Elastic liposome composition for enhancing skin penetration comprising polyglyceryl-based surfactant, and preparation method therefor

Abstract

One aspect relates to elastic liposomes comprising lecithin and a polyglyceryl-based surfactant, and a preparation method therefor. The elastic liposomes according to one aspect contain lecithin and a polyglyceryl-based surfactant in a specific ratio, thereby enhancing elasticity, deformability, flexibility, skin permeability, active ingredient encapsulation efficiency, and stability. In addition, the elastic liposomes can be effectively applied to cosmetic compositions, and thus can be useful in the manufacture of cosmetics with improved skin absorption.

Description

Elastic liposome composition for enhancing skin penetration containing a polyglyceryl-based surfactant and method for preparing the same

[0001] The present invention relates to an elastic liposome composition for enhancing skin penetration comprising a polyglyceryl-based surfactant and a method for preparing the same.

[0002]

[0003] Skin aging progresses due to photo-oxidative damage induced by reactive oxygen species (ROS) generated by ultraviolet (UV) exposure. There is a demand for the development of skin delivery systems to effectively deliver functional ingredients, such as antioxidants, to the skin—which can eliminate ROS, the primary cause of skin aging, and protect skin tissues and cells. Accordingly, active development is underway regarding skin delivery systems for active ingredients utilizing liposomes, which are spherical lipid vesicles composed of a lipid bilayer.

[0004] Liposomes have the advantage of being able to encapsulate active ingredients and poorly soluble substances within the vesicle; however, their effectiveness is limited due to low encapsulation efficiency of active ingredients and poor stability and skin permeability. To address these issues, new types of carriers that improve upon liposomes have been developed, such as ethosomes, cell-penetratin-peptides liposomes, and deformable liposomes. Among these, elastic liposomes exhibit higher encapsulation efficiency of active ingredients and superior stability compared to conventional liposomes, while possessing elasticity, deformability, and flexibility. The elastic liposomes are composed of lecithin, which forms a double layer, and a surfactant acting as an edge activator, and possess elasticity and deformability. Consequently, due to their deformability and flexibility, elastic liposomes can effectively penetrate the stratum corneum, thereby enabling excellent skin delivery efficiency of active ingredients.

[0005] Accordingly, the inventors have developed an elastic liposome composition and a method for manufacturing the same that possess not only excellent properties such as elasticity, deformability, flexibility, skin permeability, and active ingredient capture efficiency, but also stability, thereby completing the present invention.

[0006]

[0007] One aspect provides an elastic liposome comprising hydrogenated lechitin, a polyglyceryl-based surfactant, a water-soluble solvent, and a fatty acid.

[0008] Another aspect is to provide a cosmetic composition comprising the above-mentioned elastic liposomes.

[0009] Another aspect provides a method for manufacturing elastic liposomes comprising the steps of: mixing a water-soluble solvent, hydrogenated lechitin, a polyglyceryl-based surfactant, and a fatty acid to obtain a mixture; and pressurizing the mixture.

[0010]

[0011] One aspect provides an elastic liposome comprising hydrogenated lechitin, a polyglyceryl-based surfactant, a water-soluble solvent, and a fatty acid.

[0012] The above lecithin is a representative naturally derived surfactant and encompasses a group of yellowish-brown fatty substances occurring in animal and plant tissues, composed of phosphate, choline, fatty acids, glycerol, glycolipids, and triglyceride phospholipids. Lecithin according to one aspect includes both naturally derived lecithin extracted from animals and plants such as egg yolks, soybeans, and corn, and microorganisms such as E. coli, as well as synthetic lecithin. Examples of lecithin include natural phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, lysophosphatidylcholine, sphingomyelin, egg yolk lecithin, and soybean lecithin, or synthetic lecithins such as dilauroylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, palmitoylphosphatidylcholine, and oleoylphosphatidylcholine.

[0013] In addition, the above "hydrogenated lecithin" refers to a hydrogenated lecithin and plays a role in increasing the stability of the structure, and the above "hydrogenated lecithin" refers to lecithin that has been hydrogenated by more than 90%.

[0014] In one embodiment, the polyglyceryl-based surfactant may be one or more selected from the group consisting of polyglyceryl 3-methylglucose diastearate, polyglyceryl-10 laurate, polyglyceryl-10 stearate, polyglyceryl-10 myristate, polyglyceryl-10 pentastearate, polyglyceryl 10 distearate, polyglyceryl-10 linoleate, polyglyceryl-10 oleate, polyglyceryl-10 caprate, polyglyceryl-6 pentastearate, polyglyceryl 4-diisostearate, polyglyceryl-2 sesquiisostearate, polyglyceryl-2 isostearate, polyglyceryl-2 tetraisostearate, and polyglyceryl-2 diisostearate, and specifically, it may be polyglyceryl 3-methylglucose diastearate.

[0015] In one embodiment, the water-soluble solvent may be one or more selected from the group consisting of water and alcohols having 1 to 5 carbon atoms, and specifically, the water-soluble solvent may be water, for example, distilled water. In addition, the alcohol having 1 to 5 carbon atoms may be ethanol.

[0016] In one embodiment, the fatty acid may be one or more selected from the group consisting of caprylic / capric triglycerides, oleic acid, linoleic acid, linolenic acid, lauric acid, palmitic acid, stearic acid, elaidic acid, myristic acid, arachidonic acid, and isopropyl myristate, and specifically may be caprylic / capric triglycerides.

