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EP-3500236-B1 - A PRESERVATIVE MIXTURE

EP3500236B1EP 3500236 B1EP3500236 B1EP 3500236B1EP-3500236-B1

Inventors

  • PESARO, Manuel
  • LANGE, SABINE
  • SCHADE, Vanessa

Dates

Publication Date
20260506
Application Date
20160824

Claims (15)

  1. A preservative mixture comprising or consisting of (a) 2 to 50 % b.w. 4-isopropyl-3-methylphenol; (b) 40 to 97 % b.w. at least one hydrophilic solvent having a log P O/W of 1.2 or below; and (c) 1 to 38 % b.w. at least one lipophilic solvent having a log P O/W of above 1.2, on condition that the amounts add to 100 % b.w..
  2. The mixture of Claim 1, wherein said hydrophilic solvents are selected from the group consisting of alcohols, diols, polyols, phenols or esters.
  3. The mixture of Claim 2, wherein said hydrophilic solvents are selected from the group consisting of ethanol, 1-propanol, isopropanol phenoxyethanol, benzyl alcochol, ethylene glycol, propylene glycol, 1,3-propanediol, butylene glycol, pentylene glycol, 1,2-hexanediol, hexylene glycol dipropylene glycol, ethoxydiglycol, propylene carbonate, glycerine carbonate, butylene carbonate, triethyl citrate, ethyl lactate, butyl lactate, ethylacetate, diethylmalonate, diacetin, dimethyl isosorbide, diethylene glycol, PPG-3 ,methyl ether or any of their mixtures.
  4. The mixture of Claim 1, wherein said lipophilic solvents are selected from the group consisting of 2-methyl-5-cyclohexylpentanol, 2-methyl 5-phenylpentanol, dimethyl phenylpropanol, dimethyl phenylbutanol, 3-methyl-4-phenylbutan-2-ol, phenylisohexanol, iso adipate, farnesol, 4-hydroxyacetophenone, cetearyl ethylhexanoate, triisononanoin, caprylic/capric triglycerides, glyceryl caprylate, glyceryl caprate, glyceryl laurate, decyl alcohol, lauryl alcohol, cetyl alcohol, hexyldecanol, ethylhexyl isononanoate, ethylhexylglycerin, diethyl succinate, caprylyl glycol, decylene glycol, phenylpropanol, menthyl antranilate, homosalate, ethylhexyl salicylate, benzyl benzoate, benzyl salicylate, diethylhexyl 2,6-naphthalate, 2-benzylheptanol, isopropyl myristate, isopropyl palmitate, methyldihydrojasmonate, tetramethyl acetyloctahydronaphthalenes, trimethylbenzenepropanol, ethylbutyrate, menthyl acetate, carvacrol, methylsalicylate, eugenol, menthone, carvone, anethole, cinnamic aldehyde, limonene, isoamylacetate, dihydromyrcenol, methyldihydrojasmonate (hedione), tetramethyl acetyloctahydronaphtalenes (iso E super), isosorbide dicyprylate, menthone glycerin acetal, mentyl lactate, phenyl salicylate, farnesyl acetate, ethyl laurate, phenethyl benzoate, Persea gratissima (avocado oil), isoamyl-p methoxycinnamate, 4-methylbenzylidene camphor, ethylhexyl methoxycinnamate or any of their mixtures.
  5. The mixture of Claim 1, comprising or consisting of (a) 10 to 40 % b.w. 4-isopropyl-3-methylphenol; (b) 60 to 90 % b.w. at least one hydrophilic solvent having a log P O/W of 1.2 or below; and (c) 3 to 30 % b.w. at least one lipophilic solvent having a log P O/W of above 1.2. on condition that the amounts add to 100 % b.w.
