GB2357968A - Use of hydroxy diphenylethers as disinfectants - Google Patents

Abstract

Use of hydroxy diphenylethers of the formula shown, wherein R<SB>1</SB>-R<SB>4</SB> are independently of each other hydrogen or C<SB>1</SB>-C<SB>20</SB> alkyl groups, for sanitization and disinfection of skin, mucous membranes and inanimate surfaces. The inanimate surfaces may be selected from textiles, plastics and other hard surfaces. Preferably the compound is 4-(2-tert-butyl-5-methylphenoxy)-phenol, i.e. R<SB>1</SB> is tert-butyl, R<SB>2</SB> and R<SB>4</SB> are hydrogen and R<SB>3</SB> is methyl. Compounds of the formula shown may be incorporated in cosmetic products such as deodorants, skin care lotions and creams, shampoos, shower gels and toothpastes and household products such as all-purpose cleaners and laundry care products. The compounds may be applied to textiles and plastics in a finishing process.

Description

2357968 The use of hydroxy diphenylethers in personal care, household and

laundy care products Hydroxy diphenyiethers as described in patent EP-A-1,053,989, comprising derivatives with the generic formula OH R3 0 R2 RI R4 with OH in o-, m- or p-position and wherein R, - R 4 are independently from each other H, c)-c W-Alkyl (linear, branched, cyclo) (e.g. 4-(2 - tert. -B utyl -5 -m ethyiph enoxy)-p hen ol) have been successfully tested in cosmetic applications such as deodorants (sprays, roll-ons, lotions, creams, powders, sticks), skin care lotions and creams, skin cleaning lotions, sun care products, nourishing cremes, day creams, night creams, after-sun lotions, skin gels, hydrogels, alcoholic skin care gels, foot care products (lotions, cremes, sprays), hair shampoos, hair tonics and rinses, shower gels, baths and oral care products such as toothpastes and mouth rinses.

Other important applications for hydroxy diphenylethers e.g. 4-(2-ter. butyl-5methyl p h enoxy)-ph enol) are cleaning products such as ailpurpose cleaners, dishwashing products, carpet cleaners, bathroom and toilet cleaners and other products for cleaning and disinfection of hard surfaces as well as laundry care products such as powder and liquid detergents and softeners.

Beside a preservative activity in these formulations, the hydroxy diphenylethers have an excellent efficacy against skin bacteria causing body malodour including underarm and foot odour, microorganisms such as Malassezia furfur causing dandruff and bacteria such as Propionibacterium acnes involved in acne. Therefore hydroxydiphenylethers such as 4-(2ter. butyl-S-methylphenoxy)-phenol) are ideal products for anti-dandruff hair care formulations, anti-acne products, deodorising products for skin and foot care and antiseptic and disinfecting products.

Beside of a strong bacteriostatic activity hydroxy diphenylethers have also a good bactericidal activity which makes them suitable for sanitation and disinfection of skin, mucous membranes and inanimate surfaces such as textiles, plastics and other hard surfaces. For applications such as textiles and plastic materials a treatment with the hydroxy diphenylether can be also done by a finishing process, by coating or by incorporation of the antimicrobial before or during the extrusion process.

The efficacy of hydroxy diphenylethers was shown in various in-vitro and in-vivo studies. AS an example for the efficacy of hydroxy diphenylethers tests with 4-(2-tert.-Butyf-Smethyl ph enoxy)-phenol are reported in the following.

As non-ionic substances hydroxy diphenylethers such as 4-(2-tert. - Buty]5 -methyl p hen oxy)phenol can be easily combined with cationic, anionic and non-ionic antimicrobials. For improvement of the antimicrobial activity, combinations with other antimicrobials can be used in order to achieve additional antimicrobial effects or synergistic activity (e.g. expansion of antimicrobial activity profile such as better activity against gram-negative bacteria or better overall bacteriostatic and/or bactericidal activity).

In the following, antimicrobials which can be combined with hydroxy diphenylethers because of additional or synergistic antimicrobial effects are listed exemplary (in most cases the INC1 name of the antimicrobial substances is mentioned):

Typical antimicrobials for combination with hydroxy diphenylethers such as 4-(2-tert.-Butyl5-methylphenoxy)-phenol are:

