). .
  • the inoculum was inoculated into each well at 5 / L, and the amount of bacteria in the drug-free medium used as a target was measured to determine the amount of inoculated bacteria.
  • the minimum drug concentration in the tube where growth of the bacteria was not visually observed was defined as MIC.
  • C. albicans was cultured on Sabouraud dextrose agar medium (BBL) at 35 ° C. for 24 to 48 hours, and then adjusted to McFarland ⁇ .5 with sterile physiological saline. It was diluted 1000-fold with RPMI 1640 medium containing 0.165 mol / L MOPS to obtain a test bacterial solution (1 to 5 ⁇ 10 3 cells / mL).
  • T. rubrum was modified 2% on a modified 1Z10 Sabouraud glucose agar slant. Then, after culturing for 1 to 2 weeks, sterile physiological saline solution containing 0.1% Tween 80 was added, conidia were collected, and the conidia were filtered with sterile gauze. The conidia suspension was further diluted with sterile physiological saline containing 0.1% Tween 80, and the number of bacteria was adjusted to 10 6 cellsZmL using a hemocytometer to obtain a test bacterial solution.
  • the drug to be measured was dissolved in DMSO and adjusted to 12,800 Mg / mL (titer) for each of miconazole and triclosan.
  • the miconazole and triclosan drug solutions prepared at 12,800 / xg / mL (titer) were further prepared in 2-fold dilution series using DMSO to obtain 12,800-60 g / mL (titer). It was adjusted.
  • the minimum drug concentration in the tube where growth of the bacteria was not visually observed was defined as MIC.
  • evaluation MIC value (g / mL)
  • Example 2 The liquid stone prepared in Example 2 was a clear, slightly yellow liquid immediately after preparation, and no insolubles were observed. In addition, this liquid stone was stored in a plastic container for 6 months at a temperature of 40 ° C and a relative humidity of 75%. As a result, the residual ratio of miconazole nitrate and triclosan was 95% or more in each case. Quantified by the usual method used), and no precipitation, coloring, etc. were observed. (Example 4) Use of liquid stone (1)
  • the liquid stone prepared in Example 2 was hand-washed and used for the whole body according to a conventional method. Uncomfortable feeling during and after washing, tingling of skin, and bulkiness of skin are observed. It had excellent usability.
  • stamp-stamp medium commercially available SCDLP agar medium; containing soybean casein hydrolyzate, lecithin and polysorbate 80
  • Example 2 Liquid stone prepared in Example 2 diluted to 7% and placed in a foam ejection container (invention stone) and liquid stone prepared by removing miconazole nitrate from the composition of Example 2 (control stone) ), The subject's right and left palms were washed with one hand for a certain period of time.
  • Washing was carried out by each person in charge of the present invention stones and the control stones, washing the hands of all subjects randomly under the blinds, left and right randomly (2 pushes for 5 seconds). .
  • Washing was carried out by the person in charge of the stone of the present invention and the control stone by washing the feet of all subjects randomly under the blind, left and right with a fixed method (2 pushes for 5 seconds). .
  • Inoculated bacterial solution was inoculated into each well in an amount of 5 L, and the amount of bacteria in the drug-free medium used as a control was measured to determine the amount of inoculated bacteria.
  • the minimum drug concentration in the tube where growth of the bacteria was not visually observed was defined as MIC.
  • C. albicans was cultured on Sabouraud dextrose agar medium (88) at 35 ° (:, 48 hours), and then prepared with sterile physiological saline to McFarland No. 0.5. It was diluted 1000-fold with RPMI 1640 medium containing mol / L MOPS to obtain a test bacterial solution (1 to 5 ⁇ 10 3 cells ZmL).
  • T. rubrwn was cultured on a modified 1/10 sub-oral glucose agar slant medium for 271 weeks and then added with 0.1% Tween n80 in sterile physiological saline to collect conidia and filtered through sterile gauze. .
  • the conidia suspension was further diluted with RPMI 1640 medium containing 0.165 mol / L MOPS, and the number of bacteria was adjusted to 10 6 cells / mL using a hemocytometer to obtain a test bacterial solution.
  • the measurement medium prepared in (3) was dispensed in 100 L portions. As a control, 100 L of drug-free medium was dispensed. (5) Inoculate 100 L of the bacterial solution prepared in (1), C. albicans at 35 ° C for 48 hours, and T. rubrim at 21. And cultured for 1 week.
  • Triclosan 0.30 g Miconazole nitrate 0.75 g N-coconut oil fatty acid acyl-L-potassium monoglutamate 5.00 g
  • Triclocarban 0.50 g Miconazole nitrate 0.75 g
  • the cleaning composition of the present invention for a novel drug, quasi-drug, or cosmetic, which contains an antifungal agent and an antibacterial agent.
  • cleaning compositions containing an azole antifungal agent and an antibacterial agent as antifungal agents have a strong and broad antibacterial and antifungal spectrum, are stable in the product itself, and have excellent usability. Excellent detergency, no adverse effects such as skin irritation, prevention of scalp and body itch and deodorization effects, prevention of infectious diseases caused by resident bacteria and passing bacteria It has at least one excellent property.

Abstract

It is intended to provide a cleansing composition for drugs, quasi drugs or cosmetics which has broad antibacterial and antifungal spectra and is excellent in efficacy and safety. Namely, a cleansing composition for drugs, quasi drugs or cosmetics which contains an azole-type antifungal agent and an antibacterial agent. As the azole-type antifungal agent as described above, miconazole nitrate is particularly preferable.

Description

明細 抗真菌剤および抗細菌剤配合洗浄用組成物 技術分野  Description Cleaning composition containing antifungal agent and antibacterial agent
本発明は、 広い抗細菌、 抗真菌スペクトルを有し、 有効性および安全性に優れ た医薬品、 医薬部外品または化粧品用の洗浄用組成物に関する。 背景技術  The present invention relates to a cleaning composition for pharmaceuticals, quasi-drugs or cosmetics, which has a broad antibacterial and antifungal spectrum and is excellent in efficacy and safety. Background art
日常的な手洗いの最も一般的な方法は、 石鹼と流水によるもので、 これは手に 付着した汚れ、 有機物、 一過性微生物 (細菌、 真菌、 ウィルスなど) の物理的除 去法である。 このような手洗による除菌効果を調べるための実験では、 人為的に 手に付着させた菌の除菌効果は、 手洗いの時間に依存し、 菌量は手洗い時間 1 5 秒で 1 / 1 0、 3 0秒で 1 Z 1 0 0、 1分以上で 1 1 0 0 0になるとの報告が ある。 つまり通常の石験と流水とにより 1分以上洗浄すれば、 付着した菌を充分 に除去することができる。 しかしながら、 日常の手洗いにおいて、 1分以上の手 洗い時間を確保することはなかなか困難である。  The most common method of daily hand washing is with stones and running water, which is the physical removal of dirt, organic matter and transient microorganisms (bacteria, fungi, viruses, etc.) from the hands. . In experiments to examine the germicidal effect of hand washing, the bactericidal effect of bacteria that have been artificially attached to hands depends on the time of hand washing, and the amount of bacteria is 1/10 in 15 seconds of hand washing. It has been reported that 1Z100 in 30 seconds and 11000 in more than 1 minute. In other words, by washing with ordinary stone stones and running water for 1 minute or more, the attached bacteria can be sufficiently removed. However, in daily hand washing, it is very difficult to secure a hand washing time of 1 minute or more.
そこで、 洗浄時の除菌効率を高めるための抗細菌剤配合石鹼が市販されてい る。 食中毒の予防、 土壌あるいはペットなどから付着する環境由来の細菌の殺菌 消毒、 院内感染防止などのために、 特に菌感染が重要視される食品製造、 医療現 場などの従事者に使用されているだけでなく、 一般家庭での抗細菌剤配合石鹼で の洗浄は日常的になりつつある。 このような抗細菌剤配合石鹼として、 トリクロサン、 トリクロカルバンおよ び Zまたはィソプロピルメチルフエノールなどの抗細菌剤を含む抗細菌剤配合石 鹼が市販されている。 For this reason, antibacterial agent-containing stones for increasing the disinfection efficiency during washing are commercially available. Used by workers in food production and medical facilities, where bacterial infection is particularly important, to prevent food poisoning, disinfect and disinfect bacteria from the environment that adhere to soil or pets, etc. In addition, cleaning with antibacterial agent-containing stones in ordinary households is becoming commonplace. As such an antibacterial agent-containing stone, an antibacterial agent-containing stone containing triclosan, triclocarban and an antibacterial agent such as Z or isopropylmethylphenol is commercially available.
