Hollow mesoporous spicule, method for manufacturing same, and method for supporting active substance

Abstract

The present invention provides a hollow mesoporous spicule, a method for manufacturing same, and a method for supporting an active substance. The hollow mesoporous spicule of the present invention stably supports the active substance and effectively penetrates the skin through the tip parts of both ends, thereby effectively delivering the active substance to a target site.

Description

Hollow mesoporous spicules, methods for manufacturing the same, and methods for carrying active substances

[0001] The present invention relates to a hollow mesoporous spicule and a method for manufacturing the same, and more specifically, to a spicule capable of supporting an active substance in its internal hollow and a method for manufacturing the same.

[0002] Raphide is a needle-shaped microcrystalline structure found within plant cells, composed primarily of calcium oxalate. Plants are known to utilize these rapide crystals as part of a defense mechanism against herbivores. Raphide has a long, sharp needle shape, and individual crystals appear in a microscopic size requiring microscopic observation.

[0003] Silica refers to silicon dioxide (SiO2) and is known by various names depending on its size and shape. Silica is a biocompatible material with low toxicity and low raw materials that can be produced as very uniform particles using simple synthesis methods, and it is utilized in various fields such as catalysts, materials, fibers, and agriculture.

[0004] Mesoporous silica has mesopores ranging in size from 2 nm to 50 nm on its surface, and these mesopores significantly increase its specific surface area. To fabricate mesoporous silica, a silica precursor and a pore-directing agent that subsequently forms the mesopores are required. Polymeric materials and surfactants are used as pore-directing agents. The pore-directing agent, dispersed in a mixture of water and alcohol, forms spherical micelles, which are stacked in layers and stabilized into a cylindrical shape. Silica grows on the surface of the micelle cylinders through the polymerization reaction of the silica precursor, and when the pore-directing agent is subsequently removed, the pores become mesopores, resulting in mesoporous silica.

[0005] For example, Korean Patent Publication No. 10-2006-0129824 discloses a technology for encapsulating L-menthol in mesoporous silica prepared in this manner; however, the types, quantities, and ease of accommodating effective substances are limited. Therefore, research and development on mesoporous silica materials capable of easily accommodating large quantities of various effective substances is required.

[0006] Accordingly, the inventors of the present invention have strived to develop a hollow mesoporous spicule capable of not only easily carrying a large amount of active material but also stably maintaining the carried active material internally and delivering it to a target site, and as a result, have completed a hollow mesoporous spicule according to the present invention.

[0007] One embodiment of the present invention provides a hollow mesoporous spicule.

[0008] One embodiment of the present invention provides a method for manufacturing a hollow mesoporous spicule.

[0009] One embodiment of the present invention provides a method for supporting an active substance within a hollow mesoporous spicule.

[0010] One embodiment of the present invention provides a cosmetic composition comprising hollow mesoporous spicules.

[0011] One embodiment of the present invention provides a pharmaceutical composition comprising a hollow mesoporous spicule.

[0012] According to specific embodiments of the present invention, the hollow mesoporous spicule of the present invention can easily encapsulate a large amount of active material through its internal hollow space and surface mesopores, and can stably maintain the encapsulated active material within. Furthermore, by having pointed ends at both ends of the spicule, it can easily penetrate the surface of the skin and effectively deliver the encapsulated active material to a predetermined depth. Additionally, by possessing anisotropy, the particles are aligned, facilitating the entry and exit of the material in a specific direction. The hollow mesoporous spicule of the present invention can possess high mechanical strength by having a polygonal cross-sectional structure. Therefore, the hollow mesoporous spicule of the present invention can effectively deliver a large amount of active material to the epidermal layer.

[0013] The hollow mesoporous spicules of the present invention can be manufactured economically and efficiently through readily available materials and simple processes. Furthermore, according to embodiments of the present invention, hollow mesoporous spicules having a high aspect ratio and uniform size and length within a predetermined range suitable for penetrating the epidermal layer can be effectively manufactured.

[0014] Figure 1 is a microscopic image of laphide.

[0015] Figure 2 is a schematic flowchart illustrating a method for manufacturing hollow mesoporous spicules.

[0016] Figure 3 is a schematic flowchart illustrating the process of preparing a lapid acicular body from a Dracaena marginata leaf.

[0017] Figure 4 is a microscopic image of a lapid acicular body obtained from Dracaena marginata through the process of Figure 3.

[0018] Figure 5 is a microscopic image of laphaid acicular bodies obtained from a) Alocasia, b) Monstera deliciosa, c) Dracaena Waneke, d) Anthurium, e) Traveler's palm, and f) Sansevieria (Dracaena trifasciata) through the process of Figure 3.

[0019] Figure 6 is a microscopic image of a core-shell composite prepared using silicon alkoxide.

[0020] Figure 7 is a microscopic image of a hollow mesoporous spicule prepared by etching the lapide from the lapide core-shell composite of Figure 6.

[0021] Figure 8 is an electron microscope image of the overall shape and cross-section of the lapid needle body of Figure 4 and the hollow mesoporous lapid spicule of Figure 7.

[0022] Figure 9 is a fluorescence microscope image of a core-shell composite prepared using a silicate compound.

[0023] Figure 10 is a schematic flowchart illustrating the process of loading an effective substance onto a hollow mesoporous spicule.

[0024] Figure 11 is a microscopic image of the hollow meporous spicules of Figures 8 and 9 before and after the MCT solution was immersed in them.

[0025] One embodiment of the present invention provides a hollow mesoporous spicule. The hollow mesoporous spicule comprises a mesoporous silica shell; and an internal hollow defined as the inner surface of the mesoporous silica shell, wherein the internal hollow and the mesoporous silica shell each have a length in a first direction longer than the lengths in a second direction and a third direction, respectively, which are perpendicular to the first direction, and have tip portions at both ends of the first direction, and the internal hollow may have a polygonal cross-section perpendicular to the first direction.

[0026] Specifically, referring to FIG. 2, the hollow mesoporous spicule (10) includes an internal hollow (100) defined by a mesoporous silica shell (200) and an internal surface (210) of the mesoporous silica shell (200).

[0027] As used in this specification, the term “spicule” refers to a needle-shaped, pointed three-dimensional structure having tip portions at both ends that gradually taper in width away from the center of the three-dimensional structure. Due to the unique shape described above, the hollow mesoporous spicule of the present invention can effectively deliver a supported active substance to a predetermined depth.

[0028] As used herein, the term “shell” refers to a member that encloses an internal material or space and distinguishes the inside from the outside. The shell may have a predetermined thickness defined by an outer surface facing outward, an inner surface facing inward, and the distance between the outer surface and the inner surface.

[0029] The internal hollow (100) and the mesoporous silica shell (200) have a length in the first direction that is longer than the lengths in the second and third directions, which are each perpendicular to the first direction.

[0030] As used in this specification, the term “first direction” refers to the long axis direction of the hollow mesoporous spicule.

[0031] As used in this specification, the term “second direction” means a direction perpendicular to the first direction.

[0032] As used in this specification, the term “third direction” means a direction perpendicular to the first direction.

[0033] The above second and third directions may be in a vertical relationship.

[0034] Each of the above first, second, and third directions may be perpendicular to each other.

[0035] The internal hollow (100) and the mesoporous silica shell (200) have tip portions (105, 205) at both ends of the first direction. The tip portions (105, 205) have a shape in which the thickness, width, or girth gradually decreases in the direction away from the center of the first direction. The tip portions (205) of the mesoporous silica shell (200) and the hollow mesoporous spicule (10) have a pointed and sharp shape, thereby allowing the hollow mesoporous spicule (10) to easily penetrate to a predetermined depth of the target (e.g., skin tissue).

[0036] In one embodiment, the tips of both ends may be equally pointed, or the tip of one end may be more pointed than the tip of the other end.

[0037] As used herein, the term “internal hollow” refers to an empty space surrounded by the inner surface of the mesoporous silica shell. An active material may be supported in the internal hollow.

[0038] The internal hollow (100) has a polygonal cross-section perpendicular to the first direction. The polygon may be defined as the internal surface of the mesoporous silica shell (200) or as the boundary between the internal hollow (100) and the mesoporous silica shell (200).

[0039] As used in this specification, the term “polygon” may include not only shapes with angled vertices, but also shapes that are recognized as a polygon as a whole, formed by the extensions of line segments defining the outline or surface of an object meeting to form vertices.

[0040] In one embodiment, the polygon may be a triangle, a square, a pentagon, a hexagon, a heptagon, an octagon, a nonagon, a decagon, a decagon, a decagon, a dodecagon, a thirteen-sided polygon, a fifteen-sided polygon, a sixteen-sided polygon, a seventeen-sided polygon, an eighteen-sided polygon, a nineteen-sided polygon, a twenty-sided polygon, a twenty-one-sided polygon, a twenty-two-sided polygon, a twenty-four-sided polygon, a twenty-five-sided polygon, a twenty-seven-sided polygon, a twenty-eight-sided polygon, a twenty-nine-sided polygon, or a thirty-sided polygon.

[0041] [Correction pursuant to Rule 91 24.12.2025] In one specific example, the polygon may be a convex polygon or a concave polygon. For example, the convex polygon may be in the shape of a square, a hexagon, or an octagon. For example, the concave polygon may be in the shape of an H.