[0017] According to one aspect, "elastic liposome" may refer to a colloidal particulate formulation in which nano-sized spherical particles composed of a phospholipid bilayer are the main component, or may refer to an overall formulation comprising the colloidal particulate formulation or a constituent such as some unencapsulated active ingredients. In this specification, "elastic liposome" may refer to an elastic liposome suspension.

[0018] In one embodiment, the elastic liposome may further include one or more selected from the group consisting of glycerin and ceramide, and specifically may further include both glycerin and ceramide.

[0019] In one embodiment, the ceramide may be one or more selected from the group consisting of ceramide NS, ceramide AS, ceramide EOS, ceramide NDS, ceramide ADS, ceramide EODS, ceramide NP, ceramide AP, ceramide EOP, ceramide NH, ceramide AH, and ceramide EOH, and specifically may be ceramide NP.

[0020] In one embodiment, the elastic liposome may further include an antioxidant.

[0021] In one embodiment, the antioxidant may be a flavonoid antioxidant, specifically one or more selected from the group consisting of quercetin, apigenin, catechin, and rutin, and more specifically quercetin.

[0022] The above elastic liposomes have excellent skin permeability, enabling effective delivery of the antioxidant into the skin. Furthermore, the antioxidant is merely an example of an active ingredient and can be appropriately modified depending on the ingredient to be delivered into the skin.

[0023] In one embodiment, the average particle size of the elastic liposome is 100 to 300 nm, 100 to 280 nm, 100 to 260 nm, 100 to 240 nm, 100 to 220 nm, 100 to 200 nm, 100 to 180 nm, 100 to 160 nm, 100 to 150 nm, 100 to 140 nm, 110 to 280 nm, 110 to 260 nm, 110 to 240 nm, 110 to 220 nm, 110 to 200 nm, 110 to 180 nm, 110 to 160 nm, 110 to 150 nm, 110 to 140 nm, 120 to 260 nm, 120 to 240 nm It may be nm, 120 to 220 nm, 120 to 200 nm, 120 to 180 nm, 120 to 160 nm, 120 to 150 nm, 120 to 140 nm, or 130 to 140 nm.

[0024] If the average particle size of the elastic liposomes is smaller than 100 nm, the amount of active ingredient loaded is reduced, and the amount of active ingredient delivered into the skin may be reduced, and if the average particle size of the elastic liposomes is 300 nm or more, skin permeability may be reduced.

[0025] In one embodiment, the polydispersity index of the elastic liposome may be 0.10 to 0.26, 0.12 to 0.26, 0.14 to 0.26, 0.16 to 0.26, 0.18 to 0.26, 0.20 to 0.26, 0.22 to 0.26, 0.22 to 0.25, 0.22 to 0.24, 0.22 to 0.23, 0.23 to 0.26, 0.23 to 0.25, or 0.23 to 0.24.

[0026] If the polydispersity index of the above elastic liposomes exceeds 0.3, the particle size distribution becomes too wide, which may reduce the delivery efficiency of the active ingredient.

[0027] In one embodiment, the absolute value of the zeta potential of the elastic liposome may be 25 to 30 mV, 26 to 32 mV, 28 to 32 mV, 24 to 31 mV, 22 to 31 mV, 20 to 31 mV, 18 to 30 mV, or 15 to 30 mV.

[0028] When the absolute value of the zeta potential of the above elastic liposomes is less than 25 mV, the electrostatic repulsion between particles decreases, and particle aggregation or precipitation may occur.

[0029] The above liposomes may have a high "entrapment efficiency" of active ingredients. The entrapment efficiency is a value representing the ratio of a specific substance (e.g., active ingredient) that is entrapped within a delivery system such as a liposome, expressed as a percentage (%) of the amount of substance actually loaded within the delivery system relative to the amount of substance initially introduced. For example, the entrapment efficiency of the elastic liposome may be a value calculated according to the following Equation 1, after removing unentrapped active ingredients from a certain amount of the elastic liposome using a syringe filter, destroying the elastic liposome to measure the amount of substance entrapped internally:

[0030] [Mathematical Formula 1]

[0031] Entrapment efficiency(%) = {(T - Q ) / T} x 100.

[0032] Here, T is the concentration of the active ingredient initially administered (µg / mL), and Q is the concentration of the active ingredient that did not pass through the 0.45 µm syringe filter (µg / mL).

[0033] In one embodiment, the effective ingredient capture rate of the elastic liposome may be 38 to 65%, 40 to 65%, 42 to 65%, 45 to 70%, 50 to 65%, or 55 to 65%. For example, if the effective ingredient of the elastic liposome is an antioxidant, the elastic liposome may have an effective ingredient capture rate of about 56 to 60%.

[0034] The above elastic liposomes may possess high "skin permeability." Skin permeability refers to the ability of a specific substance (e.g., active ingredient) to pass through the skin barrier (particularly the stratum corneum) and penetrate deeper layers of the skin (epidermis, dermis, etc.), and this is derived from physical properties such as the elasticity, deformability, and flexibility of the liposomes. The skin permeability of the above liposomes can be quantitatively verified through the Deformability Index. For example, the above skin permeability can be measured using the permeability of an artificial barrier using a small extruder; specifically, it may be a value calculated according to the following Equation 2 by measuring the amount of elastic liposomes passing through a polycarbonate membrane having pores of 0.1 μm and the particle size of the elastic liposomes that passed through the membrane:

[0035] [Mathematical Formula 2]

[0036] Deformability index = J Flux x (r v / r p ) 2 .