またふけ防止のために抗真菌剤を配合した組成物がいくつか知られている。 真菌尸, ora/eに対し、 強い抗真菌効果を示すミコナゾ一ルまたはその硝酸塩を 含ませたふけ防止剤の開示がある (特開平 8— 3 0 4 2号公報) 。 ここでの防止 剤は、 P. ovaleによるふけを防止するためのたとえばシャンプーなどであるが、 当該防止剤には、 上述したような抗細菌剤は配合されていない。  Some compositions containing an antifungal agent for preventing dandruff are known. There is a disclosure of an anti-dandruff agent containing miconazole or its nitrate, which has a strong antifungal effect against fungi and ora / e (Japanese Patent Application Laid-Open No. 8-3042). The inhibitor used herein is, for example, shampoo for preventing dandruff caused by P. ovale, but the inhibitor does not contain the antibacterial agent as described above.
菌 ·カビのエルゴステロールの生合成を阻害する 1種以上の抗菌 ·抗カビ剤と リン脂質を含む組成物を開示するものもある (特表 2 0 0 1— 5 1 9 8 2 2号公 報) 。 当該文献には、 抗菌 ·抗カビ剤として、 抗真菌剤であるァゾールが例示さ れ、 抗細菌剤として公知の化合物は例示されていない。 皮膚糸状菌 (dermatophy te fungi) に対して効果がある旨の記載からみても、 当該文献における菌は実質 的に真菌を意味しており、 抗細菌剤は含まれていない。  Some disclose compositions containing one or more antibacterial and antifungal agents and phospholipids that inhibit the biosynthesis of fungi and mold ergosterol (Table 2) Report). In the literature, azole which is an antifungal agent is exemplified as an antibacterial and antifungal agent, and a compound known as an antibacterial agent is not exemplified. Judging from the statement that it is effective against dermatophyte fungi, the bacteria in this document substantially means fungi and do not include antibacterial agents.
特定の界面活性剤とともに活性剤として、 抗脂漏性活性剤および Zまたは抗菌 剤を含ませた脂性またはざ瘡傾向の皮膚のための起泡性クレンジングクリームを 開示しているものがある (特開 2 0 0 2 - 1 4 5 7 3 6号公報) 。 当該文献に は、 上記坊菌剤の例示群のうちには、 抗生物質とともに抗真菌剤であるミコナ ゾールおよびその塩酸塩なども例示されている。 抗菌剤は 2種以上使用してもよ いと記載しているが、 抗菌剤を 2種以上含む必要性は格別に示されていない。 殺菌剤と、 水膨潤性粘度鉱物との複合体を含む皮膚保護効果の殺菌剤組成物も 提案されている (特開平 1 0— 2 6 5 4 0 8号公報) 。 当該文献中には、 殺菌剤 として、 トリクロサン、 イソプロピルメチルフエノールなどの抗細菌剤、 ァゾ一 ル系抗真菌剤などが記載されている。 また当該文献には、 殺菌剤を上記粘度鉱物 との複合体にして使用すると抗菌力の持続性があるとし、 殺菌剤は、 任意に 1種 または 2種以上が選択される旨記載されているが、 各用途別に例示された実施例 では、 各用途に応じた 1種の薬剤を上記粘度鉱物との複合体に形成したときの持 続性効果が示されている。 Some actives, along with certain surfactants, disclose foaming cleansing creams for greasy or acne-prone skin that include antiseborrheic actives and Z or antimicrobial agents. Japanese Patent Application Laid-Open No. 2002-14045 736). In the literature, among the exemplified groups of the above-mentioned bacilli, miconazole and its hydrochloride, which are antifungals, as well as antibiotics are also exemplified. It states that two or more antimicrobial agents may be used, but there is no particular indication that two or more antimicrobial agents should be used. A fungicide composition having a skin-protecting effect containing a complex of a fungicide and a water-swellable viscosity mineral has also been proposed (Japanese Patent Application Laid-Open No. 10-265408). In the literature, there are fungicides Antibacterial agents such as triclosan and isopropylmethylphenol, azolic antifungal agents and the like are described. In addition, the document states that when a fungicide is used in a complex with the above viscous mineral, the antibacterial activity is persistent, and that one or more fungicides are arbitrarily selected. However, the examples exemplified for each application show the sustained effect when one kind of drug corresponding to each application is formed into a complex with the above-mentioned viscous mineral.
上記各文献には、 抗細菌剤と抗真菌剤とを組み合わせて使用する必要性は示さ れていない。  The above documents do not indicate the necessity of using a combination of an antibacterial agent and an antifungal agent.
ヒトの皮膚には通常、 多数の常在菌ゃ通過菌が存在する。 たとえば、 S. aureus は、 皮膚感染症の最も頻度の高い原因細菌であり、 日常的にみられる疾患として は、 とびひ (水疱性膿痂疹) 等がある。 また、 T. nibrum や T. mentagrophytes は、 皮膚糸状菌症 (白癬) の原因真菌である。 足白癬 (水虫) は、 重篤な例を除 いて自覚症状が弱く、 他人に感染する伝染病であることの認識が十分ではないこ と、 自覚症状がなくなると治療をやめてしまう (コンプライアンスが悪い) こと などから、 風呂場のマットやスリッパ等から感染する機会が多い。 宿主によって は通過菌量が少なくても水虫を発症するとの報告がある。  Human skin usually contains a large number of indigenous and transmissible bacteria. For example, S. aureus is the most frequent causative bacterium for skin infections, and routinely seen diseases include rash (bullous impetigo). T. nibrum and T. mentagrophytes are fungi that cause dermatophytosis (ringworm). Tinea pedis (athlete's foot) has weak subjective symptoms, except in severe cases, and lacks sufficient awareness that it is an infectious disease that infects others, and stops treatment when the subjective symptoms disappear (poor compliance) Therefore, there are many chances of infection from bathroom mats and slippers. It has been reported that athlete's foot may develop depending on the host even with a small amount of bacteria.
また皮膚疾患のみならず、 手に付着した真菌が経口的に体内に侵入し、 各種臓 器において真菌感染症を発症することもある。  In addition to skin diseases, fungi attached to the hands can enter the body orally, causing fungal infections in various organs.
また真菌 (力ビ) は、 アレルギー性疾患の原因 (アレルゲン) の一つとされ、 ァレルギ一性皮膚疾患としてのァトピー性皮膚炎との関わりにおいて、 力ンジダ ( C. albicans) が重要視されている。  Fungi are also considered as one of the causes (allergens) of allergic diseases, and C. albicans is regarded as important in relation to atopic dermatitis as an allergic skin disease. .
昨今、 生活環境の変化、 抗生物質、 ステロイド剤などの薬剤の日常的な使用な どにより、 感染症に対する抵ぉ性は低下する傾向にあるといえ、 宿主の免疫機能 の低下により発症する日和見感染も問題視されている。 日和見感染の予防の観点 では、 皮膚の洗浄により感染予防するには、 細菌だけでなく真菌除去の必要性も 重要視され!!台めている。 In recent years, changes in living environment, daily use of drugs such as antibiotics and steroids However, opportunistic infections caused by a decrease in the immune function of the host are also viewed as a problem. From the standpoint of preventing opportunistic infections, the importance of removing bacteria as well as bacteria is important for preventing infection by washing the skin !!
しかしながら上記従来の抗細菌剤配合石鹼の抗真菌効果を調べたところ、 上記 T. rubrum などへの抗真菌効果はほとんどないか、 不十分であることが分かつ た。 これら抗細菌剤配合石験は、 食中毒の予防、 環境由来の細菌の殺菌消毒など を主たる目的とするため、 大腸菌、 サルモネラ菌、 ブドウ球菌などの細菌の殺 菌、 滅菌などの抗細菌効果を目的とし おり、 特に皮膚に付着する真菌への抗真 菌効果はそれほど重要視されていたとはいえないのが実状である。  However, when the antifungal effect of the conventional antibacterial agent-containing stones was examined, it was found that the antifungal effect on T. rubrum or the like was scarce or insufficient. These stone tests with antibacterial agents are mainly aimed at preventing food poisoning and disinfecting and disinfecting environmentally-derived bacteria. In fact, in particular, the antifungal effect on fungi attached to the skin has not been regarded as very important.
上記のような情況に鑑み、 本発明者は、 広い抗細菌、 抗真菌スペクトルを有す る洗浄用組成物の必要性を認識した。  In view of the circumstances described above, the present inventors have recognized the need for a cleaning composition having a broad antibacterial and antifungal spectrum.
本発明者は、 この認識に基づいて抗真菌剤および抗細菌剤を配合した洗浄用組 成物について種々検討する過程において、 抗真菌剤のうちには、 これを通常の抗 細菌性石鹼にそのまま配合しても、 その溶解性、 効果、 安定性などが大きく変動 してしまい、 安定な洗浄用組成物を得ることが困難なものがあるという課題があ ることがわかった。  Based on this recognition, the inventor of the present invention, in the process of variously examining a cleaning composition containing an antifungal agent and an antibacterial agent, found that among the antifungal agents, this was used as a normal antibacterial stone. It was found that there is a problem that even if it is blended as it is, its solubility, effect, stability, and the like vary greatly, and it is difficult to obtain a stable cleaning composition.
