WO2003070231A1 - Antibacterial compositions - Google Patents

Antibacterial compositions Download PDF

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Publication number
WO2003070231A1
WO2003070231A1 PCT/JP2003/001757 JP0301757W WO03070231A1 WO 2003070231 A1 WO2003070231 A1 WO 2003070231A1 JP 0301757 W JP0301757 W JP 0301757W WO 03070231 A1 WO03070231 A1 WO 03070231A1
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Prior art keywords
antibacterial
agent
composition
agents
antibacterial composition
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PCT/JP2003/001757
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French (fr)
Japanese (ja)
Inventor
Masako Katsuyama
Hisanori Akiyama
Takashi Oono
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Shiseido Company, Ltd.
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Publication of WO2003070231A1 publication Critical patent/WO2003070231A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/65—Tetracyclines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to an antimicrobial composition.
  • the problem to be solved by the present invention is to find a means that can treat resistant bacteria with conventional antibacterial agents. Disclosure of the invention
  • the present inventors have conducted intensive studies to solve this problem, and as a result, the antibacterial composition combining antibacterial agents such as antibiotics and fuarnesol used as an antibacterial fragrance synergistically improves the antibacterial effect. Surprisingly, it has been found that an antibacterial effect can be exerted against a resistant bacterium even when used in combination with an antibacterial agent which is originally not effective. Thus, the present invention has been completed.
  • the present invention is an invention which provides an antibacterial composition containing fuarnesol and an antibacterial agent (hereinafter, also referred to as the present antibacterial composition).
  • Huarnesol 3,7,11-trimethyl_2,6,10-dodecatrien-l-l-ol.
  • Huarnesol Is a component contained in neroli oil, ylang-ylang oil, etc., and is used as an antibacterial synthetic fragrance (a commercial product is also available). It has a fresh green note with a floral-like scent, and can be used in cosmetics. Is recognized.
  • the antibacterial agent which is the other essential component of the antibacterial composition, may be an antibiotic or a synthetic antibacterial agent.
  • neomycin paromomycin, ribidomycin, kanamycin, bekanamicin, dibekacin, tobramycin, amikacin, gentamicin, streptomycin, ribostamycin
  • Aminoglycoside agents such as piomycin, tobacactinomycin, succinomycin, kasugamycin; sinoxacinic acid, naliditasic acid, enoxacin, pidmidic acid, nonolefloxacin, ofloxacin, diprofloxacin Pyridonecarboxylic acid or quinolone such as subarufloxacin, tosfloxacin tosinoleate, and fleroxacin; macrolides such as erythromycin and kitasamycin; chlorte torasa Tetracycline-based agents such as Iculin, Oxytetracycline,
  • One antibacterial agent can be used, or two or more antibacterial agents can be used in combination.
  • the present antimicrobial composition can be applied to all bacteria and fungi.
  • Staphylococcus Staphyl ococcus
  • Bacteria belonging to the genus Bacteria belonging to the genus (Streptococcus), for example, Staphylococcus aureus, Coagul-i, Sinus larva, and 'coagulase-negative Staphylococci:
  • Staphylococcus aureus which is known as a causative bacterium of serious nosocomial infections due to resistant bacteria (MRSA, VRSA, etc.), can be a suitable target.
  • antibacterial agents benzalkonium chloride, dalconic acid Chlorhexidine (the content of the first two agents in the present antibacterial composition is preferably about 1 to 50% based on the agent), popyondo (the content in the present antibacterial composition is 1 to It is also possible to use a germicidal disinfectant (such as about 10%) as the antibacterial composition for the purpose of disinfecting the skin or disinfecting medical instruments.
  • a germicidal disinfectant such as about 10%
  • biofilm-forming organisms for example, form biofilms that settle in wounds and burns, exhibiting resistance to treatment, and in the worst case replace drug-resistant organisms, which is very troublesome. It has been acknowledged that the situation will end up.
  • the antibacterial composition at a target site (a wound or a burn site) on the skin first to accelerate the healing of the target site and to suppress the emergence of resistant bacteria.
  • the content of fuarnesol in the present antibacterial composition in the form of an external preparation can be freely selected, it is usually preferably about 0.001 to 10% by mass based on the preparation.
  • the content of fuarnesol is 0.00001 mass based on the preparation. / 0 below the Der Ru, generally sufficient difficult der to exert a synergistic antibacterial effect with the antimicrobial agent is, even though the amount is more than the 1 0% by weight, the increase of the amount It cannot be expected that the antibacterial effect will be improved accordingly.
  • the content of the antibacterial agent in the present antibacterial composition in the form of an external preparation is preferably set to a content at which an effective amount of the antibacterial agent is applied to the affected area when applied to the skin as an external preparation. It is. Specifically, depending on the type of antibacterial agent to be used and the type of main bacteria for antibacterial purposes, the content is generally in the range of about 0.01 to 10% by mass of the agent. It is preferred that
  • the present antibacterial composition is an antibacterial composition that can be in the form of an oral agent.
  • the antibacterial effect of the antibacterial agent expected by oral administration is enhanced by the combination with S and huarnesol, which is effective against various medical diseases and skin diseases caused by pathogenic bacteria. It is considered to be. In particular, it is expected to be effective against diseases caused by resistant bacteria.
  • the content of fuarnesol in the present antibacterial composition in the form of an oral preparation can be freely selected, it is usually preferably about 0.001 to 50% by mass relative to the preparation.
  • the content of funaresol is less than 0.001% by mass with respect to the agent. Therefore, in general, it is difficult to exhibit a synergistic antibacterial effect with a sufficient antibacterial agent, and even if the amount exceeds 50% by mass, the antibacterial effect is commensurate with the increased amount. No improvement can be expected.
  • the content of the antibacterial agent in the present antibacterial composition in the form of an internal preparation is preferably about 0.01 to 20% by mass based on the preparation.
  • the content of the antibacterial agent is less than 0.01% by mass with respect to the agent, it is generally difficult to exert a synergistic antibacterial effect with sufficient funaresol. %, The antibacterial effect cannot be expected to increase in proportion to the increase in the amount.