  6. The mixture of Claim 1, consisting of (a) 30 % b.w. 4-isopropyl-3-methylphenol; (b) 65 % b.w. dipropylene glycol; and (c) 5 % b.w. decylene glycol.
  7. The mixture of Claim 1, consisting of (a) 20 % b.w. 4-isopropyl-3-methylphenol; (b) 70 % b.w. propylene glycol; and (c) 10 % b.w. lauryl alcohol.
  8. The mixture of Claim 1, consisting of (a) 25 % b.w. 4-isopropyl-3-methylphenol; (b) 70 % b.w. pentylene glycol; and (c) 5 % b.w. 2-benzylheptanol.
  9. The mixture of Claim 1, consisting of (a) 20 % b.w. 4-isopropyl-3-methylphenol; (b) 70 % b.w. butylene carbonate; and (c) 10 % b.w. ethylhexylglycerin.
  10. The mixture of Claim 1, consisting of (a) 25 % b.w. 4-isopropyl-3-methylphenol; (b) 70 % b.w. triethyl citrate; and (c) 5 % b.w. ethylhexylglycerin.
  11. A method for making a preservative mixture with improved solubility, encompassing the following steps: (i) Providing a source for 4-isopropyl-3-methylphenol; (ii) Blending source (a) und stirring with a mixture of at least one hydrophilic solvent having a log P O/W of 1.2 or below and at least one lipophilic solvent having a log P O/W of above 1.2; and (iii) Adding to the mixture of step (ii) a surfactant, wherein the mixture of step (ii) comprises 2 to 50 % b.w. 4-isopropyl-3-methylphenol; 40 97 % b.w. at least one hydrophilic solvent having a log PO/W of 1.2 or below; and 1 to 38 % b.w. at least one lipophilic solvent having a log PO/W of above 1.2.
  12. The use of a mixture comprising or consisting of at least one hydrophilic solvent having a log P O/W of 1.2 or below and at least one lipophilic solvent having a log P O/W of above 1.2 for improving the solubility of 4-isopropyl-3-methylphenol particularly in cosmetic or household compositions.
  13. A preservative mixture comprising or consisting of (a) 2 to 50 % b.w. 4-isopropyl-3-methylphenol; (b) 40 to 97 % b.w. at least one hydrophilic solvent having a log P O/W of 1.2 or below; and (c) 1 to 38 % b.w. at least one lipophilic solvent having a log P O/W of above 1.2, on condition that the amounts add to 100 % b.w., wherein said hydrophilic solvents (b) are selected from the group consisting of ethanol, 1-propanol, isopropanol phenoxyethanol, ethylene glycol,1,3-propanediol, 1,2-hexanediol, hexylene glycol, ethoxydiglycol, propylene carbonate, glycerine carbonate, butylene carbonate, ethyl lactate, butyl lactate, ethylacetate, diethylmalonate, diacetin, dimethyl isosorbide, diethylene glycol, PPG-3 -methyl ether or any of their mixtures.
  14. A preservative mixture comprising or consisting of (a) 2 to 50 % b.w. 4-isopropyl-3-methylphenol; (b) 40 to 97 % b.w. at least one hydrophilic solvent having a log P O/W of 1.2 or below; and (c) 1 to 38 % b.w. at least one lipophilic solvent having a log P O/W of above 1.2, on condition that the amounts add to 100 % b.w., wherein said lipophilic solvents (c) are selected from the group consisting of 2-methyl-5-cyclo-hexylpentanol, 2-methyl 5-phenylpentanol, dimethyl phenylpropanol, dimethyl phenylbutanol, 3-methyl-4-phenylbutan-2-ol, phenylisohexanol, iso adipate, farnesol, 4-hydroxyacetophenone, cetearyl