NOVEL COMPOSITIONS

Abstract

The present invention relates cosmetic compositions comprising a mixture of 1,4-di(benzoxazol-2′-yl)benzene and a preservative as well as to the use of said mixture as antimicrobial agent.

Claims

1. A topical composition comprising comprising 1,4-di(benzoxazol-2′-yl)benzene and at least one compound selected from the group of hydroxyacetophenone, an alkanediol and benzoic acid or a salt thereof.

2. The topical composition according to claim 1, wherein the amount of 1,4-di(benzoxazol-2′-yl)benzene is selected in the range from 1 to 20 wt.-%, more preferably in the range from 0.25 to 15 wt.-%, most preferably in the range from about 0.3 to 10 wt.-%, based on the total weight of the composition.

3. The topical composition according to claim 1 or 2, wherein the amount of the hydroxyacetophenone is selected in the range from 0.001 to 5 wt.-%, preferably in the range from 0.01 to 4 wt-%, most preferably in the range from 0.1 to 3 wt-%, based on the total weight of the composition.

4. The topical composition according to claim 1, wherein the amount of the alkane diol is selected in the range from 0.01 to 5 wt.-%, preferably in the range from 0.1 to 4 wt-%, most preferably in the range from 0.5 to 3 wt-%, based on the total weight of the composition.

5. The topical composition according to claim 1, wherein the amount of the benzoic acid or a salt thereof is selected in the range from 0.001 to 6 wt.-%, preferably in the range from 0.01 to 4 wt-%, most preferably in the range from 0.1 to 3 wt-%, based on the total weight of the composition.

6. The topical composition according to claim 1, wherein the weight-ratio of the 1,4-di(benzoxazol-2′-yl)benzene to the at least one compound selected from the group of hydroxyacetophenone, an alkanediol and benzoic acid or a salt thereof is selected in the range of between 50:1 to 1:10, preferably between 40:1 to 1:5, most preferably between 30:1 and 1:1.

7. The topical composition according to claim 1, wherein the hydroxyacetophenone is p-hydroxyacetophenone, the alkane diol is 1,3-propandiol and the benzoic acid or a salt thereof is sodium benzoate.

8. The topical composition according to claim 1, wherein the composition is an O/W emulsion, a W/O emulsion or a gel.

9. The topical composition according to claim 1, wherein the composition comprises water and at least one agent selected from the group consisting of surfactants, emulsifiers, thickeners and oils.

10. A topical method of treating the skin and/or the scalp, said method comprising the steps of contacting the skin and/or scalp with a cosmetic composition according to claim 1.

11. A method according to claim 10 for maintaining a healthy skin homeostasis and/or for maintaining skin microbiome balance.

12. Use of a mixture of 1,4-di(benzoxazol-2′-yl)benzene and at least one compound selected from the group of hydroxyacetophenone, an alkanediol and benzoic acid or a salt thereof as a synergistic antimicrobial agent mixture.

13. The use according to claim 12, wherein the wherein the hydroxyacetophenone is p-hydroxyacetophenone, the alkane diol is 1,3-propandiol and the benzoic acid or a salt thereof is sodium benzoate.

14. The use according to claim 12, to enhance shelf life and/or storage stability of a topical composition.

15. A method of inhibiting or delaying microbial breakdown of a topical composition, wherein said method comprises the step of adding to the cosmetic composition an effective amount of 1,4-di(benzoxazol-2′-yl)benzene and at least one compound selected from the group of hydroxyacetophenone, an alkane diol and benzoic acid or a salt thereof.

Description

EXAMPLE

[0099] 1. Preparation of 1,4-di(benzoxazol-2′-yl)benzene:

[0100] A mixture of 702 g polyphosphoric acid and 4.28 ml methanesulfonic acid was heated to 90° C. 65 g terephthalic acid and 107 g 2-aminophenol were added. The mixture was stirred under inert atmosphere at 180° C. for 8 hours and then transferred to ice water. The precipitated product was filtered and washed with water and acetic acid. The precipitate was dispersed in water and the pH adjusted to 8.0 with sodium hydroxide, filtered and washed with water. The crude product was suspended in a mixture of toluene and 1-butanol 3.3:1, stirred at 85° C. for one hour, filtered, washed with diethyl ether, and dried resulting in coarse particles of solid amorphous 1,4-di(benzoxazol-2′-yl)benzene (in the following referred to as DBO).

