WO2020201271A1

WO2020201271A1 - Use of specific hyperbranched copolymers to enhance antimicrobial action of antimicrobial agents

Info

Publication number: WO2020201271A1
Application number: PCT/EP2020/059097
Authority: WO
Inventors: Christine Mendrok-Edinger
Original assignee: Dsm Ip Assets B.V.
Priority date: 2019-04-01
Filing date: 2020-03-31
Publication date: 2020-10-08
Also published as: EP3945820A1

Abstract

The present invention relates to the use of a specific hyperbranched copolymer (HBC) of the monomers dodecenyl succinic acid anhydride, diisopropanol amine and bis-dimethylaminopropyl amineand an antimicrobial agent as a synergistic antimicrobial agent mixture. It has been found that said hyperbranched copolymer synergistically enhances the antimicrobial action of the antimicrobial agent.

Description

USE OF SPECIFIC HYPERBRANCHED COPOLYMERS TO ENHANCE

ANTIMICROBIAL ACTION OF ANTIMICROBIAL AGENTS

Technical Field

The reduction of growth of microorganisms is an economically highly important field of research.

Background of the invention

Microorganisms lead to the decay of food and goods of daily use such as cosmetic compositions, household products, plastics, paper or paints. Particularly, cosmetic products are prone to be attacked by microorganism. The reduction of growth of microorganisms is essential for the consumers safety and health when using a cosmetic product. By reducing the growth of microorganisms, the shelf life of a cosmetic product can be increased. Currently a variety of substances are known to reduce the growth of microorganism. As the use of certain antimicrobial agents are under public discussions a reduction of antimicrobial agents is a strong desire in the cosmetic industry.

EP 2 794 729 B1 disclose the preparation of specific hyperbranched polyesters which can be used as flocculants in paper production and in dishwater detergents.

EP 2 296 619 B1 discloses that specific hyperbranched copolymers have an advantageous effect in a shampoo for increasing the volume of hair.

Summary of the invention

Therefore, the problem to be solved by the present invention is to offer a new possibility to inhibit microbial growth.

It has been surprisingly found that a specific hyperbranched copolymer is able to enhance the antimicrobial action of existing antimicrobial agents, particularly when used in a cosmetic composition. This effect is a synergistic effect of the specific hyperbranched polymer on to the antimicrobial effect of said antimicrobial agents. This surprising finding is very advantageous as this invention can lead to higher stability, longer shelf life, respectively, to the reduction of antimicrobial agents in cosmetic compositions by, nevertheless, maintaining the antimicrobial properties.

Further aspects of the invention are subject of further independent claims.

Particularly preferred embodiments are subject of dependent claims.

Detailed description of the invention

In a first aspect the present invention relates to the use of a mixture of a) a hyperbranched copolymer (HBC) of the monomers

(i) dodecenyl succinic acid anhydride

(ii) diisopropanol amine

(iii) bis-dimethylaminopropyl amine

having terminal groups of the formula

and having a molecular weight Mn of between 1200 and 4000 g/mol; and additionally

b) an antimicrobial agent

as a synergistic antimicrobial agent mixture.

The term "molecular weight Mn" stands for the number average molecular weight.

The term "preparation" or "formulation" is used in this document as equivalent to the term "composition".

The term "antimicrobial agent" is used in this document for an organic chemical substance which reduces the growth of microorganisms. However, monohydroxy-Ci-C6 alkanes, such as methanol, ethanol, propanol or /so-propanol, for this invention, are not considered to be antimicrobial agents. For sake of clarity, it is worthwhile that antioxidants are not to be regarded as antimicrobial agents.

Hyperbranched copolymer

The hyperbranched copolymer (HBC) is preferably prepared by the following consecutive steps of:

a1 ) polymerizing the monomers (i) and monomers (ii) and monomers (iii) to yield a polyesteramide having terminal dimethyl amino groups of the

- N

formula \

a2) quaternization of the dimethyl amino groups of the polyesteramide of step a1 ) by 2-chloroacetate, particularly by sodium 2-chloroacetate. Details for the polymerization step a1 ) to yield the respective polyesteramide

- N /

having terminal dimethyl amino groups of the formula \ are disclosed for example by EP 2 794 729 B1.

Preferably in the polymerization step a1 ) the monomer (iii) is added to a mixture of monomers (ii) and (iii) under stirring, followed by heating.

Details of the quaternization step a2) are disclosed as well by

EP 2 794 729 B1. Therefore, the entire content of EP 2 794 729 B1 is hereby incorporated by reference. It is preferred that the molar ratio of the monomers (i) to monomers (ii) is between 5: 1 and 0.5 : 1 , particularly between 4 : 1 and 1 : 1 , preferably between 3 : 1 and 3 : 2.

It is further preferred that the molar ratio of the monomers (i) to monomers (iii) is between 5 : 1 and 0.5 : 1 , particularly between 3 : 1 and 1 : 1 , preferably between 2.5 : 1 and 1.1 : 1.

