Hollow mesoporous silica rod, method for producing the same, and method for supporting an active substance thereon.

Abstract

This invention provides a hollow mesoporous silica rod, a method for producing the same, and a method for supporting an active substance with it. The hollow mesoporous silica rod of this invention has a large internal hollow portion and a large aspect ratio, can stably support a large amount of active substance, can penetrate the skin surface and easily reach a predetermined depth inside the skin, and can effectively deliver the active substance.

Description

Technical Field

[0001] The present invention relates to hollow mesoporous silica rods and a method for manufacturing the same. In particular, it relates to a silica rod capable of supporting an active substance in a hollow portion and a method for manufacturing the same.

Background Art

[0002] Silica is silicon dioxide (SiO2) and is known by various names depending on its size and shape. Silica is inexpensive in terms of raw materials, can produce highly uniform particles by a simple synthesis method, and is a biocompatible substance with low toxicity, so it is used in various fields such as catalysts, materials, fibers, and agriculture. The Stöber method is the most typical silica synthesis method and can synthesize uniform silica particles of various sizes. The Stöber method uses an alcohol / water mixture as a solvent and ammonia as a catalyst to synthesize silica by a chain reaction of hydrolysis and condensation of a silica precursor. Silica usually grows in a spherical shape. Instead of using it directly, additional reactions and surface modifications are performed as needed to obtain the desired shape.

[0003] Mesoporous silica has mesopores with a size of 2 nm to 50 nm on its surface, and these mesopores significantly increase the specific surface area. To produce mesoporous silica, a silica precursor and a pore inducer that forms mesopores later are required. As the pore inducer, a polymer, a surfactant, or the like is used. The pore inducer dispersed in a mixture of water and alcohol forms spherical micelles, and these are stacked to form a stable cylindrical shape. By the polymerization reaction of the silica precursor, silica grows on the surface of the micelle cylinder. When the pore inducer is removed, the pores become mesopores, and mesoporous silica is obtained.

[0004] For example, Korean Patent Application Publication No. 10-2006-0129824 discloses a technique for capturing L-menthol in mesoporous silica produced in this manner. However, there are limitations to the types and amounts of active ingredients that can be contained, as well as ease of use. Therefore, there is a need for research and development of mesoporous silica materials that can easily contain a wide variety of active substances in large quantities. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Korean Patent Application Publication No. 10-2006-0129824 [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] The object of the present invention is to provide a hollow mesoporous silica rod.

[0007] The object of the present invention is to provide a method for producing hollow mesoporous silica rods.

[0008] The object of the present invention is to provide a method for supporting an active substance within a hollow mesoporous silica rod.

[0009] The object of the present invention is to provide a cosmetic composition containing a hollow mesoporous silica rod.

[0010] The object of the present invention is to provide a pharmaceutical composition containing a hollow mesoporous silica rod. [Means for solving the problem]

[0011] In one embodiment of the present invention, a hollow mesoporous silica rod is provided, comprising a mesoporous silica shell and a hollow portion within the silica shell, wherein the silica shell is rod-shaped and has an aspect ratio of 1:2 to 1:100.

[0012] In some embodiments, the silica shell may have a thickness of 5 nm to 100 nm.

[0013] In some embodiments, the volume of the hollow portion may be 50% to 99% based on the volume defined by the outer surface of the silica shell.

[0014] In some embodiments, the volume of the hollow portion may be 10 times or more the total volume of mesopores contained in the mesoporous silica shell.

[0015] In some embodiments, the silica shell may be formed from organic silica.

[0016] In some embodiments, the active substance supported within the hollow portion may be further included.

[0017] In some embodiments, the active substance may include a hydrophobic substance.

[0018] In some embodiments, the active substance may include any one selected from mineral oil, oleic acid, methyl oleate, vegetable oil, caprylic / capric triglyceride, ascorbyl tetraisopalmitate, oil-soluble licorice extract, α-bisabolol, retinyl palmitate, tocopherol, madeca, or terpenes.