[0101] 2. Preparation of 1,4-di(benzoxazol-2′-yl)benzene, 30 wt.-% aqueous dispersion:

[0102] Afterwards, a suspension of 175 g of the coarse particles, 324 g of water and 65 g Green APG 0810 was prepared and the suspension was milled for 2 h with a LabStar laboratory mill using yttrium-stabilized zirconium oxide grinding beads (0.3 mm, from Tosoh Ceramic, Japan) and cooling of the milling chamber (−12° C. brine). After removal of the grinding beads, a 30% aqueous dispersion of micronized 1,4-di(benzoxazol-2′-yl)benzene (in the following referred to as DBO aq.) was obtained which was used in the antimicrobial tests and formulations as outlined below.

[0103] 1. Antimicrobial Activity

[0104] The antimicrobial efficacy was assessed in analogy to the regulatory challenge test method (NF EN ISO11930). Thus, mixtures of the respective active(s) with physiological serum with 0.85 wt.-% NaCl in the concentrations as outlined below are prepared under sterile conditions. Controls were also prepared under sterile conditions. The control as well as the mixtures were then deposed in 96-deep well plates (1.6 ml/well). The wells were contaminated with the respective bacterial or the fungal strains at 2.5*10.sup.5 to 5.6*10.sup.5 cfu/ml for the bacteria and 1*10.sup.4 to 2.5*10.sup.4 cfu/ml for the fungi to obtain the initial contamination as outlined below. After the contamination, each well was thoroughly mixed to ensure a homogeneous distribution of microbes. Then each plate was incubated at 22° C. for 24 h. The counting of the (remaining) population is carried out 24 h after contamination. Then, the average log reduction is calculated [−log 10{(value inoculum)/(value sample)}] which is represented in tables 1-5.

TABLE-US-00001 TABLE 1 Results using 0.3 wt.-% DBO inoculum 24 h Log Microbe colony count [cfu/ml] reduction Candida albicans 32000 10000 −0.51 (preser., yeast) Aspergillus brasiliensis 45000 400 −2.05 (preserv., mold)

TABLE-US-00002 TABLE 2 Results using 1 wt.-% DBO aq. (0.3 wt.-% active) inoculum 24 h Log Microbe colony count [cfu/ml] reduction Candida albicans 70000 40000 −0.24 Escherichia coli 400000 10000 −1.60 Staphylococcus aureus 550000 100000 −0.74 Pseudomonas aeruginosa 330000 1000 −2.52 Aspergillus brasiliensis 40000 1000 −1.60 *Δ = ({microorganism count t = 0} − {microorganism count t = 24 h}/{microorganism count t = 0})*100

[0105] As can be seen in the tables above 1,4-di(benzoxazol-2′-yl)benzene has an antimicrobial effect over a broad range of microbes and can thus be used as preservation booster. Since it is known that typically the water phase of a product is most susceptible to microbial growth, 1,4-di(benzoxazol-2′-yl)benzene is thus particularly suitable to protect products comprising a water phase such as e.g. cosmetic compositions in the form of an O/W or W/O emulsion against microbial decay and breakdown and is thus suitable for improving its preservation.

TABLE-US-00003 TABLE 3 Synergistic effect with p-Hydroxyacetophenone (HAP) Time Staphylococcus aureus Log Test solution [h] colony count [cfu/ml] reduction 1.0 wt.-% DBO aq.* 0 550000 24 100000 −0.74 0.3 wt.-% HAP 0 550000 24 70000 −1.16 1.0 wt.-% DBO aq.* 0 550000 0.3 wt.-% HAP 24 100 −3.74 Control 0 550000 24 1000000 +0.26 *0.3 wt.-% active

[0106] As can be retrieved from table 2 DBO synergistically enhances the antimicrobial activity of p-Hydroxyacetophenone.

TABLE-US-00004 TABLE 4 Synergistic effect with sodium benzoate Time Escherichia coli Log Test solution [h] colony count [cfu/ml] reduction 1.0 wt.-% DBO aq.* 0 400000 24 10000 −1.60 0.2 wt.-% Sodium Benzoate 0 400000 24 1000000 +0.40 1.0 wt.-% DBO aq.* 0 400000 0.2 wt.-% Sodium Benzoate 24 100 −3.60 Control 0 400000 24 1000000 +0.40 *0.3 wt.-% active

[0107] As can be retrieved from table 3 the combination of DBO and sodium benzoate exhibits a synergistic antimicrobial activity.