ethylhexanoate, triisononanoin, caprylic/capric triglycerides, glyceryl caprylate, glyceryl caprate, glyceryl laurate, decyl alcohol, lauryl alcohol, hexyldecanol, ethylhexyl isononanoate, diethyl succinate, caprylyl glycol, decylene glycol, phenylpropanol, menthyl antranilate, homosalate, ethylhexyl salicylate, benzyl benzoate, benzyl salicylate, diethylhexyl 2,6-naphthalate, 2-benzylheptanol, isopropyl myristate, isopropyl palmitate, methyldihydrojasmonate, tetramethyl acetyloctahydronaphthalenes, trimethylbenzenepropanol, ethylbutyrate, menthyl acetate, carvacrol, methylsalicylate, eugenol, menthone, carvone, anethole, cinnamic aldehyde, isoamylacetate, dihydromyrcenol, methyldihydrojasmonate (hedione), tetramethyl acetyloctahydronaphtalenes (iso E super), isosorbide dicyprylate, menthone glycerin acetal, mentyl lactate, phenyl salicylate, farnesyl acetate, ethyl laurate, phenethyl benzoate, Persea gratissima (avocado oil), isoamyl-p methoxycinnamate, 4-methylbenzylidene camphor, or any of their mixtures.
  15. A preservative mixture according to Claim 13 and/or 14 comprising or consisting of (a) 2 to 50 % b.w. 4-isopropyl-3-methylphenol; (b) 40 to 97 % b.w. at least one hydrophilic solvent having a log P O/W of 1.2 or below; and (c) 1 to 38 % b.w. at least one lipophilic solvent having a log P O/W of above 1.2, on condition that the amounts add to 100 % b.w., wherein said hydrophilic solvents (b) are selected from the group consisting of ethanol, 1-propanol, isopropanol phenoxyethanol, ethylene glycol,1,3-propanediol, 1,2-hexanediol, hexylene glycol, ethoxydiglycol, propylene carbonate, glycerine carbonate, butylene carbonate, ethyl lactate, butyl lactate, ethylacetate, diethylmalonate, diacetin, dimethyl isosorbide, diethylene glycol, PPG-3 -methyl ether or any of their mixtures, and said lipophilic solvents (c) are selected from the group consisting of 2-methyl-5-cyclo-hexylpentanol, 2-methyl 5-phenylpentanol, dimethyl phenylpropanol, dimethyl phenylbutanol, 3-methyl-4-phenylbutan-2-ol, phenylisohexanol, iso adipate, farnesol, 4-hydroxyacetophenone, cetearyl ethylhexanoate, triisononanoin, caprylic/capric triglycerides, glyceryl caprylate, glyceryl caprate, glyceryl laurate, decyl alcohol, lauryl alcohol, hexyldecanol, ethylhexyl isononanoate, diethyl succinate, caprylyl glycol, decylene glycol, phenylpropanol, menthyl antranilate, homosalate, ethylhexyl salicylate, benzyl benzoate, benzyl salicylate, diethylhexyl 2,6-naphthalate, 2-benzylheptanol, isopropyl myristate, isopropyl palmitate, methyldihydrojasmonate, tetramethyl acetyloctahydronaphthalenes, trimethylbenzenepropanol, ethylbutyrate, menthyl acetate, carvacrol, methylsalicylate, eugenol, menthone, carvone, anethole, cinnamic aldehyde, isoamylacetate, dihydromyrcenol, methyldihydrojasmonate (hedione), tetramethyl acetyloctahydronaphtalenes (iso E super), isosorbide dicyprylate, menthone glycerin acetal, mentyl lactate, phenyl salicylate, farnesyl acetate, ethyl laurate, phenethyl benzoate, Persea gratissima (avocado oil), isoamyl-p methoxycinnamate, 4-methylbenzylidene camphor, or any of their mixtures.