The hyperbranched copolymer (HBC) has preferably a number average molecular weight M_n of between 1400 and 3000 g/mol, preferably between 2100 and 2400 g/mol.

Preferably, the hyperbranched polymer (HBC) is polyquaternium-110, also identified by CAS Number 1323977-82-7.

Antimicrobial agent

Said mixture comprises an antimicrobial agent.

Antimicrobial agents are known as such to the person skilled in the art. The field of use, however, limits the choice of antimicrobial agents which are mainly due particularly to regulatory issues. In the field of food and cosmetics the choice of antimicrobial agents is rather limited.

Therefore, preferred antimicrobial agents suitable for this invention, are antimicrobial agents which are acceptable in the field of food and cosmetics.

In one of the preferred embodiments the antimicrobial agent is selected from the group consisting of:

-monoesters or monoethers of glycerol;

-salts or esters of aromatic acids;

-alkylarylic alcohols;

-phenolic ether alcohols;

-hydroxyacetophenone

-aliphatic diols; and

-hydroxamic acids. Preferred monoesters or monoethers of glycerol are those of formula (I)

wherein R is a C5-C10 alkyl group or C5-C10 cyclo alkyl group, preferably a C₆-C₉ alkyl group or a C₆-C₉ cyclo alkyl group, more preferably a Ce alkyl group or a Ce alkyl group or a Ce cyclo alkyl group;

and wherein n is either 1 or 0, preferably 0.

In case, where n=0, R is preferably cyclohexyl or n-octyl or n-hexyl or a branched octyl group, preferably an n-hexylgroup or an ethylhexyl group, more preferably a 2-ethylhexyl group.

In case, where n=1 , R is preferably a branched or unbranched saturated or olefinically unsaturated heptyl or nonyl group, preferably a saturated or olefini- cally unsaturated heptyl or nonyl group, more preferably n-octyl or n-nonyl group, most preferred n-nonyl group. A preferred embodiment is glyceryl caprylate.

The monoester or monoethers of glycerol of the formula (I) is preferably selected from the group consisting of cyclohexyl glycerin, hexyl glycerine, ethylhexyl glycerine, glyceryl caprate and glyceryl caprylate, more preferably, hexyl glycerine, ethylhexyl glycerine or glyceryl caprate, most preferably ethylhexyl glycerine or hexyl glycerine. In the most preferred embodiment compound of the formula (I) is 3-(2-ethylhexyloxy)-1 ,2-propandiol. Preferred salts of aromatic acids are salts of benzoic acid. Preferred salts are salts of potassium or sodium, preferably sodium salts. Preferred esters of aromatic acids

Preferred esters of aromatic acids are alkylesters, particularly C₁-C₆ alkyl esters of benzoic acid.

Most preferred salts or esters of aromatic acids is sodium benzoate.

Preferred alkylarylic alcohols are alcohols which have a C₁-C₆ alkylene group, preferably a methylene group, between the hydroxyl group and the aromatic part of the alkylarylic alcohols. Benzyl alcohol is the most preferred alkylarylic alcohols.

Phenolic ether alcohols are alcohols which comprise an alcoholic hydroxyl group as well as a ether of a phenol. The aromatic ring of the phenol is optionally substituted. The ether oxygen and the hydroxyl group are preferably separated by a C2-C4 alkylene group, preferably by an ethylene group. Phenoxyethanol is the most preferred phenolic ether alcohol.

The preferred hydroxyacetophenone is p-hydroxyacetophenone.

Aliphatic diols are alkanes which have 2 hydroxyl groups. These hydroxyl groups are preferably separated by a linear or branched C2-C10 alkylene group. Preferred aliphatic diols are propane diols, butylene glycol, pentanediols, 1 ,2 hexanediol, most preferably, 1 ,3-propane-diol.

Preferred hydroxamic acids are hydroxamic acids of a saturated C3-C12 alkanoic acid. Preferred hydroxamic acid is N-hydroxyoctanamide (=caprylhydrox- amic acid).

Preferably the antimicrobial agent is selected from the group consisting of hexyl glycerine, ethylhexyl glycerine or glyceryl caprate, sodium benzoate, benzyl alcohol, phenoxyethanol, 1 ,3-propane-diol and N-hydroxyoctanamide.

More preferably, the antimicrobial agent is selected from the group consisting of hexyl glycerine, ethylhexyl glycerine or glyceryl caprate, 1 ,3-propane- diol and N-hydroxyoctanamide.

Most preferred, the antimicrobial agent is hexyl glycerine or ethylhexyl glycerine.

In one of the most preferred embodiments, the antimicrobial agent is N- hydroxyoctanamide, particularly as commercially available under the tradename Zeastat™ from Index.