[0037] Here, J Flux is the amount of elastic liposomes (mL) that passed through the membrane, and r v is the elastic liposome particle size (nm) after extrusion, and r p is the membrane pore size (nm).

[0038] In one embodiment, the deformability index of the elastic liposome may be 1.6 to 3, 1.8 to 3, 2 to 3, 2.2 to 3, 2.4 to 3, 2.6 to 3, 1.6 to 2.9, 1.8 to 2.9, 2 to 2.9, 2.2 to 2.9, 2.4 to 2.9, or 2.6 to 2.9.

[0039] The elastic liposome may include both the hydrogenated lechitin and the polyglyceryl-based surfactant, and may exhibit a smaller particle size, a high active ingredient capture rate, and variable formation compared to an elastic liposome that does not include the hydrogenated lechitin or the polyglyceryl-based surfactant.

[0040] In one embodiment, the elastic liposome may comprise the hydrogenated lechitin and the polyglyceryl-based surfactant in a weight ratio of 1:0.25 to 4, 1:0.25 to 3, 1:0.25 to 2, 1:0.5 to 4, 1:0.5 to 3, 1:0.5 to 2, 1:0.75 to 4, 1:0.75 to 3, 1:0.75 to 2, 1:0.75 to 1.5, or 1:1.

[0041] An elastic liposome containing the hydrogenated lechitin and the polyglyceryl-based surfactant in the above weight ratio can exhibit a smaller particle size, a higher active ingredient capture rate, and variable formation compared to an elastic liposome that does not contain the hydrogenated lechitin and the polyglyceryl-based surfactant in the above weight ratio range.

[0042] In one experimental example, it was confirmed that the elastic liposomes exhibited excellent particle size, polydispersity index, zeta potential, capture rate of active ingredients, and variable formation when the weight ratio of hydrogenated lechitin to polyglyceryl-based surfactant was 1:0.25 to 4 (see Experimental Example 1).

[0043] According to another experimental example, in the case of an elastic liposome containing both the hydrogenated lechitin and the polyglyceryl-based surfactant, the degree of change in particle size was 0.5 to 6% even after storage at room temperature for 12 weeks, which was significantly lower than the degree of change in particle size of 6 to 20% for an elastic liposome containing only one of the hydrogenated lechitin and the polyglyceryl-based surfactant, thus confirming excellent stability (see Experimental Example 2).

[0044] In addition, in one embodiment, the elastic liposome comprises the hydrogenated lecithin, the polyglyceryl-based surfactant, the fatty acid, the glycerin, and the ceramide in a weight ratio of 1 : 0.25 to 4 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, a weight ratio of 1 : 0.25 to 3 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, a weight ratio of 1 : 0.25 to 2 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, and a weight ratio of 1 : 0.25 to 1.5 : 1.125 to 5 : 6.25 to 25 : A weight ratio of 0.0625 to 0.25, a weight ratio of 1 : 0.5 to 4 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, a weight ratio of 1 : 0.5 to 3 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, a weight ratio of 1 : 0.5 to 2 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, a weight ratio of 1 : 0.5 to 1.5 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, 1 : 0.75 to 4 : 1.125 to 5 : 6.25 to 25 : It may be included in a weight ratio of 0.0625 to 0.25, a weight ratio of 1 : 0.75 to 3 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, a weight ratio of 1 : 0.75 to 2 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25, or a weight ratio of 1 : 0.75 to 1.5 : 1.125 to 5 : 6.25 to 25 : 0.0625 to 0.25.

[0045] An elastic liposome containing the hydrogenated lechitin, the polyglyceryl-based surfactant, the fatty acid, the glycerin, and the ceramide in the above weight ratios can exhibit a smaller particle size, a higher active ingredient capture rate, and variable formation compared to an elastic liposome that does not contain the hydrogenated lechitin, the polyglyceryl-based surfactant, the fatty acid, the glycerin, and the ceramide in the above weight ratio ranges.

[0046] Therefore, elastic liposomes according to one aspect exhibit excellent elasticity, deformability, flexibility, skin permeability, active ingredient capture efficiency, and stability, making them useful for delivering active ingredients into the skin.

[0047] Another aspect provides a cosmetic composition comprising the above-mentioned elastic liposomes.

[0048] The above "elastic liposome" may be within the aforementioned range.

[0049] The above elastic liposome may further include an antioxidant, and the elastic liposome further including the antioxidant may be utilized as an antioxidant cosmetic composition.

[0050] The above "antioxidant" refers to an activity that prevents and improves the aging process of cells and the oxidation process of the skin by removing free radicals, which are the main causative substances of skin aging, and can be measured through experiments measuring phenol content and flavonoid content.

[0051] The above cosmetic composition may have the efficacy to prevent or improve skin aging by improving skin oxidation, that is, by having a skin antioxidant effect. In this case, the skin aging may be one or more selected from the group consisting of wrinkles, decreased skin elasticity, melasma, freckles, skin damage caused by ultraviolet rays, skin dryness, weakening of the skin barrier, weakening of skin transparency, keratinization, skin texture damage, and skin cancer.

