Composition comprising ceramide and mono-rhamnolipid

Abstract

To provide compositions comprising ceramides with a clear appearance.SOLUTION: A composition comprising A) at least one ceramide and B) at least one rhamnolipid is provided, wherein the component B) comprises at least 50 wt.% mono-rhamnolipids, and the weight percentages refer to all rhamnolipids comprised in the total composition. A method for producing a cosmetic or pharmaceutical formulation comprising at least one ceramide is also provided.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition containing ceramide and monolam-nolipid.

Background Art

[0002] Ceramide is a kind of lipophilic amide that forms the lipid matrix of the skin together with fatty acids and cholesterol. These amides play an important role in cosmetics and are ingredients established in various formulations for their beneficial effects on the skin barrier, transepidermal water loss, and further functions. Many formulations are based on emulsions containing more oil. Since ceramide is a poorly soluble substance in an aqueous environment, only a few aqueous formulations are known.

[0003] International Publication No. 2023 / 161179 discloses a liposome composition containing a biosurfactant and the use of the liposome composition for encapsulating at least one active ingredient of a cosmetic, a pharmaceutical, and / or a dietary supplement. Thereby, a liposome composition is provided that enables solubilization of poorly soluble substances and has excellent long-term stability in terms of reprecipitation.

[0004] Korean Patent Publication No. 2019-0080060 discloses a transparent formulation containing ceramide. One of the drawbacks of these formulations is the use of an ethoxylated surfactant. Another drawback is the need for an oily compound, which may not be desirable for aqueous applications.

[0005] U.S. Patent No. 8,313,755 discloses a clear aqueous ceramide composition using a polyhydric alcohol.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object of the present invention is to provide a composition containing ceramide having a clear appearance.

Means for Solving the Problems

[0008] Surprisingly, it has been found that the combination of monolamellar lipid and ceramide results in a clear aqueous composition.

[0009] Therefore, the present invention provides a composition containing monolamellar lipid and ceramide.

[0010] One of the advantages of the composition according to the present invention is that the deposition of ceramide on the skin is enhanced.

[0011] A further advantage is that the penetration of ceramide is improved in the presence of monolamellar lipid.

[0012] Another advantage is the very high compatibility with organic acids.

[0013] Another advantage is that the foam quality of the composition according to the present invention is improved.

[0014] A further advantage is the foam enhancing effect of the composition according to the present invention.

[0015] Another advantage is the good compatibility of the composition according to the present invention with other components.

[0016] A further advantage is that skin barrier protection is enhanced.

[0017] A further advantage is that the deposition of ceramides on the hair is enhanced in the composition according to the invention.

[0018] A further advantage is that the skin feel of the composition according to the invention is improved.

[0019] A further advantage is that the conditioning effect on the hair is improved by the composition according to the invention.

[0020] A further advantage is that the thickening property of the formulation is improved.

[0021] A further advantage is that the composition according to the invention can be easily incorporated into various formulations.

[0022] Another advantage is that the composition according to the invention can be obtained without a heating step.

[0023] Another advantage is the high stability of the composition according to the invention.

[0024] A further advantage is the low irritation of the composition according to the invention.

[0025] Accordingly, the present invention provides A) at least one ceramide, and B) at least one rhamnolipid in a composition, characterized in that component B) comprises at least 50% by weight of monorhamnolipid, the weight percentage being based on the total rhamnolipids comprised in the whole composition.

[0026] In the context of the present invention, the term "ceramide" is understood to mean an acylated sphingoid base, where the sphingoid base is preferably selected from sphingosine, sphinganine, 6-hydroxysphingosine and phytosphingosine and is also in glycosylated form such as glucosylceramide.

[0027] When determining the amount of ramnolipid, only the mass of the ramnolipid is considered, and when the ramnolipid exists as a salt, the counterion of the salt is ignored.

[0028] When the average value is described below, unless otherwise specified, it is the number average value.

[0029] Unless otherwise specified, the percentage is data in weight percent. The same applies to parts per million (ppm).

[0030] When the measured value is described below, unless otherwise specified, it is always determined at a temperature of 25 °C and a pressure of 1013 mbar.