It is possible that the mixture comprises more than one antimicrobial agent. The weight ratio of said hyperbranched copolymer (HBC) and

antimicrobial agent is preferably in the range of between 1 :30 and 30:1 , preferred between 1 :20 and 20:1 , more preferred between 1 :10 and 10:1.

In a preferred embodiment the weight ratio of said hyperbranched copolymer (HBC) and antimicrobial agent is larger than 1.

The mixture of hyperbranched copolymer (HBC) and antimicrobial agent have synergistic antimicrobial activity against microorganisms. The antimicrobial agent mixture is an antimicrobial agent mixture which preferably inhibits the growth of a microorganism selected from the group consisting of Kocuria rhizophila, Staphylococcus aureus, Enterobacter gergoviae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Aspergillus brasiliensis, Penicillium pinophilum and Candida albicans.

Preferably the antimicrobial agent mixture in that the inhibits the growth of Staphylococcus aureus or Escherichia coli.

The antimicrobial agent mixture can be used in different fields.

Particularly, the antimicrobial agent mixture can be used in a product selected from the group of cosmetic compositions, household products, plastics, paper and/ or paints, preferably in a cosmetic composition.

The antimicrobial agent is preferably used in an amount of 0.01 - 5.0 % by weight, preferably 0.05 - 3.0 % by weight, more preferably 0.1 - 3.0 % by weight, based on the weight of a composition to which the antimicrobial agent is to be added.

The hyperbranched copolymer (HBC) is preferably used in an amount of 0.005 to 5.0 % by weight, more preferably of 0.05 - 3.0 % by weight, even more preferably of 0.1 - 3.0 % by weight, most preferably of 0.5-2.5 % by weight, based on the weight of a composition to which the hyperbranched copolymer (HBC) is to be added as antimicrobial agent. Said microbial agent mixture can be used in a both in a pharmaceutical (i.e. therapeutic) sense or in a non-therapeutic sense.

It is preferred that said microbial agent mixture is used in a non- therapeutic sense.

Hence, the preferred use is a non-therapeutic use, preferably a cosmetic use.

In all embodiments of the present invention, the use is, however, preferably a cosmetic (i.e. a non-therapeutic) use, such as for maintenance of skin homeostasis and/or balancing the skin microbiome and/or hair microbiome.

The above mentioned synergistic antimicrobial agent mixture is preferably used in a cosmetic composition.

The cosmetic composition further preferably comprises at least one emulsifier, preferably an anionic emulsifier. Preferably the anionic emulsifier is an anionic emulsifier selected from the group consisting of potassium cetyl phosphate, disodium cetearyl sulfosuccinate, sodium stearoyl glutamate, sodium stearoyl lactylate, glyceryl stearate citrate and sodium cocoyl isethionate.

Potassium cetyl phosphate is commercially available as Amphisol® K at DSM Nutritional Products Ltd Kaiseraugst.

The amount of emulsifier is preferably in the range between 0.1 - 6.0 % by weight, more preferably between 0.25 - 5.0 % by weight, particularly between 0.5 - 4.0 % by weight, based on the total weight of the cosmetic composition.

The composition is preferably sulfate-free.

Hence, the cosmetic composition is preferably particularly free of sulfates of the group consisting of alkyl sulfates, alkyl ether sulfates, alkyl amido ether sulfates, alkylaryl polyether sulfates and monoglycerides sulfate as well as mixtures thereof.

The term "free" as used in the present document, for example in "sulfate- free", is used to mean that the respective substance is only present at amounts of less than 0.5 % by weight, particularly less than 0.1 % by weight, more particularly below 0.05 % by weight, relative to the weight of the composition. Preferably, "free" means that the respective substance is completely absent in the composition.

The term "sulfate-free" is used in the present document to mean that the composition is free of any anionic tenside having a terminal anionic group of the formula

The cosmetic composition is preferably free of cationic emulsifiers. Typical example for such cationic emulsifiers are isostearamidopropyl dimethylamine, stearalkonium chloride, stearamidoethyl diethylamine, behentrimonium metho- sulfate, behenoyl PG-trimonium chloride, cetrimonium bromide, behenamidopropyl dimethylamine behenate, brassicamidopropyl dimethylamine, stearamidopropyl dimethylamine stearate, cocam idopropyl PG-dimonium chloride, distearoylethyl hydroxyethylmonium methosulfate, dicocoylethyl hydroxyethylmonium metho- sulfate, distearoylethyl dimonium chloride, shea butteramidopropyltrimonium chloride, behenamidopropyl dimethylamine, brassicyl isoleucinate esylate, acrylamidopropyltrimonium chloride/acrylates copolymer, linoleam idopropyl ethyldimonium ethosulfate, dimethyl lauramine isostearate, isostearamidopropyl laurylacetodimonium chloride, particularly behentrimonium chloride, distearyldi- monium chloride, cetrimonium chloride, steartrimonium chloride, and palmitamido- propyltrimonium chloride.