  • the amount of the antimicrobial composition used can be appropriately selected according to the patient's condition, the use form and dosage form of the agent, and the like.
  • the antibacterial composition is an external preparation, generally, about 0.001 to 0.1 lg of the active ingredients funaresol and the antibacterial agent are applied to the skin per adult per day. As described above, it is preferable to use once or several times a day.
  • the antibacterial composition is an oral preparation, generally, about 0.001 to 0.1 lg of the active ingredients funaresol and the antibacterial agent are administered per adult per day. As described above, it is preferable to use once or several times a day.
  • the dosage form and product form of the antimicrobial composition as an external preparation include all the dosage forms and product forms that the external preparation can take, specifically, lotions, gels, emulsions, creams, ointments, and powders. Agents, cleaning agents, bath agents, spray agents, etc. can be selected. It can also be used as nasal drops and ear drops.
  • the antimicrobial composition used as an external preparation according to the strength, the dosage form and the product form usually contains known base components such as oils, surfactants, higher alcohols, preservatives, humectants, and thickeners. , A chelating agent, a coloring matter, a fragrance, and the like.
  • the dosage form and product form of the antibacterial composition as an oral preparation include all dosage forms and product forms that the oral preparation can take, specifically, tablets, powders, granules, pills, and the like. It can be made into injections such as preparations, solutions, suspensions and emulsions. In addition, it can be used as a preparation at the time of use.
  • the present antibacterial composition of this embodiment may contain a generally known pharmaceutical carrier such as a filler, a bulking agent, a binder, a moisturizer, a disintegrant, a surfactant, and the like. Excipients and diluents can be freely selected and blended.
  • the antibacterial composition in the form of an internal medicine may be administered by an appropriate route of administration depending on the embodiment, for example, In the case of injection, it can be administered by intravenous, intramuscular, subcutaneous, intradermal, intraperitoneal administration and the like, and in the case of solid form, it can be administered by oral or enteral administration.
  • the pharmacologic agent and the antibacterial agent are also possible to administer as separate agents to achieve a synergistic antibacterial effect according to the antibacterial composition.
  • a synergistic antibacterial effect according to the antibacterial composition.
  • the agents in this group a synergistic effect on skin diseases can be expected.
  • the antibacterial agent reaches the affected area of the skin by the internal route, and this antibacterial agent exerts a synergistic antibacterial effect from the external preparation and the pharmacosol applied to the affected area, resulting in an excellent therapeutic effect. Can be given.
  • the present invention is also an invention which provides an antibacterial composition set comprising a pair of an antibacterial composition for internal use containing an antibacterial agent and an antibacterial composition for external use containing huanesol.
  • the general contents of the antibacterial composition for internal use in this antibacterial composition set are the same as those described above in the case where the present antibacterial composition takes the form of an internal medicine, and the general content of the antibacterial composition for external use is as described above. This applies to the case where the present antibacterial composition takes an aspect as an external preparation.
  • the contents of the antibacterial agent and farnesol in the respective preferred agents also conform to the above-mentioned antibacterial agent content when the present antibacterial composition is an internal medicine and farnesol content when it is an external preparation. .
  • the blending amounts are% by mass based on the blending target.
  • Egret plasma was added to Muller-Hinton agar medium (manufactured by Difco).
  • test strain was pre-cultured at 37 ° C for 24 hours, inoculated at about 10 6 cfu / ml, and allowed to stand at 37 ° C for 48 hours.
  • the minimum concentration at which the test strain did not grow under these culture conditions was defined as the MIC.
  • the case where the MIC was 64 // g / ml or more was regarded as the case where the test strain had resistance to the test antibacterial agent.
  • Fosfomycin (Fosfomycin-based IJ)
  • Chloram fuenikonore Chloram fuenikonore
  • the aqueous phase of B was added to the alcohol phase of A and solubilized to obtain a lotion (a)
  • the aqueous phase of B was prepared by heating and dissolving the oil phase of A at 70 ° C and 75 ° C, and the oil phase was added to the aqueous phase and emulsified with a homomixer to prepare an OZW emulsion. Subsequently, the mixture was stirred and cooled while being subjected to a homomixer treatment from 70 ° C. to obtain an emulsion.
  • a cream was obtained according to the method for producing an emulsion of Example 2.
  • a means capable of coping with resistant bacteria with a conventional antibacterial agent is provided.

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Abstract

It is found out that by using an antibacterial agent in combination with farnesol, the antibacterial effect can be synergistically improved and an antibacterial effect can be exerted on tolerant bacteria and the like even by an antibacterial agent inherently showing no effect. Namely, antibacterial compositions wherein an antibacterial agent such as an antibiotic is used in combination with farnesol having been employed as an antibacterial perfume.

Description

明細書 抗菌組成物 技術分野  Description Antimicrobial composition Technical field
本発明は、 抗菌組成物に関する発明である。 背景技術  The present invention relates to an antimicrobial composition. Background art
従来から、 病原性菌に対する対処は、 抗生物質等の抗菌剤の使用に頼っている 面が強い。 その一方で、 抗菌剤の乱用により、 抗菌剤に耐性を有する、 MR S A 等の耐性菌が出現し、 治療を難航させている。 現在まで、 新薬の開発、 耐性菌の 出現、 使用薬剤の使用濃度の上昇、 耐性菌の出現、 という悪循環が、 延々と繰り 返されており、 危機的な状況に陥っている。  Traditionally, measures against pathogenic bacteria have relied heavily on the use of antibacterial agents such as antibiotics. On the other hand, abuse of antibacterial agents has led to emergence of resistant bacteria, such as MRSA, that are resistant to antibacterial agents, making treatment difficult. Until now, the vicious cycle of the development of new drugs, the emergence of resistant bacteria, the increase in the concentration of drugs used, and the emergence of resistant bacteria has been repeated endlessly, and has entered a crisis situation.
