Collagen biovector comprising an anionic micelle-cationic polymer complex, cosmetic composition comprising the same, method for its preparation, and use thereof

Abstract

The invention relates to a composition comprising an anionic micelle–cationic polymer complex as an active ingredient vector, wherein the anionic micelle consists of a compound of Formula (I) and capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II) and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction. The composition optionally comprises additional active ingredient and an excipient, and the anionic micelle-cationic polymer complex active ingredient vector has a diameter in the range of 1 to 10 nm, preferably in the range of 1 to 6 nm. The invention also relates to a method for producing an anionic micelle-cationic polymer complex and a composition containing it, and their use. The anionic micelle–cationic polymer complex structure according to the invention is smaller than expected, which makes it more effective in penetrating the skin and stimulating collagen protein synthesis. A further advantage of the complex is that it is acidic and is stable even in the ideal pH range of the skin.

Description

[0001] COLLAGEN BIOVECTOR COMPRISING AN ANIONIC MICELLE-CATIONIC POLYMER COMPLEX, COSMETIC COMPOSITION COMPRISING THE SAME, METHOD FOR ITS PREPARATION, AND USE THEREOF

[0002] SUMMARY OF THE INVENTION

[0003] The invention relates to a composition containing an anionic micelle-cationic polymer complex as an active ingredient vector, wherein the anionic micelle consists of a compound of Formula (I) and capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II) and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction. The composition optionally comprises additional active ingredient and an excipient, and the active ingredient vector anionic micelle -cationic polymer complex has a diameter in the range of 1 to 10 nm, preferably in the range of 1 to 6 nm. The invention also relates to a method for producing an anionic micellecationic polymer complex and a composition containing it, and their use. The anionic micelle-cationic polymer complex structure according to the invention is smaller than expected, which makes it more effective in penetrating the skin and stimulating collagen protein synthesis. A further advantage of the complex is that it is acidic and is stable even in the ideal pH range of the skin.

[0004] THE STATE OF THE ART

[0005] The outermost layer of the epidermis is called stratum comeum. This layer consists of comeocytes (dead skin cells) and lipids (components of the lipid barrier) that help sealing the gaps between cells. This complex structure forms the skin’s barrier, which prevents the penetration of larger molecules, generally those with a molecular weight above 500 Da. Molecules with a molecular weight of 500 Da or less can effectively penetrate the stratum comeum, although other important factors may also play a role in the penetration of molecules into the deeper layers of the skin, such as the physico-chemical properties of the materials (molecular size, stability, binding affinity, solubility); the duration of penetration; the thickness and composition of the skin; skin metabolism; the place, area, and duration of the application, and the properties of the transdermal penetration enhancer or ingredient.

[0006] There are several publications and proposals for activating the synthesis collagen protein, as collagen plays a fundamental role in providing the structure, strength, and elasticity of tissues. Collagen is the most abundant protein in the human body, accounting for approximately 25% of all human proteins. Collagen is the dominant component of the extracellular matrix (ECM) of connective tissue cells. It plays an important role in regeneration, healing, tissue growth, cell growth, and differentiation. Collagen consists of chains that are twisted into a triple helix. A special amino acid sequence enables the triple helix to be especially stable. The primary amino acid sequence of collagen is glycine -proline -X or glycine-X-hydroxyproline, where X represents any of the other 17 amino acids. Every third amino acid is glycine, and since glycine is the smallest of all the amino acids, it enables a tight chain configuration, thus making it resistant. The process of collagen synthesis takes place in the fibroblast cells both intra- and extracellularly.

[0007] Currently available and topically applicable collagens (such as soluble collagen with a molecular weight of 300,000 Da or hydrolyzed collagen with a molecular weight of 120,000 Da) are unable to penetrate the outer layer of the skin due to their high molecular weight, thus remaining on the skin's surface. Certain low molecular weight amino acids (such as collagen amino acids) and short peptides, with the appropriate formulation background, may be able to penetrate the layers of the epidermis. However, amino acids available on the market and applied in free form are typically found in aqueous solutions, and based on current literature data, there is no clear evidence that they can penetrate the skin's lipid barrier in significant amounts without a carrier molecule or a penetration-enhancing system (see Ramadon, D., Kam, P. R., Anjani, Q. K., Kim, M.-H., Cho, D. Y., Hwang, H., Kim, D. H., Kim, G., Lee, K., Eum, J. H., Im, J. Y., Aileen, V., Hamda, O. T., & Donnelly, R. F. (2024). Delivery of small hydrophilic molecules across the stratum corneum: Identification of model systems and parameters to study topical delivery of free amino acids. International Journal of Pharmaceutics, 660, Article 124372 and Kumar, L., Verma, R., & Singh, S. (2021). Current status of amino acid-based permeation enhancers in transdermal drug delivery. Membranes, 11(5), 343).

[0008] CN105078814A discloses a facial cleansing liquid containing sodium PCA and a hyaluronic acid derivative. The application describes a new composition for a facial cleansing liquid designed to reduce skin irritation, provide effective removal of impurities without excessively drying the skin by the combination of surfactants and moisturizing agents, it has a bactericidal effect and increases skin hydration by 5% after use, which is attributable to the mixture of moisturizing and skin -conditioning agents. The composition comprises water, moisturizing and moisture-retaining agents, soothing ingredients, pH regulators, thickening and stabilizing ingredients, soluble collagen and sodium hyaluronate as moisturizing and skin-conditioning ingredients, plant extracts for their antioxidant and skin-nourishing properties, hydrolyzed elastin to enhance skin elasticity, and finally colloidal gold, which is known for its anti-aging and anti-inflammatory effects.

[0009] CN112168741 A discloses a method for the recognition of skin barrier channels and for the transport of materials through these channels and cell membranes by hydration and liposomes for anti-aging purposes. The method uses liposomes for transporting encapsulated active ingredients that can be either water-soluble or fat-soluble compounds. They comprise zwitterionic moisturizers and various moisturizing compounds such as hyaluronic acid, collagen, vitamins, fatty acids, amino acids, and coenzyme Q10. The advantages of using this composition include its biocompatibility, that the components are released in a controlled manner, it effectively retains skin moisture, wrinkles are visibly reduced, and the signs of skin aging become less visible. The invention described in WO2023198919A1 relates to a new drug delivery system and to topical compositions for application to human skin and to their use in maintaining or improving the condition and appearance of the skin. The composition according to the invention consists of an aqueous dispersion of spheres composed of a lipid bilayer. These spheres consist of a bilayer of lipids encapsulating an aqueous phase comprising at least one active ingredient. The bilayer consists of at least one copolymer (glycerylamidomethyl methacrylate and stearyl methacrylate) and at least one type III ceramide and optionally at least one other compound soluble in the apolar phase. The composition can also comprise active ingredients such as bakuchiol, a-tocopheryl acetate, seawater, Scenedesmus obliquus extract, tranexamic acid, niacinamide, D-panthenol, peptides, probiotics, and vitamin C derivatives. During the manufacturing process, the copolymers are mixed with ceramides and, in some cases, other compounds, and then an aqueous solution containing the active ingredients is added. The composition can be used in various cosmetic or dermatological products that are applied topically to treat healthy skin, prevent aging, moisturize, and support skin homeostasis. Furthermore, the therapeutic application of the composition is also enabled by its effectiveness in treating skin inflammation, restoring the skin after treatment, healing wounds, etc.

[0010] US2008181919A1 describes the formulation and application of a nanomicelle for skin treatment. The nanomicelle consists of an oily substance (extracts of Angelica Radix and Lithospermum Radix) and a phospholipid layer. These components form micelles with a diameter in the nanometer range. The oil is selected from sesame oil, mineral oil, or olive oil fatty acid. The phospholipid layer contains glycerol and phospholipids. The micelles have a diameter of less than 100 nm. Nanomicelles are designed to treat various skin conditions, including wounds, bums, dry skin, cracks, frostbite, ulcers, and proliferative skin diseases. Nanomicelles can also be incorporated into gels or hydrophilic ointments for skin treatment.

[0011] RU2580649C1 discloses a nanoscale delivery system, in particular micelles, for transporting biologically active ingredients. The nanoscale delivery system delivers at least one biologically active ingredient, which can be either soluble or insoluble in water. The active ingredients can include plant extracts such as curcumin, hibiscus, pomegranate, or raspberry ketone. The system can also transport various drug molecules, including antibiotics, antivirals, antispasmodics, analgesics, anti-inflammatories, enzymes, and vitamins (e.g., vitamins A, E, D, and K). Other deliverable active ingredients include salicylic acid, hyaluronic acid and oils.

[0012] W02016043620A1 relates to novel amphiphilic polymers that form nanoscale drug delivery systems suitable for transporting biologically active ingredients. The amphiphilic polymer is produced by one-step radical polymerization in the presence of long -chain aliphatic mercaptans or their derivatives that are capable of controlling chain growth. These polymers form micelles that can transport biologically active ingredients such as plant extracts, vitamins, antibiotics, antiviral agents, and other drugs. The system can be used for ingredients that are difficult or very easy to dissolve in water and it is particularly useful for transporting vitamins, hyaluronic acid, salicylic acid, etc. Fibroblast cells are the main cells of the dermis. They are specialized in the synthesis of collagen and elastin fibers. To stimulate them, the activating molecules must penetrate the stratum comeum, but the skin poses a significant barrier to topically applied preparations, with the stratum comeum itself being the greatest barrier. Due to penetration problems, there is an urgent need for a suitable carrier that can deliver the active ingredients through the skin to their target. The most widely used delivery systems are liposomes, which are used in numerous skincare and anti-aging products. Liposomes are capable of encapsulating various active ingredients, such as collagen and delivering them deep into the cells. Liposomal collagens are collagen amino acids enclosed in liposomes that are able to penetrate the epidermis and the lipid barrier, but due to their complexity, we have very little scientific evidence on how they behave between skin layers and whether they are able to sufficiently release the amino acid mixture enclosed in the liposomes. In addition, liposomes have certain disadvantages. Firstly, liposomes require phospholipids, which are extremely prone to oxidative degradation, making them unstable. Secondly, in order to maintain their stability, liposomes and phospholipids must be stored and handled in an inert nitrogen atmosphere. Thirdly, as phospholipids are of natural origin, their purity varies and they require thorough purification. All these issues contribute to the high cost of liposomal formulations [see Daraee, H., Etemadi, A., Kouhi, M., Alimirzalu, S., & Akbarzadeh, A. (2016). Application of liposomes in medicine and drug delivery. Artificial Cells, Nanomedicine, and Biotechnology, 44(\), 381-391],