The cosmetic composition further may comprise cosmetic carriers, excipients and diluents as well as additives and active ingredients commonly used in the skin care industry which are suitable for use in the cosmetic are for example described in the International Cosmetic Ingredient Dictionary & Handbook by Personal Care Product Council (http://www.personalcarecouncil.org/), accessible by the online INFO BASE (http://online.personalcarecouncil.org/jsp/Home.jsp), without being limited thereto.

Such possible ingredients of the cosmetic composition are particularly enhance the performance and/or consumer acceptability such as preservatives, antioxidants, fatty substances/oils, thickeners, softeners, light-screening agents, moisturizers, fragrances, co-surfactants, fillers, sequestering agents, cationic-, nonionic- or amphoteric polymers or mixtures thereof, acidifying or basifying agents, viscosity modifiers, and natural hair nutrients such as botanicals, fruit extracts, sugar derivatives and/or amino acids or any other ingredients usually formulated into cosmetic compositions. The necessary amounts of the adjuvants and additives can, based on the desired product, easily be chosen by a person skilled in the art in this field and will be illustrated in the examples, without being limited hereto.

The additional ingredients can either be added to the oily phase, the aqueous phase or separately as deemed appropriate.

In an advantageous embodiment, the cosmetic compositions comprise from 50% to 99%, preferably from 60% to 98%, more preferably from 70% to 98%, such as in particular from 80% to 95% of a carrier, based on the total weight of the cosmetic composition.

In a particular advantageous embodiment, the carrier consists furthermore of at least 40 wt. %, more preferably of at least 50 wt.-%, most preferably of at least 55 wt.-% of water, such as in particular of 55 to 90 wt.-% of water.

Furthermore, it is preferred that the cosmetic composition comprises at least one UV filter. The UV filter may be a liquid or solid UV filter. The UV filter may be a UV-A or UV-B filters.

Suitable liquid UV-filter absorb light in the UVB (280 - 315 nm) and/ or UVA (315 - 400 nm) range and are liquid at ambient temperature (i.e. 25°C). Such liquid UV-filter are well known to a person in the art and encompass in particular cinnamates such as e.g. octyl methoxycinnamate (PARSOL® MCX) and isoamyl methoxycinnamate (Neo Heliopan® E 1000), salicylates such as e.g. homosalate (3,3,5 trimethylcyclohexyl 2-hydroxybenzoate, PARSOL® HMS) and ethylhexyl salicylate (also known as ethylhexyl salicylate, 2 ethylhexyl 2-hydroxybenzoate, PARSOL® EHS), acrylates such as e.g. octocrylene (2 ethylhexyl 2-cyano-3,3- diphenylacrylate, PARSOL® 340) and ethyl 2-cyano-3,3 diphenylacrylate, esters of benzalmalonic acid such as in particular dialkyl benzalmalonates such as e.g. di (2-ethylhexyl) 4-methoxybenzalmalonate and polysilicone 15 (PARSOL® SLX), dialkylester of naphthalates such as e.g. diethylhexyl 2,6-naphthalate (Corapan® TQ), syringylidene malonates such as e.g. diethylhexyl syringylidene malonate (Oxynex® ST liquid) as well as benzotriazolyl dodecyl p-cresol (Tinoguard® TL) as well as benzophenone-3 and drometrizole trisiloxane.

Particular advantageous liquid UV-filter are octyl methoxycinnamate, homosalate, ethylhexyl salicylate, octocrylene, diethylhexyl 2,6-naphthalate, diethylhexyl syringylidene malonate, benzotriazolyl dodecyl p-cresol, benzo- phenone-3, drometrizole trisiloxane, Polysilicone-15 as well as mixtures thereof.

Suitable solid UV-filter absorb light in the UVB and/ or UVA range and are solid at ambient temperature (i.e. 25°C). They are particularly solid organic UV filters. Particularly suited solid UV-filters are of the group consisting of bis-ethyl- hexyloxyphenol methoxyphenyl triazine, butyl methoxydibenzoyl methane, methy lene bis-benzotriazolyl tetramethylbutylphenol, diethylamino hydroxybenzoyl hexyl benzoate, ethylhexyl triazone, diethylhexyl butamido triazone and 4-methylbenzyli- dene camphor.

The amount of an individual organic UV filter is preferably in the range of 0.1 to about 6 % by weight, preferable in the range of 0.5 to 5 % by weight, most preferably in the range of 1 to 4 % by weight, based on the total weight of the cosmetic composition.

In case of a sun care composition, the total amount of organic UV filter (s) depends strongly on the targeted UV protection of said composition and is typically in the range of between 1 to 50% by weight, preferably between 5 to 40% by weight, based on the total weight of said composition.

A sun creme with an SPF 15 (SPF=sun protection factor), for example, comprises preferably a total amount of organic UV filter (s) of between 4 to 20% by weight, more preferably between 7 and 15 % by weight, based on the total weight of said composition.

