N-HEPTYL-GLYCERYL ETHER AND SYNERGISTICALLY ACTIVE PRESERVATIVES

Abstract

A composition contains n-heptyl-glyceryl ether and at least one further carefully chosen and synergistically active preservative.

Claims

1: A composition, comprising; A) n-heptyl-glyceryl ether, and B) at least one selected from the group consisting of p-anisic acid, benzoic acid, levulinic acid, sorbic acid, lactic acid, mandelic acid, salicylic acid, dehydroacetic acid, cinnamic acid, geranic acid, and salts of any of the before mentioned acids, methylparaben, ethylparaben, phenylpropanol, benzyl alcohol, phenethyl alcohol, phenoxyethanol, propanediol, pentylene glycol, 1,2-hexanediol, caprylyl glycol, undecyl alcohol, methylpropanediol, ethylhexylglycerin, n-octylglycerin, methylchloroisothiazolinone, triethyl citrate, and citral.

2: The composition according to claim 1, wherein component B) is selected from the group consisting of p-anisic acid, sorbic acid, benzoic acid, levulinic acid, lactic acid, and salts of any of the before mentioned acids, benzyl alcohol, and phenylpropanol.

3: The composition according to claim 1, wherein component A) and component B) are comprised in a weight ratio of from 99:1 to 1:99.

4: The composition according to claim 1, wherein component A) is comprised in an amount of from of from 0.005 wt.-% to 99.0 wt.-%, wherein the weight percentages refer to a total composition.

5: The composition according to claim 1, wherein component B) is comprised in an amount of from 0.005 wt,-% to 99.0 wt.-%, wherein the weight percentages refer to a total composition.

6: The composition according to claim 1, wherein the composition has a pH in the range of 4.0 to 8.5.

7: The composition according to claim 1, wherein the composition comprises C) at least one selected from the group consisting of deodorant and antiperspirant active ingredients.

8: The composition according to claim 1, wherein the composition comprises D) at least one antioxidants.

9: A formulation, comprising the composition according to claim 1, wherein the formulation is selected from the group consisting of cleaning formulations, defoamers, coating formulations, and cosmetic formulations.

10: The formulation according to claim 9, wherein component A) is comprised in an amount of from of from 0,005 wt.-% to 10.0 wt-%, and component B) is comprised in an amount of from 0.005 wt.-% to 30.0 wt % and optionally, component C), which is at least one selected from the group consisting of deodorant and antiperspirant active ingredients, is comprised in an amount of from 0.005 wt 3% to 25.0 wt.-%, wherein the weight percentages refer to a total formulation.

11: A method for preserving a formulation, the method comprising: adding the following components to the formulation A) n-heptyl-glyceryl ether, and B) at least one selected from the group consisting of p-anisic acid, benzoic acid, levulinic acid, sorbic acid, lactic acid, mandelic acid, salicylic acid, dehydroacetic acid, cinnamic acid, geranic acid, and salts of any of the before mentioned acids, methylparaben, ethylparaben, phenylpropanol, benzyl alcohol, phenethyl alcohol, phenoxyethanol, propanediol, pentylene glycol, 1,2-hexanediol, caprylyl glycol, undecyl alcohol, methylpropanediol, ethylhexylglycerin, n-octylglycerin, methylchloroisothiazolinone, triethyl citrate, and citral.

12: The method according to claim 11, wherein the preserving comprises growth reduction of a micro-organism.

13: A preservative, comprising the composition according to claim 1.

14: A method for increasing critical micelle concentration of n-heptyl-glyceryl ether in water, the method comprising: adding to the water and the n-heptyl-gly ceryl ether, at least one selected from the group consisting of B) p-anisic acid, benzoic acid, levulinic acid, sorbic acid, lactic acid, mandelic acid, salicylic acid, dehydroacetic acid, cinnamic acid, geranic acid, and the salts of any of the before mentioned acids, methylparaben, ethylparaben, phenylpropanol, benzyl alcohol, phenethyl alcohol, phenoxyethanol, propanediol, pentylene glycol, 1,2-hexanediol, caprylyl glycol, undecyl alcohol, methylpropanediol, ethylhexylglycerin, n-octylglycerin, methylchloroisothiazolinone, triethyl citrate, and citral.