また抗真菌剤、 抗細菌剤および洗浄成分のうちには、 皮膚刺激作用を有するも のがあるため、 その組合せや配合量の調節により、 効果 (抗真菌効果、 抗細菌効 果、 洗浄効果、 抗細菌剤 ·抗真菌剤の残留効果等) と安全性 (皮膚刺激性が少な い等) とのバランスを図ることも必要である。 発明の開示 In addition, some of the antifungals, antibacterials, and cleaning ingredients have a skin irritating effect, and their effects (antifungal, antibacterial, cleaning, It is also necessary to balance the balance between antibacterial agents and residual effects of antifungal agents) and safety (less skin irritation). Disclosure of the invention
本発明は、 これらの課題を解決し、 抗真菌剤および抗細菌剤を配合した洗浄用 組成物、 特に医薬品、 医薬部外品または化粧品用として使用しうる洗浄用組成物 であって、 強力かつ広い抗細菌、 抗真菌スペクトルを有し、 安定で使用感に優 れ、 洗浄力に優れ、 皮膚刺激性が少なく、 頭皮や身体のかゆみの防止や防臭効果 が得られ、 常在菌ゃ通過菌による感染症の予防効果が得られる洗浄用組成物を提 供することを目的としている。  The present invention solves these problems and provides a cleaning composition containing an antifungal agent and an antibacterial agent, particularly a cleaning composition that can be used for pharmaceuticals, quasi-drugs, or cosmetics. It has a wide spectrum of antibacterial and antifungal properties, is stable and has excellent usability, has excellent detergency, has little skin irritation, and has the effect of preventing itching and deodorizing of the scalp and body. An object of the present invention is to provide a cleaning composition capable of preventing infectious diseases caused by shampoo.
本発明者は、 抗真菌剤と抗細菌剤とを配合した洗浄用組成物について鋭意研究 を行ったところ、 ァゾール系抗真菌剤と抗細菌剤とを配合した洗浄用組成物が、 強力かつ広い抗細菌、 抗真菌スペクトルを有する、 製品自体が安定である、 使用 感に優れる、 洗浄力に優れる、 皮膚刺激などの有害事象を認めない、 頭皮や身体 のかゆみの防止や防臭効果が得られる、 常在菌ゃ通過菌による感染症の予防効果 が得られる、 等、 上記課題の少なくとも一つを解決することを見出し、 本発明を 完成した。  The present inventors have conducted intensive studies on a cleaning composition containing an antifungal agent and an antibacterial agent, and found that a cleaning composition containing an azole-based antifungal agent and an antibacterial agent has a strong and broad It has an antibacterial and antifungal spectrum, the product itself is stable, it has excellent usability, it has excellent detergency, it does not cause skin irritation or other adverse events, and it can prevent itching and deodorant effects on the scalp and body. The present inventors have found that at least one of the above-mentioned problems can be solved, such as an effect of preventing infectious diseases caused by indigenous bacteria and passing bacteria, and thus completed the present invention.
このような本発明では、 ァゾール系抗真菌剤および抗細菌剤が配合された医薬 品、 医薬部外品または化粧品用の洗浄用組成物を提供する。  According to the present invention, there is provided a cleaning composition for a pharmaceutical, a quasi-drug, or a cosmetic, which contains an azole antifungal agent and an antibacterial agent.
上記洗浄用組成物において、 上記抗真菌剤は、 好ましくはミコナゾールおよ び/またはその塩である。 また上記抗細菌剤は、 好ましくはトリクロサン、 トリ クロカルバンおよびィソプロピルメチルフエノールから選ばれる少なくとも 1種 である。  In the cleaning composition, the antifungal agent is preferably miconazole and / or a salt thereof. The antibacterial agent is preferably at least one selected from triclosan, triclocarban and isopropylmethylphenol.
抗真菌剤が硝酸ミコナゾールであり、 抗細菌剤がトリク口サンである洗浄用組 成物は、 本発明の好ましい態様例である。 本発明の洗浄用組成物において、 通常、 抗真菌剤の含有量は、 0. 1〜2 . 0 w t %の量であり、 抗細菌剤の含有量は 0. 0 1〜1 . 5 w t %である。 A cleaning composition in which the antifungal agent is miconazole nitrate and the antibacterial agent is Tricsan is a preferred embodiment of the present invention. In the cleaning composition of the present invention, usually, the content of the antifungal agent is 0.1 to 2.0 wt%, and the content of the antibacterial agent is 0.01 to 1.5 wt%. It is.
本発明の洗浄用組成物は、 洗浄成分として、 低刺激性の界面活性剤を含むこと ができる。  The cleaning composition of the present invention may contain a mild surfactant as a cleaning component.
本発明の洗、净用組成物は、 たとえば石鹼の形態で提供される。 図面の簡単な説明  The washing and cleaning composition of the present invention is provided, for example, in the form of stone. BRIEF DESCRIPTION OF THE FIGURES
図 1は、 本発明の石鹼の洗浄効果を対照石鹼との比較において示す、 実施例 5 における細菌試験の結果を示すグラフである。  FIG. 1 is a graph showing the results of a bacterial test in Example 5, showing the cleaning effect of the stone of the present invention in comparison with a control stone.
図 2は、 本発明の石鹼の洗浄効果を対照石鹼との比較において示す、 実施例 5 における真菌試験の結果を示すグラフである。 発明を実施するための最良の形態  FIG. 2 is a graph showing the results of a fungal test in Example 5, showing the cleaning effect of the stone of the present invention in comparison with a control stone. BEST MODE FOR CARRYING OUT THE INVENTION
以下に本発明を詳細に説明する。  Hereinafter, the present invention will be described in detail.
本発明は、 医薬品、 医薬部外品または化粧品用の抗真菌性 '抗細菌性洗浄用組 成物であり、 広い抗真菌および抗細菌スペクトルを有する。 本発明の洗浄用組成 物は、 抗真菌剤と抗細菌剤とを必須配合成分として含み、 この抗真菌剤としてァ ゾール系抗真菌剤を含むことを特徴としている。  The present invention is an antifungal 'antibacterial cleaning composition for pharmaceuticals, quasi-drugs or cosmetics, having a broad antifungal and antibacterial spectrum. The cleaning composition of the present invention contains an antifungal agent and an antibacterial agent as essential components, and is characterized by containing an azole antifungal agent as the antifungal agent.
本発明でのァゾ一ル系抗真菌剤としては、 たとえばミコナゾール、 クロトリマ ゾ一ル、 ェコナゾ一ル、 チォコナゾ一ル、 ォキシコナゾ一ル、 フルコナゾール、 イトラコナゾール、 ケトコナゾール、 クロコナゾ一ル、 ネチコナゾ一ル、 イソコ ナゾール、 スルコナゾール、 ビフォナゾールおよびそれらの塩などが挙げられ る。 塩としては、 硝酸塩、 塩酸塩などが挙げられ、 好ましくは硝酸塩である。 本発明では、 これらの 2種以上を洗浄用組成物中に含ませることもできる。 これらのうちでも、 好ましくはミコナゾ一ル、 クロトリマゾール、 ェコナゾ一 ル、 チォコナゾ一ル、 ォキシコナゾ一ル、 スルコナゾ一ル、 ビフォナゾ一ルおよ びそれらの塩であり、 さらに好ましくは硝酸ミコナゾ一ルである。 Examples of the azolic antifungal agent in the present invention include miconazole, clotrimazole, econazole, choconazole, oxiconazole, fluconazole, itraconazole, ketoconazole, croconazole, neticonconazole, and isoconazole. Nazole, sulconazole, bifonazole and their salts You. Examples of the salt include nitrate and hydrochloride, and preferably nitrate. In the present invention, two or more of these may be included in the cleaning composition. Of these, miconazole, clotrimazole, econazole, choconazole, oxyconazole, sulconazole, bifonazole and their salts are preferred, and miconazole nitrate is more preferred. It is.
本明細書において、 上記ミコナゾールおよび硝酸ミコナゾールは、 下記 (I ) および (Π ) で表される構造を有する化合物を意味する。  In the present specification, the above-mentioned miconazole and miconazole nitrate mean a compound having a structure represented by the following (I) and (Π).
Figure imgf000008_0001
Figure imgf000008_0001
( I ) ミコナゾ一ル ( ID 硝酸ミコナゾ一ル  (I) Miconazole (ID
上記ァゾール系抗真菌剤は、 市販品として入手可能である。  The above azole antifungal agent is available as a commercial product.
本発明に用いる抗細菌剤は、 細菌に対して増殖抑制作用を有するものであれば 特に限定されないが、 ジフエ二ルエーテル化合物、 カルバニリド化合物または フエノール化合物が、好ましく、 具体的には、 トリクロサン、 トリクロカルバン、 ィソプロピルメチルフエノ一ルなどが挙げられる。 なかでもトリク口サンが好ま しい。  The antibacterial agent used in the present invention is not particularly limited as long as it has a growth inhibitory effect on bacteria, but a diphenyl ether compound, a carbanilide compound or a phenol compound is preferable, and specifically, triclosan, triclocarban And isopropylmethylphenol. Among them, Trik mouth sun is preferred.