[0013] The following patent applications are related to the more extended state of the art. The cosmetic, pharmaceutical, and food industries constantly require antimicrobial agents to preserve perishable products and to directly control microorganisms harmful to humans and animals. Although many antimicrobial compounds are already in use, alternatives are constantly being sought to ensure more targeted treatments and to reduce side effects. WO2020182318 Al discloses an antimicrobial composition, in particular a cosmetic composition, which may contain olivoil PCA K salt, an antimicrobial agent such as capryloyl glycine, hyaluronic acid, cocoyl proline, etc. The new compositions must meet certain criteria, including the following: non-toxic, skin-friendly, stable formulation, odorless, cost-effective to produce, easy to formulate. In addition, they must have a broad-spectrum antimicrobial activity against both Gram -positive and Gram-negative bacteria, yeasts, and molds, especially A. brasiliensis. and must be active in various formulations at different pH values. WO2022122137A1 relates to specific formulations such as hygiene products, deodorants, antiperspirants, and products for treating acne or dandruff comprising a specific 1,2- alkanediol or a 2,3 -alkanediol or a mixture thereof, as well as to a method for reducing excess sebum production on the skin or scalp or for treating dandruff. It uses, among others, olivoil PCA K-salt as an excipient, hyaluronic acid as a film-forming / moisturizing component, and capryloyl glycol as an antimicrobial agent. In the perfume industry there is a particularly high demand for fragrances that even in small doses have a strong effect on other scents and capable to modify them. WO2022218505A1 discloses a solution to this demand by describing a cosmetic composition containing isocitronellol and other fragrances, as well as olivoil PCA K salt and capryloyl glycine as surfactants, hyaluronic acid as a film- forming / moisturizing agent, etc. KR20100013850B1 discloses hydroxypropyl trimonium hyaluronate as a film-forming / moisturizing component for use in cosmetics. Its application in cleansing cosmetic preparations is suitable for enhancing skin and hair affinity and minimizing moisture loss. The cosmetic preparation is formulated and used as a cleansing cream, cleansing foam, cleansing water, solid soap, or liquid soap.

[0014] BRIEF DESCRIPTION OF THE FIGURES

[0015] Figure 1: Autocorrelation functions derived from DLS measurements

[0016] Figure 2: Effect of the anionic micelle -cationic polymer complex according to the invention on collagen synthesis.

[0017] Figure 3: Cross-sectional image of human skin and Raman mapping measurement points Figure 4: Raman mapping results in black and white (using Raman's proprietary software)

[0018] TECHNICAL PROBLEM TO BE SOLVED BY THE INVENTION

[0019] Collagen-producing fibroblast cells are located exclusively in the dermis, i.e., the inner layer of the skin. In case of cosmetic compositions containing active ingredients promoting collagen production, it is therefore crucial that the active ingredients are able to penetrate the skin barrier, i.e., the epidermis. The technical problem to be solved is the production of a complex system that not only contains the building blocks necessary for collagen production i.e. the amino acids glycine, proline and hydroxyproline, but is also able to deliver them to where the collagen production takes place. The object of the invention is to provide an advanced skin care solution by improving the delivery and release of active ingredients through an effective delivery system.

[0020] THE RECOGNITION UNDERLYING THE INVENTION

[0021] An anionic micelle comprised of N-olive oil, L-pyrrolidone carboxylic acid potassium salt and capryloyl glycine was linked with a hydroxypropyl trimonium hyaluronate cationic polymer. Contrary to our previous knowledge, the anionic micelle -cationic polymer complex formed by linking the components surprisingly achieves kinetic stability by the size reduction. This characteristic is especially favorable, as its small size enables it to penetrate the skin effectively. We observed that since our composition contains the building blocks necessary for collagen production, i.e. the amino acids glycine, proline, hydroxyproline, it is also able to deliver them to the suitable location, enabling increased collagen production, thus improving skin elasticity. Due to its cationic character, hyaluronic acid adheres to the negative charges of the skin, thus remaining on the surface of the skin even after washing. We were surprised to find that in addition to the more effective penetration and stimulation of collagen protein synthesis, there is also an increase in cell proliferation activity. Another advantage of the anionic micelle -cationic polymer complex is that it is acidic and has a stable structure within the ideal pH range of the skin.

[0022] BRIEF DESCRIPTION OF THE INVENTION

[0023] 1. A composition comprising: a) an anionic micelle-cationic polymer complex as an active ingredient vector, wherein the anionic micelle consists of the following: i) a compound of Formula (I) wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II) wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally an additional excipient; characterised in that the active ingredient vector according to point a) has a diameter in the range of 1 to 10 nm, preferably in the range of 1 to 6 nm, measured by dynamic light scattering using an LSI Nanolab 3D device at a wavelength of 625 nm, at 25°C. 2. A composition comprising: a) an anionic micelle-cationic polymer complex as an active ingredient, wherein the anionic micelle consists of the following: i) a compound of Formula (I) wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II) wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the anionic micelle-cationic polymer complex according to point a) can be prepared by the following method:

[0024] 1. An aqueous solution of 0.2 to 15.0% by weight of compound (I) and 0.1 to 3.0% by weight crystalline capryloyl glycine are measured and the mixture is heated; 2. During the heating phase, 0.01 to 1.00% by weight KOH is added as a catalyst, and the mixture is heated to 60 to 80°C, preferably 70 to 75°C, and most preferably 70 to 73°C under continuous stirring in order to obtain an anionic lipoamino acid micelle;

[0025] 3. The mixture is cooled to below 40°C and by using the STP method, it is combined with 0.001 to 3.000% by weight cationic hydroxypropyl trimonium hyaluronate previously hydrated in water, in order to obtain the anionic micelle-cationic polymer complex.

[0026] 3. The composition according to point 1 or 2, comprising one or more compounds selected from the following as additional active ingredients according to point b): peptides and their derivatives, amino acids and their derivatives, vitamin C and its derivatives, vitamin B and its derivatives, vitamin A and its derivatives, vitamin K and its derivatives, plant and fruit extracts and waters, allantoin, AHA and BHA acids, ectoine, algae extracts, arbutin, astaxanthin, azelaic acid and its derivatives, bakuchiol, bisabolol, ferulic acid, caffeine, kojic acid, coenzyme Q10, proteins and their derivatives, enzymes, cyclodextrin, alpha-glucan, beta-glucan, bacillus / saccharomyces / pseudoalteromonas ferment, biotin, glycoin, phospholipids and their derivatives, RNA and DNA derivatives, saccharide isomerate, pantolactone, carnitine, zinc-, copper-, sulfur- and magnesium compounds.

[0027] 4. A composition according to any one of points 1 to 3, comprising one or more of the following compounds as excipients as described in point (d): da) humectants selected from the group consisting of glycerol and its derivatives, propanediol, glycols and glycol ethers, plant extracts, sugar alcohols, hyaluronic acid and its derivatives, mono-, di- and polysaccharides, lactic acid and its derivatives, amino acids and their derivatives, urea and its derivatives, betaine, gluconolactone, glyceryl esters, xylityl glucoside, aldonic acids, flavonoids, acetamido ethoxyethanol;

[0028] (b) emollients selected from the group consisting of ceramides, vegetable squalane, polyethylene glycol and its derivatives, shea butter and its derivatives, vegetable oils and their derivatives, silicone oils, lanolin and its derivatives, vegetable esters, beeswax and its derivatives, vegetable waxes, cholesterol, lipid derivatives, hydrocarbon oils and waxes, silicone derivatives, creatine, alkanes, triglyceride esters, acetoglyceride esters, ethoxylated glyceride esters, alkyl esters, alkenyl esters, fatty acids and their esters, fatty alcohols and their derivatives, fatty alcohol ethers, ether esters, polyols and polyether derivatives, polyol ethers, wax esters, phospholipids, sterols, amides and their derivatives; de) preservatives selected from the group consisting of sodium benzoate, potassium sorbate, phenethyl alcohol, caprylyl glycol, phenoxyethanol, benzyl alcohol, dihydroxyacetic acid, benzoic acid, sorbic acid, sodium hydroxymethyl glycinate, octenidine HC1, chlorophene sin, PEG-4 laurate (and) iodopropynyl butylcarbamate, chloroxylenol, undecylenic acid, sodium levulinate, sodium anisate; dd) gelling agents selected from the group consisting of polysaccharides and their derivatives, starch, xanthan gum, guar gum and its derivatives, carrageenan, alginates, pectins, cellulose derivatives, acrylic acid-based polymers, polyacrylamides and alkylene oxide-based polymers, carbohydrates, hectorite, silicon dioxide dimethyl silylate, silicon dioxide, carbomer, gum arabic, ammonium acryloyldimethyltaurate / VP copolymer, sodium polyacryloyl dimethyltaurate, hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer; de) emulsifiers selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, polyethylene glycol derivatives and esters, phospholipids, fatty acid mono- and diglycerides, polyglycerol esters, sucrose esters of fatty acids, emulsifying waxes, alkyl sulfates, alkoxylated alcohols, alkyl polyglucosides, stearates, proteins, hydrocolloids and their derivatives, quaternary ammonium compounds, alcohol polyethylene glycol ethers, fatty acid polyethylene glycol esters, polyoxyethylene / polyoxypropylene block copolymers, fatty alcohols, fatty acids, ammonium acryloyldimethyl taurate / VP copolymer, sodium polyacryloyldimethyl taurate, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, acrylate polymers, glutamates, alkyl carbamates, fatty acid amido propyl dimethylamines, lipoamides, phosphate esters; df) chelating agents selected from the group consisting of tetrasodium glutamate diacetate, EDTA and its derivatives, sodium phytate, sodium gluconate, phytic acid, caprylhydroxamic acid, trisodium ethylenediamine disuccinate, trisodium dicarboxymethyl alaninate; dg) surfactants selected from the group consisting of alkyl ether sulfates, alkyl sulfates, alkyl benzene sulfonates, fatty acid soaps, alkyl phenol ethoxylates, alcohol ethoxylates, nonylphenols, quaternary ammonium compounds and their esters, pyridine and imidazoline derivatives, alkyl sulfonates, alkyl aryl sulfonates, alkyl ethanolamine sulfates, alkyl ethanolamine sulfonates, alkyl benzimidazole sulfonates, betaine derivatives, amino oxides, phosphate esters, sorbitan fatty acid esters and ethoxylates, carboxylates, alkanolamides, sulfonium compounds, amino carboxylic acids, glycolipids, lipopeptides and lipoproteins, phospholipids, polymeric surfactants, alkyl phosphates, glycerol sulfates, alkyl sulfoacetates, alkyl sulfosuccinates, polyglycol ether sulfates, sarcosinates, acyl acrylates, alkyl pyridinium compounds, sapamine-type substances, disulfimides, saponins, di- and triol fatty acid esters, polyglycol derivatives, alkyl polyglycosides, lipoamino acids and their derivatives, polysorbates, taurates, isethionates.

