Cosmetic and pharmaceutical composition containing bacillus strain or fermentation broth thereof

Abstract

The present invention relates to cosmetic and pharmaceutical compositions containing Bacillus spp. Strains or fermentation broth thereof and methods of producing and using such strains.

Description

Technical Field

[0001] The present invention relates to cosmetic and pharmaceutical compositions containing Bacillus strains or fermentation broths thereof, and methods of producing and using such compositions. Background Art

[0002] Many Bacillus strains are known to be suitable as probiotic active food and feed ingredients, whereby their usability as food and feed ingredients is mainly due to specific enzymatic activities and growth inhibitory activities, such as growth inhibition against typical human and animal pathogens of the human or animal intestine, such as Clostridia or Escherichia coli.

[0003] On the other hand, it has been disclosed that several bacteria, in particular Lactobacilli and Bifidobacteria, are suitable as probiotic active substances in cosmetic compositions. In addition, for several Bacillus strains, it has been shown that they have growth inhibitory activity against pathogenic skin bacteria, which makes them also suitable as probiotic active substances for cosmetic applications. Therefore, WO 2022 / 119895 discloses Bacillus velezensis strains with growth inhibitory activity against Staphylococci and Malassezia, making them useful for treating dandruff. In addition, CN 115044505A discloses a Bacillus velezensis strain that produces lipopeptides with growth inhibitory activity against Propionibacterium acnes.

[0004] Skin inflammation ("dermatitis") is caused by harmful bacteria or fungi, such as Propionibacterium acnes (C. acnes) or Staphylococcus aureus (S. aureus), which colonize the skin but proliferate strongly under certain conditions. Uncontrolled proliferation of such bacteria or fungi can cause "impure skin" or acne vulgaris, so that in such cases, the microorganisms or their uncontrolled proliferation are classified as pathogenic.

[0005] On the other hand, the bacterial microbiome also includes species that do not cause harm and, by virtue of their continued growth, keep pathogenic bacterial species in check, thus performing important protective functions. The coagulase-negative staphylococcus, Staphylococcus epidermidis (S. epidermidis), is a prominent representative of this class of species. Generally speaking, the term "saprophyte" is used to designate these benign, protective bacterial species.

[0006] Antimicrobial agents that non-selectively target skin bacteria, such as those commonly used in commercial cosmetic products to prevent and combat acne, kill not only pathogenic skin bacteria but also beneficial skin bacteria, thereby disturbing the biological balance (also called ecological balance) on the skin, which can cause a variety of undesirable consequences.

[0007] Therefore, there is a need for agents that selectively promote the growth and / or survival of desired bacteria of the skin microbiome on the skin area to which they are applied, rather than the growth and / or survival of pathogenic microorganisms present in the skin microbiome. Surprisingly, this problem can be solved by the fermentation broths of the present invention, in particular by the fermentation broths of Bacillus strain CECT 5940 and Bacillus subtilis DSM 32315. Furthermore, according to the present invention, it was surprisingly found that a mixture of Bacilli fermentation broths and ceramides effectively enhances the growth-inhibiting activity against pathogenic Propionibacterium acnes bacteria. Summary of the Invention

[0008] In a preferred embodiment of the present invention, the Bacillus strain, fermentation broth and composition are capable of inhibiting the growth of at least one pathogenic skin bacterium, particularly Propionibacterium acnes, while they have a much weaker growth inhibitory effect on the growth of beneficial skin bacteria, particularly Staphylococcus epidermidis.

[0009] In a very preferred embodiment of the present invention, the Bacillus strains, fermentation broths and compositions are capable of inhibiting the growth of at least one pathogenic skin bacterium, in particular Propionibacterium acnes, while they have no negative effect or even a positive effect on the growth of beneficial skin bacteria, in particular Staphylococcus epidermidis, thus leading to a very beneficial modulation of the skin microbiome.

[0010] Therefore, a first subject matter of the present invention is a cosmetic composition comprising at least one Bacillus strain or a fermentation broth thereof and at least one ceramide, wherein the composition is preferably a topical skin care or dermatological composition.

[0011] A further subject matter of the present invention is therefore also a pharmaceutical composition for topical or dermatological application, in particular for the treatment or prevention of acne vulgaris, dermatitis, rosacea or erythritis, which contains at least one Bacillus strain or a fermentation broth thereof and at least one ceramide.

[0012] Therefore, a further subject of the present invention is also a cosmetic composition containing the Bacillus Velez strain CECT 5940 (also known as B. amyloliquefaciens CECT 5940 strain) or a mutant thereof, or a fermentation broth of such a strain, wherein the mutant has a sequence identity of at least 99%, preferably at least 99.5%, more preferably at least 99.9% with respect to the genomic DNA of the strain CECT 5940, wherein the composition is preferably a topical skin care or dermatological composition, and wherein the composition preferably comprises at least one ceramide. The strain Bacillus Velez / Bacillus amyloliquefaciens CECT 5940 is deposited at the Spanish Type Culture Collection, Parc Científic Universitat de València, C / Catedrático Agustín Escardino, 9, 46980 Paterna (Valencia), Spain.

[0013] Therefore, a further subject matter of the present invention is also a cosmetic composition containing the Bacillus subtilis strain DSM 32315 or a mutant thereof or a fermentation broth of such a strain, wherein the mutant has a sequence identity of at least 99%, preferably at least 99.5%, more preferably at least 99.9% with respect to the genomic DNA of the strain DSM 32315, wherein the composition is preferably a topical skin care or dermatological composition, and wherein the composition preferably comprises at least one ceramide. The strain Bacillus subtilis DSM 32315 was deposited under the rules of the Budapest Treaty with the DSMZ-German Collection of Microorganisms and Cell Cultures GmbH, Inhoffenstraße 7B, 38124 Braunschweig, Germany.

[0014] Therefore, a further subject of the present invention is also a pharmaceutical composition for topical or dermatological application, in particular for the treatment or prevention of acne vulgaris, dermatitis, rosacea or red blood streaks, said pharmaceutical composition containing the Bacillus Velez / Bacillus amyloliquefaciens strain CECT 5940 or a mutant thereof or a fermentation broth of such a strain, wherein said mutant has a sequence identity of at least 99%, preferably at least 99.5%, more preferably at least 99.9% with respect to the genomic DNA of the strain CECT 5940, wherein said composition preferably comprises at least one ceramide.

[0015] Therefore, a further subject matter of the present invention is also a pharmaceutical composition for topical or dermatological application, in particular for the treatment or prevention of acne vulgaris, dermatitis, rosacea or redness, which contains the Bacillus subtilis strain DSM 32315 or a mutant thereof or a fermentation broth of such a strain, wherein the mutant has a sequence identity of at least 99%, preferably at least 99.5%, more preferably at least 99.9% with respect to the genomic DNA of the strain DSM 32315, wherein the composition preferably comprises at least one ceramide.

[0016] Therefore, a further subject matter of the present application is also the use of at least one Bacillus strain, a fermentation broth or a composition according to the invention for the topical treatment of human skin, in particular for the treatment of irritated, impure, dry, blemished or acne-prone human skin and / or for beneficially modulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin.

[0017] Therefore, a further subject matter of the present application is also the use of Bacillus Velez / Bacillus amyloliquefaciens strain CECT5940 for the topical treatment of human skin, in particular for the treatment of inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially regulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin.

[0018] Therefore, a further subject matter of the present application is also the use of the Bacillus subtilis strain DSM 32315 for the topical treatment of human skin, in particular for the treatment of inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially modulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin.

[0019] Therefore, a further subject matter of the present application is also the combined use of at least one Bacillus strain or a fermentation broth thereof and at least one ceramide for the topical treatment of human skin, in particular for the treatment of inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially regulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin.

[0020] Therefore, a further subject of the present application is also the combined use of a Bacillus strain or a fermentation broth thereof and at least one ceramide for the preparation of a topical composition or a pharmaceutical composition for treating human skin, in particular for the preparation of a topical composition or a pharmaceutical composition for treating or preventing diseases associated with pathogenic Propionibacterium acnes and / or for treating or preventing acne vulgaris, dermatitis, rosacea or red blood streaks.

[0021] Therefore, a further subject of the present application is also the non-therapeutic use of the Bacillus strain according to the invention or its fermentation broth or composition for topical treatment of the skin, in particular for treating inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially regulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin.

[0022] Therefore, a further subject matter of the present application is also a non-therapeutic method for the topical treatment of human skin, in particular for the treatment of inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially modulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin, wherein a Bacillus strain according to the invention or a fermentation broth thereof or a cosmetic composition thereof is applied to the human skin.

[0023] Therefore, a further subject matter of the present application is also a non-therapeutic method for the topical treatment of human skin, in particular for the treatment of inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially regulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin, wherein the Bacillus strain CECT 5940 or a mutant thereof or a fermentation broth of such a strain or a cosmetic composition containing such a strain or fermentation broth is applied to human skin, wherein the mutant has a sequence identity of at least 99%, preferably at least 99.5%, more preferably at least 99.9% with respect to the genomic DNA of the strain CECT 5940.

[0024] Therefore, a further subject matter of the present application is also a non-therapeutic method for the topical treatment of human skin, in particular for the treatment of inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially modulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin, wherein the Bacillus strain DSM 32315 or a mutant thereof or a fermentation broth of such a strain or a cosmetic composition containing such a strain or a fermentation broth is applied to human skin, wherein the mutant has a sequence identity of at least 99%, preferably at least 99.5%, more preferably at least 99.9% with respect to the genomic DNA of the strain DSM 32315.

[0025] Therefore, a further subject matter of the present invention is also a method for treating or preventing human skin diseases, in particular for treating or preventing diseases associated with pathogenic Propionibacterium acnes and / or diseases selected from acne vulgaris, dermatitis, rosacea or erythritis, wherein a Bacillus strain according to the invention or a fermentation broth or a pharmaceutical composition thereof is applied to the human skin.

[0026] Therefore, a further subject of the present invention is also a Bacillus strain according to the invention or a fermentation broth or composition thereof for use in a method for treating or preventing human skin diseases, in particular for treating or preventing diseases associated with pathogenic Propionibacterium acnes and / or for treating or preventing diseases selected from acne vulgaris, dermatitis, rosacea or erythritis.

[0027] Therefore, a further subject of the present invention is also a process for preparing a cosmetic or pharmaceutical composition according to the invention, comprising the following steps:

[0028] a) providing a fermentation broth of Bacillus cells having growth inhibitory activity against skin pathogens, in particular Propionibacterium acnes, wherein the Bacillus cells preferably do not have growth inhibitory activity against Staphylococcus epidermidis,

[0029] b) killing all or a substantial portion of the Bacillus cells, preferably by heat treatment and / or pH change,

[0030] c) mixing the fermentation broth thus obtained with substances suitable for cosmetic skin application.

[0031] The compositions according to the present invention are preferably topical skin care compositions.

[0032] According to the invention, the term "skin" preferably refers to the skin itself, in particular to human skin, but may also refer to mucous membranes and skin appendages, as long as they comprise living cells, in particular hair follicles, hair roots, hair follicle bulbs, the ventral epithelial layer of the nail bed (lectulus) and sebaceous glands and sweat glands.

[0033] According to the present invention, the Bacillus strain is preferably selected from the species Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus Velez, Bacillus licheniformis, Bacillus paralicheniformis and Bacillus pumilus, more preferably selected from the species Bacillus subtilis, Bacillus Velez or Bacillus amyloliquefaciens, in particular the species Bacillus subtilis or Bacillus Velez, particularly preferably the species Bacillus Velez.

[0034] The term "fermentation liquid" according to the present invention relates to the product of culturing bacillus in a suitable fermentation medium. The method of producing such fermentation liquid is well known to those skilled in the art. The fermentation liquid of the present invention can be obtained, for example, by using the culture medium, conditions and methods described in US 6,060,051, EP 0287699, US2014 / 0010792 or FAO Report 179 (2016): "Probiotics in Animal Nutrition" to cultivate bacterial strains. Conventional large-scale microbial culture processes include submerged fermentation, solid-state fermentation or liquid surface culture. Typically, fermentation is carried out until a certain cell density is reached, such as an optical density (OD 600) of about 1 to 5, more preferably 3 to 5, especially 4 to 5. The fermentation liquid thus obtained can be directly used for the purpose of the present invention. Alternatively, the fermentation liquid thus obtained can also be processed in different ways, for example, by concentrating or drying the fermentation liquid and / or by completely or partially inactivating or removing bacterial cells and / or by lysing bacterial cells or a combination of such methods.

[0035] Cell inactivation can be carried out, for example, by heat treatment and / or by adjusting the acidic or alkaline pH. Thermal inactivation of cells is preferably carried out by raising the temperature to between 60°C and 80°C and incubating for at least 30 minutes. pH inactivation at an acidic pH is preferably carried out by adding an acid, such as 5M H2SO4, to lower the pH to at least 3 and incubating for at least 30 minutes, preferably at least 1 hour. pH inactivation at an alkaline pH is preferably carried out by increasing the pH to at least 10 and incubating for at least 30 minutes, preferably at least 1 hour. Alternatively, cell inactivation can also be carried out by applying gamma or UV irradiation. In a preferred embodiment of the present invention, a fermentation broth is used in which at least 90%, more preferably at least 95 or 99%, and in particular all of the bacterial cells are inactivated. Accordingly, in a preferred embodiment of the present invention, a fermentation broth is used that does not contain viable cells. Such preparations are also referred to as "paraprobiotics." The fermentation broth of the present invention from which cells have been removed, ie the cell-free supernatant and the metabolite-containing fractions of the fermentation broth, are also referred to as "postbiotics", "metabiotics" or "biogenics".

[0036] According to the present invention, it is further preferred to prevent the bacterial cells of the fermentation broth from transforming into spores, preferably by timely interrupting the cultivation process. Thus, in a preferred embodiment of the present invention, less than 10%, more preferably less than 5%, of the cells in the fermentation broth are present as spores, wherein the remaining spores are preferably non-viable spores due to heat and / or pH inactivation. Very preferably, the fermentation broth does not contain any spores at all.

[0037] The separation of the microorganisms from the fermentation broth can be carried out, for example, by centrifugation, flotation, filtration, in particular ultrafiltration or microfiltration and / or decantation.

[0038] Drying of the fermentation broth can be carried out, for example, by freeze drying, spray drying, vacuum drying, tray drying, drum drying, fluidized bed drying or spray granulation of the fermentation broth.

[0039] Lysis of the cells can be performed mechanically, chemically and / or enzymatically, in particular by osmotic shock, heat shock, sonication, homogenization or by shearing, for example using a French press.

[0040] The cell-containing fermentation broth of the present invention preferably contains 1×10 3 to 1x10 11 The amount of CFU, more preferably 1x10 5 to 1x10 10 The amount of CFU, especially 1x10 7 to 1x10 9 Cells in the amount of CFU. As in a preferred embodiment of the present invention, due to cell inactivation, the fermentation broth contains no living cells or only a very small number of living cells, the term CFU (colony forming units) relates to the fermentation broth before cell inactivation.

[0041] Preferably, according to the present invention, an effective amount of the strains, fermentation broths and compositions of the present invention is always used in the embodiments of the present invention. The term "effective amount" refers to an amount that produces at least one beneficial effect on human skin, in particular with respect to the previously mentioned characteristics, compared to human skin that has not been exposed to the strains, fermentation broths and compositions of the present invention, but may have been exposed to the same cosmetic composition and / or the same treatment in the absence of such strains or fermentation broths.

[0042] The cosmetic or pharmaceutical composition according to the present invention may be in any form suitable for administration, such as a soap, lotion, serum, spray, jelly, cream, gel, paste, pomade, balm, ointment, foam, mousse, emulsion, stick, patch, powder, cleansing liquid or milk, deodorant, antiperspirant, ointment, conditioner or shampoo. The composition may also be applied to a facial mask or bandage, in particular a gel reservoir mask or bandage or a matrix mask or bandage.

[0043] The composition of the present invention preferably has a pH in the range of 3 to 8, in particular in the range of 4.0 to 8.0, more preferably in the range of 4.5 to 7.4, particularly preferably in the range of 5.0 to 7.2. The pH of the composition is preferably determined after stirring for 5 minutes at 22 ° C using a pH electrode calibrated in accordance with ISO 4319 (1977).

[0044] The application area may be the skin of any part of the body, in particular the skin of the face, the scalp, the skin on the hands and feet, the skin under the arms, and the mucous membranes, with the skin of the face being particularly preferred.

[0045] The composition of the present invention preferably comprises at least one ceramide. "Ceramide" according to the present invention refers to an acylated sphingosine base, wherein the sphingosine base is selected from sphingosine, dihydrosphingosine, 6-hydroxysphingosine and phytosphingosine.

[0046] According to the present invention, ceramide is preferably selected from ceramide NP, ceramide AP, ceramide EOP, ceramide NDS, ceramide ADS, ceramide EODS, ceramide NS, ceramide AS, ceramide EOS, ceramide NH, ceramide AH, ceramide EOH and mixtures thereof, more preferably selected from ceramide NP, ceramide AP, ceramide NS, ceramide EOP, ceramide EOS and mixtures thereof, especially selected from ceramide NP, ceramide AP and mixtures thereof. Ceramide nomenclature is commonly used and is described in more detail in Farwick et al. Developments in Ceramide Identification, Synthesis, Function and Nomenclature, Cosmet Toil 2009; 124: 63-72.

[0047] The composition according to the present invention is preferably an emulsion, in particular a W / O or O / W emulsion. This means that the composition preferably contains at least one surface-active substance as an emulsifier or dispersant. Emulsifiers act at the interface to produce a water- or oil-stabilized adsorption layer that protects the dispersed droplets from coalescence, thereby stabilizing the emulsion. Therefore, emulsifiers, such as surfactants, are composed of hydrophobic and hydrophilic molecular parts. Hydrophilic emulsifiers preferably form O / W emulsions, and hydrophobic emulsifiers preferably form W / O emulsions. An emulsion is understood to mean a dispersion of a liquid in another liquid in the form of droplets that uses energy input to provide an interface stabilized by a surfactant. The choice of this emulsifying surfactant or emulsifier depends on the material to be dispersed and the corresponding external phase as well as the fineness of the emulsion.

[0048] The composition according to the invention preferably comprises a nonionic emulsifier, more preferably a polyglycerol carboxylate or a mixture of such compounds. The polyglycerol groups of the polyglycerol carboxylate preferably have a degree of polymerization of 2.0 to 25, more preferably 2.5 to 20, in particular 3.0 to 15, and the carboxylic acid groups are preferably fatty acids, in particular fatty acids having 12 to 26, preferably 14 to 24, more preferably 16 to 22 carbon atoms. The composition according to the invention preferably comprises at least two different polyglycerol carboxylates, wherein the at least two different compounds preferably vary in degree of polymerization and carboxylic acid groups.

[0049] Due to its polymeric properties, polyglycerol is a statistical mixture of various compounds. Polyglycerol can have an ether bond formed between two primary positions, one primary position and one secondary position, or two secondary positions of a glycerol monomer. For this reason, the polyglycerol basic skeleton is usually not only composed of linearly connected glycerol units, but can also include side chains and rings. In addition, in addition to polyglycerol, monomeric glycerol can also be present in polyglycerol carboxylates to a certain extent. In order to calculate the amount, quality and numerical value of polyglycerol carboxylates, this point must be taken into account. To a certain extent, the value is always related to the average. For details, see, for example, "Original synthesis of linear, branched and cyclic oligoglycerol standards", Cassel et al., J.Org.Chem.2001, 875-896. For further preferred features of the polyglycerol carboxylates used according to the present invention, see also WO 2022 / 073909.

[0050] Emulsifiers useful according to the invention can also be chosen from addition products of 4 to 30 mol of ethylene oxide and / or 0 to 5 mol of propylene oxide on linear C8-C22 fatty alcohols, C12-C22 fatty acids or C8-C15 alkylphenols; C12-C22 fatty acid monoesters and diesters of addition products of 1 to 30 mol of ethylene oxide on C3-C6 polyols, preferably glycerol; linear and branched C8-C30 fatty acids and their Na, K, ammonium, Ca, Mg and Zn salts; fatty acid esters of sugars and sugar alcohols such as sorbitol; ethylene oxide and polyglycerol addition products on methyl glucoside fatty acid esters, fatty acid alkanolamides or fatty acid glucamides; polyglycerols and polyglycerol derivatives, such as polyglycerol-2-dipolyhydroxystearate or polyglycerol-3-diisostearate; C8-C22 alkyl monoesters and diesters. Glycosides and oligoglycosides and their ethoxylated analogs, wherein the degree of oligomerization is preferably 1.1 to 5, in particular 1.2 to 2.0, and glucose is preferably used as the sugar component; mixtures of alkyl (oligo)glucosides and fatty alcohols; addition products of 5 to 60 mol of ethylene oxide onto castor oil or hydrogenated castor oil; partial esters of polyols containing 3 to 6 carbon atoms with C8-C22 fatty acids; phospholipids such as lecithin or phosphatidylcholine (PC), which can be obtained in particular from egg yolk or plant seeds (e.g. soybean); and sterols (sterols), wherein "sterol" is understood to mean a group of steroids that carry a hydroxyl group on carbon atom 3 of the steroid skeleton and are isolated from animal tissue (zoosterols), plant fats (phytosterols) or fungi such as yeast (mycosterols). Examples of zoosterols are cholesterol and lanosterol. Examples of suitable phytosterols are β-sitosterol, stigmasterol, campesterol and ergosterol.

[0051] In a particular embodiment of the present invention, at least one nonionic emulsifier having an HLB value of 8 or less (according to - Definition of HLB values shown in Lexikon Chemie (Eds.: J. Falbe, M. Regitz), 10th edition, Georg Thieme Verlag Stuttgart, New York, (1997), page 1764). Exemplary suitable emulsifiers of this type are of the general formula R <1> -OR <2> A compound wherein R <1> is a primary straight chain alkyl, alkenyl or acyl group having 20 to 30 carbon atoms, and R <2> is hydrogen, a radical of the formula -(CnH2nO)xH wherein x = 1 or 2 and n = 2 to 4, a polyhydroxyalkyl radical having 4 to 6 carbon atoms and 2 to 5 hydroxyl groups. <1> -OR <2> Particularly preferred emulsifiers are behenyl or erucyl derivatives, wherein R <1> represents a primary straight-chain alkyl, alkenyl or acyl group having 22 carbon atoms.

[0052] Other preferred suitable emulsifiers with an HLB value of 8 and below are addition products of 1 or 2 mol of ethylene oxide or propylene oxide onto behenyl alcohol, erucyl alcohol, arachidyl alcohol, or also onto behenic acid or erucic acid. Monoesters of C16-C30 fatty acids with polyols such as, for example, pentaerythritol, trimethylolpropane, diglycerol, sorbitol, glucose or methylglucose are also suitable and preferred. Examples of such products are, for example, sorbitol monobehenate or pentaerythritol monoerucate.

[0053] In another specific embodiment of the present invention, instead of or in addition to the nonionic emulsifiers described above, at least one ionic emulsifier selected from anionic, zwitterionic, amphoteric, and cationic emulsifiers is included. Preferred anionic emulsifiers are alkyl sulfates, alkyl polyglycol ether sulfates, ether carboxylic acids having 10 to 18 carbon atoms in the alkyl group and up to 12 glycol ether groups in the molecule, monoalkyl and dialkyl sulfosuccinates having 8 to 18 carbon atoms in the alkyl group, monoalkyl polyoxyethyl sulfosuccinates having 8 to 18 carbon atoms in the alkyl group and 1 to 6 oxyethylene groups, monoglyceride sulfates, alkyl ether phosphates, and alkenyl ether phosphates, as well as condensates of proteins and fatty acids. Zwitterionic emulsifiers carry at least one quaternary ammonium group and at least one -COO<->- or SO<-> group in the molecule. Particularly suitable zwitterionic emulsifiers are the so-called betaines, such as N-alkyl-N,N-dimethylammonium glycinate, N-acyl-aminopropyl-N,N-dimethylammonium glycinate and 2-alkyl-3-carboxymethyl-3-hydroxyethyl-imidazolines (each having 8 to 18 carbon atoms in the alkyl or acyl group), and cocoylaminoethyl hydroxyethylcarboxymethylglycinate.

[0054] Amphoteric emulsifiers contain, in addition to C8-C24 alkyl or acyl groups, at least one free amino group and at least one COOH or SO3H group in the molecule and are capable of forming internal salts. Examples of suitable amphoteric emulsifiers are N-alkylglycines, N-alkylaminopropionic acid, N-alkylaminobutyric acid, N-alkyliminodipropionic acid, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acid and alkylaminoacetic acid, each of which has about 8 to 24 carbon atoms in the alkyl group.

[0055] The composition according to the invention preferably comprises an emulsifier, in particular a nonionic emulsifier, especially polyglycerol carboxylic acid, in an amount of 0.1 to 25 wt%, more preferably 0.5 to 15 wt%, especially 2 to 8 wt% or 4 to 8 wt%, based on the total composition.

[0056] In a very preferred embodiment of the present invention, the composition according to the invention is a lamellar composition, wherein this lamellar composition forms the basis for preparing a skin-friendly cosmetic composition, wherein the lamellar composition is preferably used in an amount of 1 to 5% by weight (corresponding to a dilution factor of 1:20 to 1:100) for preparing the cosmetic composition. The cosmetic composition obtained in this way is also a very preferred embodiment of the present invention.

[0057] The lamellar composition preferably contains at least one fermentation broth, at least one ceramide, and at least one polyglycerol carboxylic acid as described above, wherein the fermentation broth is preferably present in an amount of 2 to 30 wt%, more preferably 5 to 25 wt%, and in particular 8 to 20 wt%, the ceramide is preferably present in an amount of 0.1 to 5 wt%, more preferably 0.2 to 4 wt%, and in particular 0.5 to 2.5 wt%, and the polyglycerol carboxylic acid is preferably present in an amount of 1 to 12 wt%, more preferably 4 to 8 wt%. In the cosmetic composition obtained by using such a lamellar composition for preparing a cosmetic composition, the aforementioned compounds are therefore preferably present in an amount 20-100 times lower.

[0058] Instead of or in addition to ceramide, the composition of the present invention may further comprise at least one sphingosine base, wherein the sphingosine base is preferably selected from sphingosine, dihydrosphingosine, 6-hydroxysphingosine, N-acetylsphingosine and phytosphingosine, with phytosphingosine being preferred. In a preferred embodiment of the present invention, a combination of ceramide and phytosphingosine is used in the composition.

[0059] In another preferred embodiment of the present invention, composition comprises at least one phospholipid.The phospholipid that preferably uses according to the present invention is phosphatidylcholine (PC) (also referred to as lecithin), phosphatidylethanolamine (PE) (also referred to as cephalin), phosphatidic acid (PA) (also referred to as phosphatidic acid (phosphatidates)), phosphatidylserine (PS), phosphoinositol such as phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidylinositol diphosphate (PIP2), phosphatidylinositol triphosphate (PIP3), sphingomyelin such as ceramide phosphorylcholine (SPH), ceramide phosphorylethanolamine (Cer-PE) and ceramide phosphoryl lipid.Phospholipid can be obtained from biological sources such as plants and animals, particularly from egg yolk, milk, fish eggs or plant seeds (such as soybean, rapeseed or sunflower seeds).

[0060] "Sterol" is understood to mean a group of steroids which carry a hydroxyl group on carbon atom 3 of the steroid backbone and are isolated from animal tissues (zoosterols), vegetable fats (phytosterols) or fungi such as yeast (zymosterols). Examples of zoosterols are cholesterol and lanosterol. Examples of suitable phytosterols are β-sitosterol, stigmasterol, campesterol and ergosterol. Preferred sterols for inclusion in the compositions according to the invention are selected from cholesterol, 7-dehydrocholesterol, potassium cholesterol sulfate, cholesterol succinate, 25-hydroxy-7-dehydrocholesterol, ergosterol, fucoxanthin, hopanes, hydroxysteroids, phytosterols such as, for example, campesterol, sitosterol, stigmasterol, steroids and zoosterols, with cholesterol being particularly preferred.

[0061] In another preferred embodiment of the present invention, the composition comprises at least one free fatty acid, wherein the free fatty acid preferably has a chain length of 12 to 40, more preferably 14 to 24, particularly preferably 16 to 22 carbon atoms, and wherein the free fatty acid is preferably a saturated fatty acid.

[0062] A particularly preferred embodiment of the present invention is a composition comprising:

[0063] a) Bacillus fermentation broth in an amount of 2 to 30 wt%, preferably in an amount of 5 to 25 wt%, in particular in an amount of 8 to 20 wt%, wherein the fermentation broth preferably contains no living cells;

[0064] b) ceramide in an amount of 0.1 to 5 wt%, more preferably in an amount of 0.2 to 4 wt%, especially in an amount of 0.5 to 2.5 wt%;

[0065] c) polyglycerol carboxylic acid in an amount of 1 to 12 wt%, more preferably in an amount of 4 to 8 wt%;

[0066] d) preferably at least one phospholipid, more preferably cholesterol or a derivative thereof, in an amount of 0.1 to 3 wt%, more preferably in an amount of 0.1 to 2 wt%;

[0067] e) preferably at least one sphingosine base in an amount of 0.01 to 2 wt %, preferably in an amount of 0.02 to 1 wt %;

[0068] f) preferably at least one free fatty acid in an amount of 0.01 to 3 wt%, more preferably in an amount of 0.05 to 2 wt%.

[0069] Another particularly preferred embodiment of the present invention is a composition comprising:

[0070] a) a fermentation broth of Bacillus strain CECT 5940 or Bacillus strain DSM 32315 or a mutant of such a strain in an amount of 2 to 30 wt %, more preferably in an amount of 5 to 25 wt %, in particular in an amount of 8 to 20 wt %, wherein the fermentation broth preferably contains no living cells;

[0071] b) ceramide in an amount of 0.1 to 5 wt%, more preferably in an amount of 0.2 to 4 wt%, especially in an amount of 0.5 to 2.5 wt%;

[0072] c) preferably polyglycerol carboxylic acid in a total amount of 1 to 12 wt%, more preferably in an amount of 4 to 8 wt%;

[0073] d) preferably at least one phospholipid, more preferably cholesterol or a derivative thereof, in an amount of 0.1 to 3 wt%, more preferably in an amount of 0.1 to 2 wt%;

[0074] e) preferably at least one sphingosine base in an amount of 0.01 to 2 wt %, preferably in an amount of 0.02 to 1 wt %;

[0075] f) preferably at least one free fatty acid in an amount of 0.01 to 3 wt%, more preferably in an amount of 0.05 to 2 wt%.

[0076] Therefore, further particularly preferred embodiments of the present invention are also cosmetic compositions which are obtainable by using such compositions in amounts of 1 to 5 wt % and which therefore contain preferably 20 to 100 times lower amounts of the compounds as described above.

[0077] In addition to or instead of the emulsifiers described above, the compositions according to the invention may also comprise foaming nonionic, zwitterionic, anionic and / or cationic surfactants as further surface-active ingredients.

[0078] Examples of nonionic surfactants are those of formula R <1> CO-(OCH2CHR <2> )xOR <3> Alkoxylated fatty acid alkyl esters, wherein R <1> CO represents a linear or branched saturated and / or unsaturated acyl group having 6 to 22 carbon atoms, R <2> represents hydrogen or methyl, R <3> represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and x represents a number from 1 to 20; addition products of ethylene oxide onto fatty acid alkanolamides and fatty amines; fatty acid N-alkylglucamides; C8-C22 alkylamine-N-oxides; alkyl polyglycosides corresponding to the general formula RO-(Z)x, where R represents a C8-C16 alkyl group, Z represents a sugar, and x represents the number of sugar units. The alkyl polyglycosides used according to the present invention may simply contain a defined alkyl group R. However, these compounds are typically made from natural fats and oils or mineral oils, in which case the alkyl group R is present as a mixture corresponding to the starting compound or each compound that is worked up. Alkyl polyglycosides in which R is essentially selected from C8 and C10 alkyl groups, C12 and C14 alkyl groups, C8 to C16 alkyl groups, or C12 to C16 alkyl groups are particularly preferred.

[0079] Any monosaccharide or oligosaccharide can be added as the sugar building block Z. Typically, sugars with 5 or 6 carbon atoms and corresponding oligosaccharides are added, such as glucose, fructose, galactose, arabinose, ribose, xylose, lyxose, allose, altrose, mannose, gulose, idose, talose and sucrose. Preferred sugar building blocks are glucose, fructose, galactose, arabinose and sucrose; glucose is particularly preferred. The alkyl polyglycosides usable according to the invention contain an average of 1.1 to 5, preferably 1.1 to 2.0, particularly preferably 1.1 to 1.8 sugar units. According to the invention, alkoxylated homologues of the cited alkyl polyglycosides can also be used. These homologues can contain an average of up to 10 ethylene oxide and / or propylene oxide units per alkyl polyglycoside unit.

[0080] Zwitterionic surfactants are surface-active compounds that carry at least one quaternary ammonium group and at least one -COO<(-)> or SO<(-)> group in the molecule. Particularly suitable zwitterionic surfactants are the so-called betaines, such as N-alkyl-N,N-dimethylammonium glycinates, for example cocoalkyldimethylammonium glycinate, N-acylaminopropyl-N,N-dimethylammonium glycinates, for example cocoacylaminopropyldimethylammonium glycinate, and 2-alkyl-3-carboxymethyl-3-hydroxyethylimidazolines (having 8 to 18 carbon atoms in each of the alkyl or acyl groups), as well as cocoacylaminoethylhydroxyethylcarboxymethylglycinate. Preferred zwitterionic surfactants are the fatty acid amide derivatives known under the INCI name cocamidopropyl betaine.

[0081] Suitable anionic surfactants according to the present invention are all anionic surface-active substances suitable for use on the human body. They are characterized by a water-soluble anionic group, such as, for example, a carboxylate, sulfate, sulfonate or phosphate group, and a lipophilic alkyl group containing about 8 to 30 C atoms. In addition, the molecule may contain glycol or polyglycol ether groups, esters, ethers and amide groups and hydroxyl groups. Exemplary suitable foaming anionic surfactants are: acyl glutamates of formula (I), each in the form of sodium, potassium and ammonium and mono-, di- and trialkanol ammonium salts having 2 to 4 carbon atoms in the alkanol group,

[0082]

[0083] where R <1> CO represents a straight-chain or branched acyl group having 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds, and X represents hydrogen, alkali metal and / or alkaline earth metal, ammonium, alkylammonium, alkanolammonium or gluconammonium, for example acylglutamates derived from fatty acids having 6 to 22, preferably 12 to 18 carbon atoms, such as, for example, C12 / 14 or C12 / 18 coconut fatty acids, lauric acid, myristic acid, palmitic acid and / or stearic acid, in particular sodium N-cocoyl-L-glutamate and sodium N-stearoyl-L-glutamate; esters of hydroxy-substituted di- or tricarboxylic acids of the general formula (II),

[0084]

[0085] wherein X is H or a -CH2COOR group and Y is H or -OH, provided that if Y is H and if X is CH2COOR, R, R <1> and R <2> independently of one another represent a hydrogen atom, an alkali metal or alkaline earth metal cation, an ammonium group, a cation of an ammonium organic base or a group Z derived from a polyhydroxylated organic compound selected from etherified (C6-C18)-alkylpolysaccharides having 1 to 6 monomeric sugar units and / or etherified aliphatic (C6-C16)-hydroxyalkylpolyols having 2 to 16 hydroxyl groups, with the proviso that at least one of the radicals R, R1 and R2 is a group Z; an ester of sulfosuccinic acid of the general formula (III),

[0086]

[0087] wherein R1 and R2 independently of one another represent a hydrogen atom, an alkali metal or alkaline earth metal cation, an ammonium group, a cation of an ammonium organic base or a group Z derived from a polyhydroxylated organic compound selected from etherified (C6-C18)-alkylpolysaccharides having 1 to 6 monomeric sugar units and / or etherified aliphatic (C6-C16)-hydroxyalkylpolyols having 2 to 16 hydroxyl groups, with the proviso that at least one of the groups R1 and R2 is a group Z;

[0088] Mono- and dialkyl sulfosuccinates having 8 to 24 carbon atoms in the alkyl group and monoalkylpolyoxyethyl sulfosuccinates having 8 to 24 carbon atoms in the alkyl group and 1 to 6 ethoxy groups;

[0089] Esters of tartaric and citric acid with alcohols, which represent addition products of about 2 to 15 ethylene oxide and / or propylene oxide molecules onto fatty alcohols having 8 to 22 C atoms,

[0090] Straight-chain and branched fatty acids with 8 to 30 C atoms (soaps);

[0091] Ether carboxylic acids of the formula RO-(CH2-CH2O)x-CH2-COOH, where R is a straight-chain alkyl group having 8 to 30 C atoms and x=0 or 1 to 16;

[0092] Acyl sarcosinates having a straight-chain or branched acyl group containing 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds;

[0093] acyltaurates having a straight-chain or branched acyl group containing 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds;

[0094] acyl isethionates having a straight-chain or branched acyl group containing 6 to 22 carbon atoms and 0, 1, 2 or 3 double bonds;

[0095] linear alkylsulfonates having 8 to 24 C atoms;

[0096] linear α-olefin sulfonates having 8 to 24 C atoms;

[0097] α-Sulfofatty acid methyl esters of fatty acids having 8 to 30 C atoms;

[0098] Alkyl sulfates and alkyl polyglycol ether sulfates of the formula RO(CH2-CH2O)2-SO3X, where R is preferably a linear alkyl radical having 8 to 30 carbon atoms, particularly preferably 8 to 18 carbon atoms, z=0 or 1 to 12, particularly preferably 3, and X is sodium, potassium, magnesium, zinc, ammonium ion or a mono-, di- or trialkanolammonium ion having 2 to 4 carbon atoms in the alkanol radical, a particularly preferred example being zinc cocoyl ether sulfate with a degree of ethoxylation z=3;

[0099] Mixtures of surface-active hydroxysulfonates according to DE-A-37 25 030,

[0100] Sulfated hydroxyalkyl polyethylene and / or hydroxyalkylene propylene glycol ethers according to DE-A-37 23 354,

[0101] Sulfonated unsaturated fatty acids having 8 to 24 C atoms and 1 to 6 double bonds according to DE-A-39 26 344,

[0102] Alkyl and / or alkenyl ether phosphates of formula (IV),

[0103]

[0104] wherein R1 preferably represents an aliphatic hydrocarbon radical having 8 to 30 carbon atoms, R2 represents hydrogen, a (CH2CH2O)nR1 radical or X, n represents a number between 1 and 10, and X represents hydrogen, an alkali metal or an alkaline earth metal or NR3, R4, R5, R6, wherein R3 to R6 independently of one another represent a C1 to C4 hydrocarbon radical, sulfated fatty acid alkylene glycol esters of the formula R7CO(AlkO)nSO3M, wherein R7CO represents a linear or branched aliphatic saturated and / or unsaturated acyl radical having 6 to 22 carbon atoms, Alk represents CH2CH2, CHCH3CH2 and / or CH2CHCH3, n represents a number from 0.5 to 5, and M represents a cation, such as those described in DE-OS 197 36906.5, and / or monoglyceride sulfates and monoglyceride ether sulfates of the formula (V),

[0105]

[0106] wherein R8CO represents a linear or branched acyl group having 6 to 22 carbon atoms, the sum of x, y and z is 0 or represents a number between 1 and 30, preferably between 2 and 10, and X represents an alkali metal or alkaline earth metal. Typical examples of suitable monoglyceride (ether) sulfates in the context of the present invention are the reaction products of lauric acid monoglyceride, coconut fatty acid monoglyceride, palmitic acid monoglyceride, stearic acid monoglyceride, oleic acid monoglyceride and tallow fatty acid monoglyceride and their ethylene oxide adducts with sulfur trioxide or chlorosulfonic acid in the form of the sodium salt. Preferably, a monoglyceride sulfate of formula (VI) is added, wherein R8CO represents a linear acyl group having 8 to 18 carbon atoms.

[0107] Instead of or in addition to the surfactants as described above, the composition according to the present invention may also comprise a biosurfactant, wherein according to the present invention, the term "biosurfactant" is understood to mean all glycolipids produced by fermentation, but also encompasses glycolipids chemically and / or enzymatically modified after fermentation, as long as the glycolipid is structurally retained. The raw materials for the production of biosurfactants that can be used are carbohydrates, particularly sugars, such as, for example, glucose, and / or lipophilic carbon sources, such as fats, oils, partial glycerides, fatty acids, fatty alcohols, long-chain saturated or unsaturated hydrocarbons. Where average values are stated hereinafter, these average values are number-average values unless otherwise stated. Preferred biosurfactants according to the present invention are rhamnolipids, sophorolipids, glycolipids, cellulose lipids, mannose erythritol lipids and algae glycolipids, particularly rhamnolipids, sophorolipids and glycolipids, most preferably rhamnolipids.

[0108] Biosurfactants can be produced as disclosed, for example, in EP 0499434, US 7,985,722, WO 03 / 006146, JP 60183032, DE 19648439, DE 19600743, JP 01304034, CN 1337439, JP 2006274233, KR 2004033376, JP 2006083238, JP 2006070231, WO 03 / 002700, FR 2740779, DE 2939519, US 7,556,654, FR 2855752, EP 1445302, JP 2008062179 and JP 2007181789 or the literature cited therein. Suitable biosurfactants can be obtained, for example, from Soliance, France. Preferably, the composition according to the invention contains as biosurfactant at least one compound selected from the group consisting of rhamnolipids, in particular mono-, di- or polyrhamnolipids, glycolipids, in particular mono-, di- or polysaccharide lipids, and sophorolipids, in particular mono-, di- or polysaccharide lipids, most preferably rhamnolipids.

[0109] In addition, the composition according to the invention may also contain at least one protein hydrolysate or a derivative thereof. According to the invention, the added protein hydrolysate may be of plant or animal origin. Animal protein hydrolysates are, for example, elastin, collagen, keratin, silk and milk protein hydrolysates, which may also be present in the form of their salts. According to the invention, plant protein hydrolysates, such as soy, wheat, almond, pea, potato and rice protein hydrolysates, are preferred.

[0110] The above-mentioned protein hydrolysate can be replaced by amino acid mixtures or individual amino acids and their physiologically compatible salts. Preferred amino acids for this purpose include, for example, glycine, serine, threonine, cysteine, asparagine, glutamine, pyroglutamic acid, alanine, valine, leucine, isoleucine, proline, tryptophan, phenylalanine, methionine, tyrosine, aspartic acid, glutamic acid, lysine, arginine and histidine, as well as zinc salts and acid addition salts of these amino acids.

[0111] Likewise, derivatives of protein hydrolysates can be added, for example in the form of their fatty acid condensation products.

[0112] According to the present invention, cationic protein hydrolysate can also be adopted, it can be obtained from a variety of biological sources (including but not limited to animals, plants, marine organisms), or obtained from protein hydrolysates derived from biotechnology. Preferred cationic protein hydrolysates have a molecular weight of 100 to 25,000 daltons, preferably a basic protein content of 250 to 5,000 daltons. In this context, cationic protein hydrolysate should be understood to include quaternized amino acids and their mixtures. In addition, cationic protein hydrolysate can also be further derivatized. Typical examples of cationic protein hydrolysate and derivatives thereof are commercially available and are included in those cited in "International Cosmetic Ingredient Dictionary and Handbook" (sixteenth edition 2016, The Cosmetic, Toiletry, and Fragrance Association 1101 17th Street, NW, Suite 300, Washington, DC 20036-4702). Examples are cocodimonium hydroxypropyl hydrolyzed collagen, cocodimonium hydroxypropyl hydrolyzed casein, steardimonium hydroxypropyl hydrolyzed collagen, steardimonium hydroxypropyl hydrolyzed hair keratin, lauryldiamonium hydroxypropyl hydrolyzed keratin, cocodimonium hydroxypropyl hydrolyzed rice protein, cocodimonium hydroxypropyl hydrolyzed silk, cocodimonium hydroxypropyl hydrolyzed soy protein, cocodimonium hydroxypropyl hydrolyzed wheat protein, cocodimonium hydroxypropyl silk amino acids, hydroxypropyl arginine lauryl / myristyl ether HCl, hydroxypropyltrimonium gelatin. Cationic protein hydrolysates and derivatives obtained from plants are very particularly preferred.

[0113] The composition according to the invention comprises protein hydrolysates and their derivatives or amino acids and their derivatives (if present) in an amount of preferably 0.01 to 10 wt %, based on the total composition. Amounts of 0.1 to 5 wt %, in particular 0.1 to 3 wt %, are very particularly preferred.

[0114] Furthermore, the composition according to the invention may comprise at least one mono-, oligo- or polysaccharide or a derivative thereof.

[0115] Suitable monosaccharides include, but are not limited to, glucose, fructose, galactose, arabinose, ribose, xylose, lyxose, allose, altrose, mannose, gulose, idose and talose, deoxy sugars fucose and rhamnose and amino sugars such as glucosamine or galactosamine. Glucose, fructose, galactose, arabinose and fucose are preferred.

[0116] Suitable oligosaccharides are composed of two to ten monosaccharide units, such as sucrose, lactose or algal sugars. Sucrose is a particularly preferred oligosaccharide. It is also particularly preferred to use honey, which mainly contains glucose and sucrose.

[0117] Suitable polysaccharides consist of more than ten monosaccharide units. Preferred polysaccharides are starches and starch degradation products based on [α]-D-glucose units, such as amylose, amylopectin and dextrin. According to the present invention, chemically and / or thermally modified starches, such as hydroxypropyl starch phosphate or dihydroxypropyl distarch phosphate. Glucans and their derivatives, such as dextran sulfate, are also preferred. Nonionic cellulose derivatives, such as methylcellulose, hydroxypropyl cellulose or hydroxyethyl cellulose, and cationic cellulose derivatives, polyquaternium-10 and polyquaternium-24 are similarly preferred. Further preferred examples are polysaccharides from fucose units. Polysaccharides based on amino sugar units, in particular chitin and their deacetylated derivatives, chitosan and mucopolysaccharides are particularly preferred. According to the present invention, preferred mucopolysaccharides include hyaluronic acid and its derivatives, such as sodium hyaluronate or dimethylsilanol hyaluronate, and chondroitin and its derivatives, such as chondroitin sulfate.

[0118] In a particular embodiment, the composition according to the invention comprises at least one film-forming polymer, emulsion-stabilizing polymer, thickening polymer or adhesive polymer chosen from naturally occurring and synthetic polymers (which may be cationic, anionic, amphoteric or nonionic). Preferred cationic polymers include polysiloxanes with quaternary groups.

[0119] Preferred anionic polymers contain carboxylate and / or sulfonate groups and, for example, acrylic acid, methacrylic acid, crotonic acid, maleic anhydride, and 2-acrylamido-2-methylpropanesulfonic acid as monomers. Here, the acidic groups can be present in whole or in part in the form of sodium salts, potassium salts, ammonium salts, monoethanolammonium salts, or triethanolammonium salts. Preferred monomers are 2-acrylamido-2-methylpropanesulfonic acid and acrylic acid. Particularly preferred anionic polymers contain 2-acrylamido-2-methylpropanesulfonic acid as the sole monomer or comonomer, wherein the sulfonic acid groups can be present in whole or in part as salts. In this embodiment, copolymers of at least one anionic monomer and at least one nonionic monomer are preferably used. With regard to the anionic monomers, reference is made to the above-mentioned substances. Preferred nonionic monomers are acrylamide, methacrylamide, acrylic esters, methacrylic esters, vinyl pyrrolidone, vinyl ethers, and vinyl esters. Preferred anionic copolymers are acrylic acid-acrylamide copolymers, particularly polyacrylamide copolymers with monomers containing sulfonic acid groups. Particularly preferred anionic copolymers are composed of 70 to 55 mol % acrylamide and 30 to 45 mol % 2-acrylamido-2-methylpropanesulfonic acid, wherein the sulfonic acid groups may be present completely or partially as sodium, potassium, ammonium, monoethanolammonium, or triethanolammonium salts. These copolymers may also be crosslinked, with preferred crosslinking agents including polyethylenically unsaturated compounds such as tetraallyloxyethane, allylsucrose, allylpentaerythritol, methylenebisacrylamide, and sodium acryloyldimethyltaurate copolymers.

[0120] Further preferred anionic homopolymers and copolymers are uncrosslinked and crosslinked polyacrylic acids. Preferred crosslinking agents here may be pentaerythritol, sucrose, and allyl ethers of propylene. Particularly preferred anionic copolymers comprise 80-98% of monomers of unsaturated, optionally substituted C3-6 carboxylic acids or their anhydrides and 2-20% of optionally substituted acrylic esters of saturated C10-30 carboxylic acids, wherein the copolymers can be crosslinked with the above-mentioned crosslinking agents.

[0121] Suitable nonionic polymers include partially saponifiable polyvinyl alcohol as well as vinyl pyrrolidone / vinyl ester copolymers and polyvinyl pyrrolidone.

[0122] The cosmetic composition according to the present invention may also contain at least one organic, mineral, or modified mineral light stabilizer. Light stabilizers are liquid or crystalline substances at room temperature that absorb UV radiation and emit the resulting energy as longer-wavelength radiation (e.g., as heat). Generally, a distinction is made between UVA filters and UVB filters. Naturally, UV-A and UV-B filters can also be added as a mixture. According to the present invention, if UV filters are used in the composition, it is preferred to add a mixture of filters.

[0123] The compositions according to the invention may also comprise further cosmetically active ingredients, such as glycogen, peptides, amino acids, phenols, polyphenols, vitamins, extracts from plants or algae, and cosmetic oils.

[0124] Preferred peptides comprised in the composition according to the invention are selected from palmitoyl hexapeptide-12, palmitoyl oligopeptide, palmitoyl pentapeptide-3, palmitoyl tetrapeptide-7, palmitoyl tripeptide-1, collagen, elastin, epidermal growth factor (EGF), epitalon and fibronectin.

[0125] Preferred amino acids comprised in the composition according to the invention are selected from the group consisting of proteinogenic amino acids, preferably alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine and tryptophan.

[0126] Preferred phenols and polyphenols for inclusion in the composition according to the invention are selected from the group consisting of resveratrol, quercetin, rutin, tannic acid, apigenin, phloretin, caftaric acid, caffeic acid phenethyl ester, pterostilbene, luteolin, fisetin, honokiol, ferulic acid and sinapinic acid.

[0127] Preferred vitamins for inclusion in the composition according to the invention are selected from the group consisting of coenzyme Q10 (ubiquinone), biotin, vitamin A, all-trans retinoic acid, retinoids, retinol, retinal, retinyl palmitate, retinyl ascorbate, retinyl palmitate, retinyl retinoate, vitamin D, cholecalciferol, ergocalciferol, vitamin E, preferably α-, β-, γ- and δ-tocopherol, tocopherol, tocopheryl acetate, tocopheryl acetate, tocopheryl linoleate, tocopheryl linoleate, tocopheryl linoleate / oleate, tocopheryl nicotinate, tocopheryl succinate, tocotrienols, vitamin K and vitamin C, preferably ascorbyl palmitate.

[0128] Preferred extracts of plants or algae for inclusion in the composition according to the invention are selected from the group consisting of aloe vera (especially vera) extract, horse chestnut extract, calendula extract, centella asiatica extract, bakuchiol, ascophyllum nodosum extract, acetomorphan, coleus forskohlii extract, cranberry seed extract, ginkgo leaf extract, ginseng extract, grapefruit peel extract, green tea extract, barley extract, horse chestnut extract, rice (orchid) extract, pectin, knotweed root extract, pomegranate extract, spirulina extract, squalane, st.-john's wort extract, willow bark extract, capsaicin, pepper extract, glycyrrhiza glabra extract, madecassoside, rosemary extract, spirogynin, carotenoids, preferably astaxanthin, beta-carotene, canthaxanthin, capsaicin, capsanthin, cryptoxanthin, lutein, luteoxanthin, tomatine and zeaxanthin, chamomile (matricaria) flower extract, sesamin, apple fruit extract, baicalein, puerarin, phloridzin, 1,4-dicaffeoylquinic acid, myricetin-3-o-beta-rhamnoside, dihydromyricetin, diosmetin, 6-gingerol and mangnolol.

[0129] Preferred cosmetic oils for inclusion in the composition according to the invention are selected from the group consisting of argan oil, almond oil, blackcurrant oil, salvia officinalis oil, avocado oil (Avocado spp.), caprylic / capric triglycerides, cottonseed oil, rapeseed oil, marula oil, peach kernel oil, perilla seed oil, pomegranate seed oil, pumpkin seed oil, sea buckthorn oil, coconut oil, coconut oil-derived fatty acids, soybean oil, sunflower seed oil, jojoba oil, macadamia oil, Avocado spp. oil, triticum vulgare (wheat) germ oil, grapeseed oil, MCT oil, grapefruit oil, ginger oil, shea butter, camellia sinensis seed oil, cocoa butter, coconut oil and evening primrose oil.

[0130] In another preferred embodiment of the present invention, the composition according to the present invention is a liposome composition, ie a composition containing liposomes. The liposome composition of the present invention preferably contains a phospholipid or a sterol (sterol) as described above.

[0131] In the liposome composition of the present invention, the liposomes preferably have an average particle size of 15 nm to 800 nm, in particular 50 nm to 500 nm, more preferably 60 nm to 350 nm, even more preferably 80 nm to 240 nm. The average particle size is preferably determined using photon correlation spectroscopy. Preferably, the measurement is performed using a Zetasizer Nano ZS90, Malvern Instruments Ltd., UK according to the manufacturer's instructions. The Z-average is the intensity-weighted average hydrodynamic size of a collection of particles measured by dynamic light scattering (DLS). The Z-average is derived from a cumulant analysis of the measured correlation curves, where a single particle size is assumed and a single exponential fit is applied to the autocorrelation function (see Zetasizer Nano ZS90 User Manual MAN0485-1-109 June 2017).

[0132] The composition according to the present invention may further comprise at least one additional component selected from emollients, thickeners, viscosity regulators, stabilizers, antioxidants, hydrotropes, solids, fillers, film formers, pearlescence additives, deodorant and antiperspirant active ingredients, insect repellents, self-tanning agents, preservatives, conditioners, fragrances, dyes, odor absorbers, superfatting agents, other solvents.

[0133] With regard to further optional components and the amounts of these components used, reference is expressly made to the relevant handbooks known to the person skilled in the art, for example K. Schrader, "Grundlacen und Rezpturen der Kosmetika [Cosmetics—fundamentals and formulations]", 2nd edition, pp. 329-341, Hüthig Buch Verlag Heidelberg. The amount of the particular additive is determined by the intended use. Example

[0134] Example 1: Production of fermentation broth of Bacillus velez / Bacillus amyloliquefaciens CECT5940 and Bacillus subtilis DSM32315

[0135] Fermentation broth production was performed by inoculating LB Kelly fermentation medium with an aliquot of Bacillus strain CECT5940 or an aliquot of Bacillus subtilis strain DSM32315 and incubating the medium at 37°C and 200 rpm for approximately 16 hours until an optical density (OD600) of 5 was reached. LB Kelly medium contains 40 g soy peptone, 40 g dextrin 10, 1.8 g KH2PO4, 4.5 g K2HPO4, 0.3 g MgSO4*7H2O and 0.2 ml KellyT trace metal solution per liter, wherein the KellyT trace metal solution contains 25 mg EDTA disodium salt dihydrate, 0.5 g ZnSO4*7H2O, 3.67 g CaCl2, 2H2O, 1.25 g MnCl2*4H2O, 0.25 g CoCl2*6H2O, 0.25 g ammonium molybdate, 2.5 g FeSO4*7H2O and 0.1 g CuSO4*5H2O, and is adjusted to pH 6 with NaOH and 500 ml H2O.

[0136] The fermentation broth obtained was about 1x10 8 The amount of CFU includes Bacillus CECT5940 cells or Bacillus subtilis DSM32315 cells.

[0137] Example 2: Inactivation of the fermentation broth of Bacillus strain CECT5940

[0138] The fermentation broth obtained according to Example 1 was treated in various ways to inactivate the Bacillus cells contained therein. Inactivation was performed by heat inactivation, pH inactivation, or a combination of the two. Heat inactivation was performed by raising the temperature to 60°C and incubating for 1 hour or by raising the temperature to 80°C and incubating for 30 minutes, and pH inactivation was performed by lowering the pH to 3 by adding 5 M H2SO4 and incubating for 1 hour. After incubation at elevated temperature and / or reduced pH, 50 ml aliquots of the treated fermentation broth were cooled to -20°C for storage.

[0139] Example 3: Test of the inhibitory activity of inactivated fermentation broth of Bacillus sp. CECT5940 and Bacillus subtilis DSM32315 on Propionibacterium acnes and Staphylococcus epidermidis

[0140] The effects of inactivated fermentation broths of Bacillus strains CECT5940 and Bacillus subtilis DSM32315 on Propionibacterium acnes were measured in a plate-based inhibition assay. P. acnes subsp. acnes ATCC6919 and Staphylococcus epidermidis ATCC12228 strains were cultured anaerobically in TSB medium supplemented with 0.2% Tween 80 for 24 hours. The P. acnes culture was adjusted to an OD of 2.5 by measuring the optical density at 600 nm, and 135 μl of this culture was subsequently plated on TSB plates supplemented with 0.2% Tween 80. 4 to 5 wells with a diameter of 9 mm were pressed into the agar plate, and 100 μl of the test substance were placed in the wells. After a short drying time, the plates were incubated anaerobically at 37°C for 24 hours. The halo size was determined as the average of 2 measurements (vertical and horizontal) minus the diameter of the well.

[0141] Table 1: Inhibitory activity of inactivated fermentation broths of Bacillus sp. CECT5940 and Bacillus subtilis DSM32315 against skin bacteria

[0142]

[0143] It can be seen that the inactivated fermentation broths of Bacillus strain CECT5940 and Bacillus subtilis DSM32315 selectively inhibit the growth of the pathogenic skin bacterium Propionibacterium acnes, whereas they do not inhibit the growth of the saprophytic skin bacterium Staphylococcus epidermidis.

[0144] Example 4: Preparation of a composition containing ceramide and inactivated fermentation broth of Bacillus strain CECT5940 or Bacillus subtilis DSM32315

[0145] In this example, a mixture of polyglyceryl fatty acids polyglyceryl-10 stearate, polyglyceryl-10 palmitate, and polyglyceryl-10 behenate was used as an emulsifier, as mixtures of different polyglyceryl fatty acids are known to be very beneficial for the skin (see WO 2022 / 073909). The preparation of the polyglyceryl fatty acids was carried out as disclosed in the working examples of WO 2022 / 073909 (page 9, Example 1c).

[0146] Table 2: Compositions containing inactivated Bacillus fermentation broth and ceramide

[0147]

[0148]

[0149] The thin-layered preparation is prepared as follows: all phases are heated to about 90° C. Phase B is then added to phase A with gentle stirring, and the mixture A / B is subsequently added to phase C with stirring. After homogenizing the mixture A / B / C for 2 minutes using an Ultra Turrax, this mixture is cooled to 40° C. with gentle stirring and added to phase D. The mixture A / B / C / D thus obtained is further cooled to 30° C. with gentle stirring, while phase E is added.

[0150] Example 5: Testing the inhibitory activity of the thin layer composition against Propionibacterium acnes

[0151] To test the inhibitory activity of the lamellar composition, an inhibition test was performed in a manner similar to that described for the inactivated fermentation broth in Example 3. Instead of P. acnes ATCC6919, the acne-related strain P. acnes type 1A-IDSM1897, isolated from acne lesions on human facial skin, was used. To test the inhibitory efficacy, 1:2 and 1:10 dilutions of the liposome composition with water were tested in parallel with the inactivated fermentation broth itself and the undiluted liposome composition. The results are shown in the following table:

[0152] Table 3: Effect of a composition containing heat-killed (80°C) fermentation broth (FB) of Bacillus sp. CECT5940 and ceramide on Propionibacterium acnes DSM1897

[0153]

[0154] Table 4: Effect of a thin layer composition containing pH-inactivated (pH 3) fermentation broth (FB) of Bacillus sp. CECT5940 and ceramide on Propionibacterium acnes DSM1897

[0155]

[0156] As can be seen, compositions containing a mixture of Bacillus sp. CECT5940 and ceramide as active ingredients exhibit very strong growth inhibitory activity against the acne-associated Propionibacterium acnes strain type 1a-DSM1897. Despite the fact that the fermentation broth was used in the composition in amounts of only approximately 10 or 20 wt%, the composition exhibited growth inhibitory activity comparable to, or even slightly stronger than, that of the fermentation broth itself. Furthermore, the diluted, thin-layered composition also exhibited very high growth inhibitory activity against P. acnes DSM1897, leading to the hypothesis of a synergistic effect between the fermentation broth and the ceramide. Whether the fermentation broth was inactivated by heating or pH treatment is clearly irrelevant, as the results were comparable.

[0157] Example 6: Testing of further Bacillus Velezii and Bacillus subtilis strains for activity against Propionibacterium acnes and Staphylococcus epidermidis

[0158] The positive results obtained for the strains Bacillus sp. strain CECT5940 (which is currently classified as a strain of Bacillus velez) and Bacillus subtilis DSM32315 prompted further testing of the activity of Bacillus velez and Bacillus subtilis strains against pathogenic Propionibacterium acnes and, therefore, the usability of their fermented broths as ingredients in skin care products. A total of 13 strains of Bacillus velez and 5 strains of Bacillus subtilis were tested. The tests were performed as described in Examples 1 to 3 above. It was found that all 13 strains of Bacillus velez and all 5 strains of Bacillus subtilis tested showed, without exception, very strong activity against the acne-associated Propionibacterium acnes strain type 1A-IDSM1897 (halo sizes of 12 to 20 mm for Bacillus velez strains and 17 to 27 mm for Bacillus subtilis strains), while showing no inhibitory activity against the beneficial skin strain Staphylococcus epidermidis. Therefore, strains of Bacillus velez and Bacillus subtilis are clearly well-suited as ingredients for skin care products overall.

[0159] Example 7: Testing of the activity of Bacillus licheniformis and Bacillus paralicheniformis strains against Propionibacterium acnes and Staphylococcus epidermidis

[0160] A total of four strains of Bacillus licheniformis and one strain of Bacillus paralicheniformis were tested for activity against the pathogenic Propionibacterium acnes and the beneficial Staphylococcus epidermidis. It was found that the strains of Bacillus licheniformis and Bacillus paralicheniformis showed similar behavior to the strains of Bacillus Velez-O and Bacillus subtilis. All four strains of Bacillus licheniformis and the strain of Bacillus paralicheniformis tested showed very strong activity against the acne-associated Propionibacterium acnes type 1A-I DSM1897 (halo size of 16 to 22 mm for Bacillus licheniformis strains and halo size of 37 mm for Bacillus paralicheniformis strains), while not showing any inhibitory activity against the beneficial skin strain Staphylococcus epidermidis. Therefore, strains of Bacillus licheniformis and Bacillus paralicheniformis are also very suitable strains for skin care products.

[0161] Example 8: Testing of coagulant strains for activity against Propionibacterium acnes and Staphylococcus epidermidis

[0162] Two strains of Bacillus coagulans were tested for activity against pathogenic Propionibacterium acnes and beneficial Staphylococcus epidermidis. It was demonstrated that both tested strains did not exhibit any inhibitory activity against beneficial Staphylococcus epidermidis, but they also did not exhibit any inhibitory activity against the acne-associated Propionibacterium acnes strain 1A-IDSM1897 and therefore proved to be unsuitable strains for the purposes of the present invention.

[0163] Example 9: Other thin layer preparations containing Bacillus fermentation products

[0164]

[0165]

[0166]

[0167]

[0168]

[0169] The formulation was prepared as follows:

[0170] Heat phases A and C to 90°C. Then add phase A to phase C while stirring. This pre-emulsion is then homogenized, for example using an Ultra Turrax. Cool the emulsion to 40°C while stirring gently and add the preservative (phase B) and the inactivated Bacillus ferment (phase D). Then cool the mixture further to 30°C while stirring.

[0171] Example 10: Further Formulation Examples

[0172]

[0173]

[0174]

[0175]

[0176]

[0177]

[0178]

[0179]

[0180] Oil-in-water emulsion

[0181]

[0182]

[0183]

[0184]

[0185]

[0186]

[0187]

[0188] Water-in-oil emulsion

[0189] Cleaning preparations

[0190]

[0191]

[0192] Silicone oil in water emulsion

[0193] Table of named ingredients:

[0194]

[0195]

Claims

1. A cosmetic composition comprising at least one Bacillus strain or a fermentation broth thereof and at least one ceramide.

2. The cosmetic composition according to claim 1, wherein the composition is a topical skin care composition or a dermatological composition.

3. A pharmaceutical composition for topical or dermatological use, in particular for the treatment or prevention of diseases associated with pathogenic Propionibacterium acnes and / or for the treatment or prevention of acne vulgaris, dermatitis, rosacea or red blood streaks, comprising at least one Bacillus strain or a fermentation broth thereof and at least one ceramide.

4. The composition according to any one of the preceding claims, wherein the ceramide is selected from the group consisting of ceramide NP, ceramide AP, ceramide EOP, ceramide NDS, ceramide ADS, ceramide EODS, ceramide NS, ceramide AS, ceramide EOS, ceramide NH, ceramide AH, ceramide EOH, and mixtures thereof, preferably ceramide NP, ceramide AP, ceramide NS, ceramide EOP, ceramide EOS, and mixtures thereof, most preferably ceramide NP, ceramide AP, and mixtures thereof.

5. The composition according to any one of the preceding claims, wherein the Bacillus strain is selected from the group consisting of B. subtilis, B. amyloliquefaciens, B. velezensis, B. licheniformis, B. paralicheniformis and B. pumilus, more preferably B. subtilis, B. amyloliquefaciens and B. velezensis, most preferably B. subtilis and B. velezensis.

6. The composition according to any one of the preceding claims, wherein the Bacillus strain is selected from Bacillus Velez / Bacillus amyloliquefaciens CECT5940 and Bacillus subtilis DSM32315.

7. A cosmetic composition comprising Bacillus strain CECT5940 or Bacillus subtilis strain DSM32315 or a mutant of such a strain or a fermentation broth thereof, wherein the mutant has at least 99%, preferably at least 99.5%, more preferably at least 99.9% sequence identity with the genomic DNA of the parent strain.

8. The composition according to any one of the preceding claims, wherein the composition is an emulsion, in particular a W / O or O / W emulsion, preferably a micellar, lamellar or liposomal composition, more preferably a lamellar composition.

9. The composition according to any one of the preceding claims, wherein the Bacillus strain or a fermentation broth thereof has growth inhibitory activity against at least one skin pathogen, preferably against Propionibacterium acnes, and preferably has no growth inhibitory activity against Staphylococcus epidermidis.

10. The composition according to any one of the preceding claims, wherein more than 80%, preferably more than 90%, more preferably all Bacillus strains contained in the composition are non-viable and / or preferably less than 10%, more preferably less than 5% of the Bacillus cells are present as spores, most preferably all the Bacillus cells are not present as spores.

11. Composition according to any of the preceding claims, wherein the composition comprises at least one nonionic emulsifier, preferably at least one polyglycerol carboxylate, more preferably at least two polyglycerol carboxylates, wherein the polyglycerol groups of the polyglycerol carboxylates preferably have a degree of polymerization of 2.0 to 25, more preferably 2.5 to 20, in particular 3.0 to 15, and the carboxylic acid groups are preferably fatty acids, in particular fatty acids having 12 to 26, preferably 14 to 24, more preferably 16 to 22 carbon atoms.

12. A composition according to any one of the preceding claims, wherein the composition contains at least one additional ingredient selected from the group consisting of phospholipids, sphingoid bases, free fatty acids, surfactants, protein hydrolysates, polymers, light stabilizers, antiperspirants, deodorants, peptides, amino acids, vitamins, extracts from plants and algae, cosmetic oils, emollients, antioxidants, preservatives, thickeners, viscosity regulators, stabilizers, hydrotropes, solids, fillers, film formers, conditioners, insect repellents, self-tanning agents, odor absorbers, solvents, fragrances and dyes.

13. A method for preparing the composition of any one of claims 1 to 12, comprising the steps of: a) providing a fermentation broth of Bacillus cells having growth inhibitory activity against skin pathogens, in particular Propionibacterium acnes, wherein the Bacillus cells preferably do not have growth inhibitory activity against Staphylococcus epidermidis, b) killing all or a substantial portion of the Bacillus cells, preferably by heat treatment and / or pH change, c) mixing the fermentation broth thus obtained with substances suitable for cosmetic skin application.

14. Use of a Bacillus strain or a fermentation broth thereof or a cosmetic composition according to any of the preceding claims for topical treatment of human skin, in particular for treating inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially modulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin, wherein the Bacillus strain is preferably Bacillus strain CECT5940, Bacillus strain DSM32315 or a mutant of such strains.

15. A non-therapeutic method for treating human skin, in particular for treating inflamed, unclean, dry, scarred or acne-prone human skin and / or for beneficially modulating the skin microbiome or the immune status of the skin and / or for avoiding or reducing erythema or inflammation of the skin and / or for increasing the barrier function of the skin, wherein a Bacillus strain according to any of the preceding claims, or a fermentation broth thereof, or a cosmetic composition thereof, is applied to human skin, wherein the Bacillus strain is preferably Bacillus strain CECT5940, Bacillus strain DSM32315 or a mutant of such a strain.

16. A Bacillus strain or a fermentation liquid thereof for use in a method for treating or preventing Propionibacterium acnes-related diseases of human skin and / or a method for treating acne vulgaris, dermatitis, rosacea or red blood streaks, wherein the Bacillus strain is preferably Bacillus strain CECT5940, Bacillus strain DSM32315 or a mutant of such a strain.

Images