Description

FIELD OF INVENTION The present invention belongs to the area of cosmetics and household products and relates to a preservative mixture comprising ortho-cymen-5-ol (4-isopropyl-3-methylphenol) with improved solubility. TECHNICAL BACKGROUND 4-isopropyl-3-methyl-phenol, also called ortho-cymen-5-ol (CAS: 3228-02-2) belongs to the group of preservatives which are approved for use in cosmetic and household compositions. The product is considered to be a suitable alternative for trichlosan. A disadvantage of this compound is its limited solubility in hydrophilic solvents in general and in the end-consumer formulations in particular. The compound also shows a strong tendency for recrystallization during storage. In terms of optimal antimicrobial activity it is mandatory that the compound is and stays completely dissolved in the respective formulation. Due to its high melting point of 110 to 113°C ortho-cymen-5-ol usually has to be heated up and dissolved in an appropriate solvent before adding to a formulation. Especially for surfactant based products e.g. shampoos, shower gel, liquid soap, dish washing liquid including a heating step into product formulation is highly unwanted, since it requires additional technical effort and energy. RELEVANT STATE OF THE ART In US 2008 069784 A1 (MILLIKIN), a specific personal care composition (L) is disclosed, comprising 2% by weight of p-thymol (4-isopropyl-3-methylphenol), 0.4% by weight of benzyl alcohol (LOG Po/w = 1.1), and 0.32% by weight of cetyl alcohol (LOG Po/w = 7.3). FR 2 895 247 A1 (DERMATOLOGIQUES D URIAGE) discloses in Example II a composition containing 0.1 wt% o-cymen-5-ol (4-isopropyl-3-methylphenol), 1 wt% butylene glycol (log Po/w = -0.29) and 5-20 wt% dicaprylyl carbonates. WO 2007 132439 A1 (HLAVIN) relates to the deodorant formulations in Examples 2-4 and 6 comprising 0.1 wt% o-cymen-5-ol, 53.90 wt% propylene glycol (log Po/w = -0.9) and 3.0 wt% ethylhexyl glycerol (log Po/w = 2.22). OBJECT OF THE PRESENT INVENTION Therefore there is a demand to find a technical solution which allows an easier incorporation of ortho-cymen-5-ol into product formulation, which on one hand avoids an additional heating step and on the other improves stability without recrystallization. DESCRIPTION OF THE INVENTION The object of the present invention is directed to a preservative mixture according to claim 1. Surprisingly, it has been observed that the solubility of 4-isopropyl-3-methyl-phenol in a hydrophilic solvent can be significantly increased by adding a small amount of a lipophilic solvent, while at the same time tendency for recrystallisation is significantly decreased. The hydrophilic solvent should be the main part of the composition due to better solubility properties in finished formulations. Preferably, the difference between the log P O/W values of the hydrophilic and the lipophilic solvent in the mixture is at least 0.5, preferably at least 0.7 and more preferred at least 1.0. The log PO/W concept The partition coefficient, abbreviated P, is defined as a particular ratio of the concentrations of a solute between the two solvents (a biphase of liquid phases), specifically for un-ionized solutes, and the logarithm of the ratio is thus log P When one of the solvents is water and the other is a non-polar solvent, then the log P value is a measure of lipophilicity or hydrophobicity. The defined precedent is for the lipophilic and hydrophilic phase types to always be in the numerator and denominator, respectively; for example, in a biphasic system of n-octanol (hereafter simply "octanol") and water:logPO/W=logsoluteoctanol/solutewater To a first approximation, the non-polar phase in such experiments is usually dominated by the un-ionized form of the solute, which is electrically neutral, though this may not be true for the aqueous phase To measure the partition coefficient of ionizable solutes, the pH of the aqueous phase is adjusted such that the predominant form of the compound in solution is the un-ionized, or its measurement at another pH of interest requires consideration of all species, un-ionized and ionized (see following). Therefore, the octanol/water partition coefficient (abbreviated PO/W or sometimes KO/W) provides information on how the chemical will partition between octanol (which represents the lipids or fats) and water. PO/W values for various chemicals range widely and for this reason the values are typically reported in log units (i.e., log PO/W). Both values provide information on how the chemical is likely to partition in biological organisms. PO/W is an important parameter that is used to by EPI Suite™ to estimate other properties including water solubility, bio-concentration, soil adsorption and aquatic toxicity. The EPI Suite™ method that estimates PO/W is KOWWIN and it uses a "fragment constant" method to predict PO/W. In the "fragment constant" method, a molecule is divided into fragments (atoms or larger functional groups) and the assigned