TABLE-US-00005 TABLE 5 Synergistic effect with 1,3-propanediol (PDO) Time Candida albicans Log Test solution [h] colony count [cfu/ml] reduction 1.0 wt.-% DBO aq.* 0 70000 24 40000 −0.24 1.0 wt.-% PDO 0 70000 24 40000 −0.24 1.0 wt.-% DBO aq.3 0 70000 1.0 wt.-% PDO 24 10000 −0.85 Control 0 70000 24 70000 0 *0.3 wt.-% active

[0108] As can be retrieved from table 4 the combination of DBO and 1,3-propanediol exhibits a synergistic antimicrobial activity.

[0109] 2. Formulation Examples

[0110] Sunscreen o/w

TABLE-US-00006 Phase INCI Weight-% A PHENYLBENZIMIDAZOLE SULFONIC ACID 0.5 0.5 0.5 AQUA 10 10 10 TRIETHANOLAMINE 0.4 0.4 0.4 B DISODIUM EDTA; AQUA 0.1 0.1 0.1 AQUA Add 100 BUTYLENE GLYCOL 4 4 4 ACACIA SENEGAL GUM; XANTHAN GUM 0.3 0.3 0.3 COCO-GLUCOSIDE; AQUA 0.5 0.5 0.5 PROPANEDIOL 3 SODIUM BENZOATE 0.4 C C15-19 ALKANE 5 5 5 OCTOCRYLENE 6 6 6 POTASSIUM CETYL PHOSPHATE 1.8 1.8 1.8 TOCOPHERYL ACETATE 0.5 0.5 0.5 METHOXYDIBENZOYLMETHANE 2.5 2.5 2.5 ETHYLHEXYL SALICYLATE 5 5 5 TITANIUM DIOXIDE; SILICA; DIMETHICONE 3 3 3 PHENOXYETHANOL; ETHYLHEXYLGLYCERIN 1 1 1 DIISOPROPYL ADIPATE; PROPYLENE GLYCOL 3 3 3 DICAPRYLATE/DICAPRATE; C12-15 ALKYL BENZOATE; DIISOPROPYL SEBACATE D SILICA 1 1 1 DBO aq. 1-3 1-3 1-3 E HYDROXYETHYL ACRYLATE/SODIUM 1 1 1 ACRYLOYLDIMETHYL TAURATE COPOLYMER; POLYISOBUTENE; PEG-7 TRIMETHYLOLPROPANE COCONUT ETHER HYDROXYACETOPHENONE 0.75 0.6 F AQUA; SODIUM HYDROXIDE 1.45 1.45 1.45

[0111] Crème Gel

TABLE-US-00007 Phase INCI Weight.-% A AQUA Add 100 GLYCERIN 3 3 3 PHENOXYETHANOL; 1 ETHYLHEXYLGLYCERIN PROPANEDIOL 3 SODIUM BENZOATE 0.5 B CAPRYLIC/CAPRIC TRIGLYCERIDE 5 5 ETHYLHEXYL OLIVATE; SODIUM 1.5 1.5 ACRYLATES COPOLYMER; POLYGLYCERYL-4 OLIVATE C DBO aq. 1-3 1-3 1-3 HYDROXYACETOPHENONE 0.1 0.7 SODIUM HYDROXIDE; AQUA 0.05 0.05 CITRIC ACID; AQUA 0.1

[0112] Sunscreen w/o

TABLE-US-00008 Phase INCI Weight-% A AQUA Add 100 PROPANEDIOL 3.0 3.0 B LAURYL PEG-10 6.0 6.0 6.0 TRIS(TRIMETHYLSILOXY)SILYLETHYL DIMETHICONE OCTOCRYLENE 3.0 3.0 3.0 BUTYL 2.0 2.0 2.0 METHOXYDIBENZOYLMETHANE POLYSILICONE-15 3.0 3.0 3.0 ZINC OXIDE; 11.7 11.7 11.7 TRIETHOXYCAPRYLYLSILANE HOMOSALATE 7.5 7.5 7.5 TITANIUM DIOXIDE; SILICA; 3.0 3.0 3.0 DIMETHICONE DIMETHICONE 3.0 3.0 3.0 ISONONYL ISONONANOATE 10.0 10.0 10.0 C CYCLOPENTASILOXANE 20.0 20.0 20.0 ALCOHOL DENAT. 5.0 5.0 5.0 DBO aq. 1-3 1-3 1-3 SODIUM BENZOATE 0.5 HYDROXYACETOPHENONE 0.2