そこで、 本発明が解決すべき課題は、 耐性菌に対しても、 従来の抗菌剤で対処 可能な手段を見出すことにある。 発明の開示  Therefore, the problem to be solved by the present invention is to find a means that can treat resistant bacteria with conventional antibacterial agents. Disclosure of the invention
本発明者は、 この課題の解決に向けて、 鋭意検討を重ねた結果、 抗生物質等の 抗菌剤と抗菌香料として用いられているフアルネソールを組み合わせた抗菌組成 物は、 相乗的に抗菌効果が向上し、 驚くべきことに、 耐性菌等に対して、 本来は 効果が認められない抗菌剤との組合せにおいても抗菌効果を発揮することを見出 し、 本発明を完成した。  The present inventors have conducted intensive studies to solve this problem, and as a result, the antibacterial composition combining antibacterial agents such as antibiotics and fuarnesol used as an antibacterial fragrance synergistically improves the antibacterial effect. Surprisingly, it has been found that an antibacterial effect can be exerted against a resistant bacterium even when used in combination with an antibacterial agent which is originally not effective. Thus, the present invention has been completed.
すなわち、 本発明は、 フアルネソールおよび抗菌剤を含有する抗菌組成物 （以 下、 本抗菌組成物ともいう） を提供する発明である。 発明を実施するための最良の形態  That is, the present invention is an invention which provides an antibacterial composition containing fuarnesol and an antibacterial agent (hereinafter, also referred to as the present antibacterial composition). BEST MODE FOR CARRYING OUT THE INVENTION
以下、 本発明の実施の形態を説明する。  Hereinafter, embodiments of the present invention will be described.
本抗菌組成物の一方の必須含有成分は、 ブアルネソール （3 , 7 , 1 1—トリ メチル _ 2， 6 , 1 0—ドデカ トリェン一 1一オール） である。 フアルネソール は、 ネロリ油、 イランイラン油等に含まれる成分で、 抗菌合成香料として用いら れており （市販品入手も可能） 、 新鮮なグリーンノートでフローラル様の香気を 持ち、 香粧品への配合が認められる。 One essential ingredient of the antimicrobial composition is buarnesol (3,7,11-trimethyl_2,6,10-dodecatrien-l-l-ol). Huarnesol Is a component contained in neroli oil, ylang-ylang oil, etc., and is used as an antibacterial synthetic fragrance (a commercial product is also available). It has a fresh green note with a floral-like scent, and can be used in cosmetics. Is recognized.
また、 本抗菌組成物の他方の必須含有成分である抗菌剤は、 抗生物質であって も、 合成抗菌剤であってもよい。  The antibacterial agent, which is the other essential component of the antibacterial composition, may be an antibiotic or a synthetic antibacterial agent.
例えば、 ペニシリン、 アンピシリン、 セフジニル、 セファロスポリン等の ]3— ラクタム系剤；ネオマイシン、 パロモマイシン、 リビドマイシン、 カナマイシン、 ベカナマイシン、 ディべカシン、 トブラマイシン、 アミカシン、 ゲンタマイシン、 ス トレプトマイシン、 リボスタマイシン、 ピオマイシン、 トウブラァクチノマイ シン、 スぺクチノマイシン、 カスガマイシン等のアミノ配糖体系剤； シノキサシ ン酸、 ナリジタス酸、 エノキサシン、 ピぺミ ド酸、 ノノレフロキサシン、 オフロキ サシン、 ジプロフロキサシン、 スバルフロキサシン、 トシノレ酸トスフロキサシン、 フレロキサシン等のピリ ドンカルボン酸系剤又はキノロン系剤 ； エリスロマイシ ン、 キタサマイシン等のマクロライ ド系剤 ； クロルテ トラサイク リン、 ォキシテ トラサイクリン、 テ トラサイクリン、 ドキシサイクリン、 ミノサイクリン等のテ トラサイクリン系剤 ； ホスホマイシン等のホスホマイシン系剤 ； ク口ラムフエ二 コール等のクロラムフエ二コール系剤 ； リンコマイシン、 クリンダマイシン等の リンコマイシン系剤；ポリミキシン B、 バンコマイシン等のポリべプチド系剤； ムピロシン等を挙げることができるが、 これらに限定されるものではない。  For example, penicillin, ampicillin, cefdinir, cephalosporin, etc.] 3-lactams; neomycin, paromomycin, ribidomycin, kanamycin, bekanamicin, dibekacin, tobramycin, amikacin, gentamicin, streptomycin, ribostamycin Aminoglycoside agents such as piomycin, tobacactinomycin, succinomycin, kasugamycin; sinoxacinic acid, naliditasic acid, enoxacin, pidmidic acid, nonolefloxacin, ofloxacin, diprofloxacin Pyridonecarboxylic acid or quinolone such as subarufloxacin, tosfloxacin tosinoleate, and fleroxacin; macrolides such as erythromycin and kitasamycin; chlorte torasa Tetracycline-based agents such as Iculin, Oxytetracycline, Tetracycline, Doxycycline, Minocycline; Fosfomycin-based agents such as Fosfomycin; Chloramphenicol-based agents such as Kuguchiramphenicol; Lincomycin-based agents; polypeptides such as polymyxin B and vancomycin; mupirocin; and the like, but are not limited thereto.
抗菌剤は、 1種を用いることも可能であり、 2種以上を組み合わせて用いるこ ともできる。  One antibacterial agent can be used, or two or more antibacterial agents can be used in combination.