[0042] In one embodiment, the mesoporous silica shell (200) may be formed with a uniform thickness over the shape of the internal hollow (100). In this case, the cross-section of the mesoporous silica shell (200) may have a shape that includes the polygon of the internal hollow (100) as a hollow inside and extends from the polygonal shape of the internal hollow (100) with a uniform thickness over the entire shape.

[0043] In this specification, the term “uniform overall” means that quantitative values ​​have a difference of within ±10%, within ±5%, within ±3%, within ±2%, or within ±1%.

[0044] In one embodiment, the thickness of the mesoporous silica shell (200) may be about 0.1 μm to about 5 μm. Preferably, the thickness of the mesoporous silica shell (200) may be about 0.1 μm to about 4 μm, about 0.1 μm to about 3 μm, about 0.1 μm to about 2.5 μm, about 0.1 μm to about 2 μm, about 0.2 μm to about 5 μm, about 0.2 μm to about 4 μm, about 0.2 μm to about 3 μm, about 0.2 μm to about 2.5 μm, about 0.2 μm to about 2 μm, about 0.4 μm to about 5 μm, about 0.4 μm to about 4 μm, about 0.4 μm to about 3 μm, about 0.4 μm to about 2.5 μm, or about 0.4 μm to about 2 μm. In this case, the active material can be easily contained within the internal hollow (100), the contained active material can be maintained in a stable state without being released, and the mesoporous silica shell (200) can be easily decomposed in the target environment to effectively deliver the active material.

[0045] In one embodiment, the mesoporous silica shell (200) may include tip portions (205) at both ends and a column portion between the two tip portions (205). The cross-section of the column portion may be defined such that the inner surface has a polygonal shape that is the cross-section of the inner hollow (100), and the outer surface has a shape that extends from the polygonal shape of the inner hollow (100) by the thickness of the mesoporous silica shell (200). Accordingly, the cross-section of the column portion may have a perforated structure in which a hole is formed in the center of the polygonal shape defined by the outer surface, which is the cross-section of the inner hollow (100).

[0046] The mesoporous silica shell (200) and the hollow mesoporous spicule (10) are structures having a polygonal cross-section and have a large internal hollow (100) relative to the total volume, and can have excellent mechanical strength. Therefore, the hollow mesoporous spicule (10) can penetrate an object such as skin tissue without being destroyed, and can effectively stimulate the epidermal or dermal layer of the skin tissue or effectively deliver internal substances to the penetration depth.

[0047] The mesoporous silica shell (200) may have mesopores that penetrate in the thickness direction. Alternatively, a plurality of mesopores may be connected to each other to form a channel, thereby penetrating the mesoporous silica shell (200) in the thickness direction.

[0048] The internal hollow (100) can be connected to the outside by the mesopores of the mesoporous silica shell (200). An effective material can be supported in the internal hollow (100) by passing through the mesopores.

[0049] In one embodiment, the volume of the internal hollow (100) may be about 50% to about 99% of the volume defined by the outer surface of the mesoporous silica shell (200). Preferably, the volume of the internal hollow (100) is about 50% to about 98%, about 50% to about 97%, about 50% to about 96%, about 50% to about 95%, about 50% to about 90%, about 50% to about 85%, about 50% to about 80%, about 50% to about 75%, about 50% to about 70%, about 50% to about 65%, about 50% to about 60%, about 60% to about 99%, about 60% to about 98%, about 60% to about 97%, about 60% to about 96%, about 60% to about 95%, about 60% to about 90%, about 60% to about 65%, about 50% to about 60%, about 60% to about 99%, about 60% to about 98%, about 60% to about 97%, about 60% to about 96%, about 60% to about 95%, about 60% to about 90%, about 60% to about It may be 85%, about 60% to about 80%, about 60% to about 75%, about 60% to about 70%, or about 60% to about 65%. In this case, a large amount of active material can be easily stored within the hollow mesoporous spicule (10), and leakage of the stored material can be prevented.

[0050] In one embodiment, the volume of the internal hollow (100) may be about 10 times or more the total volume of mesopores contained in the mesoporous silica shell (200). Preferably, the volume of the internal hollow (100) may be about 12 times or more, about 15 times or more, about 20 times or more, about 25 times or more, about 30 times or more, about 40 times or more, or about 50 times or more the total volume of mesopores contained in the mesoporous silica shell (200). For example, the volume of the internal hollow (100) may be about 100 times or less the total volume of mesopores contained in the mesoporous silica shell (200). In this case, the active material can be easily contained within the internal hollow (100), and the contained active material can be maintained in a stable state without being released.

[0051] In one embodiment, the length of the mesoporous silica shell (200) in the first direction may be about 10 μm to about 300 μm. Preferably, the length of the mesoporous silica shell (200) in the first direction is about 10 μm to about 250 μm, 10 μm to about 200 μm, about 10 μm to about 180 μm, about 10 μm to about 160 μm, about 10 μm to about 140 μm, about 10 μm to about 120 μm, about 10 μm to about 100 μm, about 20 μm to about 300 μm, about 20 μm to about 250 μm, about 20 μm to about 200 μm, about 20 μm to about 180 μm, about 20 μm to about 160 μm, about 20 μm to about 140 μm, about 20 μm to about 120 μm, about 20 μm to about 100 μm, It may be about 30 μm to about 300 μm, about 30 μm to about 250 μm, about 30 μm to about 200 μm, about 30 μm to about 180 μm, about 30 μm to about 160 μm, about 30 μm to about 140 μm, about 30 μm to about 120 μm, about 30 μm to about 100 μm, about 40 μm to about 300 μm, about 40 μm to about 250 μm, about 40 μm to about 200 μm, about 40 μm to about 180 μm, or about 40 μm to about 200 μm. In this case, a large amount of active material can be loaded into the internal hollow (100), and the loaded active material can be effectively delivered.

[0052] In one embodiment, the length in the second direction and the length in the third direction of the mesoporous silica shell (200) may each be 20 μm or less. Preferably, the length in the second direction and the length in the third direction of the mesoporous silica shell (200) may each be 18 μm or less, 15 μm or less, 12 μm or less, 10 μm or less, 8 μm or less, 5 μm or less, 3 μm or less, 2 μm or less, or 1 μm or less. The length in the second direction and the length in the third direction may be the same or different from each other. In this case, the spicule can effectively penetrate the target due to the narrow cross-sectional area.

[0053] In one embodiment, the length in the second direction and the length in the third direction of the mesoporous silica shell (200) may each be 0.5 μm or more. Preferably, the length in the second direction and the length in the third direction of the mesoporous silica shell (200) may each be 1 μm or more, 2 μm or more, 3 μm or more, 5 μm or more, 8 μm or more, or 10 μm or more. The length in the second direction and the length in the third direction may be the same or different from each other.

[0054] In one embodiment, the mesoporous silica shell (200) may be an organic silica shell or an inorganic silica shell. For example, the mesoporous silica shell (200) may be formed of organic silica or inorganic silica.

[0055] Organic silica is silica that additionally contains organic groups such as carbon and hydrogen in addition to the silicon (Si) and oxygen (O) elements that constitute ordinary silica (SiO2). Organic silica includes, for example, residual hydrocarbon groups from the polymerization reaction of organic alkoxysilanes in which hydrocarbon groups are substituted in addition to alkoxy groups on a silicon central atom. In particular, organic silica containing residual alkylene groups can be formed by the polymerization reaction of an organic silica precursor, such as an alkoxysilylalkylene in which two or more alkoxysilyl groups are linked together by an alkylene.

[0056] Inorganic silica refers to ordinary silica (SiO2) composed of silicon and oxygen.

[0057] Mesoporous organic silica or mesoporous inorganic silica is silica in which a number of mesopores with a size (diameter) of about 2 nm to about 50 nm are formed by the self-assembly of a surfactant, and the size of the pores is controlled according to the type of surfactant and additives (such as trimethylbenzene).

[0058] In one embodiment, the silicon-carbon molar ratio of the mesoporous silica shell (200) may be about 1:0.2 to about 1:1. Preferably, the silicon-carbon molar ratio of the mesoporous silica shell (200) may be about 1:0.3 to about 1:1, about 1:0.4 to about 1:1, about 1:0.5 to about 1:1, about 1:0.6 to about 1:1, about 1:0.7 to about 1:1, or about 1:0.8 to about 1:1. In this case, the size and total volume of the mesopores of the mesoporous silica shell (200) and the volume of the internal hollow (100) can be effectively controlled to the above-described ranges. Accordingly, the active material can be easily supported into the internal hollow (100), and the supported active material can be maintained in a stable state without being released.

[0059] As used herein, the term “active substance” refers collectively to substances that exhibit a specific effect on living organisms. Active substances may include cosmetics, pharmaceutical substances, diagnostic substances, insecticides, catalysts, etc. In one embodiment, a solvent may function as an active substance itself.

[0060] In one embodiment, the hollow mesoporous spicule (10) may include an effective material contained in the internal hollow (100). For example, the effective material may be introduced into the hollow mesoporous spicule (10). The effective material includes a hydrophilic or hydrophobic material.

[0061] In one embodiment, the active material may include a hydrophobic material. For example, the hydrophobic material may be dissolved in a hydrophobic solvent.

[0062] In one embodiment, the active substance may include any one selected from mineral oil, oleic acid, methyl oleate, vegetable oil, triglyceride, ascorbyl tetraisopalmitate, oil-soluble licorice extract, alpha-bisabolol, retinyl palmitate, tocopherol, madeca, or terpenes.