[0113] Skin Care O/W

TABLE-US-00009 Phase INCI Weight-% A AQUA Add 100 PROPANEDIOL DISODIUM EDTA; AQUA 0.05 0.05 0.05 XANTHAN GUM 0.2 0.2 0.2 ETHOXYDIGLYCOL 2.0 2.0 2.0 CETEARYL OLIVATE; SORBITAN 4.0 4.0 4.0 OLIVATE DIMETHICONE 2.0 2.0 2.0 B ISOPROPYL MYRISTATE 4.0 4.0 4.0 DICAPRYLYL ETHER 5.0 5.0 5.0 PARAFFINUM LIQUIDUM 2.0 2.0 2.0 STEARIC ACID; PALMITIC ACID 1.5 1.5 1.5 ISOSTEARYL ISOSTEARATE 5.0 5.0 5.0 C DBO aq. 1-3 1-3 1-3 SODIUM BENZOATE 0.6 4.0 HYDROXYACETOPHENONE 0.75 0.5 SODIUM HYDROXIDE; AQUA 0.08 0.08 0.08

[0114] Skin Care o/w

TABLE-US-00010 Phase INCI Weight-% A AQUA Add 100 HYDROXYPROPYL STARCH 1.0 1.0 1.0 PHOSPHATE; AQUA HYDROXYACETOPHENONE 0.6 0.5 PROPANEDIOL 3.0 SODIUM BENZOATE 0.5 GLYCERIN 2.0 2.0 2.0 B ISOPROPYL MYRISTATE 2.0 2.0 2.0 CETEARYL ALCOHOL 2.0 2.0 2.0 SQUALANE 2.0 2.0 2.0 POTASSIUM CETYL PHOSPHATE 3.0 3.0 3.0 COCOGLYCERIDES 5.5 5.5 5.5 C12-15 ALKYL BENZOATE 4.0 4.0 4.0 HYDROGENATED COCO- 4.0 4.0 4.0 GLYCERIDES PARAFFINUM LIQUIDUM 3.0 3.0 3.0 C TOCOPHEROL 0.2 0.2 0.2 SACCHARIDE ISOMERATE; AQUA; 1.0 1.0 1.0 CITRIC ACID; SODIUM CITRATE ARGANIA SPINOSA KERNEL OIL 2.0 2.0 2.0 DBO aq. 1-3 1-3 1-3

[0115] CC Cream o/w

TABLE-US-00011 Phase INCI Weight-% A AQUA Add 100 PROPANEDIOL 4.0 4.0 HYDROXYACETOPHENONE 0.7 0.5 SODIUM BENZOATE 0.4 B MICROCRISTALLINE 2.0 2.0 2.0 CELLULOSE; CELLULOSE GUM C ETHYLHEXYL 10.0 10.0 10.0 METHOXYCINNAMATE BEHENYL ALCOHOL 4.0 4.0 4.0 GLYCERYL MYRISTATE 4.0 4.0 4.0 ISOAMYL LAURATE 14.0 14.0 14.0 OCTYLDODECANOL 8.0 8.0 8.0 DIMETHICONE 4.0 4.0 4.0 TITANIUM DIOXIDE; AQUA; 8.0 8.0 8.0 GLYCERIN; PHENOXYETHANOL; CELLULOSE GUM; SODIUM POLYACRYLATE CI77499; AQUA; GLYCERIN; 0.25 0.25 0.25 PHENOXYETHANOL; CELLULOSE GUM; SODIUM POLYACRYLATE CI77491; AQUA; GLYCERIN; 0.545 0.545 0.545 PHENOXYETHANOL; CELLULOSE GUM; SODIUM POLYACRYLATE CI77492; AQUA; GLYCERIN; 2.2 2.2 2.2 PHENOXYETHANOL; CELLULOSE GUM; SODIUM POLYACRYLATE TITANIUM DIOXIDE; SILICA; 3.0 3.0 3.0 DIMETHICONE POTASSIUM CETYL PHOSPHATE 3.0 3.0 3.0 D DBO aq. 1-3 1-3 1-3