- formaldehyde and paraformaldehyde - hydroxy biphenyls and its salts such as ortho-phenylphenol - zinc pyrithion - chlorobutanol - hydroxy benzoic acids and their salts and esters such as methyl paraben, ethyl paraben, - propyl paraben, butyl paraben - dibromo hexamidine and its salts including isethionate (4,4'- hexamethylenedioxy-bis(3 --bromo-benzamidine) and 4,4'- h exam ethylen ed ioxy-bis(3-b romo-benzam id in iu m 2hydroxyethanesulfonate) - mercury, (aceto-0)phenyl (i.e. phenyl mercuric acetate) and Mercurate(2-), (orthoboate(3)-0)phenyl, dihydrogene (i.e. phenyl mercuric borate) - 1,3bis(2-ethyihexyi)-hexahydro-5-methyl-S-pyrimidine (Hexetidin) - 5-bromo-Snitro-1,3-dioxan - 2-bromo-2-nitro-1,3-propandiol - 2,4-dichlorobenzy] alcohol - 3,4,4' trichlorocarbanilide (Trichlorcarban) - p-chloro-mcresol - 2,4,4'-trichloro 2-hydroxy diphenylether (triclosan) - 4,4'dichloro 2-hydroxy diphenylether - 4-chloro-3,5-dimethylphenol (Chloroxylenol) - imidazolidinyl urea - poly-(hexamethylene biquanide) hydrochloride - 2-phenoxy ethanol (phenoxyethanol) - hexamethylene tetramine (Methenamine) - 1-(3-chloroaiiyi)-3,5,7-triaza-l-azoniaadam4antanchloride (Quaternium 15) - 1-(4-chlorophenyoxy)-1-(1imidazoiyl)3,3-dimethyi-2-butanone (Climbazole) - 1,3-bis(hydroxymethyi)5,5-dimethyi-2,4-imidazolidinedione (DMDM hydantoin) benzyl alcohol - 1,2dibromo-2,4-dicyano butane - 2,2' methylene-bis(6-bromo-4-chloro phenol) (bromochlorophene) - methylchloroisothiazolone, methylisothiazolone, octylisothiazolone, benzy[isothiazolone - 2-benzyl-4-chlorophenol (Chlorophenone) - chloracetamide - chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride Combinations with chelating agents can also improve the antimicrobial activity of hydroxy diphenylethers. Examples for such chelating agents resulting in additional antimicrobial effects or synergistic activity when combined with hydroxy diphenylethers are ethylene diamine tetra acetic acid (EDTA), beta-alanine diacetic acid (EDETA), hydroxyethylene diamino tetraacetic acid, nitrilotriacetic acid (NTA) and ethylenediamine disuccinic acid (S,SEDDS, R,R-EDIDS or S,R- EDDS).

Also combinations of hydroxy diphenylethers such as 4-(2-ter. Butyl-5methylphenoxy)phenol with perfumes particularly those containing plant derived oils can result in a better antimicrobial efficacy.

Also combinations with natural antimicrobials or chemically modified natural substances with antimicrobial activities such as chitosans and chitosan derivatives, farnesol, plant extracts such as clove oil, blue cypress oil etc. can result in additional antimicrobial effects or even synergistic activities.

The effect against dandruff can be particularly increased by combining the hydroxy diphenylether with other antimicrobials such as zinc pyrithion, octopirox, climbazol, sulfur, or salicylic acid.

Deodorant effects can be improved for example by combinations with farnesol, parfumes, phenoxyethanol, quaternary compounds, triclosan, triclocarban, organic acids such as benzoic acid or sorbic acid, biquanides such as poly-(hexamethylene biguanide) hydrochloride or any other antimicrobial adive listed above.

Combinations with other ingredients in deodorant or antiperspirant formulations such as antiperspirant agents (e.g. aluminium chlorhydrate, zirconium chlorhydrate and other salts of aluminium, zinc and zirconium), alcohol, chelating agents or antioxidants can also result in a better antimicorbial activity of hydroxy diphenylethers such as 4-(2-tert.-Butyl5methyl p h enoxy)-phenol.

Effects against dermatophytes can be for example improved by a combination of the hydroxy diphenylether with 1 0-undecylenic acid, sorbic acid, benzoic acid or salicylic acid.

Effects against acne can be improved by combination of hydroxy diphenylethers with other antimicrobials such as phenoxyethanol, phenoxypropanol, benzaikonium chloride, cetrimonium bromide or benzethonium chloride or salicylic acid.

Bactericidal effects and thus efficacy in antiseptic products for skin and mucous membranes as well as in sanitising and disinfecting products for skin and inanimate surfaces can be improved by combination with other antimicrobiais and biocides such as quaternary compounds such as benzalkonium chloride, cetrimonium bromide or benzethonium chloride, biguanides such as poly-(h exam ethyien e biquanide) hydrochloride, organic acids such as sorbic acid, salicylic acid, benzoic acid, formic acid and propionic acid, formaldehyde, glutaraldehyde or formaldehyde releasers and phenolic antimicrobials such as o-phenylphenol, para chloro metaxylenol (PCMX), p-chlor-m-cresol, 2,4,4'-trichloro 2hydroxy diphenylether (triclosan), 4,4-dichloro 2-hydroxy diphenylether, 4-chloro3,5dimethylphenol (Chloroxylenol), 2,2' methylene-bis(6-bromo-4-chloro phenol) (bromochlorophene), 2-phenoxy ethanol (phenoxyethanol), 2-benzyi4-chlorophenol (Chlorophenone), chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, 1-phenoxy-propane-2ol (phenoxyisopropanol), 3-(4chlorophenoxy)-1,2-propandiol (chlorophenesin) etc.