[0031] Preferred compositions according to the present invention are characterized in that at least one of the above ceramides is selected from the group consisting of, preferably 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 selected from the group consisting of ceramide NP, ceramide NG, ceramide AP and ceramide EOP, and most preferably ceramide NP.

[0032] Preferred compositions according to the present invention are characterized in that component A) is included in an amount of 0.0005 wt% to 5.0 wt%, more preferably 0.001 wt% to 2.0 wt%, more preferably 0.002 wt% to 1.5 wt%, and even more preferably 0.05 wt% to 1.0 wt%, based on the total composition, where the weight percentage is based on the entire composition.

[0033] Preferred compositions according to the present invention are characterized in that the above composition contains at least two ceramides, preferably at least three ceramides, and particularly preferably exactly three ceramides.

[0034] The term "ramnolipid" in the context of the present invention preferably refers in particular to general formula (I) [Chemical formula] [wherein, mRL = 2, 1 or 0, preferably 1 or 0, nRL = 1 or 0, R 1RL and R 2RL are, independently of one another, identical 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 monovalent, divalent or trivalent unsaturated alkyl residues, preferably pentenyl, heptenyl, nonenyl, undecenyl and tridecenyl, and o = 1 to 23, preferably 4 to 12, of (CH2) o -CH3 selected from the group consisting of] and salts thereof are understood to mean.

[0035] When 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).

[0036] The term "dirhamnolipid" in the context of the present invention is understood to mean a compound of general formula (I) wherein nRL = 1 or a salt thereof.

[0037] The term "monorhamnolipid" in the context of the present invention is understood to mean a compound of general formula (I) wherein nRL = 0 or a salt thereof.

[0038] Different rhamnolipids are abbreviated according to the following nomenclature: "diRL-CXCY" means the residues R 1RL and R 2RLOne of them is (CH2) where o = X - 4 o -CH3, and the remaining residue R 1 or R 2 is (CH2) where o = Y - 4 o -CH3, is understood to mean the dilamunolipid of general formula (I).

[0039] "Mono RL - CXCY" means that one of the residues R 1RL and R 2RL is (CH2) where o = X - 4 o -CH3, and the remaining residue R 1RL or R 2RL is (CH2) where o = Y - 4 o -CH3, is understood to mean the monolaramunolipid of general formula (I).

[0040] Therefore, in the nomenclature used, "CXCY" and "CYCX" are not distinguished.

[0041] For lamunolipids with mRL = 0, mono RL - CX or di RL - CX is used as appropriate.

[0042] When one of the above subscripts X and / or Y is appended with ":Z", each 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.

[0043] The lamunolipids listed below, considering that they contain dilamunolipids, can be adjusted to the desired high monolaramunolipid content, for example, by ramunocidase.

[0044] The rhamnolipids that can be applied in the context of the present invention can also be produced by the fermentation of Pseudomonas bacteria, which are preferably non-genetically modified cells, especially Pseudomonas aeruginosa. This technology was already disclosed in the 1980s, as described, for example, in European Patent Application Publication No. 0282942 and German Patent Application Publication No. 4127908. Rhamnolipids produced by Pseudomonas aeruginosa cells improved by genetic recombination to have a higher rhamnolipid titer can also be used in the context of the present invention. Such cells are disclosed, for example, by Lei et al. in Biotechnol Lett. 2020 Jun;42(6):997-1002.

[0045] 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, and from Locus Bio-Energy Solutions and Shanghai Yusheng Industry Co., Ltd., for example, under the trade name Bio-201 Glycolipids.

[0046] The composition according to the present invention preferably has component B) 12% to 32% by weight of mono RL-C8C10, 51% to 81% by weight of mono RL-C10C10, 1% to 9% by weight of mono RL-C10C12, 1% to 9% by weight of mono RL-C10C12:1 comprising, with the weight percentage being based on all monolamellar lipids contained in the composition, which is characterized thereby.

[0047] A preferred composition according to the present invention is characterized in that it is a non-liposomal composition.

[0048] The term "non-liposomal composition" means that the composition does not contain liposomes.

[0049] A preferred composition according to the present invention is characterized in that it does not contain phospholipids.

[0050] A preferred composition according to the present invention is characterized by containing particles having an average particle size in the range of 13 nm or less, preferably 3 nm to 12 nm.