本抗菌組成物は、 全ての細菌類や黴類を適用対象とすることが可能である。 特 に、 スタフイロコッカス（Staphyl ococcus) 属ゃス 卜レフ 卜コッカス  The present antimicrobial composition can be applied to all bacteria and fungi. In particular, Staphylococcus (Staphyl ococcus)
(Streptococcus) 属に属する細菌類、 例えば、 黄色ブドウ球菌（Staphylococcus aureus) 、 コアグフ— i 陰†生フ、 'ドウ球菌 (coagulase— negat ive Staphylococci： Bacteria belonging to the genus (Streptococcus), for example, Staphylococcus aureus, Coagul-i, Sinus larva, and 'coagulase-negative Staphylococci:
CNS)、 A群化膿レンサ球菌（Streptococcus pyogenes)等に対して有効である。 殊 に、 耐性菌 （MR S A、 V R S A等） による、 深刻な院内感染等の原因菌として 知られている黄色ブドウ球菌を好適な適用対象とすることができる。 CNS), effective against group A Streptococcus pyogenes, etc. In particular, Staphylococcus aureus, which is known as a causative bacterium of serious nosocomial infections due to resistant bacteria (MRSA, VRSA, etc.), can be a suitable target.
なお、 本発明においては、 抗菌剤として、 塩化ベンザルコニゥム、 ダルコン酸 クロルへキシジン （前 2剤の本抗菌組成物における含有量は、 剤に対して 1〜5 0 %程度が好適である） 、 ポピヨンョード （本抗菌組成物における含有量は、 剤 に対して 1〜1 0 %程度が好適である） 等の殺菌消毒剤を用いて、 皮膚の消毒や、 医療器具等の消毒目的の抗菌組成物として用いることも可能である。 In the present invention, as antibacterial agents, benzalkonium chloride, dalconic acid Chlorhexidine (the content of the first two agents in the present antibacterial composition is preferably about 1 to 50% based on the agent), popyondo (the content in the present antibacterial composition is 1 to It is also possible to use a germicidal disinfectant (such as about 10%) as the antibacterial composition for the purpose of disinfecting the skin or disinfecting medical instruments.
( 1 ) 本抗菌組成物の態様として、 まず、 外用剤としての態様を挙げることが できる。 特に、 バイオフィルム形成菌は、 例えば、 傷口や火傷箇所に定着しつつ、 バイオフィルムを形成して、 治療に対して抵抗性を表し、 最悪の場合、 薬剤耐性 菌に置き変わって非常に厄介な状況になってしまうことが認められている。  (1) As an embodiment of the present antibacterial composition, first, an embodiment as an external preparation can be mentioned. In particular, biofilm-forming organisms, for example, form biofilms that settle in wounds and burns, exhibiting resistance to treatment, and in the worst case replace drug-resistant organisms, which is very troublesome. It has been acknowledged that the situation will end up.
そこで、 本抗菌組成物を、 まず、 皮膚上の目的箇所 （傷口や火傷箇所） に用い て、 目的箇所の治癒を早め、 耐性菌の出現も抑制することが可能である。  Therefore, it is possible to use the antibacterial composition at a target site (a wound or a burn site) on the skin first to accelerate the healing of the target site and to suppress the emergence of resistant bacteria.
外用剤の態様の本抗菌組成物におけるフアルネソールの含有量は、 自由に選択 をすることが可能であるが、 通常、 剤に対して 0 . 0 0 0 1〜 1 0質量％程度が 好ましい。 フアルネソールの含有量が、 剤に対して 0 . 0 0 0 1質量。 /0未満であ ると、 一般的に、 十分な抗菌剤との相乗的抗菌効果を発揮させることが困難であ り、 同 1 0質量％を超えて配合しても、 配合量の増大に見合った抗菌効果の向上 を期待できない。 Although the content of fuarnesol in the present antibacterial composition in the form of an external preparation can be freely selected, it is usually preferably about 0.001 to 10% by mass based on the preparation. The content of fuarnesol is 0.00001 mass based on the preparation. / 0 below the Der Ru, generally sufficient difficult der to exert a synergistic antibacterial effect with the antimicrobial agent is, even though the amount is more than the 1 0% by weight, the increase of the amount It cannot be expected that the antibacterial effect will be improved accordingly.
また、 外用剤の態様の本抗菌組成物における抗菌剤の含有量は、 外用剤として、 皮膚に塗布した場合に、 抗菌剤の有効量が患部に塗布される含有量に設定するこ とが好適である。 具体的には、 用いる抗菌剤の種類や、 抗菌目的となる主要な細 菌の種類等に応じて、 一般的には、 剤に対して 0 . 0 1〜 1 0質量％程度の範囲 で含有させることが好適である。  In addition, the content of the antibacterial agent in the present antibacterial composition in the form of an external preparation is preferably set to a content at which an effective amount of the antibacterial agent is applied to the affected area when applied to the skin as an external preparation. It is. Specifically, depending on the type of antibacterial agent to be used and the type of main bacteria for antibacterial purposes, the content is generally in the range of about 0.01 to 10% by mass of the agent. It is preferred that
( 2 ) 本抗菌組成物は、 内服剤の態様もとり得る抗菌組成物である。 この態様 の抗菌組成物においては、 内服を行うことによって期待される抗菌剤の抗菌効果 力 S、 フアルネソールとの組合せにより、 抗菌効果が増強され、 病原菌による各種 の内科疾患や皮膚疾患に対して有効であると考えられる。 特に、 耐性菌による疾 患に対する効果が期待できる。  (2) The present antibacterial composition is an antibacterial composition that can be in the form of an oral agent. In the antibacterial composition of this embodiment, the antibacterial effect of the antibacterial agent expected by oral administration is enhanced by the combination with S and huarnesol, which is effective against various medical diseases and skin diseases caused by pathogenic bacteria. It is considered to be. In particular, it is expected to be effective against diseases caused by resistant bacteria.