A sun creme with an SPF 30, for example, comprises preferably a total amount of organic UV filter (s) of between 10 to 40% by weight, more preferably between 15 and 25 % by weight, based on the total weight of said composition. A sun creme with an SPF 50, for example, comprises preferably a total amount of organic UV filter (s) of between 15 to 50% by weight, more preferably between 20 and 40 % by weight, based on the total weight of said composition.

Particularly suitable thickeners are xanthan gum, gellan gum and/ or carboxymethylcellulose. Most preferably the thickener is xanthan gum or gellan gum. Further suitable thickeners are polyacrylates such as commercially available under the trade name Carbomer, or acrylate/C 10-30 alkyl acrylate crosspolymers or salts of polyacrylic acid or polyacrylamides.

Such thickener(s) are preferably used in an amount (total) selected in the range from 0.1 to 1 wt.-%, more preferably in an amount of 0.1 to 0.5 wt.-%, based on the total weight of the cosmetic composition.

It is preferred that the composition is free of polyvinylpyrrolidones (PVP), particularly free of alkylated polyvinylpyrrolidiones, such as copolymers of N-vinyl- pyrrolidones and hexadecane or eicosene, e.g. as commercially available as Antaron V-216 or Antaron V-220.

The cosmetic compositions in general have a pH in the range from 3 to 10, preferably a pH in the range from 4 to 8 and most preferably a pH in the range from 4 to 7.5. The pH is adjusted by methods known to a person skilled in the art, e.g. by using an acid such as a hydroxy acid including glycolic acid, lactic acid, malic acid, citric acid and tartaric acid or a base such as e.g. sodium or potassium hydroxide or ammonium hydroxide as well as mixtures thereof.

Preferably, in the cosmetic compositions have citric acid in an amount of at least 0.0001 wt.-%, such as e.g. in an amount of 0.01 -1 wt.-%, in particular in an amount of 0.01 to 0.5 wt.-% is used for pH adjustment.

The cosmetic composition is preferably sulfate-free and/or free of para- bens, and/or silicon oils and/or silicone surfactants and/or methylisothiazolidine and/or free of polyvinylpyrrolidones (PVP), particularly free of alkylated polyvinyl pyrrolidiones. The cosmetic composition is preferably a topical composition.

The term "topical" as used herein is understood here to mean external application to keratinous substances, which are in particular the skin, scalp, eyelashes, eyebrows, nails, mucous membranes and hair, preferably the skin.

As the topical compositions are intended for topical application, it is well understood that they comprise a physiologically acceptable medium, i.e. a medium compatible with keratinous substances, such as the skin, mucous membranes, and keratinous fibres. In particular, the physiologically acceptable medium is a cosmetically acceptable carrier.

The term "cosmetically acceptable carrier" refers to all carriers and/or excipients and/ or diluents conventionally used in cosmetic compositions such as in particular in sun care products.

Preferably the cosmetic composition is a skin care composition.

In a further embodiment, the cosmetic composition is a decorative preparation or a functional preparation.

Examples of skin care compositions are, in particular, light protective composition, anti-ageing composition, compositions/preparations for the treatment of photo-ageing, body oils, body lotions, body gels, treatment creams, skin protection ointments, skin powders, moisturizing gels, moisturizing sprays, face and/or body moisturizers, skin-tanning preparations (i.e. compositions for the artificial/sunless tanning and/or browning of human skin), for example self-tanning creams as well as skin lightening compositions.

Examples of functional preparations are cosmetic compositions containing active ingredients such as hormone preparations, vitamin preparations, vegetable extract preparations, anti-ageing preparations, and/or antimicrobial (antibacterial or antifungal) preparations without being limited thereto.

The cosmetic composition is preferably a skin care composition.

In a particular embodiment, the cosmetic composition is a sun care composition. Sun care compositions are light-protective composition (sun care products), such as sun protection milks, sun protection lotions, sun protection creams, sun protection oils, sun blocks or day care creams with a SPF (sun protection factor). Sun protection creams, sun protection lotions, sun protection milks and sun protection compositions are of particular interest.

The cosmetic compositions may be in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of oil-in-water (0/W-) or water-in-oil (W/0-)type, silicone-in-water (Si/W-) or water-in-silicone (VWSi-)type, PIT- emulsion, multiple emulsion (e.g. oil-in-water-in oil (0/W/0-) or water-in-oil-in- water (W/0/W-)type), pickering emulsion, hydrogel, alcoholic gel, lipogel, one- or multiphase solution or vesicular dispersion or other usual forms, which can also be applied by pens, as masks or as sprays.

Preferred cosmetic compositions are emulsions which contain an oily phase and an aqueous phase such as in particular O/W, W/O, Si/W, W/Si, O/W/O, W/O/W multiple or a pickering emulsions.