[0063] The above triglyceride may be an ester compound of glycerol and three molecules of saturated fatty acids. The three molecules of saturated fatty acids may be identical or different from each other. The above triglyceride may include short-chain triglycerides (SCT), medium-chain triglycerides (MCT), long-chain triglycerides (LCT), etc. For example, the above short-chain triglycerides may be formed from fatty acids having 6 or fewer carbon atoms, the above medium-chain triglycerides from fatty acids having 12 or fewer carbon atoms, and the above long-chain triglycerides from fatty acids having 13 or more carbon atoms.

[0064] In one embodiment, Madeca may include Madecassoside, Madecasicoside, Asiaticoside, Asiaticoside, etc.

[0065] The above vegetable oil may include soybean oil, sunflower oil, palm oil, coconut oil, argan oil, olive oil, avocado oil, canola oil, olive oil, etc.

[0066] The above terpenes may include terpenes or terpenoids. For example, the above terpenes may include monoterpenes, monoterpenoids, sesquiterpenoids, diterpenoids, sesquiterpenoids, triterpenoids, sesquiterpenoids, tetraterpenoids, polyterpenoids, norisopenoids, hemiterpenoids, etc. The above terpenes may have a linear (acyclic) or cyclic structure. For example, the above cyclic structure may include monocyclic, bicyclic, tricyclic, tetracyclic, etc.

[0067] The above terpenes may include squalene, vitamin A, ocimene, limonene, linalool, eucalyptol, geraniol, citronellol, etc. The above active substance may be the hydrophobic substance itself, or may be a hydrophobic substance containing a substance having functionalities such as whitening, wrinkle improvement, hair removal, relief of acne-prone skin, relief of hair loss symptoms, improvement of elasticity or skin moisturization, improvement of skin-related diseases, regulation of skin physiological activity, regulation of skin immune function.

[0068] When a hollow mesoporous spicule (10) is dispersed in a hydrophobic solvent in which an active substance is dissolved, the active substance can be supported into the interior of the hollow mesoporous spicule (10) through the mesopores along with the hydrophobic solvent. If an excess amount of a hydrophilic solvent, such as water, is added to the hydrophobic solvent, an oil-in-water emulsion can be formed. Since the surface of the mesoporous silica shell (200) is hydrophilic and disperses better in water than in a hydrophobic solvent, the dispersion medium can be changed from a hydrophobic solvent to water. In this case, the hydrophobic solvent and the active substance supported inside do not mix with water, so they do not escape to the outside and can be stably maintained within the internal hollow (100).

[0069] In one embodiment, the hydrophobic solvent may comprise an unsaturated hydrocarbon solvent. The unsaturated hydrocarbon solvent may comprise a hydrocarbon that is at least partially unsaturated with about 10 to about 50 carbon atoms. Preferably, the number of carbon atoms may be about 10 to about 40, about 20 to about 50, or about 20 to about 40. The unsaturated hydrocarbon may comprise about 1 to about 20, about 1 to about 10, about 1 to about 5, about 5 to about 20, or about 5 to about 10 unsaturated bonds (double bonds or triple bonds). For example, the unsaturated hydrocarbon solvent may comprise MCT.

[0070] In one embodiment, the active material comprises a hydrophilic material, and the step of injecting the active material may include injecting the active material into the hollow mesoporous spicule by pressurizing it.

[0071] For example, the active substance may include a hydrophilic substance. The hydrophilic substance may be dissolved in a hydrophilic solvent, but not limited to this. The hydrophilic substance may include alpha hydroxy acids (glycolic acid, lactic acid, citric acid, etc.), peptides, vitamin C and derivatives thereof, hyaluronic acid, niacinamide, panthenol, glycerin, etc. The hydrophilic solvent may include water, alcohols, glycols, glycerin, etc., but not limited to this.

[0072] In one embodiment, the hydrophilic material may be injected into the interior of the hollow mesoporous spicule (10) by pressure. For example, the hollow mesoporous spicule (10) and the hydrophilic material may be placed in a flexible container and then sealed, and the hydrophilic material may be injected into the interior of the hollow mesoporous spicule (10) by creating a vacuum inside the container or by applying pressure inside the container. The injection may be performed using a hydrophilic solvent.

[0073] In one embodiment, since the surface of the silica shell is hydrophilic, the active ingredient can easily move from the inside to the outside in a hydrophilic solvent, and in this process, the active ingredient introduced into the hollow can be easily released to the outside. In this case, the release of the active ingredient within the hollow can be blocked by capping the mesoporous pores through a capping layer.

[0074] In one embodiment, the hollow mesoporous spicule (10) may include a capping layer that caps the mesoporous pores of the mesoporous silica shell (200). The capping layer may block the entry and exit of material through the mesoporous pores. In one embodiment, the capping layer may fill the internal space of the mesoporous pores of the mesoporous silica shell (200) or partially or wholly cover the outer surface of the mesoporous silica shell (200).

[0075] For example, the active material may include a hydrophilic material. The hydrophilic material may be dissolved in a hydrophilic solvent. Since the surface of the mesoporous silica shell (200) is hydrophilic, the active material can easily move from the inside to the outside within the hydrophilic solvent, and in this process, the active material introduced into the inner hollow (100) may be easily released to the outside. In this case, the release of the active material within the inner hollow (100) can be blocked by capping the mesoporous pores through a capping layer.

[0076] In one embodiment, the capping layer may be formed of inorganic silica. In this case, the release of the active pharmaceutical ingredient inside can be effectively blocked.

[0077] The term “aspect ratio” means the ratio of the length of the first direction to the average of the lengths of the second and third directions.

[0078] In one embodiment, the mesoporous silica shell (200) may have an aspect ratio of about 1:2 to about 1:100. If the aspect ratio is less than about 1:2, a sufficient amount of active material cannot be contained within the hollow mesoporous spicule (10), and it may be difficult to deliver the active material to a target depth. If the aspect ratio is greater than about 1:100, it may be difficult for the active material to pass through the mesoporous silica shell (200) and be contained in the internal hollow (100).For example, the above aspect ratio is about 1:2 to about 1:80, about 1:2 to about 1:60, about 1:2 to about 1:50, about 1:2 to about 1:40, about 1:2 to about 1:35, about 1:2 to about 1:30, about 1:2 to about 1:25, about 1:2 to about 1:20, about 1:2 to about 1:15, about 1:2 to about 1:10, about 1:2 to about 1:8, about 1:2 to about 1:6, about 1:3 to about 1:100, about 1:3 to about 1:80, about 1:3 to about 1:60, about 1:3 to about 1:50, about 1:3 to about 1:40, about 1:3 to about 1:35, about 1:3 to About 1:30, about 1:3 to about 1:25, about 1:3 to about 1:20, about 1:3 to about 1:15, about 1:3 to about 1:10, about 1:3 to about 1:8, about 1:3 to about 1:6, about 1:4 to about 1:100, about 1:4 to about 1:80, about 1:4 to about 1:60, about 1:4 to about 1:50, about 1:4 to about 1:40, about 1:4 to about 1:35, about 1:4 to about 1:30, about 1:4 to about 1:25, about 1:4 to about 1:20, about 1:4 to about 1:15, about 1:4 to about 1:10, about 1:4 to about 1:8, about 1:4 to about It may be 1:6, about 1:5 to about 1:100, about 1:5 to about 1:80, about 1:5 to about 1:60, about 1:5 to about 1:50, about 1:5 to about 1:40, about 1:5 to about 1:35, about 1:5 to about 1:30, about 1:5 to about 1:25, about 1:5 to about 1:20, about 1:5 to about 1:15, about 1:5 to about 1:10, about 1:5 to about 1:8, or about 1:5 to about 1:6.

[0079]

[0080] One embodiment of the present invention provides a method for manufacturing a hollow mesoporous spicule. The method for manufacturing the hollow mesoporous spicule may include the steps of: preparing a needle-like body having a length in a first direction longer than the lengths in a second direction and a third direction, each perpendicular to the first direction, and having tip portions at both ends of the first direction, and having a polygonal cross-section perpendicular to the first direction; forming a mesoporous silica shell on the surface of the needle-like body to manufacture a core-shell composite; and removing the needle-like body inside the core-shell composite.

[0081] Referring to FIG. 2, a core (90) is prepared as a core, and a mesoporous silica shell (200) is formed on the surface of the core (90) to produce a core-shell composite (20), and a hollow mesoporous spicule (10) can be produced by removing the core (90) inside the core-shell composite (20).

[0082] As used in this specification, the term “needle” refers to a structure having a long, slender shape with pointed ends. The needle may have tips at both ends. The tips of the needle may have a shape corresponding to the tips of the internal hollow.

[0083] In one embodiment, the main component of the needle body (90) may be calcium oxalate or calcium carbonate. For example, the needle body (90) may be composed of calcium oxalate or calcium carbonate alone, excluding water or trace amounts of impurities.

[0084] In one embodiment, the needle body (90) may include a calcium oxalate monohydrate crystal or a calcium carbonate crystal. The calcium oxalate monohydrate crystal may be a prismatic monoclinic crystal. The calcium carbonate crystal may be a bipyramidal orthorhombic crystal.

