WO2013083582A1 - Composition antimicrobienne - Google Patents

Composition antimicrobienne Download PDF

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Publication number
WO2013083582A1
WO2013083582A1 PCT/EP2012/074403 EP2012074403W WO2013083582A1 WO 2013083582 A1 WO2013083582 A1 WO 2013083582A1 EP 2012074403 W EP2012074403 W EP 2012074403W WO 2013083582 A1 WO2013083582 A1 WO 2013083582A1
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WO
WIPO (PCT)
Prior art keywords
terpineol
antimicrobial
composition according
fused bicyclic
composition
Prior art date
Application number
PCT/EP2012/074403
Other languages
English (en)
Inventor
Robert Joseph CORNMELL
Megan Anne Diehl
Stephen Golding
John Robert HARP
Ian Peter STOTT
Katherine Mary Thompson
Carol Lynn TRUSLOW
Original Assignee
Unilever N.V.
Unilever Plc
Hindustan Unilever Limited
Conopco, Inc., D/B/A Unilever
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Publication date
Application filed by Unilever N.V., Unilever Plc, Hindustan Unilever Limited, Conopco, Inc., D/B/A Unilever filed Critical Unilever N.V.
Publication of WO2013083582A1 publication Critical patent/WO2013083582A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION 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
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations

Definitions

  • the present invention relates to an antimicrobial composition and a method for disinfection involving the antimicrobial composition. It particularly relates to an antimicrobial composition for personal cleaning, oral care or hard surface cleaning applications.
  • Sanitising and disinfecting soap or cleaning compositions are of great benefit to individuals, since proper use generally may reduce the number of germs and pathogens the individual is exposed to. Thus, such compositions may for instance play an important role in reducing the occurrence and spread of infectious diseases.
  • Sanitising and disinfecting soap compositions comprising chlorine-based antimicrobial agent such as triclosan are known. Such compositions require a rather long contact time to provide efficacious antimicrobial action.
  • users, in particular children do not spend a long time on cleansing and as a result cleaning with such compositions does not provide adequate prevention from surface or topical infection or adequate protection against diseases. The user, in spite of cleaning his hands, is generally likely to end up with relatively inadequate bacterial removal from his skin.
  • the antimicrobial in the compositions are in contact with the substrate for less than a few minutes after which the surface is either wiped off or rinsed with water.
  • These short time scales of cleaning action are ineffective in providing the desired benefit since most known antimicrobials commonly used in such products take many minutes to hours to provide the desired kill of microbes. Therefore, there is a need of providing a composition that -upon application- provides relatively more efficacious antimicrobial action during a relatively short cleaning period, preferably about 30 seconds or less.
  • phenols - even if they are antimicrobially active - may exhibit undesirable side-effects, such as corrosiveness, malodour and irritating or sensitising effects when applied on the human or animal skin.
  • WO 2010/046238 A1 describes an effective antimicrobial composition which provides rapid kill of pathogenic bacteria and which comprises 0.01 to 5% by weight of thymol, 0.01 to 5% by weight of terpineol and a carrier.
  • WO 2010/046238 A1 also discloses a method of disinfecting a surface including the step of applying the above composition to the surface.
  • EP0157436 A1 discloses perfume compositions as well as perfumed products containing at least one naphthol derivative as perfume component, characterised in that they contain at least one dihydro- or tetrahydro-1 -naphthol derivative of the formula
  • dotted lines represent carbon-carbon single or double bonds with the proviso that not more than one of them is a double bond and wherein R1 , R2 and R3 independently are methyl groups or hydrogen atoms.
  • the naphthol-derivatives have a very natural leather-like odour.
  • DE3215341 A1 discloses use of compositions according to the below general formula wherein n is 3 or 4 for controlling dandruff and compositions for the treatment of the scalp and/or cleaning, caring or strengthening of the hair.
  • the compounds have an excellent activity against dandruff and a pleasant odour. They also act as disinfectants.
  • FR 2 697 133 discloses biocidal and/or biostatic compositions, comprising mono- oxygenated sesquiterpenes of general formula Ci 5 H x O, wherein x is between 20 and 26 and aromatic compounds.
  • a particular problem of certain antimicrobial actives, and especially some phenolic compounds such as thymol is that they are generally well-perceptible due to their olfactory properties. Although the latter may - at least for some species - be appreciated in certain fragrance compositions, they are considered too intense by some users when they are applied at concentrations efficacious in rapid disinfection. Additionally, a lower concentration of odoriferous compounds or the availability of antimicrobial compounds that are less or not odoriferous allows greater flexibility to the manufacturer in providing alternative scents to his composition at lower doses. Hence there is a need to provide alternative antimicrobial compositions and methods that preferably require lower concentrations and/or have a more acceptable sensory profile.
  • an object of the invention to provide an antimicrobial composition which gives improved disinfection during cleansing of surfaces of the human body, such as the skin and the oral cavity.
  • compositions comprising selected fused bicyclic phenols and terpineol provide synergistic antimicrobial action.
  • Such compositions provide similarly fast anti-microbial action, at similar concentrations when compared to for instance thymol and alpha-terpineol.
  • combinations of fused bicyclic phenols and terpineol according to this invention are capable of very fast antimicrobial action.
  • complete microbial inactivation could be effected with compositions according to the present invention after a contact time of only 15 seconds.
  • the compositions according to the present invention do not rely on the presence of halogenated phenols for their antimicrobial efficacy.
  • the fused bicyclic phenols of this invention advantageously have an olfactory detection limit that is lower than that of comparable phenolic compounds such as thymol. Accordingly, in a first aspect the invention provides an antimicrobial composition comprising:
  • substituents R 3 , R 4 and the substituent selected from R-i and R 2 that is not a hydroxyl group are independently selected from hydrogen, linear or branched Ci to C 6 alkyl, linear or branched Ci to C 6 alkenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, phenyl, and benzyl; and wherein the bonds a, b, and c are of the order one or two, such that at most one of a, b, and c is of the order two;
  • terpineol is selected from the group consisting of alpha-terpineol, beta- terpineol, gamma-terpineol, delta-terpineol, 4-terpineol, and mixtures thereof.
  • a method of disinfecting a surface comprising the steps of
  • the invention provides the use of a composition according to the invention for improved hygiene.
  • any feature of one aspect of the present invention may be utilised in any other aspect of the invention.
  • the word “comprising” is intended to mean “including” but not necessarily “consisting of” or “composed of.”
  • the term “comprising” is meant not to be limiting to any subsequently stated elements but rather to optionally also encompass non-specified elements of major or minor functional importance. In other words, the listed steps or options need not be exhaustive.
  • Phenol in its strict sense refers to hydroxybenzene (C 6 H 5 OH), but where appropriate the word phenol may in its wider meaning as understood by the skilled person also refer to a member of the class of compounds which comprise at least one such a characteristic hydroxybenzene moiety.
  • disinfection refers to reduction of the number of viable microorganisms in a given medium or on a given surface by physical or chemical means. Typically, disinfection involves the destruction or inactivation of said
  • microorganisms Both animate and inanimate media and surfaces are contemplated.
  • microbicide refers to a compound capable of killing, inhibiting the growth of or controlling the growth of microorganisms at a locus; microbicides include
  • microorganism includes, for example, fungi (such as yeast and mould), bacteria and algae.
