cosmetics preservatives

The present invention relates to the use of alkylresorcinols for improving the antimicrobial activity of cosmetics preservatives. The invention moreover relates to a concentrate which comprises i) alkylresorcinol and ii) conventional preservative, and to the use of the concentrate for preserving cosmetics .

Substances which in some cases are listed in Annex V of Regulation (EC) no. 1223/2009 as allowed preservatives are employed for preserving cosmetics. These listed substances are restricted in their use concentration and when used alone in the permitted maximum concentration do not always lead to the desired preservation. The substances employed also in some cases display disadvantages, such as an undesirable smell, discolorations or harmful influences on the stability of the cosmetic preparations. Breaking of emulsions or massive changes in viscosity can also occur.

In order to overcome these disadvantages so-called boosters are employed. In the concentration employed these substances show no or only a very low intrinsic antimicrobial activity, but are capable of increasing the action of other preserving constituents and therefore open up the possibility of reducing the necessary content of these and thus of optimising economically and ecologically the use of preservatives. These interactions are also called synergism. Known substances of this category are various alkanediols, such as e.g. 1,2- octanediol, as well as complexing agents and also 1- (2- ethylhexyl) glycerol .

The use of resorcinols is also known in cosmetics. For example, DE 10 2008 041 971 Al discloses a method for reducing age spots. A cosmetic or pharmaceutical preparation which can contain, for example, 4-butylresorcinol (rucinol) or 4- hexylresorcinol is employed for this. WO 2008/058680 describes a cosmetic preparation for lightening skin which contains a combination of a) skin-lightening agent and b) glucosyl glyceride.

US 2009/0148391 Al discloses compositions for lightening skin or hair with a content of, for example, 0.5 to 5 wt . % of 4- butylresorcinol .

EP 1 374 849 Al discloses cosmetic compositions for bleaching skin or hair which, in addition to ascorbic acid (derivatives) , can also contain depigmenting agents, such as, for example, 4-butylresorcinol.

GB 0910629 relates to cosmetic hair colouring products which contain, for example, butylresorcinol as an antioxidant in order to avoid degradation products which irritate the skin and are formed in the oxidation of the dyestuffs.

EP 2 149 364 Al discloses cosmetic odour-reducing preparations with a content of 2-methyl-4-isothiazolin-3-one which furthermore contain hydroquinone radical scavengers.

DE 10 2013 217 244 Al describes emulsifier-free cosmetic preparations which furthermore can contain whitening substances, such as rucinol.

There is furthermore a large number of substances which are employed for preserving cosmetics. Nevertheless, these known cosmetics preservatives, when they are employed in the necessary (and often undesirably high) amounts for the antimicrobial treatment, lead to skin irritations or other topical actions which are undesirable for cosmetics, or adversely influence other use properties of the cosmetic (such as, for example, viscosity) . The present invention accordingly is based on the object of providing advantageous routes for preserving cosmetics.

It has now been found, surprisingly, that alkylresorcinols in a low use concentration cause an intensification of the activity of conventional cosmetics preservatives. The use concentrations of the alkylresorcinols which are necessary for this are in a range here in which the known lightening of the skin does not occur. For example, the addition of 0.1 wt . % of 4-hexylresorcinol or 0.1 % of 4-butylresorcinol in a model cream does not lead to this model cream having a skin- lightening effect (namely no difference could be detected between a preparation with 0.1 % of 4-hexylresorcinol or 0.1 % of 4-butylresorcinol and a placebo preparation) . In contrast, the action of conventional cosmetics preservatives is increased in these low amounts, the combinations according to the invention of alkylresorcinol with conventional cosmetics preservative advantageously imparting no skin-lightening action to the cosmetic. In a first aspect the invention therefore relates to the use of alkylresorcinols for improving the antimicrobial activity of cosmetics preservatives.

In a second aspect the invention relates to concentrates which comprise alkylresorcinol and cosmetics preservative.

In a third aspect the invention relates to the use of the concentrate for preserving cosmetics. The present invention accordingly relates to the use of alkylresorcinols in cosmetics in order to be able to reduce the necessary content of other preserving constituents and therefore to optimise economically and ecologically the use thereof and to overcome regulatory restrictions. Alkylresorcinols indeed also show an antimicrobial activity without combination with other active compounds, but not in the use concentrations necessary for the action intensification according to the invention. These are so low that the alkylresorcinols show no intrinsic antimicrobial activity, as is shown below in the examples.