[0019] In some embodiments, a capping layer may be further included to cap the mesoporous pores of the silica shell.

[0020] In some embodiments, the cap layer may be formed from inorganic silica.

[0021] In some embodiments, the silica shell may have an aspect ratio of 1:2 to 1:40.

[0022] In one embodiment of the present invention, a method for manufacturing a hollow mesoporous silica rod includes: a step of preparing a rod-shaped inorganic silica core; a step of forming a mesoporous silica shell on the surface of the inorganic silica core to produce a core-shell type silica rod; and a step of removing the inorganic silica core within the core-shell type silica rod.

[0023] In some embodiments, the step of preparing the rod-shaped inorganic silica core may include: a step of preparing a water-in-oil emulsion containing an alcohol solvent and a surfactant; and a step of adding the inorganic silica precursor to the water-in-oil emulsion to grow the inorganic silica into a rod shape.

[0024] In some embodiments, the step of preparing the rod-shaped inorganic silica core may include: a step of preparing inorganic silica nanoseeds by adding a silica precursor to a solution containing an alcohol solvent and a silica-forming catalyst; a step of preparing a water-in-oil emulsion containing the inorganic silica nanoseeds, an alcohol solvent, and a surfactant; and a step of adding an inorganic silica precursor to the water-in-oil emulsion to grow the inorganic silica into a rod shape.

[0025] In some embodiments, the mesoporous silica shell may be formed by reacting the inorganic silica core with a surfactant and an organic silica precursor in a mixed solvent of water and an alcohol solvent.

[0026] In some embodiments, the step of removing the inorganic silica core may include etching the core-shell type silica rod with an alkaline solution.

[0027] In some embodiments, the alkaline solution may contain an alkali metal hydroxide.

[0028] In some embodiments, the reaction temperature of the alkaline solution can be 50°C to 90°C.

[0029] One embodiment of the present invention provides a method for supporting an active substance, comprising: a step of mixing the hollow mesoporous silica rod with the active substance; and a step of injecting the active substance into the hollow portion of the hollow mesoporous silica rod.

[0030] In some embodiments, the active substance may include a hydrophobic substance, and the step of injecting the active substance may include forming an oil-in-water emulsion from a mixed solution of the hollow mesoporous silica rod and the active substance.

[0031] In some embodiments, the method for supporting the active substance may include a step of removing any remaining active substance that was not injected into the hollow portion by centrifugation.

[0032] In some embodiments, the method for supporting the active substance may further include the step of capping the mesoporous pores present in the shell of the silica rod into which the active substance has been injected.

[0033] In one embodiment of the present invention, a cosmetic composition is provided which includes the hollow mesoporous silica rod, wherein the active substance is supported as an active ingredient within the hollow portion.

[0034] In some embodiments, the cosmetic composition may be used for whitening, wrinkle improvement, hair removal, soothing acne-prone skin, alleviating hair loss symptoms, improving elasticity, or moisturizing the skin.

[0035] In one embodiment of the present invention, a pharmaceutical composition is provided which includes the hollow mesoporous silica rod, wherein the active substance is supported as an active ingredient within the hollow portion. [Effects of the Invention]

[0036] The hollow mesoporous silica rod of the present invention can easily support a large amount of active material through its internal hollow portion and surface mesopores, and can stably retain the supported active material within the rod. Furthermore, due to its large aspect ratio, it easily penetrates the skin surface, allowing for effective delivery of the supported active material to a predetermined depth. In addition, its anisotropy allows for particle alignment, facilitating the movement of active material in a specific direction. Therefore, the hollow mesoporous silica rod of the present invention can effectively deliver a large amount of active material to the epidermal layer.

