Encapsulation and stability improving method of active ingredient by using micelle

Abstract

To provide a micelle composition containing saccharide-based surfactant and glycoside active ingredient encapsulated into the saccharide-based surfactant, and a method for producing the composition.SOLUTION: A composition of the present invention can stably encapsulate glycoside active ingredient by using saccharide-based surfactant, and improve a skin absorption rate of active ingredient. Further, the composition of the present invention can further improve encapsulation stability of glycoside active ingredient in a micelle by adding citric acid, tannic acid or tocopherol.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to a micelle composition containing a sugar-based surfactant, which can stably encapsulate a glycoside active ingredient and increase its cutaneous absorption, and a method for producing the same. [Background technology]

[0002] Conventional methods that simply use surfactants to improve the solubility of poorly soluble substances fail to enhance the pharmacological efficacy of the active ingredient, and even if micelles are formed, there is a risk of the encapsulated active ingredient leaking out. Therefore, polymer block copolymer micelles are widely used as active ingredient carriers. First, polymer block copolymer micelles have a much lower critical micelle concentration than low-molecular-weight surfactants, making them highly stable. Furthermore, the polymer chains provide a slow dissociation rate, allowing for continuous action. Furthermore, the method of encapsulating poorly soluble substances in micelles is simple, and they easily redisperse upon reconstitution, eliminating the need for additional additives during administration.

[0003] However, because polymeric micelles are made using synthetic polymers, they are not suitable for environmental social governance (ESG). Active glycoside ingredients are widely distributed in the plant kingdom, so they require a suitable, environmentally friendly, and safe carrier. Furthermore, while glycoside active ingredients are poorly soluble in water, they contain structurally hydrophilic sugars, which means that their particle size increases when encapsulated in polymeric micelles, making them unsuitable for encapsulation in polymeric micelles.

[0004] Therefore, there is a need to develop a carrier for encapsulating poorly water-soluble glycoside components, along with safe and sustainable raw materials and methods. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Korean Patent Registration No. 2072439 [Non-patent literature]

[0006] [Non-Patent Document 1] Heliyon,Volume 9,Issue 4,2023,e14803, [Non-patent document 2] Planta Med 2011;77:2029-2036 Summary of the Invention [Problem to be solved by the invention]

[0007] In one aspect, the present invention provides a micelle composition comprising a saccharide-based surfactant and a glycoside active ingredient encapsulated in the saccharide-based surfactant.

[0008] In another aspect, the present invention provides a method for producing the micelle composition, comprising the steps of hydrating a saccharide surfactant with water and dissolving a glycoside active ingredient in at least one alcohol selected from the group consisting of C1 to C6 alcohols. [Means for solving the problem]

[0009] In one embodiment, a micelle composition is provided that includes a saccharide-based surfactant and a glycoside active ingredient encapsulated in the saccharide-based surfactant.

[0010] In one embodiment, the saccharide surfactant may be a glucoside surfactant.

[0011] In one embodiment, the glucoside surfactant may be at least one selected from the group consisting of decyl glucoside, lauryl glucoside, coco glucoside, caprylyl / capryl glucoside, cetearyl glucoside, arachidyl glucoside, and C12-20 alkyl glucoside.

[0012] In one embodiment, the glycoside active ingredient may be a saponin glycoside.

[0013] In one embodiment, the saponin glycoside may be at least one glycoside selected from the group consisting of purified ginseng saponin, purified green tea saponin, purified red ginseng saponin, purified bean saponin, and purified camellia saponin.

[0014] In one embodiment, the ginseng purified saponin may contain compound K.

[0015] In one embodiment, the green tea purified saponin may include green tea saponin R12.

[0016] In one embodiment, the saccharide surfactant may be contained in an amount of 0.001 to 50% by weight based on the total weight of the composition.

[0017] In one embodiment, the active glycoside ingredient may be contained in an amount of 0.001 to 20% by weight based on the total weight of the composition.

[0018] In one embodiment, the weight ratio of the saccharide surfactant to the glycoside active ingredient may be 1 to 50:1.

[0019] In one embodiment, the composition may further comprise a non-covalent crosslinker.

[0020] In one embodiment, the non-covalent cross-linking agent may be citric acid or tannic acid.

[0021] In one embodiment, the non-covalent crosslinking agent may be contained in an amount of 0.0001 to 5% by weight based on the total weight of the composition.

[0022] In one embodiment, the weight ratio of the saccharide surfactant:glycoside active ingredient:non-covalent cross-linking agent may be 1-50:1:0.002-0.2.

[0023] In one embodiment, the average particle size of the micelles may be 5 to 200 nm.

[0024] In one embodiment, the particle size of at least 90% of the micelle particles contained in the micelle composition may be 5 to 200 nm.

[0025] In one embodiment, the composition may further comprise tocopherol.

[0026] In one embodiment, the tocopherol may be contained in an amount of 0.0001 to 5% by weight relative to the total weight of the composition.

[0027] In one embodiment, the weight ratio of the saccharide surfactant: glycoside active ingredient: tocopherol may be 1-50:1:0.006-0.6.

[0028] In one embodiment, the composition may be for cosmetic use.

[0029] In another aspect, a method for producing the micelle composition is provided, comprising the steps of hydrating a saccharide surfactant with water and dissolving a glycoside active ingredient in at least one alcohol selected from the group consisting of C1 to C6 alcohols.

[0030] In one embodiment, the method may further include the step of mixing the water-hydrated solution with the alcohol-dissolved solution and evaporating the alcohol. [Effects of the Invention]

[0031] In one embodiment, the composition of the present invention allows micelles formed in the composition to maintain a constant and stable size.

[0032] In one embodiment, the compositions of the present invention can be used as transparent solubilizers.

[0033] In one embodiment, the composition of the present invention has excellent micelle stability.

[0034] In one embodiment, the compositions of the present invention are highly useful as carriers.

[0035] In one embodiment, the compositions of the present invention exhibit excellent absorption at the skin surface.

[0036] In one embodiment, the composition of the present invention encapsulates an active ingredient derived from a naturally occurring substance, and therefore is highly safe when applied to a living body.

[0037] In one embodiment, the compositions of the present invention are environmentally friendly.

[0038] In one embodiment, the composition of the present invention has a high encapsulation efficiency of a poorly soluble glycoside active ingredient. [Brief explanation of the drawings]

[0039] [Figure 1] This is a diagram summarizing the chemical structural formulas of each type of ginsenoside that can be contained in purified ginseng saponins. [Figure 2] FIG. 1 is a diagram showing the structural formulas of compounds that may be contained in purified green tea saponins. [Figure 3] 1 is a diagram showing the results of preparing a micelle composition containing purified ginseng saponin as an active ingredient according to one embodiment of the present invention. [Figure 4] FIG. 1 shows the results of preparing a micelle composition containing purified green tea saponin as an active ingredient according to an embodiment of the present invention. [Figure 5] FIG. 1 is a diagram showing the chemical structure of codyl methylenedioxycinnamate. [Figure 6] FIG. 1 shows the results of preparing a comparative micelle composition containing codyl methylenedioxycinnamate as an active ingredient according to an embodiment of the present invention. [Figure 7]FIG. 1 shows the results of measuring the compound K release profile of a micelle composition containing citric acid, tannic acid, or tocopherol according to an embodiment of the present invention. [Figure 8] FIG. 1 shows the results of skin absorption evaluation of a micelle composition according to an embodiment of the present invention. [Figure 9] FIG. 1 shows the results of a size distribution analysis of nanoparticles in a micelle composition according to one embodiment of the present invention. [Figure 10] FIG. 1 shows the results of morphology and size analysis of particles in a micelle composition according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0040] The terms used in this specification are currently commonly used and general terms that have been selected as much as possible, taking into consideration the functions of the present invention. However, they may differ depending on the intentions of engineers in the relevant field, legal precedents, the emergence of new technology, etc. In addition, in certain cases, the applicant may have arbitrarily selected terms, and in such cases, the meanings thereof will be explained in detail in the relevant description of the invention. Therefore, the terms used in this specification should be defined based on the meanings of the terms and the overall content of the present invention, rather than simply by their names.

[0041] Unless otherwise specified, all terms used in the present invention, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which the present invention belongs. Commonly understood terms should be interpreted as having the same meaning as in the context of the relevant art, and in the present invention, unless otherwise specified, they should not be interpreted in an ideal or overly formal sense.

[0042] Numerical ranges are inclusive of the numerical values ​​defined herein. Every upper limit herein includes every lower upper limit, as if such lower limits were expressly written. Every lower limit herein includes every higher lower limit, as if such higher limits were expressly written. Every numerical limit herein includes every narrower numerical limit, as if such narrower numerical limits were expressly written.

[0043] As used herein, the terms "comprise," "have," and "contain" are inclusive or open-ended and do not exclude additional, unrecited elements, methods, or steps. As used herein, "or combinations thereof" refers to all permutations and combinations of the preceding listed items. For example, "A, B, C, or combinations thereof" is intended to include at least one of A, B, C, AB, AC, BC, ABC, and, if order is important in the particular context, BA, CA, CB, CBA, BCA, ACB, BAC, and CAB. Similarly, combinations having at least one repeat of an item or term are included, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, etc. One of ordinary skill in the art will understand that, unless otherwise specified, there are typically no limitations on the number of items or terms in any combination.

[0044] The present invention will be described in detail below with reference to examples.

[0045] In one embodiment, a micelle composition is provided that includes a saccharide-based surfactant and a glycoside active ingredient encapsulated in the saccharide-based surfactant.

[0046] As used herein, the term "saccharide-based surfactant" refers to a surfactant that contains sugar in its structure.

[0047] In one embodiment, the sugar-based surfactant may be a glucoside surfactant.

[0048] In one embodiment, the glucoside surfactant may be at least one selected from the group consisting of decyl glucoside, lauryl glucoside, coco glucoside, caprylyl / capryl glucoside, cetearyl glucoside, arachidyl glucoside, and C12-20 alkyl glucoside.

[0049] As used herein, the term "glycoside" refers to a molecule in which a sugar molecule is linked to another functional group via a glycosidic bond. Such glycosides are found primarily in plants.

[0050] As used herein, the term "active ingredient" refers to an ingredient that exhibits a desired activity alone or exhibits activity together with a carrier that is inactive by itself.

[0051] In one embodiment, the glycoside active ingredient may be a saponin glycoside.

[0052] In one embodiment, the saponin glycoside may be at least one glycoside selected from the group consisting of purified ginseng saponin, purified green tea saponin, purified red ginseng saponin, purified bean saponin, and purified camellia saponin.

[0053] "Ginseng" as used herein refers to a plant belonging to the genus Panax in the family Araliaceae. The ginseng used in the present invention may be of any type and any root, and either dried or undried ginseng may be used. Furthermore, the ginseng used in the present invention may be any part of the plant, and specifically, ginseng root may be used. For example, the ginseng used in the present invention includes Panax ginseng (Panax ginseng CA Meyer).

[0054] As used herein, "green tea" refers to green tea belonging to the genus Camellia in the family Theaceae. For example, the green tea may be the evergreen tea plant (Camellia sinensis). Also, for example, the green tea may be the Yabukita variety.

[0055] In this specification, "red ginseng" refers to a Korean ginseng product made by steaming and drying undried ginseng. Through this steaming and drying process, many new physiologically active components beneficial to the body that are not found in undried ginseng are produced, specifically saponin, ginseng aroma components (panacen), nitrogen-containing components, polyacetylene compounds, and flavonoids.

[0056] As used herein, "beans" refers to beans belonging to the genus Glycine in the family Fabaceae. For example, black pea (Seoritae; Glycine max MERR), tankiri pea (Seomoktae; Rhynchosia Volubilis), black soybean (Glycine max (L.) Merr.), blue bean (Glycine max MERR), yellow bean (Glycine max MERR), field bean (Viciafaba), kidney bean (Paseolus vulgaris), pinto bean (Paseolus vulgaris L.), small red bean (Vigna angularis), small black bean (Paseolus angularis WFWIGHT.), sprout beans (Glycine max (L.) Merr.) or soybean (Glycine max max).

[0057] As used herein, "camellia" refers to camellias belonging to the genus Camellia in the family Theaceae, such as Camellia japonica and Camellia oleifera.

[0058] In one embodiment, the ginseng purified saponin may include saponin obtained from a ginseng extract. The green tea purified saponin may include saponin obtained from a green tea extract. The red ginseng purified saponin may include saponin obtained from a red ginseng extract. The bean purified saponin may include saponin obtained from a bean extract. The camellia purified saponin may include saponin obtained from a camellia extract.

[0059] In one embodiment, the term "extract" refers to any substance obtained by extracting components from ginseng, green tea, red ginseng, or camellia, regardless of the extraction method, extraction solvent, extracted component, or extract form. It also refers to any substance obtained by an extraction method that involves treating with heat, acid, base, enzyme, or the like during the extraction process. It also refers to any substance obtained by processing or treating the extracted component from ginseng, green tea, red ginseng, or camellia with other methods after extraction. Specifically, the processing or treatment may involve further fermentation or enzyme treatment of the ginseng, green tea, red ginseng, or camellia extract.

[0060] In one embodiment, the ginseng purified saponin may include compound K. In addition, compound K may exist in the form of a stereoisomer of compound K, a salt thereof, a hydrate thereof, or a solvate thereof.

[0061] In this specification, Compound K is represented by Chemical Formula 1.

[0062] [ka]

[0063] In one embodiment, the purified green tea saponin may include rogchaponin R12, which may exist in the form of a stereoisomer, a salt thereof, a hydrate thereof, or a solvate thereof.

[0064] In this specification, green tea ponin R12 is represented by chemical formula 2.

[0065] [ka]

[0066] In one embodiment, the saccharide surfactant may be contained in an amount of 0.001 to 50 wt % relative to the total weight of the composition, for example, 0.001 or more, 0.005 or more, 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more, 0.07 or more, 0.08 or more, 0.09 or more, 0.1 or more, 0.2 or more, 0.3 or more, 0.4 or more, 0.5 or more, 0.6 or more, 0.7 or more, 0.8 or more, 0.9 or more, 1.0 or more, 1.1 or more, 1.2 or more, 1.3 or more, 1.4 or more, 1.5 or more, 1.6 or more, 1.7 or more, 1.8 or more, 1.9 or more, 1.10 or more, 1.20 or more, 1.30 or more, 1.40 or more, 1.50 or more, 1.60 or more, 1.70 or more, 1.80 or more, 1.9 ... It may be present at a weight percent of 0.6 or more, 1.7 or more, 1.8 or more, 1.9 or more, 2.0 or more, 2.1 or more, 2.2 or more, 2.3 or more, 2.4 or more, 2.5 or more, 2.6 or more, 2.7 or more, 2.8 or more, 2.9 or more, 3.0 or more, 3.1 or more, 3.2 or more, 3.3 or more, 3.4 or more, 3.5 or more, 3.6 or more, 3.7 or more, 3.8 or more, 3.9 or more, 4.0 or more, 4.1 or more, 4.2 or more, 4.3 or more, 4.4 or more or 4.5 or more. The saccharide surfactant may be contained in an amount of 50 or less, 48 ​​or less, 46 or less, 44 or less, 42 or less, 40 or less, 38 or less, 36 or less, 34 or less, 32 or less, 30 or less, 28 or less, 26 or less, 24 or less, 22 or less, 20 or less, 19.0 or less, 18.0 or less, 17.0 or less, 16.0 or less, 15.0 or less, 14.0 or less, 13.0 or less, 12.0 or less, 11.0 or less, 10.0 or less, 9.5 or less, 9.0 or less, 8.5 or less, 8.0 or less, 7.5 or less, 7.0 or less, 6.5 or less, 6.0 or less, or 5.5 or less by weight percent, relative to the total weight of the composition.

[0067] In one embodiment, the glycoside active ingredient may be contained in an amount of 0.001 to 20 wt% based on the total weight of the composition. For example, the glycoside active ingredient may be contained in an amount of 0.001 or more, 0.005 or more, 0.01 or more, 0.05 or more, 0.1 or more, 0.15 or more, 0.2 or more, 0.25 or more, 0.30 or more, 0.35 or more, 0.40 or more, 0.45 or more, 0.50 or more, 0.51 or more, 0.52 or more, 0.53 or more, 0.54 or more, 0.55 or more, 0.56 or more, 0.57 or more, 0.58 or more, 0.59 or more, 0.60 or more, 0.61 or more, 0.62 or more, 0.63 or more, 0.64 or more, 0.65 or more, 0.66 or more, 0.67 or more, 0.68 or more, 0.69 or more, 0.70 or more, 0.71 or more, 0.72 or more, 0.73 or more, 0.74 or more, 0.75 or more, 0.76 or more, 0.77 or more, 0.78 or more, 0.79 or more, 0.80 or more, 0.81 or more, 0.82 or more, 0.83 or more, 0.84 or more, 0.85 or more, 0.86 or more, 0.87 or more, 0.88 or more, 0.89 or more, 0.90 or more, 0.91 or more, 0.92 or more, 0.93 or more, 0.94 or more, 0 0.80 or more, 0.81 or more, 0.82 or more, 0.83 or more, 0.84 or more, 0.85 or more, 0.86 or more, 0.87 or more, 0.88 or more, 0.89 or more, 0.90 or more, 0.91 or more, 0.92 or more, 0.93 or more, 0.94 or more, 0.95 or more, 0.96 or more, 0.97 or more, 0.98 or more, or 0.99 or more by weight. Furthermore, the glycoside active ingredient may be contained in an amount of 20 or less, 19 or less, 18 or less, 17 or less, 16 or less, 15 or less, 14 or less, 13 or less, 12 or less, 11 or less, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4.9 or less, 4.8 or less, 4.7 or less, 4.6 or less, 4.5 or less, 4.4 or less, 4.3 or less, 4.2 or less, 4.1 or less, 4.0 or less, 3.9 or less, 3.8 or less, 3.7 or less, 3.6 or less, 3.5 or less, 3.4 or less, 3.3 or less, 3.2 or less, 3.1 or less, 3.0 or less, 2.9 or less, 2.8 or less, 2.7 or less, 2.6 or less, 2.5 or less, 2.4 or less, 2.3 or less, 2.2 or less, or 2.1 or less by weight% relative to the total weight of the composition.

[0068] In one embodiment, the weight ratio of the saccharide surfactant to the glycoside active ingredient may be 1 to 50:1. For example, the weight ratio of the saccharide surfactant to the glycoside active ingredient may be 1 to 50:1, 1 to 49:1, 1 to 48:1, 1 to 47:1, 1 to 46:1, 1 to 45:1, 1 to 44:1, 1 to 43:1, 1 to 42:1, 1 to 41:1, 1 to 40:1, 1 to 39:1, 1 to 38:1, 1 to 37:1, 1 to 36:1, 1 to 35 ... ~34:1, 1~33:1, 1~32:1, 1~31:1, 1~30:1, 1~29:1, 1~28:1, 1~27:1, 1~26:1, 1~25:1, 1~24:1, 1~23:1, 1~22:1, 1~21:1, 1~20:1, 1~19:1, 1~18:1, 1~17:1, 1~16:1, 1~15:1, 1~ 14:1, 1-13:1, 1-12:1, 1-11:1, 1-10:1, 1-9:1, 1-8:1, 1-7:1, 1-6:1, 2-10:1, 2-9:1, 2-8:1, 2-7:1, 2-6:1, 3-10:1, 3-9:1, 3-8:1, 3-7:1, 3-6:1, 4-10:1, 4-9:1, 4-8:1, 4-7 :1, 4-6:1, 1-10:2, 1-9:2, 1-8:2, 1-7:2, 1-6:2, 2-10:2, 2-9:2, 2-8:2, 2-7:2, 2-6:2, 3-10:2, 3-9:2, 3-8:2, 3-7:2, 3-6:2, 4-10:2, 4-9:2, 4-8:2, 4-7:2 or 4-6:2.

[0069] In one embodiment, the composition may further include a non-covalent crosslinker. The non-covalent crosslinker refers to a crosslinker that strengthens interactions within micelles using electrostatic interactions and hydrogen bonds. By including the non-covalent crosslinker, the composition of the present invention can strengthen the shell of the micelles and further improve their stability.

[0070] In one embodiment, the non-covalent cross-linking agent may be citric acid or tannic acid.

[0071] In one embodiment, the non-covalent crosslinking agent may be present in an amount of 0.0001 to 5 wt % based on the total weight of the composition, for example, 0.0001 or more, 0.0005 or more, 0.001 or more, 0.0015 or more, 0.002 or more, 0.0025 or more, 0.003 or more, 0.0035 or more, 0.004 or more, 0.0045 or more, 0.005 or more, 0.0055 or more, 0.006 or more, 0.0065 or more, 0.007 or more, 0.0075 or more, 0.008 or more, 0.0085 or more, 0.009 or more, 0.0065 or more, 0.0075 or more, 0.008 or more, 0.0085 or more, 0.009 ... The content may be 0.0095 or more, 0.01 or more, 0.0105 or more, 0.011 or more, 0.0115 or more, 0.012 or more, 0.0125 or more, 0.013 or more, 0.0135 or more, 0.014 or more, 0.0145 or more, 0.015 or more, 0.0155 or more, 0.016 or more, 0.0165 or more, 0.017 or more, 0.0175 or more, 0.018 or more, 0.0185 or more, 0.019 or more, or 0.0195 or more by weight. Alternatively, the non-covalent crosslinker may be present in an amount of 5 or less, 4.5 or less, 4 or less, 3.5 or less, 3 or less, 2.5 or less, 2 or less, 1.5 or less, 1 or less, 0.95 or less, 0.9 or less, 0.85 or less, 0.8 or less, 0.75 or less, 0.7 or less, 0.65 or less, 0.6 or less, 0.55 or less, 0.5 or less, 0.45 or less, 0.4 or less, 0.35 or less, 0.3 or less, based on the total weight of the composition. or less, 0.25 or less, 0.2 or less, 0.15 or less, 0.1 or less, 0.095 or less, 0.09 or less, 0.085 or less, 0.08 or less, 0.075 or less, 0.07 or less, 0.065 or less, 0.06 or less, 0.055 or less, 0.05 or less, 0.045 or less, 0.04 or less, 0.035 or less, 0.03 or less, or 0.025 or less by weight percent.

[0072] In one embodiment, the weight ratio of the saccharide surfactant:glycoside active ingredient:non-covalent crosslinking agent may be 1-50:1:0.002-0.2, for example, 1-50:1:0.002-0.2, 1-45:1:0.002-0.2, 1-40:1:0.002-0.2, 1-35:1:0.002-0.2, 1-30:1:0.002-0.2, 1-25:1:0.002-0.2, 1-20:1:0.002-0.2, 1-15:1:0.002-0.2, 1-10:1:0.002-0.2, 1-9:1 :0.002 to 0.2, 1-8:1:0.002 to 0.2, 1-7:1:0.002 to 0.2, 1-6:1:0.002 to 0.2, 1-5:1:0.002 to 0.2, 1-4:1:0.002 to 0.2, 1-3:1:0.002 to 0.2, 2-3:1:0.002 to 0.2, 2-3:1:0.004 to 0.15, 2-3:1:0.008 to 0.1, 2-3:1:0.012 to 0.05, or 2-3:1:0.016 to 0.03.

[0073] In one embodiment, the average particle size of the micelles may be 5 to 200 nm, for example, 5 to 200, 6 to 190, 7 to 180, 8 to 170, 9 to 160, 10 to 150, 11 to 140, 12 to 130, 13 to 120, 14 to 110, 15 to 100, 16 to 90, 17 to 80, 18 to 70, 19 to 60, 20 to 50, 21 to 48, 22 to 46, 23 to 44, 24 to 42, 25 to 40, 25.5 to 39, 26 to 38, 26.5 to 37, 27 to 36, 27.5 to 35, 28 to 34, 28.5 to 33, 29 to 32, or 29.5 to 31 nm.

[0074] In one embodiment, at least 90% or more of the micelle particles contained in the micelle composition may have a particle size of 5 to 200 nm. For example, the particle size of at least 90% of the micelle particles contained in the micelle composition may be 5 to 200, 6 to 190, 7 to 180, 8 to 170, 9 to 160, 10 to 150, 11 to 140, 12 to 130, 13 to 120, 14 to 110, 15 to 100, 16 to 90, 17 to 80, 18 to 70, 19 to 60, 20 to 50, 21 to 48, 22 to 46, 23 to 44, 24 to 42, 25 to 40, 25.5 to 39, 26 to 38, 26.5 to 37, 27 to 36, 27.5 to 35, 28 to 34, 28.5 to 33, 29 to 32, or 29.5 to 31 nm.

[0075] In one embodiment, the composition may further comprise tocopherol, which strengthens the core inside the micelle shell and further improves stability.

[0076] In one embodiment, the tocopherol may be contained in an amount of 0.0001 to 5 wt % relative to the total weight of the composition, for example, 0.001 to 5.0, 0.003 to 4.75, 0.005 to 4.5, 0.007 to 4.25, 0.009 to 4.0, 0.011 to 3.75, 0.013 to 3.5, 0.015 to 3.25, 0.017 to 3.0, 0.019 to 2.75, 0.021 to 2.5, 0.023 to 2.25, 0.025 to 2.0, 0.027 to 1.75, , 0.029 to 1.5, 0.031 to 1.25, 0.033 to 1.0, 0.035 to 0.9, 0.037 to 0.8, 0.039 to 0.7, 0.041 to 0.6, 0.043 to 0.5, 0.045 to 0.4, 0.047 to 0.3, 0.049 to 0.2, 0.051 to 0.1, 0.053 to 0.09, 0.055 to 0.08, or 0.057 to 0.07% by weight.

[0077] In one embodiment, the weight ratio of the saccharide surfactant:glycoside active ingredient:tocopherol may be 1-50:1:0.006-0.6, for example, the weight ratio of the saccharide surfactant:glycoside active ingredient:tocopherol may be 1-50:1:0.006-0.6, 1-45:1:0.006-0.6, 1-40:1:0.006-0.6, 1-35:1:0.006-0.6, 1-30:1:0.006-0.6, 1-25:1:0.006-0.6, 1-20:1:0.006-0.6, 1-15:1:0.006-0.6, 1-10:1:0.006-0.6, 1-9:1:0.006-0.6, The ratio may be 0.006 to 0.6, 1-8:1:0.006 to 0.6, 1-7:1:0.006 to 0.6, 1-6:1:0.006 to 0.6, 1-5:1:0.006 to 0.6, 1-4:1:0.006 to 0.6, 1-3:1:0.006 to 0.6, 2-3:1:0.006 to 0.6, 2-3:1:0.01 to 0.5, 2-3:1:0.0015 to 0.45, 2-3:1:0.018 to 0.425, or 2-3:1:0.02 to 0.04.

[0078] In one embodiment, the composition may be characterized as a cosmetic composition.

[0079] In one embodiment, the cosmetic composition may contain, in addition to the above-described components, other components that exert useful effects separate from the main effect, as long as the effects are not impaired. Those skilled in the art will readily be able to appropriately select and incorporate other components other than the active ingredient of the present invention depending on the formulation or intended use of the cosmetic composition. Furthermore, in one embodiment, the cosmetic composition of the present invention may, if necessary, contain other components typically incorporated into cosmetic compositions, in addition to the above-described components. Examples of such components include moisturizers, emollients, organic and inorganic pigments, organic powders, UV absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, blood circulation enhancers, cooling agents, antiperspirants, and purified water. The other components contained in the cosmetic composition of the present invention are not limited to these, and the amounts of the above-described components may be within a range that does not impair the objectives and effects of the present invention.

[0080] In one embodiment, the cosmetic composition is in at least one form selected from the group consisting of, but not limited to, massage cream, oil, body product, pack, mask, eye product, lotion, cream, and makeup cosmetic. Each of these compositions may contain appropriate additives necessary for formulating the formulation.

[0081] In one embodiment, the cosmetic composition may further contain functional additives and ingredients commonly found in cosmetic compositions in addition to the active ingredient. The functional additives may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymeric peptides, polymeric polysaccharides, sphingolipids, and seaweed extracts. If necessary, ingredients commonly found in cosmetic compositions may be blended together with the functional additives. Other ingredients may include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, blood circulation enhancers, cooling agents, antiperspirants, purified water, etc.

[0082] In another aspect, the present invention provides a method for producing a micelle composition, comprising the steps of hydrating a saccharide surfactant with water and dissolving a glycoside active ingredient in at least one alcohol selected from the group consisting of C1 to C6 alcohols. The micelle composition, saccharide surfactant, and glycoside active ingredient are as described above.

[0083] In one embodiment, the hydrating and dissolving steps can be performed in any order.

[0084] In one embodiment, the step of hydrating with water can be any method known in the art for hydrating a sugar surfactant with water.

[0085] In one embodiment, the step of dissolving in alcohol may be any method known in the art for dissolving the glycoside active ingredient in alcohol.

[0086] In one embodiment, the method may further comprise the steps of mixing the water-hydrated solution with the alcohol-dissolved solution and evaporating the alcohol.

[0087] In one embodiment, the at least one alcohol selected from the group consisting of C1 to C6 alcohols may be ethanol or methanol.

[0088] In one embodiment, the evaporation step can be any method known in the art to evaporate the alcohol used as a solvent in the solution.

[0089] The present invention provides the following embodiment as an example.

[0090] In a first embodiment, a micelle composition is provided, which comprises a saccharide surfactant and a glycoside active ingredient encapsulated in the saccharide surfactant.

[0091] In a second embodiment, there is provided the composition of the first embodiment, wherein the saccharide surfactant is a glucoside surfactant.

[0092] In a third embodiment, there is provided the composition of the second embodiment, wherein the glucoside surfactant is at least one selected from the group consisting of decyl glucoside, lauryl glucoside, coco glucoside, caprylyl / capryl glucoside, cetearyl glucoside, arachidyl glucoside, and C12-20 alkyl glucoside.

[0093] In a fourth embodiment, there is provided a composition according to at least any one of the first to third embodiments, wherein the glycoside active ingredient is a saponin glycoside.

[0094] In a fifth embodiment, there is provided the composition according to the fourth embodiment, wherein the saponin glycoside is at least one glycoside selected from the group consisting of purified ginseng saponin, purified green tea saponin, purified red ginseng saponin, purified bean saponin, and purified camellia saponin.

[0095] In a sixth embodiment, there is provided the composition according to the fifth embodiment, wherein the ginseng purified saponin comprises compound K.

[0096] In a seventh embodiment, there is provided the composition according to the fifth embodiment, wherein the green tea purified saponin comprises rogchaponin R12.

[0097] In an eighth embodiment, there is provided a composition according to at least any one of the first to seventh embodiments, wherein the saccharide surfactant is contained in an amount of 0.001 to 50% by weight relative to the total weight of the composition.

[0098] In a ninth embodiment, the present invention provides a composition according to at least any one of the first to eighth embodiments, wherein the glycoside active ingredient is contained in an amount of 0.001 to 20% by weight relative to the total weight of the composition.

[0099] In a tenth embodiment, there is provided a composition according to at least any one of the first to ninth embodiments, wherein the weight ratio of the saccharide surfactant to the glycoside active ingredient is 1 to 50:1.

[0100] In an eleventh embodiment, there is provided a composition according to at least one of the first to tenth embodiments, wherein the composition further comprises a non-covalent crosslinker.

[0101] In a twelfth embodiment, the composition of the eleventh embodiment is provided, wherein the non-covalent crosslinking agent is citric acid or tannic acid.

[0102] In a thirteenth embodiment, there is provided the composition according to the eleventh or twelfth embodiment, wherein the non-covalent crosslinking agent is contained in an amount of 0.0001 to 5 wt % relative to the total weight of the composition.

[0103] In a fourteenth embodiment, there is provided a composition according to at least any one of the eleventh to thirteenth embodiments, wherein the weight ratio of the saccharide surfactant:glycoside active ingredient:non-covalent crosslinking agent is 1-50:1:0.002-0.2.

[0104] In a fifteenth embodiment, there is provided the composition according to at least any one of the first to fourteenth embodiments, wherein the average particle size of the micelles is 5 to 200 nm.

[0105] In a sixteenth embodiment, there is provided a composition according to at least any one of the first to fifteenth embodiments, wherein at least 90% or more of the micelle particles contained in the micelle composition have a particle size of 5 to 200 nm.

[0106] In a seventeenth embodiment, there is provided a composition according to at least one of the first to sixteenth embodiments, wherein the composition further comprises tocopherol.

[0107] In an eighteenth embodiment, there is provided the composition according to the seventeenth embodiment, wherein the tocopherol is contained in an amount of 0.0001 to 5% by weight relative to the total weight of the composition.

[0108] In a 19th embodiment, there is provided a composition according to at least any one of the 1st to 18th embodiments, wherein the weight ratio of the saccharide surfactant:glycoside active ingredient:tocopherol is 1-50:1:0.006-0.6.

[0109] In a twentieth embodiment, there is provided a composition according to at least any one of the first to nineteenth embodiments, wherein the composition is for use in cosmetics.

[0110] In the 21st embodiment, there is provided a method for producing a micelle composition according to at least any one of the 1st to 20th embodiments, comprising the steps of hydrating a saccharide surfactant with water and dissolving a glycoside active ingredient in at least one alcohol selected from the group consisting of C1 to C6 alcohols.

[0111] In a 22nd embodiment, the method of the 21st embodiment is provided, further comprising the steps of mixing the water-hydrated solution with the alcohol-dissolved solution and evaporating the alcohol.

[0112] The present invention will be described in more detail below with reference to examples. These examples are merely for the purpose of illustrating the present invention, and it will be obvious to those skilled in the art that the present invention is not limited to these examples.

[0113] [Example] 1. Preparation of naturally derived purified saponin Ginseng was prepared from roots of Panax Ginseng CA Meyer that were over 4 years old. Green tea was prepared from roots of the Yabukita variety of tea plant that were over 30 years old (purchased from Osulloc Farm).

[0114] 2 kg of ginseng or green tea was added to 4 L of water, water-in-methanol, or methanol, and reflux extraction was performed three times. The extract was then allowed to settle at 15°C for six days. The residue and filtrate were separated by cloth filtration and centrifugation. The filtrate was concentrated under reduced pressure to obtain an extract, which was suspended in water and then extracted five times with 1 L of ether to remove pigments. The aqueous layer was then extracted three times with 50 mL of 1-butanol. The entire 1-butanol layer was treated with 5% KOH, washed with distilled water, and then concentrated under reduced pressure to obtain the 1-butanol extract. This extract was dissolved in a small amount of methanol, added to a large amount of ethyl acetate, and the resulting precipitate was dried to yield 40–80 g of purified natural saponin extract.

[0115] 2. Preparation and evaluation of micellar compositions containing glycoside active ingredients First, the glycosides, purified ginseng saponin and purified green tea saponin (Figures 1 and 2), were prepared by dissolving them in ethanol or an aqueous ethanol solution, and each sugar-based surfactant was thoroughly hydrated in water. Here, purified ginseng saponin contains compound K as its main substance (Non-Patent Document 1), and purified green tea saponin contains Rogchaponin R12 as its main substance (Non-Patent Document 2).

[0116] The components are shown in Tables 1 and 2. The ethanol part was mixed with the water part, and the ethanol was completely evaporated using an evaporator (Hei-VAP Advantage ML / G3; Heidolph, Germany) to produce micelles, which were then visually evaluated for encapsulation.

[0117] Whether or not the substance was encapsulated in a micelle was evaluated based on whether or not transparency was maintained by visual inspection after production.

[0118] [Table 1]

[0119] [Table 2]

[0120] As a result of the experiment, it was confirmed that the active ingredient was stably encapsulated in the micelles in the Examples, as it was solubilized transparently. In contrast, in the Comparative Examples, it was confirmed that the active ingredient was not stably encapsulated in the micelles, as precipitation occurred (Figures 3 and 4).

[0121] 3. Preparation and evaluation of micellar compositions containing non-glycoside active ingredients First, the non-glycoside active ingredient, methylenedioxycinnamate (ACT Co., Ltd., South Korea), was thoroughly dissolved in THF or a THF aqueous solution, and each sugar-based surfactant was thoroughly hydrated in water. The components are listed in Table 3. The THF part was mixed with the water part, and the THF was completely evaporated using an evaporator to produce micelles, which were then visually evaluated for encapsulation.

[0122] Kojyl methylenedioxycinnamate has the chemical formula shown in Figure 5.

[0123] Whether or not the substance was encapsulated in a micelle was evaluated based on whether or not transparency was maintained by visual inspection after production.

[0124] [Table 3]

[0125] As a result of the experiment, it was confirmed that in the examples containing glycoside active ingredients, the active ingredients were solubilized transparently (Figure 3), but in the active ingredients that were not glycosides (Comparative Examples 6 to 8), precipitation occurred after production (Figure 6).

[0126] 4. Confirmation of the effect of adding citric acid or tannic acid on improving the stability of micellar compositions To confirm the effect of adding citric acid (Sigma-Aldrich, USA), tannic acid (Sigma-Aldrich, USA), and tocopherol (TAMA BIOCHEMICAL CO., LTD., Japan) to improve the strength of the micelle composition, the composition was prepared as shown in Table 4.

[0127] The ethanol portion was mixed with the water portion, and the ethanol was completely evaporated using an evaporator to produce micelles. The micelle composition was placed in a dialysis bag (Spectra / Por, Spectrum Laboratories, Inc., USA), and the release profile of compound K from distilled water (DW) was monitored over time. Compound K was quantified by high-performance liquid chromatography (HPLC; Waters, USA).

[0128] [Table 4]

[0129] The experimental results are shown in Figure 7. It was confirmed that the release of compound K was reduced in Examples 6 and 7 compared to Example 5. This indicates that the stability of the micelle composition was further improved when citric acid or tannic acid was added.

[0130] It was also confirmed that the stability of the micelle composition was further improved when tocopherol was added as in Example 8.

[0131] 5. Confirmation of the skin absorption improvement effect of micellar composition To confirm the improvement of skin permeation by the micelle composition, the composition was prepared as shown in Table 5. The micelle composition was also loaded into the donor chamber of a Franz diffusion cell system (Hanson Research, USA), and absorption was monitored over time.

[0132] The receptor chamber was filled with a PBS:ethanol mixture (9:1, v / v), and human skin (Biohead, South Korea) was fixed between the donor and receptor chambers.

[0133] [Table 5]

[0134] The experimental results are shown in Figure 8. Compared with Comparative Examples 1 and 2, it was confirmed that the absorption of compound K increased when the micelle compositions of the present invention (Examples 5 and 6) were used. Furthermore, it was confirmed that the absorption of compound K in Example 6 tended to be lower than that in Example 5, but there was no significant difference.

[0135] 6. Preparation of micelle composition and confirmation of encapsulation effect at various masses To confirm the preparation of micellar compositions and the encapsulation effect at each mass, the compositions were prepared as shown in Table 6. The ethanol part was mixed with the water part, and the ethanol was completely evaporated using an evaporator to prepare micelles, which were then visually inspected to determine whether or not they were encapsulated.

[0136] [Table 6]

[0137] When the mass ratio approached 1:1 as in Example 11, complete precipitation did not occur, but fine precipitates were observed during storage after production.

[0138] The micellar composition of the present invention was realized through experiments based on combinations selected through structure-based simulations. Because it has a mixed micelle morphology, it maintains stability despite having a higher loading than other micelles.

[0139] 7. Particle size measurement and morphology observation of micelle compositions For particle size measurement and morphology observation of the micelle composition, the composition of Example 8 was used to confirm the preparation and encapsulation effect at each mass.

[0140] The particle size was measured by DLS (Zetasizer, Malvern Instruments Ltd., UK), and the results are shown in Figure 9. The particle morphology was also measured by CryoTEM (Tecnai G2 Spirit TWIN FEI microscope, USA), and the approximate micelle size is shown in Figure 10.

Claims

1. A micelle composition comprising a saccharide-based surfactant and a glycoside active ingredient encapsulated in the saccharide-based surfactant.

2. The composition of claim 1 , wherein the sugar-based surfactant is a glucoside surfactant.

3. 3. The composition of claim 2, wherein the glucoside surfactant is at least one selected from the group consisting of decyl glucoside, lauryl glucoside, coco glucoside, caprylyl / capryl glucoside, cetearyl glucoside, arachidyl glucoside, and C12-20 alkyl glucoside.

4. The composition according to claim 1 , wherein the glycoside active ingredient is a saponin glycoside.

5. The composition according to claim 4, wherein the saponin glycoside is at least one glycoside selected from the group consisting of purified ginseng saponin, purified green tea saponin, purified red ginseng saponin, purified bean saponin, and purified camellia saponin.

6. The composition according to claim 5, wherein the ginseng purified saponin comprises compound K.

7. The composition according to claim 5, wherein the purified green tea saponin comprises rogchaponin R12.

8. The composition according to claim 1, wherein the sugar-based surfactant is contained in an amount of 0.001 to 50% by weight based on the total weight of the composition.

9. 2. The composition according to claim 1, wherein the glycoside active ingredient is contained in an amount of 0.001 to 20% by weight based on the total weight of the composition.

10. The composition according to claim 1, wherein the weight ratio of the saccharide surfactant to the glycoside active ingredient is 1 to 50:

1.

11. The composition of claim 1, wherein the composition further comprises a non-covalent crosslinker.

12. The composition of claim 11 , wherein the non-covalent cross-linking agent is citric acid or tannic acid.

13. The composition of claim 11, wherein the non-covalent crosslinking agent is present in an amount of 0.0001 to 5% by weight based on the total weight of the composition.

14. The composition according to claim 11, wherein the weight ratio of the saccharide surfactant:glycoside active ingredient:non-covalent cross-linking agent is 1-50:1:0.002-0.

2.

15. 2. The composition according to claim 1, wherein the average particle size of the micelles is 5 to 200 nm.

16. The composition according to claim 1, wherein at least 90% or more of the micelle particles contained in the micelle composition have a particle size of 5 to 200 nm.

17. The composition of claim 1 , wherein the composition further comprises tocopherol.

18. The composition according to claim 17, wherein the tocopherol is contained in an amount of 0.0001 to 5% by weight based on the total weight of the composition.

19. The composition according to claim 17, wherein the weight ratio of the saccharide surfactant:glycoside active ingredient:tocopherol is 1-50:1:0.006-0.

6.

20. The composition of claim 1 , wherein the composition is a cosmetic composition.

21. 10. A method for producing the micelle composition of claim 1, comprising: A method comprising the steps of hydrating a saccharide surfactant with water and dissolving a glycoside active ingredient in at least one alcohol selected from the group consisting of C1 to C6 alcohols.

22. 22. The method of claim 21, further comprising the steps of mixing the water hydrated solution with the alcohol dissolved solution and evaporating the alcohol.

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