[0052] In addition, the cosmetic composition may be prepared in any formulation conventionally manufactured in the technical field to which the present invention belongs. For example, the composition may be formulated into a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, spray, etc. Specifically, the cosmetic composition may be manufactured in the form of a lotion such as a softening lotion or a nourishing lotion, a fluid such as a facial lotion or a body lotion, a cream such as a nourishing cream, a moisturizing cream, or an eye cream, an essence, a cosmetic ointment, a spray, a gel, a pack, a sunscreen, a makeup base, a foundation in liquid, solid, or spray form, a powder, a makeup remover such as a cleansing cream, a cleansing lotion, or a cleansing oil, a cleanser such as a cleansing foam, a soap, or a body wash, a liquid or gel formulation of mesotherapy that can be injected into the skin layer, and a formulation mixed with hyaluronic acid gel. More specifically, the cosmetic composition may be manufactured in one or more formulations selected from the group consisting of a serum, lotion, essence, paste, mask pack, patch, gel, cream, lotion, nourishing lotion, nourishing cream, moisturizing cream, massage cream, powder, soap, cleanser, oil, foundation, makeup base, wax, and spray.

[0053] The above cosmetic composition may further comprise any conventional cosmetic ingredient selected from additional ingredients commonly used in cosmetics, such as excipients, thickeners, dispersants, fragrances, fillers, preservatives, antiseptics, neutralizing agents, sweeteners, vitamins, free radical scavengers, metal ion chelating agents, functional ingredients, and mixtures thereof. A person skilled in the art may select any additional ingredient and / or the amount thereof so that the advantageous properties of the cosmetic composition according to one aspect are not adversely affected or are substantially affected by the expected addition.

[0054] For example, the above excipients may include surfactants, emulsifiers, saponic acid, solvents, coloring agents, preservatives, antioxidants, antifoaming agents, antibacterial agents, anti-redeposition agents, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, hydrotropy-inducing substances, humectants, fragrances, preservatives, proteins, silicones, solubilizers, sugar derivatives, sunblocks, vitamins, plant extracts, waxes, fatty acids, higher alcohols, hydrocarbon oils, ester oils, triglycerides, vegetable oils, etc.

[0055] The above cosmetic composition may additionally include ingredients typically added to cosmetic compositions, such as purified water, surfactants, moisturizers, lower alcohols, chelating agents, disinfectants, preservatives, antioxidants, stabilizers, solubilizers, vitamins, pigments, and fragrances.

[0056] In addition, the above cosmetic composition may be appropriately formulated with ingredients commonly used in external skin preparations such as cosmetics or pharmaceuticals, for example, aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, UV absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, various skin nutrients, or combinations thereof as needed. The above cosmetic composition may also appropriately include metal chelating agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid; caffeine, tannin, bellapamil, licorice extract, glablidin, hot water extract of the fruit of *calin*, various herbal medicines, pharmaceuticals such as tocopherol acetate, glycyrrhizic acid, tranexamic acid and its derivatives or salts, vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, trehalose, etc.

[0057] In the case where the above cosmetic composition is a surfactant-containing cleansing formulation, it may further include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linolenic acid derivative, or ethoxylated glycerol fatty acid ester, etc., as a carrier component.

[0058] In addition, if the above cosmetic composition is in the form of a cream or gel, it may further include animal oil, vegetable oil, wax, paraffin, starch, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide as a carrier component.

[0059] In addition, if the above cosmetic composition is in the form of a solution or emulsion, it may further include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, propylene glycol, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan as a solvent, solvating agent, or emulsifying agent.

[0060] In the case where the above cosmetic composition is in the form of a suspension, it may further include, as a carrier component, a liquid diluent such as water, ethanol, or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanth.

[0061] In the case where the above cosmetic composition is in the form of a powder or spray, it may further include lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder as a carrier component, and in particular, in the case of a spray formulation, it may further include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0062] The above cosmetic composition may be used by applying it alone or in combination, or by applying it in combination with other cosmetic compositions other than the cosmetic composition according to one aspect. Furthermore, all ingredients included in the above cosmetic composition do not exceed the regulations set by each country. Additionally, the cosmetic composition according to one aspect may be used according to a standard method of use, and the frequency of use may be varied depending on the user's skin condition or preference.

[0063] Another aspect provides a method for manufacturing an elastic liposome comprising the steps of: mixing a water-soluble solvent, hydrogenated lechitin, a polyglyceryl-based surfactant, and a fatty acid to obtain a mixture; and pressurizing the mixture.

[0064] The above "water-soluble solvent," "elastic liposome," "hydrogenated lechitin," "polyglyceryl-based surfactant," and "fatty acid" may be within the aforementioned range.

[0065] The step of pressurizing the above mixture may be performed at a pressure of 1,000 to 1,500 bar, 1,000 to 1,400 bar, 1,000 to 1,300 bar, 1,100 to 1,500 bar, 1,100 to 1,400 bar, 1,100 to 1,300 bar, 1,200 to 1,500 bar, or 1,200 to 1,400 bar.

[0066] If the pressure of the step of pressurizing the above mixture is less than 1,000 bar, the homogeneity and dispersibility of the liposomes may be reduced due to the low pressure, and if the pressure of the step of pressurizing is 1,500 bar or more, the structure of the liposomes may be destroyed by excessive pressure or the particles may be made too small, thereby reducing the physical stability of the liposomes.

[0067] In one embodiment, the step of obtaining the mixture may involve mixing ceramide as well.