これら抗細菌剤は、 市販品として入手可能である。  These antibacterial agents are available as commercial products.
本発明の特に好ましい態様は、 抗真菌剤が硝酸ミコナゾ一ルであり、 抗細菌剤 がトリク口サンである組合せである。  A particularly preferred embodiment of the present invention is the combination, wherein the antifungal agent is miconazole nitrate and the antibacterial agent is Tricsan.
抗真菌剤および抗細菌剤の組成物中への配合量は、 特に限定されないが、 通常 抗真菌剤の配合量が 0. 1〜2. 0 セ%であり、 抗細菌剤の配合量が 0. 0 :!〜 1. 5wt%である。 具体的に、 抗真菌剤が硝酸ミコナゾ一ルの場合には、 その配合量は 0. 1〜1. 0wt%が好ましく、 抗細菌剤がトリクロサンの場合 には、 その配合量は 0. 05〜1. 0 セ%が好ましい。 The amount of the antifungal agent and the antibacterial agent in the composition is not particularly limited, but is usually The compounding amount of the antifungal agent is 0.1 to 2.0%, and the compounding amount of the antibacterial agent is 0.0 :! ~ 1.5 wt%. Specifically, when the antifungal agent is miconazole nitrate, the amount is preferably 0.1 to 1.0 wt%, and when the antibacterial agent is triclosan, the amount is 0.05 to 0.5 wt%. 1.0% is preferred.
抗真菌剤と抗細菌剤との配合比は、 特に限定されないが、 抗真菌剤:抗細菌剤 (wt : wtの重量比) で、 通常 1 : 5〜5 : 1、 好ましぐは 1 : 1〜5 : 1、 より好ましくは 1 : 1〜2. 5 : 1であり、 さらに好ましくは抗真菌剤:抗細菌 剤 =2 : 1〜2. 5 : 1である。 具体的に、 特に好ましい抗真菌剤、 抗細菌剤お よびその配合比の組み合わせは、 抗真菌剤が硝酸ミコナゾ一ルであり、 抗細菌剤 がトリクロサンであり、 それらの配合比が硝酸ミコナゾ一ル: トリクロサン = 2. 5 : 1である。  The mixing ratio of the antifungal agent to the antibacterial agent is not particularly limited, but is usually 1: 5 to 5: 1, preferably 1: 5 to 5: 1, and preferably 1: 1 to 5: 1, more preferably 1: 1 to 2.5: 1, and still more preferably antifungal agent: antibacterial agent = 2: 1 to 2.5: 1. Specifically, a particularly preferable combination of the antifungal agent, the antibacterial agent, and the combination ratio thereof is such that the antifungal agent is miconazole nitrate, the antibacterial agent is triclosan, and the combination ratio is miconazole nitrate. : Triclosan = 2.5: 1.
本発明では、 洗浄用組成物に配合される洗浄成分としては、 抗真菌剤および抗 細菌剤の薬効を損なわない洗浄成分であれば特に限定されないが、 陰イオン性界 面活性剤を含ませることが好ましい。 具体的には、 アルキル硫酸エステルナトリ ゥム塩などの陰イオン性界面活性剤に、 アルキルジメチルアンモニゥムべタイン などの両イオン性界面活性剤、 ポリォキシエチレンアルキルエーテルなどの非ィ オン性界面活性剤などを適宜組み合わせて使用することができる。  In the present invention, the cleaning component to be added to the cleaning composition is not particularly limited as long as the cleaning component does not impair the efficacy of the antifungal agent and the antibacterial agent, and may include an anionic surfactant. Is preferred. Specifically, anionic surfactants such as alkyl sulfate sodium salt, amphoteric surfactants such as alkyl dimethyl ammonium betaine, and nonionic surfactants such as polyoxyethylene alkyl ether Surfactants and the like can be used in appropriate combination.
またこれら界面活性剤は低刺激性のものが好ましく、 低刺激性の陰イオン性界 面活性剤としては、 モノアルキルリン酸塩、 ァシルグルタミン酸塩、 ァシルメチ ルタウリン酸塩、 ココイルイセチオン酸塩、 ラウロイルメチルー |8—ァラニン塩 などが挙げられ、 低刺激性の両イオン性界面活性剤としてはべタイン型両イオン 性界面活性剤、 たとえば 2—アルキル一 N—カルポキシメチル _ N—ヒドロキシ ェチルイミダゾリ二ゥムべタインなどが挙げられる。 低刺激性の陰イオン性界面 活性剤と低刺激性の両イオン性界面活性剤の組合せが好ましい。 These surfactants are preferably low irritants, and examples of low irritant anionic surfactants include monoalkyl phosphates, acyl glutamates, acyl methyl taurates, cocoyl isethionates, Lauroyl-methyl | 8-alanine salt, etc. Examples of the low-irritating amphoteric surfactant include betaine-type amphoteric surfactants such as 2-alkyl-1-N-carboxymethyl_N-hydroxy. And ethyl imidazolidine betaine. A combination of a mildly anionic surfactant and a mildly amphoteric surfactant is preferred.
本発明の洗浄用組成物には、 更に通常の洗浄用組成物に用いられる成分、 例え ばプロピレングリコール、 グリセリンなどの保湿剤、 カチオン性ポリマ一などの コンディショニング成分、 色素、 顔料などの着色剤、 メチルセルロース、 ポリエ チレングリコールなどの粘度調整剤、 クェン酸、 ΤΚ酸化カリウムなどの p H調節 剤、 塩化ナトリウムなどの塩類、 植物エキス類、 防腐剤、 ビタミン剤、 香料、 紫 外線吸収剤、 抗酸化剤、 水などを適宜配合できる。  The cleaning composition of the present invention further includes components used in ordinary cleaning compositions, for example, humectants such as propylene glycol and glycerin, conditioning components such as cationic polymers, coloring agents such as pigments and pigments, Viscosity modifiers such as methylcellulose and polyethylene glycol, pH regulators such as citric acid and potassium oxide, salts such as sodium chloride, plant extracts, preservatives, vitamins, fragrances, ultraviolet absorbers, antioxidants , Water and the like can be appropriately added.
本明細書において、 洗浄用組成物とは、 洗浄成分を配合し、 使用後に流水等で 洗い流して使用する形態の組成物を意味する。 その形態は特に限定されないが、 石鹼 (固形石鹼、 液体石鹼、 泡状石鹼、 ボディ一ソープ、 ハンドソープ、 等) 、 クレンジンダフオーム、 シャンプー (頭髪用シャンプー、 ドライシャンプ一、 等) などが挙げられる。 これらのうちでも石鹼が好ましく、 とりわけ、 液体石 鹼、 ボディ一ソープが好ましい。 以下に、 本発明の洗浄用組成物の実施例を示すが、 本発明はこれらに限定され るものではない。  In the present specification, the term “cleaning composition” refers to a composition in which a cleaning component is blended, and after use, is washed away with running water or the like. Although the form is not particularly limited, stone (solid stone, liquid stone, foamed stone, body soap, hand soap, etc.), cleansing foam, shampoo (hair shampoo, dry shampoo, etc.) And the like. Of these, stones are preferred, and liquid stones and body soaps are particularly preferred. Examples of the cleaning composition of the present invention are shown below, but the present invention is not limited thereto.
• (実施例 1 ) 硝酸ミコナゾ一ルおよびトリクロサンの//? 0 における抗細 菌、 抗真菌作用  • (Example 1) Antibacterial and antifungal activities of miconazole nitrate and triclosan at //?
[対象菌株]  [Target strain]
〈細菌〉  <Bacteria>
Stapnylococcus aureus ATCC 29213 Escherichia coli ATCC 25922 Stapnylococcus aureus ATCC 29213 Escherichia coli ATCC 25922
Candida albicans IFM 40213 Candida albicans IFM 40213
Trichophyton rubrim IFM 45626 Trichophyton rubrim IFM 45626
[M I C値の測定]  [Measurement of MIC value]
〈細菌〉  <Bacteria>
(1) ミュ一ラーヒントン II寒天培地 (BBL) にて 35°C、 18〜20時間培 養後、 滅菌生理食塩液にて、 McFarland ΝαΟ. 5に調製した。 その後、 滅菌生理 食塩液にて 10倍希釈をし、 供試菌液とした。  (1) After culturing on Mueller Hinton II agar medium (BBL) at 35 ° C for 18-20 hours, it was adjusted to McFarland ΝαΟ.5 with sterile physiological saline. Then, it was diluted 10-fold with sterile physiological saline to obtain a test bacterial solution.
(2) 測定薬剤は DMSOで溶解し、 ミコナゾ一ルは 102, 400 M g/mL (力価) 、 トリクロサンは 409, 600 ^ g/mL (力価) に調製した。  (2) The test drug was dissolved in DMSO, and miconazole was adjusted to 102,400 Mg / mL (titer) and triclosan was adjusted to 409,600 ^ g / mL (titer).