内服剤の態様の本抗菌組成物におけるフアルネソールの含有量は、 自由に選択 をすることが可能であるが、 通常、 剤に対して 0 . 0 0 0 1〜5 0質量％程度が 好ましい。 フアルネソールの含有量が、 剤に対して 0 . 0 0 0 1質量％未満であ ると、 一般的に、 十分な抗菌剤との相乗的な抗菌効果を発揮させることが困難で あり、 同 5 0質量％を超えて配合しても、 配合量の増大に見合った抗菌効果の向 上を期待できない。 また、 内服剤の態様の、 本抗菌組成物における抗菌剤の含有 量は、 剤に対して 0 . 0 1〜2 0質量％程度が好ましい。 抗菌剤の含有量が、 剤 に対して 0 . 0 1質量％未満であると、 一般的に、 十分なフアルネソールとの相 乗的な抗菌効果を発揮させることが困難であり、 同 2 0質量％を超えて配合して も、 配合量の増大に見合った抗菌効果の向上を期待できない。 Although the content of fuarnesol in the present antibacterial composition in the form of an oral preparation can be freely selected, it is usually preferably about 0.001 to 50% by mass relative to the preparation. The content of funaresol is less than 0.001% by mass with respect to the agent. Therefore, in general, it is difficult to exhibit a synergistic antibacterial effect with a sufficient antibacterial agent, and even if the amount exceeds 50% by mass, the antibacterial effect is commensurate with the increased amount. No improvement can be expected. Further, the content of the antibacterial agent in the present antibacterial composition in the form of an internal preparation is preferably about 0.01 to 20% by mass based on the preparation. If the content of the antibacterial agent is less than 0.01% by mass with respect to the agent, it is generally difficult to exert a synergistic antibacterial effect with sufficient funaresol. %, The antibacterial effect cannot be expected to increase in proportion to the increase in the amount.
本抗菌組成物の使用量は、 患者の症状や剤の使用形態や剤形等に応じて適宜選 択することが可能である。 本抗菌組成物が外用剤の場合には、 一般的には、 有効 成分であるフアルネソールと抗菌剤が、 一日成人当り、 約 0 . 0 0 0 0 1〜0 . l g 程度が皮膚に塗布されるように、 一日 1回又は数回に分けて用いるのが好適 である。 また、 本抗菌組成物が内服剤の場合には、 一般的には、 有効成分である フアルネソールと抗菌剤が、 一日成人当り、 約 0 . 0 0 0 0 1〜0 . l g程度が 内服されるように、 一日 1回又は数回に分けて用いるのが好適である。  The amount of the antimicrobial composition used can be appropriately selected according to the patient's condition, the use form and dosage form of the agent, and the like. When the antibacterial composition is an external preparation, generally, about 0.001 to 0.1 lg of the active ingredients funaresol and the antibacterial agent are applied to the skin per adult per day. As described above, it is preferable to use once or several times a day. In addition, when the antibacterial composition is an oral preparation, generally, about 0.001 to 0.1 lg of the active ingredients funaresol and the antibacterial agent are administered per adult per day. As described above, it is preferable to use once or several times a day.
外用剤としての本抗菌組成物の剤形や製品形態は、 外用剤がとりえる全ての剤 形や製品形態、 具体的には、 ローション剤、 ゲル剤、 乳液剤、 クリーム剤、 軟膏 剤、 粉末剤、 洗浄剤、 入浴剤、 スプレー剤等を選択することができる。 また、 点 鼻剤や点耳剤として用いることもできる。  The dosage form and product form of the antimicrobial composition as an external preparation include all the dosage forms and product forms that the external preparation can take, specifically, lotions, gels, emulsions, creams, ointments, and powders. Agents, cleaning agents, bath agents, spray agents, etc. can be selected. It can also be used as nasal drops and ear drops.
力、かる剤形や製品形態に応じて、 外用剤として用いる本抗菌組成物には、 通常 公知の基剤成分、 例えば、 油分、 界面活性剤、 高級アルコール、 防腐剤、 保湿剤、 増粘剤、 キレート剤、 色素、 香料等を配合することができる。  The antimicrobial composition used as an external preparation according to the strength, the dosage form and the product form usually contains known base components such as oils, surfactants, higher alcohols, preservatives, humectants, and thickeners. , A chelating agent, a coloring matter, a fragrance, and the like.
また、 内服剤としての本抗菌組成物の剤形や製品形態は、 内服剤がとりえる全 ての剤形や製品形態、 具体的には、 錠剤、 粉末剤、 顆粒剤、 丸剤等の固剤や液剤、 懸濁剤、 乳剤等の注射剤とすることができる。 また、 用時調製剤とすることも可 能である。  The dosage form and product form of the antibacterial composition as an oral preparation include all dosage forms and product forms that the oral preparation can take, specifically, tablets, powders, granules, pills, and the like. It can be made into injections such as preparations, solutions, suspensions and emulsions. In addition, it can be used as a preparation at the time of use.
かかる内服剤の剤形に応じて、 この態様の本抗菌組成物には、 通常公知の医薬 製剤担体、 例えば、 充填剤、 増量剤、 結合剤、 付湿剤、 崩壊剤、 界面活性剤等の 賦形剤や希釈剤等を自由に選択して配合することができる。  Depending on the dosage form of such an internal preparation, the present antibacterial composition of this embodiment may contain a generally known pharmaceutical carrier such as a filler, a bulking agent, a binder, a moisturizer, a disintegrant, a surfactant, and the like. Excipients and diluents can be freely selected and blended.
この内服剤態様の本抗菌組成物は、 その態様に応じて適切な投与経路、 例えば、 注射剤形態の場合には、 静脈内、 筋肉内、 皮下、 皮内、 腹腔内投与等により、 固 剤形態の場合には、 経口や経腸投与等により投与され得る。 The antibacterial composition in the form of an internal medicine may be administered by an appropriate route of administration depending on the embodiment, for example, In the case of injection, it can be administered by intravenous, intramuscular, subcutaneous, intradermal, intraperitoneal administration and the like, and in the case of solid form, it can be administered by oral or enteral administration.