Products with hydroxy diphenylethers such as 4-(2-ter. Butyi-5methylphenoxy)-phenol can be used in cosmetic and personal care formulations as well as in household products, laundry care products and disinfectants for skin and inanimate surfaces.

Typical product types are gels (aqueous gels and oleogels), emulsions (w/o systems, o/w systems, water in silicone systems), microemulsions, multiple emulsions (o/w/o and w/o/w systems), sprays (with and without alcohol), sticks (based on synthetic and/or natural soaps), powders, anhydrous creams, oils etc.

Such formulations for personal care, household and laundry care applications may contain raw materials such as preservatives, bactericides and bacteriostatic agents (see list above), perfumes, anti- foaming agents, dyes, pigments, thickening agents, moisturizing agents, humectants, fats, oils, waxes or other typical ingredients of cosmetic and personal care formulations as well as household products and laundry care products such as alcohols, poly-alcohols, polymers, foam stabilizers, electrolytes, organic solvents, silicon derivatives, emollients, emulgators, surfactants, UV absorbers, antioxidants, anti-irritants and antiinflammatory agents etc.

Antioxidants can be amino acids or amino acid derivatives, imidazoles and their derivatives, peptides such as D.L-carnosin, carotinoids, carotines and their derivatives, liponic acid, metal chelating agents (such as alpha-hydroxy fatty acids, palmitinic acid, phytinic acid, factoferrine), alpha-hydroxyacids (e.g. citric acid, lactic acid, maleic acid), humic acid, gallate, EDTA, ECTA and their derivatives, unsaturated fatty acids and their derivatives, vitamine C and its derivatives, rutinic. acid and its derivatives, alpha-glycosyl rutin, ferulic acid, butylhydroxytoluol, butylhydroxyanisol and suitable derivatives of these substances. Moreover an antioxidant in such formulations might be tetradibutyl pentaerithrityl hydroxyhydrocinnamate (Tinogard T' TT).

UV absorbers in the formulations might be benzophenone-type substances such as Benzophenone-1, Benzophenone-2, Benzophenone-3 or Benzophenone-4 or benzotriazoltype substances such as: - benzenesulfonic acid, 3-(2Hbenzotriazol-2-yl)-4-hydroxy-5-(1 -methyl p ropyl)-, monosodium salt - 2(5-chloro-2H-benzotriazol-2-yi)-6-(1,1 -dimethylethyi)-4-methyi-phenol (i. e. bumetrizole) - 2-(2H-benzotriazol-2-yi)-6-dodecyl-4-methyl-phenol, branched and linear In emulsions, typical emulgators used are: carboxylic acids and their salts such as palmitinic acid, stearic acid, oleic acid, lauric acid etc.

- alkyl phosphates or phosphoric acid esters such as diethanolamine cetyl phosphate, potassium cetyl phosphate etc. - alkylamines - alkyl imidazolines - ethoxylated amines - quaternary emulgators - sorbitol and sorbitan (polysorbates, sorbitan esters) - sucrose and glucose derivatives such as sorbitan stearate, sucrose cocoate, methyl glucose sesquistearate, methyl glucose dioleate, methyl glucose isostearate - alkanolamides and ethoxylated amides such as PEC-n acyiamides (with n=l - 50) - ethoxylated carboxylic acids or polyethylene glycol esters (PEG-n acylates with n= 1-200) such as fatty alcohol polyglycolethers, laureth-n (with a=l -200) ceteareth-n (with n=l -200), - steareth-n (with n=l -100), oleth-n (with n=l -200) and PEC-n stearate (with n=l -200), PEG-n oieate (with n=l -200), PEG-n cocoate (with n=2-1 50) - polyglyceryl esters and fatty acid esters - dimethicone copolyols such as silicone polyethylene oxide copolymer, silicone glycol copolymer - propoxylated or Polyoxyethylene ethers - polaxamers -polymeric emulsifiers such as acrylate copolymers or crosspolymers and acrylamides or polyacrylamides The lipid phase can be chosen from the following substance groups: mineral oils, mineral waxes oils such as triglycerides of capric and caprylic acid, natural oils such as castor oil fats, waxes and other natural and synthetic fats e.g. esters of fatty acids with short chain alcohols such as isopropanol, propylene glycol or glycerin, or esters of fatty alcohols with fatty acids or carboxylic acids with low number of carbon atoms. alkylbenzoate silicone oils such as dimethylpolysiloxane, diethylpolysiloxane, cliphenylpolysiloxane or mixtures thereof.