102, 400 /mL (力価) に調製したミコナゾ一ル薬液は、 さらに D MS 0を用いて 2倍希釈系列を作製し、 102, 400〜50 w gZmL (力 価) となるよう調製した。  The miconazole solution prepared at 102, 400 / mL (titer) was further prepared in a two-fold dilution series using DMS0 to prepare 102, 400 to 50 wgZmL (titer).
409, 600 M g/mL (力価) に調製したトリクロサン薬液はさらに DM SOを用いて 2倍希釈系列を作製し、 409, 600〜6. 00 g/mL (力 価) となるよう調製した。  Triclosan drug solution adjusted to 409, 600 M g / mL (titer) was further prepared in a 2-fold dilution series using DMSO, and adjusted to 409, 600 to 6.00 g / mL (titer). .
(3) ミコナゾ一ルは 1, 024〜0. 5 gZmL、 トリクロサンは 4, 09 6〜0. 06 gZmLとなるように、 (2) で調製した各薬剤の希釈系列をそ れぞれカチオン調整した Mueller- Hintonブロス (CAMHB) に添加した (この とき、 最終 DMSO濃度は 2%以下となるようにした) 。  (3) Cation adjustment of each dilution series of each drug prepared in (2), so that miconazole is 1,024-0.5 gZmL and triclosan is 4,096-0.06 gZmL. Was added to the obtained Mueller-Hinton broth (CAMHB) (at this time, the final DMSO concentration was adjusted to 2% or less).
(4) (3) で調製した測定培地をそれぞれ 1 0 0 Lずつ分注した。 対照とし て薬剤不含有培地を 100 Lずつ分注した。 (4) Each 100 L of the measurement medium prepared in (3) was dispensed. As a control 100 L of the drug-free medium was dispensed.
(5) 接種菌液を各ゥエルに 5/ Lずつ接種し、 対象として用いた薬剤不含有培 地内の菌量を計測し、 接種菌量を求めた。  (5) The inoculum was inoculated into each well at 5 / L, and the amount of bacteria in the drug-free medium used as a target was measured to determine the amount of inoculated bacteria.
(6) 対照に用いた薬剤不含有培地での菌の発育を確認した後、 菌の発育が肉眼 的に認められないゥエルの最小の薬剤濃度を M I Cとした。  (6) After confirming the growth of the bacteria in the drug-free medium used as a control, the minimum drug concentration in the tube where growth of the bacteria was not visually observed was defined as MIC.
(1) C. albicans はサブローデキストロース寒天培地 (BBL) で 35°C、 2 4〜48時間培養後、 滅菌生理食塩液にて、 McFarland ΝαΟ. 5に調製した。 0. 165 mol/L MOP Sを含む RPM I 1640培地で 1000倍に希釈 し、 供試菌液 (1〜5 X 103 cells/mL) とした。 (1) C. albicans was cultured on Sabouraud dextrose agar medium (BBL) at 35 ° C. for 24 to 48 hours, and then adjusted to McFarland ΝαΟ.5 with sterile physiological saline. It was diluted 1000-fold with RPMI 1640 medium containing 0.165 mol / L MOPS to obtain a test bacterial solution (1 to 5 × 10 3 cells / mL).
T. rubrum は、 改変 1 Z 10サブロー ·グルコース寒天斜面培地で 2 Ί。に、 1〜 2週間培養後、 0. l%Twe e n 80加滅菌生理食塩液を加え分生子を採 取し、 滅菌ガーゼで濾過した。 分生子懸濁液はさらに 0. 1 % T w e e n 80加 滅菌生理食塩液で希釈し、 血球計算板を用いて菌数を 106 cellsZmLに調製 し供試菌液とした。 T. rubrum was modified 2% on a modified 1Z10 Sabouraud glucose agar slant. Then, after culturing for 1 to 2 weeks, sterile physiological saline solution containing 0.1% Tween 80 was added, conidia were collected, and the conidia were filtered with sterile gauze. The conidia suspension was further diluted with sterile physiological saline containing 0.1% Tween 80, and the number of bacteria was adjusted to 10 6 cellsZmL using a hemocytometer to obtain a test bacterial solution.
. (2) 測定薬剤は DMSOで溶解し、 ミコナゾ一ルおよびトリクロサン各々 1 2, 800 M g/mL (力価) に調製した。 12, 800 /x g/mL (力価) に 調製したミコナゾールおよびトリクロサン薬液は、 さらに DM SOを用いて各々 2倍希釈系列を作製し、 12, 800〜60 g/mL (力価) となるよう調整 した。  (2) The drug to be measured was dissolved in DMSO and adjusted to 12,800 Mg / mL (titer) for each of miconazole and triclosan. The miconazole and triclosan drug solutions prepared at 12,800 / xg / mL (titer) were further prepared in 2-fold dilution series using DMSO to obtain 12,800-60 g / mL (titer). It was adjusted.
(3) (2) で調製した各薬剤の希釈系列をそれぞれ、 0. 165 mol/L M OPSを含む RPMI 1640培地に、 128〜0. 06 g/mLとなるよう 添加した (このとき、 最終 DMSO濃度は 2%以下となるようにした) 。 (3) The dilution series of each drug prepared in (2) was adjusted to 128-0.06 g / mL in RPMI 1640 medium containing 0.165 mol / LM OPS. (At this time, the final DMSO concentration was adjusted to 2% or less).
(4) (3) で調製した測定培地 100 Lに対し、 (2) で調製した菌液 10 0 Lを接種し、 C. albicans は、 35 °Cで 24〜 48時間、 T. rubrum は、 2 7 で1〜2週間培養した。 但し、 薬剤不含有培地での菌の発育状況によって培 養時間は適宜延長した。 対照として薬剤不含有培地を 100 Lずつ分注した。 (4) 100 L of the culture solution prepared in (2) was inoculated to 100 L of the measurement medium prepared in (3), C. albicans was inoculated at 35 ° C for 24-48 hours, and T. rubrum was Cultured at 27 for 1-2 weeks. However, the cultivation time was appropriately extended depending on the growth of the bacteria in the drug-free medium. As a control, 100 L of a drug-free medium was dispensed.
(5) 対照に用いた薬剤不含有培地での菌の発育を確認した後、 菌の発育が肉眼 的に認められないゥエルの最小の薬剤濃度を M I Cとした。 (5) After confirming the growth of the bacteria in the drug-free medium used as a control, the minimum drug concentration in the tube where growth of the bacteria was not visually observed was defined as MIC.
M I C値 g/mL) 評価した結果を表 1中に示す。 表 1 (MIC value g / mL) The evaluation results are shown in Table 1. table 1
Figure imgf000013_0001
Figure imgf000013_0001
表中、 評 価 M I C値 ( g/mL) In the table, evaluation MIC value (g / mL)
< 0. 1  <0.1
〇 0. 1〜1未満  〇 0.1 to less than 1
Δ 1〜: L 0未満  Δ1 ~: Less than L0
X 10≤ 卜リク口サンは細菌に対して、 硝酸ミコナゾ一ルは真菌に対して強力な増殖抑 制効果を示した。 両者を混合することで強力かつ幅広い抗真菌、 抗細菌スぺクト ルが得られることがわかった。 ' (実施例 2) 液体石鹼の調製例 (1) X 10 ≤ Trik mouth sun showed a strong growth inhibitory effect on bacteria, and miconazole nitrate showed a strong growth inhibitory effect on fungi. It was found that by mixing both, a powerful and broad antifungal and antibacterial spectrum could be obtained. ' (Example 2) Preparation example of liquid stone (1)
本 OP 00 g中 In this OP 00 g
トリクロサン 0. 30 g Triclosan 0.30 g
硝酸ミコナゾ一ル 0. 75 g 0.75 g of miconazole nitrate
ラウロイルメチルー /3—ァラニンナトリウム 12. 00 g Lauroylmethyl-3-alanan sodium 12.00 g
2―アルキル一 N—力ルポキシメチルー N—ヒドロキシェチルイミダゾリニゥム ベタイン 12. 00 g  2-alkyl-1-N-hydroxypropyloxy-N-hydroxyethylimidazolinium betaine 12.00 g
プロピレングリコール 8. 00 g Propylene glycol 8.00 g
抗酸化剤 適量 Antioxidant appropriate amount
pH調節剤 適量 pH adjuster qs
精製水 purified water
(実施例 3 ) 液体石鹼の安定性試験 (Example 3) Stability test of liquid stone
実施例 2で作成した液体石鹼は、 調製直後は微黄色澄明な液体であり、 不溶物 等は認められなかった。 さらにこの液体石鹼を、 温度 40°C、 相対湿度 75% で、 プラスチック容器にて 6ヶ月間保存した結果、 硝酸ミコナゾール、 トリクロ サンの残存率は、 いずれも 95%以上 (液体クロマトグラフ法を用いた常法によ り定量) であり、 また、 沈殿、 着色なども認められなかった。 (実施例 4) 液体石鹼の使用 (1)  The liquid stone prepared in Example 2 was a clear, slightly yellow liquid immediately after preparation, and no insolubles were observed. In addition, this liquid stone was stored in a plastic container for 6 months at a temperature of 40 ° C and a relative humidity of 75%. As a result, the residual ratio of miconazole nitrate and triclosan was 95% or more in each case. Quantified by the usual method used), and no precipitation, coloring, etc. were observed. (Example 4) Use of liquid stone (1)
実施例 2で作成した液体石鹼を常法に従って手洗いおよび全身に使用した。 洗 浄時および洗浄後の違和感、 皮膚のひりひり感、 皮膚のかさつき等は認められ ず、 使用感に優れていた。 The liquid stone prepared in Example 2 was hand-washed and used for the whole body according to a conventional method. Uncomfortable feeling during and after washing, tingling of skin, and bulkiness of skin are observed. It had excellent usability.