  • the antimicrobial composition comprises one or more fused bicyclic phenols, terpineol and a carrier. Various components of the antimicrobial composition are described below.
  • compositions of the present invention are preferred for non-therapeutic use, and more particularly preferred for use in cleaning surfaces of human body including skin, hair or oral cavity or for hard surface cleaning applications.
  • the antimicrobial composition according to the invention comprises 0.001 to 5% by weight of one or more fused bicyclic phenols.
  • the composition comprises preferably 0.005 to 4.5 wt-%, more preferably 0.01 to 4 wt-%, even more preferably 0.02 to 3 wt- %, yet more preferably 0.03 to 2 wt-%, still more preferably 0.04 to 1 wt-%, even more preferably 0.05 to 0.75 wt-% and still more preferably 0.1 to 0.5 wt-% of the one or more fused bicyclic phenols.
  • the minimum preferred concentrations of the one or more fused bicyclic phenols can be higher.
  • compositions according to the invention intended for dilution upon use preferably comprise 0.05 to 4.5 wt-%, more preferably 0.1 to 4 wt-%, even more preferably 0.2 to 3 wt-%, still more preferably 0.4 to 1 wt-%, and still more preferably 0.5 to 1 wt-% of the one or more fused bicyclic phenols.
  • the concentration of the one or more fused bicyclic phenols in the antimicrobial composition is preferably such that, when the composition is diluted or dissolved with a suitable medium during use, the concentration in the diluted or dissolved mixture is still sufficient to be antimicrobially efficacious.
  • the fused bicyclic phenol can be a single compound or may be a mixture of the fused bicyclic phenols as detailed below. In certain preferred embodiments, mixtures of fused bicyclic phenols are preferred, since such mixtures may show increased antimicrobial activity against a wider range of microbes. On the other hand, for reasons including e.g. control over the formulation, it is preferred that in case the composition according to the invention comprises a mixture of such fused bicyclic phenols, the mixture preferably comprises at least 30%, more preferably at least 50%, even more preferably at least 70% and still more preferably at least 90% by weight of one fused bicyclic phenol with respect to the total weight of the one or more fused bicyclic phenols.
  • Thench phenols have the following structure
  • substituents selected from R-i and R 2 are a hydroxyl group; and wherein the substituents R 3 , R 4 and the substituent selected from R-i and R 2 that is not a hydroxyl group, are independently selected from hydrogen, linear or branched Ci to C 6 alkyl, linear or branched Ci to C 6 alkenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, phenyl, and benzyl;
  • bonds a, b, and c are of the order one or two, such that at most one of a, b, and c is of the order two.
  • a cyclopentenyl or cyclohexenyl group if present, comprises a C-C double bond, which may take any position in the ring.
  • a cyclopentenyl group can be a (cyclopent-1 -en-1 -yl)-, a (cyclopent-2-en-1 -yl)-, or a (cyclopent-3-en-1 -yl)- group. It is preferred that the bonds a, b, and c are of the order one.
  • the compounds with a, b, and c are also known as (substituted) tetrahydrophenols or hydroxy-tetralins.
  • substituents R 3 , R 4 and the substituent selected from R-i and R 2 that is not a hydroxyl group are independently selected from hydrogen, linear or branched Ci to C 6 alkyl, linear or branched Ci to C 6 alkenyl, cyclohexyl, phenyl, and benzyl.
  • the one or more fused bicyclic phenols are sufficiently water-soluble.
  • the fused bicyclic phenols are sufficiently water-soluble if they are soluble to at least the minimum concentration required in the antimicrobial composition according to the invention. Therefore, preferably, the substituents R 3 , R 4 and the substituent selected from R-i and R 2 that is not a hydroxyl group, are independently selected from hydrogen, a linear or branched Ci to C 3 alkyl group, a linear or branched Ci to C 3 alkenyl group.
  • the substituents R 3 , R 4 , and the substituent selected from R-i or R 2 that is not a hydroxyl group is not hydrogen. Even more preferably, the substituents R 3 , R 4 and the substituent selected from R-i and R 2 that is not a hydroxyl group are hydrogen. Therefore, it is even more preferred that the one or more fused bicyclic phenols are selected from 5,6,7,8-tetrahydro-1 -naphthol, 5,6,7,8-tetrahydro-2-naphthol,
  • the one or more fused bicyclic phenols are selected from 5,6,7,8-tetrahydro-1 -naphthol and 5,6,7,8-tetrahydro-2-naphthol, and mixtures thereof.
  • some of the fused bicyclic phenols according to the invention have a weaker odour, when compared to that of thymol, or an odour which can be more appreciable to the consumer, when dosed into the compositions according to the invention at efficacious levels. This benefit especially applies to
  • the synergistic mode of antimicrobial action of the fused bicyclic phenols according to the present invention in combination with terpineol is similar for the different respective fused bicyclic phenols.
  • the extent to which the fused bicyclic phenols according to the present invention are soluble in water or in organic solvents may be suitably expressed by the logarithm of the octanol/water partitioning coefficient, log ⁇ P ⁇ .
  • This partition coefficient is a measure for the distribution of a solute between water and octanol at equilibrium.
  • the value of the partitioning coefficient may also be predicted using computational methods. A commonly used predicted value is the so-called AlogP value.
  • a definition and preferred method of calculation of AlogP values is provided in A.K. Ghose, V.N.
  • AlogP values of different compounds can be compared with one another and used to assess the similarity of or difference between different compounds. For instance, phenol has an AlogP value of 1 .59 and thymol has an AlogP value of 3.27. Such comparison may also extend to other properties that are believed to be related to the same molecular properties that are believed to be related to the same molecular properties that underlie the value of AlogP.
  • the fused bicyclic phenols according to the present invention preferably have an AlogP value of between 2.0 and 4.5, more preferably between 2.2 and 4.4, even more preferably between 2.4 and 4.1 and still more preferably between 2.5 and 4.0.
  • Suitable fused bicyclic phenols according to the present invention may be commercially sourced or obtained via synthetic chemical methods. Such methods are generally well- known to the person skilled in the art. For example, methods to prepare the
  • the antimicrobial composition according to the invention comprises 0.001 to 5% by weight of terpineol.
  • the composition comprises preferably 0.005 to 4.5 wt-%, more preferably 0.01 to 4 wt-%, even more preferably 0.02 to 3 wt-%, yet more preferably 0.03 to 2 wt-%, still more preferably 0.04 to 1 wt-%, still more preferably 0.05 to 0.75 wt-% and even more preferably 0.1 to 0.5 wt-% of terpineol.
  • the minimum preferred concentrations of the terpineol can be higher, for the same reasons as for the fused bicyclic phenols.
  • compositions according to the invention intended for dilution upon use preferably comprise 0.05 to 4.5 wt-%, more preferably 0.1 to 4 wt-%, even more preferably 0.2 to 3 wt-%, still more preferably 0.4 to 1 wt-%, and still more preferably 0.5 to 1 wt-% of the terpineol.
  • Any of the concentrations ranges for the terpineol is preferably combined with any of the concentration ranges for the one or more fused bicyclic phenols specified above. Therefore, the antimicrobial composition according to the invention for example comprises: a. 0.01 to 0.4% by weight of the one or more fused bicyclic phenols; and b. 0.05 to 1 % by weight of the terpineol.
  • the terpineol may be a single compound or may be a mixture of the terpineol isomers as detailed below. Mixtures of terpineols are preferred, since such mixtures may show increased antimicrobial activity against a wider range of microbes.