The oil phase of emulsions, oleogels, hydrodispersions or lipodispersions can be chosen from the group of esters of saturated and/or unsaturated, branched and/or linear alkane carbonic acids with a chain length of 3 to 30 C-atoms and saturated and/or unsaturated, branched or linear alcohols with a chain length of 3 to 30 C-atoms. from the group of esters of aromatic carbonic acids and saturated and /or unsaturated, branched andlor linear alcohols with a chain length of 3-30 C-atoms.

Examples of such ester oils are isopropyimyristate, isopropylpalmitate, iso p ropylstea rate, isopropyloleate, n-butylstea rate, n-hexyllaurate, n-decyloleate, isooctylstea rate, isononylstearate, isononylisononanoate, 2-ethyllhexylpa Imitate, 2-hexyllaurate, 2h exyid ecylstea rate, 2octyidodecylpaimitate, oleyloleate, oleylerucate, erucyloleate, erucylerucate as well as synthetic, semi-synthetic and natural mixtures of such esters such as jojoba oil.

The oil phase can be also chosen from the group of saturated and unsaturated hydrocarbons and waxes, silicon oils, dialkylethers, the group of saturated, unsaturated, linear or branched alcohols, fatty acid triglyerides e.g. triglycerin esters of saturated andlor unsaturated, linear and/or branched alkane carbonic acids with a chain length of 8-24 C-atoms particularly 12 to 18 C-atoms. The fatty acid triglycerides can be chosen from the groups synthetic, semi-synthetic and natural oils e.g. olive oil, sunflower oil, soy oil, peanut oil, rape-seed oil, palm oil, almond oil, coconut oil and similar oils.

Mixtures of such oil and wax components or waxes such as cetyl palmitate can be used as sole oil phase.

Other preferred ingredients in the oil phase are from the group of 2ethy1h exylisostea rate, octyidodecanol, isotridecylisononanoate, isoeicosane, 2-ethy[hexylcocoate, Cl 2-Cl 5-alkyl benzoate, capryliccaprinic acid -trig lyce rides and dicaprylic ether or mixtures of those ingredients such as mixtures of 2-ethy 1 h exyl isostea rate with Cl 2-Cl 5 alkylbenzoate, mixtures of C] 2-CI5 a I kylbenozoate and isotridecylisononanoate and mixtures of C] 2-CII5 with 2-ethy[hexylisostea rate and isotridecylisononanoate. Moreover cyclic or linear silicone oils can be used and are in some cases the only ingredient in the oil phase. A preferred silicone oil is cyclomethicone (octamethylcyclotetrasiloxane), hexamethylcyclotrisiloxane, polydinnethylsiloxane and poiy(methylphenyisiloxane).

From the hydrocarbons the groups of paraffin oil, squalan and squalene are preferred.

The aqueous phase contains for example ingredients such as alcohols, diols or polyols with a low number of C-atoms or their ethers (e.g. ethanol, isopropanol, propyleneglycol, glyerin, ethylene glycol, ethylene glycol monoethylether, ethylene glycol monobutylether, propylene glycol monomethylether, propylene glycol monoethylether, propylene glycol monobutylether, diethylene glycol monomethylether; diethylene glycol monoethylether, diethylene glycol monobutylether and similar products). lower homologs of alcohols such as ethanol, isopropanole, 1,2dipropandiol, glyerin as well as one or more thickeners for example of the groups of silicium dioxide, aluminium silicates, polysaccharides or derivatives thereof for example hyaluronic acid, xanthan gum, hyd roxypropyimethylcel lu lose, polyacrylates e.g. substances from the Carbopol range (e.g. Carbopol types 980, 981, 1382, 2984, 5984) or Salcare range (Salcare SC80, Salcare SC8], Salcare SC9], Salcare AST, Salcare SC 92, Salcare SC95, Salcare SC96).

The hydroxy diphenyl ethers such as 4-(2-teh.-Buty]-5-methylphenoxy)phenol have a strong antimicrobial activity against oral bacteria and exhibit an anti-plaque effectiveness, anti-gingivitis activities and help to reduce paradontitis. The activity can be improved by combinations with other antimicrobial actives or antiplaque and anti-gingivits actives such as chlorhexidine, quaternary compounds such as cetrimonium bromide, benzalkonium chloride and/or phenolic substances such as 2,4,4, trichloro 2'-hydroxy diphenylether, 4,4'-clichloro 2-hydroxy diphenylether, thymol, and other phenolic compounds having the following generic formula:

OH R 4 2 R3 wherein R 21 R 3 and R4are independently from each other alkyl (branched, cyclo or linear), aryi, 0-aryl, o-alkyl (linear, cyclo, or branched).

