Sterilization use

Abstract

The present invention relates to the use of 1,4-di(benzoxazol-2'-yl)benzene as an antimicrobial agent.

Description

[0001] The present invention relates to the use of 1,4-di(benzoxazol-2'-yl)benzene as an antimicrobial agent.

[0002] To protect cosmetic or pharmaceutical compositions, household items, plastics, paper and / or coatings from mold and bacteria, most products currently on the market contain preservatives. While these preservatives protect against bacteria and fungi, studies have linked daily exposure to many of these substances to an increased risk of skin irritation, cancer and / or endocrine problems. Therefore, many manufacturers are looking for alternative antimicrobial actives that allow a reduction in the amount of preservatives and do not appear to pose any health risks.

[0003] Antimicrobial active compounds also play a key role in many cosmetic applications. For example, they are added to deodorants to reduce body odor caused by bacterial growth (e.g. caused by Staphylococcus) or to balance the microbiome by inhibiting the growth of undesirable bacteria on the skin (e.g. Staphylococcus aureus, Escherichia coli and / or Pseudomonas aeruginosa).

[0004] Surprisingly, it has now been found that 1,4-di(benzoxazol-2'-yl)benzene exhibits antimicrobial activity against various microorganisms, such as in particular Candida albicans (C. albicans), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and / or Aspergillus brasiliensis (A. brasiliensis).

[0005] The present invention therefore relates to the use of 1,4-di(benzoxazol-2'-yl)benzene as an antimicrobial agent, i.e. an agent exhibiting antimicrobial activity. In particular, the present invention relates to the use of 1,4-di(benzoxazol-2'-yl)benzene as an antifungal and / or antibacterial agent, more particularly as an agent for killing and / or inhibiting the growth of fungi and / or Gram-positive bacteria, such as, in particular, Candida albicans, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and / or Aspergillus brasiliensis.

[0006] In another embodiment, the present invention relates to a method for killing and / or inhibiting the growth of microbial cells, particularly fungal cells and / or bacterial cells, the method comprising contacting the microbial cells with 1,4-di(benzoxazol-2'-yl)benzene. In a preferred embodiment, the microbial cells are selected from the group consisting of fungi and / or gram-positive bacteria, more preferably selected from the group consisting of Candida albicans, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and / or Aspergillus brasiliensis and mixtures thereof.

[0007] The term "antimicrobial activity" (or "antimicrobial effect") as used herein refers to the ability to kill and / or inhibit the growth of microbial cells, such as, in particular, bacteria and fungi, more particularly Candida albicans, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Aspergillus brasiliensis, and mixtures thereof.

[0008] 1,4-Di(benzoxazol-2'-yl)benzene [CAS 904-39-2] is a colorless to pale yellow solid which can be prepared as outlined in WO200239972 or as illustrated in the examples.

[0009] Due to its low solubility, in all embodiments of the present invention, 1,4-di(benzoxazol-2'-yl)benzene is preferably used in micronized form, ie in the form of solid particles having an average particle size of less than 1 μm.

[0010] In a particularly advantageous embodiment, the micronized form exhibits an average particle size of at most 300 nm. Even more preferably, the micronized 1,4-di(benzoxazol-2'-yl)benzene exhibits an average particle size selected from the range of 50 nm to 300 nm, more preferably the range of 100 nm to 300 nm, most preferably the range of 120 nm to 280 nm, for example the range of 140 nm to 240 nm or the range of 150 nm to 220 nm.

[0011] The term 'average particle size' as used herein refers to the particle size distribution D based on the average number as determined by laser diffraction (eg using a Malvern Mastersizer 2000 (ISO 13320:2009)). n 50 (also known as D n 0.5).

[0012] Micronized 1,4-di(benzoxazol-2'-yl)benzene according to the present invention may be produced by standard micronization methods in the art as outlined, for example, in WO9522959 and WO9703643, both incorporated herein by reference.

[0013] The micronized 1,4-di(benzoxazol-2′-yl)benzene according to the invention can be used in powder form or as a dispersion thereof.

[0014] The micronized 1,4-di(benzoxazol-2'-yl)benzene according to the invention may also be in crystalline or solid amorphous form. In all embodiments of the invention, it is preferred that the micronized 1,4-di(benzoxazol-2'-yl)benzene is in solid amorphous form.

[0015] The term "solid amorphous form" as used herein refers to solid particles formed by the rapid formation / separation of a solid phase from a liquid phase in a solution or mixture such that the solid does not have time to selectively form a crystalline network, so that the solid obtained is mainly in a disordered form (also referred to herein as 'solid amorphous 1,4-di(benzoxazol-2'-yl)benzene'), which can be unambiguously identified by XRPD analysis by showing no baseline separation of peaks at 25-28° 2θ (Cu k-alpha radiation) when measured using a Bruker D8 advanced powder X-ray diffractometer in reflection (Bragg-Brentano) geometry with a LynxEye detector and CuKα radiation.

[0016] The solid amorphous form of 1,4-di(benzoxazole-2'-yl)benzene according to the present invention is preferably prepared by a method comprising the following steps: (1) reacting terephthalic acid with 2-aminophenol to form 1,4-di(benzoxazole-2'-yl)benzene, and (2) precipitating the 1,4-di(benzoxazole-2'-yl)benzene thus obtained, preferably in the presence of (ice) water, to obtain solid amorphous 1,4-di(benzoxazole-2'-yl)benzene, and micronizing the solid amorphous 1,4-di(benzoxazole-2'-yl)benzene in successive steps according to standard methods in the art. Optionally, the method may include an intermediate purification step. Alternatively, the solid amorphous 1,4-di(benzoxazole-2'-yl)benzene may be further purified by washing with a solvent, wherein the 1,4-di(benzoxazole-2'-yl)benzene is only poorly soluble or insoluble in, for example, toluene and / or alcohols (e.g., 1-butanol), but is not limited thereto.