[0037] The hollow mesoporous silica rod of the present invention can be manufactured economically and efficiently using readily available materials and a simple process. [Brief explanation of the drawing]

[0038] [Figure 1] Figure 1 is a schematic flowchart illustrating the growth process of inorganic silica rods. [Figure 2] Figure 2 shows scanning electron microscope (SEM) images of inorganic silica rods fabricated according to several embodiments. [Figure 3] Figure 3 shows transmission electron microscope (TEM) images of inorganic silica rods fabricated according to several embodiments. [Figure 4] Figure 4 shows optical microscope and scanning electron microscope (SEM) images of inorganic silica rods fabricated according to several embodiments. [Figure 5] Figure 5 is a schematic flowchart illustrating the manufacturing process of hollow mesoporous silica rods. [Figure 6] Figure 6 is a transmission electron microscope (TEM) image of a hollow mesoporous silica rod fabricated based on the inorganic silica rod shown in Figure 2. [Figure 7] Figure 7 shows optical microscope and scanning electron microscope (SEM) images of a hollow mesoporous silica rod fabricated based on the inorganic silica rod shown in Figure 2. [Figure 8]Figure 8 is a schematic flowchart of the process for supporting an active substance on a hollow mesoporous silica rod. [Figure 9] Figure 9 shows transmission electron microscope images of a hollow mesoporous silica rod before (left) and after (right) squalene loading. [Figure 10] Figure 10 shows photographs and optical microscope images of a hollow mesoporous silica rod before and after Madeca loading. [Figure 11] Figure 11 shows transmission electron microscope images of a hollow mesoporous silica rod before (left) and after (right) squalene loading. [Figure 12] Figure 12 shows optical microscope images, fluorescence microscope images, and photographs of a hollow mesoporous silica rod and a fluorescently labeled hollow mesoporous silica rod. [Figure 13] Figure 13 shows a fluorescence microscope image of a hollow mesoporous silica rod supported with a fluorescently labeled active substance. [Figure 14] Figure 14 shows graphs of red and green fluorescence intensities in the same cross-section of a hollow mesoporous silica rod supported by a fluorescently labeled active substance. [Figure 15] Figure 15 shows optical and fluorescence microscope images comparing the penetration of active substances in sample-treated groups, active substance-only-treated groups, and control groups in study pig skin. [Figure 16] Figure 16 is a graph showing the fluorescence intensity within the epidermis, excluding the stratum corneum, of the fluorescence images of the active substance in Figure 15. [Modes for carrying out the invention]

[0039] In one embodiment of the present invention, a hollow mesoporous silica rod is provided. The hollow mesoporous silica rod may comprise a mesoporous silica shell and a hollow portion within the silica shell, where the silica shell may be rod-shaped and have an aspect ratio of 1:2 to 1:100.

[0040] Specifically, referring to Figures 4 and 6, the hollow mesoporous silica rod includes a mesoporous silica shell and a hollow portion within the silica shell.

[0041] In some embodiments, the silica shell may be an organic silica shell. For example, the silica shell may be formed from organic silica.

[0042] Organic silica is silica that, in addition to the silicon (Si) and oxygen (O) elements that make up typical silica (SiO2), further contains organic groups such as carbon and hydrogen. For example, organic silica contains hydrocarbon groups derived from the polymerization reaction of organic alkoxysilanes in which the silicon central atom is substituted with hydrocarbon groups in addition to alkoxy groups. In particular, organic silica with residual alkylene groups can be formed by the polymerization reaction of organic silica precursors such as alkoxysilylalkylenes, in which two or more alkoxysilyl groups are bonded by an alkylene group.

[0043] Mesoporous organic silica is silica in which numerous mesopores ranging in size (diameter) from 2 nm to 50 nm are formed by the self-assembly of surfactants. The size of the pores is controlled by the type of surfactant and additives (such as trimethylbenzene).

[0044] The term "shell" refers to a component that encloses an internal substance or space, separating the inside from the outside. A shell may have an outer surface facing outward and an inner surface facing inward, and may have a predetermined thickness defined by the distance between the outer and inner surfaces.