[0068] In one embodiment, the step of obtaining the mixture may also involve mixing an antioxidant together.

[0069] In addition, in one embodiment, the step of obtaining the mixture may be to mix the ceramide and the antioxidant together.

[0070] The above antioxidant may be a flavonoid-based antioxidant, and according to one embodiment, may be quercetin, apigenin, catechin, and rutin, and more specifically, may be quercetin.

[0071] In one embodiment, if the step of obtaining the mixture involves mixing ceramide as well, the method may further include the step of mixing an antioxidant after the step of obtaining the mixture.

[0072] In one embodiment, if the step of obtaining the mixture also involves mixing an antioxidant, the method may further include the step of mixing ceramide after the step of obtaining the mixture.

[0073] In one embodiment, prior to the pressurizing step, the method may further include a step of heating and stirring the mixture to a temperature of 60 to 100 ℃, 70 to 100 ℃, 60 to 90 ℃, 70 to 90, and 75 to 85 ℃.

[0074] If the temperature at which the mixture is heated is 60°C or lower prior to the pressurizing step, the solubility of the mixture may be significantly reduced and a uniform mixture may not be achieved; and if the temperature at which the mixture is heated is 100°C or higher prior to the pressurizing step, the phospholipid layer structure of the liposome may be destroyed or deformed.

[0075] In one embodiment, the step of obtaining the mixture may be to mix the hydrogenated lechitin and the polyglyceryl-based surfactant in a weight ratio of 1:0.25 to 4, 1:0.25 to 3, 1:0.25 to 2, 1:0.5 to 4, 1:0.5 to 3, 1:0.5 to 2, 1:0.75 to 4, 1:0.75 to 3, 1:0.75 to 2, 1:0.75 to 1.5, or 1:1.

[0076] The elastic liposome prepared by mixing the hydrogenated lechitin and the polyglyceryl-based surfactant in the weight ratio in the step of obtaining the above mixture may exhibit a smaller particle size, a higher active ingredient capture rate, and variable formation compared to the elastic liposome not prepared by mixing the hydrogenated lechitin and the polyglyceryl-based surfactant in the weight ratio range.

[0077] In addition, in one embodiment, the step of obtaining the mixture comprises the hydrogenated lechitin, the polyglyceryl-based surfactant, the fatty acid, and the ceramide in a weight ratio of 1 : 0.25 to 4 : 1.125 to 5 : 0.0625 to 0.25, a weight ratio of 1 : 0.25 to 3 : 1.125 to 5 : 0.0625 to 0.25, a weight ratio of 1 : 0.25 to 2 : 1.125 to 5 : 0.0625 to 0.25, a weight ratio of 1 : 0.25 to 1.5 : 1.125 to 5 : 0.0625 to 0.25, and a weight ratio of 1 : 0.5 to 4 : 1.125 to 5 : 0.0625 to 0.25. Weight ratio, weight ratio of 1 : 0.5 to 3 : 1.125 to 5 : 0.0625 to 0.25, weight ratio of 1 : 0.5 to 2 : 1.125 to 5 : 0.0625 to 0.25, weight ratio of 1 : 0.5 to 1.5 : 1.125 to 5 : 0.0625 to 0.25, weight ratio of 1 : 0.75 to 4 : 1.125 to 5 : 0.0625 to 0.25, weight ratio of 1 : 0.75 to 3 : 1.125 to 5 : 0.0625 to 0.25, weight ratio of 1 : 0.75 to 2 : 1.125 to 5 : 0.0625 to 0.25, weight ratio of 1 : 0.75 to It may be mixed in a weight ratio of 1.5 : 1.125 to 5 : 0.0625 to 0.25.

[0078] The elastic liposome prepared by mixing the hydrogenated lechitin, the polyglyceryl-based surfactant, the fatty acid, the glycerin, and the ceramide in the weight ratio in the step of obtaining the above mixture may exhibit a smaller particle size, a higher active ingredient capture rate, and variable formation compared to an elastic liposome not prepared by mixing the hydrogenated lechitin, the polyglyceryl-based surfactant, the fatty acid, the glycerin, and the ceramide in the weight ratio range.

[0079] The elastic liposomes produced by the above method exhibit excellent elasticity, deformability, flexibility, skin permeability, and active ingredient capture efficiency, making them useful for use in cosmetic compositions for delivering active ingredients.

[0080]

[0081] An elastic liposome composition and a method for preparing the same according to one aspect may enable the realization of superior elasticity, deformability, flexibility, skin permeability, active ingredient capture efficiency, and stability by containing lecithin and a polyglyceryl-based surfactant in specific proportions. Furthermore, a cosmetic composition comprising the elastic liposome composition of the present invention can achieve excellent skin improvement effects by effectively delivering active ingredients to the skin.

[0082]

[0083] Figure 1 is a graph comparing the particle size (nm) of elastic liposomes of Examples 1 to 7 and Comparative Examples 1 to 2 immediately after preparation and after 12 weeks of storage at room temperature.

[0084] Figure 2 is a graph showing the skin penetration amount of quercetin over time for the control group (1,3-butylene glycol), Comparative Example 1, and Examples 1 to 7.

[0085] Figure 3 is a graph showing the amount of quercetin present in the stratum corneum (Tape), the amount of quercetin present in the skin (epidermis and dermis) (Skin), and the amount of quercetin that passed through the skin (Transdermal) after 12 hours, expressed as a percentage (%) for the control group (1,3-butylene glycol), Comparative Example 1, and Examples 1 to 7.