[0051] Photon correlation spectroscopy is preferably used to determine the average particle size at a total concentration of 0.5 wt% of component A) using a composition containing water. The measurement is performed using a Zetasizer Nano ZS90 from Malvern Instruments Ltd. in the UK according to the manufacturer's instructions. The Z-average is the intensity-weighted average hydrodynamic size of the ensemble of the particle population 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 function fit is applied to the autocorrelation function (see Zetasizer Nano ZS90 User Manual MAN0485-1-1 09 June 2017).

[0052] A preferred composition according to the present invention is characterized in that component B) is contained in an amount of 0.1 wt% to 15.0 wt%, preferably 0.5 wt% to 10.0 wt%, more preferably 1.0 wt% to 8.0 wt%, with the weight percentage being based on the whole composition.

[0053] According to the present invention, the weight ratio of component A) to component B) in the composition according to the present invention is preferably 0.0005:15 to 0.1:1, preferably 0.005:10 to 0.5:5, and particularly preferably 0.05:7 to 0.1:5.

[0054] A preferred composition according to the present invention C) cholesterol and / or at least one cholesterol derivative selected from the group consisting of cholesterol sulfate, cholesteryl hydrogen succinate, and 7-dehydrocholesterol is characterized by comprising.

[0055] Preferably, component C) is contained in an amount of 0.01% by weight to 3.0% by weight, preferably 0.02% by weight to 2.0% by weight, more preferably 1.0% by weight to 0.05% by weight, and the weight percentage is based on the whole composition.

[0056] A preferred composition according to the present invention D) at least one sphingoid base, preferably a sphingoid base selected from the group consisting of sphingosine, sphinganine, 6-hydroxysphingosine, N-acetylphytosphingosine, and phytosphingosine, particularly phytosphingosine is characterized by comprising.

[0057] Preferably, component D) is contained in an amount of 0.001% by weight to 2.0% by weight, preferably 0.002% by weight to 1.5% by weight, more preferably 0.05% by weight to 1.0% by weight, and the weight percentage is based on the whole composition.

[0058] A preferred composition according to the present invention, instead of or in addition to component D), E) at least one fatty acid, preferably a fatty acid containing 12 to 28 carbon atoms, particularly a fatty acid selected from the group consisting of palmitic acid, stearic acid, octadecanoic acid, arachidic acid, behenic acid, docosanoic acid, and lignoceric acid is characterized by comprising.

[0059] Preferably, component E) is contained in an amount of 0.01% to 3.0% by weight, preferably 0.02% to 2.0% by weight, more preferably 0.05% to 1.0% by weight, and the weight percentage is based on the entire composition.

[0060] A preferred composition according to the present invention is characterized by having a pH in the range of 4.0 to 8.0, preferably 4.5 to 7.4, particularly preferably 5.0 to 7.2.

[0061] "pH" in relation to the present invention is defined as the value measured for the relevant composition at 22°C after stirring for 5 minutes using a pH electrode calibrated in accordance with ISO 4319 (1977).

[0062] A preferred composition according to the present invention is characterized by containing water in the range of 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 entire composition.

[0063] The present invention relates to a method for producing a cosmetic or pharmaceutical formulation containing at least one ceramide, a) a method step of preparing a composition according to the present invention, b) a method step of adding a carrier acceptable in cosmetics or pharmaceuticals, preferably water, and preferably further one component of a cosmetic and pharmaceutical formulation and further relates to a method comprising.

[0064] The above further one component of a cosmetic and pharmaceutical formulation in step b) is of course different from any of the components A) to E) contained in the composition of the present invention.

[0065] A preferred composition according to the present invention is preferably used in the context of the method according to the present invention.

[0066] The components of the above further cosmetic and pharmaceutical formulations, which are preferably added in step b) of the method of the present invention, are preferably selected from the group consisting of surfactants, emollients, emulsifiers, thickeners, ultraviolet protection screening agents, antioxidants, hydrotropes, solids and fillers, film formers, pearlescent additives, opacifiers, deodorizing and antiperspirant active ingredients, insect repellents, self-tanning agents, preservatives, quality improvers, fragrances, dyes, odor absorbers, superfatting agents and solvents, preferably from the group consisting of fragrances, quality improvers and thickeners.

[0067] A preferred method according to the present invention is that the above method c) solubilizing the formulation is characterized by comprising.