15: The composition according to claim 8, wherein the at least one antioxidant is tocopherol or naringenin.

16: The method according to claim 11, wherein the formulation is selected from the group consisting of cleaning formulations, defoamers, coating formulations, and cosmetic formulations.

17: The method according to claim 12, wherein the micro-organism is selected from the group consisting of yeast, mould, and bacteria.

18: The method according to claim 12, wherein the bacteria is A. brasiliensis, S. aureus, or C. albicans.

19: The preservative according to claim 13, wherein the preservative is a preservative against a micro-organism selected from the group consisting of yeast, mould, and bacteria.

20: The preservative according to claim 19, wherein the bacteria is A. brasiliensis, S. aureus, or C. albicans.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0110] FIG. 1 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and anisic acid, either separately or jointly, at pH 5.3 over the course of 28 days.

[0111] FIG. 2 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and anisic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0112] FIG. 3 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and anisic acid, either separately or jointly, at different pH values over the course of 28 days.

[0113] FIG. 4 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and sorbic acid, either separately or jointly, at pH 5.3 over the course of 28 days.

[0114] FIG. 5 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and sorbic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0115] FIG. 6 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and phenyl propanol, either separately or jointly, at pH 6.5 after 28 days.

[0116] FIG. 7 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and lactic acid, either separately or jointly, at pH 5.3 over the course of 28 days.

[0117] FIG. 8 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and lactic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0118] FIG. 9 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and sodium benzoate, either separately or jointly, at pH 5.3 over the course of 28 days.

[0119] FIG. 10 shows the log 10 reduction of A. brasiliensis for dosage of n-heptyl glyceryl ether and sodium benzoate, either separately or jointly, at pH 6.5 over the course of 28 days.

[0120] FIG. 11 shows the log 10 reduction of A. brasiliensis for dosage of ethylhexylglycerin and anisic acid, either separately or jointly, at pH 5.3 over the course of 28 days.

[0121] FIG. 12 shows the log 10 reduction of A. brasiliensis for dosage of ethylhexylglycerin and anisic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0122] FIG. 13 shows the log 10 reduction of S. aureus for dosage of n-heptyl glyceryl ether and anisic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0123] FIG. 14 shows the log 10 reduction of S. aureus for dosage of n-heptyl glyceryl ether and sorbic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0124] FIG. 15 shows the log 10 reduction of S. aureus for dosage of n-heptyl glyceryl ether and phenylpropanol, either separately or jointly, at pH 6.5 over the course of 14 days.

[0125] FIG. 16 shows the log 10 reduction of S. aureus for dosage of n-heptyl glyceryl ether and lactic acid, either separately or jointly, at pH 5.3 over the course of 28 days.

[0126] FIG. 17 shows the log 10 reduction of S. aureus for dosage of n-heptyl glyceryl ether and sodium benzoate, either separately or jointly, at pH 5.3 over the course of 28 days.

[0127] FIG. 18 shows the log 10 reduction of S. aureus for dosage of n-heptyl glyceryl ether and sodium benzoate, either separately or jointly, at pH 6.5 over the course of 28 days.

[0128] FIG. 19 shows the log 10 reduction of S. aureus for dosage of ethylhexylglycerin and anisic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0129] FIG. 20 shows the log 10 reduction of C. albicans for dosage of n-heptyl glyceryl ether and anisic acid, either separately or jointly, at pH 6.5 after 14 and 28 days.

[0130] FIG. 21 shows the log 10 reduction of C. albicans for dosage of n-heptyl glyceryl ether and sorbic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0131] FIG. 22: shows the log 10 reduction of C. albicans for dosage of n-heptyl glyceryl ether and phenylpropanol, either separately or jointly, at pH 6.5 over the course of 28 days.

[0132] FIG. 23 shows the log 10 reduction of C. albicans for dosage of n-heptyl glyceryl ether and lactic acid, either separately or jointly, at pH 5.3 over the course of 28 days.

[0133] FIG. 24 shows the log 10 reduction of C. albicans for dosage of n-heptyl glyceryl ether and lactic acid, either separately or jointly, at pH 6.5 over the course of 28 days.