[0086]

[0087] The present invention will be explained in more detail below through examples. However, these examples are intended to illustrate the invention and the scope of the invention is not limited to these examples.

[0088]

[0089] Preparation Example

[0090] Preparation Example 1. Preparation of elastic liposomes in Examples 1 to 7

[0091] To prepare the elastic liposomes of Examples 1 to 7, mixtures were prepared by dissolving Phase A and Phase B, respectively, with different ratios of polyglyceryl-3-methylglucose distearate and hydrogenated lecithin as shown in the composition of Table 1 below. Subsequently, the prepared mixtures of Phase A and B were heated to 80°C and mixed using a homogenizer at 4,000 rpm for 30 minutes, and passed through an ultra-high pressure disperser three times under high pressure conditions of 1,300 bar to prepare the elastic liposomes of Examples 1 to 7 with different ratios of polyglyceryl-3-methylglucose distearate and hydrogenated lecithin.

[0092]

[0093] Ingredient Weight (%) Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 A Purified Water Top to 100 Glycerin 5555555 Hydrogenated Lecithin 0.20.30.40.50.60.70.8 B Polyglyceryl-3 Methylglucose Distearate 0.80.70.60.50.40.30.2 Quercetin 0.10.10.10.10.10.10.10.1 Caprylic / Capric Triglyceride 1111111 Ceramide NP 0.050.050.050.050.050.050.05

[0094]

[0095] Preparation Example 2. Preparation of elastic liposomes in Comparative Examples 1 and 2

[0096] A mixture was prepared by dissolving phase A and phase B, respectively, according to the composition of Table 2. Subsequently, the prepared mixture of phases A and B was heated to 80°C and mixed using a homogenizer at 4,000 rpm for 30 minutes, and then passed through an ultra-high pressure disperser three times under high pressure conditions of 1,300 bar to prepare liposomes and nanoemulsions.

[0097]

[0098] Ingredient Weight (%) Comparative Example 1 Comparative Example 2 A Purified Water Top to 100 Glycerin 55 Hydrogenated Lecithin 1.0-B Polyglyceryl-3 Methylglucose Distearate-1.0 Quercetin 0.10.1 Caprylic / Capric Triglyceride 11 Ceramide NP 0.05 0.05

[0099]

[0100] Experimental Example

[0101] Experimental Example 1. Measurement of Physical Properties

[0102] (1) Method for measuring particle size, zeta potential, and polydispersity index of elastic liposomes

[0103] Particle size, polydispersity index, and zeta potential were measured using a Zetasizer nano ZS analyzer, and 750 µl of each sample was dispensed into a cell (DTS1070, Malvern Instruments Ltds) and measured three times.

[0104]

[0105] (2) Method for measuring the capture efficiency of elastic liposomes

[0106] For the measurement of quercetin capture efficiency, a certain amount of the elastic liposome composition was taken, and uncaptured quercetin was removed by repeating the process three times using a 0.45 µm syringe filter (Hyundai Micro, Polyvinylidene fluoride, 25 mm, Korea). 10 mL of ethanol was mixed with 1 mL of the elastic liposome composition from which the uncaptured quercetin had been removed, and the lipid membrane of the elastic liposomes was disrupted by ultrasound. Subsequently, the ethanol was removed using a rotary evaporator, 1 mL of ethanol was added, and the quercetin captured in the elastic liposomes was quantitatively analyzed using a microplate reader. A calibration curve for quercetin at different concentrations was constructed to calculate the concentration of quercetin captured within the elastic liposomes, and the capture efficiency was calculated according to Equation 1 below:

[0107] [Mathematical Formula 1]

[0108] Entrapment efficiency(%) = {(TQ) / T} x 100.

[0109] Here, T is the initial concentration of quercetin (µg / mL), and Q is the concentration of quercetin that did not pass through a 0.45 µm syringe filter (µg / mL).

[0110]

[0111] (3) Method for measuring variable formation of elastic liposomes

[0112] For variable formation, the permeability of the artificial barrier was measured using a small extruder. After applying a constant pressure of 0.2 MPa to the elastic liposomes for 1 minute, the amount of elastic liposomes passing through a polycarbonate membrane with pores of 0.1 μm was measured, and the particle size of the elastic liposomes that passed through was measured and calculated according to Equation 2 below:

[0113] [Mathematical Formula 2]

[0114] Deformability index = J Flux x (r v / r p ) 2 .

[0115] Here, J Flux is the amount of elastic liposomes (mL) that passed through the membrane, and r v is the elastic liposome particle size (nm) after extrusion, and r p is the membrane pore size (nm).

[0116]

[0117] As described above, to confirm the physical properties of the elastic liposomes of Examples 1 to 7 and Comparative Examples 1 to 2, the particle size (nm), zeta potential (mV), quercetin entrapment efficiency (%), and deformability index of the elastic liposomes were evaluated, and the results are shown in Table 3.