[0068] As a result, the cosmetic or pharmaceutical formulation produced by the method according to the present invention is preferably an aqueous surfactant formulation.

[0069] In order to facilitate the solubilization step c) of the method according to the present invention, according to the present invention, it is preferred that at least one additional surfactant is present in method step c).

[0070] The at least one additional surfactant present in method step c) of the present invention is preferably selected from the group consisting of anionic, cationic, nonionic, semi-polar, amphoteric and zwitterionic surfactants.

[0071] The nonionic surfactant used is preferably alkoxylated, advantageously ethoxylated, and in particular a primary alcohol having preferably 8 to 18 carbon atoms and on average 1 to 12 moles of ethylene oxide (EO) per mole of alcohol. In this case, the alcohol radical may be linear or preferably branched at the 2-position methyl, or may contain a mixture of linear radicals and methyl-branched radicals as commonly present in oxo alcohol radicals. However, in particular, an alcohol ethoxylate having a linear radical derived from a natural origin alcohol having 12 to 18 carbon atoms, such as coconut, palm, tallow or oleyl alcohol, and having on average 2 to 8 EO per mole of alcohol is preferred. 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, 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 described is a statistical average value and can be an integer or a fraction for a particular product. Preferred alcohol ethoxylates have a narrow homolog distribution.

[0072] In addition to these nonionic surfactants, it is also possible to use fatty alcohols having more than 12 EO. Examples thereof are tallow fatty alcohols having 14 EO, 25 EO or 40 EO. It is also possible to use nonionic surfactants containing EO and PO (propylene oxide) groups together in the molecule. In this connection, it is possible to use not only block copolymers having EO-PO block units or PO-EO block units, but also EO-PO-EO copolymers or PO-EO-PO copolymers.

[0073] It is of course also possible to use a mixed alkoxylated nonionic surfactant in which the EO units and PO units are not in block form but are randomly distributed. Such products can be obtained as a result of the simultaneous action of ethylene oxide and propylene oxide on a fatty alcohol.

[0074] Furthermore, alkyl glycosides can also be used as further nonionic surfactants.

[0075] A further type of nonionic surfactant that is preferably used, either 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 a fatty acid methyl ester, for example as described in JP-A-58 / 217598 or preferably prepared by the method described in WO 90 / 13533.

[0076] 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 may also be suitable. The amount of these nonionic surfactants preferably does not exceed the amount of the ethoxylated fatty alcohol, especially does not exceed half of it.

[0077] A further suitable surfactant is a polyhydroxy fatty acid amide. A polyhydroxy fatty acid amide is a substance that can usually be obtained by reductively aminating a reducing sugar with ammonia, an alkylamine or an alkanolamine, followed by acylation with a fatty acid, a fatty acid alkyl ester or a fatty acid chloride.

[0078] More suitable nonionic surfactants are polyglycerol partial esters based on monocarboxylic acids and dicarboxylic acids, as well as crosslinked polyglycerol partial esters based on monocarboxylic acids and dicarboxylic acids.

[0079] The anionic surfactants used are, for example, of the sulfonate and sulfate types. Suitable sulfonate-type surfactants here are preferably C9-C13 alkylbenzene sulfonates, olefin sulfonates, i.e., mixtures of alkene sulfonates and hydroxyalkane sulfonates, and further, for example, disulfonates obtained by sulfonating C12-C18 monoolefins having terminal or internal double bonds with gaseous sulfur trioxide and subsequently hydrolyzing the sulfonation product with an alkali or an acid. Alkane sulfonates obtained from C12-C18 alkanes, for example, by sulfochlorination or sulfoxidation followed by hydrolysis or neutralization, are also suitable. 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.

[0080] More suitable anionic surfactants are sulfated fatty acid glycerol esters. Fatty acid glycerol esters are understood to mean monoesters, diesters and triesters, and mixtures thereof, obtained by the esterification of monoglycerol with 1-3 mol of fatty acid or by the transesterification of triglycerides with 0.3-2 mol of glycerol. Preferred sulfated fatty acid glycerol esters here are the sulfation products of saturated fatty acids having 6-22 carbon atoms, such as caproic acid, caprylic acid, capric acid, myristic acid, lauric acid, palmitic acid, stearic acid or behenic acid.

[0081] Preferred alkyl (alkenyl) sulfates are, for example, the half-esters of sulfuric acid of C12 - C18 fatty alcohols derived from coconut fatty alcohol, tallow fatty alcohol, lauryl, myristyl, cetyl or stearyl alcohol, or C10 - C20 oxo alcohols, and the alkali metal salts, especially the sodium salts, of the half-esters of secondary alcohols of these chain lengths. Further preferred are alkyl (alkenyl) sulfates of a specified chain length that contain synthetic linear alkyl radicals prepared on a petrochemical basis and have a decomposition behavior similar to that of suitable compounds based on fatty chemical raw materials.

[0082] Also suitable are linear or branched C7 - C20 alcohols ethoxylated with 1 - 6 mol of ethylene oxide, such as 2-methyl branched C9 alcohol having an average of 3.5 mol of ethylene oxide (EO), or the sulfuric acid monoesters of C12 - C18 fatty alcohols having 1 - 4 EO. These are used in the cleaning composition in a relatively small amount, for example, in an amount of 1 - 5 wt%, because of their high foaming behavior.

[0083] Furthermore, more preferred anionic surfactants are the salts of alkyl sulfosuccinic acid, which are also referred to as sulfosuccinates or sulfosuccinic esters and consist of the mono- and / or diesters of sulfosuccinic acid with alcohols, preferably fatty alcohols, especially ethoxylated fatty alcohols. Preferred sulfosuccinates contain C8 - C18 fatty alcohol radicals or mixtures thereof. Particularly preferred sulfosuccinates contain fatty alcohol radicals derived from ethoxylated fatty alcohols. In this context, sulfosuccinates derived from ethoxylated fatty alcohols having a narrow homolog distribution are particularly preferred in this case. Similarly, it is also possible to use alkyl (alkenyl) succinic acids or their salts having preferably 8 - 18 carbon atoms in the alkyl (alkenyl) chain.

[0084] Particularly preferred anionic surfactants are soaps. Saturated and unsaturated fatty acid soaps, such as salts of lauric acid, myristic acid, palmitic acid, stearic acid, (hydrogenated) erucic acid and behenic acid, and furthermore soap mixtures derived in particular from natural fatty acids, such as coconut, palm kernel, olive oil or tallow fatty acids, are also suitable.

[0085] Anionic surfactants containing soap may be in the form of their sodium, potassium or ammonium salts, and soluble salts of organic bases such as monoethanolamine, diethanolamine or triethanolamine. Preferably, the anionic surfactant is in the form of its sodium or potassium salt, particularly the sodium salt.

[0086] The amphoteric surfactants that can be used according to the present invention are surfactant compounds having at least one quaternary ammonium group and at least one -CO2- or -SO3- group in the molecule. Particularly preferred amphoteric surfactants in this context are betaine surfactants such as alkyl betaines or alkylamidopropyl betaines. In particular, in each case having 8 to 18 carbon atoms in the alkyl or acyl group, N-alkyl-N,N-dimethylammonium glycinate, such as cocoalkyl dimethylammonium glycinate, N-acylaminopropyl-N,N-dimethylammonium glycinate, such as cocoacylaminopropyl dimethylammonium glycinate, C12-C18 alkyl dimethylacetobetaine, cocoamidopropyl dimethylacetobetaine, betaines such as 2-alkyl-3-carboxymethyl-3-hydroxyethylimidazoline and sulfobetaine, and furthermore cocoacylaminoethyl hydroxyethyl carboxymethyl glycinate are preferred here. A particularly preferred zwitterionic surfactant is N,N-dimethyl-N-(lauroylamidopropyl)ammonium acetobetaine known under the INCI name cocoamidopropyl betaine.

[0087] Even more suitable amphoteric surfactants are amphoacetates and amphodiacetates, in particular, for example, the group of cocoamphoacetate or lauryl amphoacetate, or cocoamphodiacetate or lauryl amphodiacetate, the group of amphopropionates and amphodipropionates, and acylglutamates, in particular disodium cocooyl glutamate and sodium cocooyl glutamate, acylglycinates, in particular cocooyl glycinate, and acylsarcosinates, in particular ammonium lauroyl sarcosinate and sodium cocooyl sarcosinate, etc., which are formed by the group of amino acid-based surfactants.

