Preservatives

The present invention relates to clear, liquid compositions comprising 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones such as, for example, 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof and at least one alcohol containing one or more aromatic groups, for the preservation of preparations.

The use of piroctone olamine (2-aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone; the commercial product is Octopirox®) and also of 2-phenoxyethanol or benzyl alcohol for preserving cosmetic compositions is known. “Seifen-Öle-Fette-Waschse”, 116, No. 9/1990, pp. 345-356 describes how piroctone olamine can be used in shampoos, with sufficient preservation requiring an amount by weight of piroctone olamine of 0.5% to 1%. For O/W, emulsions and W/O emulsions the antimicrobial activity of piroctone olamine used in an amount of 0.5% by weight is inadequate.

In accordance with European Cosmetics Directive 76/768/EEC, ANNEX 6, piroctone olamine can be used in rinse-off products in concentrations of not more than 1% by weight, and in all other cosmetic products in concentrations of not more than 0.5% by weight.

The ease of incorporation of piroctone olamine into cosmetics is restricted by the low solubility of the active substance in water and its no more than moderate solubility in oil.

The object was to provide high-activity preservative compositions for cosmetic, pharmaceutical, and dermatological preparations, said preservative compositions being dermatologically and toxicologically unobjectionable, highly compatible with aqueous systems and with oil systems, having a clear visual appearance, being easy to process, and exhibiting temperature and storage stability.

It has surprisingly been found that this object is achieved by means of clear liquid preservative compositions comprising

a) one or more 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones and/or one or more salts thereof, alkyl being a linear, branched or cyclic alkyl group having 1 to 12 carbon atoms and b) one or more alcohols containing one or more aromatic groups.

The antimicrobial activity, not only of 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones such as piroctone olamine, for example, but also of the alcohols containing one or more aromatic groups, is synergistically boosted. The concentrations in which these active antimicrobial substances are used in cosmetic, dermatological, and pharmaceutical products can be lowered significantly as a result.

It has additionally been found that the preservative compositions of the invention are suitable for use in both rinse-off and leave-on products, more particularly in emulsions, preferably in O/W emulsions or W/O emulsions, and produce sufficient preservation of the products at effective piroctone olamine use concentrations of below 0.1% by weight.

Likewise advantageous is the clear appearance of the liquid preservative compositions, and their ease of formulation.

The invention provides clear liquid preservative compositions comprising

a) one or more 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones and/or one or more salts thereof, alkyl being a linear, branched or cyclic alkyl group having 1 to 12 carbon atoms, preferably 2,4,4-trimethylpentyl or cyclohexyl, and b) one or more alcohols containing one or more aromatic groups.

In one preferred embodiment of the invention the preservative compositions of the invention comprise

a) 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof and b) one or more alcohols containing one or more, preferably one, aromatic group(s).

In one particularly preferred embodiment the preservative compositions of the invention contain

a) 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof in amounts by weight of 0.1% to 20%, preferably 1.1% to 10%, more preferably 1.5% to 7%, and with particular preference 5%, and b) one or more alcohols containing one or more aromatic groups, in amounts by weight of 35% to 99.9% and preferably of 80% to 99.9%.

In a further particularly preferred embodiment the preservative compositions of the invention comprise

a) 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof, b) one or more alcohols containing one or more aromatic groups, c) water, d) optionally one or more further active antimicrobial substances, e) optionally one or more hydrotropes, and f) optionally one or more further additives.

The preservative compositions of the invention comprising one or more 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones such as, for example, 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof, one or more alcohols containing one or more aromatic groups, and water are clear liquids which even after months of storage do not display any crystallization tendencies.

In a further particularly preferred embodiment the preservative compositions of the invention contain

a) 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof in amounts by weight of 0.1% to 20%, preferably 1.1% to 10%, more preferably 1.5% to 7%, and with particular preference 5%, b) one or more alcohols containing one or more aromatic groups, in amounts by weight of 35% to 99.8% and preferably of 59.8% to 99.8%, and c) water in amounts by weight of 0.1% to 35%, preferably 0.1% to 20%, more preferably 0.5% to 5%, and with particular preference 1% to 3%.

The preservative compositions of the invention comprise one or more 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones such as, for example, 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof, it being possible for the salts to be Li + , Na + , Mg ++ , Ca ++ , Zn ++ , Al +++ , NH 4 + , monoalkylammonium, dialkylammonium, trialkyl-ammonium and/or tetraalkylammonium salts, it being possible for the alkyl substituents of the amines independently of one another to be (C 1 -C 22 )-alkyl radicals or (C 2 -C 10 )-hydroxyalkyl radicals.

Preference among the stated salts is given to the monoalkylammonium, dialkylammonium, trialkylammonium, and tetraalkylammonium salts.