本液体石鹼にて洗浄後に寒天培地に掌および足底を押捺 (スタンプ法) し、 常 法に従って培養を行った。 対照として、 市販の抗細菌石鹼を用いて同様の試験を 実施した。 培養後に検出される細菌数、 真菌数は、 本発明の液体石鹼を使用した 場合のほうが、 市販の抗細菌石鹼を使用した場合に比べて明らかに少なかった。  After washing with this liquid stone, the palms and soles were imprinted on the agar medium (stamp method), and cultivation was performed according to a conventional method. As a control, a similar test was carried out using a commercially available antibacterial stone. The number of bacteria and fungi detected after culturing was clearly lower when the liquid stone of the present invention was used than when a commercially available antibacterial stone was used.
(実施例 5 ) 液体石鹼の使用 (2 ) (Example 5) Use of liquid stone (2)
[方法]  [Method]
実施例 2で作成した液体石鹼を用いて、 以下の比較試験を実施した。  Using the liquid stone prepared in Example 2, the following comparative test was performed.
1 . 細菌試験  1. Bacterial test
(1-1) パ一ムスタンプ培地 (市販の S C D L P寒天培地;ダイズカゼイン分解 物、 レシチンおよびポリソルべ一ト 8 0含有) を用いて、 被験者 (N= 5 ) の試 験前の菌を採取した。 試験 5時間前から手洗いは禁止した。  (1-1) Using a stamp-stamp medium (commercially available SCDLP agar medium; containing soybean casein hydrolyzate, lecithin and polysorbate 80), pre-test bacteria were collected from test subjects (N = 5) . Hand washing was prohibited 5 hours before the test.
(1-2) 7 %に希釈し泡噴出容器に入れた実施例 2で作成した液体石鹼 (本発明石 鹼) および実施例 2の組成から硝酸ミコナゾールを除いた液体石鹼 (対照石鹼) を用い、 被験者の右手掌、 左手掌を片手づっ、 一定の時間洗浄した。 (1-2) Liquid stone prepared in Example 2 diluted to 7% and placed in a foam ejection container (invention stone) and liquid stone prepared by removing miconazole nitrate from the composition of Example 2 (control stone) ), The subject's right and left palms were washed with one hand for a certain period of time.
洗浄は本発明石鹼、 対照石鹼の各担当者が、 被験者に対してブラインド下、 左 右ランダムに被験者全員の手を一定の方法 (2プッシュで 5秒間) で洗浄する方 法により実施した。  Washing was carried out by each person in charge of the present invention stones and the control stones, washing the hands of all subjects randomly under the blinds, left and right randomly (2 pushes for 5 seconds). .
(1-3) 水道水 (e LZmin ) で一定の時間 (5秒: 5 0 O mL) で洗浄剤を洗い 流した。 (1-3) The detergent was rinsed with tap water (e LZmin) for a certain period of time (5 seconds: 50 O mL).
(1-4) 両手をドライヤー (冷風) で乾燥し、 再度菌を採取した。 (1-5) 採取後 5時間手を洗わずにいて、 5時間後再度菌を採取した。 (1-4) Both hands were dried with a dryer (cold air), and the bacteria were collected again. (1-5) The bacteria were collected again 5 hours after washing without washing hands.
(1-6) 菌を採取した培地を 24時間 35 °Cのインキュベータ一で培養した。 ' (1-7).検出された培地の写真を撮影し、 細菌のコロニー数を測定した。 (1-6) The medium from which the bacteria were collected was cultured in an incubator at 35 ° C for 24 hours. '(1-7). A photograph of the detected medium was taken, and the number of bacterial colonies was measured.
2. 真菌試験 2. Fungal test
(2-1) フットプレス用培地 (バクトァガ一15 g、 ネオペプトン 10 g、 ブドウ 糖 20 g、 シクロへキシミド 100 Omg、 クロラムフエニコ一ル 5 Omg、 硫 酸ゲン夕マイシン 100mg、 蒸留水 100 OmL) を使用し、 被験者 (N = 5) の試験前の足の菌を採取した。 (2-1) Use the media for foot press (15 g of Bactogaga, 10 g of neopeptone, 20 g of glucose, 100 Omg of cycloheximide, 5 Omg of chloramphenicol, 100 mg of genyumycin sulfate, 100 OmL of distilled water) Before the test, the fungi on the feet of the subjects (N = 5) were collected.
(2-2) 7%に希釈し泡噴出容器に入れた本発明石鹼および対照石鹼を用い、 被験 者の右足裏、 左足裏を片足づっ、 一定の時間洗浄した。  (2-2) Using the stone of the present invention 対 照 and the control stone 希 釈 diluted to 7% and placed in a foam ejection container, the right sole and the left sole of the subject were washed with one foot for a certain period of time.
洗浄は本発明石鹼、 対照石鹼の各担当者が、 被験者に対してブラインド下、 左 右ランダムに被験者全員の足を一定の方法 (2プッシュで 5秒間) で洗浄する方 法により実施した。  Washing was carried out by the person in charge of the stone of the present invention and the control stone by washing the feet of all subjects randomly under the blind, left and right with a fixed method (2 pushes for 5 seconds). .
(2-3) 水道水 (6LZmin ) で一定の時間 (5秒: 50 OmL) 洗浄剤を洗い流 した。  (2-3) The cleaning agent was rinsed with tap water (6 LZmin) for a certain period of time (5 seconds: 50 OmL).
(2-4) 両足をドライヤー (冷風) で乾燥し、 再度菌を採取した。  (2-4) Both feet were dried with a dryer (cold air), and the bacteria were collected again.
(2-5) 菌を採取した培地を 7日〜 14日 27 °Cのインキュベータ一で培養した。 (2-6) 検出された培地の写真を撮影し、 真菌のコロニー数を数えた。 (2-5) The culture medium from which the bacteria were collected was cultured in an incubator at 27 ° C for 7 to 14 days. (2-6) A photograph of the detected medium was taken, and the number of fungal colonies was counted.
[結果]  [Result]
結果を図 1 (細菌) および図 2 (真菌) に示す。  The results are shown in Figure 1 (bacteria) and Figure 2 (fungi).
図 1に示す通り、 本発明石鹼を用いた場合の、 平均細菌コロニー数 (洗浄前を 100%として%で表示) は、 洗浄直後には顕著な低下を示し、 洗浄 5時間後に おいても、 洗浄前よりも低い値であった。 一方、 対照石鹼は、 洗浄直後には一時 的にコロニー数が減少したが、 洗浄 5時間後の値は、 洗浄前よりも高いもので あった。 As shown in Fig. 1, when the stone of the present invention was used, the average number of bacterial colonies (expressed as% with 100% before washing) showed a marked decrease immediately after washing, and 5 hours after washing. The value was lower than before cleaning. On the other hand, in Control Stone I, the number of colonies temporarily decreased immediately after washing, but the value 5 hours after washing was higher than that before washing.
図 2に示す通り、 本発明石鹼を用いた場合の、 平均真菌コロニー数 (洗浄前を 1 0 0 %として%で表示) は、 洗浄直後に顕著な低下を示した。 一方、 対照石鹼 は、 洗浄直後にコロニー数の減少は認められず、 却って、 洗浄前よりも高い値と なった。  As shown in FIG. 2, when the stone of the present invention was used, the average number of fungal colonies (expressed as 100% before washing) was markedly decreased immediately after washing. On the other hand, the control stone No. showed no decrease in the number of colonies immediately after washing, and on the contrary, the value was higher than that before washing.
以上より、 本発明石鹼は、 対照石鹼に比し、 抗細菌、 抗真菌作用に優れること が確認された。  From the above, it was confirmed that the stone of the present invention was superior to the control stone in antibacterial and antifungal activities.