The object is achieved in particular by providing a combination of alkylresorcinols, such as e.g. 4- butylresorcinol or 4-hexylresorcinol, with known active compounds for preserving cosmetics, such as e.g. aromatic alcohols (such as benzyl alcohol, phenoxyethanol , phenylethyl alcohol, phenoxyisopropanol , dichlorobenzyl alcohol and phenylpropanol ) or also polyhydric aliphatic alcohols (such as e.g. 1, 2-pentanediol, chlorphenesin, 1, 2-hexanediol, 1,2- octanediol and 1 , 3-propanediol ) . Further substance classes, such as organic acids (such as e.g. benzoic acid, sorbic acid, salicylic acid, anisic acid, dehydroacetic acid, 4- hydroxybenzoic acid) or salts or esters thereof can furthermore be used. Formaldehyde, paraformaldehyde or agents which split off formaldehyde (such as e.g. methenamine, DMDM hydantoin, diazolidinylurea, imidazolidinylurea, sodium hydroxymethylglycinate, 7-ethylbicyclooxazolidine, benzyl hemiformal, hexetidine, quaternium-15 or also Bronidox and bronopol) can furthermore be combined. Heterocyclic active compounds (such as e.g. methylchloroisothiazolinone, methylisothiazolinone, pyrithione zinc, piroctone olamine or climbazole) are likewise possible. Phenol derivatives known for their preserving activity (such as e.g. chlorocresol , triclosan, chloroxylenol , bromochlorophene, o-cymen-5-ol , chlorophen, 2-hydroxybiphenyl) or salts thereof are furthermore suitable. Quaternary ammonium salts (such as e.g. alkyl (C12-22) trimethylammonium bromide and chloride, benzalkonium chloride, benzethonium chloride, octenidine dihydrochloride) and also biguanides and amidines (such as e.g. dibromohexamidine, hexamidine, chlorhexidine or polyaminopropyl biguanide) can furthermore be used in the combinations found. In addition to aldehydes (such as e.g. glutaraldehyde) or amino acid derivative (such as ethyl lauroyl arginate HC1) , organic halogen compounds (such as triclocarban, chloroacetamide, 3-iodo-2-propynyl butylcarbamate, chlorobutanol ) are also promising combination partners for alkylresorcinols . The combinations of i) alkylresorcinol and ii) cosmetics preservative can be formed in the products to be preserved by separate metering in of the individual components during the preparation of the cosmetic product, or provided in the form of a premix. Premixes, above all of a liquid type, provide the processing company with easier handling and a smaller number of individual raw materials to be held in stock, which also means less outlay in goods inwards testing.

An example of an embodiment as a liquid preparation preferably contains one, two or more alkylresorcinols in one, two or more aromatic alcohols, and optionally further solvents, microbicidal active compounds, one, two or more selected stabilisers and optionally further functional additives or auxiliary substances.

The use of alkylresorcinols in cosmetic products for synergistically increasing the activity of preserving constituents is furthermore claimed. A concentrate preparation containing: i) at least one alkylresorcinol or salts thereof, preferably 4-butylresorcinol or 4-hexylresorcinol, and

ii) at least one aromatic alcohol, preferably phenoxyethanol , benzyl alcohol or phenylpropanol , and iii) optionally a solvent (such as, for example, water, alcohols or glycols or glycol ethers) and

iv) optionally further microbicidal active compounds, functional additives or auxiliary substances,

moreover claimed.

The use of said combination of ingredients for preserving cosmetic products is furthermore claimed. Detailed description of the invention

According to the first aspect, the invention relates to the use of one, two or more alkylresorcinols for improving the antimicrobial activity of one, two or more cosmetics preservatives, wherein the amount of alkylresorcinol is at most 0.2 wt.%, based on the weight of the cosmetic.

Preferably, the amount of alkylresorcinol employed according to the invention is 0.01 to 0.15 wt.%, more preferably 0.02 to 0.12 wt.%, in particular 0.03 to 0.1 wt.%, in each case based on the weight of the cosmetic.

Preferred alkylresorcinols employed according to the invention are 4-alkylresorcinols .

A preferred alkyl group of the alkylresorcinol is selected from linear or branched alkyl groups, wherein the alkyl group is preferably a linear alkyl group.