[0134] FIG. 25 shows the log 10 reduction of C. albicans for dosage of ethylhexylglycerin and anisic acid either separately or jointly, at pH 6.5 over the course of 28 days.

[0135] FIG. 26 shows the results of the evaluation of the formation and stability of emulsions

EXAMPLES

Example 1: Determination of the Synergistic Antimicrobial Activity, Basics

[0136] An O/W emulsion (base #1) was prepared as follows, and n-heptyl glyceryl ether, further antimicrobial compounds and combinations thereof were added to these bases:

TABLE-US-00001 TABLE 1 Preparation of base #1 Phase Ingredient INCI (EU) Supplier % A Deionised Water Aqua ad 100 dermofeel PA-3 Sodium Phytate; Aqua; Alcohol Evonik 0.10 Glycerin 99.5% Ph. Eur. Glycerin Highchem 5.00 Antimicrobial compound tbd A1 Keltrol CG-RD Xanthan Gum CP Kelco 0.30 B dermofeel GSC Glyceryl Stearate Citrate Evonik 3.50 Miglyol 812 N Caprylic/Capric Triglyceride IOI Oleo 6.00 Phytosqualan Squalane Sophim 6.00 Sunflower Oil Helianthus Annuus Seed Oil diverse 5.00 Lanette O Cetearyl Alcohol BASF 2.00 dermofeel Toco 70 non Tocopherol; Helianthus Annuus Seed Evonik 0.15 GMO Oil C n-heptyl glyceryl ether tbd

[0137] Processing: [0138] 1. Premix phase A and B separately and heat up to 78 C. [0139] 2. Add phase A1 to A under stirring and wait until everything is dissolved. [0140] 3. Add phase B to A under stirring. (Speed 6, for 30 sec.) Homogenize for 90 sec. using an Ultra Turrax. [0141] 4. Cool down using a water bath [0142] 5. Adjust pH.

[0143] The antimicrobial activity against specific microorganisms was then evaluated as follows:

[0144] Preparation of the Inoculum:

[0145] Preparatory to the test, the surface of casein soya bean digest agar for bacteria or Saboraud-dextrose agar without the addition of antibiotics for fungi is inoculated with the recently grown stock culture of each of the specified microorganisms. The bacterial cultures are inoculated at 30-35 C. for 18-24 hours, the culture of C. albicans at 20-25 C. for 48 hours, and the culture of A. brasiliensis at 20-25 C. for 1 week or until good sporulation is obtained.

[0146] Method:

[0147] To count the viable microorganisms in the inoculated products, the agar medium used for the initial cultivation of the respective microorganism is used. The test sample is inoculated with a suspension of the test organism to give an inoculum of 10.sup.5 to 10.sup.6 microorganisms per milliliter of the preparation. The volume of the suspension of inoculum does not exceed 1 percent of the volume of the product. The suspension is mixed thoroughly to ensure homogeneous distribution. The inoculated product is maintained at 20-25 C., protected from light. At zero hour and at 7, 14 and 28 days 1 ml is removed from the sample and the number of viable microorganisms is determined by plate count.

[0148] The criteria for the evaluation of the antimicrobial activity are given in the table below in terms of the log reduction in the number of viable microorganisms against the value obtained for the inoculum.

Example 2: Determination of the Synergistic Antimicrobial Activity Against the Microbial Strain A. brasiliensis

[0149] To determine the efficacy of the antimicrobial composition, n-heptyl glyceryl ether, another antimicrobial compound and combinations thereof were incorporated into base # as shown above. The antimicrobial activity against A. brasiliensis was then evaluated as described above. The antimicrobial activities are given in the figures below in terms of the log reduction in the number of viable microorganisms against the value obtained for the inoculum.

[0150] As shown in FIGS. 1 to 12 it was observed that n-heptyl glyceryl ether shows synergistic antimicrobial effects when combined with another antimicrobial component. Synergistic in this context means that the log 10 reduction created from the combination of n-heptyl glyceryl ether and another antimicrobial component is greater than the sum of the effects produced by the addition of the two components individually.

[0151] No such synergism was observed when ethylhexyl glycerin was combined with the same component.