(実施例 6 ) 硝酸ミコナゾールおよびトリクロサン混合液の in vitro における 抗細菌、 抗真菌作用 (Example 6) In vitro antibacterial and antifungal activities of a mixed solution of miconazole nitrate and triclosan
[対象菌株]  [Target strain]
〈細菌〉  <Bacteria>
Staphylococcus aureus ATCC 29213 , Staphylococcus aureus ATCC 29213,
Escherichia coli ATCC 25922 Escherichia coli ATCC 25922
Candida albicans IFM 40213 Candida albicans IFM 40213
Trichophyton rubruin IFM 45626  Trichophyton rubruin IFM 45626
[薬剤配合比]  [Drug mix ratio]
( 1 ) 硝酸ミコナゾール: トリクロサン = 2 . 5  (1) Miconazole nitrate: Triclosan = 2.5
( 0 . 7 1 0 7 g: 0 . 2 8 6 3 g ) (2) 硝酸ミコナゾ一ル: トリクロサン =2 : 1 (0.710g: 0.2863g) (2) Miconazole nitrate: Triclosan = 2: 1
(0. 6634 g : 0. 3340 g)  (0.6634 g: 0.3340 g)
(3) 硝酸ミコナゾ一ル: トリクロサン =1 : 1  (3) Miconazole nitrate: Triclosan = 1: 1
(0. 4975 g: 0. 5010 g)  (0.4975 g: 0.5010 g)
[薬剤調製方法]  [Drug preparation method]
(1) 硝酸ミコナゾールおよびトリクロサンを上記薬剤配合比の割合で 1 gとな るよう秤量した。  (1) Miconazole nitrate and triclosan were weighed so as to be 1 g at the above-mentioned drug compounding ratio.
(2) この 1 gをジメチルスルホキシド (DMSO) 39. 06mLに溶解し、 25, 600 gZmLの溶液を作成した。  (2) This 1 g was dissolved in 39.06 mL of dimethyl sulfoxide (DMSO) to prepare a solution of 25,600 gZmL.
(3) 25, 60 O^gZmL溶液を原液として、 以下の試験に使用した。  (3) A 25, 60 O ^ gZmL solution was used as a stock solution for the following tests.
[M I C値の測定]  [Measurement of MIC value]
〈細菌〉  <Bacteria>
(1) ミユーラ一ヒントン II寒天培地 (BBL) にて 35° (、 18時間培養後、 滅菌生理食塩液にて、 McFarland ΝαΟ. 5に調製した。 その後、 滅菌生理食塩液 にて 10倍希釈をし、 供試菌液とした。  (1) After culturing on a Myura-Hinton II agar medium (BBL) at 35 ° (18 hours), adjusted to McFarland ΝαΟ.5 with sterile physiological saline. Then, dilute 10-fold with sterile physiological saline. And used as a test bacterial solution.
(2) 上記薬剤調製方法にて作製した原液を DMSOを用いて 2倍希釈し、 1 2, 800 gZmLに調整後、 さらに DMSOを用いて 2倍希釈系列を作製 し、 12, 800〜0. 8 g/mL (力価) となるよう調整した。  (2) The stock solution prepared by the above drug preparation method was diluted 2-fold with DMSO, adjusted to 12,800 gZmL, and then a 2-fold dilution series was prepared with DMSO. It was adjusted to 8 g / mL (titer).
(3) 128〜0. 008 g/mLとなるように、 (2) で調製した薬剤の希 釈系列をそれぞれカチオン調整した Mueller- Hintonブロス (CAMHB) に添加 した (このとき、 最終 DMSO濃度は 2%以下となるようにした) 。  (3) The dilution series of the drug prepared in (2) was added to each cation-adjusted Mueller-Hinton broth (CAMHB) so that the concentration became 128 to 0.008 g / mL. 2% or less).
(4) (3) で調製した測定培地をそれぞれ 100 Lずつ分注した。 対照とし て薬剤不含有培地を 100 Lずつ分注した。 (4) Each 100 L of the measurement medium prepared in (3) was dispensed. As a control 100 L of the drug-free medium was dispensed.
(5) 接種菌液を各ゥエルに 5 Lずつ接種し、 対照として用いた薬剤不含有培 地内の菌量を計測し、 接種菌量を求めた。  (5) Inoculated bacterial solution was inoculated into each well in an amount of 5 L, and the amount of bacteria in the drug-free medium used as a control was measured to determine the amount of inoculated bacteria.
(6) 対照に用いた薬剤不含有培地での菌の発育を確認した後、 菌の発育が肉眼 的に認められないゥエルの最小の薬剤濃度を M I Cとした。  (6) After confirming the growth of the bacteria in the drug-free medium used as a control, the minimum drug concentration in the tube where growth of the bacteria was not visually observed was defined as MIC.
(1) C. albicans はサブローデキストロ一ス寒天培地 (88 ) で35°(:、 4 8時間培養後、 滅菌生理食塩液にて、 McFarland No.0. 5に調製した。 0. 16 5 mol/L MOP Sを含む RPM I 1640培地で 1000倍に希釈し、 供試 菌液 (1〜5 X 103 cells ZmL) とした。 (1) C. albicans was cultured on Sabouraud dextrose agar medium (88) at 35 ° (:, 48 hours), and then prepared with sterile physiological saline to McFarland No. 0.5. It was diluted 1000-fold with RPMI 1640 medium containing mol / L MOPS to obtain a test bacterial solution (1 to 5 × 10 3 cells ZmL).
T. rubrwn は、 改変 1 / 10サブ口一 ·グルコース寒天斜面培地で 271、 1 週間培養後、 0. l%Twe e n80加滅菌生理食塩液を加え分生子を採取し、 滅菌ガーゼで濾過した。 分生子懸濁液はさらに 0. 165 mol/L MOPSを 含む RPM I 1640培地で希釈し、 血球計算板を用いて菌数を 106 cells / mLに調製し供試菌液とした。 T. rubrwn was cultured on a modified 1/10 sub-oral glucose agar slant medium for 271 weeks and then added with 0.1% Tween n80 in sterile physiological saline to collect conidia and filtered through sterile gauze. . The conidia suspension was further diluted with RPMI 1640 medium containing 0.165 mol / L MOPS, and the number of bacteria was adjusted to 10 6 cells / mL using a hemocytometer to obtain a test bacterial solution.
(2) 上記薬剤調製方法にて作製した原液を、 さらに DMSOを用いて 2倍希釈 系列を作製し、 25, 600〜1. 5 g/mL (力価) となるよう調整した。 (2) A two-fold dilution series was prepared from the stock solution prepared by the above-mentioned drug preparation method using DMSO, and adjusted to 25,600 to 1.5 g / mL (titer).
(3) (2) で調製した各薬剤の希釈系列をそれぞれ、 0. 165 molZL M OP Sを含む RPM I 1640培地に、 256〜0. 015 gZmLとなるよ う添加した (このとき、 最終 DMSO濃度は 2%以下となるようにした) 。(3) The dilution series of each drug prepared in (2) was added to RPMI 1640 medium containing 0.165 molZL MOPS to obtain 256-0.015 gZmL (in this case, final DMSO The concentration was adjusted to 2% or less).
(4) (3) で調製した測定培地を 100 ^Lずつ分注した。 対照として、 薬剤 不含有培地を 100 Lずつ分注した。 (5) ( 1 ) で調製した菌液 100 Lを接種し、 C. albicans は 35 °C、 48 時間、 T. rubrim は、 21。 、 1週間培養した。 (4) The measurement medium prepared in (3) was dispensed in 100 L portions. As a control, 100 L of drug-free medium was dispensed. (5) Inoculate 100 L of the bacterial solution prepared in (1), C. albicans at 35 ° C for 48 hours, and T. rubrim at 21. And cultured for 1 week.