Examples are e.g. thymol, 2-tert.-Butyi-S-(4-tert.-butylphenyl)-phenol, 2, 4-di-t-butyl phenol, 2-cyclohexyimethyi-4-t-butylphenol, 2-t-octyi-Scycloh exyim ethyl p he no[, 2-t-butyi-4-(1,1 dimethylpropyl)phenol, 2-tbutyi-4-(1,1-dimethylbutyi)phenol, 2,4-di-t-butyl-5methylphenol, 2-tbuty]-4-(1,1,2,2-tetramethyl pro pyl)-5 -methyl p h enol, 2-t-butyi-4-(], 1,2,2tetra methyl p ropyi)p henol, 2-t-buty]-5-cyclo h exyl methyl phenol, 2-t-butyi-4-n-heptylphenol, 2- iso pro pyl-5 -cycloh exyIm ethyl phenol, 2-isopropyi-4-cyclo h exyl methyl p h enol, 2-cyclohexyl4-n-heptylphenol. Typical oral compositions containing the hydroxy diphenylethers alone or in combinations with one or more of the above mentioned antimicrobials and anti-plaque agents are e.g. mouthrinses, semi-solids such as toothpastes or gel dentifrices, chewing gums or solid lozenge or the like.

Such oral compositions may contain a hydroxy diphenylether compound such as 4-(2-tert.Buty]-5-methylphenoxy)-phenol or a combination of a hydroxy diphenylether compound such as 4-(2-tert.-Butyi-5 -methyl p hen oxy)phenol and one or more of the above mentioned antimicrobial andlor antiplaque compounds. Furthermore the oral composition may contain: polishing agents such as silica gels, colloidal silica or complex amorphous alkali metal aluminosilicate, sodium bicarbonate, sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dehydrated dicalcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, calcium carbonate, aluminium silicate, hydrated alumina, silica, bentonite and mixtures thereof.

- humectants such as glycerin, sorbitol, an alkylene glycol such as polyethylene glycol or propylene glycol and mixtures thereof - water natural or synthetic thickener or gelling agent such as irish moss, iotacarragenan, kappacarrageenan, gum tragacanth, starch, polyvinyl pyrrol id one, hydroxyethyl propyl cellulose, hdroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose and sodium carboxymethyl cellulose. - alcohol such as ethanol or isopropanol organic surface-active agents which can be cationic, anionic or non-ionic. Typical anionic surface-active agents are water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monosulfated monoglycerides of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxy propane sulfonate, and the substantially saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds, such as those having 12 to 16 carbons in the fatty acid, alkyl or acyl radicals and alkoyl taurines, and the like. Examples of the last mentioned amides and taurates are N-lauroyl sarcosine, and the sodium, potassium and ethanolamine salts of N-Jauroy], N-myristoy], or N-palmitoyl sarcosine which should be substantially free from soap or similar higher fatty acid material as well as N-methyl-N-cocoyl (or oleoyl or palmitoyl) taurines. Typical nonionic surface-active agents are cc;ndensated products of ethylene oxide with various reactive hydrogen-containing compounds reactive therewith having long hydrophobic chains (e.g. aliphatic chains of about 12-20 carbon atoms), which condensation products ("ethoxamers")contain hydrophilic polyoxyethylene moieties, such as condensation products of poly(ethyleneoxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitan monostearate) and polypropylene oxide (e.g. Pluronic @ materials). Polyoxamers are e.g. block copolymers of polyoxyethylene and polyoxypropylene having an average molecular weight from about 3000 to 5000 and a preferred average molecular weight from about 3500 to 4000 and containing about 10- 80% hydrophilic polyoxyethylene groups, by weight, of the block copolymer (e.g. Pluronic F1 27). - flavoring agents such as flavoring oils, e.g. oil of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, cinnamo, lemon, orange and methyl salicylate. - sweetening agents such as sucrose, lactose, maltose, xylitol, sodium cyclamate, perillartine, aspartyl phenyl alanine methyl ester, saccharine and the like. - agents used to diminish teeth sensitivity such as strontium chloride, potassium nitrate and potassium citrate. - whitening agents such as urea peroxide and hydrogene peroxide - preservatives such as sodium benzoate - substances which release fluoride ions to protect against caries such as anorganic fluoride salts, e.g. sodium, potassium, ammonium or calcium fluoride or organic fluorides such as amine fluoride. - other agents such as chlorophyll compounds and/or ammoniated materials such as urea, diammonium phosphate and mixtures thereof Antibacterial enhancing agents may be included in the oral composition. Such antibacterial enhancing agents contain a delivery enhancing group (attaches or substantively, adhesively, cohesively or otherwise bonds the antibacterial enhancing agents with the antibacterial and/or anti-plaque agent to the oral (e.g. tooth and gum) surface and a retentionenhancing group (generally a hydrophobic group which attaches or otherwise bonds the antimicrobial and/or anti-plaque agent to the antibacterial enhancing agent). These substances thus deliver the antimicrobial and/or antiplaque agent to the surface and promote retention of the active on the surface which improves the retardation of plaque growth on oral surfaces.