The total amount of the oily phase present in such emulsions is preferably at least 10 wt.-%, such as in the range from 10 to 60 wt.-%, preferably in the range from 15 to 50 wt.-%, most preferably in the range from 15 to 40 wt.-%, based on the total weight of the cosmetic composition.

The amount of the aqueous phase present in such emulsions is preferably at least 20 wt. %, such as in the range from 40 to 90 wt.-%, preferably in the range from 50 to 85 wt.-%, most preferably in the range from 60 to 85 wt.-%, based on the total weight of the cosmetic composition.

The cosmetic compositions can be in the form of a liquid, lotion, a thickened lotion, a gel, a cream, a milk, an ointment or a paste.

More preferably, the cosmetic compositions are in the form of an oil-in- water (O/W) emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O/W- respectively Si/W-emulsifier.

The cosmetic compositions in form of O/W emulsions can be provided, for example, in all the formulation forms for O/W emulsions, for example in the form of serum, milk or cream, and they are prepared according to the usual methods. The cosmetic compositions are preferably intended for topical application and can in particular constitute a dermatological or cosmetic composition, for example intended for protecting human skin against the adverse effects of UV radiation (antiwrinkle, anti-ageing, moisturizing, anti-sun protection and the like).

It is preferred that the cosmetic composition is a shampoo or a hair conditioner.

It is further preferred, that the cosmetic composition is a topical composition applied to the human skin, scalp and/ or hair.

Preferably, that the use is a non-therapeutic use in a deodorant, a shampoo, a conditioner, a cream or a sunscreen.

It has been observed that, when adding the above hyperbranched copolymer (HBC) together with the said antimicrobial agent, the antimicrobial action is increased significantly. In other words, by adding the synergistic antimicrobial agent mixture to a composition, a smaller number of microbes are observed to grow than without the use of said hyperbranched copolymer (HBC)., i.e. with said antimicrobial agent alone. The above hyperbranched copolymer (HBC) has, hence, a synergistic effect on the antimicrobial action of an

antimicrobial agent, particularly in a cosmetic composition.

This is very advantageous also in such a way that the amount of an existing antimicrobial agents can be reduced by adding the effective amount of the above hyperbranched copolymer (HBC) to maintain the same antimicrobial action This is particularly advantageous because certain existing antimicrobial agents are under public discussion and, hence, there exists a great desire in decreasing the amount of such antimicrobial agents.

It has been further observed that the antimicrobial action is particularly pronounced in an aqueous phase. This is very advantageous as it is known that it is typically the water phase of a product which is most susceptible to microbial growth. In a further aspect, the invention relates to a method of synergistically inhibiting or delaying microbial breakdown of a cosmetic composition, household product, plastic, paper and/ or paint, wherein said method comprises the step of adding to the cosmetic composition, household product, plastic, paper and/ or paint a mixture of

a) a hyperbranched copolymer (HBC) of the monomers

(i) dodecenyl succinic acid anhydride

(ii) diisopropanol amine

(iii) bis-dimethylaminopropyl amine

having terminal groups of the formula

and having a molecular weight Mn of between 1200 and 4000 g/mol; and

b) an antimicrobial agent

in an amount of

0.005 to 5.0 % by weight, preferably of 0.05 - 3.0 % by weight, more preferably of 0.1 - 3.0 % by weight, most preferably of 0.5 - 2.5 % by weight, of said hyperbranched copolymer (HBC) and

0.01 - 5.0 % by weight, preferably 0.05 - 3.0 % by weight, more preferably 0.1 - 3.0 % by weight, of said antimicrobial agent; based on the total weight of the composition. The details to the hyperbranched copolymer (HBC) and antimicrobial agent have been described above for the use in great details.

In a final aspect, the invention relates to the use of a hyperbranched copolymer (HBC) of the monomers

(i) dodecenyl succinic acid anhydride (ii) diisopropanol amine

(iii) bis-dimethylaminopropyl amine

having terminal groups of the formula

and having a molecular weight Mn of between 1200 and 4000 g/mol; to enhance synergistically the antimicrobial activity of an antimicrobial agent;

particularly of an antimicrobial agent selected from the group consisting of hexyl glycerine, ethylhexyl glycerine, glyceryl caprate, sodium benzoate, benzyl alcohol, phenoxyethanol, 1 ,3-propane-diol and N-hydroxyoctanamide; more preferably of an antimicrobial agent selected from the group consisting of n-hexyl glycerine, 1 ,3-propane-diol, sodium benzoate, phenoxyethanol, glyceryl caprate and N-hydroxyoctanamide.

The details to the hyperbranched copolymer (HBC) and antimicrobial agent have been described above for the use in great details.

Examples

The present invention is further illustrated by the following experiments. These examples are illustrative only and are not intended to limit the scope of the invention in any way.