なお、 フアルネソール製剤と抗菌剤とを別々の薬剤として投与して、 本抗菌組 成物に準じた、 相乗的な抗菌効果をあげることも可能である。 この場合の典型的 な態様として、 フアルネソールを含有する外用剤と抗菌剤を含有する内服剤の組 があげられる。 この組となった剤を用いることにより、 皮膚疾患に対する相乗的 な効果を期待することができる。 すなわち、 抗菌剤が内服ルートにより、 皮膚の 患部に到達し、 この抗菌剤が、 外用剤から、 患部に塗布されたフアルネソ一ルに より、 相乗的な抗菌効果を発揮して、 優れた治療効果をあげることができる。 本 発明は、 この、 抗菌剤を含有する内服用抗菌組成物とフアルネソールを含有する 外用抗菌組成物の組からなる、 抗菌組成物セットを提供する発明でもある。 なお、 この抗菌組成物セットの内服用抗菌組成物の一般的内容は、 上述した、 本抗菌組成物が内服剤としての態様をとる場合に準じ、 同外用抗菌組成物の一般 的内容は、 上述した、 本抗菌組成物が外用剤としての態様をとる場合に準じる。 また、 抗菌剤とフアルネソールのそれぞれの好適な剤における含有量も、 上述の 本抗菌組成物が内服剤である場合の抗菌剤の含有量と、 外用剤である場合のファ ルネソールの含有量に準ずる。 実施例  In addition, it is also possible to administer the pharmacologic agent and the antibacterial agent as separate agents to achieve a synergistic antibacterial effect according to the antibacterial composition. As a typical embodiment in this case, there is a combination of an external preparation containing funaresol and an oral preparation containing an antibacterial agent. By using the agents in this group, a synergistic effect on skin diseases can be expected. In other words, the antibacterial agent reaches the affected area of the skin by the internal route, and this antibacterial agent exerts a synergistic antibacterial effect from the external preparation and the pharmacosol applied to the affected area, resulting in an excellent therapeutic effect. Can be given. The present invention is also an invention which provides an antibacterial composition set comprising a pair of an antibacterial composition for internal use containing an antibacterial agent and an antibacterial composition for external use containing huanesol. The general contents of the antibacterial composition for internal use in this antibacterial composition set are the same as those described above in the case where the present antibacterial composition takes the form of an internal medicine, and the general content of the antibacterial composition for external use is as described above. This applies to the case where the present antibacterial composition takes an aspect as an external preparation. In addition, the contents of the antibacterial agent and farnesol in the respective preferred agents also conform to the above-mentioned antibacterial agent content when the present antibacterial composition is an internal medicine and farnesol content when it is an external preparation. . Example
以下、 本発明を、 実施例により具体的に説明する。 なお、 配合量は、 特に断わ らない限り、 配合対象に対する質量％である。  Hereinafter, the present invention will be described specifically with reference to examples. Unless otherwise specified, the blending amounts are% by mass based on the blending target.
〔試験例〕 黄色ブドウ球菌に対する感受性試験  [Test Example] Susceptibility test for Staphylococcus aureus
本試験においては、 皮膚病巣部から分離した、 黄色ブドウ球菌  In this test, Staphylococcus aureus isolated from skin lesions
(Staphylococcus aureus) に対する、 抗菌剤の M I C値に与えるフアルネソール の添加の影響を検討した。 (Staphylococcus aureus) was investigated for the effect of the addition of funaresol on the antimicrobial MIC value.
本試験では、 寒天平板法を、 常法に基づき行うことにより、 上記の検討を行つ た。  In this test, the above study was conducted by performing the agar plate method based on the ordinary method.
すなわち、 Mul ler- Hinton 寒天培地（Difco社製） に、 1 0 %のゥサギプラズマ That is, 10% Egret plasma was added to Muller-Hinton agar medium (manufactured by Difco).
(デン力生研社製） を添加したものに、 下記の被験抗菌剤を、 1 2段階の各濃度 (0. 06、 0. 1 2、 0. 25、 0. 5、 1、 2、 4、 8、 1 6、 32、 64、 1 28 g/ml) となるように添加し、 調製した。 フアルネソール CDragoco 社製 ：供試菌株 （皮膚病巣部から分離された黄色ブドウ球菌菌株を 14株） について、 M I C= 1 200 μ g/mlであった） 〕 は、 予め、 Tween 80の 0. 5 %溶液に懸濁 して、 2%溶液として用い、 抗菌剤含有培地に添加する場合は、 100 /ig/ml ( 1/1 2MI C) となるように添加した。 供試菌株は、 3 7 °Cで 24時間前培養 したものを用い、 約 106cfu/ml 接種し、 37°Cで 48時間の静置培養を行った。 供試菌株が、 この培養条件で生育しなくなる最小濃度を M I Cとした。 MI Cが、 64 // g/ml以上の場合を、 供試菌株が、 被験抗菌剤に対して耐性を有する場合と した。 (Manufactured by Den Rikken Co., Ltd.) and the following test antimicrobial agents were added to each of the 12 levels. (0.06, 0.12, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, 128 g / ml). (Fuarnesol manufactured by CDragoco: MIC = 1200 μg / ml for 14 test strains (14 Staphylococcus aureus strains isolated from skin lesions))] was 0.5% of Tween 80 in advance. Suspended in the solution, used as a 2% solution, and added to the antimicrobial-containing medium, it was added at 100 / ig / ml (1 / 12MIC). The test strain was pre-cultured at 37 ° C for 24 hours, inoculated at about 10 6 cfu / ml, and allowed to stand at 37 ° C for 48 hours. The minimum concentration at which the test strain did not grow under these culture conditions was defined as the MIC. The case where the MIC was 64 // g / ml or more was regarded as the case where the test strain had resistance to the test antibacterial agent.
結果を、 第 1表に示す。  The results are shown in Table 1.