Preferably, the antibacterial enhancing agent is an anionic polymer comprising a chain or backbone containing repeating units each preferably containing at least one carbon atom and preferably at least one directly or indirectly pendent, monovalent delivery-enhancing group and at least one directly or indirectly pendent monovalent retention-enhancing group geminally, vicinally or less preferable otherwise bonded to atoms, preferably carbon, in the chain. The antibacterial enhancing agent may be a simple compound, preferably a polymerizable monomer, more preferably a polymer, including for example oligomers, homopolymers, copolymers, of two or more monomers, ionomers, block copolymers, graft polymers, crosslinked polymers and copolymers, and the like. The antibacterial enhancing agent may be natural or synthetic, and water soluble or preferably water(saliva) soluble or swellable (hydratable, hydrogel forming) having an (weight) average molecular weight of about 100 to about 5,000,000, preferably about 1000 to about 1,000,000, more preferably about 25,000 to 500,000.

In the case of the polymeric antibacterial enhancing agents, it is desirable, for maximizing delivery and retention of the antimicrobial and/or anti-plaque agent to oral surfaces, that the repeating units in the polymer chain or back-bone containing the acidic delivery enhancing groups constitute at least about 10%, preferably at least about 50%, more preferably at least about 80% up to 95% or 100% by weight of the polymer. The antibacterial enhancing agent generally contains at least one delivery-enhancing group, which is preferably acidic such as sulfonic, phosphinic, or more preferably phosphonic or carboxylic, or a salt thereof, e.g. alkali metal or ammonium and at least one organic retentionenhancing group, such typically groups having the formula -(X),-R wherein X is 0, N, S, SO, SO 2/ P, PO or Si or the like, R is hydrophobic alkyl, alkenyi, acyl, aryl, alkary], aralkyl, heterocyclic or their inertsubstituted derivatives, and n is zero or 1 or more. The aforesaid "inertsubstituted derivatives", are intended to include substituents on R which are generally non-hydrophilic and do not significantly interfere with the desired function of the antibacterial enhancing agent as enhancing the delivery of the antimicrobial and/or anti-plaque agent to and retention thereof on oral surfaces such as halo, e.g. Cl, Br, and carbo and the like. Preferably the antibacterial enhancing agent is a natural or synthetic anionic polymeric carboxylate having a molecular weight of about 1000 to about 5,000,000 preferably about 30,000 to about 500.000.

-is- Beside of the ingredients mentioned above, typical surfactant formulations for cleaning and disinfecting skin, hair, mucous membranes and inanimate surfaces (including textile care) may contain the following ingredients:

- anionic, non-ionic, amphoteric, or cationic surfactants - anionic surfactants can be sulfates such as fatty alcohol sulfates, e.g. sulfated laurylaicohoi, fatty acohol ether sulfates such as the acidic esters or their salts of a polymer with 2 to 30 Mol ethylene oxide on 1 Mol eof a C 8 -C 22 -fatty alcohol, alkali metals and/or ammonium salts and/or amine salts of C 8 -C 20 -fatty, alkylamide sulfates. alkylamine sulfates (such as monoethanolamine lauryl sulfate), alkylamide ethersulfate, alkylarylpolyethersulfate, monoglyceride sulfate, alkane sulfonate such as those containing alkyl chains with 8 to 20 carbon atoms (e.g. dodecyl sulfonate), alkylamide sulfonate, Alkylaryisuifonate, cc-olefine sulfonate, suffosuccinate derivatives (e.g. alkyl sulfosuccinate, alkylethersulfosuccinate or alkylsulfosuccinamide derivative) Y N-[alkylamidoalkyi]aminoacids with the formula CH3(CH2)jC0-N with CH-Z-COUM' X is a hydrogen, Cl-C 4-alkyl or -COO-M+, Y is a hydrogen or Cl-C 4-alky], z -(CH2) m -1 1 m is 1 to 5, ni is a number of 6 to 18 and m is an alkali metal- or amine cation, alkyl- und alkylarylethercarboxylates of the formula CH 3 -X-Y-A, with X is a chain with the general formula -(CH,),-,,-0-, -(CH,),,' 0-0- R or -(CH,),,--N R is a hydrogen or C,-C 4-alkyl, Y is -(CHCHO),_,,,-, 0 11..