[0029] 5. The composition according to any of points 1 to 4 for dermatological or cosmetic use.

[0030] 6. Use of the composition according to any of points 1 to 4 for the production of a dermatological composition.

[0031] 7. Use of the composition according to any of points 1 to 4 for the production of a cosmetic composition, most preferably a skincare composition.

[0032] 8. An anionic micelle-cationic polymer complex, wherein the anionic micelle consists of the following i) a compound of Formula (I) wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid and linolenic acid or mixtures thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II) wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the active ingredient vector according to point a) has a diameter in the range of 1 to 10 nm, preferably in the range of 1 to 6 nm, measured by dynamic light scattering using an LSI Nanolab 3D device at a wavelength of 625 nm, at 25°C.

[0033] 9. An anionic micelle-cationic polymer complex, wherein the anionic micelle consists of the following i) a compound of Formula (I) (I) wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid, and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II) wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the anionic micelle-cationic polymer complex according to point a) can be prepared by the following method:

[0034] 1. An aqueous solution of 0.2 to 15.0% by weight of a compound (I) and 0.1 to 3.0% by weight of crystalline capryloyl glycine are measured and the mixture is heated;

[0035] 2. During the heating phase, 0.01 to 1.00% by weight KOH is added as a catalyst, and the mixture is heated to 60 to 80°C, preferably 70 to 75°C, and most preferably 70 to 73°C under continuous stirring in order to obtain an anionic lipoamino acid micelle;

[0036] 3. The mixture is cooled to below 40°C and by using the STP method, it is combined with 0.001 to 3.000% by weight cationic hydroxypropyl trimonium hyaluronate, previously hydrated in water, in order to obtain the anionic micelle-cationic polymer complex.

[0037] 10. Method for producing an anionic micelle-cationic polymer complex, wherein the anionic micelle consists of the following i) a compound of Formula (I) wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid, and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II) wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the anionic micelle-cationic polymer complex according to point a) can be prepared by the following method:

[0038] 1. An aqueous solution of 0.2 to 15.0% by weight of a compound (I) and 0.1 to 3.0% by weight of crystalline capryloyl glycine are measured and the mixture is heated;

[0039] 2. During the heating phase, 0.01 to 1.00% by weight KOH is added as a catalyst, and the mixture is heated to 60 to 80°C, preferably 70 to 75°C, and most preferably 70 to 73°C under continuous stirring in order to obtain an anionic lipoamino acid micelle;

[0040] 3. The mixture is cooled to below 40°C and by using the STP method, it is combined with 0.001 to 3.000% by weight cationic hydroxypropyl trimonium hyaluronate, previously hydrated in water, in order to obtain the anionic micelle-cationic polymer complex. 11. The anionic micelle-cationic polymer complex according to point 8 or 9 for dermatological or cosmetic use.

[0041] 12. Use of the anionic micelle -cationic polymer complex according to point 8 or 9 for the production of a dermatological composition.

[0042] 13. Use of the anionic micelle -cationic polymer complex according to point 8 or 9 for the production of a cosmetic composition, more preferably a skincare composition.

[0043] DETAIUED DESCRIPTION OF THE INVENTION

[0044] Abbreviations:

[0045] PC A: L-pyrrolidone carboxylic acid

[0046] POPCA: potassium salt of N-olive oil and L-pyrrolidone carboxylic acid

[0047] CG: capryloyl glycine

[0048] HPT-HA: hydroxypropyl trimonium hyaluronate

[0049] CMC: critical micelle concentration

[0050] STP method: surfactant to polymer method

[0051] ELISA: enzyme-linked immunosorbent assay

[0052] NMF: natural moisturizing factor

[0053] The present invention discloses a complex system and its preparation which, in addition to containing the building blocks necessary for collagen production, namely the amino acids glycine, proline, and hydroxyproline, is capable of delivering them to the appropriate layer of the skin where collagen production occurs. Due to the technology we developed, an anionic micelle-cationic polymer complex is produced, which immediately binds to the negative charges of the skin through its cationic groups.

[0054] Hydration is extremely important in skincare, as it affects the lipid matrix of the outermost layer of the skin. This lipid layer is responsible for maintaining the skin's barrier function. When well hydrated, lipids are able to maintain a more orderly lamellar structure, which helps to effectively preserve the skin's moisture balance. The ideal moisture content of the skin contributes to increased permeability of the barrier layer, thereby supporting the deeper penetration of active ingredients. The complex hyaluronate component intensively moisturizes the skin, thereby facilitating the easier penetration of lipoamino acid molecules.

[0055] The skin barrier is a protective layer formed by stratum comeum lipids including ceramides, cholesterol, and free fatty acids, comeocytes, and NMF. The double layers of stratum comeum lipids can be affected by hydration: when water interacts with the lipid layer, the fatty acid chains move more freely and this results in increased fluidity, or lipid fluidization. As a result of hydration, the stratum comeum thus absorbs water and swells, increasing the intracellular space and allowing small molecules to pass through more easily. Hydration also reduces the water gradient between the outer and inner layers of the stratum comeum, which promotes the movement of hydrophilic and amphiphilic molecules towards the inner layers of the skin. The apolar chain of lipoamino acids also plays a role in penetration. Lipoamino acids are amphiphilic molecules, as they contain both hydrophobic and hydrophilic parts. This dual nature allows them to interact with both the polar and apolar (lipid) components of the stratum comeum, thereby facilitating their own penetration. The deeper layers of the skin are separated from the outside world by the lipid bilayer (skin barrier) between the comeocytes, wherein surfactants can enter. Due to their hydrophobic parts they dissolve easily in the lipid domains of the stratum comeum thus are able to pass through the lipid barrier more easily. Their surface tension-reducing effect further enhances their ability to penetrate the intercellular space. Lipoamino acids can be fully utilized by fibroblasts in the dermis for basic metabolic processes through cell uptake. These lipoamino acids transport the main building blocks of collagen protein, namely glycine, proline, and hydroxyproline. The availability of amino acids, especially those necessary for collagen synthesis, namely glycine, proline, and hydroxyproline, is essential for collagen production.

[0056] The composition according to the invention contains N-olive oil and L-pyrrolidone carboxylic acid potassium salt, capryloyl glycine, hydroxypropyl trimonium hyaluronate, and optionally tetrasodium glutamate diacetate and cocoyl proline. Importantly, both POPCA and CG are natural moisturizing factor (NMF) molecules. These NMF molecules, which are found in the outer layer of the skin, the stratum comeum, have water-binding properties. By absorbing water from the environment and retaining it in the skin, they help maintain skin hydration. NMF is essential for maintaining the skin's barrier function, ensuring that the skin remains supple, hydrated, and resistant to external stressors.

[0057] The anionic micelle -cationic polymer complex according to the invention contains the starting materials listed in Table 1.

[0058] Table 1. Components for anionic micelle -cationic polymer complexes

[0059] *Fallacara, A., Baldini, E., Manfredini, S., & Vertuani, S. (2021). Hyaluronic acid: A key ingredient in the therapy of inflammation. Biomolecules, 77(10), 1518.

[0060] POPCA is a compound formed during the condensation reaction between olive oil fatty acids and Na- PCA (Schotten-Bauman method), which is converted into salt through the reaction of the carboxyl group with potassium hydroxide. Pyroglutamic acid (PCA) and its salt are found in several tissues and biological fluids. L-PCA is an intermediate compound of the two main amino acids of collagen, proline and hydroxyproline. Pyroglutamic acid is also an excellent agent for supporting epidermal differentiation, as it promotes the synthesis of epidermal lipids and filaggrin, as detailed in FR2872043B1. PCA constitutes 12% of the natural moisturizing factor (NMF), has water-binding properties, and interacts with the stratum comeum. POPCA provides fatty acids and PCA to the skin as hydrolytic enzymes present in the skin react on the amide group of the molecule, breaking it down into fatty acids and PCA. PCA, as an NMF and amino acid vector, supports the maintenance of healthy skin, while the fatty acids in olive oil, which are rich in oleic acid and linoleic acid, are incorporated into the skin's lipid composition. Oleic acid and palmitoleic acid are monounsaturated fatty acids that are stable, have a strong affinity for the skin, and are easily incorporated into the composition of cell membranes.

[0061] Capryloyl glycine is a lipoamino acid that can be produced by the acylation of glycine and octanoic fatty acid chain. Glycine is the simplest amino acid and the only one that does not have a chiral carbon atom. It plays an important role in the biosynthesis of vital molecules in the body. It is one of the main components of dermal structural proteins - collagen - and thus plays a prominent role in the skin, particularly in skin cell metabolism and skin hydration as an NMF. Lipoamino acids are molecules that contain an amino acid derivative and at least one lipophilic chain. Amino acids are naturally hydrophilic molecules that can be anionic or cationic depending on the pH value. The addition of one or more hydrogroups grants them amphiphilic properties, which enhances their biological effects or surface properties and this is the essence of lipoamino acid technology. These molecules have a wide range of biological effects because they demonstrate strong similarity to biological substances.

[0062] Hydroxypropyl trimonium hyaluronate is a cationic variant of sodium hyaluronate improving its adhesive properties. In addition to the primary functions of sodium hyaluronate, such as high water-binding capacity, tissue affinity, and increased penetration, its adhesion to skin or hair is also improved through cationization.

[0063] Table 1, listed in Table 2. The use of these excipients can reduce the CMC value of the associated lipoamino acids. As an additional beneficial effect, they increase the stability of the anionic micelle -cationic polymer complex.

[0064] Table 1. Excipients in cosmetic preparations and their properties

[0065] To verify the complex structure according to the invention, we proceeded as described in Example 2. In the first step, the formation of the POPCA + CG micelle was verified, and in the second step the association of the cationic polymer hydroxypropyl trimonium hyaluronate with the POPCA-CG micelle was verified. The anionic surfactants produced in the first step of the method are linked to produce an anionic lipoamino acid micelle then the micelle is linked to the cationic hydroxypropyl trimonium hyaluronate pre-hydrated in water, using the STP method (adding surfactant to the polymer). Since polymer / surfactant systems are non-equilibrium systems, their properties are significantly influenced by the preparation process itself. We monitored the size change using dynamic light scattering, thus confirming the formation of the complex structure. In order to do this, we first measured the starting materials separately and prepared the following samples for measurement: Al) POPCA dissolved in water; A2) CG and KOH dissolved in water; A3) HPT-HA dissolved in water. Then we measured the anionic micelle produced in the first step of the new process, i.e., sample B): POPCA-CG+KOH, also in an aqueous solution. This was followed by the examination of the complex produced by the method according to the invention: Cl) POPCA-CG-KOH-HPT-HA in an aqueous solution. Finally, as a control, we measured a dispersion mixture produced by a method different from the method disclosed in the present invention: C2) POPCA-CG-KOH-HPT-HA in an aqueous solution. Based on the results of the measurements and by monitoring the size changes, we can confirm the linking of the components: anionic micelle-cationic polymer. In addition, we confirmed that the size distribution of the colloidal complex produced by the method according to the invention (sample Cl) is monodisperse, while the colloidal mixture produced by the method known from the state of the art (sample C2) is polydisperse.

[0066] The results confirm the greater stability and more efficiency of the new structure based on the following. The composition according to the invention is characterized by a narrow size distribution and favorable surface properties, i.e., the surface characteristics of the particles. Due to the monodisperse nature of the resulting anionic micelle-cationic polymer complex, the composition is able to cover the skin surface more evenly, thereby improving the interaction between the skin surface and the active ingredient, thus the potential absorption. The uniform particle size ensures a much more controlled release of the active ingredient, as the skin can be penetrated at a steady rate. This prevents smaller particles from being absorbed too quickly and larger particles from being absorbed too slowly, thus ensuring a balanced release of the active ingredient over time. Furthermore, it prevents larger particles from reducing the penetration efficiency of smaller particles capable of deeper absorption. Another important feature is the surface properties of the particles. These include surface charge, which refers to the electrical charge on the surface of the particles. This influences how the particles interact with biological tissues and other particles. The anionic micelle-cationic polymer complex according to the invention binds to the negatively charged skin with its cationic part. Cationic molecules generally provide better skin surface contact than anionic molecules because their positive charge attracts them to the negatively charged skin surface. This improves adhesion and increases permeability due to its moisturizing effect. In addition, the complex according to the invention is able to remain on the surface during washing due to the electrostatic interaction. The longer the duration of interaction between the active ingredient and the skin, the more favorable the penetration of the active ingredient is expected to be. It is also important to consider surface chemistry, i.e., which groups of the particle can interact with its environment: other molecules, cells, tissue structures; as well as surface topography, which refers to the physical structure of the particle surface that can influence the extent to which the particles are able to bind or penetrate biological systems. The composition according to the invention also provides a solution to these challenges. Due to its small particle size and hydrophilic- lipophilic character, it is able to penetrate the skin barrier, thereby improve bioavailability. Prior art literature data [see Filon, F. L, Mauro, M, Adami, G, Bovenzi, M, Crosera, M. (2015). Nanoparticles skin absorption: New aspects for a safety profde evaluation. Regulatory Toxicology and Pharmacology, 72(2), 310-322] discloses that particles of a size of 4 nm or below demonstrate almost maximum penetration through intact skin, particles between 4 and 20 nm can potentially permeate intact and damaged skin, particles between 21 and 45 nm can only penetrate damaged skin, and particles larger than 45 nm cannot penetrate or permeate the skin.

[0067] In the production of the anionic micelle-cationic polymer complex according to the invention, two lipoamino acids are linked to form an anionic micelle, and then, due to the positive charge of the cationic polymer, the negatively charged micelle is linked to the polymer. Light microscope images show the presence of micrometer-sized aggregates of the starting materials, and the reduction of the new complex formed as a result of the linking to nanoscale size is indicated by the fact that the size of the particles is now below the detection limit of the optical microscope and therefore cannot be directly observed. Further investigation of the size of the resulting nanoparticles in solution was performed using dynamic light scattering.

[0068] Through the formation of the anionic micelle -cationic polymer complex according to the invention, the constituent elements achieve chemical stability as the complex has improved water solubility compared to the solubility of the constituents.

[0069] The anionic micelle-cationic polymer complex according to the invention binds to the skin surface in an electrostatically controlled manner.

[0070] The hyaluronate component of the anionic micelle -cationic polymer system according to the invention strongly hydrates the stratum comeum, thereby increasing the permeability of the upper skin layers.

[0071] Due to the small particle size of the monodisperse colloidal system containing the anionic micellecationic polymer complex according to the invention and the amphiphilic character of the lipoamino acid components, they are able to penetrate the lipid barrier of the skin and reach the dermis, where they can be fully utilized by skin cells for basic metabolic processes, such as collagen production.

[0072] An advantage of the method according to the invention is that after reaching CMC, the formation of the anionic micelle-cationic polymer complex stabilizes the poorly soluble, recrystallizing capryloyl glycine, which can thus be safely integrated into emulsions and aqueous systems without recrystallization.

[0073] The anionic micelle-cationic polymer complex formed as a result of the linking reaction can be used in cosmetic compositions. Upon contact with the skin, the complex strongly hydrates the upper skin layer, thus providing more favorable conditions for the components to penetrate deeper into the skin. Due to their optimal physicochemical properties in terms of penetration, the amino acid vectors of the complex can easily penetrate the epidermis and transport the main amino acids constituting ECM proteins to the upper layer of the dermis, where they stimulate collagen protein production, thereby improve skin elasticity.

[0074] Due to its cationic nature, hyaluronic acid adheres to the negative charges of the skin, thus remains on the surface even after washing. This characteristic makes it an ideal active ingredient in cosmetic and cleansing products.

[0075] Surprisingly, the anionic micelle-cationic polymer complex formed by linking the components achieves kinetic stability through a reduction in size, which can be easily monitored through the temporal stability of the particle size distribution. This is extremely favorable for its application, as its small size makes it more effective at penetrating the skin.

[0076] We used dynamic light scattering to determine the size of the nanoparticles in a solution. Dynamic light scattering provides quick and easy access to accurate information about the hydrodynamic diameter of particles. Due to the Brownian motion of the measured particles, the intensity of the light scattered by the particles fluctuates continuously over time. We analyze the temporal variation of the intensity fluctuations using an autocorrelation function, which allows us to infer the hydrodynamic radius, motion, and distribution of the particles from the dynamics of the scattered light.

[0077] Consequently, the autocorrelation function obtained during dynamic light scattering (DLS) describes the temporal correlation of the detected scattered light intensity, which provides information about the motion of the particles and the characteristics of the system. The decay of the function characterizes the Brownian motion of the particles, from which their size can be determined, r (lag time) is the time shift at which the measured intensities are compared in the autocorrelation function; this time scale reflects the dynamics of particle motion.

[0078] Statistical data on particle size distribution can be obtained from the analysis of the autocorrelation function obtained during DLS measurement, and the width of the distribution can be characterized by the polydispersity index, which reflects the heterogeneity of the particles. The polydispersity index (PDI) for biological nanomolecules is the following (see W02020115140Aiy.

[0079] PDI > 0.1: highly monodisperse (uniform particle size);

[0080] 0.1 < PDI < 0.4: moderately monodisperse (homogeneous population);

[0081] PDI >0.7: highly poly disperse.

[0082] According to further literature, PDI values between 0 and 0.5 reflect the uniformity of particle size in homogeneously dispersed colloids and vesicles (see Jarrar, Q. B., Hakim, M. N., Cheema, M. S., & Zakaria, Z. A. (2019). In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes. Brazilian Journal of Pharmaceutical Sciences, 55, QYI IQ ).

[0083] The z-average radius of the anionic micelle particles formed in the first step of the method according to the invention was determined by light scattering measurement based on Example 2 to be 5.3 ± 1.2 nm, while the complex system formed with the linked cationic polymer had a z-average radius of 5.0 ± 1.1 nm. This reduction in size compared to the sizes of the individual components suggests greater stability for the complex structure formed. Compared to the preparation method known from the prior art (see Example 2, sample C2), the size of the complex according to the present invention is smaller than that of the particles formed therein.

[0084] The ELISA test is a commonly used analytical biochemical test method based on the interaction of specific antibodies and antigens, enabling the quantitative determination of various biomolecules, such as proteins, in samples. Using this test, we examined the amount of collagen produced by fibroblast cells (ng / ml) compared to the concentration of collagen produced by cells not treated with the sample. Based on our results, the anionic micelle -cationic polymer complex according to the invention is capable of stimulating collagen protein synthesis, see Example 4. We found that a 0.01 mg / ml solution of the anionic micelle-cationic polymer complex was the most effective, showing a 159.7% result after 24 hours, i.e., a 59.7% increase in collagen protein quantity compared to the untreated sample (100%).

[0085] The anionic micelle-cationic polymer complex according to the invention induces an increase in cell viability and cell proliferation. After 24 and 48 hours, the cell count based on Table 7 showed an increase of 112.14% after 24 hours, i.e. an increase of 12.14% as a result of the 0.01 mg / ml solution of the anionic micelle-cationic polymer complex, and after 48 hours, the result was 117.76% compared to untreated cells (100%).

[0086] The cosmetic gel composition according to the invention comprises allantoin, glycerol, panthenol, tetrasodium glutamate diacetate, hydroxyethyl cellulose, a pH regulator, and a preservative in addition to the anionic micelle-cationic polymer complex produced by the method according to the invention.

[0087] The cream-gel composition according to the invention was prepared by the following method. Following the preparation of the anionic micelle -cationic polymer complex according to the invention, the second step involved combining the components of phase A (aqueous) including water, allantoin, glycerol, xanthan gum, acrylates / C(io-3O) alkyl acrylate crosspolymer, panthenol and phase B (oily) including shea butter, olive oil, fractionated coconut oil, tocopheryl acetate, triethanolamine, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer. The ingredients are measured into two separate containers and heated to 70 to 75°C while stirring slowly until they are completely melted. Once the specified temperature is reached, the prepared ingredients are blended using a homogenizer. Then, under vacuum and with constant stirring, the emulsion is cooled to below 40°C, where the phase C component including the complex according to the invention, 1% aqueous solution of sodium ascorbyl phosphate, pH regulator, preservative is added with slow stirring.

[0088] The micellar water composition according to the invention comprises allantoin, cocoyl proline, glycerol, panthenol, tetrasodium glutamate diacetate, pH regulator, and preservative in addition to the anionic micelle-cationic polymer complex prepared by the method according to the invention.

[0089] As described in Example 4, measurements were performed to compare the penetration efficacy of the cosmetic composition according to the invention. Our results show that the components of the complex according to the invention are capable of passing through the skin barrier. This result represents an advance over the prior art. Based on our results, the anionic micelle-cationic polymer complex structure demonstrates the following: (i) smaller size than expected, which makes penetration more effective, (ii) cell number growth can be observed, and (iii) collagen protein synthesis is stimulated. An additional advantage of the complex is that (iv) it is acidic thus have a stable structure even in the ideal pH range of the skin.

[0090] EXAMPLES

[0091] Example 1: Preparation of an anionic micelle-cationic polymer complex

[0092] Starting materials:

[0093] The starting materials are commercially available components.

[0094] Active ingredients:

[0095] 1) INCI name of component: Potassium Olivoyl PCA

[0096] - Ingredients: potassium olive oil PCA, Na-PCA, water, KC1, preservatives: sodium benzoate, potassium sorbate, benzyl alcohol

[0097] 2) INCI name of component: Capryloyl Glycine

[0098] - Ingredients: capryloyl glycine

[0099] 3) INCI name of component: Hydroxypropyl trimonium Hyaluronate

[0100] - Ingredients: hydroxypropyl trimonium hyaluronate

[0101] Method:

[0102] 1) To prepare the anionic micelle-cationic polymer complex, the two lipoamides are weighed and transferred into a flask and heated, the catalyst (KOH) is added, and the mixture is heated to 70 to 75 °C with continuous stirring. In this step, the anionic lipoamide micelle is obtained.

[0103] 2) Next, the lipoamino acid mixture is cooled to below 40°C and using the STP (surfactant to polymer) method, it is combined with the cationic hyaluronic acid that was pre-hydrated in water.

[0104] During the preparation process, only the correct ratio of lipoamino acid components will result in an optimal, stable anionic micelle and a clear solution. However, without the addition of the polymer, the two surfactants may become unstable over time. Raising the reaction temperature above 75°C may result in the oxidation of the molecules, while below 60°C, only partial linking is likely to occur between the two lipoamino acids.

[0105] Preparation of combinations according to the invention:

[0106] Various combinations according to the invention were prepared, in which the amount of the active ingredient phase was stabilized at a predetermined, application-specific value, while the weight ratio of the constituent POPCA and capryloyl glycine lipoamino acid components to each other was systematically varied. The mixture of the two components was subjected to an addition reaction in the presence of a catalyst and then added to the hydroxypropyl trimonium hyaluronate prehydrated in water.

[0107] The concentration of the hydroxypropyl trimonium hyaluronate component was kept in the range of 0.01 to 0.5 % by weight in order to achieve the objective of the invention.

[0108] The resulting anionic micelle-cationic polymer combinations were dissolved in water at a total concentration of at least 0.01 % by weight and at most 15 % by weight.

[0109] The objective of the invention can be achieved with the concentration ratios shown in the table below:

[0110] Table 3 Components for the preparation of the complex according to the invention

[0111] POPCA Capryloyl glycine Hydroxypropyl trimonium hyaluronate

[0112] Ratio Ratio % by weight

[0113] 30 70 0.01 to 0.5

[0114] 40 6 0.01 to 0.5

[0115] 50 5 0.01 to 0.5

[0116] 60 4 0.01 to 0.5

[0117] 70 30 0.01 to 0.5

[0118] The POPCA / CG ratio is as shown in Table 3. If, for example, POPCA is less than 30, the hydrodynamic particle size increases above 10 nm and the system is polydisperse, furthermore it is unstable and will separate after a certain period of time.

[0119] The above-mentioned concentration ratios are suitable in the pH range of 4 to 6. Under other conditions, the concentration ratios can presumably be expanded.

[0120] Preparation method:

[0121] Each composition was prepared according to the following method, based on a total amount of 100 % by weight: the POPCA and CG components were mixed in a 250 ml flask according to the ratios shown in the table above (Table 3). After adding the KOH catalyst, the mixture was heated to 60 to 75°C while stirring (different types of stirrers can be used: spatula, propeller, magnetic stirrer), and then the mixture was allowed to cool to a temperature below 40°C. The concentration of hydroxypropyl trimonium hyaluronate was adjusted to between 0.01 and 0.5 % by weight and it was pre-hydrated in water in an amount suitable for the application at room temperature.

[0122] The surfactant combination cooled to below 40°C was added to the aqueous solution of the hydroxypropyl trimonium hyaluronate component. The resulting anionic micelle-cationic polymer combinations were dissolved in a suitable amount of water based on a concentration of 100 % by weight, wherein the total concentration of the active ingredient combinations was at least 0.01 % by weight and at most 15 % by weight.

[0123] Conformity testing:

[0124] Visual and microscopic examination of the combinations was generally sufficient to determine whether the samples were clean and free of coacervates and precipitates. The solutions were examined at specified intervals: immediately, after 30 minutes, 1 hour, 24 hours, and 48 hours, by microscopic observation and visual examination. Based on the results, conclusions could be drawn about the ideal ratio of surfactant components and the pH-dependent solubility behavior of the ingredients.

[0125] We examined numerous compositions with the parameters above in order to optimize the performance of the system. The samples selected for further testing are shown in Table 4, of which the composition named Cl proved to be the most favorable. The samples were subjected to detailed analysis in the following examples.

[0126] Table 4 Composition of samples

[0127] Components Sample 1 (Cl) Sample 2 Sample 3

[0128] Description % by weight % by weight % by weight water qs. to 100 qs. to 100 qs. to 100

[0129] POPCA 10 9 12 capryloyl glycine 1.5 1.5 1.8 hydroxypropyl trimonium hyaluronate 0.1 0.1 0 potassium hydroxide 0.2 0.22 0.25

[0130] Example 2: Verification of the complex structure by dynamic light scattering measurement

[0131] The particles move in the solvent driven by Brownian motion, which causes fluctuations in the intensity of the scattered light. The statistical characteristics of these fluctuations are reflected in the autocorrelation function.

[0132] For DLS measurement of the solutions, we used an LSI Nanolab 3D device operating with a 625 nm wavelength laser. The samples were measured without dilution or fdtration at a temperature of 25°C. Detectable particle sizes range from 0.15 nm to particles with a radius of 5 pm. When determining the hydrodynamic size of colloidal micelles, values below 1 nm belong to the limits of the DLS method, so only values above 1 nm were taken into account in the analysis. For the DLS measurements, the samples listed in Table 5 were prepared using the novel two-step technological solution disclosed in the invention, wherein, as a first step, two lipoamino acids with amphiphilic properties for cosmetic use (active ingredients Al and A2) were mixed in the presence of a catalyst (A1+A2=B) to produce the micelle marked B. In the second step, the aqueous solution containing the micelle marked (B) was mixed with an aqueous solution marked A3 containing a water-soluble polymer for cosmetic use. In the process, the component marked Cl, i.e. the anionic micelle -cationic polymer complex was obtained (B+A3=C1). For a control measurement, while maintaining the concentration of the components, a mixture labeled C2 was prepared containing lipoamides and cationic polymer by a method different from the method disclosed in the invention. Five parallel measurements were performed per sample. Size data was obtained in two ways from the experimentally determined autocorrelation functions. One is the commonly used second-order cumulant expansion method. In this case, a unimodal population is assumed, and in addition to the intensity average (z-average) size, the polydispersity index (PDI) also provides information about the width of the size distribution. In case of nanoparticles, if the PDI value is less than 0.1, the size distribution is narrow, if it is between 0. 1 and 0.4, the distribution is of medium width (uniform particle size), and if it is above 0.7, the sample is highly polydisperse. The CORENN algorithm was used as another evaluation method, which provides more accurate information about multimodal size distribution systems. In this case, multiple populations can be identified and the relative proportion, maximum, coefficient of variation (CV), and skewness of each peak can be determined. In addition, it is also possible to determine the distributions by number and volume.

[0133] Table 5. Labeling and identification of samples

[0134] Sample Results

[0135] Al POPCA dissolved in water

[0136] A CG+KOH dissolved in water

[0137] A HPT-HA dissolved in water

[0138] B POPCA-CG+KOH in aqueous solution anionic lipoamino acid micelle prepared in the first step of the new technology

[0139] Cl POPCA-CG-KOH-HPT-HA aqueous solution complex prepared by the method described in the invention

[0140] POPCA-CG-KOH-HPT-HA aqueous solution

[0141] C2 disperse mixture prepared by a method different from the method according to the invention

[0142] The results of the dynamic light scattering measurements are summarized in Table 6.

[0143] Table 6. z-average radius and polydispersity of the samples calculated using the second -order cumulants method

[0144] Sample r (nm) PDI

[0145] Al 55.1 ± 0.3 0.285 ± 0.028

[0146] A 1680 ± 1426 3.67 ± 2.94

[0147] A 683 ± 167 1.10 ± 0.27

[0148] B 5.3 ± 1.2 0.483 ± 0.167

[0149] C 5.0 ± 1.1 0.457 ± 0.337

[0150] C2 6.8 ± 1.6 0.996 ± 0.769

[0151] In general, it can be concluded that mixing surfactants (lipoamino acids) (sample B) eliminates the inhomogeneity characteristic of surfactant A2, small particles are formed whose size corresponds to that of a small-molecule micelle system. The inhomogeneity observed in the case of the cationic polymer A3 also disappears when mixed with surfactants Cl and C2. In addition to the slight difference in size between the two mixtures, a more important difference is that in the case of C2, high polydispersity is observed, which indicates the presence of a small number of aggregates in the sample. The most striking difference between samples Cl and C2 can be seen in their measured autocorrelation functions (Figure 1).

[0152] Apart from the increased noise level due to their small size, samples B and Cl show an ideal function shape with a monotonic decrease. In contrast, sample C2 shows a two-step function. This indicates that the sample contains a small number of large particles. To quantify this, the CORENN algorithm was used, the results of which are shown in Table 7.

[0153] Table 7. Size parameters of the measured samples determined using the CORENN algorithm

[0154] „ . Numerical distribution Distribution by volume

[0155] Sampler cv sk ratio r cv sk ratio

[0156] B 2.2 nm 0.361 2.826 100% 3.8 nm 0.737 4.816 100%

[0157] Cl 1.7 nm 0.412 3.498 100% 3.9 nm 1.547 211 100%

[0158] C2 3.6 nm 0.183 0.513 100% 3.6 nm 0.086 0.499 99.1%

[0159] 92.1 nm 0.103 518 0.6%

[0160] 792 nm 0.127 0.491 0.3%

[0161] Based on the results, it can be concluded that mixing cationic polymers and lipoamino acids generally results in small complexes with both mixing methods, but in the case of sample Cl, a more homogeneous system is formed, while in the case of C2, a highly polydisperse system is formed containing larger aggregates, presumably with a structure significantly different from that of the complex of sample Cl . This is confirmed by the three particle sizes shown in Table 6.

[0162] In the case of sample B, small particles with a z-average radius of 5.3 ± 1.2 nm were formed, the size of which corresponds to that of a small molecular surfactant micelle. Sample B is characterized by a narrow size distribution. These results support the kinetic stability of the system, which indicates the formation of anionic micelles.

[0163] The complex system created by mixing the cationic polymer and the anionic micelle (sample Cl) shows an ideal function shape, which is also accompanied by a narrow size distribution: the particles have a z- average radius of 5.0 ± 1.1 nm. Surprisingly, the micelle -polymer complex does not achieve stability through an increase in size, but rather through a decrease, which suggests a strong interaction between the cationic polymer and the anionic micelle. pH range of the solutions used in DLS measurements:

[0164] The DLS measurements were performed in the skin-friendly acidic pH range of 4.5 to 5.5. The systems were tested up to the neutral pH of 7. It can be concluded that an acidic pH is favorable for the stabilization of the molecules.

[0165] Example 3: ELISA test

[0166] The aim of the study is to quantitatively evaluate the effect of the tested sample on collagen I synthesis induction in human fibroblasts using the ELISA method. Fibroblasts are the basic cells of the connective tissue of the skin, capable of synthesizing large amounts of collagen and elastin, which play a decisive role in the elasticity and appearance of the skin.

[0167] The study is performed on human primary fibroblast culture (HSF: human skin fibroblasts, ATCC code: CRL-2522, lot: 70005437). The cells were cultured in MEM containing 10% FBS and antibiotics. The cells were allowed to grow for 24 hours in an incubator under constant conditions: at 37°C and with 5% CO2 After one day, the cells were placed in a low-serum environment for an additional day with a medium containing 0.4% FBS, before treatment was started. Then a fresh medium with 0.4% FBS was added to the cells, supplemented with a series of dilutions of the test sample (0.1 and 0.01 mg / ml POPCA+CG+KOH+HPT-HA complex, which concentration was decided on after a preliminary cytotoxicity test). The sample was dissolved directly in the culture medium. Untreated cells were used as negative controls (NC). Three parallel measurements were performed. After 24 and 48 hours of exposure, total proteins were extracted following the manufacturer's instructions (M-PER ® Mammalian Protein Extraction Reagent and Halt Protease Inhibitor Cocktail - Thermo Scientific).

[0168] A commercially available ELISA kit was used to evaluate collagen I synthesis. The microplate included in the kit is pre-coated with a collagen I-specific antibody. Standards and samples were placed in the appropriate wells of the microplate, where the presence of specific proteins leads to a color change. The color change can be measured by spectrophotometry at a wavelength of 450 nm, which was used to determine the collagen I concentration in the samples.

[0169] Based on the results, the viability of the cells was 112.14% (after 24 h exposure) and 117.76% (after 48 h exposure) compared to the negative control (untreated cells) (100%) under the influence of 0.01 mg / ml anionic micelle-cationic polymer, according to Table 8. Statistical analysis was performed after 5 to 10 sampling.

[0170] Table 8. Cell viability

[0171] Sample concentration Cell viability (%) Cell viability (%)

[0172] (mg / ml) after 24 h after 48 h

[0173] 0.00 (NC) 100.00 (16.33) 100.00 (7.12)

[0174] 0.01 112.14 (9.78) 117.76 (2.05)

[0175] Collagen I dosage in the protein extract of human fibroblasts treated with the sample compared to untreated cells (NC, negative control) after 24 and 48 hours of exposure (Table 9).

[0176] Table 9. Collagen production after 24 and 48 hours using the composition according to the invention.

[0177] Sample Collagen production Collagen production concentration After 24 h After 48 h pg / ml % (synthesis vs. NC) pg / ml % (synthesis vs. NC)

[0178] 0.01 3.30 159.7 6.72 93.2

[0179] 0.00 (NC) 2.07 100.0 7.21 100.0

[0180] Based on our results presented in Table 8, the complex prepared by the method disclosed in the invention is capable of stimulating collagen protein synthesis. The composition according to the invention is capable of improving collagen I synthesis by 59.7% after 24 hours of exposure at a concentration of 0.01 mg / ml in human fibroblasts, compared to untreated cells (Figure 2). Example 4: Raman spectroscopy measurements

[0181] During the tests, ex vivo excised human skin was treated with the composition according to the invention and with a control sample. After skin treatment, frozen skin sections were prepared and subsequently examined using Raman spectroscopy. The results show that the anionic micelle-cationic polymer complex according to the invention is capable of penetrating the skin barrier and reaching the dermis.

[0182] Human skin penetration studies are subject to ethical approval. The studies were reported to the Scientific and Research Ethics Committee of the Health Science Council (ETT TUKEB), who acknowledged them and recorded them in its register (BM / 4286-1 / 2025).

[0183] Among the methods used in materials science, vibration spectroscopy is known to be non-destructive, i.e., it does not cause damage, and it is also suitable for creating chemical maps. It is a set of structural analysis methods based on the excitation of vibrational energy transitions. This includes Raman spectroscopy, which provides information based on the analysis of the vibrational state of molecules, similar to infrared (IR) spectroscopy. Raman spectroscopy is based on inelastic light scattering, where the material to be examined is irradiated with intense monochromatic (laser) light, and the frequency shifts of the light scattered by the examined material can be analyzed.

[0184] Raman spectrometry is a supplement to IR spectroscopy, in fact a complement thereof, as both analyze the molecular vibrations of the material. The relative sensitivity of the two methods differs, allowing for the examination of different molecular bonds and bond groups. There are numerous vibrational transitions that are inactive in IR spectroscopy but active in Raman spectroscopy, and vice versa. Raman spectrometry is primarily used to analyze the most common chromophore groups, i.e., C — O, C — N, C — S, S — S, C — CI bonds, and C=C, C=O, C=N, N=O, C=S bonds and groups, while IR spectroscopy is more sensitive to polar bonds and functional groups. Water, which has an intense IR absorption spectrum, exhibits only weak Raman scattering, so its presence does not interfere with the measurement.

[0185] Recording the Raman spectra of preparations and their components

[0186] A Thermo Scientific DXR Raman confocal microscope was used to record the Raman spectra. The samples were placed on a stage. The wavelength of the applied laser source was 780 nm and the power of the laser for the measurements was 24 mW. The laser light source was directed onto the sample through a 25 pm slit aperture and a lOx magnification objective lens. Each spectrum was recorded for 5 seconds, and the final spectrum was obtained by averaging a total of 24 recorded spectra. The spectra were recorded in the wavelength range of 3200-200 cm1. When evaluating the spectra recorded for the preparations, the spectrum section suitable for profiling during Raman mapping of skin samples was determined. When evaluating the results, we evaluated the 1800-200 cm'1fingerprint range characteristic of Raman.

[0187] Testing the skin penetration of the samples During the examination of skin penetration of the samples, the composition according to the invention (Cl) and a reference sample (C3) were analyzed (Table 10).

[0188] Table 10: Samples for the skin penetration test

[0189] Sample Contents number

[0190] C 1 Composition according to the invention, see Example 1

[0191] (Aqueous solution of anionic micelle + cationic polymer)

[0192] C3 Sample outside the particle size range according to the invention, hereinafter referred to as reference sample (Aqueous solution of anionic micelle + cationic polymer)

[0193] Composition of formula C3 (% by weight):

[0194] - POPCA 2.4%

[0195] - CG 1.5%

[0196] - KOH 0.432%

[0197] - HPT-HA 0.3%

[0198] - Water qs. to 100%

[0199] In this case, the POPCA / capryloyl glycine ratio differs from 30 / 70, with the POPCA ratio being less than 30. As a result, the hydrodynamic particle size is above 10 nm and the system is polydisperse.

[0200] Treatment of skin samples with the composition, preparation of microscopic samples

[0201] During skin penetration tests, skin excised during abdominal reduction surgery performed at the Plastic Surgery Unit of the Department of Dermatology and Allergology at the University of Szeged was used, from which subcutaneous fat tissue was removed (ethical approval number: ETT TUKEB BMEU / 2339- 3 / 2022 / EKU). The human skin samples used for skin treatment were female abdominal skin samples. An area on the skin samples was treated by applying the same amount of composition (0.20 g) to each sample. The skin samples were placed on cotton wool and fdter paper soaked in physiological saline solution in a Petri dish to prevent the skin sample from drying out. The skin samples were kept at 32±10°C, and the duration of the treatment was 2 hours. After the treatment time had elapsed, the compositions were removed from the skin surface and the treated area was excised with a scalpel. Microscopic sections were prepared from the excised skin samples using a Leica CM 1950 cryomicrotome. The prepared sections were placed on aluminum -coated microscope slides.

[0202] Recording Raman microscopic mapping measurements from skin samples treated with the compositions

[0203] Penetration through the skin can be tracked using a technique known as chemical mapping. Chemical mapping is a type of vibrational spectroscopy, the required equipment consists of a vibrational spectrometer such as Raman and a suitable optical unit such as a microscope. Raman spectrometry is highly selective, and the almost fingerprint-like spectrum allows for clear molecular identification. The radiated light can be focused onto a very small spot using a suitable microscope objective, thus providing reliable chemical information even from a microscopic area of the sample. During chemical mapping, a specific area on the surface of the sample is mapped by recording spectra at each point. The spectra constituting the map can be used to qualitatively determine the spatial distribution of the components of the sample. During mapping, the individual spectra were recorded using the same method as the one used for recording the spectra of the components and compositions. In the case of skin samples, we examined an area of 100x500 pm when recording maps, with 50-50 pm increments in the x and y directions (Figure 3). Thus, a total of 33 spectra were recorded to create a correlation map, and the total mapping time was one and a half hours. During mapping, the spectra were recorded from the stratum comeum to the deeper layers of the skin (epidermis, dermis). Figure 3 shows a cross-sectional image of human skin and the measurement points of Raman mapping.

[0204] During the evaluation of the completed map, the spectra of the map were compared with the spectra of the sample C 1 according to the invention and the reference sample C3. For mapping, we used the entire fingerprint range of the samples for profiling, which means the wavelength range of the spectra was between 1800 and 200 cm1. The map provides a "heat map," which is compared to a map of untreated skin. On the map, warmer colors indicate the presence of the sample in the different layers of the skin (the heat map was converted into a black-and-white image using the device's software, where dark shades indicate the depth of skin penetration of the tested samples). The presence of the examined samples can be determined qualitatively during the examination.

[0205] Results

[0206] When evaluating the results, the chemical mapping results of skin treated with the composition Cl according to invention and reference sample C3 were compared with the Raman map of the same but untreated skin (Table 11, Figure 4). Table 11 clearly shows the advantages of the composition according to the invention.

[0207] Table 11: Raman intensity values of the tested samples as a function of skin depth

[0208] _ _ .. • . • Raman intensity

[0209] Meas. no. Dep

[0210] Kth in skin , untreated Cl C3

[0211] 1 - 0.0 0.022 0.002

[0212] 2 0 pm 0.005 0.015 0.092

[0213] 3 50 pm 0.012 0.028 0.105

[0214] 4 100 pm 0.0193 0.11 0.005

[0215] 5 150 pm 0.075 0.002 0.004

[0216] 6 200 pm 0.0143 0.014 0.007

[0217] 7 250 pm 0.0318 0.002 0.008

[0218] 8 300 pm 0.0 0.014 0.003

[0219] 9 350 pm 0.041 0.014 0.006

[0220] 10 400 pm 0.0077 0.015 0.001

[0221] 11 450 pm 0.0072 0.016 0.001

[0222] In Figure 4, created by Raman's proprietary software, the dark shaded areas indicate the depth of skin penetration of the tested samples. Based on the results, it is clear that the penetration of sample Cl was deeper during the 2-hour treatment period. The presence of the composition Cl according to the invention was detectable at around 100 pm, indicating localization in the upper part of the dermis. Based on literature data, the average thickness of the epidermis is 80 pm in the abdomen (see Lintzeri et al. Epidermal thickness in healthy humans: a systematic review and meta-analysis. JEADV 2022, 36, 1991-1200, DOI: 10. 1111 / jdv.18123 and this means the composition reached the upper layer of the dermis. In the case of reference C3, after a 2-hour treatment period the substance was detectable in the upper layer of the skin i.e. the epidermis,

[0223] In summary, it can be concluded that two samples, the composition according to the invention and a reference composition different from the composition according to the invention that was also outside the particle size range of the invention were mapped by Raman spectroscopy, during which it was found that the composition according to the invention showed deeper skin penetration (affecting the dermis layer) than the reference material C3 different from the composition according to the invention. This confirmed the unexpected and hitherto unsolved additional technical effect that our invention exhibits, compared to the state of the art, thereby confirming that our invention is based on inventive activity.

[0224] Example 5: Cosmetic gel composition

[0225] Table 12. Ingredients of the cosmetic gel composition.

[0226] Ingredients Example

[0227] % by weight water qs. to 100

[0228] POPCA 10 capryloyl glycine 1.5 hydroxypropyl trimonium hyaluronate 0 potassium hydroxide 0.20 allantoin 0.2 glycerol 5 panthenol 1 tetrasodium glutamate diacetate 0.1 hydroxyethyl cellulose 1 preservative qs pH regulator qs.

[0229] In the method to prepare the cosmetic gel containing the anionic micelle-cationic polymer complex according to the invention, first the anionic micelle -cationic polymer complex is prepared by the method according to the invention. First, a solution containing N-olive oil and L-pyrrolidone carboxylic acid potassium salt (POPCA) and caprolyl glycine is measured into a heatable flask and heating is started. The KOH catalyst is added during the heating phase and the mixture is heated to 65 to 75 °C while stirring with a spatula, propeller or magnetic stirrer. The mixture is allowed to cool to below 40°C. The cationic polymer (hydroxypropyl trimonium hyaluronate) is prehydrated in water in an amount corresponding to the application amount and added to the anionic micellar system (STP method). Second, the remaining components of the composition are dissolved in the remaining amount of water in a separate container at room temperature, stirring continuously. Then, while stirring continuously, the hydroxyethyl cellulose is slowly added and dispersed in the mixture, allowing the polymer chains to hydrate, then the pre-prepared anionic micelle-cationic polymer complex is added to the gel. The final pH of the composition is adjusted to a skin-friendly pH of 5.0 to 6.0 by a pH regulator additive.

[0230] Example 6: Cream-gel composition

[0231] Table 13. Ingredients of the cream-gel composition.

[0232] Ingredients Example

[0233] Phase A (aqueous) water qs. to 100 allantoin 0.2 glycerol 5 xanthan gum 0.3 acrylates / Cw-30 alkyl acrylate crosspolymer 0.2 panthenol 1

[0234] Phase B (oily) shea butter 3 olive oil 3 fractionated coconut oil 4.5 tocopheryl acetate 0.3 triethanolamine 0.1 hy droxy ethyl acrylate / sodium 1.7 acryloyldimethyl taurate copolymer

[0235] Phase C

[0236] POPCA 9 capryloyl glycine 1.5 hydroxypropyl trimonium hyaluronate 0.1 potassium hydroxide 0.22 cocoyl proline 0.1 tetrasodium glutamate diacetate 0.1

[0237] 1% aqueous solution of sodium ascorbyl 3 phosphate preservative qs pH regulator qs

[0238] The anionic micelle-cationic polymer complex is prepared by the method according to the invention. First, a solution containing N-olive oil L-pyrrolidone carboxylic acid potassium salt (POPCA), capryloyl glycine, tetrasodium glutamate diacetate and cocoyl polyne are measured into a heatable flask, and heating is started. During the heating phase the KOH catalyst is added and the mixture is heated to 60 to 75 °C while stirring with a spatula, propeller or magnetic stirrer. The mixture is allowed to cool to below 40°C. The cationic polymer (hydroxypropyl trimonium hyaluronate) is prehydrated in an amount corresponding to the application amount and the anionic micellar system is added. Second, the components of phase A (aqueous) and phase B (oily) are measured into two separate flasks and are heated to 70 to 75 °C until the materials are completely melted, while stirring slowly. Once the specified temperature is reached, the prepared mixtures are blended using a homogenizer. Then, under vacuum and with constant stirring, the emulsion is cooled to below 40°C, where the components of phase C are added under slow stirring. The final pH of the composition is adjusted to a skin-friendly pH of 5.0 to 6.0 by a pH regulator additive.

[0239] 7. Example: Micellar water composition

[0240] Table 14. Ingredients of the micellar water composition

[0241] Ingredients Example water qs. to 100

[0242] POPCA 12 capryloyl glycine 1.8 hydroxypropyl trimonium hyaluronate 0.2 potassium hydroxide 0.25 allantoin 0.2 cocoyl proline 0.3 glycerol 5 panthenol 1 tetrasodium glutamate diacetate 0. 1 preservative qs. pH regulator qs.

[0243] In the method to prepare the micellar water containing the anionic micelle -cationic polymer complex according to the invention, first the anionic micelle -cationic polymer complex is prepared by the method according to the invention. First, a solution containing N-olive oil and L-pyrrolidone carboxylic acid potassium salt (POPCA) and caprolyl glycine is measured into a heatable flask and heating is started. The KOH catalyst is added during the heating phase and the mixture is heated to 65 to 75 °C while stirring with a spatula, propeller or magnetic stirrer. The mixture is allowed to cool to below 40°C. The cationic polymer (hydroxypropyl trimonium hyaluronate) is prehydrated in water in an amount corresponding to the application amount and the anionic micellar system is added (STP method). Second, the pre-prepared anionic micelle-cationic polymer complex is added to the remaining water, homogenized, and then the remaining components of the formula are added and dissolved at room temperature with continuous stirring. The final pH of the preparation is adjusted to a skin-friendly pH of 5.0 to 6.0 by a pH regulator additive.

[0244] INDUSTRIAL APPLICABILITY

[0245] Based on the above, the composition according to the invention is suitable for penetrating the skin barrier, thus promoting collagen synthesis in the skin. Therefore, the composition according to the invention is suitable for use in the industry, particularly in the cosmetics industry, in the field of manufacturing cosmetic compositions.

Claims

CLAIMS1. A composition comprising a) an anionic micelle-cationic polymer complex as an active ingredient vector, wherein the anionic micelle consists of the following: i) a compound of Formula (I)wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II)wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally an additional excipient; characterised in that the active ingredient vector according to point a) has a diameter in the range of 1 to 10 nm, preferably in the range of 1 to 6 nm, measured by dynamic light scattering using an LSI Nanolab 3D device at a wavelength of 625 nm, at 25°C.

2. A composition comprising a) an anionic micelle-cationic polymer complex as an active ingredient, wherein the anionic micelle consists of the following i) a compound of Formula (I)wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II)wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the anionic micelle-cationic polymer complex according to point a) can be prepared by the following method:

1. An aqueous solution of 0.2 to 15.0% by weight of compound (I) and 0.1 to 3.0% by weight crystalline capryloyl glycine are measured and the mixture is heated;2. During the heating phase, 0.01 to 1.00% by weight KOH is added as a catalyst, and the mixture is heated to 60 to 80°C, preferably 70 to 75°C, and most preferably 70 to 73°C under continuous stirring in order to obtain an anionic lipoamino acid micelle;3. The mixture is cooled to below 40°C and by using the STP method, it is combined with 0.001 to 3.000% by weight cationic hydroxypropyl trimonium hyaluronate previously hydrated in water, in order to obtain the anionic micelle-cationic polymer complex.

3. The composition according to Claim 1 or 2, comprising one or more compounds selected from the following as additional active ingredients according to point b): peptides and their derivatives, amino acids and their derivatives, vitamin C and its derivatives, vitamin B and its derivatives, vitamin A and its derivatives, vitamin K and its derivatives, plant and fruit extracts and waters, allantoin, AHA and BHA acids, ectoine, algae extracts, arbutin, astaxanthin, azelaic acid and its derivatives, bakuchiol, bisabolol, ferulic acid, caffeine, kojic acid, coenzyme Q10, proteins and their derivatives, enzymes, cyclodextrin, alpha-glucan, beta-glucan, bacillus / saccharomyces / pseudoalteromonas ferment, biotin, glycoin, phospholipids and their derivatives, RNA and DNA derivatives, saccharide isomerate, pantolactone, carnitine, zinc-, copper-, sulfur- and magnesium compounds.

4. A composition according to any one of Claims 1 to 3, comprising one or more of the following compounds as excipients as described in point (d): da) humectants selected from the group consisting of glycerol and its derivatives, propanediol, glycols and glycol ethers, plant extracts, sugar alcohols, hyaluronic acid and its derivatives, mono-, di- and polysaccharides, lactic acid and its derivatives, amino acids and their derivatives, urea and its derivatives, betaine, gluconolactone, glyceryl esters, xylityl glucoside, aldonic acids, flavonoids, acetamido ethoxyethanol; db) emollients selected from the group consisting of ceramides, vegetable squalane, polyethylene glycol and its derivatives, shea butter and its derivatives, vegetable oils and their derivatives, silicone oils, lanolin and its derivatives, vegetable esters, beeswax and its derivatives, vegetable waxes, cholesterol, lipid derivatives, hydrocarbon oils and waxes, silicone derivatives, creatine, alkanes, triglyceride esters, acetoglyceride esters, ethoxylated glyceride esters, alkyl esters, alkenyl esters, fatty acids and their esters, fatty alcohols and their derivatives, fatty alcohol ethers, ether esters, polyols and polyether derivatives, polyol ethers, wax esters, phospholipids, sterols, amides and their derivatives; de) preservatives selected from the group consisting of sodium benzoate, potassium sorbate, phenethyl alcohol, caprylyl glycol, phenoxyethanol, benzyl alcohol, dihydroxyacetic acid, benzoic acid, sorbic acid, sodium hydroxymethyl glycinate, octenidine HC1, chlorophene sin, PEG-4 laurate (and) iodopropynyl butylcarbamate, chloroxylenol, undecylenic acid, sodium levulinate, sodium anisate; dd) gelling agents selected from the group consisting of polysaccharides and their derivatives, starch, xanthan gum, guar gum and its derivatives, carrageenan, alginates, pectins, cellulose derivatives, acrylic acid-based polymers, polyacrylamides and alkylene oxide-based polymers, carbohydrates, hectorite, silicondioxide dimethyl silylate, silicon dioxide, carbomer, gum arabic, ammonium acryloyldimethyltaurate / VP copolymer, sodium polyacryloyl dimethyltaurate, hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer; de) emulsifiers selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, polyethylene glycol derivatives and esters, phospholipids, fatty acid mono- and diglycerides, polyglycerol esters, sucrose esters of fatty acids, emulsifying waxes, alkyl sulfates, alkoxylated alcohols, alkyl polyglucosides, stearates, proteins, hydrocolloids and their derivatives, quaternary ammonium compounds, alcohol polyethylene glycol ethers, fatty acid polyethylene glycol esters, polyoxyethylene / polyoxypropylene block copolymers, fatty alcohols, fatty acids, ammonium acryloyldimethyl taurate / VP copolymer, sodium polyacryloyldimethyl taurate, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, acrylate polymers, glutamates, alkyl carbamates, fatty acid amido propyl dimethylamines, lipoamides, phosphate esters; df) chelating agents selected from the group consisting of tetrasodium glutamate diacetate, EDTA and its derivatives, sodium phytate, sodium gluconate, phytic acid, caprylhydroxamic acid, trisodium ethylenediamine disuccinate, trisodium dicarboxymethyl alaninate; dg) surfactants selected from the group consisting of alkyl ether sulfates, alkyl sulfates, alkyl benzene sulfonates, fatty acid soaps, alkyl phenol ethoxylates, alcohol ethoxylates, nonylphenols, quaternary ammonium compounds and their esters, pyridine and imidazoline derivatives, alkyl sulfonates, alkyl aryl sulfonates, alkyl ethanolamine sulfates, alkyl ethanolamine sulfonates, alkyl benzimidazole sulfonates, betaine derivatives, amino oxides, phosphate esters, sorbitan fatty acid esters and ethoxylates, carboxylates, alkanolamides, sulfonium compounds, amino carboxylic acids, glycolipids, lipopeptides and lipoproteins, phospholipids, polymeric surfactants, alkyl phosphates, glycerol sulfates, alkyl sulfoacetates, alkyl sulfosuccinates, polyglycol ether sulfates, sarcosinates, acyl acrylates, alkyl pyridinium compounds, sapamine-type substances, disulfimides, saponins, di- and triol fatty acid esters, polyglycol derivatives, alkyl polyglycosides, lipoamino acids and their derivatives, polysorbates, taurates, isethionates.

5. The composition according to any of Claims 1 to 4 for dermatological or cosmetic use.

6. Use of the composition according to any of Claims 1 to 4 for the production of a dermatological composition.

7. Use of the composition according to any of Claims 1 to 4 for the production of a cosmetic composition, most preferably a skincare composition.

8. An anionic micelle-cationic polymer complex, wherein the anionic micelle consists of the following (i) a compound of Formula (I)wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid and linolenic acid or mixtures thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II)wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the active ingredient vector according to point a) has a diameter in the range of 1 to 10 nm, preferably in the range of 1 to 6 nm, measured by dynamic light scattering using an LSI Nanolab 3D device at a wavelength of 625 nm, at 25°C.

9. An anionic micelle-cationic polymer complex, wherein the anionic micelle consists of the following i) a compound of Formula (I)(I) wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid, and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II)wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the anionic micelle-cationic polymer complex according to point a) can be prepared by the following method:

1. An aqueous solution of 0.2 to 15.0% by weight of a compound (I) and 0.1 to 3.0% by weight of crystalline capryloyl glycine are measured and the mixture is heated;2. During the heating phase, 0.01 to 1.00% by weight KOH is added as a catalyst, and the mixture is heated to 60 to 80°C, preferably 70 to 75°C, and most preferably 70 to 73°C under continuous stirring in order to obtain an anionic lipoamino acid micelle;3. The mixture is cooled to below 40°C and by using the STP method, it is combined with 0.001 to 3.000% by weight cationic hydroxypropyl trimonium hyaluronate, previously hydrated in water, in order to obtain the anionic micelle-cationic polymer complex.

10. Method for producing an anionic micelle-cationic polymer complex, wherein the anionic micelle consists of the following i) a compound of Formula (I)wherein R represents a group selected from palmitic acid, stearic acid, arachidic acid, behenic acid, myristic acid, lignoceric acid, oleic acid, palmitoleic acid, linoleic acid, and linolenic acid, or a mixture thereof; and ii) capryloyl glycine, and wherein the cationic polymer is a hydroxypropyl trimonium hyaluronate of Formula (II)wherein n = 1100 to 1800 and the anionic micelle and the cationic polymer are linked to each other by electrostatic interaction; b) optionally an additional active ingredient; c) as excipient, at least one compound selected from tetrasodium glutamate diacetate and cocoyl proline; and d) optionally additional excipients; characterised in that the anionic micelle-cationic polymer complex according to point a) can be prepared by the following method:

1. An aqueous solution of 0.2 to 15.0% by weight of a compound (I) and 0.1 to 3.0% by weight of crystalline capryloyl glycine are measured and the mixture is heated;2. During the heating phase, 0.01 to 1.00% by weight KOH is added as a catalyst, and the mixture is heated to 60 to 80°C, preferably 70 to 75°C, and most preferably 70 to 73°C under continuous stirring in order to obtain an anionic lipoamino acid micelle;3. The mixture is cooled to below 40°C and by using the STP method, it is combined with 0.001 to 3.000% by weight cationic hydroxypropyl trimonium hyaluronate, previously hydrated in water, in order to obtain the anionic micelle-cationic polymer complex.

11. The anionic micelle -cationic polymer complex according to Claim 8 or 9 for dermatological or cosmetic use.

12. Use of the anionic micelle -cationic polymer complex according to Claim 8 or 9 for the production of a dermatological composition.

13. Use of the anionic micelle -cationic polymer complex according to Claim 8 or 9 for the production of a cosmetic composition, more preferably a skincare composition.

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