Composition comprising ceramide and single rhamnolipid

Abstract

The present invention relates to a composition comprising a ceramide and a single rhamnolipid.

Description

Field of the Invention

[0001] The present invention relates to a composition comprising ceramide and mono - rhamnolipid. Prior Art

[0002] Ceramides are a class of lipophilic amides that, together with fatty acids and cholesterol, form the lipid matrix of the skin. These amides play an important role in cosmetics and are established ingredients in various formulations, having beneficial effects on the skin barrier, trans - epidermal water loss, and other functions. Many formulations are based on emulsions with a relatively high oil content. Since ceramides are poorly soluble substances in an aqueous environment, only a few examples of water - based formulations are known.

[0003] WO2023161179 discloses liposomal compositions comprising biosurfactants and the use of such liposomal compositions for encapsulating at least one cosmetic, pharmaceutical, and / or nutraceutical active ingredient. Thereby, it provides liposomal compositions that allow solubilization of poorly soluble substances and have excellent long - term stability in terms of reprecipitation.

[0004] KR20190080060 discloses clear formulations containing ceramide. One disadvantage of these formulations is the use of ethoxylated surfactants. Another disadvantage is the need for oily compounds, which may be undesirable in aqueous applications.

[0005] US8313755B2 discloses clear aqueous ceramide compositions having polyols.

[0006] The object of the present invention is to provide a composition comprising ceramide with a clear appearance. Summary of the Invention

[0007] Surprisingly, it has been found that the combination of mono - rhamnolipid and ceramide gives a clear aqueous composition.

[0008] The present invention thus provides a composition comprising mono - rhamnolipid and ceramide.

[0009] One advantage of the compositions according to the present invention is that they enhance the deposition of ceramide on the skin.

[0010] Another advantage is that the permeability of ceramide is improved in the presence of mono - rhamnolipid.

[0011] Another advantage is the very high compatibility with organic acids.

[0012] Another advantage is that the foam quality of the compositions according to the present invention is improved.

[0013] Another advantage is that the compositions according to the present invention have a foam - promoting effect.

[0014] Another advantage is that the composition according to the invention has good compatibility with other ingredients.

[0015] A further advantage is the enhanced skin barrier protection.

[0016] A further advantage is that the composition according to the invention enhances the deposition of ceramides on the hair.

[0017] A further advantage is that the composition according to the invention has an improved skin feel.

[0018] A further advantage is the improved conditioning effect on the hair by the composition according to the invention.

[0019] A further advantage is the improved thickening of the formulation.

[0020] A further advantage is that the composition according to the invention can be easily incorporated into different formulations.

[0021] Another advantage is that the composition according to the invention can be obtained without any heating step.

[0022] Another advantage is the high stability of the composition according to the invention.

[0023] A further advantage is the mildness of the composition according to the invention.

[0024] The present invention thus provides a composition comprising

[0025] A) at least one ceramide, and

[0026] B) at least one rhamnolipid,

[0027] characterized in that component B) comprises at least 50% by weight of mono-rhamnolipid, where the weight percentages are relative to all rhamnolipids comprised in the total composition.

[0028] In the context of the present invention, the term "ceramide" is to be understood as meaning acylated sphingoid bases, where the sphingoid bases are preferably selected from sphingosine, sphinganine, 6-hydroxysphingosine and phytosphingosine, and may also be in glycosylated form, such as glucosylceramide.

[0029] When determining the amount of rhamnolipid, if the rhamnolipid is present in the form of a salt, only the mass of the rhamnolipid is considered, while ignoring the counterions of the salt.

[0030] When mean values are mentioned hereinafter, these are number-average mean values unless otherwise stated.

[0031] Unless otherwise stated, percentages are data expressed as weight percentages. The same applies to parts per million (ppm).

[0032] Wherever measured values are mentioned hereinafter, unless otherwise stated, they are determined at a temperature of 25 °C and a pressure of 1013 mbar.

[0033] The preferred composition according to the invention is characterized in that the at least one ceramide is selected from the group consisting of ceramide NP, ceramide AP, ceramide EOP, ceramide NG (also known as ceramide NDS and ceramide 2), ceramide ADS, ceramide EODS, ceramide NS, ceramide AS, ceramide EOS, ceramide NH, ceramide AH and ceramide EOH, preferably the group consisting of them, preferably selected from the group consisting of ceramide NP, ceramide NG, ceramide AP and ceramide EOP, and most preferably ceramide NP.

[0034] The preferred composition according to the invention is characterized in that component A) is included in an amount of 0.0005% to 5.0% by weight, more preferably 0.001% to 2.0% by weight, more preferably 0.002% to 1.5% by weight, and even more preferably 0.05% to 1.0% by weight, where the weight percentages are relative to the total composition.

[0035] The preferred composition according to the invention is characterized in that the composition contains at least two ceramides, preferably at least three ceramides, and particularly preferably exactly three ceramides.

[0036] The term "rhamnolipid" is preferably understood in the context of the present invention to particularly refer to the compounds of general formula (I) and their salts,

[0037]

[0038] where

[0039] mRL = 2, 1 or 0, preferably 1 or 0,

[0040] nRL = 1 or 0,

[0041] R 1RL and R 2RL = independently of each other are the same or different organic residues having 2 to 24, preferably 5 to 13 carbon atoms, in particular optionally branched, optionally substituted, in particular hydroxy-substituted, optionally unsaturated, in particular optionally mono-, di- or tri-unsaturated alkyl residues, preferably selected from pentenyl, heptenyl, nonenyl, undecenyl and tridecenyl and those in (CH2) o -CH3, where o = 1 to 23, preferably 4 to 12.

[0042] If nRL = 1, the glycosidic bond between the two rhamnose units is preferably in the α-configuration. The optically active carbon atoms of the fatty acid are preferably present as the R-enantiomer (e.g., (R)-3-{(R)-3-[2-O-(α-L-rhamnopyranosyl)-α-L-rhamnopyranosyl]oxydecanoyl}oxydecanoate).

[0043] The term "dirhamnolipid" is understood in the context of the present invention to mean a compound of formula (I) or a salt thereof in which nRL = 1.

[0044] The term "monorhamnolipid" is understood in the context of the present invention to mean a compound of formula (I) or a salt thereof in which nRL = 0.

[0045] The different rhamnolipids are abbreviated according to the following nomenclature:

[0046] "diRL-CXCY" is understood to mean a dirhamnolipid of formula (I) in which one of the residues R 1RL and R 2RL is = (CH2) o -CH3, where o = X - 4, and the remaining residue R 1 or R 2 is = (CH2) o -CH3, where o = Y - 4.

[0047] "monoRL-CXCY" is understood to mean a monorhamnolipid of formula (I) in which one of the residues R 1RL and R 2RL is = (CH2) o -CH3, where o = X - 4, and the remaining residue R 1RL or R 2RL is = (CH2) o -CH3, where o = Y - 4.

[0048] Thus, the nomenclature used does not distinguish between "CXCY" and "CYCX".

[0049] For rhamnolipids in which mRL = 0, monoRL-CX or diRL-CX is used accordingly.

[0050] If one of the above-mentioned labels X and / or Y bears ":Z", this means that the corresponding residue R 1RL and / or R 2RL is equal to an unbranched, unsubstituted hydrocarbon residue having X - 3 or Y - 3 carbon atoms with Z double bonds.

[0051] Considering the rhamnolipids listed below which contain dirhamnolipids, they can be adjusted to the desired high content of monorhamnolipids by, for example, rhamnosidase.

[0052] The rhamnolipids applicable in the context of the present invention can also be produced by fermentation of Pseudomonas, especially Pseudomonas aeruginosa, which are preferably non-genetically modified cells, a technique that was already disclosed in the 1980s, as described in, for example, EP0282942 and DE4127908. The rhamnolipids produced in Pseudomonas aeruginosa cells that have been improved by genetic modification for higher rhamnolipid titers can also be used in the present invention; for example, such cells have been disclosed by Lei et al. in Biotechnol Lett. June 2020; 42(6): 997-1002.

[0053] The rhamnolipids produced by Pseudomonas aeruginosa are commercially available from Jeneil Biotech Inc., for example, under the trade name Zonix; from Logos Technologies (technology acquired by Stepan), for example, under the trade name NatSurFact; from Biotensidion GmbH, for example, under the trade name Rhapynal; from AGAE technologies, for example, under the names R90, R95, R95Md, R95Dd, from Locus Bio-Energy Solutions and from Shanghai Yusheng Industry Co., Ltd., for example, under the trade name Bio-201 Glycolipids.

[0054] The composition according to the present invention is preferably characterized in that component B) comprises

[0055] 12% to 32% by weight of monoRL-C8C10,

[0056] 51% to 81% by weight of monoRL-C10C10,

[0057] 1% to 9% by weight of monoRL-C10C12,

[0058] 1% to 9% by weight of monoRL-C10C12:1,

[0059] where the weight percentages are relative to all the monorhamnolipids comprised in the composition.

[0060] The preferred composition according to the present invention is characterized in that it is a non-liposomal composition.

[0061] The term "non-liposomal composition" means that the composition does not contain liposomes.

[0062] The preferred compositions according to the invention are characterized in that they do not contain phospholipids.

[0063] The preferred compositions according to the invention are characterized in that they contain particles having an average particle size of 13 nm or less, preferably between 3 nm and 12 nm.

[0064] Photon correlation spectroscopy is used to measure the average particle size, preferably at a total concentration of component A) of 0.5% by weight, where the composition contains water. Measurements are carried out 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 the particle ensemble measured by dynamic light scattering (DLS). The Z-average is derived from the cumulant analysis of the measured correlation curve, where a single particle size is assumed and a single-exponential fit is applied to the autocorrelation function (see Zetasizer Nano ZS90 User Manual MAN0485-1-12 09 June 2017).

[0065] The preferred compositions according to the invention are characterized in that component B) is included in an amount of 0.1% to 15.0% by weight, preferably 0.5% to 10.0% by weight, more preferably 1.0% to 8.0% by weight, where the weight percentages are relative to the total composition.

[0066] According to the invention, the weight ratio of component A) to component B) in the compositions according to the invention is preferably from 0.0005:15 to 0.1:1, preferably from 0.005:10 to 0.5:5, particularly preferably from 0.05:7 to 0.1:5.

[0067] The preferred compositions according to the invention are characterized in that they contain

[0068] C) cholesterol and / or at least one cholesterol derivative selected from cholesterol sulfate, cholesterol succinate and 7-dehydrocholesterol.

[0069] Component c) is preferably included in an amount of 0.01% to 3.0% by weight, preferably 0.02% to 2.0% by weight, more preferably 1.0% to 0.05% by weight, where the weight percentages are relative to the total composition.

[0070] The preferred compositions according to the invention are characterized in that they contain

[0071] D) at least one sphingoid base, preferably selected from sphingosine, dihydrosphingosine, 6-hydroxysphingosine, N-acetyl phytosphingosine and phytosphingosine, especially phytosphingosine.

[0072] Component D) is preferably included in an amount of 0.001% to 2.0% by weight, preferably 0.002% to 1.5% by weight, more preferably 0.05% to 1.0% by weight, where the weight percentages are relative to the total composition.

[0073] Preferred compositions according to the invention are characterized in that they comprise, as an alternative or in addition, component D)

[0074] E) at least one fatty acid, preferably selected from fatty acids having 12 to 28 carbon atoms, in particular palmitic acid, stearic acid, octadecanoic acid, arachidic acid, behenic acid, docosanoic acid and tetracosanoic acid.

[0075] Component E) is preferably included in an amount of 0.01% to 3.0% by weight, preferably 0.02% to 2.0% by weight, more preferably 1.0% to 0.05% by weight, where the weight percentages are relative to the total composition.

[0076] Preferred compositions according to the invention are characterized in that they have a pH of 4.0 to 8.0, preferably 4.5 to 7.4, particularly preferably 5.0 to 7.2.

[0077] The "pH" in connection with the present invention is defined as the value measured after stirring the relevant composition for five minutes at 22 °C using a pH electrode calibrated according to ISO 4319 (1977).

[0078] Preferred compositions according to the invention are characterized in that they comprise

[0079] water, preferably 75.0% to 99.5% by weight, preferably 80.0% to 98.5% by weight, more preferably 85.0% to 98.0% by weight, based on the total composition.

[0080] The present invention further relates to a method for producing a cosmetic or pharmaceutical preparation comprising at least one ceramide, which comprises the following method steps:

[0081] a) providing a composition according to the invention;

[0082] b) adding a cosmetically or pharmaceutically acceptable carrier, preferably water, and preferably adding another cosmetic and pharmaceutical preparation ingredient.

[0083] Said one additional cosmetic and pharmaceutical preparation ingredient in step b) is of course different from any of the components A) to E) comprised in the composition according to the invention.

[0084] Preferred compositions according to the invention are preferably used in the context of the method according to the invention.

[0085] In step b) of the process according to the invention, the additional cosmetic and pharmaceutical formulation ingredients preferably added are preferably selected from surfactants, emollients, emulsifiers, thickeners, UV protection filters, antioxidants, hydrotropes, solids and fillers, film formers, pearlescent additives, opacifiers, deodorant and antiperspirant active ingredients, insect repellents, self-tanning agents, preservatives, conditioners, fragrances, dyes, odor absorbers, lipid-rich agents and solvents, preferably fragrances, conditioners and thickeners.

[0086] A preferred process according to the invention is characterized in that the process comprises

[0087] c) solubilization of the formulation.

[0088] Thus, the cosmetic or pharmaceutical formulation produced by the process according to the invention is preferably an aqueous surfactant formulation.

[0089] To promote the solubilization step c) of the process according to the invention, at least one additional surfactant is preferably present in process step c) according to the invention.

[0090] The at least one additional surfactant present in process step c) of the invention is preferably selected from anionic, cationic, nonionic, semi-polar, amphoteric and zwitterionic surfactants.

[0091] The nonionic surfactants used are preferably alkoxylated, advantageously ethoxylated, particularly preferably primary alcohols having 8 to 18 carbon atoms and on average 1 to 12 moles of ethylene oxide (EO) per mole of alcohol, where the alcohol group can be straight-chain or preferably branched in the 2-position with a methyl group, or can contain straight-chain and methyl-branched groups in a mixture, as is usually present in oxo alcohol groups. However, particular preference is given to alcohol ethoxylates having a straight-chain group of alcohols having 12 to 18 carbon atoms from natural sources, such as from coconut, palm, tallow or oleyl alcohol, and on average 2 to 8 EO per mole of alcohol. Preferred ethoxylated alcohols include, for example, C12-C14 alcohols having 3 EO, 4 EO or 7 EO, C9-C11 alcohols having 7 EO, C13-C15 alcohols having 3 EO, 5 EO, 7 EO or 8 EO,

[0092] - 9-C12-C18 alcohols having 3 EO, 5 EO or 7 EO and mixtures thereof, such as a mixture of C12-C14 alcohols having 3 EO and C12-C18 alcohols having 7 EO. The degree of ethoxylation is a statistical average and for a particular product it can be an integer or a fraction. Preferred alcohol ethoxylates have a narrow homolog distribution.

[0093] In addition to these nonionic surfactants, fatty alcohols having more than 12 EO can also be used. Examples thereof are tallow fatty alcohols having 14 EO, 25 EO or 40 EO. Nonionic surfactants containing both EO and PO (propylene oxide) groups in the molecule can also be used. In this regard, block copolymers having EO-PO block units or PO-EO block units can be used, and EO-PO-EO copolymers or PO-EO-PO copolymers can also be used.

[0094] Of course, mixed alkoxylated nonionic surfactants in which the EO and PO units are randomly distributed rather than block-distributed can also be used. Such products can be obtained by the simultaneous action of ethylene oxide and propylene oxide on fatty alcohols.

[0095] In addition, alkyl glycosides can also be used as other nonionic surfactants.

[0096] Another type of preferably used nonionic surfactant, which can be used as the sole nonionic surfactant or in combination with other nonionic surfactants, is an alkoxylated, preferably ethoxylated or ethoxylated and propoxylated fatty acid alkyl ester, preferably having 1 to 4 carbon atoms in the alkyl chain, especially fatty acid methyl esters, such as those described in Japanese Patent Application JP 58 / 217598 or preferably prepared by the method described in International Patent Application WO-A-90 / 13533.

[0097] Amine oxide type nonionic surfactants, such as N-cocoalkyl-N,N-dimethylamine oxide and N-tallowalkyl-N,N-dihydroxyethylamine oxide, and fatty acid alkanolamide type nonionic surfactants are also suitable. The amount of these nonionic surfactants is preferably not more than the amount of ethoxylated fatty alcohol, especially not more than half of it.

[0098] Other suitable surfactants are polyhydroxy fatty acid amides; polyhydroxy fatty acid amides are substances that can generally be obtained by reductive amination of reducing sugars with ammonia, alkylamines or alkanolamines, followed by acylation with fatty acids, fatty acid alkyl esters or fatty acyl chlorides.

[0099] Other suitable nonionic surfactants are polyglycerol partial esters based on monocarboxylic acids and dicarboxylic acids and crosslinked polyglycerol partial esters based on monocarboxylic acids and dicarboxylic acids.

[0100] The anionic surfactants used are, for example, surfactants of the sulfonate and sulfate types. Suitable surfactants of the sulfonate type here are preferably C9-C13 alkylbenzene sulfonates, olefin sulfonates (i.e., mixtures of olefins and hydroxyalkane sulfonates), and disulfonates, for example, as obtained by sulfonating C12-C18 monoolefins having terminal or internal double bonds with gaseous sulfur trioxide at -10- and subsequently subjecting the sulfonation product to alkaline or acidic hydrolysis. Also suitable are alkane sulfonates obtained from C12-C18 alkanes, for example, by sulfochlorination or sulfoxidation and subsequent hydrolysis or neutralization. Similarly, esters of α-sulfo fatty acids (ester sulfonates), such as α-sulfonated methyl esters of hydrogenated coconut, palm kernel, or tallow fatty acids, are also suitable.

[0101] Other suitable anionic surfactants are sulfated fatty acid glycerides. Fatty acid glycerides are to be understood to mean monoesters, diesters, and triesters, and mixtures thereof, such as prepared by esterifying monoglycerides with 1 to 3 moles of fatty acid or by transesterifying triglycerides with 0.3 to 2 moles of glycerol. Preferred sulfated fatty acid glycerides here are the sulfation products of saturated fatty acids having 6 to 22 carbon atoms, such as caproic acid, caprylic acid, capric acid, myristic acid, lauric acid, palmitic acid, stearic acid, or behenic acid.

[0102] Preferred alkyl (alkenyl) sulfates are the alkali metal salts of the sulfuric acid half-esters of C12-C18 fatty alcohols, and especially the sodium salts, such as those of coconut fatty alcohol, tallow fatty alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, or stearyl alcohol or the half-esters of C10-C20 oxo alcohols and secondary alcohols of these chain lengths. In addition, alkyl (alkenyl) sulfates having a specific chain length are preferred, which contain synthetic straight-chain alkyls prepared on a petrochemical basis and have a degradation behavior similar to that of suitable compounds based on oleochemical raw materials.

[0103] Also suitable are the sulfuric acid monoesters of linear or branched C7-C20 alcohols ethoxylated with 1 to 6 moles of ethylene oxide, for example, 2-methyl branched C9 alcohol having an average of 3.5 moles of ethylene oxide (EO) or C12-C18 fatty alcohols having 1 to 4 EO. Due to their high foaming behavior, they are used only in relatively small amounts in cleaning compositions, for example, in amounts of 1 to 5% by weight.

[0104] Other suitable anionic surfactants are salts of alkyl sulfosuccinic acids, which are also known as sulfosuccinates or sulfosuccinates and consist of mono- and / or diesters formed from sulfosuccinic acid and alcohols (preferably fatty-11-alcohols and especially ethoxylated fatty alcohols). Preferred sulfosuccinates contain C8-C18 fatty alcohol groups or mixtures of these groups. Particularly preferred sulfosuccinates contain fatty alcohol groups derived from ethoxylated fatty alcohols. In this regard, sulfosuccinates in which the fatty alcohol groups are derived from ethoxylated fatty alcohols with a narrow homolog distribution are particularly preferred. Likewise, alkyl(ene)succinic acids or their salts having preferably 8 to 18 carbon atoms in the alkyl(ene) chain can also be used.

[0105] Particularly preferred anionic surfactants are soaps. Saturated and unsaturated fatty acid soaps are also suitable, such as salts of lauric acid, myristic acid, palmitic acid, stearic acid, (hydrogenated) erucic acid and behenic acid, and especially mixtures of soaps derived from natural fatty acids (such as coconut, palm kernel, olive oil or tallow fatty acids).

[0106] The anionic surfactants (including soaps) can be in the form of their sodium, potassium or ammonium salts, as well as soluble salts of organic bases (such as monoethanolamine, diethanolamine or triethanolamine). Preferably, the anionic surfactants are in the form of their sodium or potassium salts, especially in the form of sodium salts.

[0107] The zwitterionic surfactants that can be used according to the invention are surface-active compounds having at least one quaternary ammonium group and at least one -CO2- or -SO3- group in the molecule. Particularly preferred zwitterionic surfactants in this regard are betaine surfactants, such as alkyl or alkylamidopropyl betaines. In particular, betaines are preferred here, such as ammonium salts of N-alkyl-N,N-dimethylglycine, such as ammonium cocoalkyldimethylglycinate, ammonium N-acylaminopropyl-N,N-dimethylglycine, such as ammonium cocoacylaminopropyldimethylglycinate, C12-C18-alkyl dimethyl acetyl betaine, cocoamidopropyl dimethyl acetyl betaine, 2-alkyl-3-carboxymethyl-3-hydroxyethyl imidazoline and sulfobetaines, where the alkyl or acyl group each has 8 to 18 carbon atoms, and cocoacylaminoethyl hydroxyethyl carboxymethyl glycinate. A particularly preferred zwitterionic surfactant is N,N-dimethyl-N-(laurylamidopropyl)ammonium acetyl betaine, which is known by the INCI name cocoamidopropyl betaine.

[0108] Other suitable zwitterionic surfactants are formed from the groups of zwitterionic acetates and zwitterionic diacetates (especially, for example, coco- or lauro-zwitterionic acetate or diacetate), the groups of zwitterionic propionates and zwitterionic dipropionates, and the group of amino acid-based surfactants, the group of amino acid-based surfactants such as acylglutamates, especially disodium coco-12-glutamate and sodium coco-glutamate, acylglycinates, especially sodium coco-glycinate, and acylsarcosinates, especially ammonium lauroylsarcosinate and sodium coco-sarcosinate.

[0109] The at least one additional surfactant present in step c) of the method according to the invention is preferably selected from biosurfactants different from rhamnolipids, preferably glycolipids, more preferably selected from sophorolipids and trehalolipids.

[0110] A preferred method according to the invention is characterized in that the method comprises

[0111] d) adjusting the pH of the preparation to 4.0 to 8.0, preferably 4.5 to 7.4, particularly preferably 5.0 to 7.2.

[0112] The preparation prepared according to the method of the invention is in particular a physically stable preparation. In the context of the present invention, the term "physically stable preparation containing at least one ceramide" is in particular understood to mean a preparation which, after storage at 25 °C for six months, in particular does not exhibit any crystallization of ceramides and sphingoid bases and does not show any separation or inhomogeneity.

[0113] The present invention further relates to the use of mono-rhamnolipid for solubilizing and / or physically stabilizing ceramide-containing compositions, in particular with respect to homogeneity, and / or for preventing crystallization of at least one ceramide in the composition, preferably in an amount of 0.1% to 15.0% by weight, preferably 0.5% to 10.0% by weight, more preferably 1.0% to 8.0% by weight, where the percentages are relative to the total composition.

[0114] In the context of the use according to the invention, the ceramide-containing composition is preferably the same as the preferred composition according to the invention, in particular with respect to components A) and B).

[0115] The examples given below describe the invention by way of illustration, without any intention of restricting the invention to the embodiments specified in the examples, the scope of application of the invention being evident from the entire description and the claims. Examples

[0116] Example 1: Preparation of high-concentration mono-rhamnolipid

[0117] The mono-rhamnolipid is produced by fermenting the Pseudomonas strain pBBR1MCS2-Plac-rhIAB, which is produced in exactly the same way as the Pseudomonas strain pBBR1MCS2-Plac-rhIABC-T-Ptac-rhIC-T described in EP2786743, but the Bsu36I restriction site is directly inserted behind the stop codon of the rhIB gene, thus omitting rhIC. The preculture in shake flasks was carried out as described in EP2598646. For the main culture, the mineral medium (M9) was also used. The fermentation was carried out in a 2-liter fermenter by glucose feed input in a carbon-limited manner. The glucose feed input was referenced to the dissolved oxygen signal. The dissolved oxygen was adjusted to 20% saturation by the stirrer speed. The pH was adjusted to 7 by the pH electrode and adding 2M sulfuric acid or 20 wt% ammonia water. To prevent excessive foaming of the fermentation broth, the antifoaming agent Dow Corning 1500 was added as needed. The fermentation was carried out for 4 days until the dry biomass was 16 g / L. The mono-rhamnolipid concentration was determined by HPLC and it was 8.5 g / L.

[0118] After separating the cells by centrifugation at 10,000 g, the fermentation broth was adjusted to pH 3.1 by adding concentrated H2SO4.

[0119] A multiphase composition was obtained, separated by centrifugation at 10,000 g, and the upper aqueous phase was discarded.

[0120] The remaining part was further processed.

[0121] The compositions listed in Table 1 were obtained by raising the pH with KOH(aq) and diluting with water to the given mono-rhamnolipid concentration; the weight percentages are relative to the total composition.

[0122] Example 2: Preparation of a clarified aqueous ceramide solution

[0123] The dissolution ability was investigated by mixing the mono-rhamnolipid with ceramide.

[0124] Ceramide was added to the mono-rhamnolipid solution and heated to 50 °C, then water was added in the proportions given in Table 1 and the pH was adjusted to the given value. The solution was cooled to room temperature and directly subjected to optical evaluation 24 hours after solution preparation.

[0125] The evaluation of the maximum amount of dissolved ceramide depends on the mixture producing a clarified formulation. The samples were evaluated visually and also by microscopic analysis using polarized light. When no light was observed in the sample, the solution was free of crystals and was defined as clarified.

[0126] As shown in Table 1, surprisingly, the combination of monorhamnolipid and ceramide produced a clear solution, while the combination of ceramide and dirhamnolipid or PEG-40 hydrogenated castor oil produced a turbid solution.

[0127] Table 1: Examples of combinations of monorhamnolipid, dirhamnolipid, PEG-40 hydrogenated castor oil and ceramide

[0128]

[0129]

[0130] Example 3

[0131] The dissolution ability was studied by mixing monorhamnolipid with ceramide.

[0132] Ceramide was added to the monorhamnolipid solution and heated to 70 °C. Then water was added in the proportions given in Table 1 and the pH was adjusted to the given value. The solution was cooled to room temperature and optically evaluated directly 24 hours after solution preparation.

[0133] The evaluation of the maximum amount of dissolved ceramide depended on the mixture producing a clear formulation. The samples were evaluated visually and also by microscopic analysis using polarized light. When no light was observed through the sample, the solution was free of crystals and was by definition clear.

[0134] As shown in Table 2, surprisingly, the combination of monorhamnolipid and ceramide produced a clear solution, while the combination of ceramide and dirhamnolipid or PEG-40 hydrogenated castor oil produced a turbid solution.

[0135] Table 2: Examples of combinations of monorhamnolipid, dirhamnolipid, PEG-40 hydrogenated castor oil and ceramide

[0136]

[0137]

[0138] Formulation examples

[0139] "Composition A" hereinafter refers to the following two compositions A1 and A2, the numbers given in weight %:

[0140] Composition A1 Composition A2 L-(+)-Lactic acid 3 3 Ceramide NP 3 - Ceramide NG - 3 Monorhamnolipid from Example 1 75 75 Water Added to 100 Added to 100 pH 3 pH 3

[0141] Therefore, each formulation listed below is disclosed in two versions.

[0142] Example formulation 1: Volume and Body Shampoo

[0143]

[0144]

[0145] Example Preparation 2: Repair Shampoo

[0146]

[0147]

[0148] Example Preparation 3: Anti-Dandruff Shampoo

[0149]

[0150]

[0151] Example Preparation 4: Strengthening Shampoo

[0152] Ingredient ％ Water Added to 100 Sodium lauryl sulfate 6.0 Sodium laureth sulfate 4.0 Cocamidopropyl betaine 3.0 Composition A 3.0 Ethylene glycol distearate 2.5 Polydimethylsiloxane 2.0 Sodium citrate 1.5 Cocamide MEA 1.0 Sodium xylene sulfonate 1.0 Citric acid Adjusted to pH 5.0 Sodium benzoate 0.7 Sodium chloride 0.8 Sodium ethylenediaminetetraacetate 0.3 Polyquaternium-6 0.5 Honey (Mel) 0.5 Apricot (Prunus Armeniaca) fruit extract 0.5 Methylchloroisothiazolinone 0.1 Methylisothiazolinone 0.1 Fragrance, dye q.s.

[0153] Example Preparation 5: Shampoo

[0154] Ingredient ％ Water Added to 100 Sodium laureth sulfate 9.0 Cocamidopropyl betaine 3.0 Composition A 3.0 Glycerol 2.5 Sodium chloride 1.7 Ethylene glycol distearate 1.5 Panthenol 0.2 Propylene glycol 0.3 Hydroxypropyl guar hydroxypropyltrimonium chloride 0.3 Sodium benzoate 0.7 PEG-55 propylene glycol oleate 0.5 Citric acid Adjusted to pH 5.5 Hydrolyzed wheat protein 0.3 Argan (Argania Spinosa) kernel oil 0.1 Laureth-4 0.5 Potassium sorbate 0.2 Fragrance, dye q.s.

[0155] Example Preparation 6: Moisturizing Shampoo

[0156]

[0157]

Claims

1. A composition comprising A) at least one ceramide, and B) at least one rhamnolipid, Characterized in that, Component B) comprises at least 50% by weight of mono-rhamnolipid, where the percentage by weight is relative to all rhamnolipids comprised in the total composition.

2. The composition according to claim 1, wherein The at least one ceramide is selected from the group consisting of ceramide NP, ceramide AP, ceramide EOP, ceramide NG, ceramide ADS, ceramide EODS, ceramide NS, ceramide AS, ceramide EOS, ceramide NH, ceramide AH, and ceramide EOH, preferably selected from the group consisting of ceramide NP, ceramide NG, ceramide AP, and most preferably ceramide NP.

3. The composition according to claim 1 or 2, characterized in that, Component A) is comprised in an amount of 0.0005% to 5.0% by weight, more preferably 0.001% to 2.0% by weight, more preferably 0.002% to 1.5% by weight, even more preferably 0.05% to 1.0% by weight, where the percentage by weight is relative to the total composition.

4. The composition according to at least one of the preceding claims, characterized in that, Component B) comprises 12% to 32% by weight monoRL-C8C10, 51% to 81% by weight monoRL-C10C10, 1% to 9% by weight monoRL-C10C12, 1% to 9% by weight monoRL-C10C12:1, where the percentage by weight refers to all mono-rhamnolipids comprised in the composition.

5. The composition according to at least one of the preceding claims, characterized in that Component B) is comprised in an amount of 0.1% to 15.0% by weight, preferably 0.5% to 10.0% by weight, more preferably 1.0% to 8.0% by weight, where the percentage by weight is relative to the total composition.

6. The composition according to at least one of the preceding claims, characterized in that, It comprises C) cholesterol and / or at least one cholesterol derivative selected from cholesterol sulfate, cholesteryl hydrogen succinate, and 7-dehydrocholesterol, where preferably component C) is comprised in an amount of 0.01% to 3.0% by weight, preferably 0.02% to 2.0% by weight, more preferably 1.0% to 0.05% by weight, where the percentage by weight is relative to the total composition.

7. The composition according to at least one of the preceding claims, characterized in that, It comprises d) at least one sphingoid base where preferably component D) is comprised in an amount of 0.001% to 2.0% by weight, preferably 0.002% to 1.5% by weight, more preferably 0.05% to 1.0% by weight, where the percentage by weight is relative to the total composition.

8. The composition according to at least one of the preceding claims, characterized in that, It comprises in place of component D) or in addition to component D) the following component E) at least one fatty acid, which is preferably selected from fatty acids having 12 to 28 carbon atoms, especially palmitic acid, stearic acid, octadecanoic acid, arachidic acid, behenic acid, docosanoic acid, and tetracosanoic acid, where preferably component E) is comprised in an amount of 0.01% to 3.0% by weight, preferably 0.02% to 2.0% by weight, more preferably 1.0% to 0.05% by weight, where the percentage by weight is relative to the total composition.

9. The composition according to at least one of the preceding claims, characterized in that, The composition has a pH of 4.0 to 8.0, preferably 4.5 to 7.4, particularly preferably 5.0 to 7.

2.

10. The composition according to at least one of the preceding claims, characterized in that, The composition comprises water, preferably from 75.0% to 99.5% by weight, more preferably from 80.0% to 98.5% by weight, even more preferably from 85.0% to 98.0% by weight, based on the total composition.

11. A method for producing a cosmetic or pharmaceutical preparation comprising at least one ceramide, which method comprises the following steps: a) providing a composition according to at least one of claims 1 to 10; b) adding a cosmetically or pharmaceutically acceptable carrier and preferably adding a further cosmetic and pharmaceutical preparation ingredient.

12. The method according to claim 11, wherein The method comprises c) solubilization of the preparation.

13. The method according to claim 11 or 12, characterized in that The method comprises d) adjusting the pH of the preparation to from 4.0 to 8.0, preferably from 4.5 to 7.4, particularly preferably from 5.0 to 7.

2.

14. Use of monorhamnolipid for solubilizing and / or physically stabilizing a ceramide-containing composition, in particular with respect to homogeneity, and / or for preventing crystallization of at least one ceramide in the composition, preferably in an amount of from 0.1% to 15.0% by weight, preferably from 0.5% to 10.0% by weight, more preferably from 1.0% to 8.0% by weight, where the percentages are relative to the total composition.

Images