[0017] Furthermore, it is advantageous that in all embodiments of the invention, micronized 1,4-di(benzoxazol-2'-yl)benzene is used in the form of its aqueous dispersion, since this can be easily incorporated into the desired product form, for example into a cosmetic or pharmaceutical composition.

[0018] The amount of 1,4-di(benzoxazol-2'-yl)benzene in this aqueous dispersion is preferably selected from the range of 10 wt% to 90 wt%, 20 wt% to 80 wt%, or 30 wt% to 70 wt%, more preferably from 25 wt% to 60 wt%, most preferably from 25 wt% to 55 wt%, for example from 25 wt% to 50 wt%, from 25 wt% to 40 wt%, or from 25 wt% to 35 wt%, based on the total weight of the aqueous dispersion.

[0019] The aqueous dispersion may also contain one or more additives, for example to aid in micronization and / or to stabilize the aqueous dispersion, for example to prevent sedimentation.

[0020] In the aqueous dispersion, the amount (total amount) of one or more additives, if present, is preferably selected from the range of 0.01 wt.-% to 25 wt.-%, more preferably from the range of 0.1 wt.-% to 20 wt.-%, most preferably from the range of 0.5 wt.-% to 15 wt.-%, for example in the range of 1 wt.-% to 10 wt.-%, based on the total weight of the aqueous dispersion.

[0021] In all embodiments according to the invention, the at least one additive is preferably selected from the group consisting of surface-active ingredients, such as in particular anionic, nonionic, amphoteric and cationic surfactants, defoamers, salts, wetting agents and thickeners and mixtures thereof.

[0022] In particular, suitable surfactant ingredients to be used in aqueous dispersions are alkyl polyglucosides (APGs) having the general formula C n H 2+n O(C6H 10 O5) x H, wherein n is an integer selected from the range of 2 to 22 and x refers to the average polymerization level of the glucoside moiety (monoglucosides, diglucosides, triglucosides, oligoglucosides and polyglucosides). Such alkyl polyglucosides are commercially available, for example, from Shanghai Fine Chemical under the trade name Green APG0810 (a C 8-10 Alkyl polyglucosides, which are derived from corn glucose and C8 and C 10 The surfactant component is preferably selected from the group consisting of 1% to 20% by weight, more preferably 5% to 15% by weight, and most preferably 7% to 12.5% ​​by weight, based on the total weight of the aqueous dispersion.

[0023] Particularly suitable defoamers to be used in the aqueous dispersion are silicone oils, such as in particular polydimethylsiloxanes, and / or silicon defoamers, such as in particular anhydrous dispersions of pyrolyzed or hydrophobized silicon dioxide in silicone oil. The most preferred defoamer is dimethicone. If present, such defoamers are preferably used in an amount (total amount) selected from the range of 0% to 1% by weight, more preferably in an amount of 0.01% to 0.2% by weight, based on the total weight of the aqueous dispersion.

[0024] Suitable salts to be used in the aqueous dispersion include alkali metal salts of phosphate, hydroxide and alkaline earth metal salts, such as disodium hydrogen phosphate and / or sodium hydroxide. If present, the salt or mixture thereof (total amount) is preferably used in an amount of 0.01 wt % to 5 wt %, more preferably 0.1 wt % to 4 wt %, most preferably 0.5 wt % to 2.5 wt %, based on the total weight of the aqueous dispersion.

[0025] Particularly suitable thickeners to be used in the aqueous dispersion include xanthan gum, gellan gum and / or carboxymethyl cellulose. Most preferably, the thickener is xanthan gum or gellan gum. If present, such thickeners are preferably used in an amount (total amount) selected from the range of 0.1 wt % to 1 wt %, more preferably 0.1 wt % to 0.5 wt %, based on the gross weight of the aqueous dispersion.

[0026] A particularly suitable wetting agent to be used in the aqueous dispersion is (poly)propylene glycol, most preferably propylene glycol. If present, the amount of such wetting agent is preferably selected from the range of 0.1 wt% to 1 wt%, more preferably an amount of 0.2 wt% to 0.6 wt%, based on the total weight of the aqueous dispersion.

[0027] In all embodiments according to the invention, preference is given to using an aqueous dispersion consisting essentially of micronized 1,4-di(benzoxazol-2'-yl)benzene, water and optionally at least one additive, with all definitions and preferences as given herein.

[0028] Even more advantageously, the aqueous dispersion consists essentially of

[0029] (i) 25 to 60% by weight, preferably 25 to 50% by weight, based on the total weight of the aqueous dispersion, of micronized 1,4-di(benzoxazol-2'-yl)benzene having all the preferences and definitions given herein,

[0030] (ii) 5 to 15 wt %, preferably 7 to 12.5 wt %, based on the total weight of the aqueous dispersion, of C 8-16 Alkyl polyglucoside,

[0031] (iii) 0 to 3 wt. %, preferably 0 to 2.5 wt. %, based on the total weight of the aqueous dispersion, of at least one additive selected from the group consisting of thickeners, wetting agents and / or defoamers, and

[0032] (iv) Supplementing with water to 100 wt % based on the total weight of the aqueous dispersion.

[0033] The term 'essentially consisting of' as used according to the present invention means that the amounts of components (i) to (iv) add up to 100% by weight, said amounts being adjusted with the amount of water (iv). However, the presence of small amounts of impurities or additives, for example introduced by the corresponding raw materials of the components, is not excluded.

[0034] Most advantageously, the aqueous dispersion contains as additive (iii): propylene glycol; A sort of A thickener selected from xanthan gum or gellan gum; and optionally dimethicone.

[0035] Due to the antimicrobial activity, 1,4-di(benzoxazol-2'-yl)benzene is also suitable for maintaining skin homeostasis and / or balancing the skin microbiome by treating overpopulation of microorganisms such as Escherichia coli, Staphylococcus aureus and / or Pseudomonas aeruginosa on the skin.

[0036] To utilize the antimicrobial activity of 1,4-di(benzoxazol-2'-yl)benzene, 1,4-di(benzoxazol-2'-yl)benzene can be incorporated into a variety of formulations or applications, such as cosmetic or pharmaceutical compositions, medical products, household items, plastics, plastisols, paper and / or coatings.

[0037] The amount of 1,4-di(benzoxazol-2'-yl)benzene employed according to the invention is preferably selected from the range of 0.1% to 20% by weight, more preferably from about 0.25% to 15% by weight, most preferably from about 0.5% to 10% by weight, for example in the range of 0.3% to 7.5% by weight (always based on active substance). Further suitable ranges encompass 0.25% to 10% by weight, 0.25% to 7.5% by weight, 0.25% to 5% by weight, 1% to 7.5% by weight, and 1% to 5% by weight.

[0038] In a specific embodiment, the present invention also relates to the use of 1,4-di(benzoxazol-2'-yl)benzene for improving the preservation, in particular the preservation of a product selected from the group consisting of cosmetic and / or pharmaceutical compositions, household products, plastics, paper and / or coatings, preferably against Aspergillus brasiliensis.

[0039] The use optionally encompasses the step of evaluating the effect compared to a corresponding product without 1,4-di(benzoxazol-2'-yl)benzene.

[0040] In another embodiment, the present invention relates to a method for preventing microbial decay and decomposition of a product selected from the group consisting of cosmetic compositions and / or pharmaceutical compositions, household products, plastics, paper and / or coatings, wherein the method comprises adding to the product an amount of 0.1% to 20% by weight, more preferably 0.25% to 15% by weight, most preferably 0.3% to 10% by weight, for example 0.3% to 7.5% by weight of 1,4-di(benzoxazole-2'-yl)benzene. In a specific embodiment, the method further encompasses a step of evaluating the results, particularly compared to a corresponding product without 1,4-di(benzoxazole-2'-yl)benzene. Further suitable ranges include 0.25% to 10% by weight, 0.25% to 7.5% by weight, 0.25% to 5% by weight, 1% to 7.5% by weight, and 1% to 5% by weight.

[0041] In yet another embodiment, the present invention relates to a method for preserving a product selected from the group consisting of cosmetic and / or pharmaceutical compositions, household products, plastics, paper and / or coatings to prevent microbial contamination or growth, wherein the method comprises adding to the product an amount of 0.1 to 20 wt%, more preferably an amount of 0.25 to 15 wt%, most preferably an amount of 0.3 to 10 wt%, such as an amount of 0.3 to 7.5 wt%, of 1,4-di(benzoxazol-2'-yl)benzene. Further suitable ranges include 0.25 to 10 wt%, 0.25 to 7.5 wt%, 0.25 to 5 wt%, 1 to 7.5 wt%, and 1 to 5 wt%.

[0042] In a particularly advantageous embodiment, the present invention relates to a method for preventing microbial decay and decomposition of a cosmetic or pharmaceutical composition, which also comprises water and at least one other agent selected from the group consisting of surfactants, emulsifiers, thickeners and oils, and which is therefore particularly susceptible to microbial growth.

[0043] The invention also relates to the use of 1,4-di(benzoxazol-2'-yl)benzene as a deodorant compound, since 1,4-di(benzoxazol-2'-yl)benzene has an antimicrobial effect against the bacteria which are responsible for the decomposition of sweat and thus the formation of odors.

[0044] Advantageously, 1,4-di(benzoxazol-2'-yl)benzene can also be used in admixture with conventional preservatives to improve the preservative activity of the preservatives.

[0045] A particularly suitable mixture is a combination of 1,4-di(benzoxazol-2'-yl)benzene and at least one compound selected from the group consisting of hydroxyacetophenone, alkanediol and benzoic acid or its salt, because 1,4-di(benzoxazol-2'-yl)benzene synergistically enhances the antimicrobial activity of the compound. The mixture is still novel. Therefore, the present invention also relates to a mixture comprising 1,4-di(benzoxazol-2'-yl)benzene and at least one compound selected from the group consisting of hydroxyacetophenone, alkanediol and benzoic acid or its salt.

[0046] Preferably, the mixture is used as an antimicrobial mixture which can be added to any product as defined herein to improve the resistance of the product to microorganisms. It is well understood that the mixture can be added to the corresponding product as a premix, however, alternatively, 1,4-di(benzoxazol-2'-yl)benzene and at least one compound selected from the group consisting of hydroxyacetophenone, alkanediol and benzoic acid or its salt can also be added separately to the corresponding product.

[0047] It is particularly preferred that the mixture or the product comprising the mixture does not contain hyperbranched copolymers, such as, in particular, hyperbranched copolymers of the monomers dodecenylsuccinic anhydride, diisopropanolamine, bisdimethylaminopropylamine having terminal groups of the formula

[0048]

[0049] The weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to at least one compound selected from the group consisting of hydroxyacetophenone, alkanediol and benzoic acid or its salt is preferably selected from the range between 40:1 and 1:40, more preferably between 30:1 and 1:30, even more preferably between 20:1 and 1:20, for example in the range of 15:1 to 1:15 or 15:1 to 1:10.

[0050] Most preferably, in the case of hydroxyacetophenone, the weight ratio is selected from the range between 30:1 and 1:2, such as between 25:1 and 1:1.

[0051] Most preferably, in the case of alkane diols, the weight ratio is selected from the range between 15 to 1 and 1 to 5, such as between 10: 1 and 1 to 1 :3.

[0052] Most preferably, in the case of benzoic acid or its salts, the weight ratio is selected from the range between 30:1 and 1:1, more preferably between 25:1 and 1:1.

[0053] In all embodiments, preferably, the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to at least one compound selected from the group consisting of hydroxyacetophenone, alkanediol and benzoic acid or its salt is ≥0.5, more preferably ≥0.75, most preferably ≥1.

[0054] The term hydroxyacetophenone refers to o-hydroxyacetophenone, m-hydroxyacetophenone or p-hydroxyacetophenone. Particularly preferred in all embodiments of the invention is p-hydroxyacetophenone [CAS 99-93-4], which is also known as 1-(4-hydroxyphenyl)-ethanone and which is commercially available from Symrise as H is commercially available.

[0055] In all embodiments of the present invention, the amount of hydroxyacetophenone used is selected from the range of 0.001 wt % to 5 wt %, more preferably 0.01 wt % to 4 wt %, most preferably 0.1 wt % to 3 wt %, based on the total weight of the product. Further preferred ranges are 0.005 wt % to 4.5 wt %, 0.05 wt % to 4 wt %, and 0.25 wt % to 3 wt %, based on the total weight of the product.

[0056] Alkanediols, especially straight-chain and branched C 1-10 Alkanediols are well-known preservative synergists in cosmetic applications. Particularly suitable alkanediols according to the present invention include straight-chain 1,2-alkanediols, 1,3-alkanediols or 1,4-alkanediols containing from about 2 to about 10 carbon atoms, for example from about 3 to about 8 carbon atoms, or from about 3 to about 7 carbon atoms, such as in particular 1,2-propylene glycol, 1,3-propylene glycol, 1,4-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol and 1,2-decanediol. The most preferred alkanediol in all embodiments of the present invention is 1,3-propylene glycol [CAS 504-63-2], which is available, for example, from DuPont Tate & Lyle Bioproducts under the trade name Zemea TM Propylene glycol is commercially available.

[0057] In all embodiments of the present invention, the amount of alkanediol used is preferably selected from the range of 0.01 wt% to 6 wt%, more preferably from 0.1 wt% to 5 wt%, most preferably from 0.5 wt% to 4 wt%, based on the total weight of the product. Further preferred ranges are 0.5 wt% to 3.5 wt% and 0.5 wt% to 3 wt%, based on the total weight of the product.

[0058] Benzoic acid and its salts are well known preservatives commonly used in food, medicine and cosmetics. Preferred salts are potassium or sodium salts, most preferably sodium salts. In all embodiments of the present invention, it is particularly preferred to use benzoic acid [CAS 65-85-0] and / or sodium benzoate [CAS 532-32-1], most preferably such as available from Emerald Kalama Chemicals under the trade name Sodium benzoate was commercially available from S Grains.

[0059] In all embodiments of the present invention, the amount of benzoic acid or its salt used is selected from the range of 0.001 wt % to 6 wt %, more preferably 0.01 wt % to 4 wt %, most preferably 0.1 wt % to 3 wt %, based on the total weight of the product. Further preferred ranges include 0.1 wt % to 1 wt % and 0.1 wt % to 0.8 wt %, based on the total weight of the product.

[0060] The use of 1,4-di(benzoxazol-2'-yl)benzene according to the invention, optionally in combination with at least one compound selected from the group consisting of hydroxyacetophenone, alkanediol and benzoic acid or its salts, can occur both in a cosmetic sense and in a pharmaceutical sense. However, in all embodiments of the invention, the use is preferably cosmetic (non-therapeutic).

[0061] The cosmetic or pharmaceutical composition according to the invention is in particular a composition intended for topical application to mammalian keratinous tissue, such as in particular to human skin or human scalp and hair.

[0062] As used in this application, the term "cosmetic composition" refers to Cosmetic compositions as defined under the heading "Kosmetika" in Lexikon Chemie, 10th edition, 1997, Georg Thieme Verlag Stuttgart, New York, and as disclosed in A. Domsch, "Cosmetic Compositions", Verlag für chemische Industrie (ed. H. Ziolkowsky), 4th edition, 1992.

[0063] Suitable surfactants, emulsifiers, thickeners and oils for the purposes of the present invention are all surfactants, emulsifiers, thickeners and oils commonly used in cosmetic applications and listed, for example, in the International Cosmetic Ingredient Dictionary & Handbook of the Personal Care Product Council (http: / / www.personalcarecouncil.org / ), but not limited thereto, which can be accessed via the online INFO BASE (http: / / online.personalcarecouncil.org / jsp / Home.jsp).

[0064] The composition according to the invention is typically prepared by admixing 1,4-di(benzoxazol-2'-yl)benzene, preferably in the form of an aqueous dispersion as defined herein, the amount of the aqueous dispersion (based on 1,4-di(benzoxazol-2'-yl)benzene) being selected from the range of 0.1 wt% to 20 wt%, more preferably from about 0.25 wt% to 15 wt%, most preferably from about 0.3 wt% to 10 wt%, for example in the range of 0.3 wt% to 7.5 wt%, based on the total weight of the composition containing a suitable carrier. Further suitable ranges encompass 0.25 wt% to 10 wt%, 0.25 wt% to 7.5 wt%, 0.25 wt% to 5 wt%, 1 wt% to 7.5 wt%, and 1 wt% to 5 wt%.

[0065] The cosmetic or pharmaceutical composition according to the invention preferably also comprises a physiologically acceptable medium, ie a medium that is compatible with keratinous substances such as the skin, mucous membranes and keratin fibers. In particular, the physiologically acceptable medium is a cosmetically acceptable or pharmaceutically acceptable carrier.

[0066] The term cosmetically or pharmaceutically acceptable carrier refers to all carriers and / or excipients and / or diluents conventionally used in cosmetic or pharmaceutical compositions.

[0067] Preferably, the cosmetic or pharmaceutical composition according to the invention is in the form of a suspension or dispersion in a solvent or a fatty substance, or alternatively in the form of an emulsion or microemulsion (in particular O / W type or W / O type), a PIT emulsion, a nanoemulsion, a multiple emulsion (for example O / W / O type or W / O / W type), a Pickering emulsion, a hydrogel, a lipid gel, a single-phase or multiphase solution or a vesicular dispersion.

[0068] The cosmetic or pharmaceutical composition according to the present invention may be in the form of a liquid, a lotion, a thickened lotion, a gel, a cream, an emulsion, an ointment or a paste.

[0069] The pH of the cosmetic or pharmaceutical composition according to the present invention is generally in the range of 3-10, preferably in the range of 3-8, most preferably in the range of 3.5-7.5. The pH is adjusted by methods known to those skilled in the art, for example by using an acid (e.g., a hydroxy acid, including glycolic acid, lactic acid, malic acid, citric acid and tartaric acid) or a base (e.g., sodium hydroxide or potassium hydroxide or ammonium hydroxide and mixtures thereof).

[0070] Preferably, in the composition according to the invention, the acid or base, if present, is used in an amount of at least 0.0001 wt.-%, for example in an amount of 0.01 to 1 wt.-%, in particular in an amount of 0.01 to 0.5 wt.-%.

[0071] The cosmetic composition according to the invention is in particular a skin care preparation, a functional preparation and / or a hair care preparation, such as most in particular a skin care preparation or a hair care preparation.

[0072] Examples of skin care preparations are, in particular, photoprotective preparations (sunscreen preparations), anti-aging preparations, preparations for the treatment of photoaging, body oils, body milks, body gels, care creams, skin ointments, moisturizing preparations (for example moisturizing gels or moisturizing sprays), face and / or body moisturizers, and skin-lightening preparations.

[0073] Examples of functional preparations are cosmetic compositions containing active ingredients, such as, but not limited to, hormone preparations, vitamin preparations, plant extract preparations, anti-aging preparations, and / or antimicrobial (antibacterial or antifungal) preparations.

[0074] Examples of hair care products that are suitable according to the invention and that may be mentioned are shampoos, conditioners (also called hair serums), hair styling compositions, hair tonics, hair rejuvenating compositions, hair washes, water waving washes, hair sprays, hair creams, hair gels, hair oils, hair pomades or hair brilliantines. These products are therefore always products that are applied to the hair and scalp for a shorter or longer period of time, depending on the actual purpose of their use.

[0075] Preferably, in all embodiments of the invention, the skin care preparation is a sunscreen preparation.

[0076] It is preferred that the sunscreen preparation comprises at least one ultraviolet (UV) filter. The UV filter may be a liquid or solid UV filter. The UV filter may be a UV-A or UV-B filter.

[0077] Suitable liquid UV filters 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 filters are well known to those skilled in the art and include in particular cinnamic acid esters, such as octyl methoxycinnamate ( MCX) and isoamyl methoxycinnamate (Neo E 1000); salicylates, such as homosalate (3,3,5-trimethylcyclohexyl 2-hydroxybenzoate, HMS) and ethylhexyl salicylate (also known as ethylhexyl salicylate, 2-ethylhexyl 2-hydroxybenzoate, EHS); acrylates, such as octocrylene (2-ethylhexyl 2-cyano-3,3-phenylacrylate, 340) and ethyl 2-cyano-3,3-diphenylacrylate; esters of benzylidenemalonic acid, such as, in particular, dialkyl benzylidenemalonates, such as di(2-ethylhexyl)-4-methoxybenzylidenemalonate and polysilicone-15( SLX); dialkyl esters of naphthalene dicarboxylic acid, such as diethylhexyl 2,6-naphthalene dicarboxylate ( TQ); syringylidenemalonate, for example diethylhexyl syringylidenemalonate ( ST liquid), and benzotriazolyl dodecyl p-cresol ( TL) as well as benzophenone-3 and drometrizole trisiloxane.

[0078] Particularly advantageous liquid UV filters are octyl methoxycinnamate, homosalate, ethylhexyl salicylate, octocrylene, diethylhexyl 2,6-naphthalene dicarboxylate, diethylhexyl syringylidenemalonate, benzotriazolyl dodecyl p-cresol, benzophenone-3, drometrizole trisiloxane, polysilicone-15 and mixtures thereof.

[0079] Suitable solid UV filters absorb light in the UVB and / or UVA range and are solid at ambient temperature, i.e. 25° C. They are in particular solid organic UV filters. Particularly suitable solid UV filters are the group consisting of bis-ethylhexyloxyphenol methoxyphenyl triazine, butyl methoxydibenzoylmethane, methylene bis-benzotriazolyl tetramethylbutylphenol, diethylaminohydroxybenzoyl hexyl benzoate, ethylhexyl triazone, diethylhexyl butamido triazone and 4-methylbenzylidene camphor.

[0080] The amount of individual organic UV filters is preferably in the range of 0.1% to about 10% by weight, preferably in the range of 0.5% to 7.55% by weight, most preferably in the range of 1% to 5% by weight, based on the total weight of the sunscreen preparation.

[0081] In the case of sunscreen compositions, the total amount of organic UV filters depends strongly on the targeted UV protection of the composition and is generally in the range between 1% and 50% by weight, preferably between 5% and 40% by weight, based on the total weight of the sunscreen preparation.

[0082] Sunscreen preparations with an SPF of 15 (SPF=Sun Protection Factor) comprise, for example, preferably between 4 and 20% by weight, more preferably between 7 and 15% by weight, of a total amount of organic UV filters, based on the total weight of the sunscreen preparation.

[0083] Sunscreen preparations with an SPF of 30 comprise, for example, preferably a total amount of organic UV filters of between 10% and 40% by weight, more preferably between 15% and 25% by weight, based on the total weight of the sunscreen preparation.

[0084] Sunscreen preparations with an SPF of 50 comprise, for example, preferably a total amount of organic UV filters of between 15% and 50% by weight, more preferably between 20% and 40% by weight, based on the total weight of the sunscreen preparation.

[0085] In a preferred embodiment, the cosmetic composition according to the invention is an emulsion and / or a gel. Even more preferably, the cosmetic composition is an emulsion containing an oil phase and an aqueous phase, such as in particular an O / W, W / O, Si / W, W / Si, O / W / O, W / O / W multiple or Pickering emulsion.

[0086] The amount of oil phase (i.e. the phase containing all oils and fats (including polar oils)) present in such emulsions is preferably at least 10 wt%, such as in the range of 10 to 60 wt%, preferably in the range of 15 to 50 wt%, most preferably in the range of 15 to 40 wt%, based on the total weight of the topical composition.

[0087] The amount of aqueous phase present in such emulsions is preferably at least 20 wt%, such as in the range of 20 to 90 wt%, preferably in the range of 30 to 80 wt%, most preferably in the range of 30 to 70 wt%, based on the total weight of the topical composition.

[0088] The O / W emulsion according to the invention advantageously comprises (i) 1,4-di(benzoxazol-2'-yl)benzene in an amount selected from the range of 0.1% to 20% by weight, more preferably from about 0.25% to 15% by weight, most preferably from about 0.3% to 10% by weight, for example from 0.3% to 7.5% by weight, based on the total weight of the composition; (ii) water; and (iii) at least one O / W or Si / W type emulsifier selected from the following list: glyceryl stearate citrate, glyceryl stearate (self-emulsifying), stearic acid, stearates, polyglyceryl-3-methylglucose distearate, ceteareth-20, steareth-2, steareth-12, PEG-40 stearate, phosphates, and their salts, such as cetyl phosphate ( A), diethanolamine cetyl phosphate ( DEA), potassium cetyl phosphate ( K), sodium cetearyl sulfate, sodium glyceryl oleate phosphate, hydrogenated vegetable glyceride phosphate, sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, dodecyl glucoside, decyl glucoside, sodium stearoyl glutamate, sucrose polystearate and hydrated polyisobutene, and mixtures thereof. In addition, one or more synthetic polymers may be used as emulsifiers, such as PVP eicosene copolymer, acrylates / C10-30 alkyl acrylate crosspolymer, acrylates / steareth-20 methacrylate copolymer, PEG-22 / dodecyl glycol copolymer, PEG-45 / dodecyl glycol copolymer, and mixtures thereof. In a particular preferred embodiment, the O / W emulsifier is selected from the group consisting of: cetyl phosphate (such as, in particular, potassium cetyl phosphate (as K commercially available)), glyceryl stearate (and) PEG-100 stearate (as 165 commercially available), polyacrylamide, sodium polyacrylate, sodium polyacryloyldimethyl taurate, decyl glucoside, cetearyl glucoside, capryl / capryl glucoside, sorbitan olivate, polyglyceryl-4 olivate, polyglyceryl-3 methylglucose distearate, polysorbate 20, polysorbate 60 and / or polyalkylene glycol ethers (for example, in particular laureth-35 (lauryl alcohol with 35 EO units; as 35 is commercially available). The at least one O / W emulsifier is preferably used in an amount of about 0.001% to 10% by weight, more preferably 0.1% to 7% by weight, relative to the total weight of the composition. In addition, the cosmetic composition in the form of an O / W emulsion advantageously contains at least one auxiliary emulsifier selected from the following list: alkyl alcohols such as, but not limited to, cetyl alcohol (Lorol C16, Lanette 16), cetearyl alcohol ( O), stearyl alcohol ( 18) Behenyl alcohol 22), Glyceryl Monostearate, Glyceryl Myristate ( 3650), hydrogenated coconut acid glyceride (Lipocire Na10), and mixtures thereof.

[0089] The W / O emulsion according to the present invention advantageously comprises (i) 1,4-di(benzoxazol-2'-yl)benzene in an amount selected from the range of 0.1 wt% to 20 wt%, more preferably from about 0.25 wt% to 15 wt%, most preferably from about 0.3 wt% to 10 wt%, for example from 0.3 wt% to 7.5 wt%, based on the total weight of the composition; (ii) water; and (iii) at least one W / O emulsifier or W / Si emulsifier, the at least one W / O emulsifier or W / Si emulsifier being selected from the following: The following list: polyglyceryl-2-dipolyhydroxystearate, PEG-30 dipolyhydroxystearate, cetyl dimethicone copolyol, polyglyceryl-3 diisostearate polyglyceryl oleate / isostearate, polyglyceryl-6 hexaricinolate, polyglyceryl-4-oleate, polyglyceryl-4-oleate / PEG-8 propylene glycol cocoate, magnesium stearate, sodium stearate, potassium laurate, potassium ricinoleate, sodium cocoate, sodium tallowate, potassium castorate, sodium oleate, and mixtures thereof. Other suitable W / Si emulsifiers are lauryl polyglyceryl-3 polydimethylsiloxyethyl dimethicone and / or PEG-9 polydimethylsiloxyethyl dimethicone and / or cetyl PEG / PPG-10 / 1 dimethicone and / or PEG-12 dimethicone crosspolymer and / or PEG / PPG-18 / 18 dimethicone. The at least one W / O emulsifier is preferably used in an amount of about 0.001% to 10% by weight, more preferably 0.2% to 7% by weight, relative to the total weight of the composition.

[0090] The gel preparation according to the present invention advantageously comprises (i) 1,4-di(benzoxazol-2'-yl)benzene in an amount selected from the range of 0.1 wt% to 20 wt%, more preferably from about 0.25 wt% to 15 wt%, most preferably from about 0.3 wt% to 10 wt%, for example from 0.3 wt% to 7.5 wt%, based on the total weight of the composition; (ii) water; and (iii) at least one water-soluble thickener.

[0091] Such water-soluble thickeners are well known to those skilled in the art and are listed, for example, in "Handbook of Water-soluble gums and resins" by Robert L. Davidson (Mc Graw Hill Book Company (1980)). Particularly suitable water-soluble thickeners are selected from the group consisting of polyacrylic acids (for example those sold under the trade names Carbomer or Commercially available), 2-acrylamido-2-methylpropanesulfonic acid homopolymer (e.g. as 11-80 commercially available), acrylate copolymers (e.g., under the trade name or 33), branched poly(methacryloyloxyethyltrimethylammonium chloride) (INCI name Polyquaternium-37), unmodified guar gum (commercially available, for example, under the trade name Jaguar), starch or its derivatives and / or hydroxyalkylcellulose. Preferably, the water-soluble thickener is used in an amount of about 0.001% to 10% by weight, more preferably 0.1% to 7% by weight, based on the total weight of the composition.

[0092] The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are merely illustrative and are not intended to limit the scope of the present invention in any way. Example

[0093] 1. Preparation of 1,4-di(benzoxazol-2'-yl)benzene

[0094] A mixture of 702 g of polyphosphoric acid and 4.28 ml of methanesulfonic acid was heated to 90° C. 65 g of terephthalic acid and 107 g of 2-aminophenol were added. The mixture was stirred at 180° C. for 8 hours under an inert atmosphere and then transferred to ice water. The precipitated product was filtered out and washed with water and acetic acid. The precipitate was dispersed in water, and the pH was adjusted to 8.0 with sodium hydroxide, filtered and washed with water. The crude product was suspended in a 3.3:1 mixture of toluene and 1-butanol, stirred at 85° C. for one hour, filtered, washed with ether, and dried to obtain coarse particles of solid amorphous 1,4-di(benzoxazol-2'-yl)benzene (hereinafter referred to as DBO).

[0095] 2. Preparation of 30 wt% aqueous dispersion of 1,4-di(benzoxazol-2'-yl)benzene:

[0096] Then, a suspension containing 175 g of the coarse particles, 324 g of water and 65 g of Green APG 0810 was prepared and ground for 2 hours using a LabStar laboratory mill using yttrium-stabilized zirconium oxide grinding beads (0.3 mm, purchased from Tosoh Ceramic, Japan) and a cooling grinding chamber (-12°C saline). After removing the grinding beads, a 30% aqueous dispersion of micronized 1,4-di(benzoxazol-2'-yl)benzene (hereinafter referred to as DBO aqueous solution) was obtained, which was used in the antimicrobial tests and formulations described below.

[0097] 3. Antimicrobial activity

[0098] The antimicrobial efficacy was evaluated similarly to the regulatory challenge test method (NF EN ISO 11930). Therefore, a mixture of the corresponding active substance with physiological serum with 0.85 wt.% NaCl was prepared under sterile conditions at the concentrations outlined below. A control was also prepared under sterile conditions. The control and the mixture were then placed in a 96-deep well plate (1.6 ml / well). The corresponding bacterial or fungal strain was used at 2.5*10 5 cfu / ml to 5.6*10 5 cfu / ml of bacteria and 1*10 4 cfu / ml to 2.5*10 4 Each well was contaminated with fungi at 100 cfu / ml to obtain an initial contamination as outlined below. After contamination, each well was mixed thoroughly to ensure uniform distribution of the microorganisms. Each plate was then incubated at 22°C for 24 h. The (remaining) population was counted 24 hours after contamination. The average log reduction [-log10{(inoculum value (value inoculum)) / (sample value (value sample))}] was then calculated and is represented in Tables 1 to 5.

[0099] Table 1: Results obtained using 0.3 wt% DBO

[0100]

[0101] Table 2: Results obtained using a 1 wt% aqueous solution of DBO (0.3 wt% active substance)

[0102]

[0103]

[0104] As can be seen in the table above, 1,4-di(benzoxazol-2'-yl)benzene has an antimicrobial effect against a wide range of microorganisms and can therefore be used as a preservative synergist. Since the aqueous phase of known products is usually the most susceptible to microbial growth, 1,4-di(benzoxazol-2'-yl)benzene is particularly suitable for protecting products containing an aqueous phase (e.g. cosmetic compositions in the form of O / W or W / O emulsions) from microbial decay and decomposition and is therefore suitable for improving their preservation.

[0105] Table 3: Synergistic effect of using parahydroxyacetophenone (HAP)

[0106]

[0107] *0.3% active substance by weight

[0108] As can be retrieved from Table 2, DBO synergistically enhanced the antimicrobial activity of p-hydroxyacetophenone.

[0109] Table 4: Synergistic effect of using sodium benzoate

[0110]

[0111]

[0112] *0.3% active substance by weight

[0113] As can be retrieved from Table 3, the combination of DBO and sodium benzoate exhibits synergistic antimicrobial activity.

[0114] Table 5: Synergistic effect of using 1,3-propylene glycol (PDO)

[0115]

[0116] *0.3% active substance by weight

[0117] As can be retrieved from Table 4, the combination of DBO and 1,3-propanediol exhibits synergistic antimicrobial activity.

[0118] 4. Formulation Examples

[0119] Sunscreen o / w

[0120]

[0121] Gel Cream

[0122]

[0123] Sunscreen w / o

[0124]

[0125]

[0126] Skin care o / w

[0127]

[0128] Skin care o / w

[0129]

[0130] CC Moisturizer o / w

[0131]

[0132]

Claims

1. Non-therapeutic use of 1,4-di(benzoxazol-2'-yl)benzene as an antimicrobial agent, wherein the 1,4-di(benzoxazol-2'-yl)benzene is used in combination with a compound selected from the group consisting of p-hydroxyacetophenone, benzoic acid, sodium benzoate and 1,3-propylene glycol; and in: - the antimicrobial agent is an agent that inhibits the growth of Staphylococcus aureus and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and p-hydroxyacetophenone, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to p-hydroxyacetophenone is selected in the range of 30:1 to 1:2; or - the antimicrobial agent is an agent that inhibits the growth of E. coli and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and benzoic acid or sodium benzoate, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to benzoic acid or sodium benzoate is selected in the range of 30:1 to 1:1; or - The antimicrobial agent is an agent that inhibits the growth of Candida albicans and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and 1,3-propylene glycol, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to 1,3-propylene glycol is selected in the range between 15:1 and 1:

5.

2. The use according to claim 1, in a product selected from the group consisting of cosmetic compositions, household products, plastics, paper and / or coatings.

3. The use according to any one of claims 1 to 2 for improving preservation.

4. The use according to claim 1, wherein the 1,4-di(benzoxazol-2'-yl)benzene is used in micronized form.

5. A method for preventing microbial decomposition of a product selected from the group consisting of a cosmetic composition, a pharmaceutical composition, a household product, a plastic, a paper and / or a coating, wherein the method comprises adding 1,4-di(benzoxazol-2'-yl)benzene in an amount selected from the range of 0.1 wt % to 20 wt % based on the total weight of the product to the product, wherein the 1,4-di(benzoxazol-2'-yl)benzene is used as an antimicrobial agent in combination with a compound selected from the group consisting of p-hydroxyacetophenone, benzoic acid, sodium benzoate and 1,3-propylene glycol; and in: - the antimicrobial agent is an agent that inhibits the growth of Staphylococcus aureus and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and p-hydroxyacetophenone, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to p-hydroxyacetophenone is selected in the range of 30:1 to 1:2; or - the antimicrobial agent is an agent that inhibits the growth of E. coli and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and benzoic acid or sodium benzoate, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to benzoic acid or sodium benzoate is selected in the range of 30:1 to 1:1; or - The antimicrobial agent is an agent that inhibits the growth of Candida albicans and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and 1,3-propylene glycol, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to 1,3-propylene glycol is selected in the range between 15:1 and 1:

5.

6. A method for preventing microbial decay of a product selected from the group consisting of a cosmetic composition, a pharmaceutical composition, a household product, a plastic, a paper and / or a coating, wherein the method comprises adding 1,4-di(benzoxazol-2'-yl)benzene in an amount selected from the range of 0.1 wt% to 20 wt% based on the total weight of the product to the product, wherein the 1,4-di(benzoxazol-2'-yl)benzene is used as an antimicrobial agent in combination with a compound selected from the group consisting of p-hydroxyacetophenone, benzoic acid, sodium benzoate and 1,3-propylene glycol; and in: - the antimicrobial agent is an agent that inhibits the growth of Staphylococcus aureus and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and p-hydroxyacetophenone, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to p-hydroxyacetophenone is selected in the range of 30:1 to 1:2; or - the antimicrobial agent is an agent that inhibits the growth of E. coli and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and benzoic acid or sodium benzoate, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to benzoic acid or sodium benzoate is selected in the range of 30:1 to 1:1; or - The antimicrobial agent is an agent that inhibits the growth of Candida albicans and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and 1,3-propylene glycol, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to 1,3-propylene glycol is selected in the range between 15:1 and 1:

5.

7. The method according to claim 5 or 6, wherein the product further comprises water and at least one agent selected from the group consisting of surfactants, thickeners and oils.

8. The method according to claim 5 or 6, wherein the product further comprises water and at least one agent selected from emulsifiers.

9. The method according to claim 5 or 6, wherein the product is a cosmetic composition in the form of an O / W emulsion, a W / O emulsion or a gel.

10. A non-therapeutic method for killing microbial cells and / or inhibiting the growth of microbial cells, the method comprising contacting the microbial cells with 1,4-di(benzoxazol-2'-yl)benzene, wherein the 1,4-di(benzoxazol-2'-yl)benzene is used in combination with a compound selected from the group consisting of p-hydroxyacetophenone, benzoic acid, sodium benzoate and 1,3-propylene glycol; and in: - the microorganism is Staphylococcus aureus, and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and p-hydroxyacetophenone, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to p-hydroxyacetophenone is selected from the range of 30:1 to 1:2; or - the microorganism is Escherichia coli, and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and benzoic acid or sodium benzoate, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to benzoic acid or sodium benzoate is selected from the range of 30:1 to 1:1; or - The microorganism is Candida albicans, and the combination is a combination of 1,4-di(benzoxazol-2'-yl)benzene and 1,3-propylene glycol, wherein the weight ratio of 1,4-di(benzoxazol-2'-yl)benzene to 1,3-propylene glycol is selected in the range of 15:1 to 1:5.

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