WO2003070231A1 - Compositions antibacteriennes - Google Patents

Compositions antibacteriennes 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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WO
WIPO (PCT)
Prior art keywords
antibacterial
agent
composition
agents
antibacterial composition
Prior art date
Application number
PCT/JP2003/001757
Other languages
English (en)
Japanese (ja)
Inventor
Masako Katsuyama
Hisanori Akiyama
Takashi Oono
Original Assignee
Shiseido Company, 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.)
Filing date
Publication date
Application filed by Shiseido Company, Ltd. filed Critical Shiseido Company, Ltd.
Publication of WO2003070231A1 publication Critical patent/WO2003070231A1/fr

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Classifications

    • 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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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation d'un agent antibactérien combiné avec du farnesol, l'effet antibactérien pouvant être amélioré sur le plan synergique et un effet antibactérien pouvant être exercé sur des bactéries tolérantes et similaire, même par un agent antibactérien qui ne présente pas d'effet de manière inhérente. En outre, cette invention a trait à des compositions antibactériennes, dans lesquelles un agent antibactérien, tel qu'un antibiotique, est utilisé en combinaison avec du farnesol employé comme parfum antibactérien.
PCT/JP2003/001757 2002-02-22 2003-02-19 Compositions antibacteriennes WO2003070231A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002045856A JP2003246726A (ja) 2002-02-22 2002-02-22 抗菌組成物
JP2002-45856 2002-02-22

Publications (1)

Publication Number Publication Date
WO2003070231A1 true WO2003070231A1 (fr) 2003-08-28

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JP (1) JP2003246726A (fr)
WO (1) WO2003070231A1 (fr)

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

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
MX2008015193A (es) * 2006-06-02 2009-04-02 Univ Columbia Composiciones que contienen sales de zinc para recubrir articulos medicos.
JP2008231058A (ja) * 2007-03-22 2008-10-02 Hirosaki Univ イソプレノイド系化合物を含む抗菌剤
JP2013099543A (ja) * 2012-12-27 2013-05-23 Trustees Of Columbia Univ In The City Of New York 医用物品を被覆するための亜鉛塩含有組成物

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6069015A (ja) * 1983-09-27 1985-04-19 Nitto Electric Ind Co Ltd 外用製剤用基剤および外用製剤
JPH11507356A (ja) * 1995-06-07 1999-06-29 アブマックス，インコーポレイティド 経口薬理化合物の生物有用性を高めるためのエッセンシャルオイルの利用
WO1999066796A1 (fr) * 1998-06-22 1999-12-29 Wisconsin Alumni Research Foundation Procede pour sensibiliser des cellules microbiennes vis-a-vis de composes antimicrobiens
JP2002284604A (ja) * 2001-03-29 2002-10-03 Shiseido Co Ltd 抗菌防黴助剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6069015A (ja) * 1983-09-27 1985-04-19 Nitto Electric Ind Co Ltd 外用製剤用基剤および外用製剤
JPH11507356A (ja) * 1995-06-07 1999-06-29 アブマックス，インコーポレイティド 経口薬理化合物の生物有用性を高めるためのエッセンシャルオイルの利用
WO1999066796A1 (fr) * 1998-06-22 1999-12-29 Wisconsin Alumni Research Foundation Procede pour sensibiliser des cellules microbiennes vis-a-vis de composes antimicrobiens
JP2002284604A (ja) * 2001-03-29 2002-10-03 Shiseido Co Ltd 抗菌防黴助剤

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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