被験抗菌剤  Test antibacterial agent
アンピシリン （/3—ラタタム系剤）  Ampicillin (/ 3-ratatum)
セフジニル （ —ラタタム系剤）  Cefdinir (-ratatum-based agent)
ゲンタマイシン （アミノ配糖体系剤）  Gentamicin (aminoglycoside agent)
ホスホマイシン （ホスホマイシン系斉 IJ)  Fosfomycin (Fosfomycin-based IJ)
テトラサイクリン （テトラサイクリン系剤）  Tetracycline (tetracycline-based agent)
クロラムフエニコーノレ （クロラムフエニコーノレ系斉 1」）  Chloram fuenikonore (chloram fuenikonore 1)
エリスロマイシン （マクロライ ド系剤）  Erythromycin (macrolide)
リ ンコマイシン （リ ンコマイシン系剤）  Lincomycin (Lincomycin)
オフロキサシン （ピリ ドンカルボン酸系剤） Ofloxacin (pyridonecarboxylic acid agent)
娘 Daughter
Figure imgf000008_0001
Figure imgf000008_0001
第 1表に示す通り、 黄色ブドウ球菌の供試菌株は、 9種類 · 8系統の抗菌剤の 単独投与において、 さまざまな感受性を示した。 これに対して、 フアルネソール を 100 / g/ml添加すると、 抗菌剤単独投与に対する耐性が認められている供試 菌株においても、 M I Cが最大でも 0. 1 2 jug/mlで、 多くは 0. 06 μ g/ml以 下であり、 著効を示すことが明らかとなった。 As shown in Table 1, the test strains of Staphylococcus aureus showed various sensitivities when administered 9 types and 8 types of antibacterial agents alone. In contrast, Huarnesol Of MIC is 0.12 jug / ml at most, even less than 0.06 μg / ml, even in test strains that have been found to be resistant to antibacterial agent administration when 100 / g / ml is added. It was found to be highly effective.
これにより、 たとえ、 特定の抗菌剤に耐性を獲得している菌株であっても、 そ の抗菌剤にフアルネソールを組み合わせて用いることにより、 抗菌効果が認めら れることが明らかとなった。 特に、 フアルネソールの添加量が、 菌の増殖に影響 しない程度の濃度であっても、 相乗的な抗菌効果が発揮されることが明らかとな り、 抗菌剤とフアルネソールとを組み合わせて含有させることによる、 本抗菌組 成物における優れた抗菌効果が認められた。  This has revealed that even if a strain has acquired resistance to a particular antibacterial agent, the antibacterial effect can be recognized by using the antibacterial agent in combination with farnesol. In particular, it has been clarified that a synergistic antibacterial effect is exerted even when the amount of added funaresol does not affect the growth of bacteria. However, an excellent antibacterial effect of this antibacterial composition was recognized.
以下に、 本抗菌組成物の製剤例を記載する。  Hereinafter, formulation examples of the present antibacterial composition will be described.
〔実施例 1〕 ローション剤  [Example 1] lotion
含有成分 含有量 （質量％)  Ingredients Content (% by mass)
A： 95 %ェタノール 5. 0  A: 95% ethanol 5.0
POE (20) リン酸エステル 1. 5  POE (20) phosphate 1.5
フアルネソール 0. 02  Huarnesol 0.02
防腐剤 適 量  Preservative qs
B ：濃グリセリン 3. 0  B: concentrated glycerin 3.0
キシリ トーノレ 8. 0  Kisiri Tonole 8.0
ゲンタマイシン 0. 1  Gentamicin 0.1
クェン酸 0. 05  Cuic acid 0.05
クェン酸ナトリ ウム 0. 1  Sodium citrate 0.1
精製水 残 量  Purified water balance
<製造方法〉  <Manufacturing method>
Aのアルコール相に、 Bの水相を添加し、 可溶化して、 ローション剤を得た ( The aqueous phase of B was added to the alcohol phase of A and solubilized to obtain a lotion (
〔実施例 2〕 乳液剤 (Example 2) Emulsion
含有成分 含有量 （質量％)  Ingredients Content (% by mass)
A：セタノール 0. 7  A: Cetanol 0.7
グリセリンモノ脂肪酸エステル 1. 6  Glycerin monofatty acid ester 1.6
モノステアリン酸 POE (40) 1. 0 硬化油 2. 0 スクヮラン 8. 0 Monostearic acid POE (40) 1.0 Hardened oil 2.0 Squalane 8.0
酸化チタン 2. 0  Titanium oxide 2.0
シリコン KF— 96 A— 6 2. 0  Silicon KF— 96 A— 62.0
フアルネソーノレ 0. 0 1  Huarnesonore 0.0 1
B ：濃グリセリン 1 0. 0  B: concentrated glycerin 10.0
キシリ トール 5. 0  Xylitol 5.0
カルボキシビ二ルポリマー 0. 3  Carboxyvinyl polymer 0.3
水酸化ナトリウム 適 量  Sodium hydroxide qs
クロラムフエニコーノレ 0. 2  Chloram Huenikonore 0.2
精製水 残 量  Purified water balance
ぐ製造方法 >  Manufacturing method>
Bの水相は 70°Cで、 Aの油相は 75 °Cで加熱溶解して調製し、 油相を水相に 添加し、 ホモミキサーで乳化を行い、 OZW型エマルシヨンを調製した。 引続き 70°Cからホモミキサー処理を行いながら、 攪拌冷却して、 乳液剤を得た。  The aqueous phase of B was prepared by heating and dissolving the oil phase of A at 70 ° C and 75 ° C, and the oil phase was added to the aqueous phase and emulsified with a homomixer to prepare an OZW emulsion. Subsequently, the mixture was stirred and cooled while being subjected to a homomixer treatment from 70 ° C. to obtain an emulsion.
〔実施例 3〕 クリーム剤  [Example 3] Cream
含有成分 含有量 （質量％)  Ingredients Content (% by mass)
A ： セタノ一ノレ 4. 0 A: Setano 1 4.0
ヮセリン 7. 0  Serine 7.0
スクヮラン 1 5. 0  Squalane 15.0
ステアリン酸モノグリセリンエステル 2. 2  Stearic acid monoglycerin ester 2.2
POE (20) ソルビタンモノステアレート 2. 8  POE (20) Sorbitan monostearate 2.8
ビタミン Eニコチネート 2. 0  Vitamin E nicotinate 2.0
ファノレネソーノレ 0. 1  Fano Lene Sonore 0.1
バンコマイシン 0. 1  Vancomycin 0.1
酸化防止剤 適 量  Antioxidant appropriate amount
防腐剤 適 量  Preservative qs
B : グリセリン 10. 0  B: Glycerin 10.0
キシリ トール 1 2. 0 ピロリ ドンカルボン酸ナトリ ウム 1. 0 Xylitol 1 2.0 Sodium pyrrolidonecarboxylate 1.0
精製水 残 量  Purified water balance
ぐ製造方法〉  Manufacturing method>
実施例 2の乳液剤の製造方法に準じて、 クリーム剤を得た。  A cream was obtained according to the method for producing an emulsion of Example 2.