[0045] Silica shells are rod-shaped with an aspect ratio of 1:2 to 1:100. If the aspect ratio is less than 1:2, it may be difficult to load a sufficient amount of active material into the hollow mesoporous silica rod, making it difficult to deliver the active material to the desired depth. If the aspect ratio exceeds 1:100, the active material may not pass through the silica shell and enter the hollow portion, making it difficult to load. For example, aspect ratios include 1:2-1:90, 1:2-1:80, 1:2-1:70, 1:2-1:60, 1:2-1:50, 1:2-1:40, 1:2-1:30, 1:2-1:20, 1:3-1:100, 1:3-1:90, 1:3-1:80, 1:3-1:70, 1:3-1:60, 1:3-1:50, 1:3-1:40, 1:3-1:30, 1:3-1:20, and 1:4 It could be ~1:100, 1:4~1:90, 1:4~1:80, 1:4~1:70, 1:4~1:60, 1:4~1:50, 1:4~1:40, 1:4~1:30, 1:4~1:20, 1:5~1:100, 1:5~1:90, 1:5~1:80, 1:5~1:70, 1:5~1:60, 1:5~1:50, 1:5~1:40, 1:5~1:30, or 1:5~1:20.

[0046] The term "rod-shaped" refers to a shape having a first minor axis, a second minor axis, and a major axis, in increasing order of length. The length of the first minor axis is the same as the length of the second minor axis, and the major axis is longer than both the first and second minor axes, and it has no vertices. Examples of rod-shaped shapes include cylinders, ellipsoids, capsules, and so on.

[0047] The term "aspect ratio" refers to the ratio of the length of the major axis to the average length of the first and second minor axes.

[0048] In some embodiments, the thickness of the silica shell may be 5 nm to 100 nm. Preferably, the silica shell may have a thickness of 5 nm to 80 nm, 5 nm to 60 nm, 5 nm to 50 nm, 5 nm to 40 nm, 10 nm to 100 nm, 10 nm to 80 nm, 10 nm to 60 nm, 10 nm to 50 nm, 10 nm to 40 nm, 20 nm to 100 nm, 20 nm to 80 nm, 20 nm to 60 nm, 20 nm to 50 nm, or 20 nm to 40 nm. In this case, the active substance can be easily supported in the hollow portion, the supported active substance can be stably held without being released, the silica shell can be easily decomposed in the target environment, and thereby the active substance can be effectively delivered.

[0049] The length (length of the long axis) of the hollow mesoporous silica rod may be 10 μm or more. For example, the length of the hollow mesoporous silica rod may be 12 μm or more, 15 μm or more, or 18 μm or more. In this case, the hollow mesoporous silica rod can penetrate the stratum corneum and reach the epidermal layer. At this time, the active substance supported within the hollow mesoporous silica rod can be delivered into the epidermis. Alternatively, the length of the hollow mesoporous silica rod may be 100 μm or less.

[0050] The thickness of the hollow mesoporous silica rod (length or diameter of the first or second short axis) may be 5 μm or less. For example, the thickness of the hollow mesoporous silica rod may be 4 μm or less, 3 μm or less, or 2 μm or less. In this case, the hollow mesoporous silica rod can penetrate the stratum corneum without being damaged and reach the epidermal layer, and can carry an appropriate amount of active substance inside. This allows a large amount of active substance to be delivered into the epidermis. Alternatively, the thickness of the hollow mesoporous silica rod may be 0.1 μm or more.

[0051] The silica shell may have mesopores that penetrate along its thickness. Alternatively, multiple mesopores may be interconnected to form channels that penetrate along the thickness of the silica shell.

[0052] The "hollow portion" may refer to the empty space enclosed by the inner surface of the silica shell. The active substance may be placed inside the hollow portion and supported thereon.

[0053] The hollow portion may communicate with the outside through mesopores in the silica shell. The active substance may be supported within the hollow portion via mesopores.