[0085] In one embodiment, the needle body (90) may be a lapid needle body. The lapid needle body may be derived from a plant. Specifically, the above-mentioned lapid needle-like body may be derived from the fruit, root, or stem of a plant of the Actinidiaceae family, Amaranthaceae family, Araceae family, Strelitziaceae family, Araliaceae family, Areceae family, Asparagaceae family, Bromeliaceae family, Commelinaceae family, Onagraceae family, Poaceae family, Polygonaceae family, Rubiaceae family, Pandanaceae family, or Vitaceae family.

[0086] For example, the above-mentioned plant of the Actinidia family may be a plant of the genus Actinidia. The above-mentioned plant of the genus Actinidia may include Actinidia Deliciosa (Actinidia Deliciosa 'Hayward', etc.), Actinidia Chinensis, etc. The fruit of the plant of the genus Actinidia may be kiwifruit.

[0087] For example, the above-mentioned Amaranthaceae plant may be a plant of the genus Beta or Spina. The above-mentioned plant of the genus Beta may be beets or Swiss chard. The above-mentioned plant of the genus Spina may be spinach.

[0088] For example, the above-mentioned Araceae plant may be a plant of the genus Dracaena, Alocasia, Arisaema, Anthurium, Arum, Caladium, Colocasia, Dieffenbachia, Epipremnum, Monstera, Philodendron, Spathiphyllum, Lasia, Dracontium, Amorphophallus, or Zantedeschia. The above-mentioned plant of the genus Dracaena may be Dracaena marginata, Dracaena Waneke, or Sansevieria (Dracaena trifasciata). The above-mentioned plant of the genus Alocasia may be Alocasia indica or Alocasia odora. The above-mentioned plant of the genus Araceae may be Cobra Lily. The above-mentioned plant of the genus Arum may be Arum maculatum (Cuckoopint). The above-mentioned plant of the genus Caladium may be Caladium schomburgkii or sea cabbage (Senecio candicans). The above-mentioned plants of the genus Taro may be Colocasia esculenta, Colocasia gigantia, Colocasia nymphaeifolia, Taro, Cocoyam, or Colocasia antiquorum (Eddoe). The above-mentioned plants of the genus Epipremnum may be Scandapsus (Devil's Ivy) or Epipremnum pinnatum.The above-mentioned plant of the genus Dieffenbachia may be Dieffenbachia picta. The above-mentioned plant of the genus Monstera may be Monstera deliciosa (Swiss Cheese Plant). The above-mentioned plant of the genus Lacia may be Lacia heterophylla. The above-mentioned plant of the genus Dracontium may be Dracontium nivosum. The above-mentioned plant of the genus Amorphophallus may be Amorphophallus sylvaticus or Amorphophallus campanulatus.

[0089] For example, the above-mentioned plant of the family Birdfloweria may be a plant of the genus Ravenala. The above-mentioned plant of the genus Ravenala may be Traveller's palm.

[0090] For example, the above-mentioned Araliaceae plant may be a plant of the genus Brassaia. The above-mentioned Brassaia plant may be the Umbrella Tree.

[0091] For example, the above-mentioned palm family plant may be a plant of the genus Caryota, a plant of the genus Ptychosperma, or a plant of the genus Arengah. The above-mentioned plant of the genus Caryota may be a fishtail palm.

[0092] For example, the above-mentioned plant of the family Asclepiadaceae may be a plant of the genus Agave or a specimen of the genus Cordyline. The above-mentioned plant of the genus Agave may be Agave. The above-mentioned plant of the genus Cordyline is Cordyline Terminalis (Cordyline Terminalis 'Rededge', CORDYLINE TERMINALIS 'CHOCOLATE QUEEN', etc.)

[0093] For example, the above-mentioned pineapple plant may be a pineapple.

[0094] For example, the above-mentioned Commelinaceae plant may be a plant of the genus Commelina, a plant of the genus Tradescantia, or a plant of the genus Triceratella. The above-mentioned Commelina plant may be Dayflower. The above-mentioned Tradescantia plant may be Wandering Jew.

[0095] For example, the above-mentioned plant of the Onagraceae family may be a plant of the genus Fuchsia. The above-mentioned plant of the genus Fuchsia may be Fuchsia.

[0096] For example, the above grass may be *Cenchrus echinatus* or *Cenchrus longispinus*.

[0097] For example, the above-mentioned knotweed plant may be rhubarb (Rheum rhabarbarum).

[0098] For example, the above grape family plant may be Virginia creeper.

[0099] For example, the above-mentioned plant of the Pandanaceae family may be a plant of the genus Pandanus. The above-mentioned plant of the genus Pandanus may be Pandanus Boninensis.

[0100] Figure 1 is an image of the shape of laphide observed under a microscope. Referring to Figure 1, the shape of laphide is needle-like.

[0101] In one embodiment, the lapid-based needles may be derived from Dracaena Marginata. In this case, due to the availability, low cost, high lapid content, and uniform lapid size of Dracaena Marginata, it is possible to prepare lapid-based needles of uniform size suitable for overall epidermal penetration at low cost and high efficiency through a simple process.

[0102] In one embodiment, the aspect ratio of the needle body (90) may match the aspect ratio of the hollow mesoporous spicule. For example, the above aspect ratio is 1:2 to 1:100, 1:2 to 1:90, 1:2 to 1:80, 1:2 to 1:70, 1:2 to 1:60, 1:2 to 1:50, 1:2 to 1:40, 1:2 to 1:30, 1:2 to 1:20, 1:3 to 1:100, 1:3 to 1:90, 1:3 to 1:80, 1:3 to 1:70, 1:3 to 1:60, 1:3 to 1:50, 1:3 to 1:40, 1:3 to 1:30, 1:3 to 1:20, 1:4 to 1:100, 1:4 to 1:90, 1:4 to 1:80, 1:4 to It may be 1:70, 1:4 to 1:60, 1:4 to 1:50, 1:4 to 1:40, 1:4 to 1:30, 1:4 to 1:20, 1:5 to 1:100, 1:5 to 1:90, 1:5 to 1:80, 1:5 to 1:70, 1:5 to 1:60, 1:5 to 1:50, 1:5 to 1:40, 1:5 to 1:30, or 1:5 to 1:20.

[0103] In one embodiment, the cross-section perpendicular to the first direction of the needle body (90) may be a polygon. The polygon may be defined as the outer surface of the needle body (90). In one embodiment, if the needle body (90) is a layered crystal, the polygon may be defined as a line segment connecting both ends in the width direction of each layer.

[0104] In one embodiment, the polygon may be a triangle, a square, a pentagon, a hexagon, a heptagon, an octagon, a nonagon, a decagon, a decagon, a decagon, a dodecagon, a thirteen-sided polygon, a fifteen-sided polygon, a sixteen-sided polygon, a seventeen-sided polygon, an eighteen-sided polygon, a nineteen-sided polygon, a twenty-sided polygon, a twenty-one-sided polygon, a twenty-two-sided polygon, a twenty-four-sided polygon, a twenty-five-sided polygon, a twenty-seven-sided polygon, a twenty-eight-sided polygon, a twenty-nine-sided polygon, or a thirty-sided polygon.

[0105] [Correction pursuant to Rule 91 24.12.2025] In one specific embodiment, the polygon may be a convex polygon or a concave polygon. Preferably, the convex polygon may be in the shape of a square, a hexagon, or an octagon. For example, the concave polygon may be in the shape of an H.

[0106] In one embodiment, the cross-section perpendicular to the first direction of the needle body (90) may correspond to the shape of the internal hollow (100).

[0107] In one embodiment, the aspect ratio of the needle body (90) may match the aspect ratio of the hollow mesoporous spicule (10), the mesoporous silica shell (200), or the internal hollow (100). The length (length of the major axis) of the needle body (90) may be 10 μm or more. For example, the length of the needle body (90) may be 12 μm or more, 15 μm or more, or 18 μm or more. Additionally, the length of the needle body (90) may be 100 μm or less.

[0108] The thickness (length or diameter in the second or third direction) of the needle body (90) may be 5 μm or less. For example, the thickness of the needle body (90) may be 4 μm or less, 3 μm or less, or 2 μm or less. In addition, the thickness of the needle body (90) may be 0.1 μm or more.

[0109] FIG. 3 is a schematic flowchart illustrating the process of preparing a lapid needle-like body from a Dracaena marginata leaf. Referring to FIG. 3, the leaves of Dracaena marginata are collected, washed, cut and crushed, the crushed material is filtered, the filtrate is centrifuged, and the separated material is washed and dispersed with acetic acid to obtain the lapid needle-like body.

[0110] In one embodiment, centrifugation of the filtrate may be repeated several times. For example, the centrifugation may be performed two or three times. In this case, between repeated centrifugation, the filtrate may be further dispersed in a solvent such as water, acetic acid, ammonium nitrate, or ethanol by a dispersion method such as ultrasonic dispersion.

[0111] A core-shell composite (20) can be manufactured by forming a mesoporous silica shell (200) on the surface of a needle body (90). For example, the mesoporous silica shell (200) can cover part or all of the surface of the needle body (90).

[0112] In one embodiment, a mesoporous silica shell (200) can be formed by reacting a needle body (90) with a surfactant and a silica precursor in a mixed solvent of water and an alcohol-based solvent. For example, the needle body (90) can be dispersed in the mixed solvent, and the surfactant and the silica precursor can be added and reacted to form a mesoporous silica shell (200). The surfactant can induce mesopores in the mesoporous silica shell (200).

[0113] In one embodiment, the alcohol-based solvent may include a monohydric or polyhydric alcohol having about 1 to about 20 carbon atoms. For example, the alcohol-based solvent may include methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, etc.

[0114] For example, the ratio of water and alcohol-based solvent in the above mixed solvent may be 40:60 to 90:10, 40:60 to 80:20, 40:60 to 70:30, 40:60 to 65:35, 50:50 to 90:10, 50:50 to 80:20, 50:50 to 70:30, 50:50 to 65:35, 60:40 to 90:10, 60:40 to 80:20, 60:40 to 70:20, or 60:40 to 65:35. In this case, a mesoporous silica shell can be effectively formed with a uniform thickness on a rod-shaped inorganic silica rod.

[0115] The above surfactant may include a polymeric surfactant or an ionic surfactant. The above surfactant may be used by dissolving it in the above alcohol-based solvent.

[0116] The above-mentioned polymeric surfactant may include polyvinylpyrrolidone or a polyoxyalkylene block copolymer. The polyoxyalkylene block copolymer may be at least one selected from the group consisting of polyethylene oxide-polyethylene oxide (PEO-PEO) dioblock copolymer, polyethylene oxide-polypropylene oxide (PEO-PPO) dioblock copolymer, polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) triblock copolymer, polyethylene oxide-polybutylene oxide-polyethylene oxide (PEO-PBO-PEO) triblock copolymer, and polypropylene oxide-polyethylene oxide-polypropylene oxide (PPO-PEO-PPO) triblock copolymer, butylene oxide-polyethylene oxide (PEO-PBO-PEO) triblock copolymer.

[0117] In one embodiment, the polymeric surfactant may be one or more selected from the group consisting of polyvinylpyrrolidone (PVP) with an average molecular weight of 10,000 Da to 100,000 Da, Brij 52, Brij 58, Brij 30, Brij 76, Brij 78, Brij 97, Brij 35, Tritox X-100, Trton C-114, Tween 20, Tween 40, Tween 60, Tween 80, Span 40, Pluronic L121, Pluronic L64, Pluronic P103, Pluronic P123, Pluronic F68, Pluronic F127, Pluronic F88, Pluronic F108, Tetronic 908, Tetronic 901, and Tetronic 90R4.

[0118] In one embodiment, the ionic surfactant may include cationic surfactants such as cetrimonium bromide (CTAB), cetrimonium chloride (CTAC), cetylpyridinium chloride (CPC), benzalkonium chloride (BAC), benzethonium chloride (BZT), dimethyldioctadecylammonium chloride, and dioctadecyldimethylammonium bromide (DODAB).

[0119] In one embodiment, the surfactant may include the polymeric surfactant and the ionic surfactant together.

[0120] In one embodiment, a silica forming catalyst may be used in the reaction for forming a mesoporous silica shell (200).

[0121] In one embodiment, the silica-forming catalyst may include ammonia, ammonium chloride, an amine compound, a hydroxide of an alkali metal or alkaline earth metal, a metal fluoride, a transition metal catalyst, an inorganic acid such as hydrochloric acid, etc. The amine compound may include triethylamine, etc. The metal fluoride may be at least one selected from the group consisting of sodium fluoride (NaF), calcium fluoride (CaF2), aluminum fluoride (AlF3), lithium fluoride (LiF), magnesium fluoride (MgF2), potassium fluoride (KF), cesium fluoride (CsF), zinc fluoride (ZnF2), tin(II) fluoride (SnF2), and iron(III) fluoride (FeF3), but not limited to one. The metal fluoride is used as a catalyst to promote the condensation of a silica precursor and may be additionally used when the silica condensation rate by other catalysts such as ammonia is insufficient.

[0122] In one embodiment, the mesoporous silica shell may be formed of organic silica or inorganic silica. The organic silica may be formed from an organic silica precursor. The inorganic silica may be formed from an inorganic silica precursor.

[0123] The above organic silica precursor includes an organic alkoxysilane. The above organic alkoxysilane is one in which a hydrocarbon group is substituted in addition to an alkoxy group on a silicon central atom, and may include an alkoxysilylalkylene in which two or more alkoxysilyl groups are connected to each other by an alkylene.

[0124] In one embodiment, the organic silica precursor may be one or more of BTSE (bis(triethoxysilyl)ethane), BTSEY (bis(triethoxysilyl)ethylene), BTES (Bis-[3-(triethoxysilyl)tetrasulfide]), bis[3-(triethoxysilyl)propyl]tetrasulfide, 1,4-bis(triethoxysilyl)benzene, BTEB (Bis(triethoxysilyl)phenylene), and BTEBP (Bis(triethoxysilyl)-biphenyl).

[0125] The above inorganic silica precursor may include a silicon alkoxide compound or a silicate compound.

[0126] The silicon alkoxide compound may include tetraalkoxysilane. For example, the tetraalkoxysilane may be a compound in which four alkoxy groups are substituted on a silicon central atom. The alkoxy groups may have 1 to 6 carbon atoms. For example, the alkoxy groups may be methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy. The four alkoxy groups of the tetraalkoxysilane may be identical or different from each other.

[0127] In one embodiment, the silicon alkoxide compound may be one or more of TEOS (Tetraethyl orthosilicate), TMOS (Tetramethyl orthosilicate), and TPOS (Tetrapropyl orthosilicate).

[0128] The above silicate compound may include a metasilicate salt or a disilicate salt. The metasilicate salt is a metasilicate anion (SiO3 2- It may be a salt of the cation corresponding to ), and the disilicate salt is a disilicate anion (Si2O5 2-It may be a salt of a cation corresponding to ). In one embodiment, the silicate salt compound may include at least one of sodium metasilicate (Na2SiO3), potassium metasilicate (K2SiO3), lithium metasilicate (Li2SiO3), magnesium metasilicate (MgSiO3), ammonium metasilicate ((NH4)2SiO3), calcium metasilicate (CaSiO3), and sodium disilicate (Na2Si2O5).

[0129] In one embodiment, the mesoporous silica shell (200) may be formed by two or more shell-forming steps. For example, the mesoporous silica shell (200) may be formed by a first shell-forming step and a second shell-forming step, wherein the first shell-forming step is as described above. After the first shell-forming step, the supernatant may be separated from the reaction solution, and the second shell-forming step may proceed in the supernatant.

[0130] For example, the second shell forming step may use less ionic surfactant than the first shell forming step. For example, compared to the first shell forming step, the second shell forming step may use less ionic surfactant in an amount of about 70% or less, about 60% or less, or about 50% or less.

[0131] In one embodiment, a silica forming catalyst may not be used in the second shell forming step. For example, a silica forming catalyst may be used in the first shell forming step, and a silica forming catalyst may not be used in the second shell forming step.

[0132] In one embodiment, in order to increase the thickness of the shell during the mesoporous silica shell formation step, crosslinking of an organic material may proceed simultaneously. For example, a crosslinking component such as resorcinol or formaldehyde may additionally participate during the formation of the mesoporous silica shell. Accordingly, crosslinking between multiple silica precursor molecules, crosslinking between the silica precursor and the crosslinking component, and crosslinking between multiple crosslinking components may proceed together to form a mesoporous silica shell.

[0133] In one embodiment, auxiliary components such as a base catalyst, a chelating agent, a structure controller, a stabilizer, a pH regulator, and a hydration controller may be used in the mesoporous silica shell formation step. For example, amine compounds such as triethanolamine, metal salt compounds such as sodium chloride, etc., may be additionally used in the mesoporous silica shell formation step.

[0134] The needle-like body (90) inside the core-shell composite (20) can be removed. The internal space of the core-shell composite (20) from which the needle-like body (90) has been removed can be provided as an internal hollow (100). In this case, the needle-like body (90) and the internal hollow (100) may have complementary shapes.

[0135] In one embodiment, the step of removing the needle body (90) may include etching the core-shell composite (20) with an acidic solution. For example, the core-shell composite (20) may be dispersed in water, and the acidic solution may be added to the dispersion to remove the needle body (90). The acidic solution has high etching selectivity for the needle body (90) relative to the mesoporous silica shell (200), and can remove the needle body (90) while preserving the mesoporous silica shell (200).

[0136] In one embodiment, the acidic solution may include an inorganic acid or an organic acid. The inorganic acid may include, but is not limited to, hydrofluoric acid, hydrochloric acid, bromic acid, iodic acid, sulfuric acid, ammonium persulfate, nitric acid, perchloric acid, etc. The organic acid may include, but is not limited to, citric acid, oxalic acid, succinic acid, tannic acid, ascorbic acid, acetic acid, etc. For example, the acidic solution may include hydrochloric acid, tannic acid, and combinations thereof.

[0137] In one embodiment, the etching may be performed with an acid having a concentration of 0.5 M to 10 M. In one embodiment, the etching may be performed with an acid having a concentration of 0.5 M to 8 M, 0.5 M to 5 M, 0.6 M to 10 M, 0.6 M to 8 M, or 0.6 M to 5 M. For example, the etching may be performed with hydrochloric acid having a concentration of 0.5 M to 10 M, 0.5 M to 8 M, 0.5 M to 5 M, 0.6 M to 10 M, 0.6 M to 8 M, or 0.6 M to 5 M.

[0138] In one embodiment, a method for manufacturing a core-shell composite (20) or a mesoporous silica shell (200) may include dispersing a needle body (90) in a medium and reacting it with the organic silica precursor or inorganic silica precursor, the surfactant and / or silica forming catalyst.

[0139] In one embodiment, when manufacturing a core-shell composite (20) or a mesoporous silica shell (200) using the silicate compound, hydrochloric acid may be additionally added to the dispersion of the needle body (90) in addition to the silicate compound, the surfactant, and / or the silica forming catalyst.

[0140] In one embodiment, the silicate compound and hydrochloric acid may be added slowly at a low speed. For example, the silicate compound and hydrochloric acid may each be added at a flow rate of 1 mL / h to 40 mL / h. In this case, sufficient time can be secured for the silicate compound to form a silica shell. For example, the silicate compound and hydrochloric acid may be added at a flow rate of 1 mL / h to 30 mL / h, 1 mL / h to 25 mL / h, 1 mL / h to 20 mL / h, 1 mL / h to 15 mL / h, 5 mL / h to 40 mL / h, 5 mL / h to 30 mL / h, 5 mL / h to 25 mL / h, 5 mL / h to 20 mL / h, 5 mL / h to 15 mL / h, 5 mL / h to 40 mL / h, 10 mL / h to 30 mL / h, 10 mL / h to 25 mL / h, 10 mL / h to 20 mL / h, or 10 mL / h to 15 mL / h.

[0141] In one embodiment, the ratio of the flow rate of the silicate compound to the hydrochloric acid may be 1:0.1 to 1:10. In this case, the conversion from the silicate compound to the silica shell can occur effectively. For example, the ratio of the flow rate of the silicate compound to the hydrochloric acid may be 1:0.1 to 1:10, 1:0.1 to 1:8, 1:0.1 to 1:5, 1:0.1 to 1:4, 1:0.1 to 1:3, 1:0.1 to 1:2, 1:0.5 to 1:10, 1:0.5 to 1:8, 1:0.5 to 1:5, 1:0.5 to 1:4, 1:0.5 to 1:3, or 1:0.5 to 1:2.

[0142] In one embodiment, the silicate compound may be added in the form of an aqueous solution or an aqueous dispersion. In one embodiment, hydrochloric acid may be added in a mixed state with a mixed medium such as water or ethanol. In this case, the flow rate and ratio of the aqueous solution or aqueous dispersion of the silicate compound and the water or ethanol mixture of hydrochloric acid may be added in the same flow rate and ratio as the silicate compound and hydrochloric acid.

[0143] In one embodiment, a method for manufacturing a hollow mesoporous spicule (10) may further include filtering a needle body (90), a core-shell composite (20), or a mesoporous silica shell (200) with a filter. For example, the needle body (90), the core-shell composite (20), and the mesoporous silica shell (200) may be filtered by a mesh filter having pores of 30 μm or less, 20 μm or less, 15 μm or less, 10 μm or less, or 5 μm or less, and may be filtered in the middle of each separate or consecutive step of the manufacturing method.

[0144] In one embodiment, the method for manufacturing a hollow mesoporous spicule (10) may further include a washing step. The washing may be performed using a suitable solvent or medium such as water (e.g., distilled water, ultrapure water, etc.), ethanol, acetone, acetic acid, etc. For example, the washing may be performed at any point in time of each separate or consecutive step of the manufacturing method.

[0145] In one embodiment, the method for manufacturing hollow mesoporous spicules (10) may further include a high-temperature drying step. The high-temperature drying may be performed at a temperature of 40°C or higher, 50°C or higher, or 60°C or higher. Through this, residual solvent or dispersion medium in the manufacturing process can be removed and the structure of the hollow mesoporous spicules (10) can be stabilized.

[0146] In one embodiment, the method for manufacturing a hollow mesoporous spicule (10) may further include a sintering step. The sintering may be performed at a temperature of 200°C or higher, 300°C or higher, 400°C or higher, 500°C or higher, or 550°C or higher. Additionally, the sintering may be performed at a temperature of 1,000°C or lower, 900°C or lower, 800°C or lower, 700°C or lower, or 600°C or lower. Through this, the structure of the hollow mesoporous spicule (10) can be stabilized and the mechanical strength can be increased.

[0147]

[0148] One embodiment of the present invention provides a method for supporting an active substance in a hollow mesoporous spicule. The method for supporting an active substance in the hollow mesoporous spicule may include the steps of: mixing the hollow mesoporous spicule with the active substance; and injecting the active substance into the internal hollow of the hollow mesoporous spicule.

[0149] Referring to FIG. 10, a hollow mesoporous spicule is dispersed in a solution containing an active substance, and an oil-in-water emulsion is formed from the solution to move the solution into the hollow mesoporous spicule, thereby allowing the active substance to be loaded onto the hollow mesoporous spicule.

[0150] The above active material may include a hydrophobic material or a hydrophilic material. The above active material may be dissolved in a suitable solvent. For example, the solution may include a solvent and an active material. The solvent, the solution, and the active material may each be hydrophilic or hydrophobic.

[0151] In one embodiment, the active material comprises a hydrophobic material, and the step of injecting the active material may include forming an oil-in-water emulsion from a mixed solution of a hollow mesoporous spicule (10) and the active material. As the oil-in-water emulsion is formed, the hydrophobic material outside the hollow mesoporous spicule (10) may be injected into the inner hollow (100).

[0152] When a hollow mesoporous spicule (10) is dispersed in a hydrophobic solvent in which an active substance is dissolved, the active substance can be supported into the interior of the hollow mesoporous spicule (10) through the mesopores along with the hydrophobic solvent. If an excess amount of a hydrophilic solvent, such as water, is added to the hydrophobic solvent, an oil-in-water emulsion can be formed. Since the surface of the mesoporous silica shell (200) is hydrophilic and disperses better in water than in a hydrophobic solvent, the dispersion medium can be changed from a hydrophobic solvent to water. In this case, the hydrophobic solvent and the active substance supported inside do not mix with water, so they do not escape to the outside and can be stably maintained within the internal hollow (100).

[0153] In one embodiment, the hydrophobic solvent may comprise an unsaturated hydrocarbon solvent. The unsaturated hydrocarbon solvent may comprise a hydrocarbon that is at least partially unsaturated with about 10 to about 50 carbon atoms. Preferably, the number of carbon atoms may be about 10 to about 40, about 20 to about 50, or about 20 to about 40. The unsaturated hydrocarbon may comprise about 1 to about 20, about 1 to about 10, about 1 to about 5, about 5 to about 20, or about 5 to about 10 unsaturated bonds (double bonds or triple bonds). For example, the unsaturated hydrocarbon solvent may comprise medium-carbon triglycerides (MCT).

[0154] In one embodiment, the method for carrying an effective substance may further include the step of removing the remaining effective substance that was not injected into the internal hollow (100) by centrifugation.

[0155] In one embodiment, the method for carrying an active substance may further include the step of capping mesoporous pores present in the shell of a spicule into which the active substance is injected.

[0156] For example, after moving the solution, the mesoporous pores of the mesoporous silica shell (200) can be capped. For example, the mesoporous pores can be capped by filling the mesoporous pores or by forming a capping layer that covers the mesoporous silica shell (200).

[0157] In one embodiment, the solution may include a hydrophilic solvent and a hydrophilic active substance. The hydrophilic active substance may be dissolved in the hydrophilic solvent. Since the surface of the mesoporous silica shell (200) is hydrophilic, the active substance can easily move from the inside to the outside within the hydrophilic solvent, and in this process, the active substance introduced into the inner hollow (100) may be easily released to the outside. In this case, the release of the active substance within the inner hollow (100) can be blocked by capping the mesoporous pores through a capping layer.

[0158] In one embodiment, the capping layer may be formed of inorganic silica. In this case, the release of the active pharmaceutical ingredient inside can be effectively blocked.

[0159]

[0160] One embodiment of the present invention provides a cosmetic composition comprising the hollow mesoporous spicule as an active ingredient.

[0161] In one embodiment, the cosmetic composition may be used for whitening, wrinkle improvement, hair removal, acne relief, relief of hair loss symptoms, elasticity enhancement, or skin moisturization.

[0162] The above hollow mesoporous spicules may be included in the cosmetic composition in an amount of about 0.1% to about 10% by weight. Specifically, the hollow mesoporous spicules comprise about 0.1 wt% to about 9 wt%, about 0.1 wt% to about 8 wt%, about 0.1 wt% to about 6 wt%, about 0.1 wt% to about 5 wt%, about 0.1 wt% to about 3 wt%, about 0.1 wt% to about 2 wt%, about 0.1 wt% to about 1 wt%, about 0.2 wt% to about 10 wt%, about 0.2 wt% to about 9 wt%, about 0.2 wt% to about 8 wt%, about 0.2 wt% to about 6 wt%, about 0.2 wt% to about 5 wt%, about 0.2 wt% to about 3 wt%, about 0.2 wt% to about 2 wt%, about 0.2 wt% to about 1 wt%, about 0.3 wt% to about 10 wt%, about 0.3 It may contain weight% to about 9 weight%, about 0.3 weight% to about 8 weight%, about 0.3 weight% to about 6 weight%, about 0.3 weight% to about 5 weight%, about 0.3 weight% to about 3 weight%, about 0.3 weight% to about 2 weight%, about 0.3 weight% to about 1 weight%, about 0.5 weight% to about 10 weight%, about 0.5 weight% to about 9 weight%, about 0.5 weight% to about 8 weight%, about 0.5 weight% to about 6 weight%, about 0.5 weight% to about 5 weight%, about 0.5 weight% to about 3 weight%, about 0.5 weight% to about 2 weight%, or about 0.5 weight% to about 1 weight%.

[0163] For example, the content of the hollow mesoporous spicules is not particularly limited, but preferably may be about 0.1% to about 5% by weight relative to the total weight of the cosmetic composition.

[0164] The above cosmetic composition may be a formulation commonly used in cosmetics. In one embodiment, the composition may be prepared as a formulation including a lotion (skin lotion), skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, eye cream, hand cream, foundation, essence, nourishing essence, eye essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cream, body cleanser, suspension, gel, powder, paste, mask pack or sheet, or aerosol composition. Additionally, it may be applied in various forms suitable for providing moisture to the skin, such as a gel or cream, paste, or solid form, and specifically, it may be a gel cream form with a particle texture such as sherbet or slush. A composition of such a formulation may be prepared according to methods conventional in the field.

[0165] In one embodiment, the composition may further comprise one or more selected from the group consisting of oils, purified water, emulsifiers, dispersants, colorants, fragrances, UV blockers, sweeteners, vitamins, and metal ion chelating agents. Additionally, in one embodiment, the composition may further comprise about 0.1% by weight to about 3.0% by weight of a preservative. The amount of the additional components, such as oils, can be easily selected by a person skilled in the art within a range that does not impair the purpose and effect of the present invention.

[0166]

[0167] One embodiment of the present invention provides a pharmaceutical composition comprising the hollow mesoporous spicule as an active ingredient. For example, the hollow mesoporous spicule may support an active substance inside, and the active substance may exhibit a pharmaceutically effective effect.

[0168] The above hollow mesoporous spicules may be included in the pharmaceutical composition in an amount of about 0.1% to about 10% by weight. Specifically, the hollow mesoporous spicules comprise about 0.1 wt% to about 9 wt%, about 0.1 wt% to about 8 wt%, about 0.1 wt% to about 6 wt%, about 0.1 wt% to about 5 wt%, about 0.1 wt% to about 3 wt%, about 0.1 wt% to about 2 wt%, about 0.1 wt% to about 1 wt%, about 0.2 wt% to about 10 wt%, about 0.2 wt% to about 9 wt%, about 0.2 wt% to about 8 wt%, about 0.2 wt% to about 6 wt%, about 0.2 wt% to about 5 wt%, about 0.2 wt% to about 3 wt%, about 0.2 wt% to about 2 wt%, about 0.2 wt% to about 1 wt%, about 0.3 wt% to about 10 wt%, about 0.3 It may contain weight% to about 9 weight%, about 0.3 weight% to about 8 weight%, about 0.3 weight% to about 6 weight%, about 0.3 weight% to about 5 weight%, about 0.3 weight% to about 3 weight%, about 0.3 weight% to about 2 weight%, about 0.3 weight% to about 1 weight%, about 0.5 weight% to about 10 weight%, about 0.5 weight% to about 9 weight%, about 0.5 weight% to about 8 weight%, about 0.5 weight% to about 6 weight%, about 0.5 weight% to about 5 weight%, about 0.5 weight% to about 3 weight%, about 0.5 weight% to about 2 weight%, or about 0.5 weight% to about 1 weight%.

[0169] In one embodiment, the pharmaceutical composition may include a conventionally pharmaceutically acceptable carrier, excipient, or additive. The pharmaceutical composition may be formulated according to conventional methods and may be prepared in various forms of oral administration such as tablets, pills, powders, capsules, syrups, emulsions, microemulsions, or forms of parenteral administration such as intramuscular, intravenous, or subcutaneous administration.

[0170] When the above pharmaceutical composition is prepared in the form of an oral formulation, examples of additives or carriers used include cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate, gelatin, talc, surfactants, suspending agents, emulsifiers, diluents, etc. When the pharmaceutical composition of the present invention is prepared in the form of an injectable formulation, examples of additives or carriers include water, saline solution, glucose aqueous solution, similar sugar aqueous solution, alcohol, glycol, ether (e.g., polyethylene glycol 400), oil, fatty acid, fatty acid ester, glyceride, surfactant, suspending agent, emulsifier, etc.

[0171]

[0172] The following examples will be explained in more detail. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

[0173] Example 1. Preparation of Lapid Needle-shaped Body

[0174] Six leaves (7 to 8 g) of Dracaena marginata were collected, and the collected leaves were washed with tap water.

[0175] Washed leaves were cut into pieces 3 cm to 5 cm in length and placed in a grinder (Shinil Electronics, Product No.: SMX-C820). Then, 70 g to 80 g of tap water, equivalent to 10 times the mass of the leaves, was added to the grinder and ground for 20 to 30 seconds.

[0176] A mixture containing lapide was obtained by pouring sufficient tap water over the crushed material and filtering it through a 300 mesh nylon mesh. At this time, the presence of lapide was confirmed by observing the mixture containing lapide under a microscope.

[0177] The mixture containing the lapide was centrifuged at 4427xg for 5 minutes, the supernatant was discarded, and 40 mL of ultrapure water was added to the precipitate and transferred to a 50 mL conical tube.

[0178] After centrifuging the sample a second time at 4427xg for 5 minutes and discarding the supernatant, the precipitate was dispersed in 10 mL of ultrapure water and 30 mL of acetic acid / ethanol mixture (acetic acid:ethanol = 1:9) and sonicated for at least 5 minutes.

[0179] This was centrifuged three times at 4427xg for 5 minutes, the yellow supernatant was discarded, and the white precipitate was dispersed in 10 mL of ultrapure water and 30 mL of acetic acid / ethanol (10 v / v%).

[0180] After filtering this with a nylon membrane filter (Merck, product number: NY1004700) with a pore size of 20 μm, it was washed with 20 mL of ultrapure water and 20 mL of ethanol and dried in a drying oven at 60°C to obtain lapide needle bodies.

[0181] Figure 4 is a microscopic image of a lapide-based needle body manufactured according to an example. Referring to Figure 4, it was confirmed that needle bodies having various lengths in the first direction were manufactured through a simple method.

[0182] Example 1-1. Preparation of Lapid Needles by Plant Type

[0183] Five to ten leaves (7 to 8 g) were collected from each of the following plants: Alocasia, Monstera deliciosa, Dracaena Waneke, Anthurium, Traveler's palm, and Dracaena trifasciata, and the collected leaves were washed with tap water.

[0184] Washed leaves were treated in the same manner as in Example 1 to obtain dried lapid needle-like bodies for each plant type.

[0185] Figure 5 is a microscopic image of a lapid-based needle body according to a plant type manufactured according to an example. Referring to Figure 5, it was confirmed that needle bodies having various lengths in the first direction according to a plant type were manufactured through a simple method.

[0186] Example 2. Preparation of hollow mesoporous spicules using silicon alkoxide

[0187] Example 2.1. Preparation of a Lapid Core-Shell Composite

[0188] 64 mg of the lapide needles from Example 1 were transferred to a 50 mL conical tube and dispersed in 40 mL of an ethanol / ultrapure water / ammonia mixed solution (volume ratio 330:100:5). 800 μL of tetraethoxysilane (Tetraethyl orthosilicate: TEOS) was added to 40 mL of the lapide dispersion and reacted in an ultrasonic disperser for 1 hour. Afterward, the mixture was filtered through a nylon membrane filter (Merck, product number: NY1004700) with a pore size of 20 μm and dispersed in 40 mL of an ethanol / ultrapure water mixed solution (30 vol% ethanol).

[0189] To 40 mL of the above lapide dispersion, 4 mL of triethanolamine (TEA) solution (330 mg / 10 mL ultrapure water), 4 mL of sodium chloride solution (1 g / 40 mL ultrapure water), 1.6 mL of cetrimonium bromide (CTAB) solution (1 mg / 10 mL methanol), 1 mL of resorcinol solution (50 mg / 4 mL ethanol), 1.8 mL of tetraethyl orthosilicate (TEOS) solution (100 μL / 1 mL ethanol), and 600 μL of formaldehyde solution (1.75% ultrapure water) were added sequentially and reacted for 6 hours at 90°C and 400 rpm using a stirrer. Afterward, it was filtered through a nylon membrane filter with a pore size of 20 μm (Merck, product number: NY1004700) and dispersed in 40 mL of ultrapure water.

[0190] Figure 6 is a microscopic image of a core-shell composite fabricated based on the laphide needle body of Figure 4. Referring to Figure 6, it was confirmed that core-shell composites having various lengths in the first direction were fabricated through a simplified method.

[0191] Example 2.2. Core Etching

[0192] The core of the lapide core-shell composite was etched by adding 750 μL of hydrochloric acid solution (5 N, Daejeong Pharmaceutical) to a lapide core-shell composite dispersed in 10 mL of ultrapure water and reacting it at a rotator speed of 3 rpm for 1 hour. After etching, the progress and completion of the etching were confirmed by microscopic observation, and the mixture was filtered with a 20 μm nylon filter, washed with 50 mL of ultrapure water and 50 mL of ethanol, and dried in a drying oven at 60°C to produce hollow mesoporous spicules. The dried hollow mesoporous spicules were sintered in a furnace at 500°C for 2 hours to remove all remaining organic matter, and then stored in a dry state. Figure 7 is a microscopic image of the hollow mesoporous spicules prepared by etching the lapide from the lapide core-shell composite of Figure 6. Referring to Fig. 7, it was confirmed that hollow mesoporous spicules with various lengths in the first direction of approximately 50 μm were manufactured using a simplified method. Fig. 8 is an electron microscope image of the overall shape and cross-section of the lapide needle body of Fig. 4 and the hollow mesoporous lapide spicule of Fig. 7. Referring to Fig. 8, it was confirmed that hollow mesoporous spicules containing an internal hollow with a polygonal cross-section were manufactured by using a lapide needle body with a polygonal cross-sectional structure.

[0193] Example 3. Preparation of hollow mesoporous spicules using a silicate compound

[0194] A reaction cocktail of 400 mL (15% EtOH) was prepared by mixing 340 mL of distilled water, 60 mL of EtOH, 270 mg of CTAB, 100 mg of Pluronic F127, and 375 mg of NH4Cl. A lapide dispersion was prepared by dispersing 100 mg of the dry lapide from Example 1 and Example 1-1 in a 4 mL reaction cocktail. A 100 mM NaF solution was prepared by mixing 168 mg of NaF with 40 mL of distilled water. A sodium silicate solution was prepared by mixing 1 g of anhydrous Na2SiO3 with 40 mL of distilled water. A hydrochloric acid reaction solution was prepared by adding 2.2 mL of 5 M HCl to a mixture of 16.65 mL of distilled water and 11.1 mL of EtOH.

[0195] 40 mL of reaction cocktail was injected into a 50 mL flask containing a magnetic bar. While stirring the reaction cocktail at 600 rpm, 8 mL of lapide dispersion and 800 μL of NaF solution were added at 25°C. 7.5 mL of sodium silicate solution and 7.5 mL of hydrochloric acid reaction solution were slowly dropwise added to the reaction mixture using a syringe pump at a flow rate of 15 mL / h over 30 minutes, followed by stirring at 600 rpm for 30 minutes at 25°C. The mixture was filtered through a 20 μm mesh filter, washed with distilled water, and redispersed in 50 mL of reaction cocktail. The above reaction process was repeated three times to obtain the desired silica shell thickness. The final mixture was dried in a 60°C oven for at least 2 hours, sonicated in a 6 g / L ammonium nitrate ethanol solution, and stirred at 300 rpm for 10 minutes. The stirred mixture was filtered through a 20 μm mesh filter and redispersed in 20 mL of distilled water, after which 20 mL of 0.65 M hydrochloric acid solution was added to etch the core lapide. Subsequently, hollow mesoporous spicules were prepared by sintering at 550 °C for 2 hours to remove residual organic matter.

[0196] Figure 9 is a fluorescence microscope image of a core-shell composite prepared using a silicate compound. Referring to Figure 9, it was confirmed that a hollow mesoporous spicule containing an internal hollow with a polygonal cross-section was prepared by using a lapide needle with a polygonal cross-section structure.

[0197] Example 4. Support of hydrophobic material

[0198] A hydrophobic material was loaded onto a hollow mesoporous spicule according to the effective material loading flowchart of Fig. 10.

[0199] Specifically, 300 μL of MCT (medium-carbon triglycerides, BergaBest MCT Oil, Sternchemie GmbH+ Co. KG) was added to 10 mg of dried mesoporous spicules, and MCT impregnation was carried out for 30 minutes in an ultrasonic disperser (DH.WUC.D10H Daehan Ultrasonic Washer, 25℃, 40 kHZ, 80% output, 30 min). Subsequently, 3 mL of ultrapure water was added to the dispersion and vigorously stirred to separate and disperse the MCT-impregnated spicules into a water layer. Then, centrifugation was repeated three times to remove unimpregnated MCTs, and finally, water-dispersed MCT-impregnated spicules were prepared.

[0200] Figure 11 is a microscopic image of the hollow mesoporous spicules of Figures 8 and 9 before and after the MCT solution was loaded. Referring to Figure 11, it was confirmed that a hydrophobic active material was loaded inside the hollow mesoporous spicules.

[0201] Example 5. Support of hydrophilic material

[0202] 10 g of a mixture of 1 part by weight of hollow mesoporous spicules, 98.9 parts by weight of purified water, and 0.1 parts by weight of vitamin C (accorbic acid, Sigma Aldrich) was placed in a plastic bag and subjected to vacuum depressurization. Then, vitamin C was loaded into the pores of the spicules by applying pressure of 150 MPa for 5 minutes using a high-pressure processor (Ilshin Autoclave Co., Ltd., Suflux®). After filtering through a 20 μm nylon mesh screen, water was removed to produce hollow mesoporous spicules loaded with vitamin C.

Claims

1. Mesoporous silica shell; and It includes an internal hollow defined as the inner surface of the above-mentioned mesoporous silica shell, and The internal hollow and the mesoporous silica shell each have a length in the first direction longer than the lengths in the second and third directions, which are perpendicular to the first direction, respectively, and have tip portions at both ends of the first direction. A hollow mesoporous spicule in which the internal hollow is a polygonal cross-section perpendicular to the first direction.

2. In Paragraph 1, The above internal hollow is a hollow mesoporous spicule derived from a lapid-based needle body.

3. In Paragraph 1, A hollow mesoporous spicule having a thickness of about 0.1 μm to about 5 μm of the mesoporous silica shell.

4. In Paragraph 1, A hollow mesoporous spicule, wherein the volume of the internal hollow is about 50% to about 99% of the volume defined by the outer surface of the mesoporous silica shell.

5. In Paragraph 1, A hollow mesoporous spicule, wherein the volume of the internal hollow is at least about 10 times the total volume of mesopores contained in the mesoporous silica shell.

6. In Paragraph 1, The length of the mesoporous silica shell in the first direction is about 10 μm to about 300 μm; A hollow mesoporous spicule, wherein the length in the second direction and the length in the third direction of the mesoporous silica shell are each 20 μm or less.

7. In Paragraph 1, The above mesoporous silica shell is a hollow mesoporous spicule formed of organic silica or inorganic silica.

8. In Paragraph 1, A hollow mesoporous spicule containing an effective material in the internal hollow space.

9. In Paragraph 8, The above active material is a hollow mesoporous spicule that is a hydrophobic material.

10. In Paragraph 9, The above active ingredient is a hollow mesoporous spicule comprising any one selected from mineral oil, oleic acid, methyl oleate, vegetable oil, triglyceride, ascorbyl tetraisopalmitate, oil-soluble licorice extract, alpha-bisabolol, retinyl palmitate, tocopherol, madeca, or terpenes.

11. In Paragraph 1, A hollow mesoporous spicule further comprising a capping layer that caps the mesoporous pores of the mesoporous silica shell.

12. In Paragraph 1, A hollow mesoporous spicule having an aspect ratio of about 1:2 to about 1:100 of the mesoporous silica shell.

13. A step of preparing a needle-like body having a length in a first direction longer than the lengths in a second direction and a third direction, each perpendicular to the first direction, and having tip portions at both ends of the first direction, and a polygonal cross-section perpendicular to the first direction; A step of manufacturing a core-shell composite by forming a mesoporous silica shell on the surface of the above needle-shaped body; and A method for manufacturing a hollow mesoporous spicule, comprising the step of removing the needle-like body inside the core-shell composite.

14. In Paragraph 13, A method for manufacturing hollow mesoporous spicules, wherein the above needle-like body comprises calcium oxalate or calcium carbonate.

15. In Paragraph 13, A method for manufacturing hollow mesoporous spicules, wherein the above needle-like body is a lapid-based needle-like body.

16. In Paragraph 15, A method for manufacturing hollow mesoporous spicules in which the above-mentioned laphide-based needle-like body is derived from Dracaena marginata, Alocasia, Monstera deliciosa, Dracaena Waneke, Anthurium, Traveler's palm, Sansevieria trifasciata, etc.

17. In Paragraph 13, A method for manufacturing a hollow mesoporous spicule, wherein the step of removing the above needle-like body includes etching the core-shell composite with an acidic solution.

18. A step of mixing the hollow mesoporous spicule of claim 1 with an active material; and A method for carrying an active substance, comprising the step of injecting the active substance into the internal hollow of the hollow mesoporous spicule.

19. In Paragraph 18, The above active material includes a hydrophobic material, and A method for carrying an active substance, wherein the step of injecting the active substance comprises forming an oil-in-water emulsion from a mixed solution of the hollow mesoporous spicule and the active substance.

20. In Paragraph 18, The above active material includes a hydrophilic material, and A method for carrying an active substance, wherein the step of injecting the active substance comprises injecting the active substance into the hollow mesoporous spicule by pressurizing it.

21. In Paragraph 18, A method for carrying an effective substance, further comprising the step of removing residual effective substance not injected into the internal hollow by centrifugation.

22. In Paragraph 18, A method for carrying an active substance, further comprising the step of capping mesoporous pores present in the shell of a spicule injected with an active substance.

23. A cosmetic composition comprising, as an active ingredient, a hollow mesoporous spicule of claim 1 in which an active substance is supported in an internal hollow.

24. In Paragraph 23, A cosmetic composition used for whitening, wrinkle improvement, hair removal, acne relief, relief of hair loss symptoms, elasticity enhancement, or skin moisturization.

25. A pharmaceutical composition comprising, as an active ingredient, a hollow mesoporous spicule of claim 1 in which an active substance is supported in an internal hollow.

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