Example 3: Determination of the Synergistic Antimicrobial Activity Against the Microbial Strain S. aureus

[0152] To determine the efficacy of the antimicrobial composition, n-heptyl glyceryl ether, another antimicrobial compound and combinations thereof were incorporated into base as shown above. The antimicrobial activity against S. aureus was then evaluated as described above. The antimicrobial activities are given in the figures below in terms of the log reduction in the number of viable microorganisms against the value obtained for the inoculum.

[0153] As shown in FIGS. 12 to 19 it was observed that n-heptyl glyceryl ether shows synergistic antimicrobial effects when combined with another antimicrobial component. Synergistic in this context means that the log 10 reduction created from the combination of n-Heptyl glyceryl ether and another antimicrobial component is greater than the sum of the effects produced by the addition of the two components individually.

[0154] No such synergism was observed when ethylhexylglycerin was combined with the same component.

Example 4: Determination of the Synergistic Antimicrobial Activity Against the Microbial Strain C. albicans

[0155] To determine the efficacy of the antimicrobial composition, n-heptyl glyceryl ether, another antimicrobial compound and combinations thereof were incorporated into base #1 as shown above. The antimicrobial activity against C. albicans was then evaluated as described above. The antimicrobial activities are given in the figures below in terms of the log reduction in the number of viable microorganisms against the value obtained for the inoculum.

[0156] As shown in FIGS. 20 to 25 it was observed that n-heptyl glyceryl ether shows synergistic antimicrobial effects when combined with another antimicrobial component. Synergistic in this context means that the log 10 reduction created from the combination of n-heptyl glyceryl ether and another antimicrobial component is greater than the sum of the effects produced by the addition of the two components individually.

[0157] No such synergism was observed when ethylhexylglycerin was combined with the same component.

Example 5: Evaluation of the influence on emulsification and emulsion stability

[0158] Emulsification means the formation of cosmetic emulsions by input of thermal energy and shear into a liquid two-phase system. Classical emulsions are only kinetically stabilized.

[0159] Surfactants/emulsifiers and other additives are used to stabilize emulsions e. g. by reducing the interfacial tensions and consequently, enhancing the dispersion of droplets and preventing coalescence. Another important feature affecting the stability of emulsions is the droplet size: small droplets favor the stabilization of an emulsion.

[0160] The influence of the synergistic compositions according to the invention on the formation and stability of cosmetic emulsions was evaluated in comparison to the individual components and to a composition not according to the invention by means of light microscopy and optical assessment. The following variants of O/W emulsions (base #1) were used for this evaluation and prepared as described above (see table 1)

TABLE-US-00002 TABLE 2 variants of base #1 used for the evaluation of the formation and stability of emulsions Emulsion Emulsion Emulsion Emulsion Emulsion Phase INCI (EU) #1 #2 #3 #4 *) #5 A Aqua ad 100 ad 100 ad 100 ad 100 ad 100 Sodium Phytate; Aqua; 0.10 0.10 0.10 0.10 0.10 Alcohol Glycerin 5.00 5.00 5.00 5.00 5.00 p-Anisic Acid 0.20 0.20 0.20 A1 Xanthan Gum 0.30 0.30 0.30 0.30 0.30 B Glyceryl Stearate Citrate 3.50 3.50 3.50 3.50 3.50 Caprylic/Capric Triglyceride 6.00 6.00 6.00 6.00 6.00 Squalane 6.00 6.00 6.00 6.00 6.00 Helianthus Annuus Seed Oil 5.00 5.00 5.00 5.00 5.00 Cetearyl Alcohol 2.00 2.00 2.00 2.00 2.00 Tocopherol; Helianthus 0.15 0.15 0.15 0.15 0.15 Annuus Seed Oil C n-heptyl glyceryl ether 0.40 0.40 0.40 ethylhexyl glycerin *) formulation containing the composition according to the invention

[0161] As shown in FIG. 26, surprisingly, it was found that, compared to the individual components (emulsions #2 and #3) and the composition not according to the invention (emulsion #5), the composition according to the invention (emulsion #4) improves the emulsification process and leads to stable emulsions with a smaller and more homogeneous bubble size.