A is (CH),n,.,-COO-W or -p-om m is a number of 1 to 6 and 2 M is an alkali metal- or amine cation Moreover anionic surfactants can be fatty acid methyl tauride, alkylisothionate, fatty acid polypeptide condensation products and fatty alcohol phosphoric acid esters. The alkyl radicals in the compounds mentioned above have a C-atom number of typically 8 to 24.

Anionic surfactants are usally used as water-soluble salts such as alkali metal salts, ammonium salts or anime salts. Examples for such salts are lithium salts, sodium salts, potassium salts, ammonium salts, triethanolamine salts, ethanolamine salts, diethanolsamine salts ant others. Particularly the sodium salt, potassium salt and ammonium (NR 1 R 2 R)-salt is preferred. R,, R 2 and R 3 can be hydrogen, C JC 4-alkyl or C JC 4_ hydroxyalkyl.

Of particular interest for the formulations are monoethanolamine lauryisulfate or alkali metal salts of fatty alcohol sulfates such as sodium lauryisulfate and sodium lauryiethersulfate.

As amphoteric surfactants C 8 -C 18 -betains, C 8-C Jsulfobetains, C 8-C 24-alkylamido-C 1 -C 4 alkylene betains, imidazoline carboxylates, alkylamphocarboxycarbonic acids, alkylamphocarbonic acid (e.g. lauroamphoglycinate) and N-alkyl-p- aminopropionate or -iminodipropionate can be used. In particular the C 10- C 2,-aikylamidoC,-C 4 -alkylenbetaine and coco fatty acid amide propylbetaine.

Non-ionic surfactants can be e.g. derivatives of adducts of propyleneoxide /ethylene oxide with a molecular weight of 1.000 to 15.000, fatty fatty alcoholethoxylates (1 -50 EO), alkylphenolpolyglykolethers (1 -50 EO), polyglucosides, ethoxylated carbon hydrogens, fatty acid glycol(partiai)esters such as d i ethyleng lycol monostea rate, fatty acid alkanolamides and -dial kano lam ides, fatty acid alkanolamidethoxylate and fatty amineoxide.

Moreover the salts of saturated and unsaturated C B-C 22- fatty acids, alone or in combinations with other substances of this group or combinations with other surfactants mentioned above, can be used. Examples of those fatty acids are capric acid, lauric acid, myristic acid, myristinic acid, palmitinic acid, stearic acid, arachnic acid, behenic acid, caproleinic acid, dodecenic acid, tetradecenic acid, octadecenic acid, oleic acid, eicosenic acid, erucaic acid as well as combinations thereof such as coco fatty acid. The acids can be used in their salt form, e.g. as alkali metal salts such as sodium salts, potassium salts, or metal salts such as Zn and/or aluminium salts or other alkaline reacting, nitrogen-containing organic compounds such as amines or ethoxylated amines. These salts can be also produced in situ.

Examples:

Determination of Minimum InhibitoEX Concentrations (MIC) The minimum inhibitory concentrations (MIC) have been determined using an agar incorporation method. Suspensions of the test bacteria have been dropped on the surface of agar medium which contains a certain concentration of 4-(2-ter. Butyl-5 -methyl ph en oxy)phenol. After incubation, the bacterial growth was assessed. The lowest concentration which showed a full growth inhibition is the minimum inhibitory concentration for this test organism.

The substance shows a strong activity against a broad range of bacteria, yeasts and moulds particularly bacteria involved in underarm and body malodor, pathogenic microorganisms (bacteria, yeats and moulds), aerobic and anaerobic bacteria involved in diseases of the oral cavity and the gum, bacteria and fungi which are involved in pimple generation, acne, athlete's foot, veneral diseases, dandruff and other diseases of the skin, scalp and mucous membranes caused by bacteria, yeasts, dermatophytes or moulds.

Results of MIC determination with 4-(2-tert.-Butyi-S-methylphenoxy)12henol (I1D 166) Substance --- > ID 166 Microorganisms Staphylococcus aureus ATCC 6538 6.75ppm Staphylococcus epidermidis ATCC 12228 3.4ppm Corynebacterium xerosis ATCC 373/ATCC 7711 3.4ppm Staphylococcus hominis DSM 20328 5.Oppm Corynebacterium minutissimum ATCC 23348 3.4ppm Propionibacterium acnes ATCC 11829 5ppm Substance --- > ID 166 Microorganisms Escherichia coli NCTC 8196 >'I 0Opprn Proteus vulgaris ATCC 6896 >] OOPPM Pseudomonas aeruginosa CIP A-22 >II 0Opprn Candida albicans ATCC 10231 12.5ppm Aspergillus niger ATCC 6275 6.75pprn Epidermophyton floccosum CBS 55384 1.65ppm Trichophyton mentagrophytes ATCC 9553 3.4pprn Trichophyton rubrurn DSM 4167 1 Opprn Chaetomium globosum DSM 1962 5.Oppm Paecilomyces variotii ATCC 18502 >loooppm Trichoderma longibrachiatum DSM 768 >]00OPPM Malassezia furfur DSM 6171 2.5ppm Actinomyces viscosum DSM 43329 Sppm Porphyromonas gingivalis DSM 20709 1.25ppm Selenomonas artemidis ATCC 43528 5pprn Streptococcus sobrinus DSM 20742 5pprn Calf skin test Calf skin discs of 2 cm diameter were re-hydrated in water and then immersed in the test formulation. After a 1 minute contact time, the discs were either directly applied on agar plates which contain the test organisms (10.000 cfu/mi agar) or rinsed under tap water before applied on the agar plates.

After incubation of the plates, the inhibition zones (E) around the calf skin discs were measured. The inhibition of growth below the calf skin was also assessed. A vinson rating (VR) of 4 means a total inhibition of growth below the calf skin. VIR of 0 means a full growth under the calf skin. The active shows a strong substantivity to the calf skin resulting in a strong antimicrobial activity on the skin even after washing.

Results of the calfskin test with 4-(2-tert.-BuW-5-methyII2henoxy)-phenol (ID 1 6ll inhibition zone in mm microorga- S.aureus S.epidermidis C.xerosis E.floccosum T.mentagroph nisms ATCC 9144 ATCC 12228 ATCC 373 CBS 55384 ytes substances ATCC 9535 lZ V11 _lZ VIR lZ VR lZ VR lZ VR 1.0%]D 166 6/6 414 6/6 4/4 4/4 4/4 1011 4/4 717 4/4 in ROH 0 1.0% ID 166 5/5 4/4 5/5 4/4 313 4/4 9/9 4/4 5/5 4/4 in ROH (rinsed) Forearm test For an assessment of the activity on skin, a formulation of 1 % active in 70% ethanol was applied on the skin of the forearm (3m]). The activity was investigated immediately after application of the product and 2 hours after application as well as after a 1 minute rinse of the skin with running tap water. For the determination of the activity, filter paper discs (2 cm diameter) were soaked in ethanol and then placed on the treated skin for 4 minutes. Afterwards the discs are dried to evaporate the alcohol and then placed in the center of agar plates containing the test bacteria (10.000 cfu per m] agar). After the incubation the inhibition zones (IZ) around the discs were measured.

The growth of bacteria under the filter disc was also measured. A Vinson Rating (VR) of 4 means a total inhibition of growth below the filter disc. VR of 0 means a full growth under the filter disc. The active shows a strong substantivity to the human skin resulting in a strong antimicrobial activity even after washing.

Results of the forearm test 4-(2-tert.-Buiyi-S-methyII2henox,y)-phenol Q1) 166) inhibition zone in mm microorganisms S.aureus S.epidermidis C.xerosis C.minutissu P.acnes substances ATCC 9144 ATCC 12228 ATCC 373 mum ATCC 6919 ATCC 23348 1.0%]D 166 in 70 ethanol immediately 5/5 4/4 2/3 4/4 -- 10/1 4/4 0 two hours after 4/4 414 616 4/4 4/4 4/4 application of the test product two hours after 2/2 4/4 5/5 4/4 3/3 4/4 application of the test product and a rinse with water --: not tested Bactericidal activity The bactericidal (killing) activity of 4-(2-ter. B utyl-5 -methyl phe noxy)-ph en ol was investigated in a suspension test according to the European Norm (EN) 1040. The reduction of bacteria (in log) was determined after 5 minutes and 15 minutes contact of the test formulation with the bacteria.

Results of the EN 1040 test with 4-(2-tert.-Butyi-5-methylphenoxy)-phenol (]D 1661 Test concentration: 90% 10% Texapon N 70 10% Texapon N 70 containing 1.0% ID 166 containing 1.0%]D 166 test strain after 5 minutes contact after 15 minutes contact Staphylococcus aureus ATCC 6538 2.15 2.63

Claims (3)

Claims:

1. Use of hydroxy diphenylethers of formula OH R 3 0 -,-Q R2 R1 R4 for sanitation and disinfection of skin, mucous membranes and inanimate surfaces.

2. Use according to claim 1 wherein the inanimate surfaces are selected from textiles, plastics and other hard surfaces.

3. Use according to claim 1 or 2 wherein the hydroxy diphenylether is 4(2-tert.-Butyl-5methyl p henoxy)-ph eno 1.