〇△ X  〇 △ X
(6) 対照に用いた薬剤不含有培地での菌の発育を確認した後、 菌の発育が肉眼 的に認められないゥエルの最小の薬剤濃度を M I Cとした。 MI C値 ( gZmL) 評価した結果を表 2中に示す。 表 2  (6) After confirming the growth of the bacteria in the drug-free medium used as a control, the minimum drug concentration in the tube where growth of the bacteria was not visually observed was defined as MIC. The results of the evaluation of the MI C value (gZmL) are shown in Table 2. Table 2
Figure imgf000020_0001
Figure imgf000020_0001
表中、 評 価 M I C値 (β g/mL) In the table, the evaluation MIC value (β g / mL)
< 0. 1  <0.1
0. 1〜1未満  0.1 to less than 1
1〜10未満  1 to less than 10
1 0≤  1 0≤
硝酸ミコナゾ一ル トリクロサンを 2. 5 : 1〜1 : 1の割合で配合した混合 液は、 細菌、 真菌に対して、 強力な増殖抑制効果を示した。 両者を混合すること で強力かつ幅広い抗真菌、 抗細菌スぺクトルが得られることがわかった。 (実施例 7) 液体石鹼の調製例 (2) A mixture of miconazole nitrate and triclosan in a ratio of 2.5: 1 to 1: 1 showed a strong growth inhibitory effect against bacteria and fungi. It was found that by mixing both, a strong and broad antifungal and antibacterial spectrum could be obtained. (Example 7) Preparation example of liquid stone (2)
本品 100 g中 100 g of this product
トリクロサン 0. 30 g 硝酸ミコナゾ一ル 0. 75 g N—ヤシ油脂肪酸ァシル一L一グルタミン酸カリウム 5. 00 gTriclosan 0.30 g Miconazole nitrate 0.75 g N-coconut oil fatty acid acyl-L-potassium monoglutamate 5.00 g
2—アルキル一 N—カルボキシメチル一 N—ヒドロキシェチルイミダゾリニゥム 2-alkyl-1-N-carboxymethyl-1-N-hydroxyethylimidazolinium
10. 00 g プロピレングリコール 5. 00 g 抗酸化剤  10.00 g Propylene glycol 5.00 g Antioxidant
pH調節剤 pH regulator
精製水 purified water
(実施例 8) 液体石鹼の調製例 (3) (Example 8) Preparation example of liquid stone (3)
本品 100 g中 100 g of this product
トリクロカルバン 0. 50 g 硝酸ミコナゾ一ル 0. 75 g Triclocarban 0.50 g Miconazole nitrate 0.75 g
N—ラウロイルー L—グルタミン酸カリゥム 30. 00 g プロピレングリコール 3. 00 g 抗酸化剤 N-lauroylu L- potassium glutamate 30.00 g propylene glycol 3.00 g antioxidant
p H調節剤 pH regulator
精製水 産業上の利用可能性 purified water Industrial applicability
本発明では、 抗真菌剤および抗細菌剤が配合された新規な医薬品、 医薬部外品 または化粧品用の本発明の洗浄用組成物が提供される。 特に抗真菌剤としてァ ゾール系抗真菌剤と抗細菌剤とを配合した洗浄用組成物は、 強力かつ広い抗細 菌、 抗真菌スペクトルを有し、 製品自体が安定である、 使用感に優れる、 洗浄力 に優れる、 皮膚刺激などの有害事象を認めない、 頭皮や身体のかゆみの防止や防 臭効果が得られる、 常在菌ゃ通過菌による感染症の予防効果が得られる等のうち の少なくとも一つの優れた特性を有する。  According to the present invention, there is provided the cleaning composition of the present invention for a novel drug, quasi-drug, or cosmetic, which contains an antifungal agent and an antibacterial agent. In particular, cleaning compositions containing an azole antifungal agent and an antibacterial agent as antifungal agents have a strong and broad antibacterial and antifungal spectrum, are stable in the product itself, and have excellent usability. Excellent detergency, no adverse effects such as skin irritation, prevention of scalp and body itch and deodorization effects, prevention of infectious diseases caused by resident bacteria and passing bacteria It has at least one excellent property.

Claims

請求の範囲 The scope of the claims
1. ァゾ一ル系抗真菌剤および抗細菌剤が配合された医薬品、 医薬部外品また は化粧品用の洗浄用組成物。  1. A cleaning composition for medicaments, quasi-drugs or cosmetics, which contains an azolic antifungal agent and an antibacterial agent.
2. 前記抗真菌剤が、 ミコナゾ一ルおよび Zまたはその塩である請求項 1に記 載の洗浄用組成物。  2. The cleaning composition according to claim 1, wherein the antifungal agent is miconazole and Z or a salt thereof.
3. 前記抗細菌剤が、 トリクロサン、 トリクロカルバンおよびイソプロピルメ チルフエノ一ルから選ばれる少なくとも 1種である請求項 1または 2に記載の洗 浄用組成物。 .  3. The cleaning composition according to claim 1, wherein the antibacterial agent is at least one selected from triclosan, triclocarban, and isopropylmethylphenol. .
4. 前記抗真菌剤が硝酸ミコナゾールであり、 抗細菌剤がトリクロサンである 請求項 1〜3のいずれかに記載の洗浄用組成物。  4. The cleaning composition according to any one of claims 1 to 3, wherein the antifungal agent is miconazole nitrate, and the antibacterial agent is triclosan.
5. 前記抗真菌剤の含有量が 0. 1〜2. 0 1;%の量であり、 前記抗細菌剤. の含有量が 0. 01〜1. 5wt %である請求項 1〜4のいずれかに記載の洗浄 用組成物。  5. The content of the antifungal agent is 0.1 to 2.01;%, and the content of the antibacterial agent is 0.01 to 1.5 wt%. The cleaning composition according to any one of the above.
6. 洗浄成分として、 低刺激性の界面活性剤を含む請求項 1〜 5のいずれかに 記載の洗浄用組成物。  6. The cleaning composition according to any one of claims 1 to 5, further comprising a low-irritant surfactant as a cleaning component.
7. 前記洗浄用組成物が石鹼である請求項 1〜 6のいずれかに記載の洗浄用組 成物。  7. The cleaning composition according to any one of claims 1 to 6, wherein the cleaning composition is stone.
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JP2010275198A (en) * 2009-05-26 2010-12-09 Mochida Pharmaceut Co Ltd Composition for cleaning
WO2012177986A2 (en) 2011-06-22 2012-12-27 Vyome Biosciences Conjugate-based antifungal and antibacterial prodrugs
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0520873A1 (en) * 1991-06-24 1992-12-30 L'oreal Alkylthiopoly(ethylimidazolium)compounds, process of preparation and their use as biocide agents
EP0680745A2 (en) * 1994-05-05 1995-11-08 L'oreal Use of antifungals and or halogenated antibacterial agents for diminishing hair loss
WO1997022346A2 (en) * 1995-12-16 1997-06-26 Beiersdorf Ag Use of sugar derivatives as antimicrobial, antimycotic and/or antiviral active substances
JPH09176014A (en) * 1995-12-26 1997-07-08 Taiho Yakuhin Kogyo Kk Antimycotic composition for external use
JPH10265408A (en) * 1997-03-25 1998-10-06 Lion Corp Sterilizer composition
JP2003063984A (en) * 2001-06-26 2003-03-05 L'oreal Sa Composition for cosmetic or the skin containing elastase inhibitor of n-acylaminoamido family and at least one antifungal agent or at least one antibacterial agent in combination

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2798847B1 (en) * 1999-09-29 2001-11-23 Oreal COMPOSITION FOR THE TREATMENT OF DAIRY AND SCALP HAIR, BASED ON AN ANTI-DANDLING AGENT AND AN ACRYLIC TERPOLYMER
US7074392B1 (en) * 2000-03-27 2006-07-11 Taro Pharmaceutical Industries Limited Controllled delivery system of antifungal and keratolytic agents for local treatment of fungal infections
JP5217450B2 (en) 2008-01-24 2013-06-19 沖電気工業株式会社 Automatic transaction system and automatic transaction device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0520873A1 (en) * 1991-06-24 1992-12-30 L'oreal Alkylthiopoly(ethylimidazolium)compounds, process of preparation and their use as biocide agents
EP0680745A2 (en) * 1994-05-05 1995-11-08 L'oreal Use of antifungals and or halogenated antibacterial agents for diminishing hair loss
WO1997022346A2 (en) * 1995-12-16 1997-06-26 Beiersdorf Ag Use of sugar derivatives as antimicrobial, antimycotic and/or antiviral active substances
JPH09176014A (en) * 1995-12-26 1997-07-08 Taiho Yakuhin Kogyo Kk Antimycotic composition for external use
JPH10265408A (en) * 1997-03-25 1998-10-06 Lion Corp Sterilizer composition
JP2003063984A (en) * 2001-06-26 2003-03-05 L'oreal Sa Composition for cosmetic or the skin containing elastase inhibitor of n-acylaminoamido family and at least one antifungal agent or at least one antibacterial agent in combination

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008540581A (en) * 2005-05-16 2008-11-20 ノヴァファーム リサーチ (オーストラリア) ピーティーワイ リミテッド Methods and compositions for use in preparing a patient for surgery
JP2013173758A (en) * 2005-05-16 2013-09-05 Novapharm Research (Australia) Pty Ltd Method and composition for use in preparation of patient for surgery
KR101413138B1 (en) 2005-05-16 2014-07-01 노바팜 리서치(오스트레일리아)피티와이리미티드 Method and composition for use in preparation of a patient for surgery
US9511017B2 (en) 2005-05-16 2016-12-06 Novapharm Research (Australia) Pty Ltd Method and composition for use in preparation of a patient for surgery
JP2010275198A (en) * 2009-05-26 2010-12-09 Mochida Pharmaceut Co Ltd Composition for cleaning
WO2012177986A2 (en) 2011-06-22 2012-12-27 Vyome Biosciences Conjugate-based antifungal and antibacterial prodrugs
WO2014195872A1 (en) 2013-06-04 2014-12-11 Vyome Biosciences Pvt. Ltd. Coated particles and compositions comprising same
JP2015168615A (en) * 2014-03-04 2015-09-28 持田製薬株式会社 Composition for cleaning
WO2018199303A1 (en) * 2017-04-28 2018-11-01 持田製薬株式会社 Sheet preparation containing miconazole and/or miconazole nitrate
JPWO2018199303A1 (en) * 2017-04-28 2020-05-14 持田製薬株式会社 Sheet formulation containing miconazole and / or miconazole nitrate
JP7030110B2 (en) 2017-04-28 2022-03-04 持田製薬株式会社 Sheet preparation containing miconazole and / or miconazole nitrate
JP2019081763A (en) * 2018-12-27 2019-05-30 持田製薬株式会社 Cleaning composition

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