Example 6: Evaluation of the Influence of a Synergistic Combination of n-Heptyl Glyceryl Ether and p-Anisic Acid on the Sensory Properties of an Emulsion

[0162] The sensory properties of synergistic compositions according to the invention were evaluated in comparison to the individual components and to a composition not according to the invention by means of a trained panel. Emulsions #1 to #5 (see table 2) were prepared as described above (see tables 1). A defined amount of 2.0 g of each emulsion was applied on the forearms of the panelists and different characteristics such as spreadability and gloss were evaluated on a scale of 0 (weakly pronounced) to 5 (strongly pronounced).

TABLE-US-00003 TABLE 3 results of the sensory evaluation Scores of the sensory evaluation, mean values; 0 = weakly pronounced, 5 = strongly pronounced Spreadability Gloss Emulsion #1 2.5 0.75 Emulsion #2 3.75 0.75 Emulsion #3 3 0 Emulsion #4 *) 4 1 Emulsion #5 3.75 0.5 *) formulation containing the composition according to the invention

[0163] Table 3 clearly demonstrates that the formulation containing the synergistic combination of n-heptyl glyceryl ether and p-anisic acid (emulsion #4), has better spreadability and leads to a more glossy skin compared to the emulsions containing the individual components (emulsions #2 and #3), to the emulsion containing a combination of ethylhexylglycerin and p-anisic acid (emulsion #5), and the formulation without any antimicrobial component at all (emulsion #1).

Example 7: Evaluation of the Influence of a Synergistic Combination of n-Heptyl Glyceryl Ether and Phenylpropanol on the Sensory Properties of an Emulsion

[0164] Emulsions #6 to #8 (see table 4) were prepared as described above (see tables 1). A defined amount of 2.0 g of each emulsion was applied on the forearms of the panelists and different characteristics such as spreadability and gloss were evaluated on a scale of 0 (weakly pronounced) to 5 (strongly pronounced).

TABLE-US-00004 TABLE 4 variants of base #1 used for the evaluation of the formation and stability of emulsions Emulsion Emulsion Emulsion Emulsion #9 Phase INCI (EU) #6 #7 #8 *) A Aqua ad 100 ad 100 ad 100 ad 100 Sodium Phytate; Aqua; Alcohol 0.10 0.10 0.10 0.10 Glycerin 5.00 5.00 5.00 5.00 Phenylpropanol 0.20 0.20 A1 Xanthan Gum 0.30 0.30 0.30 0.30 B Glyceryl Stearate Citrate 3.50 3.50 3.50 3.50 Caprylic/Capric Triglyceride 6.00 6.00 6.00 6.00 Squalane 6.00 6.00 6.00 6.00 Helianthus Annuus Seed Oil 5.00 5.00 5.00 5.00 Cetearyl Alcohol 2.00 2.00 2.00 2.00 Tocopherol; Helianthus Annuus Seed 0.15 0.15 0.15 0.15 Oil C n-heptyl glyceryl ether 0.40 0.40 *) formulation containing the composition according to the invention

TABLE-US-00005 TABLE 5 results of the sensory evaluation Scores of the sensory evaluation, mean values; 0 = weakly pronounced, 5 = strongly pronounced Spreadability Gloss Emulsion #6 3.3 0.7 Emulsion #7 3 0.3 Emulsion #8 3 0.3 Emulsion #9 *) 3.7 0.7 *) formulation containing the composition according to the invention

[0165] Table 5 clearly demonstrates that the formulation containing the synergistic combination of n-heptyl glyceryl ether phenyl propanol (emulsion #9), has better spreadability and leads to a more glossy skin compared to the emulsions containing the individual components (emulsions #7 and #8).

Example 8: Influence, of Component B) on Solubility of n-Heptyl-Glyceryl Ether

[0166] N-heptyl-glyceryl ether has a water solubility of approximately 2 g/l before micelles are forming. By the addition of component B) this critical micelle concentration (CMC) is dramatically increased as shown in table 6:

TABLE-US-00006 TABLE 6 Formulations without occurrence of micelles Formulatio Formulation Formulatio Formulation INCI (EU) #10 *) #11 *) #12 *) #13 *) pH 8.0 8.0 8.0 8.0 Aqua ad 100 ad 100 ad 100 ad 100 Propyleneglycol 46 Glycerin 20 n-heptyl glyceryl ether 20 20 19.00 19.00 Sodium anisate 8.7 10 7.6 7.6 *) formulation containing the composition according to the invention