[0054] In some embodiments, the volume of the hollow portion may be 50% to 99% based on the volume defined by the outer surface of the silica shell. Preferably, the volume of the hollow portion may be 50% to 98%, 50% to 97%, 50% to 96%, 50% to 95%, 50% to 90%, 50% to 85%, 50% to 80%, 50% to 75%, 50% to 70%, 50% to 65%, 50% to 60%, 60% to 99%, 60% to 98%, 60% to 97%, 60% to 96%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, or 60% to 65%, based on the volume defined by the outer surface of the silica shell. In this case, a large amount of active material can be easily supported within the hollow mesoporous silica rod, and leakage of the supported material can be prevented.

[0055] In some embodiments, the volume of the hollow portion may be 10 times or more the total volume of mesopores contained in the mesoporous silica shell. Preferably, the volume of the hollow portion may be 12 times or more, 15 times or more, 20 times or more, 25 times or more, 30 times or more, 40 times or more, or 50 times or more the total volume of mesopores contained in the mesoporous silica shell. For example, the volume of the hollow portion may be 100 times or less the total volume of mesopores contained in the mesoporous silica shell. In this case, the active substance can be easily supported in the hollow portion and can be stably held without being released.

[0056] In some embodiments, the silicon-to-carbon molar ratio of the silica shell may be 1:0.2 to 1:1. Preferably, the silicon-to-carbon molar ratio of the silica shell may be 1:0.3 to 1:1, 1:0.4 to 1:1, 1:0.5 to 1:1, 1:0.6 to 1:1, 1:0.7 to 1:1, or 1:0.8 to 1:1. In this case, the size and total volume of the mesopores of the silica shell and the volume of the hollow portion can be effectively controlled within the above ranges. Therefore, the active material can be easily supported in the hollow portion, and the supported active material can remain in a stable state without being released.

[0057] The term "active substance" refers to a general term for substances that exhibit specific effects on living organisms. Active substances may include cosmetics, pharmaceuticals, diagnostic agents, pesticides, catalysts, and the like. In some embodiments, the solvent itself may function as the active substance.

[0058] In some embodiments, the hollow mesoporous silica rod may contain an active substance supported within the hollow portion. For example, the active substance may be introduced into the hollow mesoporous silica rod. The active substance may include hydrophilic or hydrophobic materials.

[0059] In some embodiments, the active substance may include a hydrophobic substance. For example, the hydrophobic substance may be soluble in a hydrophobic solvent.

[0060] In some embodiments, the active substance may include one selected from mineral oil, oleic acid, methyl oleate, vegetable oil, caprylic / capric triglyceride, ascorbyl tetraisopalmitate, oil-soluble licorice extract, α-bisabolol, retinyl palmitate, tocopherol, madeca, or terpenes.

[0061] In some embodiments, madeca may include madecassoside, madecassic acid, asiaticoside, asiatic acid, and the like.

[0062] Vegetable oils may include soybean oil, sunflower oil, palm oil, coconut oil, argan oil, olive oil, avocado oil, canola oil, etc.

[0063] Terpenes may include terpenes or terpenoids. For example, terpenes may include monoterpenes, monoterpenoids, sesquiterpenoids, diterpenoids, sesteterpenoids, triterpenoids, sesquiterpenoids, tetraterpenoids, polyterpenoids, norisoprenoids, hemiterpenoids, etc. Terpenes may have a linear (acyclic) structure or a cyclic structure. For example, cyclic structures may include monocyclic, bicyclic, tricyclic, tetracyclic, etc.

[0064] Terpenes may include squalene, vitamin A, ocimene, limonene, linalool, eucalyptol, geraniol, citronellol, and others.

[0065] The active substance may be a hydrophobic substance itself, or it may be a hydrophobic substance containing a functional substance dissolved in it, such as a substance for whitening, wrinkle improvement, hair removal, alleviation of acne-prone skin, alleviation of hair loss symptoms, improvement of elasticity, or skin moisturizing, improvement of skin-related diseases, regulation of skin physiological activity, or regulation of skin immune function.

[0066] When a hollow mesoporous silica rod is dispersed in a hydrophobic solvent containing an active substance, the active substance can be supported within the hollow mesoporous silica rod via mesopores along with the hydrophobic solvent. