Active substance carrier containing biopolymer

Abstract

This specification relates to an active substance carrier comprising a core-shell network structure formed by using a biopolymer. In one aspect of this specification, the core-shell network structure comprises core-shell particles composed of a core containing prolamin; and a shell containing pullulan and pectin. The pullulan contained in the shell surrounds the core, and the pectin is located on the outermost layer of the shell and forms an interconnected network between the core-shell particles, thereby effectively promoting the transdermal absorption of the active substance.

Description

Technical Field

[0001] This specification relates to an active substance carrier using a biopolymer.

[0002]

Related Application

[0003] This application claims the priority of Korean Patent Application No. 10-2019-0159034, filed on December 3, 2019, the entire content of which is incorporated herein by reference. Background Art

[0004] In the cosmetic or pharmaceutical industries, when a skin topical formulation contains an active substance that is difficult to penetrate the stratum corneum, synthetic surfactants, etc. are used to promote the skin absorption of the active substance. In addition, a widely used method is to use polymer nanoparticles or liposome nanoparticles made of synthetic polymers such as polyethylene glycol as carriers to increase the skin permeability of the active substance. For example, polar solvents with small molecular weights such as ethanol, propylene glycol, dimethyl sulfoxide, and amphiphilic compounds are used simultaneously, or fatty acids, alcohols, 1-dodecylazacycloheptan-2-one (Azone), 2-nonyl-1,3-dioxolane (SEPA 009), dodecyl dimethylamino isopropyl carbonate (DDAIP) compounds, etc. having a polar head group and a hydrophobic chain of an amphiphilic compound are used. However, the amphiphilic enhancers described above are synthetic compounds or use organic solvents in the manufacturing process, so there are safety problems such as toxicity and allergies in the human body. Therefore, recently, the use of these compounds has been avoided in both the cosmetic and pharmaceutical industries.

[0005] Therefore, it is necessary to develop a carrier that is friendly to the human body and the environment and can effectively enhance the transdermal absorption of active substances. Summary of the Invention

[0006] Technical Problem

[0007] In one aspect, the problem to be solved by the present invention is to provide a carrier that has biocompatibility by using a biopolymer and can promote the transdermal absorption of an active substance.

[0008] Technical Solution

[0009] In one aspect, the present invention provides an active substance carrier comprising a core-shell network structure, the core-shell network structure comprising core-shell particles composed of a core containing prolamin and a shell containing pullulan and pectin, the pullulan contained in the shell surrounding the core, and the pectin being located on the outermost layer of the shell and forming an interconnected network between the core-shell particles.

[0010] In one aspect, the present invention provides a topical skin agent composition comprising: an active substance; and an active substance carrier comprising a core-shell network structure.

[0011] Advantageous Effects

[0012] In one aspect, the present invention can promote the transdermal absorption of an active substance by using a core-shell network structure formed of a biopolymer having biocompatibility. The core-shell network structure of the present invention can load an active substance having a low permeability through the skin stratum corneum, penetrate the skin stratum corneum, and transfer it to the granular layer, so that the skin can effectively absorb the active substance. Thus, the present invention can not only solve the safety problems caused by using existing synthetic chemicals, but also enable the skin to effectively absorb the active substance, thereby enhancing the effects of a cosmetic composition or a pharmaceutical composition containing the active substance. Description of the Drawings

[0013] Figure 1 A schematic diagram showing the core-shell network structure contained in a composition according to an embodiment of the present invention is shown.

[0014] Figure 2A An electron microscope image of a comparative example (not containing an active substance) of the present invention in which a core-shell network is not formed is shown.

[0015] Figure 2B An electron microscope image of a comparative example (containing an active substance) of the present invention in which a core-shell network is not formed is shown.

[0016] Figure 3A An electron microscope image confirming that a core-shell network structure according to an embodiment of the present invention (not containing an active substance) has been formed is shown.

[0017] Figure 3B An electron microscope image confirming that a core-shell network structure according to an embodiment of the present invention (containing an active substance) has been formed is shown.

[0018] Figure 4A is Figure 3AAn enlarged image showing an enlarged view of an electron microscope image confirming the formation of a core-shell network structure (excluding active substances) according to an embodiment of the present invention.

[0019] Figure 4B is Figure 3B An enlarged image showing an enlarged view of an electron microscope image confirming the formation of a core-shell network structure (including active substances) according to an embodiment of the present invention.

[0020] Figure 5 Shows the results of measuring the core-shell particle sizes in the respective compositions of an embodiment of the present invention and a comparative example.

[0021] Figure 6A Shows the confirmation result that in a solution containing a core-shell network structure according to an embodiment of the present invention, the core-shell particles are formed in the form of droplets.

[0022] Figure 6B Shows the confirmation result that in a solution containing a core-shell network structure according to an embodiment of the present invention, the core-shell particles are formed in the form of droplets and a network structure is formed between them, so that they exist in the solution in the form of an active substance carrier.

[0023] Figure 7A Shows the result of confirming the percutaneous penetration degree of Comparative Example 3 in which a hydrophobic fluorescent dye is treated alone as a comparative example of the present invention.

[0024] Figure 7B Shows the result of confirming that Example 3 as a core-shell network structure according to an embodiment of the present invention can promote the percutaneous penetration of a hydrophobic fluorescent dye.

[0025] Figure 8A Shows a cross-section of artificial skin as a control group (untreated group) of the present invention.

[0026] Figure 8B Shows an image taken three hours after applying Comparative Example 4 as a comparative example of the present invention to the surface of artificial skin.

[0027] Figure 8C Shows an image taken three hours after applying Example 4 as a core-shell network structure according to an embodiment of the present invention to the surface of artificial skin.

[0028] Figure 9A Shows an image taken after one night after applying Comparative Example 4 as a comparative example of the present invention to the surface of artificial skin.

[0029] Figure 9BFig. 0 shows an image taken after one night of coating Example 4 of the core-shell network structure according to an embodiment of the present invention on the surface of artificial skin. Detailed Description of the Invention

[0030] Hereinafter, embodiments of the present application will be described in more detail with reference to the accompanying drawings. However, the technology disclosed in the present application is not limited to the embodiments described in this specification and can be implemented in other forms. It should be understood that the embodiments described in this specification are provided to make the content of the present disclosure more thorough and complete and to fully convey the concept of the present application to those skilled in the art. In order to clearly show each component in the drawings, the dimensions such as the width or thickness of the components are enlarged. In addition, although only a part of the components is shown for the sake of convenience of description, those skilled in the art will be able to easily understand the rest. In addition, without departing from the technical concept of the present application, those skilled in the art can implement the concept of the present application in various other forms.

[0031] In the accompanying drawings Figure 1 show exemplary embodiments of the present invention. When described with reference to Figure 1 One embodiment of the present invention is a core-shell network structure formed by using a biopolymer. The core may contain prolamin, and the shell may contain pullulan and pectin. At this time, the pullulan surrounds the core, and the pectin is located on the outermost layer of the shell and can form an interconnected network between the core-shell particles.

[0032] In this specification, the core-shell network structure that forms an interconnected network between the core-shell particles is named "ECOWEB".

[0033] In this specification, the term "biopolymer" may also be referred to as "biopolymer", corresponding to "synthetic polymer". The biopolymer is a high molecular substance that constitutes a living organism or is produced by a living organism and is used in a broad sense, including nucleic acids, polysaccharides, proteins, etc.

[0034] In one embodiment, the present invention can provide an active substance carrier containing the core-shell network structure.

[0035] In one embodiment, the present invention can provide an active substance carrier for promoting the transdermal absorption of an active substance, which contains the core-shell network structure.

[0036] In one embodiment, the present invention can provide a topical skin agent composition, which contains: an active substance; and an active substance carrier containing the core-shell network structure.

[0037] In another embodiment, the use of the core-shell network structure as a carrier for an active substance in the preparation of a topical skin agent composition containing an active substance can be provided. In another embodiment, a method for transdermal delivery of an active substance can be provided, which includes administering an effective dose of the active substance carrier loaded with the active substance to a desired subject. In another embodiment, the core-shell network structure can be provided, which is used to promote the transdermal absorption of an active substance in a topical skin agent composition containing the active substance. In addition, the use of the core-shell network structure as a carrier for an active substance can be provided.

[0038] In the present specification, as a kind of plant storage protein, the prolamin is a simple protein containing a large amount of glutamine and proline. The prolamin has a self-assembly hydrophobicity with hydrophobic amino acids such as leucine and isoleucine distributed on the surface. Therefore, the prolamin is in a shape similar to a nanorod, which surrounds the active substance as the center to form a brick-like stacked structure, so that the active substance can be effectively trapped. In one embodiment, the prolamin may include one or more selected from zein, hordein, secalin, kafirin, gliadin, oryzin, and avenin, but is not limited thereto, as long as it belongs to prolamin. Specifically, zein can be isolated or extracted from corn, hordein can be isolated or extracted from barley, secalin can be isolated or extracted from rye, kafirin can be isolated or extracted from sorghum, gliadin can be isolated or extracted from wheat, oryzin can be isolated or extracted from rice, and avenin can be isolated or extracted from oats.

[0039] In one embodiment, based on the total weight of the core-shell network structure, the structure may contain 0.001 wt% to 7.5 wt% of the zein. Further, in one embodiment, based on the total weight of the composition containing the active substance, the content of the zein may be 0.01 wt% to 3 wt%. The zein and the active substance act as the core of a Pickering emulsion through hydrophobic interaction. When the content of the zein exceeds the above range, the problem is that the active substance and zein form a large coagulated precipitate, rather than multiple core-shell particles dispersed within the network structure. Therefore, the structure cannot be formed, and the dosage form itself separates into a poorly soluble and a water-soluble part. Specifically, based on the total weight of the composition, the content of the zein may be 0.001 wt% or more, 0.005 wt% or more, 0.01 wt% or more, 0.02 wt% or more, 0.03 wt% or more, 0.04 wt% or more, 0.05 wt% or more, 0.06 wt% or more, 0.07 wt% or more, 0.08 wt% or more, 0.09 wt% or more, 0.1 wt% or more, 0.2 wt% or more, 0.3 wt% or more, 0.4 wt% or more, 0.5 wt% or more, 0.6 wt% or more, 0.7 wt% or more, 0.8 wt% or more, 0.9 wt% or more, 1 wt% or more, 2 wt% or more, or 3 wt% or more. In one embodiment, based on the total weight of the composition, the content of the zein may be 3 wt% or less, 2 wt% or less, 1 wt% or less, 0.9 wt% or less, 0.8 wt% or less, 0.7 wt% or less, 0.6 wt% or less, 0.5 wt% or less, 0.4 wt% or less, 0.3 wt% or less, 0.2 wt% or less, 0.1 wt% or less, 0.09 wt% or less, 0.08 wt% or less, 0.07 wt% or less, 0.06 wt% or less, 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, 0.02 wt% or less, or 0.01 wt% or less.

[0040] In this specification, the pullulan is a substance obtained by separating and purifying polysaccharides from the fungus Aureobasidium pullulans, and may contain maltotriose, a trisaccharide formed by connecting three glucose molecules through α-1,4 glycosidic bonds. It is easily soluble in water due to its hydrophilicity but insoluble in alcohols. Due to its film-forming property and adhesiveness, a core-shell structure can be formed by coating the core containing the prolamin.

[0041] In one embodiment, based on the total weight of the core-shell network structure, the structure may contain 0.001% to 12.5% by weight of the pullulan. In addition, in one embodiment, based on the total weight of the composition containing the active substance, the content of the pullulan may be 0.01% to 5% by weight. When the content of the pullulan is within the above range, a film can be effectively formed on the core, and thus primarily the stability of the internal dosage form of the composition can be provided. When the content of the pullulan is less than 0.001% by weight, a core-shell structure cannot be effectively formed in the composition, and thus these structures may be decomposed and the active substance may precipitate. Specifically, based on the total weight of the composition, the content of the pullulan may be 0.001% by weight or more, 0.005% by weight or more, 0.01% by weight or more, 0.02% by weight or more, 0.03% by weight or more, 0.04% by weight or more, 0.05% by weight or more, 0.06% by weight or more, 0.07% by weight or more, 0.08% by weight or more, 0.09% by weight or more, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more, 0.9% by weight or more, 1% by weight or more, 2% by weight or more, 3% by weight or more, 4% by weight or more, or 5% by weight. In one embodiment, based on the total weight of the composition, the content of the pullulan may be 5% by weight or less, 4% by weight or less, 3% by weight or less, 2% by weight or less, 1% by weight or less, 0.9% by weight or less, 0.8% by weight or less, 0.7% by weight or less, 0.6% by weight or less, 0.5% by weight or less, 0.4% by weight or less, 0.3% by weight or less, 0.2% by weight or less, 0.1% by weight or less, 0.09% by weight or less, 0.08% by weight or less, 0.07% by weight or less, 0.06% by weight or less, 0.05% by weight or less, 0.04% by weight or less, 0.03% by weight or less, 0.02% by weight or less, or 0.01% by weight or less.

[0042] In the present specification, the pectin is a hydrated gel that surrounds the cellulose - hemicellulose network in plants and is a polysaccharide mainly composed of an oxide of galactose, namely galacturonic acid. When the core - shell structure consists only of zein and pullulan, if the content of the active substance is increased when loading a very small amount or more of the active substance, a state of core - shell precipitation may occur due to weight. In addition, when it is applied to a composition in an emulsion or oil - in - water (O / W) emulsion dosage form and coated on the skin, aggregation caused by hydrophobic interaction occurs, so that the active substance cannot be effectively delivered under the stratum corneum of the skin epidermis. That is, the active substance in the composition dosage form may be separated and unable to maintain a dispersed state, and exists in the form of large particles with a size of micrometers or more, thus unable to effectively achieve transdermal absorption. On the contrary, in one embodiment of the present invention, by including the pectin in the shell, a structure in which a network (interconnect) form is formed between the core - shell particles can be formed, so that the core - shell particles can be stably supported and the degree of precipitation can be minimized. Moreover, due to the inter - particle repulsive force generated by the negatively charged core - shell particles, the active substance can be well maintained in a uniformly dispersed state in the composition dosage form. At this time, in the composition dosage form, the core - shell particles capturing the active substance exist in the form of nanosized water droplets (droplets) in the aqueous phase, so that when coated on the skin, the active substance can effectively penetrate into the lower part of the stratum corneum of the skin epidermis.

[0043] In one embodiment, based on the total weight of the core - shell network structure, the structure may contain 0.001 wt% to 10 wt% of the pectin. In addition, in one embodiment, based on the total weight of the composition containing the active substance, the content of the pectin may be 0.01 wt% to 2 wt%. When the content of the pectin is within the above range, a structure that can be effectively formed between the core - shell particles and is physically stable can be obtained, thereby promoting the transdermal penetration of the active substance. When the content of the pectin is less than 0.001 wt%, a network for supporting the core - shell particles cannot be stably formed, so that the dosage form of the composition will be separated and the active substance will precipitate.

[0044] Specifically, based on the total weight of the composition, the content of the pectin can be 0.001% by weight or more, 0.005% by weight or more, 0.01% by weight or more, 0.02% by weight or more, 0.03% by weight or more, 0.04% by weight or more, 0.05% by weight or more, 0.06% by weight or more, 0.07% by weight or more, 0.08% by weight or more, 0.09% by weight or more, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more, 0.9% by weight or more, 1% by weight or more, or 2% by weight. In one embodiment, based on the total weight of the composition, the content of the pectin can be 2% by weight or less, 1% by weight or less, 0.9% by weight or less, 0.8% by weight or less, 0.7% by weight or less, 0.6% by weight or less, 0.5% by weight or less, 0.4% by weight or less, 0.3% by weight or less, 0.2% by weight or less, 0.1% by weight or less, 0.09% by weight or less, 0.08% by weight or less, 0.07% by weight or less, 0.06% by weight or less, 0.05% by weight or less, 0.04% by weight or less, 0.03% by weight or less, 0.02% by weight or less, or 0.01% by weight or less.

[0045] In one embodiment, the average particle size of the core-shell particles may be greater than 100 nm and less than or equal to 600 nm. The average particle size refers to the average value of the maximum diameters of the particles, and the average value of the particle sizes refers to the average value of the sizes of at least 90% or more of the core-shell particles distributed in the structure, carrier or composition. Specifically, the average value of the particle sizes may refer to the average value of the maximum diameters of the particles of at least 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more of the droplets distributed in the structure, carrier or composition. In the present invention, a hydrophilic polysaccharide containing pullulan and pectin is coated on the hydrophobic core as described above, and the core-shell particles are tightly connected to each other through a network (interconnect). Thus, in the composition containing the core-shell network structure, a structure in which particles having an average particle size greater than 100 nm and less than or equal to 600 nm are uniformly distributed can be stably maintained for a long time without precipitation, and the function of effectively delivering an active substance under the stratum corneum of the skin can be achieved as a carrier. Specifically, the average particle size of the core-shell particles may be 101 nm or more, 150 nm or more, 200 nm or more, 250 nm or more, 300 nm or more, 350 nm or more, 400 nm or more, 450 nm or more, 500 nm or more, or 550 nm or more. Specifically, the average particle size of the core-shell particles may be 600 nm or less, 550 nm or less, 500 nm or less, 450 nm or less, 400 nm or less, 350 nm or less, 300 nm or less, 250 nm or less, 200 nm or less, or 150 nm or less.

[0046] In one embodiment of the present invention, a topical skin agent composition can be provided, which comprises: an active substance; and an active substance carrier comprising the core-shell network structure as described above, wherein the active substance is trapped in the zein of the core. In one embodiment, the active substance can include, without limitation, substances having efficacy on the skin or body. In one embodiment, the active substance can be a water-insoluble or poorly water-soluble substance, which is difficult to penetrate through the skin by itself. In one embodiment, the active substance can be a hydrophilic or hydrophobic substance. In one embodiment, the active substance can be an alcohol-soluble substance. In one embodiment, the active substance can include one or more of phytochemicals and zoochemicals. In one embodiment, the active substance can be a synthetic chemical substance. In this specification, the phytochemical is also referred to as "phytochemical", which means a chemical substance contained in plants. Specifically, the active substance can include saponin, flavonoid, lignan, terpenoid or a mixture thereof, but is not limited thereto. For example, the saponin can include Ginsenoside. In one embodiment, the saponin can include Ginsenoside Rg1, Rb1, Rg3, Rh2, Rf2, Rs1, Rb2, Rs2, Rs3, Re, or Compound K (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, Compound K), etc., but is not limited thereto. In one embodiment, the terpenoid can include sterol, steroid, retinoid, gibberellin, abscisic acid, carotenoid, Menaquinone, plastoquinone or ubiquinone. Alternatively, the terpenoid can include triterpenoid compounds, which include one or more selected from Oleanolic acid, Ursolic acid, and arjunolic acid, but is not limited thereto.In one embodiment, the active substance may include polyphenols or polyphenol derivatives, which include one or more selected from amentoflavone, Ellagic acid, Apigenin, Berginin, Diosmetin, the super antioxidant Univestin, Resveratrol, Isoflavones, and Catechin, but are not limited thereto. In one embodiment, the active substance may include oily fatty acids, which include one or more selected from Salicylic acid, Alpha Lipoic Acid, Caffeine, Tocopherol, DHA - Docosahexaenoic acid, EPA - Eicosapentaenoic acid, and conjugated linolenic acid - CLA, but are not limited thereto. In one embodiment, the active substance may include sphingolipids, which include one or more selected from sphingomyelin, Ganglioside, Cerebroside, ceramide, glycosylceramide, lactosyl ceramide, galactosyl ceramide, and xylosyl ceramide, but are not limited thereto. In one embodiment, the active substance may include Carotene or Carotene derivatives, but are not limited thereto. In one embodiment, the active substance may include one or more substances selected from natural extracts, which include one or more selected from ginkgo leaf extract and red ginseng extract, but are not limited thereto. In this specification, the animal chemicals may include, for example, horse oil, mucin, etc.

[0047] In one embodiment, based on the total weight of the composition, the content of the active substance may be from 0.01% by weight to 10% by weight. When the content of the active substance is less than 0.01% by weight, the required efficacy of the active substance may not be fully exerted. In one embodiment, when the active substance is a hydrophobic single substance, if the content of the active substance is greater than 10% by weight, it may hinder the formation of the core-shell particles and precipitate the active substance and zein in a state of forming hydrophobic interaction due to its weight. Therefore, further thickening may be required to maintain the core-shell network structure. Specifically, based on the total weight of the composition, the content of the active substance may be 0.01% by weight or more, 0.02% by weight or more, 0.03% by weight or more, 0.04% by weight or more, 0.05% by weight or more, 0.06% by weight or more, 0.07% by weight or more, 0.08% by weight or more, 0.09% by weight or more, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more, 0.9% by weight or more, 1% by weight or more, 2% by weight or more, 3% by weight or more, 4% by weight or more, 5% by weight or more, 6% by weight or more, 7% by weight or more, 8% by weight or more, 9% by weight or more, or 9.99% by weight or more. In one embodiment, based on the total weight of the composition, the content of the active substance may be 10% by weight or less, 9% by weight or less, 8% by weight or less, 7% by weight or less, 6% by weight or less, 5% by weight or less, 4% by weight or less, 3% by weight or less, 2% by weight or less, 1% by weight or less, 0.9% by weight or less, 0.8% by weight or less, 0.7% by weight or less, 0.6% by weight or less, 0.5% by weight or less, 0.4% by weight or less, 0.3% by weight or less, 0.2% by weight or less, 0.1% by weight or less, 0.09% by weight or less, 0.08% by weight or less, 0.07% by weight or less, 0.06% by weight or less, 0.05% by weight or less, 0.04% by weight or less, 0.03% by weight or less, 0.02% by weight or less, or 0.01% by weight or less.

[0048] In one embodiment, the weight ratio of the active substance carrier to the total weight of the active substance may be from 0.001 to 10: from 0.02 to 22.

[0049] In one embodiment, the present invention may provide a method for preparing the structure or the active substance carrier containing the same. In one embodiment, the method may include: a step of adding zein to an alcohol solvent and dispersing to form a core; a step of drop-by-drop adding pullulan into the alcohol solution to form a shell surrounding the core; a step of coating the outermost layer of the shell by adding pectin to the alcohol solution added with the pullulan and forming a network between the shells; and a step of evaporating the alcohol from the solution added with the pectin to obtain a solution in which a core-shell network structure dissolved in the aqueous phase is formed.

[0050] In one embodiment, the present invention may provide a method for preparing a composition in which the active substance is loaded in the core-shell network structure. In one embodiment, the method may include: a step of adding zein and an active substance to an alcohol solvent and dispersing to form a core; a step of drop-by-drop adding pullulan into the alcohol solution to form a shell surrounding the core; a step of coating the outermost layer of the shell by adding pectin to the alcohol solution added with the pullulan and forming a network between the shells; and a step of evaporating the alcohol from the solution added with the pectin to obtain a solution in which a core-shell network structure dissolved in the aqueous phase is formed.

[0051] In one embodiment, the step of adding zein and an active substance to an alcohol solvent and dispersing may include: adding zein to the alcohol solvent and then adding the active substance thereto and dispersing.

[0052] The zein is a simple protein soluble in 60% to 90% alcohol, soluble in diluted alcohol, but insoluble in water and absolute alcohol solution. Therefore, in one embodiment, the zein added to the alcohol solvent may be a substance dissolved in 60% to 90% alcohol. In addition, in one embodiment, the alcohol solvent added with the active substance may be 70% to 95% alcohol. As described above, when zein and an active substance are added to alcohol, a structure in which the active substance is trapped by zein may be formed due to the hydrophobic interaction between the active substance and zein.

[0053] In one embodiment, the pullulan and pectin added to the alcohol solution may be aqueous-phase pullulan and aqueous-phase pectin, respectively. Specifically, the aqueous-phase pullulan and aqueous-phase pectin may be an aqueous pullulan solution and an aqueous pectin solution, respectively, and more specifically, may be a 1% to 10% aqueous pullulan solution and an aqueous pectin solution.

[0054] In one embodiment, when the pullulan and pectin are separately dissolved in an aqueous phase and added to an alcoholic solution in which the prolamin or the prolamin and the active substance are dispersed, a phase separation phenomenon (Phase separation) occurs. Due to the phase separation, nuclei containing the prolamin or the prolamin and the active substance dispersed in the alcohol precipitate, and at the same time, a self-assembled laminated structure of the prolamin is formed, thereby forming a hydrophobic nucleus. The pullulan is coated around the nucleus to form a shell structure, and then nucleus-shell particles surrounded by pectin on the outermost layer are formed, and these particles are stably and uniformly dispersed in the alcoholic solution to form a Pickering emulsion. At this time, if the acidity of the solution is adjusted to pH 2.5 to pH 6.5, the pectin forms an interconnected network between the nucleus-shell particles through the remaining alcohol. In the composition according to an embodiment of the present invention, the network structure serves as a nucleus-shell support, so that the composition can load a high content of the active substance and can maintain the structure in which the nucleus-shell network structure is stably dispersed for a long time.

[0055] In one embodiment, the method may further include: a step of gelation of a solution in which a nucleus-shell network structure is formed by adjusting the acidity of the alcoholic solution to pH 2.5 to pH 6.5. Pectin can be gelated in the presence of an acid or sugar. Hydrogen bonds are formed between the hydroxyl groups of the sugar or ionic bonds are formed through calcium ions. On the contrary, depolymerization occurs under alkaline conditions or when the acid is diluted. In addition, when the content of pectin is 2% by weight or more and 3% by weight or less based on the total weight of the composition, the viscosity of the solution itself becomes high, so that a gelated solution can be prepared. The advantage of forming a gel is that microbial contamination can be prevented by the principle of osmotic pressure.

[0056] In one embodiment, the temperature of the step of evaporating the alcohol is not limited as long as the temperature can evaporate the alcohol to obtain a solution in which a nucleus-shell network structure dissolved in the aqueous phase is formed. For example, the temperature range may be 20°C to 70°C.

[0057] In one embodiment, the dosage of the active substance carrier containing the core-shell network structure, or the composition containing the same, when applied to the skin, may be from 1 mg / kg / day to 1 g / kg / day. In one embodiment, the dosage of the active substance carrier containing the core-shell network structure, or the composition containing the same, may vary depending on the judgment of the age, gender, weight of the subject, the specific disease or pathological condition of the subject, the severity of the disease or pathological condition, the route of administration, etc. Determining the dosage based on these factors is within the knowledge of those skilled in the art. For example, the dosage may be 1 mg / kg / day or more, 2 mg / kg / day or more, 3 mg / kg / day or more, 4 mg / kg / day or more, 5 mg / kg / day or more, 10 mg / kg / day or more, 20 mg / kg / day or more, 30 mg / kg / day or more, 40 mg / kg / day or more, 50 mg / kg / day or more, 60 mg / kg / day or more, 70 mg / kg / day or more, 80 mg / kg / day or more, 90 mg / kg / day or more, 100 mg / kg / day or more, 110 mg / kg / day or more, 120 mg / kg / day or more, 130 mg / kg / day or more, 140 mg / kg / day or more, 150 mg / kg / day or more, 160 mg / kg / day or more, 170 mg / kg / day or more, 180 mg / kg / day or more, 190 mg / kg / day or more, 200 mg / kg / day or more, 250 mg / kg / day or more, 300 mg / kg / day or more, 350 mg / kg / day or more, 400 mg / kg / day or more, 450 mg / kg / day or more, or 500 mg / kg / day or more. In addition, the dosage may be, for example, 1 g / kg / day or less, 500 mg / kg / day or less, 450 mg / kg / day or less, 400 mg / kg / day or less, 350 mg / kg / day or less, 300 mg / kg / day or less, 250 mg / kg / day or less, 200 mg / kg / day or less, 190 mg / kg / day or less, 180 mg / kg / day or less, 170 mg / kg / day or less, 160 mg / kg / day or less, 150 mg / kg / day or less, 140 mg / kg / day or less, 130 mg / kg / day or less, 120 mg / kg / day or less, 110 mg / kg / day or less, or 100 mg / kg / day or less, provided that the dosage does not limit the scope of this specification in any way.

[0058] The topical skin agent composition according to an embodiment of the present invention may be a cosmetic composition.

[0059] In one embodiment, the cosmetic composition according to the present invention can be prepared in a dosage form containing a cosmetically or dermatologically acceptable medium or matrix. It can be all dosage forms suitable for topical application. For example, it can be prepared in the form of a solution, gel, solid, anhydrous paste, emulsion obtained by dispersing an oil phase in an aqueous phase, suspension, microemulsion, microcapsule, microsphere, or ionic (liposome) and non-ionic vesicle dispersants and films, or in the form of a cream, toner, lotion, powder, ointment, spray, or concealer stick. It can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant. These compositions can be prepared by conventional methods in the art.

[0060] In one embodiment, while containing the active ingredient, the cosmetic composition according to the present invention can preferably further contain other ingredients that can produce a synergistic effect on the main effect within the range that does not damage the main effect. Those skilled in the art can appropriately select and formulate the active ingredient and other ingredients of the present invention without difficulty according to the dosage form or use purpose of other cosmetic compositions. In addition, in one embodiment, the cosmetic composition of the present invention, in addition to containing the above ingredients, can also contain other ingredients formulated in conventional cosmetic compositions as needed. For example, humectants, emollients, organic pigments and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH regulators, alcohols, pigments, fragrances, blood circulation promoters, coolants, antiperspirants, purified water, etc. The other formulated ingredients that the cosmetic composition of the present invention can contain are not limited to this, and the blending amounts of the above ingredients can be selected within the range that does not damage the purpose and effect of the present invention.

[0061] The topical skin agent composition according to an embodiment of the present invention can be a pharmaceutical composition. The pharmaceutical composition can further contain preservatives, stabilizers, wettable powders or emulsifiers, pharmaceutical adjuvants for adjusting osmotic pressure such as salts and / or buffers, and other substances useful for treatment. In one embodiment, the pharmaceutical composition can be a parenteral dosage form, and the parenteral dosage form can be a rectal, topical, subcutaneous, or transdermal dosage form. For example, it can be dosage forms such as injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories, patches, etc., but is not limited thereto.

[0062] In one embodiment, the dosage of the pharmaceutical composition will vary according to the age, sex, weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, the route of administration, and the judgment of the prescriber. Determining the dosage based on these factors is within the knowledge of those skilled in the art. For example, the dosage may be 1 mg / kg / day or more, or 500 mg / kg / day or more, and 1 g / kg / day or less, 500 mg / kg / day or less, or 100 mg / kg / day or less, but the dosage does not limit the scope of this specification in any way.

[0063]

Example

[0064] Hereinafter, the present invention will be described in detail with reference to Examples, Comparative Examples, and Experimental Examples. Those skilled in the art should understand that these are only presented as examples for a more specific description of the present invention, and the scope of the present invention is not limited by these Examples, Comparative Examples, and Experimental Examples.

[0065]

Example 1

[0066] An active substance carrier containing a core-shell network structure according to an embodiment of the present invention was prepared by the following method.

[0067] Powdery zein was weighed to reach 0.5% by weight based on the total weight of the composition, and after adding it to a 70% aqueous alcohol solution, it was dispersed by stirring. Then, pullulan dissolved in an aqueous phase at pH 7 or below was weighed to reach 0.5% by weight based on the total weight of the composition at room temperature, and it was dropped into the alcohol solution drop by drop and dissolved by stirring. Aqueous phase pectin was weighed to reach 0.5% by weight based on the total weight of the composition and added to the solution. Then, the alcohol in the solution was evaporated using an evaporator (Evaporator) to obtain a final core-shell network solution dissolved in the aqueous phase.

[0068]

Example 2

[0069] A composition containing a core-shell network structure loaded with an active substance according to an embodiment of the present invention was prepared by the following method.

[0070] Powdery zein was weighed to reach 0.5% by weight based on the total weight of the composition, and after adding it to a 70% aqueous alcohol solution and dissolving it by stirring, ginsenoside (BioGF1K Complex), which is an active substance, was added to the solution. TM, Amorepacific Corporation), and adjust it to 1% by weight based on the total weight of the composition. Disperse it by sufficient stirring to form a hydrophobic interaction between the zein and the active substance. Next, weigh pullulan dissolved in an aqueous phase with a pH of 7 or lower at room temperature to reach 0.5% by weight based on the total weight of the composition, add it to the solution and stir to dissolve it. Then, weigh aqueous pectin to reach 0.5% by weight based on the total weight of the composition and add it to the solution. Then, evaporate the alcohol in the solution using an evaporator to obtain a final core-shell network solution dissolved in the aqueous phase.

[0071]

Comparative Example 1

[0072] Prepare an active substance carrier without a network structure as a comparative example of the present invention by the following method.

[0073] Weigh powdered zein to reach 0.5% by weight based on the total weight of the composition and add it to a 70% aqueous alcohol solution, then disperse it by stirring. Next, weigh pullulan dissolved in an aqueous phase with a pH of 7 or lower at room temperature to reach 0.5% by weight based on the total weight of the composition, and drop it into the alcohol solution drop by drop and dissolve it by stirring. Then, evaporate the alcohol in the solution using an evaporator to obtain a final core-shell solution dissolved in the aqueous phase.

[0074]

Comparative Example 2

[0075] Prepare a composition without a network structure and containing a core-shell network structure loaded with an active substance as a comparative example of the present invention by the following method.

[0076] Weigh powdered zein to reach 0.5% by weight based on the total weight of the composition and add it to a 70% aqueous alcohol solution, then dissolve it by stirring. After that, add red ginseng saponin (BioGF1K Complex TM , Amorepacific Corporation) as the active substance to reach 1% by weight based on the total weight of the composition, and disperse it by sufficient stirring to form a hydrophobic interaction between the zein and the active substance. Next, weigh pullulan dissolved in an aqueous phase with a pH of 7 or lower at room temperature to reach 0.5% by weight based on the total weight of the composition, add it to the solution and stir to dissolve it. Then, evaporate the alcohol in the solution using an evaporator to obtain a final core-shell network solution dissolved in the aqueous phase.

[0077]

Experimental Example 1

[0078] The core-shell structures formed in the respective compositions of Comparative Example 1, Comparative Example 2, Example 1, and Example 2 were confirmed using a Scanning Electron Microscope (SEM), and are shown respectively in Figure 2A , Figure 2B , Figure 3A and Figure 3B .

[0079] As a result, in the case of Comparative Example 1, although a core-shell structure was formed, the distribution distance between the particles of the structure was relatively large ( Figure 2A ). In Comparative Example 2 loaded with the active substance, the structure of the distribution could not be maintained and was disintegrated, and the particles aggregated with each other ( Figure 2B ).

[0080] On the contrary, in the case of Example 1, it was confirmed that a network like a web was formed between the core-shell structures and supported the particles uniformly distributed in the solution ( Figure 3A ). In Example 2 loaded with the active substance, it was also confirmed that the particles sized from 200 nm to 500 nm were interconnected by the interconnection network and uniformly dispersed at a certain distance apart ( Figure 3B ).

[0081] Figure 4A and Figure 4B are enlarged views of the in-solution structures of the Figure 3A and Figure 3B . It was confirmed that in the examples of the present invention, while a core-shell structure sized several hundred nanometers was formed, the particles were tightly connected by the interconnection network and uniformly distributed.

[0082] Figure 5 The results of measuring the hydrodynamic mean particle size of the particles respectively formed in the solutions of Comparative Example 1, Comparative Example 2, and Example 1, Example 2 using a Dynamic Light Scattering machine of Marven company are shown. When the active substance was loaded in Comparative Example 2 where no mutual network was formed between the core-shell particles, its volume increased by about four times or more compared with Comparative Example 1. On the contrary, when the active substance was loaded in Example 2, the size was not much different from the case without loading the active substance, and the particle size was still about 500 nm or less. This means that in the present invention, the particles are tightly connected by the mutual network and can firmly maintain the structure of the core-shell particles themselves.

[0083] Figure 6A and Figure 6BThe figure shows an image taken using a high-resolution transmission electron microscope (HRTEMⅠ(EDS), model: JEM-3010) after dropping 5 μl of the said Example 1 onto a carbon film 220-mesh copper (Carbon film 200-Mesh Copper (CF200-Cu)) TEM grid and drying it overnight, for high-resolution transmission electron microscope (TEM) image analysis. As Figure 6A and Figure 6B shown, it can be confirmed that in Example 1, the core-shell particles exist in the form of water droplets with a size of 100 nm to 300 nm in the aqueous phase ( Figure 6A ), and a network is formed between the core-shell particles ( Figure 6B ).

[0084]

Experimental Example 2

[0085] The following experiment was conducted to confirm whether the core-shell network structure according to an embodiment of the present invention functions as a carrier to promote the transdermal absorption of the active substance.

[0086] First, a core-shell network solution (Example 3) was prepared in the same manner as in Example 2, except that a hydrophobic fluorescent dye (manufacturer: Sigma-aldrich, product name: Nile Red) captured at a concentration of 318.369 g / mol was used instead of red ginseng saponin as the active substance. At this time, based on the total weight of the composition, the content of zein in Example 3 was 0.01 wt%, the content of pullulan was 0.02 wt%, and the content of pectin was 0.002 wt%.

[0087] Then, 200,000 human epidermal keratinocytes (purchased from: Gibco, catalog number: C01510C) were seeded into an artificial skin culture container (manufacturer: Corning, product name: Snapwell TM ), and then cultured for 48 hours using a serum-free medium (manufacturer: Gibco, product name: ). After removing the medium, a high-calcium medium (manufacturer: Cellntec, product name: CnT-PR-3D) was added and further cultured for 24 hours.

[0088] Only the culture medium below the membrane structure where the cells are located is left, and all the remaining culture medium is removed to expose the cells to air. Thereafter, the culture medium is changed every 48 hours for a total of 14 days. On the 14th day, the test substance was coated on the surface of the prepared artificial epidermis, that is, the said Example 3 was coated on the stratum corneum of the skin. After one night, the surface substance was removed as much as possible, and after freezing with OCT (manufacturer: Thermo, product name: cryomatrix), it was cut into a thickness of 10 μm, and then the frozen section was analyzed using a fluorescence microscope (BX53, Olympus Corporation, Japan), and a microscope photograph was taken using a microscope digital camera (DP72, Olympus Corporation, Japan). At this time, the average thickness of the stratum corneum of the cultured artificial skin was 10.73 μm. To compare the effects of the present invention, Comparative Example 3 in which a hydrophobic fluorescent dye was treated alone on the stratum corneum of the skin was prepared, and the penetration degree of the hydrophobic fluorescent dye was analyzed by the same method.

[0089] As a result, in the case of Comparative Example 3 in which a hydrophobic fluorescent dye was treated alone, the dye penetrated into the stratum corneum of the cultured artificial skin with an average thickness of 10.73 μm to about 3.62 μm ( Figure 7A ), on the contrary, in Example 3 of an embodiment of the present invention, the dye penetrated into about 10.51 μm on average ( Figure 7B ). This means that the core-shell network structure according to an embodiment of the present invention can promote the transdermal absorption of the active substance, thereby functioning as a carrier for permeating the active substance through the stratum corneum of the skin epidermis.

[0090]

Experimental Example 3

[0091] The following experiment was conducted to confirm whether the core-shell network structure according to an embodiment of the present invention has the effect of promoting the transdermal absorption of the active substance as a carrier.

[0092] First, a core-shell network solution was prepared in the same manner as in Example 1. At this time, based on the total weight of the composition, the content of zein was 0.01% by weight, the content of pullulan was 0.02% by weight, and the content of pectin was 0.002% by weight. In the said solution, by using a Thermo Fisher protein labeling kit (manufacturer: Thermo Fisher, product name: Thermo Fisher protein labeling ) in zein, which is a prolamin as the core, and using a hydrophilic fluorescent dye Alexa with a molecular weight of 819.85 g / mol through an amide bond 594 (manufacturer: Thermofisher) was used for tagging (Example 4). In Comparative Example 1 which is a comparative example of the present invention, the hydrophilic fluorescent dye Alexa 594 was also used for tagging (Comparative Example 4).

[0093] Next, 200,000 human epidermal keratinocytes (purchased from: Gibco, catalog number: C01510C) were seeded into an artificial skin culture container (manufacturer: Corning, product name: Snapwell TM ), and then cultured for 48 hours using a serum-free medium (manufacturer: Gibco, product name: ). After removing the medium, a high-calcium medium (manufacturer: Cellntec, product name: CnT-PR-3D) was added and further cultured for 24 hours. Only the medium under the membrane structure where the cells were located was left, and all the remaining medium was removed to expose the cells to air. Thereafter, the medium was changed every 48 hours and cultured for a total of 14 days. On the 14th day, the test substance was coated on the surface of the fabricated artificial epidermis, that is, Example 4 or Comparative Example 4 was coated on the stratum corneum of the skin. After 3 hours or overnight, the surface substance was removed as much as possible, and then frozen using OCT (manufacturer: Thermo, product name: cryomatrix), cut into a thickness of 10 μm, and then the frozen section was analyzed using a fluorescence microscope (BX53, Olympus Corporation, Japan), and a microscope photograph was taken using a microscope digital camera (DP72, Olympus Corporation, Japan). At this time, the average thickness of the stratum corneum of the cultured artificial skin was 11.89 μm ( Figure 8A ).

[0094] As a result, Figure 8B and Figure 8C show the microscope photograph images after 3 hours, Figure 9A and Figure 9B show the microscope photograph images after overnight. As Figure 9A shown, when Comparative Example 4 was coated on the skin, it penetrated an average of 5.37 μm from the skin surface. On the contrary, as Figure 9B shown, Example 4 as an embodiment of the present invention penetrated an average of 10.98 μm. This means that the structure of the present invention has a network containing pectin between the core-shell particles, thereby significantly improving the transdermal absorption effect of the active substance, and enabling the active substance to penetrate the stratum corneum of the skin and be delivered to the granular layer.

[0095] The present invention can provide the following embodiments as examples.

[0096] The first embodiment can provide an active substance carrier comprising a core-shell network structure, the core-shell network structure comprising core-shell particles composed of a core containing prolamin and a shell containing pullulan and pectin, the pullulan contained in the shell surrounding the core, and the pectin being located on the outermost layer of the shell and forming an interconnected network between the core-shell particles.

[0097] The second embodiment can provide the active substance carrier according to the first embodiment, wherein the prolamin comprises one or more substances selected from zein, hordein, secalin, kafirin, gliadin, oryzin, and avenin.

[0098] The third embodiment can provide the active substance carrier according to the first or second embodiment. Based on the total weight of the structure, the core-shell network structure comprises:

[0099] 0.001% to 7.5% by weight of prolamin;

[0100] 0.001% to 12.5% by weight of pullulan; and

[0101] 0.001% to 10% by weight of pectin.

[0102] The fourth embodiment can provide the active substance carrier according to any one or more of the first to third embodiments, wherein the average particle size of the core-shell particles is greater than 100 nm and less than or equal to 600 nm.

[0103] The fifth embodiment can provide the active substance carrier according to any one or more of the first to fourth embodiments, wherein the core-shell network structure is a carrier for promoting the transdermal absorption of the active substance.

[0104] The sixth embodiment can provide the active substance carrier according to any one or more of the first to fifth embodiments, wherein the active substance is a water-insoluble or poorly water-soluble substance.

[0105] The seventh embodiment can provide a topical skin composition comprising the active substance carrier according to any one or more of the first to sixth embodiments and an active substance.

[0106] The eighth embodiment can provide a topical skin agent composition according to the seventh embodiment, and based on the total weight of the composition, the composition contains 0.01% to 10% by weight of an active substance.

[0107] The ninth embodiment can provide a topical skin agent composition according to the seventh embodiment or the eighth embodiment, and the weight ratio of the active substance carrier to the total weight of the active substance is 0.001 to 10:0.02 to 22.

[0108] The tenth embodiment can provide a topical skin agent composition according to any one or more of the seventh to ninth embodiments, and the active substance is trapped by the zein contained in the core of the core-shell network structure.

[0109] The eleventh embodiment can provide a topical skin agent composition according to any one or more of the seventh to tenth embodiments, and the zein in the core forms a brick-like stacked structure centered on the active substance.

[0110] The twelfth embodiment can provide a topical skin agent composition according to any one or more of the seventh to eleventh embodiments, and the composition is a cosmetic composition.

[0111] The thirteenth embodiment can provide a topical skin agent composition according to any one or more of the seventh to twelfth embodiments, and the composition is a pharmaceutical composition.

[0112] The fourteenth embodiment can provide the use of a core-shell network structure as an active substance carrier in the preparation of a topical skin agent composition containing an active substance. The core-shell network structure includes core-shell particles composed of a core containing prolamin; and a shell containing pullulan and pectin. The pullulan contained in the shell surrounds the core, and the pectin is located on the outermost layer of the shell and forms an interconnected network between the core-shell particles.

[0113] The fifteenth embodiment can provide the use according to any one or more of the first to fourteenth embodiments, and the prolamin includes one or more substances selected from zein, hordein, secalin, kafirin, gliadin, oryzin, and avenin.

[0114] The 16th embodiment can provide the use according to any one or more of the 1st to 15th embodiments. Based on the total weight of the structure, the core-shell network structure includes: 0.001% to 7.5% by weight of zein; 0.001% to 12.5% by weight of pullulan; and 0.001% to 10% by weight of pectin.

[0115] The 17th embodiment can provide the use according to any one or more of the 1st to 16th embodiments. The average particle size of the core-shell particles is greater than 100 nm and less than or equal to 600 nm.

[0116] The 18th embodiment can provide the use according to any one or more of the 1st to 17th embodiments. The core-shell network structure is a carrier for promoting the transdermal absorption of an active substance.

[0117] The 19th embodiment can provide the use according to any one or more of the 1st to 18th embodiments. The active substance is a water-insoluble or poorly water-soluble substance.

[0118] The 20th embodiment can provide the use according to any one or more of the 1st to 19th embodiments. Based on the total weight of the composition, the composition includes 0.01% to 10% by weight of the active substance.

[0119] The 21st embodiment can provide the use according to any one or more of the 1st to 20th embodiments. The weight ratio of the active substance carrier to the total weight of the active substance is 0.001 to 10:0.02 to 22.

[0120] The 22nd embodiment can provide the use according to any one or more of the 1st to 21st embodiments. The active substance is trapped by the zein contained in the core of the core-shell network structure.

[0121] The 23rd embodiment can provide the use according to any one or more of the 1st to 22nd embodiments. The zein in the core forms a brick-like stacked structure centered on the active substance.

[0122] The 24th embodiment can provide the use according to any one or more of the 1st to 23rd embodiments. The composition is a cosmetic composition.

[0123] The 25th embodiment can provide the use according to any one or more of the 1st to 24th embodiments. The composition is a pharmaceutical composition.

Claims

1. An active substance carrier comprising a core-shell network structure, wherein, The core-shell network structure contains core-shell particles, and the core-shell particles are composed of a core containing zein and a shell containing pullulan and pectin. The pullulan contained in the shell surrounds the core, and the pectin is located in the outermost layer of the shell. The pectin is included in the shell to form an interconnected network and connection between the core-shell particles. The active substance carrier is used for preparing a topical skin agent composition containing an active substance. Based on the total weight of the composition, the content of zein is 0.01 wt% to 3 wt%, the content of pullulan is 0.01 wt% to 5 wt%, and the content of pectin is 0.01 wt% to 2 wt%. The average particle size of the core-shell particles is greater than 100 nm and less than or equal to 600 nm. The core-shell network structure is a carrier for promoting the transdermal absorption of an active substance.

2. The active substance carrier according to claim 1, characterized in that, The zein includes one or more substances selected from zein from corn, zein from barley, zein from rye, zein from sorghum, zein from wheat, Aspergillus alkaline protease, and zein from oats.

3. The active substance carrier according to claim 1, characterized in that, The active substance is a water-insoluble or poorly water-soluble substance.

4. A topical skin agent composition, comprising: the active substance carrier according to any one of claims 1 to 3; and an active substance.

5. The skin topical composition according to claim 4, characterized in that, Based on the total weight of the composition, the composition contains 0.01 wt% to 10 wt% of the active substance.

6. The skin external preparation composition according to claim 4, characterized in that, The weight ratio of the total weight of the active substance carrier to the active substance is 0.001 to 10:0.02 to 22.

7. The skin topical composition according to claim 4, characterized in that, The active substance is trapped by the zein contained in the core of the core-shell network structure.

8. The skin external preparation composition according to claim 7, wherein The zein in the core forms a brick-shaped laminated structure centered on the active substance.

9. The skin external preparation composition according to claim 4, wherein The composition is a cosmetic composition.

10. The skin external preparation composition according to claim 4, characterized in that, The composition is a pharmaceutical composition.

11. Use of a core-shell network structure as a carrier for an active substance in the preparation of a topical skin agent composition containing an active substance, wherein, The core-shell network structure contains core-shell particles, and the core-shell particles are composed of a core containing zein and a shell containing pullulan and pectin. The pullulan contained in the shell surrounds the core, and the pectin is located in the outermost layer of the shell. The pectin is included in the shell to form an interconnected network and connection between the core-shell particles. Based on the total weight of the composition, the content of zein is 0.01 wt% to 3 wt%, the content of pullulan is 0.01 wt% to 5 wt%, and the content of pectin is 0.01 wt% to 2 wt%. The average particle size of the core-shell particles is greater than 100 nm and less than or equal to 600 nm. The core-shell network structure is a carrier for promoting the transdermal absorption of an active substance.

12. The use according to claim 11, characterized in that, The zein includes one or more substances selected from zein from corn, zein from barley, zein from rye, zein from sorghum, zein from wheat, Aspergillus alkaline protease, and zein from oats.

13. The use according to claim 11, characterized in that, The active substance is a water-insoluble or poorly water-soluble substance.

14. The use according to claim 11, characterized in that, Based on the total weight of the composition, the composition contains 0.01 wt% to 10 wt% of the active substance.

15. The use according to claim 11, wherein, The weight ratio of the active substance carrier to the total weight of the active substance is from 0.001 to 10: 0.02 to 22.

16. The use according to claim 11, characterized in that, The active substance is trapped by the zein contained in the core of the core-shell network structure.

17. The use according to claim 16, characterized in that, The zein of the core forms a brick-shaped laminated structure centered on the active substance.

18. The use according to claim 11, wherein, The composition is a cosmetic composition.

19. The use according to claim 11, characterized in that, The composition is a pharmaceutical composition.

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