With particularly preference the preservative compositions of the invention comprise the monoethanolamine salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone (Octopirox®, Clariant GmbH).

The alcohols containing one or more aromatic groups that are present in the preservative compositions of the invention are preferably selected from 2-phenoxyethanol, 1-phenoxy-2-propanol, and benzyl alcohol. Among these alcohols particularly preference is given in turn to 2-phenoxyethanol.

In one further particularly preferred embodiment the preservative compositions of the invention comprise one or more further active antimicrobial substances, preferably in the concentrations of 1% to 25%, more preferably of 5% to 25%, and with particular preference of 10% to 15% by weight. The further active antimicrobial substances are preferably selected from parabens, such as methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, sodium methylparaben, sodium ethylparaben, sodium propylparaben, sodium isobutylparaben, sodium isopropylparaben or sodium butylparaben, imidazolidinylurea, diazolidinylurea, iodopropynyl butylcarbamate, 2-bromo-2-nitropropane-1,3-diol, sorbic acid, potassium sorbate, cetyltrimethylammonium chloride, cetylpyridinium chloride, benzethonium chloride, diisobutylethoxyethyldimethylbenzylammonium chloride, diiso-butylphenoxyethoxyethyldimethylbenzylammonium chloride, N-alkyl-N,N-dimethylbenzylammonium chloride, bromide or saccharinate, trimethylammonium chloride, sodium aluminum chlorohydroxylactate, triethyl citrate, tricetylmethylammonium chloride, 2,4,4′-trichloro-2′-hydroxydiphenyl ether (triclosan), 3,4,4′-trichlorocarbanilide (triclocarban), diaminoalkylamide, such as L-lysine hexadecyl amide, DMDM hydantoin, sodium hydroxymethylglycinate, benzoic acid, propionic acid, salicylic acid, 2,4-hexanedienoic acid, 2-hydroxybiphenyl, chlorbutanulum, 3-acetylmethyl-2,4-(3H)pyrandione, formic acid, undecenylic acid, 5-amino-1,3-bis(2-ethylhexyl)-5-methylhexahydro-pyrimidine, 2-bromo-2-nitro-1,3-propanediol, 2,4-dichlorobenzyl alcohol, N-(4-chlorophenyl)-N′-(3,4-dichlorophenyl)urea, 2,4,4′-trichloro-2′-hydroxy-diphenyl ether, poly(hexamethylenediguanide) hydrochloride, 1,2-dibromo-2,4-dicyanobutane, 4,4-dimethyl-1,3-oxazolidine, sodium benzoate, methyl-isothiazolinone, methylchloroisothiazolinone and methylisothiazolinone in a molar ratio of 3:1, chloroxyenol, citrate heavy-metal salts, silver chloride, salicylates such as sodium salicylate, piroctose, more particularly zinc salts, pyrithiones and their heavy-metal salts, more particularly zinc pyrithione, zinc phenol sulfate, farnesol, ketoconazole, oxiconazole, terbinafine, bifonazole, butoconazole, cloconazole, clotrimazole, econazole, enilconazole, fenticonazole, isoconazole, miconazole, sulconazole, tioconazole, fluconazole, itraconazole, terconazole, naftifine and terbinafine, and combinations of these active substances.

In one especially preferred embodiment the preservative compositions of the invention comprise one or more further active antimicrobial substances selected from parabens, preferably methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, sodium methylparaben, sodium ethylparaben, sodium propylparaben, sodium isobutylparaben and/or sodium butylparaben, organic acids, preferably sorbic acid, potassium sorbate, salicylic acid, sodium salicylate, benzoic acid and/or sodium benzoate, formaldehyde donors, preferably imidazolidinylurea, diazolidinylurea, DMDM hydantoin and/or sodium hydroxymethylglycinate, and halogenated preservatives, preferably iodopropynyl butylcarbamate and/or 2-bromo-2-nitropropane-1,3-diol.

In one extraordinarily preferred embodiment the preservative compositions of the invention comprise

I) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-phenoxyethanol, and methylparaben or II) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-phenoxyethanol, and sodium benzoate or III) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-phenoxyethanol, and benzoic acid or IV) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-phenoxyethanol, and potassium sorbate or V) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-phenoxyethanol, and sorbic acid or VI) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-phenoxyethanol, and sodium salicylate or VII) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-phenoxyethanol, and salicylic acid.

Where the preservative compositions of the invention comprise one or more active antimicrobial substances selected from salts of organic acids, the preservative compositions of the invention preferably contain from 10% to 35% by weight of water.