[0118]

[0119] Size (nm) Polydispersity Index Zeta Potential (mV) Quercetin Capture Efficiency (%) Variable Formation Comparative Example 1 2 25.32±0.98 0.26±0.01 -25.21±0.35 26.1±1.81.1±0.0 Comparative Example 2 1 60.53±1.12 0.28±0.01 -21.85±0.84 20.1±3.21.3±0.0 Example 1 1 4 2.65±0.63 0.28±0. 01-23.15±0.24 41.5±1.7 1.6±0.0 Example 2 141.86±0.74 0.27±0.00-23.83±0.51 43.0±2.2 1.6±0.1 Example 3 140.43±0.12 0.25±0.01-24.62±0.20 46.3±2.8 1.8±0.0 Example 4135.21±0.590.23±0.00-28.83±0.2862.8±1.52.9±0.0Example 5170.52±0.860.25±0.01-20.36±0.3552.1±2.31.5±0.0Example 6180.76±0.380.25±0.01-16.61±0.5051.5±1.81.3±0.0Example 7188.47±1.390.27±0.01-15.41±0.7550.4±2.11.9±0.0

[0120]

[0121] As shown in Table 3 above, the average particle size of Examples 1 to 7 and Comparative Examples 1 to 2 is 50 to 300 nm, and the polydispersity index is 0.3 or less. For improved skin permeability, the smaller the liposome size, the better. In the case of zeta potential, a higher absolute value (positive or negative) indicates greater electrostatic repulsion between particles, which means increased dispersion stability of the liposome. Generally, when the polydispersity index value is 0.3 or less, the liposome is considered monodisperse and the homogeneity of the liposome size is regarded as good. Therefore, according to Table 3, it can be seen that the liposome of Example 4 is the most superior.

[0122] The elastic liposomes of the embodiments of the present invention exhibited a higher capture efficiency (%) compared to Comparative Examples 1 and 2. In particular, it was found that the capture efficiency was best when the weight ratio of lecithin and polyglyceryl-3-methylglucose distearate in Example 4 was 1:1.

[0123] In addition, the elastic liposomes of this embodiment exhibited higher variable formation compared to Comparative Examples 1 and 2. In particular, it was found that the variable formation was best when the weight ratio of lecithin and polyglyceryl-3-methylglucose distearate in Example 4 was 1:1.

[0124]

[0125] Experimental Example 2. Stability Evaluation

[0126] Long-term storage stability was evaluated by comparing the particle size (nm) immediately after preparation and after 12 weeks of storage at room temperature of the elastic liposomes of Examples 1 to 7 and Comparative Examples 1 to 2, and the results are shown in Table 4 and Figure 1.

[0127]

[0128] Classification Immediately after manufacturing After 12 weeks (Room temperature) Comparative Example 1 2 25.32±0.98 24 0.67±1.89 Comparative Example 2 16 0.53±1.1 219 0.80±1.35 Example 1 14 2.65±0.63 15 0.34±1.21 Example 2 14 1.86±0.74 149.49±3.14 Example 3 14 0.43±0.1 215 0.73±1.51 Example 4 13 5.21±0.59 13 6.10±1.85 Example 5 17 0.52±0.86 178.35±2.12 Example 6 18 0.76±0.38 186.12±1.70 7188.47±1.39190.76±1.12

[0129]

[0130] As shown in Table 4 above, the elastic liposomes of this embodiment showed superior stability compared to the comparative example. In particular, it can be seen that in Example 4, when the mixing weight ratio of lecithin and polyglyceryl-3-methylglucose distearate is 1:1, it is possible to form elastic liposomes in a stable state.

[0131]

[0132] Experimental Example 3. Measurement of Skin Permeability

[0133] The skin permeability of the elastic liposomes of Examples 1 to 7 and Comparative Examples 1 to 2 was measured, and the results are shown in Table 5. Skin permeability was measured using a Franz diffusion cell, and the skin used in the skin permeation experiment was a synthetic skin membrane (Strat-M *?*A membrane was used. After filling the receptor chamber with 15 mL of the receptor phase without generating air bubbles, the synthetic membrane was fixed between the donor and the receptor phase with the stratum corneum portion facing upward. The experiment was conducted by maintaining the chamber temperature at 37 ± 1 ℃ using a constant temperature water bath. After dispensing 1 mL of each of Examples 1 to 7 and Comparative Examples 1 to 2 onto the skin surface, 0.5 mL of the aqueous phase (receptor phase) was taken through the sampling inlet after a certain period of time, and an equal amount of the aqueous phase (receptor phase) was replenished in the chamber. The amount of quercetin in the collected samples was measured using a microplate reader. To measure the amount of quercetin present in the stratum corneum after 12 hours, the stratum corneum was removed with tape using the tape stripping method, the tape was placed in 10 mL of ethanol, and the quercetin was extracted using an ultrasonic cleaner for 1 hour. Ethanol was separated from quercetin extracted using a rotary evaporator and then dissolved in 0.5 mL of the receptor phase. Skin from which the stratum corneum had been removed via tape stripping was cut using scissors, and the quercetin within the cut skin was similarly extracted with ethanol and dissolved in the receptor phase. The amount of quercetin in the sample from which the stratum corneum had been removed was measured using a microplate reader.

[0134] The permeability of quercetin per skin area was measured for 0 to 12 hours, and the final cumulative skin permeability of quercetin after about 12 hours was measured and shown in Table 5.

[0135] In addition, as a control group, a solution of quercetin dissolved in 1,3-butylene glycol (1,3-BG), a representative solvent widely used in cosmetics, was used instead of elastic liposomes.

[0136]

[0137] Skin penetration amount of quercetin (µg / cm²) 12 hours after classification 2 ) Control Group 3.4 Comparative Example 17.3 Comparative Example 24.8 Example 1 24.5 Example 2 25.9 Example 3 28.1 Example 4 30.9 Example 5 27.7 Example 6 23.7 Example 7 20.5

[0138]

[0139] As shown in Table 5 above, it can be seen that the elastic liposomes of Examples 1 to 7 have improved skin permeability of quercetin compared to the control group and Comparative Examples 1 to 2. Specifically, when comparing the elastic liposomes of Examples 1 to 7 with Comparative Example 1, which is a general liposome, the elastic liposomes showed a higher amount of quercetin permeability than the general liposome, which means that the skin permeability of the elastic liposomes according to the present example is excellent.

[0140] In addition, the changes in the amount of quercetin permeable to the skin over time for 1,3-butylene glycol corresponding to the control group, Comparative Example 1, and Examples 1 to 7 are shown in FIG. 2. As shown in FIG. 2, the elastic liposomes of Examples 1 to 7 exhibited superior skin permeability compared to Comparative Example 1, which is a general liposome. In particular, it can be seen that the skin permeability of Example 4, in which the weight ratio of lecithin and polyglyceryl-3-methylglucose distearate is 1:1, is the best.

[0141] Next, the results of deriving the content percentage (%) of the amount of quercetin present in the stratum corneum after 12 hours (Tape), the amount of quercetin present in the skin (epidermis and dermis) (Skin), and the amount of quercetin that passed through the skin (Transdermal) are shown in Fig. 3. As shown in Fig. 3, it can be seen that the overall skin penetration amount of quercetin is higher in Examples 1 to 7, which are elastic liposomes, than in the control group and Comparative Example 1, which is a general liposome. In other words, it can be seen that elastic liposomes can significantly increase the skin penetration rate of active ingredients such as flavonoids compared to when using a simple solvent and a general liposome.

[0142]

[0143] The foregoing description is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

Claims

1. An elastic liposome comprising hydrogenated lechitin, a polyglyceryl-based surfactant, a water-soluble solvent, and a fatty acid.

2. An elastic liposome according to claim 1, further comprising one or more selected from the group consisting of glycerin and ceramide.

3. An elastic liposome according to claim 1, further comprising an antioxidant.

4. An elastic liposome according to claim 1, wherein the average particle size of the elastic liposome is 100 to 300 nm.

5. An elastic liposome according to claim 1, wherein the polyglyceryl-based surfactant is one or more selected from the group consisting of polyglyceryl 3-methylglucose diastearate, polyglyceryl-10 laurate, polyglyceryl-10 stearate, polyglyceryl-10 myristate, polyglyceryl-10 pentastearate, polyglyceryl 10 distearate, polyglyceryl-10 linoleate, polyglyceryl-10 oleate, polyglyceryl-10 caprate, polyglyceryl-6 pentastearate, polyglyceryl 4-diisostearate, polyglyceryl-2 sesquiisostearate, polyglyceryl-2 isostearate, polyglyceryl-2 tetraisostearate, and polyglyceryl-2 diisostearate.

6. An elastic liposome according to claim 1, wherein the water-soluble solvent is one or more selected from the group consisting of water and alcohols having 1 to 5 carbon atoms.

7. An elastic liposome according to claim 1, wherein the fatty acid is one or more selected from the group consisting of caprylic / capric triglycerides, oleic acid, linoleic acid, linolenic acid, lauric acid, palmitic acid, stearic acid, elaidic acid, myristic acid, arachidonic acid, and isopropyl myristate.

8. An elastic liposome according to claim 2, wherein the ceramide is one or more selected from the group consisting of ceramide NS, ceramide AS, ceramide EOS, ceramide NDS, ceramide ADS, ceramide EODS, ceramide NP, ceramide AP, ceramide EOP, ceramide NH, ceramide AH, and ceramide EOH.

9. An elastic liposome according to claim 3, wherein the antioxidant is one or more selected from the group consisting of quercetin, apigenin, catechin, and rutin.

10. The elastic liposome of claim 1, wherein the elastic liposome comprises the hydrogenated lechitin and the polyglyceryl-based surfactant in a weight ratio of 1:0.25 to 4.

11. An elastic liposome according to claim 2, wherein the elastic liposome comprises the hydrogenated lechitin, the polyglyceryl-based surfactant, the fatty acid, the glycerin, and the ceramide in a weight ratio of 1:0.25 to 4:1.125 to 5:6.25 to 25:0.0625 to 0.

25.

12. A cosmetic composition comprising the elastic liposome of Claim 1.

13. A step of obtaining a mixture by mixing a water-soluble solvent, hydrogenated lechitin, a polyglyceryl-based surfactant, and a fatty acid; and A method for manufacturing an elastic liposome comprising the step of pressurizing the above mixture.

14. A method for manufacturing elastic liposomes according to claim 13, wherein the step of obtaining the mixture involves also mixing ceramide.

15. A method for manufacturing elastic liposomes according to claim 13, wherein the step of obtaining the mixture also involves mixing an antioxidant.

16. A method for manufacturing elastic liposomes according to claim 13, further comprising the step of heating and stirring the mixture at a temperature of 60 to 100°C prior to the pressurizing step.

17. A method for manufacturing an elastic liposome according to claim 13, wherein the step of obtaining the mixture is to mix the hydrogenated lechitin and the polyglyceryl-based surfactant in a weight ratio of 1:0.25 to 4.

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