It is furthermore preferable according to the invention for the alkyl group to be a C ₂ - to Cio-alkyl group, preferably a C3- to Cs-alkyl group, such as a butyl or hexyl group, wherein the alkyl group in particular is a butyl group.

In all the embodiments of the invention it is particularly preferable for 4-n-butylresorcinol to be employed as the alkylresorcinol .

Cosmetics preservatives which are employed according to the invention in combination with alkylresorcinols are predominantly listed in Annex V of Regulation (EC) no. 1223/2009 as allowed preservatives.

Cosmetics preservatives which are preferably used according to the invention are selected from

a) aromatic alcohols (such as benzyl alcohol, phenoxyethanol , phenylethyl alcohol, phenoxyisopropanol , dichlorobenzyl alcohol and phenylpropanol ) ,

b) polyhydric aliphatic alcohols (such as 1,2- pentanediol, chlorphenesin, 1, 2-hexanediol, 1,2- octanediol and 1 , 3-propanediol ) ,

c) organic acids (such as benzoic acid, sorbic acid, salicylic acid, anisic acid, dehydroacetic acid, 4- hydroxybenzoic acid) or salts or esters thereof, d) formaldehyde, paraformaldehyde or agents which split off formaldehyde (such as methenamine, DMDM hydantoin, diazolidinylurea, imidazolidinylurea, sodium hydroxymethylglycinate, 7- ethylbicyclooxazolidine, benzyl hemiformal, hexetidine, quaternium-15, Bronidox and bronopol) , e) heterocyclic active compounds (such as methylchloroisothiazolinone, methylisothiazolinone, pyrithione zinc, piroctone olamine or climbazole) , f) phenol derivatives (such as chlorocresol , triclosan, chloroxylenol , bromochlorophene, o-cymen-5-ol , chlorophene, 2-hydroxybiphenyl) or salts thereof, g) quaternary ammonium salts (such as alkyl (C12-22) trimethylammonium bromide and chloride, benzalkonium chloride, benzethonium chloride, octenidine dihydrochloride) ,

h) biguanides and amidines (such as dibromohexamidine, hexamidine, chlorhexidine or polyaminopropyl biguanide) ,

i) aldehydes (such as glutaraldehyde) ,

j) amino acid derivatives (such as ethyl lauroyl arginate HC1) and

k) organic halogen compounds (such as triclocarban, chloroacetamide, 3-iodo-2-propynyl butylcarbamate) .

It is furthermore preferable for the cosmetic in which i) alkylresorcinol (s) and ii) cosmetics preservative ( s ) are contained to comprise at most 1 wt . % of aromatic alcohols, more preferably 0.5 wt . % of aromatic alcohols, wherein a particularly preferred cosmetic contains no aromatic alcohols.

In a second aspect the invention relates to a concentrate which comprises

i) one, two or more alkylresorcinols and

ii) one, two or more cosmetics preservatives selected from

a) aromatic alcohols,

b) polyhydric aliphatic alcohols, c) organic acids or salts or esters thereof, d) formaldehyde, paraformaldehyde or agents which split of formaldehyde,

e) heterocyclic active compounds, f) phenol derivatives or salts thereof, g) quaternary ammonium salts, h) biguanides and amidmes,

i) aldehydes ,

j) amino acid derivatives and

k) organic halogen compounds.

Concentrates which are preferred are those which comprise

i) alkylresorcinol selected from 4-n- butylresorcinol , 4-n-hexylresorcinol and mixtures thereof and

ii) one, two or more aromatic alcohols.

In a third aspect the invention relates to the use of the concentrate according to the second aspect for preserving cosmetics. Preferred cosmetics in which the combination according to the invention of i) alkylresorcinol (s) and ii) cosmetics preservative ( s ) according to the first aspect are employed, in particular the concentrate according to the second aspect, are leave-on and rinse-off cosmetics.

The advantages of the invention emerge in particular from the following examples. Unless stated otherwise, percentage data relate to the weight. Examples

The antimicrobial activity was demonstrated in an O/W cream, the composition and preparation of which are described below (Table 1) . The 4-butylresorcinol mentioned is 4-n- butylresorcinol : Table 1.

Cognis

Croda

For the preparation, the separately prepared phases A and B were each heated to 80 °C. Phase B was slowly added to phase A, with stirring. The mixture was homogenised and cooled to room temperature with cautious mixing, in order to obtain the cream.