  • the composition according to the invention comprises such a mixture of terpineols, the mixture preferably comprises at least 30%, more preferably at least 50%, even more preferably at least 70% and still more preferably at least 90% by weight of one terpineol isomer with respect to the total weight of the terpineol.
  • said one terpineol isomer is alpha-terpineol.
  • the preferred concentrations ranges of the terpineol are important for the same reasons as the preferred concentration ranges of the one or more fused bicyclic phenols in meeting the desired fast acting antimicrobial kinetics while not being sensorially unpleasant when used in products for personal cleaning, oral care or hard surface cleaning applications.
  • Terpineol exists as different isomers, which all are considered terpineols.
  • the terpineol is selected from the group consisting of alpha-terpineol, beta- terpineol, gamma- terpineol, delta- terpineol, 4- terpineol, and mixtures thereof. More preferably, the terpineol is selected from the group consisting of alpha-terpineol, beta- terpineol, gamma- terpineol, delta- terpineol, and mixtures thereof.
  • the isomeric compounds alpha-terpineol, beta-terpineol and gamma-terpineol are among the most abundant terpineols and often occur together in mixtures. Therefore even more preferably, the terpineol is selected from the group consisting of alpha-terpineol, beta- terpineol, gamma-terpineol, and mixtures thereof.
  • the structures of these isomers are schematically depicted in Table 2 below. Table 2
  • compositions comprising enantiomerically pure radicals, racemic mixtures and other mixtures of different stereoisomers are equally preferable.
  • terpineols are all members of the menthenol class of compounds [A L
  • terpineol Combinations of these terpineol isomers are often found together in nature, because it is generally believed that their biosyntheses proceed via closely related synthetic pathways. Without wishing to be bound by theory, it is believed that the mode of antimicrobial action of these terpineol isomers in combination with the fused bicyclic phenols according to the present invention is similar.
  • the terpineols may also be referred to by the alternative names as detailed below in Table 3.
  • Terpineol may be added to the antimicrobial composition in purified form.
  • pine oil comprising terpineol may be added to the antimicrobial composition while ensuring that terpineol is present in the desired concentration in the composition of the present invention.
  • Carrier
  • the antimicrobial composition according to the invention comprises a carrier.
  • the carrier is preferably selected from the group consisting of water, oil, solvent, inorganic particulate material, starch, air, and mixtures thereof.
  • the carrier is preferably from 0.1 to 99% by weight of the composition.
  • the antimicrobial composition may be in form of a solid, liquid, gel, paste or soft solid and the carrier may be selected by a person skilled in the art depending on the format of the antimicrobial composition.
  • oils examples include mineral oils, oils of biological origin (e.g. vegetable oils), and petroleum-derived oils and waxes.
  • the oils of biological origin are preferably triglyceride-based.
  • the carrier oil is not a perfume oil.
  • the carrier oil preferably does not substantially contribute to the odour of the composition, more preferably it does not contribute to that odour.
  • solvents include alcohols, ethers and acetone.
  • the starch may be natural starch obtained from food grains or may be a modified starch.
  • suitable solvents include, for example, water;
  • glycols including ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol, and polypropylene glycol; glycol ethers; alcohols, such as methanol, ethanol, propanol, phenethyl alcohol and phenoxypropanol; ketones, including acetone and methyl ethyl ketone; esters, including ethyl acetate, butyl acetate, triacetyl citrate, and glycerol triacetate; carbonates, including propylene carbonate and dimethyl carbonate; and mixtures thereof.
  • the solvent is selected from water, glycols, glycol ethers, esters and mixtures thereof.
  • suitable solid carriers include, for example, cyclodextrin, silicas, diatomaceous earth, waxes, cellulosic materials, alkali and alkaline earth (e.g., sodium, magnesium, potassium) metal salts (e.g., chloride, nitrate, bromide, sulfate) and charcoal.
  • Air can for instance be used as a carrier when the fused bicyclic phenols according to the invention and/or the terpineol are atomised or otherwise dispersed as a fine mist.
  • the antimicrobial composition may be formulated with either an aqueous base or an oil/solvent base.
  • Compositions with an aqueous base may also for instance be products in gel format.
  • Compositions with a oil/solvent base may for instance be products in anhydrous stick form or propellant-containing products.
  • the antimicrobial composition may for instance, preferably be an antimicrobial anhydrous stick personal care composition on an oil/solvent base wherein the composition has a water content of less than 0.01 % by weight, and wherein the composition preferably is free of water.
  • the antimicrobial composition may for instance, preferably be an antimicrobial propellant-drivable personal care composition, also comprising a propellant. Air can also be used as propellant, for instance in the form of compressed or liquefied air.
  • the most preferred product format has an emulsion base (water and/or oil being the carrier) or is capable of forming an emulsion upon dilution, e.g. soap products in liquid, solid, lotion or semisolid form for hand wash, face wash, body wash, or shaving applications; toothpaste/ dentifrices for oral care applications or products for hard surface cleaning in bars or liquids form.
  • the product comprises an emulsion base, it preferably also comprises one or more surfactants as described below.
  • the antimicrobial composition according to the invention preferably comprises from 1 to 80% by weight of one or more surfactants.
  • Surfactants may for instance
  • the antimicrobial composition according to the invention preferably comprises a. 0.001 to 5% by weight of the one or more fused bicyclic phenols according to the invention,
  • the antimicrobial composition comprises from 1 to 80% by weight of one or more surfactants in combination with the one or more fused bicyclic phenols, and the terpineol at their more preferred concentrations as specified above.
  • the surfactants may be chosen from the surfactants described in well-known textbooks like "Surface Active Agents” Vol. 1 , by Schwartz & Perry, Interscience 1949, Vol. 2 by Schwartz, Perry & Berch, Interscience 1958, and/or the current edition of "McCutcheon's Emulsifiers and Detergents” published by Manufacturing Confectioners Company or in "Tenside-Taschenbuch", H. Stache, 2nd Edn., Carl Hauser Verlag, 1981 ; "Handbook of Industrial Surfactants” (4th Edn.) by Michael Ash and Irene Ash; Synapse Information Resources, 2008. Any type of surfactant, i.e.
  • anionic, cationic, nonionic, zwitterionic or amphoteric can be used, the one or more surfactants are anionic, nonionic, or a combination of anionic and nonionic surfactants. More preferably, the one or more surfactants are anionic.
  • a particularly preferred surfactant is soap.
  • Soap is a suitable surfactant for personal washing applications of the antimicrobial composition of the invention.
  • the soap is preferably C 8 -C 2 4 soap, more preferably a Ci 0 -C 2 o soap and most preferably Ci 2 -Ci 6 soap.
  • the soap may or may not have one or more carbon-carbon double bonds or triple bonds.
  • the cation of the soap can for instance be an alkali metal, alkaline earth metal or ammonium.
  • the cation of the soap is selected from sodium, potassium or ammonium. More preferably the cation of the soap is sodium or potassium.
  • the soap may be obtained by saponifying a fat and/or a fatty acid.
  • the fats or oils may be fats or oils generally used in soap manufacture, such as tallow, tallow stearines, palm oil, palm stearines, soya bean oil, fish oil, castor oil, rice bran oil, sunflower oil, coconut oil, babassu oil, palm kernel oil, and others.