In a further particularly preferred embodiment the preservative compositions of the invention comprise one or more antioxidants. The antioxidants preferably selected from superoxide dismutase, tocopherol (vitamin E), ascorbic acid (vitamin C), amino acids (e.g., glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocaninic acid) and their derivatives, peptides such as D,L-carnosine, D-carnosine, L-carnosine, and their derivatives (e.g., anserine), carotenoids, carotenes (e.g. α-carotene, β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (e.g., dihydrolipoic acid), aurothioglucose, propylthiouracil, and other thiols (e.g., thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl, and lauryl, palmitoyl, oleyl, γ-linoleyl, chlolesteryl, and glyceryl esters) and also salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides, and salts), and also sulfoximine compounds (e.g., buthionine sulfoximine, homocysteine sulfoximine, buthionine sulfones, penta-, hexa-, and heptathionine sulfoximine) in very low tolerated doses (e.g., pmol/kg), additionally (metal) chelators (e.g., α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g., citric acid, lactic acid, malic acid), humic acid, gallic acid, bile-extracts, bilirubin, biliverdin, EDTA, EGTA, and derivatives thereof, unsaturated fatty acids and their derivatives (e.g., γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives (e.g., ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g., vitamin E acetate), vitamin A and derivatives (vitamin A palmitate), coniferyl benzoate of benzoin resin, rutic acid and its derivatives, α-glycosylrutin, ferulic acid, furfurylideneglucitol, carnosine, butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguaic resin acid, nordihydroguaiaretic acid, trihydrobutyro-phenone, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (e.g., ZnO, ZnSO 4 ), selenium and its derivatives (e.g., selenomethionine), stilbenes and their derivatives (e.g., stilbene oxide, trans-stilbene oxide) and superoxide dismutase and derivatives suitable in accordance with the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these stated substances.

Oil-soluble antioxidants may be used with particular advantage for the purposes of the present invention.

With extraordinary preference the preservative compositions of the invention comprise one or more antioxidants selected from tocopheryl acetate, BHT (butylated hydroxytoluene), and EDTA.

The amount of the one or more antioxidants in the preservative compositions of the invention is preferably 0.001% to 30%, more preferably 0.05% to 20%, and with particular preference 0.1% to 5% by weight.

In a further particularly preferred embodiment the preservative compositions of the invention comprise one or more hydrotropes. The hydrotropes are preferably selected from xylene-, toluene- and cumenesulfonate. Cumenesulfonate is particularly preferred.

The weight fraction of the one or more hydrotropes in the compositions of the invention is situated preferably in the range from 1% to 15%, more preferably 4% to 10%, and with particular preference 6% to 8% by weight, based on the completed compositions.

In a further particularly preferred embodiment the preservative compositions of the invention comprise one or more solubilizers, preferably in amounts from 1% to 20% by weight.

Suitable solubilizers include in principle all monohydric or polyhydric alcohols and ethoxylated alcohols, such as ethanol, propanol, isopropanol, n-butanol, isobutanol, glycerol and mixtures thereof, glycols, such as triethylene glycol, butylene glycol, 1,2-propylene glycol, polyethylene glycols having a relative molecular mass below 2000, in particular having a relative molecular mass between 200 and 600, diols, examples being pentanediol, 1,5-pentanediol, 1,6-hexanediol, triacetin (glycerol triacetate), 1-methoxy-2-propanol, and PEG-4 laurate (polyethylene glycol-4 laurate).

With particular preference the preservative compositions of the invention comprise one or more solubilizers selected from triethylene glycol, butylene glycol, and 1,2-propylene glycol.

In one further particularly preferred embodiment the preservative compositions of the invention are composed of

a) 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof and b) one or more alcohols containing one or more aromatic groups.

In a further particularly preferred embodiment the preservative compositions of the invention are composed of

a) 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and/or one or more salts thereof and b) one or more alcohols containing one or more aromatic groups, and c) water.

The preservative compositions of the invention are advantageously suitable for preserving dermatological, cosmetic, and pharmaceutical products.

The invention therefore further provides for the use of a composition of the invention for preserving dermatological, cosmetic, and pharmaceutical products.

For the purposes of the present invention the dermatological, cosmetic, and pharmaceutical products also include, for example, corresponding formulations.

The dermatological, cosmetic, and pharmaceutical products may for example be aqueous, aqueous-alcoholic, aqueous-surfactant or alcoholic compositions or oil-based compositions, including oil-based compositions in anhydrous form, or emulsions, suspensions or dispersions, more specifically in the form of fluids, foams, sprays, gels, mousses, lotions, creams, powders or wet wipes.

In one preferred embodiment the compositions of the invention are used for preserving wet wipes. In this case the formulation for preservation that is applied to the textile fabric can be an emulsion, more particularly an O/W emulsion, or alternatively a surfactant-based formulation or an oily composition.

In another preferred embodiment the compositions of the invention are used for preserving emulsions.