〔実施例 4〕 パウダースプレー  [Example 4] Powder spray
含有成分 含有量 （質量％) 原液： アルミニウムクロロハイ ドレート 30. 0  Ingredients Content (% by mass) Stock solution: Aluminum chlorohydrate 30.0
無水ケィ酸 1 5. 0  Caic anhydride 15.0
タルク 1 5. 0  Talc 15.0
ミ リスチン酸イソプロピル 21. 0  Isopropyl myristate 21.0
ジメチルポリシロキサン 10. 0  Dimethyl polysiloxane 10.0
ソルビタン脂肪酸エステル 3. 0  Sorbitan fatty acid ester 3.0
ファノレネソーノレ 0. 5  Fanorenesoneore 0.5
キシリ トーノレ 5. 0  Kisiri Tonole 5.0
クロラムフエニコーノレ 0. 5  Chloram Huenikonore 0.5
充填処方： 原液 10. 0 Filling formula: undiluted solution 10.0
L P G 90. 0 く製造方法 >  L P G 90.0 Production method>
常法に従い、 パウダースプレーを得た。 産業上の利用可能性  According to a conventional method, a powder spray was obtained. Industrial applicability
本発明により、 耐性菌に対しても、 従来の抗菌剤で対処可能な手段が提供され る。  According to the present invention, a means capable of coping with resistant bacteria with a conventional antibacterial agent is provided.

Claims

請求の範囲 フアルネソールぉよぴ抗菌剤を含有する抗菌組成物。  Claims An antibacterial composition containing pharmasol antibacterial agent.
抗菌剤が、 ；8—ラクタム系剤、 アミノ配糖体系剤、 ピリ ドンカルボン酸系剤、 キノロン系剤、 マクロライ ド系剤、 テトラサイクリン系剤、 ホスホマイシン 系剤、 クロラムフエ二コール系剤、 リンコマイシン系剤、 および、 ポリぺプ チド系剤からなる群から選ばれる 1種または 2種以上の抗菌剤である、 請求 項 1記載の抗菌組成物。 Antibacterial agents include: 8-lactams, aminoglycosides, pyridonecarboxylic acids, quinolones, macrolides, tetracyclines, fosfomycins, chloramphenicol, lincomycins The antibacterial composition according to claim 1, which is one or more antibacterial agents selected from the group consisting of an agent and a polypeptide-based agent.
抗菌剤が、 アンピシリン、 セフジニル、 ゲンタマイシン、 ホスホマイシン、 テトラサイクリン、 クロラムフヱニコー^/、 エリスロマイシン、 リンコマィ シン、 および、 オフロキサシンからなる群から選ばれる 1種または 2種以上 の抗菌剤である、 請求項 1記載の抗菌組成物。 The antibacterial agent is one or more antibacterial agents selected from the group consisting of ampicillin, cefdinir, gentamicin, fosfomycin, tetracycline, chlorampanicol /, erythromycin, lincomacin, and ofloxacin. The antibacterial composition according to the above.
抗菌組成物の製品態様が、 外用組成物である、 請求項 1記載の抗菌組成物。 The antibacterial composition according to claim 1, wherein the product aspect of the antibacterial composition is a composition for external use.
PCT/JP2003/001757 2002-02-22 2003-02-19 Antibacterial compositions WO2003070231A1 (en)

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US8293802B2 (en) 2001-10-23 2012-10-23 The Trustees Of Columbia University Gentle-acting skin-disinfectants and hydroalcoholic gel formulations
US9421263B2 (en) 2003-07-17 2016-08-23 The Trustees Of Columbia University In The City Of New York Antimicrobial compositions containing synergistic combinations of quaternary ammonium compounds and essential oils and/or constituents thereof

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US7563461B2 (en) * 2002-02-07 2009-07-21 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of dermal and mucosal irritation
CA2654132A1 (en) * 2006-06-02 2007-12-13 The Trustees Of Columbia University In The City Of New York Compositions containing zinc salts for coating medical articles
JP2008231058A (en) * 2007-03-22 2008-10-02 Hirosaki Univ Antibacterial agent comprising isoprenoid compound
JP2013099543A (en) * 2012-12-27 2013-05-23 Trustees Of Columbia Univ In The City Of New York Zinc salt composition for coating medical product

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JPH11507356A (en) * 1995-06-07 1999-06-29 アブマックス，インコーポレイティド Use of essential oils to enhance the bioavailability of oral pharmacological compounds
WO1999066796A1 (en) * 1998-06-22 1999-12-29 Wisconsin Alumni Research Foundation Method for sensitizing microbial cells to antimicrobial compounds
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JPS6069015A (en) * 1983-09-27 1985-04-19 Nitto Electric Ind Co Ltd Base for external use preparation
JPH11507356A (en) * 1995-06-07 1999-06-29 アブマックス，インコーポレイティド Use of essential oils to enhance the bioavailability of oral pharmacological compounds
WO1999066796A1 (en) * 1998-06-22 1999-12-29 Wisconsin Alumni Research Foundation Method for sensitizing microbial cells to antimicrobial compounds
JP2002284604A (en) * 2001-03-29 2002-10-03 Shiseido Co Ltd Antibacterial and fungicidal auxiliaries

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8293802B2 (en) 2001-10-23 2012-10-23 The Trustees Of Columbia University Gentle-acting skin-disinfectants and hydroalcoholic gel formulations
US9421263B2 (en) 2003-07-17 2016-08-23 The Trustees Of Columbia University In The City Of New York Antimicrobial compositions containing synergistic combinations of quaternary ammonium compounds and essential oils and/or constituents thereof

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