  • the fatty acids are derived from oils/fats selected from coconut, rice bran, groundnut, tallow, palm, palm kernel, cotton seed, soyabean, castor etc.
  • the fatty acid soaps can also be synthetically prepared (e.g. by the oxidation of petroleum or by the hydrogenation of carbon monoxide by the Fischer-Tropsch process). Resin acids, such as those present in tall oil, may be used. Naphthenic acids are also suitable.
  • Tallow fatty acids can be derived from various animal sources. Other similar mixtures, such as those from palm oil and those derived from various animal tallow and lard are also included.
  • a typical fatty acid blend consists of 5 to 30%-wt coconut fatty acids and 70 to 95%-wt fatty acids ex hardened rice bran oil. Fatty acids derived from other suitable oils/fats such as groundnut, soybean, tallow, palm, palm kernel, etc. may also be used in other desired proportions.
  • the soap when present in solid forms of the present invention, is preferably present in an amount of 30 to 80%, more preferably from 50 to 80%, and even more preferably 55 to 75% by weight of the composition.
  • the soap, when present in liquid forms of the composition is preferably present in 0.5 to 20%, more preferably from 1 to 10% by weight of the composition.
  • fatty acid glycinates are particularly preferred in skin and hair cleaning compositions, beacause of their mild detergency and highly foaming nature.
  • the fatty acid glycinates are salts of fatty acid amides of glycine, including for example sodium cocoyl glycinate.
  • the fatty amphocarboxylates are amphoteric surfactants including for example sodium lauroamphoacetate (i.e. sodium 2-[1 -(2-hydroxyethyl)-2-undecyl-4,5-dihydroimidazol-1 - ium-1 -yl]acetate).
  • surfactants are derivatives of isethionates, including acylisethionates.
  • the antimicrobial composition of the invention is also useful in hard surface cleaning applications.
  • preferred surfactants are nonionic surfactants, such as C 8 -C 2 2, preferably C 8 -Ci 6 fatty alcohol ethoxylates, comprising between 1 and 8 ethylene oxide groups when the product is in the liquid form.
  • surfactants are preferably selected from primary alkyl sulphates, secondary alkyl sulphonates, alkyl benzene sulphonates, ethoxylated alkyl sulphates, or alcohol ethoxylate nonionic surfactants.
  • the composition may further comprise an anionic surfactant, such as alkyl ether sulphate preferably those having between 1 and 3 ethylene oxide groups, either from natural or synthetic source and/or sulphonic acid. Especially preferred are sodium lauryl ether sulphates. Alkyl polyglucoside may also be present in the composition, preferably those having a carbon chain length between C6 and C16.
  • Other classes of useful surfactants include cationic surfactants, such as long chain quaternary ammonium compounds and amphoteric surfactants such as betaines and alkyl dimethyl amine oxides. Suitable surfactant concentrations in liquid forms of hard surface cleaning application are generally from about from 0.5 to 10%, preferably from 1 to 5 % by weight of the composition.
  • surfactant is preferably present in 5 to 40%, preferably from 10 to 30% by weight of the composition.
  • the antimicrobial composition of the invention is useful in oral care compositions e.g. in a dentifrice/ toothpaste or an oral rinse product.
  • preferred surfactants are anionic, nonionic or amphoteric in nature, preferably anionic or amphoteric.
  • the anionic surfactant is preferably an alkali metal alkyl sulphate, more preferably a sodium lauryl sulphate (SLS). Mixtures of anionic surfactants may also be employed.
  • amphoteric surfactant is preferably a betaine, more preferably an alkylamidopropyl betaine (wherein the alkyl group is a linear Ci 0 -Ci 8 chain), and most preferably is cocoamidopropyl betaine (CAPB).
  • CAPB cocoamidopropyl betaine
  • Suitable surfactant concentrations in oral care application are generally from about 2% to about 15%, preferably from about 2.2% to about 10%, more preferably from about 2.5 to about 5% by weight of the total composition.
  • the antimicrobial compositions include soap, alkyl sulphate or linear alkyl benzene sulphonate as the surfactants. More preferably, the one or more surfactants are selected from the group consisting of soaps, alkyl sulphates and linear alkyl benzene sulphonates.
  • the antimicrobial composition may be in form of a solid, a liquid, a gel or a paste.
  • a person skilled in the art can prepare compositions in various formats by choosing one or more carrier materials and/or surfactant.
  • the antimicrobial compositions of the present invention are useful for cleansing and care, in particular for skin cleansing and skin care. It is envisaged that the antimicrobial composition can be used as a leave-on product or a wash-off product, preferably a wash-off product.
  • the antimicrobial composition of the present invention can also be used for cleansing and care of hard surfaces such as glass, metal, plastic and the like.
  • a particularly preferred carrier is water. When water is present, it is preferably present in at least 1 %, more preferably at least 2%, further more preferably at least 5% by weight of the composition. When water is the carrier, both liquid and solid
  • a preferred liquid antimicrobial composition according to the invention comprises:
  • the liquid antimicrobial composition is useful for skin cleansing, in particular for hand wash or a face wash.
  • a preferred solid antimicrobial composition according to the invention comprises:
  • the solid antimicrobial composition is preferably in form of a shaped solid, more preferably a bar.
  • the solid antimicrobial composition is particularly useful for skin cleansing in particular for hand wash or a face wash.
  • Such a bar-shaped solid antimicrobial composition may for instance be a soap bar.
  • Soap bar compositions are well-known and may be similar to the following non-limiting example composition, comprising 75.6 wt-% of anhydrous sodium soap, 1 .0 wt-% of glycerine, 0.5 wt-% of sodium carbonate, 0.2 wt-% of EHDP (ethane-1 -hydroxy-1 ,1 - disphosphonate) acid, 0.04 wt-% of EDTA (ethylenediaminetetraacetic acid) tetrasodium salt, 8.5 wt-% of hydrated magnesium silicate (Talc), 0.7 wt-% of sodium chloride, 0.05 wt-% of dyes, 0.75 wt-% perfume, 0.05 to 10 wt-% of antimicrobial agents including the fused bicyclic phenols and the terpineol according to the present invention, and water up to 100 wt-%.
  • EHDP ethane-1 -hydroxy-1 ,1 - disphosphonate
  • inorganic particulate material is also a suitable carrier.
  • the antimicrobial composition is in a solid form.
  • the inorganic particulate material is talc.
  • the solid antimicrobial composition is particularly useful as a talcum powder for application on face or body.
  • a solvent different from water is a preferred carrier.
  • alcohol is a preferred solvent.
  • Short chain alcohols -in particular ethanol, propanol, and isopropanol- are particularly preferred as carrier for an antimicrobial wipe or an antimicrobial hand sanitiser composition.
  • Solvents like ethanol and isopropanol generally show antimicrobial efficacy themselves. However, they are also volatile and may readily evaporate during application of the composition. Thus, their levels on the surface that is treated might even reduce until below the minimum level required for antimicrobial action, before the minimum period needed for disinfection has passed. In contrast, the terpineol and the fused bicyclic phenols according to the present invention are much less volatile and may therefore yield prolonged antimicrobial action after applying them to the skin. Additional ingredients
  • the composition may further comprise various additional ingredients known to a person skilled in the art.