The emulsions may be water-in-oil emulsions and oil-in-water emulsions, microemulsions, nanoemulsions, and multiple emulsions. The emulsions can be prepared in a known way, in other words for example by cold, hot, hot/cold or PIT emulsification. A particularly preferred embodiment are self-foaming, foam-form, after-foaming or foamable emulsions and micro-emulsions.

The present invention further provides cosmetic, dermatological or pharmaceutical formulations prepared using a preservative composition which comprises

a) one or more 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones and/or one or more salts thereof, alkyl being a linear, branched or cyclic alkyl group having 1 to 12 carbon atoms, preferably 2,4,4-trimethylpentyl or cyclohexyl, and with particular preference 2,4,4-trimethylpentyl, b) one or more alcohols containing one or more aromatic groups, and c) one or more further active antimicrobial substances,

and cosmetic, dermatological or pharmaceutical formulations which comprise such a preservative composition.

The present invention further provides cosmetic, dermatological or pharmaceutical formulations comprising

a) one or more 1-hydroxy-4-methyl-6-alkyl-2(1H)-pyridones and/or one or more salts thereof, alkyl being a linear, branched or cyclic alkyl group having 1 to 12 carbon atoms, preferably 2,4,4-trimethylpentyl or cyclohexyl, and with particular preference 2,4,4-trimethylpentyl, b) one or more alcohols containing one or more aromatic groups, and c) one or more further active antimicrobial substances.

Preference among the formulations specified is given to those in which the one or more active antimicrobial substances of component c) are selected from parabens, preferably methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, sodium methylparaben, sodium ethylparaben, sodium propylparaben, sodium isobutylparaben and/or sodium butylparaben, organic acids, preferably sorbic acid, potassium sorbate, salicylic acid, sodium salicylate, benzoic acid and/or sodium benzoate, formaldehyde donors, preferably imidazolidinylurea, diazolidinylurea, DMDM hydantoin and/or sodium hydroxymethylglycinate, and halogenated preservatives, preferably iodopropynyl butylcarbamate and/or 2-bromo-2-nitropropane-1,3-diol.

Particular preference is given to cosmetic, dermatological or pharmaceutical formulations comprising

a) aminoethanol salt of 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, b) 2-phenoxyethanol and c) one or more substances selected from methylparaben, benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, salicylic acid, and sodium salicylate.

In one especially preferred embodiment of the invention the substances of components a), b), and c), based on the completed formulations, are present in the formulations at 0.1% to 2% by weight.

In a further preferred embodiment of the invention the dermatological, cosmetic, and pharmaceutical products are rinse-off products, more particularly shampoos, hair rinses, hair treatments, shower products, including shower gels, or bath foams.

In a further preferred embodiment of the invention the dermatological, cosmetic, and pharmaceutical products are leave-on products, more particularly day creams, night creams, care creams, nutrient creams, body lotions, ointments or lipcare compositions.

Further preferred leave-on products are decorative cosmetics, more particularly makeup, eye shadow, lipstick or mascara products.

In a further preferred embodiment of the invention the dermatological, cosmetic, and pharmaceutical products are sun protection compositions. These compositions comprise one or more organic- or inorganic-based UV filters.

In a further preferred embodiment of the invention the dermatological, cosmetic, and pharmaceutical products are deodorants and antiperspirants, more particularly in the form of sprays, sticks, gels or lotions.

In a further preferred embodiment of the invention the dermatological, cosmetic, and pharmaceutical products are surfactant-free compositions, more particularly surfactant-free solid compositions or surfactant-free emulsions.

The dermatological, cosmetic and pharmaceutical products may comprise, as further auxiliaries and additives, surfactants, emulsifiers, cationic polymers, thickeners, film formers, active antimicrobial substances, astringents, antioxidants, UV light protection filters, pigments/micropigments, gelling agents, and other adjuvants customary in cosmetology, such as superfatting agents, moisturizing agents, silicones, stabilizers, conditioners, glycerol, preservatives, pearlescents, dyes, fragrance oils and perfume oils, solvents, hydrotropes, opacifiers, fatty alcohols, substances having keratolytic and keratoplastic activity, antidandruff agents, active biogenic substances (local anesthetics, antibiotics, antiphlogistics, antiallergics, corticosteroids, sebostatics), vitamins, Bisabolol®, Allantoin®, Phytantriol®, Panthenol®, AHA acids, plant extracts, aloe vera for example, and proteins.

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone and its salts from organic and inorganic acids are obtained by the methods described in EP 241 918, EP 646 368, DE 17 95 270, DE 22 14 608 and DE 22 34 009.

The preservative compositions of the invention can be prepared, for example, by combining the individual components, where appropriate with gentle heating at approximately 35° C.

The examples and applications below are intended to illustrate the invention in more detail, but without confining it to them (all percentages are by weight).

INCI names of the commercial products employed: