Use of lock water magnet

Abstract

The present invention relates to a new use of hydrous magnetite for enriching the abundance of Paracoccus marcusii within the individual's skin microbiome.

Description

[0001] The present invention relates to the new use of saccharide isomerate for enriching the abundance of Paracoccus marcusii in the skin microbiome of an individual.

[0002] It is well known that the skin surface is colonized by a wide variety of microorganisms that form the skin microbiome (also commonly referred to as skin microbiota). The resident microbiota is present on the upper part of the epidermis and is aggregated in and around hair follicles. Most of the microorganisms on human skin are commensal or mutualistic bacteria. However, the microbiota can also include or be exposed to pathogenic microorganisms, such as Brevibacterium casei (B. casei) or Rothia mucilaginosa (R. mucilaginosa), which are part of a group of opportunistic bacteria defined as “coryneforms” that are increasingly implicated in severe infections. Commensal bacteria generally coexist peacefully with the host, while benefiting from a sheltered niche. Mutualistic microorganisms confer benefits to their host. Pathogenic microorganisms can be harmful to their host, especially when their presence exceeds certain thresholds.

[0003] Carotenoids such as astaxanthin are known to have benefits for skin homeostasis, such as improving wrinkled skin and skin elasticity. However, carotenoids are inherently characterized by their strong yellow to red color. Thus, even when used in small amounts, carotenoids strongly tint the finished product. However, tinted skin care products are not widely accepted by end consumers. Thus, despite the cosmetic benefits of carotenoids having been proven for many years, they are not widely used in the cosmetics industry. Therefore, there is still a need for alternative methods of supplying carotenoids such as astaxanthin topically to the skin.

[0004] Paracoccus marcusii (P. marcusii) is a gram-negative coccus that is naturally present on human skin. Furthermore, P. marcusii is known to produce carotenoids, mainly astaxanthin, and is therefore considered a mutualistic skin microorganism.

[0005] In addition, P. marcusii is reported to be a hydrocarbon degrader, especially of polycyclic aromatic hydrocarbons (PAHs) and a producer of biosurfactants. PAHs are known to adsorb onto the skin due to environmental pollution and have a potential carcinogenic effect.

[0006] Surprisingly, it has now been found that Locksley Magnet increases the differential abundance of Paracoccus marcusii in the skin microbiome of the body skin of a human being, as said differential abundance is positively correlated with the presence of said Paracoccus marcusii and can thus be used to promote the supply of carotenoids to the body skin of a human being and to degrade polycyclic aromatic hydrocarbons after adsorption to the body skin of a human being, e.g. due to environmental pollution.

[0007] Thus, in a first embodiment, the present application relates to a method of increasing the differential abundance of Paracoccus marcusii in the skin microbiome of the body skin of an individual, said method comprising the step of topically applying an effective amount of Locksley Magnet to the outer surface of the body skin of a human being in need thereof.

[0008] The method and use according to the present application are preferably used to promote the supply of carotenoids, such as astaxanthin, to the outer surface of the body skin of a human being and / or to degrade polycyclic aromatic hydrocarbons after adsorption to the outer surface of a human being.

[0009] It has furthermore been found that Locksley Magnet also significantly reduces the differential abundance of the pathogenic microorganisms Brevibacterium casei and Roseburia amnioniphila in the skin microbiome.

[0010] Thus, in another embodiment, the present application relates to a method according to the present application, wherein the differential abundance of Brevibacterium casei and / or Roseburia amnioniphila, preferably both, in the skin microbiome is simultaneously reduced.

[0011] In another embodiment, the present application also provides a method for providing protection to the outer surface of a human being by increasing the differential abundance of Paracoccus marcusii in the skin microbiome of the body skin, said method comprising the step of topically applying Locksley Magnet to said outer surface.

[0012] In another embodiment, the present application relates to a method of supplying carotenoids, such as astaxanthin, to the outer surface of the body skin of a human being, said method comprising the step of topically applying Locksley Magnet to the outer surface of the body skin of a human being in need thereof.

[0013] In another embodiment, the present application relates to a method of degrading polycyclic aromatic hydrocarbons adsorbed to the outer surface of a human being comprising body skin, said method comprising the step of topically applying Locksley Magnet to the outer surface of the body skin of a human being in need thereof.

[0014] In another embodiment, the present application relates to the use of Locksley Magnet or a topical composition comprising Locksley Magnet for increasing the differential abundance of Paracoccus marcusii in the skin microbiome of the body skin of an individual in need thereof.

[0015] The term external surface of the human body generally includes the skin as well as the scalp (including the hair and the armpit) and the oral cavity. In all embodiments of the present application, the external surface of the human body treated according to the present application is the body skin.

[0016] The term ‘body skin’ as used herein refers to the skin of the arms, the torso, the lower part of the body such as the legs and the feet, excluding the face and the scalp. Particularly preferred is the skin of the arms such as the (volar) forearm.

[0017] The term ‘skin microbiome’ as used herein refers to the microbiome colonizing a defined skin area of an individual such as the forehead, the forearm, the cheek or the scalp, but is not limited thereto.

[0018] The term ‘differential abundance’ as used herein refers to the log-fold change in abundance of taxa between two conditions. This analysis method giving the differential as output allows to identify microbiome taxa associated with certain biological or clinical conditions. The differential can be ranked and ordered from lowest to highest. These ‘rankings’ give information about the relative association of a feature with a given covariate (i.e. treatment or time).

[0019] ‘Differential abundance’ as used herein is determined by using software called Songbird as outlined in Morton et al. (Nat. Commun., 2019. 10(1): p. 2719), which is included herein by reference, which allows to build a statistical model testing the difference between treatments and to calculate the differential starting from relative abundance data from 16S rRNA sequencing. The output is a file containing the ranking of features with certain metadata categories. The higher the ranking, the greater its association with that category (i.e. treatment).

[0020] The term ‘increase or decrease in differential abundance’ as used herein is defined as an increase or decrease in the differential abundance of a specific microorganism compared to the differential abundance on a corresponding symmetrical skin area of the same individual treated with placebo.

[0021] Osmo-lock (CAS 100843-69-4) is a well-known cosmetic agent with a unique skin binding mechanism for short- and long-lasting moisturization. Osmo-lock is commercially available, for example, under the trademark from DSM Nutritional Products Ltd) or under the tradename Waterin (from Clariant), under the tradenames ‘EPS3 Powder’, EPS4 Powder’, EPS5 Powder’ and ‘EPS15 Powder (all from Codif) and under the tradename Hyanify from Lipotec.

[0022] In all embodiments of the present application, the most preferred water-locked magnetite is a water-locked magnetite consisting essentially of:

[0023] a) 1.5 to 4 wt.-%, preferably 2 to 3 wt.-% of psicose,

[0024] b) 1 to 5 wt.-%, preferably 1.5 to 2.5 wt.-% of mannose

[0025] c) 10 to 30 wt.-%, preferably 15 to 25 wt.-% of fructose,

[0026] d) 20 to 60 wt.-%, preferably 10 to 30 wt.-% of glucose, and

[0027] e) 0 to 5 wt.-%, preferably 0 to 1 wt.-% of galactose.

[0028] The term 'consisting essentially of as used herein means that the total amount of the listed ingredients ideally adds up to at most 100 wt.-%. However, it is not excluded that small amounts of unknown (sugar) impurities originating from the isomerization process are present, but only in an amount of at most 5 wt.-%, preferably at most 2.5 wt.-%.

[0029] The water-locked magnetite is preferably prepared by isomerization of glucose of plant origin and is commercially available as from DSM Nutritional Products Ltd.

[0030] The water-locked magnetite is preferably administered in the form of a topical composition comprising an effective amount of the water-locked magnetite and a cosmetically acceptable carrier.

[0031] The term 'effective amount' means the amount necessary to achieve the desired physiological effect. The physiological effect can be achieved by one application dose or by repeated applications. The dose applied can of course vary depending on known factors such as the physiological characteristics of the particular composition comprising the water-locked magnetite and the manner and route of its administration; the age, health and weight of the recipient; the type of treatment; the frequency of treatment; and the effect desired and which can be adjusted by the person skilled in the art.

[0032] Generally, the amount of water-locked magnetite in the topical composition according to the present application is selected in the range of 0.01 to 10 wt.-%, preferably in the range of 0.1 to 7.5 wt.-%, more preferably in the range of 0.2 to 5 wt.-%, based on the total weight of the topical composition. Further suitable ranges are 0.25 to 2.5 wt.-% and 0.5 to 2 wt.-%.

[0033] The term 'cosmetically acceptable carrier' (also referred to herein as carrier) means all vehicles / carriers conventionally used for topical cosmetic compositions, i.e. which are suitable for topical application to keratinous tissue, have good aesthetic properties, are compatible with the active substances present in the composition, and do not pose any unreasonable safety or toxicity problems. Such carriers are well known to the person of ordinary skill in the art.

[0034] The precise amount of carrier will depend on the actual level of hydromagnite and the actual level of any other optional ingredients (e.g. other active ingredients) which the person of ordinary skill in the art would classify as different from the carrier.

[0035] In an advantageous embodiment, the topical composition according to the present application comprises from about 50% to about 99%, preferably from about 60% to about 98%, more preferably from about 70% to about 98%, such as in particular from about 80% to about 95% of carrier, based on the total weight of the topical composition.

[0036] In a particularly advantageous embodiment, the carrier further consists of at least 40% by weight, more preferably at least 50% by weight, most preferably at least 55% by weight of water, such as in particular from about 55% to about 90% by weight of water.

[0037] The topical composition according to the present application is preferably prepared by mixing / incorporating hydromagnite having all definitions and preferences as given herein with / into a cosmetically acceptable carrier.

[0038] The use of hydromagnite according to the present application can be therapeutic or non-therapeutic. Preferably, the use is non-therapeutic, i.e. for cosmetic applications. Thus, preferably, in all embodiments, the topical composition is a cosmetic (non-therapeutic) composition.

[0039] The term "cosmetic composition" as used in the present application means cosmetic compositions as defined under the heading "Kosmetika" in the Ullmann's Encyclopedia of Industrial Chemistry, Vol. 5, 1987, VCH Verlagsgesellschaft, Weinheim, New York, Cambridge, pp. 177-198, and in the Lexikon Chemie, 10thEdition 1997, Georg Thieme Verlag Stuttgart, New York, and cosmetic compositions as disclosed in A. Domsch, "Cosmetic Compositions", Verlag fur chemische Industrie (H. Ziolkowsky ed.), 4thEdition, 1992.

[0040] Suitable compositions according to the present application are leave-on or rinse-off products and include any product applied to the human body, preferably for cleansing the skin. Thus, the use is preferably achieved by incorporation into a rinse-off composition.

[0041] Rinse-off as used herein is defined according to the European Parliament and Council Regulation (EC) No 1223 / 2009 of 30 November 2009 on cosmetic products (amended version), i.e. a cosmetic product or composition is rinse-off when it is intended to be removed after application to the skin, hair or mucous membranes of human subjects.

[0042] The rinse-off cosmetic composition disclosed in the present application can be a rinse-off cosmetic cleansing composition, such as a rinse-off cosmetic personal care cleansing composition. Examples of rinse-off cosmetic compositions (hereinafter also referred to as "composition") are shower gel compositions, liquid soaps, body washes and shampoos. The composition is not edible or eatable like a toothpaste.

[0043] Thus, in one particular embodiment, the present application relates to a method according to the present application, comprising the steps of (i) applying a rinse-off composition to the skin of the body, preferably to the torso, arms and / or legs, and then (ii) rinsing the composition off with water.

[0044] The composition can be in the form of a liquid, lotion, cream, foam, scrub, gel, soap bar or toner, or applied with an appliance or by a mask, pad or patch. Non-limiting examples of such compositions include leave-on skin lotions and creams, shampoos, conditioners, shower gels, facial washes, body washes, toilet bars, antiperspirants, deodorants, depilatories, lipsticks, foundations, mascaras, self-tanning creams and sunscreen lotions.

[0045] The composition of the present application (including the carrier) can comprise conventional adjuvants and additives, such as preservatives / antioxidants, fatty substances / oils, organic solvents, silicones, thickening agents, emollients, antifoams, soaps, detergents, aesthetic components such as fragrances, surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorings / colorants, abrasives, absorbents, chelating agents and / or sequestering agents, essential oils, skin sensates, astringents, pigments or any other ingredient usually formulated into such compositions.

[0046] According to the present application, the composition according to the present application can also comprise additional cosmetic active ingredients conventionally used in cosmetic compositions. Exemplary active ingredients include UV filters, agents for preventing or reducing inflammation; firming agents, moisturizing agents, soothing agents and / or energizing agents and agents for improving elasticity and skin barrier.

[0047] Cosmetic excipients, diluents, adjuvants, additives, as well as active ingredients conventionally used in the skin care industry, which are suitable for use in the cosmetic compositions of the present application, are exemplified, for example, in the International Cosmetic Ingredient Dictionary & Handbook of the Personal Care Product Council (http: / / www.personalcarecouncil.org / ), which is accessible through the online INFOBASE (http: / / online.personalcarecouncil.org / jsp / Home.jsp), but are not limited thereto.

[0048] The necessary amounts of active ingredients as well as excipients, diluents, adjuvants, additives, etc. can be readily determined by the skilled person depending on the desired product form and application. Additional ingredients can be added to the oil phase, the water phase or separately, as the case can be.

[0049] The cosmetic active ingredients useful herein can in some cases provide more than one benefit or work by more than one mode of action.

[0050] Of course, the person skilled in the art will carefully select the optional additional ingredients, adjuvants, diluents and additives mentioned above and / or their amounts, such that the advantageous properties inherent to the combination according to the present application are not affected or are not substantially affected by the envisaged addition(s) of the adverse.

[0051] If the composition is an emulsion, such as in particular an O / W emulsion, a W / O emulsion, a Si / W emulsion, a W / Si emulsion, an O / W / O emulsion, a W / O / W emulsion or a pickering emulsion, the amount of oil phase present in such cosmetic emulsion is preferably at least 10% by weight, such as in the range of 10% to 60% by weight, preferably in the range of 15% to 50% by weight, most preferably in the range of 15% to 40% by weight, based on the total weight of the composition.

[0052] In one embodiment, the composition according to the application is advantageously in the form of an oil-in-water (O / W) emulsion comprising an oil phase dispersed in an aqueous phase in the presence of an O / W emulsifier. The preparation of such O / W emulsions is well known to the person skilled in the art.

[0053] If the composition according to the application is an O / W emulsion, it advantageously comprises at least one O / W emulsifier or Si / W emulsifier selected from the following list: glyceryl stearate citrate, glyceryl stearate SE (self-emulsifying), stearic acid, salts of stearic acid, polyglyceryl-3-methyl glucose distearate. Further suitable emulsifiers are phosphoric esters and salts thereof such as cetyl phosphate (e.g. as A from the company Evonik Nutrition & Care GmbH), cetyl diethanolamine phosphate (e.g. as DEA from the company Evonik Nutrition & Care GmbH), potassium cetyl phosphate (e.g. as K from the company Evonik Nutrition & Care GmbH), sodium cetearyl sulphate, sodium glyceryl oleate phosphate, hydrogenated vegetable glycerides phosphate and mixtures thereof. Further suitable emulsifiers are polyalkylene glycol ethers, sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, cetearyl glucoside, lauryl glucoside, decyl glucoside, sodium stearoyl glutamate, sucrose polystearate and hydrated polyisobutylene. Furthermore, one or more synthetic polymers can be used as emulsifiers. For example, PVP eicosene copolymer, acrylates / C10-30 alkyl acrylate crosspolymer and mixtures thereof.

[0054] The at least one O / W emulsifier or Si / W emulsifier is preferably used in an amount of 0.5 to 10 wt.-%, in particular in the range of 0.5 to 6 wt.-%, such as more particularly in the range of 0.5 to 5 wt.-%, such as most particularly in the range of 1 to 4 wt.-%, based on the total weight of the composition.

[0055] Particularly suitable O / W emulsifiers for use in the compositions according to the present application include phosphate ester emulsifiers such as advantageously 8-10 alkyl ethyl phosphate, C9-15 alkyl phosphate, Ceteth-2 phosphate, Ceteth-5 phosphate, Ceteth-8 phosphate, Ceteth-10 phosphate, Cetyl phosphate, C6-10 pareth-4 phosphate, C12-15 pareth-2 phosphate, C12-15 pareth-3 phosphate, DEA-Ceteth-2 phosphate, DEA-Cetyl phosphate, DEA-Oleth-3 phosphate, Potassium cetyl phosphate, Deceth-4 phosphate, Deceth-6 phosphate and Triceteth-4 phosphate as well as polyalkylene glycol ethers such as in particular polyethylene stearyl ethers such as Ceteth-2 and Ceteth-21.

[0056] A particularly suitable class of O / W emulsifiers for use in the compositions according to the present application are polyalkylene glycol ethers. Particularly preferred O / W emulsifiers in all embodiments of the present application are stearyl ethers of polyethylene glycol such as most preferably Ceteth-2 (polyoxyethylene (2) stearyl ether) or Ceteth-21 (polyoxyethylene (21) stearyl ether) and mixtures thereof. Such polyalkylene glycol ether emulsifiers are commercially available for example under the trade name Brij from Croda.

[0057] The cosmetic compositions according to the present application advantageously comprise a preservative. Particularly suitable preservatives in all embodiments of the present application are phenoxyethanol and ethylhexylglycerin and mixtures thereof. When present, the preservative is preferably used in an amount of 0.1 to 2 wt.-%, more preferably in an amount of 0.5 to 1.5 wt.-%, based on the total weight of the composition.

[0058] The pH of the compositions according to the present application typically ranges from 3 to 10, preferably the pH ranges from 4 to 8, and most preferably the pH ranges from 5 to 8. The pH can be adjusted as desired according to standard methods in the art with a suitable acid such as citric acid or a base such as sodium hydroxide (e.g. as an aqueous solution), triethanolamine (TEA Care), tromethamine (Trizma Base) and aminomethyl propanol (AMP-Ultra PC 2000).

[0059] Preferred topical compositions according to the present application are rinse-off formulations which are intended / required to be removed from the body by washing with a solvent, preferably water, after application of the composition.

[0060] A particularly preferred detergent wash-off composition according to the present application is a liquid detergent wash-off composition.

[0061] A particularly preferred detergent wash-off composition according to the present application is a liquid detergent wash-off composition.

[0062] Preferably, in all embodiments of the present application, the detergent wash-off composition according to the present application consists essentially of water-locking magnetite, water, at least one soap, preferably several soaps and / or surfactants, humectants, chelating agents, alkalizing or acidifying agents, active agents, solubilizers, pearlescent or opacifying agents, thickening agents, wetting agents, and additives to enhance its appearance, feel, and fragrance, such as colorants, fragrances, preservatives, and the like.

[0063] The water content of the detergent wash-off composition according to the present application is preferably selected in the range of 40 to 70 wt.-%, more preferably in the range of 45 to 65 wt.-%, most preferably in the range of 50 to 60 wt.-%.

[0064] The term "soap" is used herein in its popular sense, i.e. it refers to alkali or alkanolammonium salts of aliphatic, alkane or alkene monocarboxylic acids and mixtures thereof. Sodium, potassium, magnesium, mono-, di- and triethanolammonium cations or combinations thereof are particularly suitable for the purposes of the present application, but it is preferred to use sodium soaps or potassium soaps.

[0065] Particularly preferred soaps for the purposes of the present application are well-known alkali salts such as, in particular, sodium and / or potassium salts of natural or synthetic aliphatic acids (alkanoic or alkenoic acids) having about 8 to 22 carbon atoms, preferably about 8 to about 20 carbon atoms, most preferably about 10 to about 18 carbon atoms. Even more preferred are the salts of the corresponding saturated (alkanoic) acids.

[0066] It is further preferred that the soap used for the detergent composition according to the present application comprises at least 85% of fatty acids having 12 to 18 carbon atoms.

[0067] Particularly preferred soaps for the detergent composition of the present application are sodium and / or potassium salts of stearic acid, lauric acid, myristic acid, oleic acid, and palmitic acid.

[0068] It is to be understood that the soaps can be used as such or can be formed "in situ" in the detergent wash-off composition by adding the respective acid and the respective base to the composition.

[0069] The amount of at least one soap in the detergent wash-off composition according to the present application can be easily chosen by the person skilled in the art, such as ranging from 3 wt.% to 95 wt.%. The person skilled in the art understands that the amount depends to a large extent on the type of the detergent wash-off composition, i.e. if the detergent wash-off composition is a soap bar, the concentration is chosen in the range of 50 - 95 wt.% based on the total weight of the detergent wash-off composition, whereas if the composition is a liquid (aqueous) wash-off composition, the concentration is chosen in the range of 15 wt.% to 50 wt.%, preferably in the range of 20 wt.% to 40 wt.%, most preferably in the range of 25 wt.% to 35 wt.%.

[0070] Particularly preferred soaps for use in the detergent wash-off composition according to the present application are sodium and / or potassium salts of lauric acid, stearic acid and myristic acid and mixtures thereof.

[0071] Particularly suitable surfactants for use in the detergent wash-off composition according to the present application, such as in particular in a liquid detergent wash-off composition, are anionic, cationic, non-ionic and / or amphoteric surfactants to form a surfactant mixture.

[0072] Suitable anionic surfactants comprised in the detergent wash-off composition according to the present application include, but are not limited to, aliphatic sulfates, aliphatic sulfonates (e.g. C8to C 22 sulfonates or disulfonates), aromatic sulfonates (e.g. alkylbenzene sulfonates), alkyl sulfosuccinates, alkyl and acyl taurates, alkyl and acyl sarcosinates, sulfoacetates, alkyl phosphates, carboxylates and isethionates and mixtures thereof.

[0073] Particularly suitable anionic surfactants for the purposes of the present application are alkyl sulfates, such as preferably sodium lauryl sulfate, triethanolamine lauryl sulfate or ammonium lauryl sulfate; alkyl ether sulfates (or alkyl PEG-n sulfates), such as preferably sodium lauryl ether sulfate or ammonium lauryl ether sulfate, lauryl polyoxyl ether sulfate, C 2-15 sodium alkyl glyceryl ether sulfonate); alkyl aryl polyether sulfonates; monoglyceride sulfates; acyl isethionates, such as preferably sodium acyl isethionate, sodium cocoyl isethionate; alkyl aryl sulfonates, such as preferably sodium alkyl benzene sulfonate and / or sodium dodecyl benzene sulfonate; alkyl sulfonates, such as preferably sodium alkenyl sulfonate (C 12-14 sodium), sodium alkyl glyceryl sulfonate (sodium cocoyl monoglyceride sulfonate), sodium alkyl ether sulfonate (C 12-15Sodium sulfonated alkyl alcohols, such as preferably sodium lauryl sulfoacetate; (ii) sodium sulfosuccinates, such as preferably sodium dioctyl sulfosuccinate, disodium alkyl PEG-n sulfosuccinates, disodium alkyl amido PEG-n sulfosuccinates (disodium oleyl amido MEA-sulfosuccinate), disodium alkyl sulfosuccinates; alkyl phosphate esters (monoesters), such as preferably TEA lauryl phosphate; PEG-n alkyl phosphate esters, such as preferably DEA oleth-10 phosphate; di PEG-n alkyl phosphate esters (diesters), such as preferably di (laureth-4) phosphate; phospholipids (triesters), such as preferably lecithin; carboxylic acid esters, such as preferably monoesters of di- or tri-carboxylic acids, such as lactylates (sodium acyl lactylates, calcium stearoyl lactylate), laureth-6 citrate, myreth-9 citrate; ether carboxylic acids, such as preferably PEG-n sodium alkyl carboxylates, trideceth-13 carboxylic acid sodium, myreth-8 carboxylic acid, polyoxyalkylenated alkyl C6-C 24 ether carboxylates; acyl glutamates, such as preferably di-TEA palmitoyl aspartate and sodium hydrogenated tallow glutamate; acyl peptides with various amino acid side groups, such as preferably palmitoyl hydrolyzed milk protein, sodium cocoyl hydrolyzed soy protein, TEA-cocoyl hydrolyzed collagen or other acyl hydrolyzed protein salts; sarcosinates or acyl sarcosides, such as preferably myristoyl sarcosine, TEA-lauryl sarcosinate; and taurinates and sodium methyl acyl taurates, such as preferably sodium lauroyl taurate, sodium methyl cocoyl taurate.

[0074] Particularly suitable nonionic surfactants for the purposes of the present application include ethers comprising aliphatic (C6-C 18 ) primary or secondary linear or branched acids, alcohols or phenols, which have no functional groups other than the terminal OH group of the polyoxyethylenated (POE) chain, and ethoxylated alcohols and propoxylated POE ethers, such as preferably PEG ethers, PPG ethers, propylene glycol alkyl POE-n ethers; of the general formula C n H 2n+1 O(C6H 10 O5) xH alkyl polyglucosides, wherein x is 1 to 4, such as preferably decyl glucoside and lauryl glucoside; alkanolamides, such as preferably N-acyl derivatives of monoethanolamine (MEA) and diethanolamine (DEA), which are ethoxylated or non-ethoxylated; such as preferably PEG-n amides, coco mono- or diethanolamide, palmitamide MEA, amide DEA; esters, such as preferably ethoxylated fatty acids; mono- and diesters of fatty acids with ethylene oxide or polyethylene glycol, PEG-n acylates and diacylates such as PEG-8 laurate, PEG-8 dilaurate, PEG-100 stearate, PEG-150 distearate, ethoxylated glycerides such as preferably PEG-n glyceryl acylates, PEG-4 castor oil, PEG-120 glyceryl stearate, glyceryl trioleate PEG-6 ester, glycol esters and derivatives, monoesters of ethylene glycol or propylene glycol such as preferably glycol acylates or propylene glycol acylates, monoglycerides such as glyceryl myristate or stearate, glyceryl palmitate lactate, polyglycerol esters such as polyglyceryl-n acylates or polyglyceryl-n alkyl ethers, sorbitan / sorbitol esters such as preferably ethoxylated or non-ethoxylated acetylated sorbitan, polysorbate-n, sorbitan sesquiisostearate, alkyl carbohydrate esters or sucrose esters, which result from the ester interchange reaction of sucrose with fatty acid methyl esters or triglycerides, such as preferably alkyl polysaccharides; and amine oxides, such as preferably cocamidopropyl amine oxide and lauramine oxide. A particularly preferred group of nonionic surfactants for use in the rinse-off compositions according to the present application are alkyl polyglucosides such as lauryl glucoside, PEG-n acylates and diacylates such as PEG 100 stearate and glyceryl stearate.

[0075] Zwitterionic and amphoteric surfactants particularly suitable according to the present application include secondary or tertiary aliphatic amine derivatives having an aliphatic chain which is linear or branched, containing at least 8 to 22 carbon atoms and one anionic group selected from the group of carboxylate, sulfonate, sulfate, phosphate or phosphonate; acyl / dialkylenediamines, such as preferably acyl amphoacetates, acyl amphodipropionates disodium, acyl amphohydroxypropyl sulfonate sodium, acyl amphodiacetates disodium, acyl amphopropionates sodium and wherein acyl represents an alkyl or alkenyl group, which can be mono- or polyunsaturated and contains 5 to 29 carbon atoms; N-alkyl amino acids or iminodi acids, such as preferably aminopropyl alkyl glutamides, alkyl aminopropionates, alkyl iminopropionates sodium, alkyl glycinates and carboxyglycinates, sodium cocoyl glycinate; and betaines, such as preferably alkyl (C8-C 20 )betaines, alkylamidopropyl betaines (cocamidopropyl betaine), alkyl (C8-C 20 )amidoalkyl (C1-C6)betaines, alkylsultaine and alkyl (C8-C 20) amidoalkyl(C1-C6) sulfobetaines.

[0076] Particularly suitable cationic surfactants according to the present application include alkyl amines such as preferably dimethylalkyl amines (dimethyl lauryl amine), dihydroxyethyl alkyl amine dioleate, acyl amido propyl dimethyl amine lactate (cocamido propyl dimethyl amine lactate); alkyl imidazolines such as preferably alkyl hydroxyethyl imidazolines, ethyl hydroxymethyl oleyl oxazoline, alkyl amino ethyl imidazolines; ethoxylated alkyl amines such as preferably PEG-n alkyl amines, PEG-n alkyl amino propyl amines, poloxamines; quaternary compounds such as preferably tetraalkyl ammonium salts; alkyl trimethyl ammonium chloride, PEG-n alkyl monium chloride, dialkyl dimethyl ammonium chloride (hydroxyethyl cetyl dimethyl ammonium chloride), alkyl amido propyl alkyl dimethyl ammonium toluene sulfonate (cocamido propyl ethyl dimethyl ammonium ethyl sulfate), PEG-n acyl methyl diethyl ammonium methyl sulfate, dialkyl hydroxy propyl methyl ammonium methyl sulfate, and alkyl dimethyl ammonium hydroxy propyl protein hydrolysate (coco dimethyl ammonium hydroxy propyl hydrolyzed hair keratin).

[0077] Particularly preferred surfactants for use in the rinse-off composition according to the present application are selected from the group of glucosides such as lauroyl glucoside, arachidyl glucoside, caprylyl / capryl glucoside, and coco glucoside; PEG-n acylates and diacylates such as PEG-8 laurate, PEG-8 dilaurate, PEG-100 stearate; monoglycerides such as glyceryl myristate or stearate; and mixtures thereof.

[0078] The amount of at least one surfactant in the detergent rinse-off composition according to the present application is preferably selected in the range of 1 wt.% to 30 wt.%, preferably in the range of 2.5 wt.% to 10 wt.%, most preferably in the range of 5 wt.% to 15 wt.%, based on the total weight of the detergent rinse-off composition. Preferably, however, the amount of surfactant in the rinse-off composition is selected in the range of 15 wt.% to 50 wt.%, preferably in the range of 20 wt.% to 40 wt.%, most preferably in the range of 25 wt.% to 35 wt.%, based on the total weight of the detergent rinse-off composition.

[0079] In a particularly preferred embodiment, the detergent rinse-off composition according to the present application comprises a mixture of at least one soap, preferably several soaps, and at least one surfactant, having all the definitions and preferences as given herein. Even more preferably, the total amount of the mixture of soap(s) and surfactant(s) is selected in the range of 15 wt.% to 50 wt.%, preferably in the range of 20 wt.% to 40 wt.%, most preferably in the range of 25 wt.% to 35 wt.%, based on the total weight of the detergent rinse-off composition. It is even more preferred then that the soap makes up more than 60 wt.%, more preferably more than 65 wt.%, most preferably more than 70 wt.% of said mixture.

[0080] Suitable chelating agents incorporated into the detergent rinse-off composition according to the present application include those capable of protecting and preserving the compositions of the present application. Preferably, the chelating agent is ethylenediaminetetraacetic acid ("EDTA"), and more preferably is EDTA tetrasodium salt (commercially available under the trade name "Versene 100XL" from Dow Chemical Company of Midland, Michigan), or even EDTA disodium salt (commercially available under the trade name "EDETA BD" from BASF).

[0081] Other suitable chelating agents include phytic acid and its sodium salt, gluconic acid and its sodium salt, and etidronic acid and its sodium salt, phosphoric acid and its sodium salt, gluconic acid and its sodium salt, oxalic acid, citric acid, lauryl alcohol bisphosphonic acid, glutamic acid diacetic acid tetrasodium salt, dicarboxymethyl alanine trisodium salt, ethylenediamine disuccinic acid trisodium salt.

[0082] The amount of chelating agent is preferably selected in the range of 0.01 wt.% to 1 wt.%, preferably in the range of 0.1 wt.% to 0.75 wt.%, most preferably in the range of 0.25 wt.% to 0.75 wt.%, based on the total weight of the detergent rinse-off composition.

[0083] The acidifying agent can be, for example, an inorganic or organic acid, such as hydrochloric acid, orthophosphoric acid, a carboxylic acid, such as tartaric acid, citric acid, lactic acid, or a sulfonic acid.

[0084] Among the basifying agents that can be mentioned, for example, are alkali metal or alkaline earth metal salts such as sodium or potassium hydroxide, alkali metal carbonates, and alkanolamines such as mono-, di- and triethanolamine.

[0085] The basifying or acidifying agent serves to adjust the pH of the rinse-off composition. In a preferred embodiment, the pH of the detergent rinse-off composition according to the present application is adjusted to about 4.5 to about 10.5, and more preferably to about 5.0 to about 10.0, with a basifying or acidifying agent.

[0086] Further, the amount of alkalizing or acidifying agent in the detergent rinse-off composition according to the present application is preferably at least 0.0001 wt.%, such as in the range of 0.01 wt.% to 6 wt.%, in particular, in the range of 3 wt.% to 5 wt.%.

[0087] The detergent compositions of the present application can also contain one or more optional ingredients such as pearlizing or opacifying agents, thickeners, humectants, and additives to enhance their appearance, feel, and fragrance, such as coloring agents, perfumes, preservatives, and the like.

[0088] Commercially available pearlizing or opacifying agents capable of suspending water-insoluble additives and / or tending to indicate to the consumer that the resulting product is a detergent composition are suitable for use herein. The pearlizing or opacifying agents can be present in an amount of from about 1 wt.% to about 10 wt.%, preferably from about 1.5 wt.% to about 7 wt.%, and more preferably from about 2 wt.% to about 5 wt.%, based on the total weight of the composition.

[0089] Examples of suitable pearlizing or opacifying agents include, but are not limited to, (a) fatty acids having from about 16 to about 22 carbon atoms and (b) monoesters or diesters of ethylene glycol or propylene glycol; (a) fatty acids having from about 16 to about 22 carbon atoms, (b) monoesters or diesters of polyalkylene glycols of the formula: HO-(JO)a-H (where J is an alkylene group having from about 2 to about 3 carbon atoms and a is 2 or 3); fatty alcohols containing from about 16 to about 22 carbon atoms; fatty esters of the formula: KCOOCH2L, where K and L independently contain from about 15 to about 21 carbon atoms; inorganic solids which are insoluble in the detergent composition, and mixtures thereof.

[0090] The pearlizing or opacifying agents can be introduced into the detergent composition as a preformed stable aqueous dispersion, such as that commercially available under the trade name "Euperlan PK-3000" from Henkel Corporation of Hoboken, New Jersey. This material is a combination of diethylene glycol distearate (diester of ethylene glycol and stearic acid), laureth-4 (CH3(CH2) 10 CH2(OCH2CH2)4OH) and cocamidopropyl betaine, and preferably in a weight percent ratio of from about 25 to about 30: from about 3 to about 15: from about 20 to about 25, respectively.

[0091] Commercially available thickeners capable of imparting the proper viscosity to the detergent rinse-off composition are suitable for use herein. If used, the thickener should be present in the composition in an amount sufficient to increase the Brookfield viscosity of the composition to a value of between about 500 to about 10,000 centipoise. Examples of suitable thickeners include, but are not limited to, 1) polyethylene glycols of the formula: HO-(CH2CH2O)n-H (where n is an integer from 4 to 20)z H, wherein z is an integer from about 3 to about 200, and 2) mono- or di-esters of fatty acids containing from about 16 to about 22 carbon atoms; fatty acid esters of ethoxylated polyols; ethoxylated derivatives of mono- and di-esters of fatty acids and glycerol; hydroxyalkyl celluloses; alkyl celluloses; hydroxyalkyl alkyl celluloses; and mixtures thereof. Preferred thickening agents include polyethylene glycol esters, and more preferably PEG-150 distearate, which is available from Stepan Company of Northfield, Illinois, or from Comiel, S.p.A. of Bologna, Italy, under the trade name "PEG 6000 DS."

[0092] The amount of one or more thickening agents in the detergent rinse-off composition is preferably selected to range from 0 wt.% to 7 wt.%, preferably from 1 wt.% to 5 wt.%, most preferably from 2 wt.% to 4 wt.% based on the total weight of the detergent rinse-off composition.

[0093] Commercially available humectants capable of providing moisturization and conditioning properties to the detergent composition are suitable for use in the present application. Examples of suitable humectants include, without exclusion: 1) water-soluble liquid polyols selected from the group comprising glycerin, propylene glycol, 1,3-propanediol, hexylene glycol, butylene glycol, dipropylene glycol, and mixtures thereof; 2) polyalkylene glycols of the formula: HO-(R"O)b-H, wherein R" is an alkylene group having from about 2 to about 3 carbon atoms and b is an integer from about 2 to about 10; 3) polyethylene glycol ether of methyl glucose of the formula CH3-C6H 10 O5-(OCH2CH2)c-OH, wherein c is an integer from about 5 to about 25; 4) urea; and 5) mixtures thereof, with glycerin or PEG-32 being the preferred humectant.

[0094] Preferably, in all embodiments, the detergent rinse-off composition comprises at least one humectant. If present in the detergent composition, the amount of the at least one humectant is preferably selected to range from 0 wt.% to 90 wt.%, preferably from 5 wt.% to 40 wt.%, most preferably from 15 wt.% to 30 wt.% based on the total weight of the detergent rinse-off composition. Further suitable ranges include from 1 wt.% to 10 wt.%, from 2 wt.% to 8 wt.% and from 2.5 wt.% to 5 wt.% based on the total weight of the detergent rinse-off composition.

[0095] Suitable preservatives for inclusion in the detergent wash-off composition according to the present application include Quaternium-15, which is commercially available as "Dowicil 200" from Dow Chemical Company, Midland, Michigan, and is present in the composition in an amount ranging from about 0 wt.% to 5.0 wt.%, preferably from about 0.05 wt.% to 2 wt.%, most preferably from about 0.1 wt.% to 1.5 wt.%, based on the total weight of the detergent composition.

[0096] The detergent composition of the present application can be used on the body in combination with any personal cleansing implement known in the art, such as a towel, mesh or open cell membrane, pouf, sponge, brush, and the like. The composition can be sold in kit form together with one or more such implements.

[0097] Furthermore, the composition of the present application can be "substantially free" of oil or silicone. As used herein, "substantially free" shall mean that the detergent wash-off composition contains less than about 1 wt.%, for example less than about 0.5 wt.% or less than about 0.2 wt.% of oil and / or silicone, based on the total weight of the detergent composition.

[0098] In another preferred embodiment, the detergent wash-off composition according to the present application is a (solid) soap bar.

[0099] The most preferred detergent wash-off composition according to the present application consists essentially of water-locked magnetite, water, at least one, preferably several, soaps and / or surfactants, and optionally one or more humectants, one or more chelating agents, and an alkalizing or acidifying agent, having all definitions and preferences as given herein.

[0100] The following examples are provided to further illustrate the compositions and effects of the present application. These examples are illustrative only and are not intended to limit the scope of the present application in any way.

[0101] Figure 1 qPCR assessment of microbial load of S. epidermidis (Time 0: black and white bars: before treatment, on symmetric locations on the volar forearm of the arm as outlined in the examples; Time 1.0 to 24.0 hours: white bars: placebo, black bars: treatment; y-axis: amount of DNA per μΐ, x-axis: time (hours). For details see experimental section. Example

[0102] Example: In vivo study demonstrating the enrichment of M. lockwodyi on skin after use of Lock Water Magnet on the skin of the body Figure 1

[0103] In a 7-day placebo-controlled in vivo clinical study (30 volunteers), the wash-off body wash formulations containing 0.5% of Aquaphor® Locking Water as listed in Table 1 were applied once on the volar forearm during the first 24 hours and twice a day for the remaining days until day 7. Microbiome samples were collected at different time points (T0, 1 h, 6 h, 24 h and day 7) and the extracted DNA was subjected to 16S rRNA sequencing and qPCR. Results obtained from 16S rRNA sequencing were processed following the “reference frames” approach published by Morton et al. (Nat. Commun., 2019. 10(1): p. 2719). This approach allows to assess the microbial population changes and how these changes are associated with time and treatment. The differences were calculated starting from the relative abundance data from 16S sequencing using a software called Songbird. The reference time and treatment difference values are reported in Table 2 below.

[0104] Table 1. Formulations

[0105]

[0106] Table 2. “Reference frames” analysis gave the following results

[0107]

[0108]

[0109] The “Time point comparison” column indicates the time range in which the microbial changes were assessed. Example: T0-1 h-6 h means that the microbial shift was assessed in the time window from the beginning of the study (T0) until the 6 hours time point after the first product application. The “Intercept” column indicates the starting point for each microorganism. Positive values mean that the microorganism of interest was present to some extent on the skin before the assessment. The “Treatment” column refers to whether and to what extent a specific microorganism is associated with the active treatment. The reported values are the result of the differences obtained by the software by using placebo-valued samples as reference. Therefore, positive values indicate a positive correlation with the active treatment. The “Time” column indicates how a specific microorganism is associated with time, independently of the treatment. Positive values mean that the microorganism tends to increase its abundance over time.

[0110] Overall, the results show a strong correlation of P. mairii with the active treatment containing the hydrous magnetite at all time points considered. In contrast, so-called "coryneform bacteria", such as R. aminovorans and B. casei, show a negative correlation with the active treatment at the time points considered. The positive effect of the hydrous magnetite on the enrichment of P. mairii is further strengthened, since this bacterium will generally reduce its abundance on the skin over time, as shown in the table, probably due to skin cleansing procedures. Surprisingly, S. epidermidis, a common skin commensal, is negatively correlated with the active treatment containing the hydrous magnetite, especially during the first 6 hours, and its differential abundance is not particularly supported by this treatment in the subsequent time points evaluated (the slightly positive values indicate anyway a very weak correlation at 24h and D7).

[0111] To further strengthen our conclusions, this result was confirmed by a qPCR evaluation of the microbial load of S. epidermidis over 24 hours, as shown in Comparative Example: In vivo study demonstrating the negative correlation of M. lockwodyi after use of Lock Water Magnet on the skin of the face

[0112] The data show a reduction of the microbial load of S. epidermidis compared to the baseline (TO), most likely due to the cleansing procedure, since this reduction is observed both in the placebo and in the active treatment group. At the subsequent time points, there is no evidence of any growth promoted by the treatment compared to the placebo. These results are in perfect agreement with the differential abundance analysis, in which S. epidermidis was considered negatively correlated with the active substance.

[0113] In conclusion, the data show that the wash-off formulation containing the hydrous magnetite selectively supports and enriches P. mairii on the skin, without supporting other commensal bacteria, such as S. epidermidis, and, in addition, interferes with the colonization of pathogenic coryneform bacteria, such as R. aminovorans and B. casei, in particular.

[0114] ​

[0115] ​In a 28-day placebo-controlled in vivo clinical study, 6 Caucasian female volunteers aged between 20 and 50 years with dry skin condition applied the leave-on hydrogel formulation containing 3% Aquaphor® containing Aquaphor® Magnesia listed in Table 1 twice daily on the face for 28 days. Microbiome samples were collected on the cheeks and forehead at different time points (TO, day 7 and day 28) and subjected to 16S rRNA sequencing. Results obtained from 16S rRNA sequencing were processed following the “Reference Frame” method published by Morton et al. (Nat. Commun., 2019. 10(1): p. 2719). This method allows to assess microbiota changes and how these changes are associated with time and treatment. Differences were calculated starting from relative abundance data from 16S sequencing using a software called Songbird. Reference time and treatment difference values are reported in Table 2 below.

[0116] Table 2. Formulations

[0117]

[0118]

[0119] Table 2. “Reference Frame” analysis gave the following results

[0120]

[0121] The “Timepoint comparison” column indicates the time range in which the microbial change is assessed. Example: TO-7D means that the microbial shift is assessed in the time window from the beginning of the study (TO) until 7 days of product application. The “Intercept” column indicates the starting point for each microorganism. Positive values mean that the microorganism of interest was present to some extent on the skin before the assessment. The “Treatment” column refers to whether and to what extent a particular microorganism is associated with the active treatment. The values reported are the result of the differences obtained by the software by using the placebo-constant samples as reference. Therefore, positive values indicate a positive correlation with the active treatment. The “Time” column indicates how a particular microorganism is associated with time, independently of the treatment. Positive values mean that the microorganism tends to increase its abundance over time.

[0122] Surprisingly, contrary to the data obtained on the body, the results obtained on the face show that Paracoccus marcusii is strongly negatively correlated with the active treatment containing Aquaphor® Magnesia at all time points considered.

Claims

1. A method of increasing the differential abundance of Paracoccus marcusii in the skin microbiome of an external surface of a human body, the method comprising the step of topically applying an amount of magnetite to an external surface of a human body in need thereof, and wherein the external surface of the human body is body skin, wherein the magnetite is applied in the form of a cosmetic composition comprising an amount of magnetite and a cosmetically acceptable carrier, wherein the cosmetic composition is a rinse-off composition, and wherein the amount of magnetite is selected in the range of 0.25 to 2.5 wt.-%, based on the total weight of the cosmetic composition.

2. The method according to claim 1, wherein the rinse-off composition is a detergent rinse-off composition further comprising water and at least one surfactant and / or at least one soap.

3. The method according to claim 2, wherein the detergent rinse-off composition consists of the magnetite, water, at least one soap and / or surfactant, at least one humectant, at least one chelating agent and at least one alkalizing or acidifying agent.

4. The method according to claim 3, wherein the detergent rinse-off composition consists of the magnetite, water, several soaps and / or surfactants, at least one humectant, at least one chelating agent and at least one alkalizing or acidifying agent.

5. The method according to any one of claims 1 to 4, comprising the step of: (i) applying the rinse-off composition to the body skin and then (ii) rinsing it off with water.

6. The method according to claim 5, the body skin being the torso, arms and / or legs.

7. The method according to any one of claims 1 to 4, wherein the differential abundance of Brevibacterium casei and / or Roseomonospora amnigenus in the skin microbiome is simultaneously reduced.

8. A method of providing protection to an external surface of a human body by increasing the differential abundance of Paracoccus marcusii on the external surface of the human body, wherein the external surface of the human body is body skin, and the method comprising the step of applying magnetite to the external surface, wherein the magnetite is applied in the form of a cosmetic composition comprising an amount of magnetite and a cosmetically acceptable carrier, wherein the cosmetic composition is a rinse-off composition, and wherein the amount of magnetite is selected in the range of 0.25 to 2.5 wt.-%, based on the total weight of the cosmetic composition.

9. Use of magnetite for increasing the differential abundance of Paracoccus marcusii in the skin microbiome of an external surface of body skin of an individual in need thereof, wherein the magnetite is applied in the form of a cosmetic composition comprising an amount of magnetite and a cosmetically acceptable carrier, wherein the cosmetic composition is a rinse-off composition, and wherein the amount of magnetite is selected in the range of 0.25 to 2.5 wt.-%, based on the total weight of the cosmetic composition.

10. The use according to claim 9, wherein the differential abundance of Brevibacterium casei and / or Roseomonospora amnigenus is simultaneously reduced.

Images