Preparation of hyperbranched copolymer (HBC1)

The hyperbranched copolymer HBC1 of the monomers dodecenyl succinic acid anhydride and diisopropanol amine and bis-dimethylaminopropyl amine has been prepared according to example 3 in EP 2 794 729 B1 using 237.59 g of N,N-bis(N’N’-dimethylaminopropyl)amine and 112.6 g diisopropanol amine and 426.89 g of dodecenylsuccinic anhydride. After heating and vacuum, the residual carboxylic acid content of < 0.3 meq/g (tritrimetrical analysis)

AV=9.8mg KOH/g and amine content of 2.99 meq/g (tritrimetrical analysis) and a molecular weight Mn=2240 Da was obtained. This product has been reacted with sodium chloroacetate in water and stirred at 80°C until ¹H-NMR analysis shows a complete conversion of the chloroacetate to obtain the hyperbranched copolymer HBC1 which has terminal groups of the formula

molecular weight Mn of 2.3 kDa.

The hyperbranched copolymer HBC1 was used as a 50 % solution in water in the following experiments. The amounts indicated in the tables 1 , 2, 3 and 4 are based on the amount of polymer.

Experimental series 1

Preparation of cosmetic compositions

Shampoo compositions, to which the above hyperbranched copolymer HBC1 and/or ethylhexylglycerin (=3-(2-ethylhexyloxy)-1 ,2-propandiol) have been added, have been prepared as indicated in table 1.

Testing of antimicrobial action

The antimicrobial efficacy is assessed in analogy to the regulatory challenge test method (NF EN ISO11930). In this test the following mixture of bacteria, yeast and molds:

-gram positive bacteria : Kocuria rhizophila, Staphylococcus aureus

-gram negative bacteria : Enterobacter gergoviae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,

Pseudomonas fluorescens, Pseudomonas putida

-moulds: Aspergillus brasiliensis, Penicillium pinophilum

-yeast: Candida albicans are inoculated 6 times (once a week) into the test material. Each week before the next inoculation the germs in the test material are counted. The inoculum contains pathogenic microorganisms as germs which are well known for product spoilage. All species have to be cultivated separately and mixed directly before the addition, to ensure a constant composition and germ count of the inoculum. Its germ count is approximately 10^{7 8} cfu/ml in the sample. After the 6 inoculation cycles the microbial growth has been checked and assessed as follows:

Growth: symbol: assessment of antimicrobial action:

Free of growth: - passed

Slight growth: + passed

Moderate growth: ++ failed

Heavy growth: +++ failed

The results are compiled in table 1.

Table 1 Antimicrobial action in shampoo compositions.

The results of table 1 show that the effect that combination of these specific copolymers, i.e. the hyperbranched copolymers, and the antimicrobial agent show a synergistic effect against a broad variety of microorganisms.

Experimental series 2

Preparation of cosmetic compositions

O/W skin care emulsion to which the above hyperbranched copolymer HBC1 and/or n-hexylglycerin have been added, have been prepared as indicated in table 2.

Testing of antimicrobial action (Challenge test)

The antimicrobial action has further been tested according to ISO 11930 on the O/W skin care emulsion compositions according to table 2 for Escherichia coli.

The evaluation of the preservation of a cosmetic formulation is based on inoculation of the formulation with calibrated inocula (prepared from relevant strains of micro-organisms). The number of surviving micro-organisms is measured at defined intervals during a period of 28 days. The number of microorganisms has been counted directly after inoculation and after 7 days of growth and are indicated in table 2.

Table 2 Antimicrobial action of compositions on Escherichia coli after 7 days.

Directly after inoculation, the count was 440Ό00 [cfu/ml]. Experimental series 3

Testing of antimicrobial action (24 hours Challenge test)

Since it is known that typically a water phase of a product is most susceptible to microbial growth, the antimicrobial efficacy has been further assessed in analogy to the regulatory challenge test method (NF EN IS011930) for an aqueous solution.

Thus, a solution of HPC1 and/or the antimicrobial agents in an amount as indicated in table 3 and table 3a were prepared under sterile conditions. For this, it was solubilized in physiological serum with 0.85 wt.-% NaCI. The solutions were deposed in 96-deep well plates (1.6 ml/well). The wells were contaminated with Escherichia coli or Staphylococcus aureus or Aspergillus brasiliensis, at 6.3^*10⁵ or 4.3*10⁵ or 4.5*10⁴ cfu/ml, respectively. After the contamination each well was thoroughly mixed to ensure a homogeneous distribution of the microorganism. Then each plate was incubated at 22°C for 24h. The counting of the (remaining) population was carried out 24h after contamination and reported in table 4.

Table 3. Compositions for antimicrobial action in the 24 hours screen test.

All amounts indicated in % by weight

*Zeastat = 1 ,3-propanediol/N-hydroxyoctanamide

Table 3a. Compositions for antimicrobial action in the 24 hours

screen test.

All amounts indicated in % by weight.