  • additional ingredients include but are not limited to: perfumes, pigments, preservative, emollients, sunscreens, emulsifiers, gelling agents, thickening agents, humectants (e.g. glycerine, sorbitol), sequestrants (e.g. EDTA) or polymers (e.g. cellulose derivatives for structuring such as methyl cellulose)
  • humectants e.g. glycerine, sorbitol
  • sequestrants e.g. EDTA
  • polymers e.g. cellulose derivatives for structuring such as methyl cellulose
  • Both terpineol and some of the fused bicyclic phenols according to the invention may contribute to the olfactory properties of the composition.
  • the present invention is directed towards antimicrobial compositions. Therefore, the composition is preferably not a perfume composition, although other perfume components can
  • the inventors have surprisingly found that while one or more of the fused bicyclic phenols according to the present invention alone or the terpineol alone do not individually provide the fast antimicrobial kinetic action, a combination of one or more fused bicyclic phenols and terpineol at the selective concentrations provides a synergistic antimicrobial action which is especially important in a wash off processes where the contact time of the antimicrobial actives with the surface is low, i.e. of the order of less than 5 minutes, preferably less than 2 minutes, further more preferably less than a minute and in many cases less than 15 seconds.
  • the antimicrobial action of two or more active compounds is considered additive if the combined action merely results from the addition of the effects the individual components would have in isolation.
  • the antimicrobial action of two or more active compounds is considered to be synergistic if the combined effect of the two or more compounds is stronger than expected based on the assumption of additivity.
  • the antimicrobial action of the one compound may be enhanced by the action of the other compound and vice versa. Such enhancement may for instance originate from cooperative interplay between the mechanisms of antimicrobial action at the molecular level.
  • Such enhanced antimicrobial action may manifest itself for instance by the fact that lower concentrations of active compounds are required to obtain complete microbial kill, or alternatively, that the same extent of microbial kill is arrived at in a shorter time.
  • an antimicrobial composition comprising two or more active compounds is capable of synergistic antimicrobial action may for instance be determined following the procedures and using the criteria as outlined in Example 1 below.
  • evidence of synergistic antimicrobial action may be provided at concentrations below the minimum biocidal concentrations of each of the components when taken individually. However, it is generally believed that synergistic action can still occur when the concentration of one or more of the active compounds is raised above its minimum biocidal concentration (when taken individually).
  • the antimicrobial composition according to the present invention preferably comprises the one or more fused bicyclic phenols and terpineol according to the invention at concentrations at which they are capable of synergistic antimicrobial action.
  • concentrations of the one or more fused bicyclic phenols and of the terpineol in the antimicrobial composition are preferably such that, when the composition is diluted or dissolved with a suitable medium during use, (e.g. when washing hands with water and a composition according to the invention) the concentration in the diluted or dissolved mixture is still sufficient to be antimicrobially efficacious.
  • the concentrations of the one or more fused bicyclic phenols and the terpineol in the composition are preferably such that upon application, at a given concentration of the one or more fused bicyclic phenols in the application medium (C mec i, phenol), the terpineol is available at at least a minimum medium concentration (C mec i, t er ) or vice versa (i.e. such that at a given C mec i, ter P , a minimum C mec i, phenol is available, sufficient to provided synergistic antimicrobial action).
  • the application medium denotes the medium in which the antimicrobial action desirably takes place.
  • the composition may be a solid soap bar.
  • C CO mp refers to the concentration of the component in the soap bar
  • C mec i refers to the concentration in the lather.
  • the minimum and optimum concentrations may for instance be determined by a protocol as described for Example 1 or by one of the standards as detailed below. It is generally preferred that the concentrations of the one or more fused bicyclic phenols and the terpineol in the composition according to the invention are equal to or higher than the optimal concentrations in the application medium, because in many typical applications, the composition is either used pure or is diluted to form the application medium.
  • Example 1 when for instance antimicrobial action against E. Coli is desired, the data of Example 1 may be used to determine preferable medium concentrations C mec i- For example, in case complete microbial kill is desired in the particular medium and if the fused bicyclic phenol is 5,6,7,8-tetrahydronaphthalen-1 -ol, and C mec i, henol is selected as 0.025 %(w/v), Cmed, ter preferably is at least 0.15 %(w/v) and vice versa.
  • the desired antimicrobial effect may be obtained by selecting a ratio of the respective concentrations of the one or more fused bicyclic phenols and the thymol.
  • a concentration ratio of fused bicyclic phenols to terpineol larger than one is preferred in some applications, whereas a concentration ratio of fused bicyclic phenols to terpineol smaller than one is preferred in others, whereby the concentrations are expressed in %-wt.
  • the antimicrobial composition according to the invention preferably comprises the one or more fused bicyclic phenols and the terpineol in a concentration ratio (fused bicyclic phenols:terpineol) of between 1 :2 and 1 :12, wherein the concentration is expressed as weight percent.
  • the antimicrobial composition according to the invention preferably comprises the one or more fused bicyclic phenols and terpineol in an applicable concentration ratio as specified hereinbelow.
  • the synergistic antimicrobial composition comprises 5,6,7,8-tetrahydronaphthalen-1 -ol and terpineol.
  • a weight ratio of 5,6,7,8-tetrahydronaphthalen-1 -ol to terpineol is from 1/0.25 to 1/1 .5.
  • the synergistic antimicrobial composition comprises 5,6,7,8-tetrahydronaphthalen-2-ol and terpineol.
  • a weight ratio of 5,6,7,8-tetrahydronaphthalen-2-ol to terpineol is from 1/0.1 to 1/1 .5, preferably from 1/0.1 to 1/0.13 or 1/0.19 to 1/1 .5, preferably from 1/0.19 to 1/1 .5.
  • a further additional advantage of the present invention is that it is observed that treatment of a surface with a composition according to the invention comprising one or more fused bicyclic phenols and terpineol, surprisingly enables continued protection of the surface against growth of microbes for a substantial period of time thereafter.
  • compositions suitable in wash-off processes as described above include a surfactant for the cleaning action.
  • a surfactant for the cleaning action.
  • the surfactant alone does not provide the fast antimicrobial kill at the concentration present in wash off processes, it provides for further improvement in extent of reduction in viable microbial counts on the surface in the short period of time when surfaces are washed with a composition comprising one or more fused bicyclic phenols, terpineol and additionally surfactant.
  • surfactant is generally known to be responsible for washing off dirt and also antimicrobial actives used in the composition, in the present invention, it provides a highly useful additional benefit in that it enhances the reduction of viable microbial count in a composition comprising a combination of fused bicyclic phenols and terpineol alone.
  • the composition according to the invention preferably comprises one or more fused bicyclic phenols selected from 5,6,7,8-tetrahydro-1 -naphthol and 5,6,7,8-tetrahydro-2-naphthol. More specifically, it is preferred that in case the composition according to the invention comprises a surfactant selected from cocoyl glycinate and lauroamphoacetate, the fused bicyclic phenol is selected from 5,6,7,8-tetrahydro-1 -naphthol and
  • the invention relates to a method of disinfecting a surface comprising the steps of a. applying a composition according to the invention on to the surface; and b. removing the composition from the surface.
  • the surface is skin.
  • a surface like the hands, face, body, or the oral cavity is contacted with the composition of the invention.
  • the method preferably is a non-therapeutic method of disinfecting a surface.
  • the surface is any hard surface.
  • such hard surfaces are surfaces that commonly require cleaning and preferably also require sanitisation or disinfection.