In germ count reduction tests the killing action of various active compounds and active compound combinations was tested semiquantitatively (Table 2) . In Test A the synergistic intensification of the activity of phenoxyethanol by 4- butylresorcinol is very clear. Test B in contrast shows the effect on phenylpropanol , and Test C on benzyl alcohol. In these tests the low or non-detectable intrinsic activity of the 4-butylresorcinol employed at the use concentrations selected (i.e. without a combination partner) can also be seen .

Testing was carried out in each case over a period of one week in order to observe whether the killing required for successful testing in the preservation challenge test (KoKo test, SM 021) is achieved. In the KoKo test a sample is artificially contaminated six times at intervals of in each case one week and tested for microbial growth before each contamination. Successful preservation shows no growth over the entire period.

Table 2

Table 3 shows by way of example the results in a sample without preservative and in a sample with a combination used according to the invention of 4-hexylresorcinol with phenylpropanol . The preserving action of the combination is adequate .

Table 3

Legend :

L lawn-like growth

++++ ~10 ⁵ CFU

+++ ~10 ⁴ CFU

++ ~10 ³ CFU

+ ~10 ² CFU

0 no growth

/ test discontinued

B bacteria

Y yeast

M mould

Demonstration that 4-butylresorcinol in a small amount does not lighten the skin

Test materials

The test products were used by the testing organisation as provided by the contracting party (Table 4) : Table 4

Storage conditions room temperature

Use area volar forearm

Use volume determined by weighing the amount of test product before and after the use period. The volume employed per use was the amount which fitted on a fingertip .

Use method the test materials were applied by the test subjects at home two to three times daily according to normal use conditions. Appropriate instructions were given verbally to the test subjects, and the use was demonstrated to the test subjects on the first day of the study.

Of the 22 test subjects, two (2) were excluded during the study (N = 20) .

Methods

The study was conducted according to a protocol and corresponded to GCP guidelines (Table 5) . Table 5

The first use of the test materials took place after the instrument measurement at the study location. Results of the skin colour measurements

The skin colour was determined with a chromameter and the individual typological angle (ITA°) was calculated in order to evaluate the brownness of the skin. A higher value for ITA° corresponds to a lighter-coloured skin.

Tab. 6 shows the mean values for ITA° before (day 1) and after use of the product (57 days), the differences compared with the base line (day 1) and the results of the comparisons of the treatments and the times with the t-test for associated random samples.

Table 6: Chromameter ITA - mean values, difference from the base line and comparisons of the treatments for differences compared with the base line and times with raw data with the t-test for associated random samples (N = 20)

n.s.: not significant *: significant, p ≤ 0.05

For all the test areas a significant increase in the values for ITA° was found at the end of the study on day 57, compared with the values for the base line (day 1) .

The comparison of the treatments showed no significant differences (difference from the base line) for all the changes in ITA° . The subjective evaluation of the skin colour by the test subjects themselves also showed no significant differences between the treatments.

Demonstration that 4-hexylresorcinol in a small amount does not lighten the skin

Test materials

The test products were used by the testing organisation as provided by the contracting party (Table 7) : Table 7

The remaining conditions corresponded to those in the investigation of 4-butylresorcinol . Of the 22 test subjects, six (6) were excluded during the study (N = 16) .

Methods

The study was conducted according to a protocol and corresponded to GCP guidelines (Table 8) .

Table 8

The first use of the test materials took place after the instrument measurement at the study location. Results of the skin colour measurements

The skin colour was determined with a chromameter and the individual typological angle (ITA°) was calculated in order to evaluate the brownness of the skin. A higher value for ITA° corresponds to a lighter-coloured skin.

Tab. 9 shows the mean values for ITA° measured at both times, the differences compared with the base line (day 1) and the results of the comparisons of the products and times with the t-test for associated random samples. Table 9: Chromameter ITA (N = 16)

n.s.: not significant *: significant, p ≤ 0.05

The comparison of the values for ITA° before (day 1) and after (day 57) use of the products showed a significant increase after use of the two test products A and B. For changes in ITA no significant difference (difference from the base line) was found between the test products A and B. The subjective evaluation of the skin colour by the test subjects themselves also showed no significant differences between the treatments.

It is therefore demonstrated that a significant lowering of skin pigmentation is caused by use of the cosmetic products employed. However, no significant difference was found between the products tested. Because the cream containing no alkylresorcinol (placebo) also showed this effect, it is demonstrated that the lowering of the skin pigmentation was caused by a reduction in UV radiation acting in the course of the study.