Table 4 Antimicrobial action in the 24 hours screen test with Escherichia coli,

Staphylococcus aureus and Aspergillus brasiliensis.

n.m.: not measured.

The results of tables 1 , 2 and 4 clearly show the effect that these specific copolymers, i.e. the hyperbranched copolymers, increase the antimicrobial action of antimicrobial agents in a cosmetic composition. This effect is synergistic.

Claims

1 . Use of a mixture of

a) a hyperbranched copolymer (HBC) of the monomers

(i) dodecenyl succinic acid anhydride

(ii) diisopropanol amine

(iii) bis-dimethylaminopropyl amine

having terminal groups of the formula

b) an antimicrobial agent

as a synergistic antimicrobial agent mixture.

2. The use according to claim 1 , characterized in that the antimicrobial agent mixture is an antimicrobial agent mixture which inhibits the growth of a microorganism selected from the group consisting of Kocuria rhizophila, Staphylococcus aureus, Enterobacter gergoviae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Aspergillus brasiliensis, Penicillium pinophilum and Candida albicans.

3. The use according to claim 1 or 2, characterized in that the antimicrobial agent mixture inhibits the growth of Staphylococcus aureus or Escherichia coli.

4. The use according to anyone of the preceding claims in a product selected from the group of cosmetic compositions, household products, plastics, paper and/ or paints, preferably in a cosmetic composition.

5. The use according to anyone of the preceding claims, characterized in that the weight ratio of said hyperbranched copolymer (HBC) and antimicrobial agent is in the range of between 1 :30 and 30:1 , preferred between 1 :20 and 20:1 , more preferred between 1 :10 and 10:1.

6. The use according to anyone of the preceding claims, characterized in that the hyperbranched copolymer (HBC) is prepared by the consecutive steps of a1 ) polymerizing the monomers (i) and monomers (ii) and monomers (iii) to yield a polyesteramide having terminal dimethylamino groups of the

- N /

formula \

a2) quaternization of the dimethyl amino groups of the polyesteramide of step a1 ) by 2-chloroacetate, particularly by sodium 2-chloroacetate.

7. The use according to anyone of the preceding claims characterized in that the molar ratio of the monomers (i) to monomers (ii) is between 5 : 1 and 0.5 : 1 , particularly between 4 : 1 and 1 : 1 , preferably between 3 : 1 and 3 : 2.

8. The use according to anyone of the preceding claims characterized in that the molar ratio of the monomers (i) to monomers (iii) is between 5 : 1 and 0.5 : 1 , particularly between 3 : 1 and 1 : 1 , preferably between 2.5 : 1 and 1 .1 : 1 .

9. The use according to anyone of the preceding claims characterized in that the hyperbranched copolymer (HBC) has a number average molecular weight M_n of between 1400 and 3000 g/mol, preferably between 2100 and 2400 g/mol.

10. The use according to anyone of the preceding claims characterized in that the hyperbranched copolymer (HBC) is polyquaternium-110.

11. The use according to anyone of the preceding claims characterized in that the antimicrobial agent is selected from the group consisting of consisting of hexyl glycerine, ethylhexyl glycerine or glyceryl caprate, sodium benzoate, benzyl alcohol, phenoxyethanol, 1 ,3-propane-diol and N-hydroxyoctanamide.

12. The use according to anyone of the preceding claims characterized in that the use is a non-therapeutic use.

13. The use according to anyone of the preceding claims characterized in that the use is a non-therapeutic use in a deodorant, a shampoo, a conditioner, a cream or a sunscreen.

14. A method of synergistically inhibiting or delaying microbial breakdown of a cosmetic composition, household product, plastic, paper and/ or paint, wherein said method comprises the step of adding to the cosmetic composition, household product, plastic, paper and/ or paint a mixture of

a) a hyperbranched copolymer (HBC) of the monomers

(i) dodecenyl succinic acid anhydride

(ii) diisopropanol amine

(iii) bis-dimethylaminopropyl amine

having terminal groups of the formula

and having a molecular weight Mn of between 1200 and 4000 g/mol; and

b) an antimicrobial agent

in an amount of

of 0.005 to 5.0 wt.-% of said hyperbranched copolymer (HBC); and

of 0.01 to 5.0 wt.-% of said antimicrobial agent

based on the total weight of the composition.

15. The method of claim 14, characterized in that the microbial decay and breakdown is caused by a microorganism selected from the group consisting of of Kocuria rhizophila, Staphylococcus aureus, Enterobacter gergoviae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Aspergillus brasiliensis, Penicillium pinophilum and Candida albicans.

16. The use of a hyperbranched copolymer (HBC) of the monomers

(i) dodecenyl succinic acid anhydride

(ii) diisopropanol amine

(iii) bis-dimethylaminopropyl amine

having terminal groups of the formula

and having a molecular weight Mn of between 1200 and 4000 g/mol; to enhance synergistically the antimicrobial activity of an antimicrobial agent.