  • Such surfaces may be found in many household or industrial environments, and may include for example kitchen and bathroom surfaces, table tops, floors, walls, windows, utensils, cutlery, and crockery.
  • Such surfaces may be made from many different materials, including for instance plastics, wood, metal, ceramics, glass, concrete, marble, and painted surfaces.
  • the composition may be applied to the surface by any suitable means known to the skilled person. For instance, a suitable means may be pouring, dropping, spraying or wiping in case of liquid compositions.
  • the method includes diluting or dissolving the composition with a suitable solvent, preferably water, before or whilst applying the composition to the surface.
  • a suitable solvent preferably water
  • Such dissolving is preferred in particular in case the composition is a solid composition.
  • solid compositions may also be directly spread, rubbed, or sprayed, e.g. in the form of a powder.
  • the method according to the first aspect of the present invention also includes the step of removing the composition from the surface.
  • removing the composition also encompasses partially removing the composition, because traces of the composition may remain on the surface. In many typical situations, such as washing of the skin or hard-surface cleaning, it is acceptable or sometimes even desirable if part of the composition - in particular certain active ingredients - remains on the surface.
  • step b preferably involves removing at least 5%, more preferably at least 10%, even more preferably at least 25%, still more preferably at least 50% and yet more preferably at least 75% of the composition by weight.
  • the step of removing the composition comprises rinsing the surface with a suitable solvent or wiping the surface with a suitable wipe, more preferably, this step consists of rinsing the surface with a suitable solvent or wiping the surface with a suitable wipe.
  • the removal step can also include evaporation of part of the composition, for example when the composition comprises volatile components, e.g. solvents.
  • a suitable medium for rinsing the surface is water but it could also be for example a mixture of water and alcohol. It is then rinsed preferably with sufficient amounts of water after a pre-determined period of time to remove any visible or sensory residue of the composition.
  • an alcohol wipe or a water/alcohol impregnated wipe may be used to wipe the surface to be visibly free of the anti-microbial composition.
  • the step of removing the composition e.g.
  • the step of removing the composition from the surface is started out at least 5 seconds, preferably at least 10 seconds, more preferably at least 15 seconds after commencement of the step of applying the composition on the surface, in order to effect optimal antimicrobial action. Combinations of these times into time intervals are preferred too.
  • the step of removing the composition from the surface is started between 2 minutes and 5 seconds, more preferably between 1 minute and 10 seconds, even more preferably between 30 and 10 seconds and still more preferably between 20 and 15 seconds after commencement of the step of applying the composition on the surface (i.e. step a).
  • the invention preferably relates to a method, wherein the disinfection time T of said method is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds; wherein T is defined as the time that elapses from the moment of adding the composition to a microbial culture until the number of microbes per unit volume of the culture is reduced by a factor of 100 000; and wherein the initial number of microbes preferably exceeds about 100 000 000 microbes per millilitre and wherein the composition is preferably a liquid composition.
  • the disinfecting action of the method (as may be expressed in terms of the disinfection time T) is preferably determined according to the protocol of Example 1 as described hereinafter.
  • This test relates to a standardised test environment in which the microbial culture is kept in suspension.
  • a similarly suitable test is the standard suspension method described in European Standard EN 1276, with the proviso that the disinfection time is adapted to suit the above criteria as will be clear to a person skilled in the art.
  • one of the test methods as described in WO 2010/046238 may for instance be applied to establish the disinfecting action.
  • test methods may preferably also be used by the skilled person to determine the optimal concentrations of the one or more fused bicyclic phenols and the terpineol in an antimicrobial composition according to the present invention.
  • the invention preferably relates to a method according to the present invention, wherein the surface disinfection time T2 of said method is less than 60 seconds, preferably less than 15 seconds, wherein T2 is defined as the time starting from the moment of applying the composition to the surface to be disinfected after which the number of microbes per unit area is reduced by a factor of 10000 (i.e. a 4 log reduction), wherein the initial number of microbes preferably exceeds 10 3 , more preferably 10 5 , and even more preferably 10 7 microbes per square centimeter.
  • Such tests may for instance be performed as described in WO 2010/046238, or as described in European Standards EN 13697:2001 and EN 1500:1997.
  • the invention preferably provides for non-therapeutic benefits.
  • the invention relates to use of an antimicrobial composition according to the present invention for faster reduction in viable microbial count.
  • a composition according to the invention for improved hygiene.
  • Such use relates for example to use of an antimicrobial composition comprising the one or more fused bicyclic phenols, terpineol and a carrier, for reduction in viable microbial count, preferably fast reduction of viable microbial count.
  • an antimicrobial composition comprising the one or more fused bicyclic phenols, terpineol and a carrier, for reduction in viable microbial count, preferably fast reduction of viable microbial count.
  • a method for disinfection therefore preferably relates to use for disinfection whereby the disinfection time is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds.
  • the disinfection is preferably defined similar to the disinfection times T and T2 as described above.
  • composition according to the invention for improved hygiene of surfaces of the human body.
  • surfaces include e.g. skin, hands and the oral cavity.
  • the invention relates to use of a
  • composition according to the invention for improved hand hygiene.
  • the invention relates to use of a composition according to the invention for improved oral hygiene.
  • microbicide compositions of the present invention can be used to inhibit the growth of microorganisms by introducing a microbicidally effective amount of the compositions onto, into or at a locus subject to attack.
  • suitable loci include, for example: industrial process water including electrocoat deposition systems, cooling towers and air washers; gas scrubbers; wastewater treatment; ornamental fountains; reverse osmosis filtration; ultrafiltration; ballast water; evaporative condensers and heat exchangers; pulp and paper processing fluids and additives; mineral slurries; starch; plastics; emulsions; dispersions; paints; latices; coatings, such as varnishes; construction products, such as mastics, caulks, and sealants; construction adhesives, such as ceramic adhesives, carpet backing adhesives, and laminating adhesives; industrial or consumer adhesives; photographic chemicals; printing fluids; household and institutional products used in restaurants, healthcare facilities, schools, food processing facilities and farms including
  • the microbicidal compositions of the present invention are used to inhibit the growth of microorganisms at a locus selected from one or more of mineral slurries, pulp and paper processing fluids and additives, starch, emulsions, dispersions, paints, latices, coatings, construction adhesives (such as ceramic adhesives), carpet backing adhesives, photographic chemicals, printing fluids, household and institutional products such as cleaners, sanitizers, disinfectants, wipes, cosmetics, toiletries, shampoos, soaps, detergents, floor polishes, laundry rinse water, metal working fluids, textile products, wood and wood products, agriculture adjuvant preservation, surfactant preservation, diagnostic reagent preservation, food preservation, food, beverage, and industrial process pasteurizers and oil and gas processing fluids.
  • a locus selected from one or more of mineral slurries, pulp and paper processing fluids and additives, starch, emulsions, dispersions, paints, latices, coatings, construction adhesives (such
  • composition according to the invention can in view of the above be applied for disinfection, reduction in viable microbial count or improved hygiene, especially at a surface.
  • the composition is particularly suited for application to the skin.
  • a surface like the hands, face, body, or the oral cavity can suitably be contacted with the composition of the invention.
  • the surface is any hard surface.
  • such hard surfaces are surfaces that commonly require cleaning and often also require sanitisation or disinfection. Such surfaces can be found in many household or industrial
  • compositions can be used for such disinfection, reduction in viable microbial count or improved hygiene at loci other than the surfaces as described hereinbefore.
  • the invention relates to compositions according to the invention for use as or incorporation in home care products and personal care products. More preferably, this embodiment of the invention relates to a composition according to the invention which is a home care product or a personal care product.
  • a "home care product” is a product for the treatment, cleaning, caring or conditioning of the home or any of its contents.
  • the foregoing includes, but is not limited to, compositions, products, or combinations thereof relating to or having use or application in the treatment, cleaning, cleansing, caring or conditioning of surfaces, furniture and atmosphere of the home and household contents, such as clothes, fabrics and/or cloth fibres and the manufacture of all of the foregoing products.
  • a "personal care product” is a product for the treatment, cleaning, caring or conditioning of the person.
  • the foregoing includes, but is not limited to, chemicals, compositions, products, or combinations thereof relating to or having use or application in the treatment, cleaning, cleansing or conditioning of the person (including in particular the skin, hair and oral cavity), and the manufacture of all the foregoing.
  • Home care products and personal care products are for example products marketed under mass market brands, non- limiting examples being soap bars, deodorants, shampoos, and home surface sanitisers/disinfectants.
  • compositions according to the invention for use as or incorporation in industrial and/or institutional products. More preferably, this embodiment of the invention relates to a composition according to the invention which is an industrial and/or an institutional product.
  • institutional products are for example products being marketed under professional brands, non-limiting examples being for industrial, institutional, janitorial, and medical cleaning, cleaning-in-place, food services, veterinary, and agricultural products.
  • Industrial and/or institutional products also include products for cleaning of the person (such as hand sanitisers) for medical offices, hospitals and/or other institutions.
  • the invention also relates to a method or use according to the invention involving home care products or personal care products.
  • the method according to the invention - which comprises application of a composition according to the invention in step a - can be a method wherein that composition is a composition for use as or incorporation in home care products and personal care products as described hereinabove.
  • the invention also relates to a method or use according to the invention involving industrial and/or institutional products.
  • the method according to the invention - which comprises application of a composition according to the invention in step a - can be a method wherein that composition is a composition for use as or incorporation in industrial and/or institutional products as described hereinabove.
  • Products and/or methods for use in the home care or personal care field are generally distinct from products and/or methods for use in the industrial and/or institutional field.
  • a product that is marketed as a home or personal care product will generally not be marketed as a product for industrial and/or institutional use and vice versa. Therefore, certain embodiments of the present invention, when carried forth into practice, will relate to the one field, but not the other.
  • Fused bicyclic phenols were purchased as fine chemicals from suppliers such as Sigma Aldrich, Alfa Aesar and TCI Fine Chemicals.
  • a terpineol mixture comprising ca 88 wt-% of (S)-alpha-terpineol, and 12 wt-% of gamma-terpineol was purchased from Sigma Aldrich and used throughout the examples (being referred to as alpha-terpineol or terpineol) unless specified otherwise.
  • MBC Minimum Biocidal Concentration
  • Fractional Biocidal Concentration (component a tested as a single active)
  • the interactions between antimicrobials can be additive, synergistic or possibly antagonistic depending on whether the efficacy of the combination is equivalent to, greater than or less than that obtained for the same total concentration of the individual components when tested alone.
  • ⁇ FBC ⁇ 1 corresponds to additive or antagonistic bactericidal activity
  • ⁇ FBC ⁇ 1 corresponds to synergistic bactericidal activity
  • Antimicrobial efficacy is tested against a representative pathogenic bacterial organism, Gram negative Escherichia coli. Concentrations of actives are expressed in terms of the percentage weight/volume (%w/v) throughout Example 1 . Bacterial stock
  • the following assay describes the testing of 8 materials using 6 dilutions across half of a 96-well micro titre plate (MTP). Using this approach it is possible to assay 16 actives (without replicates) with one full dilution plate, replicating this set up in two halves of the plate columns, 1 -6 and 7-12.
  • DMSO dimethylsulphoxide
  • composition of the neutralising solution was as follows: pancreatic digest of casein, 5.0g/L; Yeast Extract, 2.5 g/L; Dextrose, 10 g/L, sodium thioglycollate, 1 .0 g/L, sodium thiosulphate, 6.0 g/L; sodium bisulphite, 2.5 g/L; Polysorbate 80, 5.0 g/L; lecithin 7.0 g/L; bromocresol purple, 0.02 g/L with a pH in the range 7.6 ⁇ 0.2.
  • 270 ⁇ of tryptone diluent solution was added to all the remaining wells of the Dilution MTP (columns 2-6).
  • Bacterial stock (30 ⁇ ) was then added to the prepared 270 ⁇ of the solution of actives in the Screening Plate and mixed, using a multichannel pipette with 8 tips to aspirate and dispense the same volume of bacterial stock in parallel to 8 wells in rows A-H. After a contact time of 15 seconds, the mixtures were quenched by transferring 30 ⁇ volumes of the mixtures into the 270 ⁇ D/E neutralising solution in the prepared dilution plate, using aspiration to mix.
  • TSA Tryptone Soya Agar
  • N M BS Mean bacterial survival numbers (expressed in Log CFU/ml) are obtained by first determining the segment of the TSA plate where the number of bacterial colonies is countable. From the colony number in this segment, N M BS is calculated by the formula:
  • N MB s log ⁇ Ncoi - 10 DF - 100 / 3 ⁇
  • N C0 is the colony count
  • DF is the dilution factor taken from the MTP-well corresponding to the TSA plate segment (i.e. DF may range from 1 for the quench, to 6 for the highest dilution).
  • the factor 100/3 is a conversion factor from the volume of the inocula spot to one millilitre.
  • control experiments A, B and D validate a test assay by not showing bacterial kill
  • control experiment C comprising a synergistic combination of thymol and alpha-terpineol according to WO 2010/046238 A1 validates a test assay by showing complete bacterial kill.
  • Table 5 shows the antibacterial activities of the fused bicyclic phenols, both alone and in conjunction with terpineol.
  • Table 5 Antibacterial activities of thymol, and fused bicyclic phenols alone and in combination with terpineol
  • MBCs Minimum Biocidal Concentrations
  • the MBC for an active can be defined as the lowest concentration of the active that provides zero bacterial bacterial survival in the particular medium.
  • Data for examples (1 :1 ) to (1 :3) demonstrate that the MBC value for thymol is 0.05% (w/v).
  • compositions (1 :4) to (1 :7) show that the MBC is 0.4% w/v.
  • Table 6 Minimum biocidal concentrations of antimicrobial components
  • the comparative examples (1 :15) and (1 :16) show that compositions comprising terpineol and fused bicyclic phenolic compounds that are not compounds according to the present invention (1 -naphthol and 2-naphthol, respectively) at concentrations comparable to those in the examples according to the invention do not give rise to fast antimicrobial action.
  • Example 2 shows that compositions comprising terpineol and fused bicyclic phenolic compounds that are not compounds according to the present invention (1 -naphthol and 2-naphthol, respectively) at concentrations comparable to those in the examples according to the invention do not give rise to fast antimicrobial action.
  • Example 2 shows that compositions comprising terpineol and fused bicyclic phenolic compounds that are not compounds according to the present invention (1 -naphthol and 2-naphthol, respectively) at concentrations comparable to those in the examples according to the invention do not give rise to fast antimicrobial action.
  • Example 2 shows that
  • Example 2 a wide range of combinations of chemicals was tested by conducting high resolution MBC assays of fused bicyclic phenols in the presence of various concentrations of terpineol.
  • the materials were sourced in the same way as for Example 1 .
  • Synergy tests were conducted using standard microtiter plate assays with phosphate buffer containing 35% dipropylene glycol (DPG).
  • High resolution MBCs were determined by adding varying amounts of microbicide to one column of a microtiter plate and doing subsequent ten-fold dilutions using an automated liquid handling system to obtain a series of endpoints ranging from 0.002% to 1 % of the test compound.
  • the MBC plate was inoculated one column at a time with the test microorganism.
  • the synergy of the combinations of the present invention was determined against a the same bacterium as in Example 1 , Escherichia coli (£. coli - ATCC #10536), at a concentration of approximately 1 x 10 8 bacteria per ml_.
  • microorganism is representative of natural contaminants in many consumer and industrial applications.
  • the plates were visually evaluated for microbial growth
  • Second Component (B) terpineol
  • the ratios of 5,6,7, 8-tetrahydronaphthalen-1 -ol to terpineol tested ranged from 1/0.025 to 1/400.
  • the synergistic ratios of 5,6,7,8-tetrahydronaphthalen-1 -ol to 2-(4-methyl-1 - cyclohex-3-enyl)propane-2-ol range from 1/0.25 to 1/1.5.
  • Second Component (B) terpineol
  • the ratios of 5,6,7, 8-tetrahydronaphthalen-2-ol to terpineol tested ranged from 1/0.025 to 1/400.
  • the synergistic ratios of 5,6,7,8-tetrahydronaphthalen-2-ol to terpineol range from 1/0.10 to 1/1 .5.
  • Examples 1 and 2 demonstrate that a synergistic antimicrobial effect of fused bicyclic phenols according to the invention and terpineol may be obtained over a wide range of concentrations and ratios.
  • compositions according to the invention comprising fused bicyclic phenols and gamma-terpineol were tested following the same protocol as described for Example 1. The results are presented in Table 10. Table 10 Antibacterial activities of thymol, and fused bicyclic phenols alone and in combination with gamma-terpineol against E. coli
  • Example 3:8 demonstrates that 5,6,7,8-tetrahydronaphthalen-1 -ol and gamma- terpineol are capable of synergistically providing antimicrobial action.
  • Table 11 Extent of synergistic interactions between binary compound mixtures for compositions providing complete bacterial kill against E. coli.
  • the efficacy of combinations of fused bicyclic phenols and terpineol were tested in a surfactant cleansing formulation comprising 2.85% sodium cocoyl glycinate and 1.85% sodium lauroamphoacetate. This corresponds to a 50% in use dilution with water of a typical neat formulation containing 5.7% cocoyl glycinate and 3.7% % sodium lauroamphoacetate during hand washing. Solutions were prepared such that the concentrations of the surfactant components and test actives were 1 .1 times the final desired concentration in order to allow for dilution with the bacterial inoculum in the test. The solutions were manually adjusted to pH 10.0 by dropwise addition of sodium hydroxide solution, as measured with a pH meter at ambient temperature. Solutions of the fused bicyclic phenols and/or terpineols were prepared at a maximum of 24 hours before testing. The same terpineol was used as in Example 1.
  • the efficacy of the combinations of the present invention was determined against the same bacterium as in Example 1 , Escherichia coli (£. coli - ATCC #10536), at a concentration of approximately 1 x 10 8 bacteria per ml_.
  • Tests were conducted using standard microtiter plate assays using an automated liquid handling system. 270 ⁇ of the surfactant test solution was pipetted into each well of the microtitre plate (Nunc F Gamma Irradiated 96F untreated microtitre plates of clear polystyrene) and 30 ⁇ of the bacterial suspension was then added. After exactly 15 seconds of bacterial exposure, a 30 ⁇ volume of bacterial cells was withdrawn and transfered to 270 ⁇ of D/E quench solution. After 5 minutes in the D/E quench, the optical density (OD) was measured for each plate in turn at two specific wavelengths (450nm and 590nm).
  • OD 450 increases by less than 0.2 absorbance unit (AU) on incubation and (2).
  • OD 590 decreases by less than 0.35 AU on incubation.
  • test system allows bacterial growth and is not deemed efficacious.
  • Four replicate measurements in the same plate have been made for each test system. The number of replicate wells showing either bacterial growth or no growth is also readily assessed by eye by following the colour change. Thymol and terpineol were tested both alone and in combination for comparison purposes.
  • N rep No. of replicates showing growth (out of 4)
  • Table 13 Minimum biocidal concentrations of antimicrobial components in 2.85% sodium cocoyl glycinate + 1 .85 % sodium lauroamphoacetate solution at pH 10
  • the surfactants used are not themselves antimicrobially active against E. coli at the concentrations employed as shown by the results of Ex. (4:1 ) in Table 12. Thus, any antimicrobial efficacy can be ascribed to the fused bicyclic phenols and/or terpineol.
  • Table 13 presents MBC-values determined similarly as described for Example 1. The tested fused bicyclic phenols have an MBC higher than the highest tested
  • fused bicyclic phenols according to the invention and in particular 5,6,7,8-tetrahydronaphthalen-1 -ol and 5,6,7,8-tetrahydronaphthalen-2-ol show enhanced antimicrobial action in combination with terpineol in the presence of surfactant, in particular cocoyl glycinate and lauroamphoacetate.

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  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Cosmetics (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

La présente invention concerne une composition antimicrobienne et un procédé de désinfection mettant en oeuvre la composition antimicrobienne. Elle concerne en particulier une composition antimicrobienne pour l'hygiène personnelle, les soins buccaux, ou des applications de nettoyage de surfaces dures. Il a été découvert que des compositions comprenant un ou plusieurs phénols bicycliques fusionnés, le terpinéol et un support présentent une action antimicrobienne synergique. Dans un aspect préféré, la composition comprend également 1 à 80% en poids d'un ou de plusieurs tensioactifs.
PCT/EP2012/074403 2011-12-06 2012-12-05 Composition antimicrobienne WO2013083582A1 (fr)

Applications Claiming Priority (4)

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US201161567388P 2011-12-06 2011-12-06
US61/567,388 2011-12-06
EP12173836.3 2012-06-27
EP12173836 2012-06-27

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WO2013083582A1 true WO2013083582A1 (fr) 2013-06-13

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WO2014082854A3 (fr) * 2012-11-29 2014-08-14 Unilever N.V. Compositions de nettoyage antibactériennes douces

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EP0157436A1 (fr) 1984-02-29 1985-10-09 Naarden International N.V. Compositions de parfum et produits parfumés comprenant des dihydro- et/ou tétrahydronaphtols comme agents parfumants
FR2697133A1 (fr) 1992-10-28 1994-04-29 Transbiotech Composition biocide et/ou biostatique et ses applications.
WO2004006876A1 (fr) 2002-07-15 2004-01-22 Unilever Plc Composition pour le traitement des cheveux et/ou du cuir chevelu
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014082854A3 (fr) * 2012-11-29 2014-08-14 Unilever N.V. Compositions de nettoyage antibactériennes douces
US9655866B2 (en) 2012-11-29 2017-05-23 Conopco, Inc. Mild antibacterial cleansing compositions

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