[0088] At least one of the additional surfactants present in process step c) of the method according to the invention is preferably selected from biosurfactants different from rhamnolipids, preferably from glycolipids, more preferably from sophorolipids and glycolipids.

[0089] A preferred method according to the invention is that the method d) adjusting the pH of the formulation to a range of 4.0 to 8.0, preferably 4.5 to 7.4, particularly preferably 5.0 to 7.2 is characterized by including this.

[0090] The formulation prepared by the method according to the invention is a physically stable formulation in particular. In the context of the present invention, the term "physically stable formulation containing at least one ceramide" particularly means a formulation that shows no crystallization, separation or inhomogeneity of ceramide and sphingoid base after storage at 25°C for 6 months.

[0091] The present invention relates to the solubilization and / or physical stabilization, in particular stabilization with respect to homogeneity, of a ceramide-containing composition and / or to the prevention of crystallization of at least one ceramide in the composition, and further to the use of a monolamellar lipid in an amount of preferably 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 based on the total composition.

[0092] In the context of the use according to the invention, the ceramide-containing composition is preferably equal to the preferred composition according to the invention, in particular with respect to constituents A) and B).

[0093] The examples presented below illustrate the invention and are not intended to limit the invention, the scope of which will be apparent from the entire specification and claims, to the embodiments specified in the examples.

[0094] Examples: Example 1: Preparation of highly concentrated monolamellar lipid The monolamellar lipid was produced by fermentation of Pseudomonas putida strain pBBR1MCS2 - Plac - rhIAB. This strain was prepared in the same manner as Pseudomonas putida strain pBBR1MCS2 - Plac - rhIABC - T - Ptac - rhIC - T described in European Patent Application Publication No. 2786743, but a Bsu36I restriction site was inserted immediately after the stop codon of the rhlB gene, thereby excluding rhlC. The preculture in a shaking flask was carried out as described in European Patent No. 2598646. The same inorganic medium (M9) was used for the main culture. Fermentation was carried out with carbon limitation by glucose feed in a 2 - liter fermenter. The glucose feed was carried out with reference to the dissolved oxygen signal. The dissolved oxygen was adjusted to 20% saturation by the stirrer speed. The pH was adjusted to 7 by adding a pH electrode and 2M sulfuric acid or a 20 wt% ammonia solution. To prevent excessive foaming of the fermentation broth, antifoaming agent Dow Corning 1500 was added as necessary. Fermentation was carried out for 4 days until a dry biomass of 16 g / L was obtained. The monolamellar lipid concentration was determined by HPLC and was 8.5 g / L.

[0095] After separating the cells by centrifugation at 10000 g, concentrated H2SO4 was added to adjust the fermentation broth to pH 3.1.

[0096] A multiphase composition was obtained, which was separated by centrifugation at 10000 g, and the upper aqueous phase was discarded.

[0097] The remainder was further processed.

[0098] The compositions listed in Table 1 were obtained by raising the pH using KOH (aqueous solution) and diluting with water to a given monolamellar lipid concentration. The weight percentages are based on the whole composition.

[0099] Example 2: Preparation of a Clear Aqueous Solution of Ceramide The solubility of the monolamellar lipid was investigated by mixing it with ceramide.

[0100] Ceramide was added to the monolamellar lipid solution, heated to a temperature of 50°C, then water was added at the ratio shown in Table 1, and the pH was adjusted to a given value. The solution was cooled to room temperature, and optical evaluations were performed immediately after the preparation of the solution and 24 hours later.

[0101] The evaluation of the maximum amount of solubilized ceramide is determined by the mixture that results in a clear formulation. The samples were evaluated visually and further by microscopic analysis using polarization. When no illumination of the sample is observed, the solution does not contain crystals and is clear by definition.

[0102] As shown in Table 1, surprisingly, a clear solution was formed by the combination of monolamellar lipid and ceramide, while the combination of ceramide and dilamellar lipid or PEG-40 hydrogenated castor oil resulted in a turbid solution.

[0103] [Table 1]

[0104] Example 3 The solubilizing ability of the monolamellar lipid was examined by mixing it with ceramide.

[0105] Ceramide was added to the monolamellar lipid solution, heated to a temperature of 70°C, then water was added at the ratio shown in Table 1, and the pH was adjusted to a given value. The solution was cooled to room temperature, and optical evaluations were performed immediately after the preparation of the solution and 24 hours later.

[0106] The evaluation of the maximum amount of solubilized ceramide is determined by the mixture that results in a clear formulation. The samples were evaluated visually and further by microscopic analysis using polarization. When no illumination of the sample is observed, the solution does not contain crystals and is clear by definition.

[0107] As shown in Table 2, surprisingly, a clear solution was formed with the combination of monolam no lipid and ceramide, while the combination of ceramide and dilam no lipid or PEG-40 hydrogenated castor oil resulted in a turbid solution.

[0108]

Table 2

[0109] Formulation Example Hereinafter, "Composition A" refers to the following two compositions A1 and A2, and the numerical values are shown in weight %:

Table 3

[0110] Therefore, each of the following formulations is disclosed in two versions.

[0111]

Table 4

[0112]

Table 5

[0113]

Table 6

[0114]

Table 7

[0115]

Table 8

[0116]

Table 9

Claims

1. A) at least one ceramide, and B) at least one rhamnolipid In the composition comprising: Component B) contains at least 50% by weight of monorhamnolipid, and the weight percentage is based on all rhamnolipids contained in the whole composition, characterized in that it is a composition.

2. 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, the composition according to claim 1.

3. Component A) is contained 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, and the weight percentage is based on the whole composition, the composition according to claim 1 or 2.

4. Component B) is 12% to 32% by weight of mono RL-C8C10, 51% to 81% by weight of mono RL-C10C10, 1% to 9% by weight of mono RL-C10C12, 1% to 9% by weight of mono RL-C10C12:1 The composition according to at least one of claims 1 to 3, characterized in that the weight percentage is based on all monorhamnolipids contained in the composition.

5. Component B) is contained 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, and the weight percentage is based on the whole composition, the composition according to at least one of claims 1 to 4.

6. The composition is C) cholesterol and / or at least one cholesterol derivative selected from the group consisting of cholesterol sulfate, cholesteryl hydrogen succinate and 7-dehydrocholesterol comprising, preferably, component C) being included in an amount of 0.01% to 3.0% by weight, preferably 0.02% to 2.0% by weight, more preferably 0.05% to 1.0% by weight, said weight percentages being based on the total composition, the composition according to at least one of claims 1 to 5.

7. wherein the composition D) at least one sphingoid base is included, preferably, component D) being 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, said weight percentages being based on the total composition, the composition according to at least one of claims 1 to 6.

8. wherein the composition, instead of or in addition to component D), E) at least one fatty acid, preferably a fatty acid containing 12 to 28 carbon atoms, in particular a fatty acid selected from the group consisting of palmitic acid, stearic acid, octadecanoic acid, arachidic acid, behenic acid, docosanoic acid and lignoceric acid is included, preferably, component E) being included in an amount of 0.01% to 3.0% by weight, preferably 0.02% to 2.0% by weight, more preferably 0.05% to 1.0% by weight, said weight percentages being based on the total composition, the composition according to at least one of claims 1 to 7.

9. wherein the composition has a pH in the range of 4.0 to 8.0, preferably 4.5 to 7.4, particularly preferably 5.0 to 7.2, the composition according to at least one of claims 1 to 8.

10. wherein the composition, based on the total composition, preferably contains water in the range of 75.0% to 99.5% by weight, preferably 80.0% to 98.5% by weight, more preferably 85.0% to 98.0% by weight, the composition according to at least one of claims 1 to 9.

11. A method for producing a cosmetic or pharmaceutical formulation comprising at least one ceramide, a) a method step of preparing the composition according to at least one of claims 1 to 10, b) a method step of adding a carrier acceptable in cosmetics or pharmaceuticals and preferably further one component of a cosmetic and pharmaceutical formulation comprising, the method.

12. c) The method according to claim 11, characterized in that it comprises solubilizing the complex.

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

2.

14. Use of a monorhamnolipid in an amount preferably 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, percentages being based on the total composition, for the solubilization and / or physical stabilization, in particular stabilization with respect to homogeneity, of a ceramide-containing composition and / or for the prevention of crystallization of at least one ceramide in the composition.

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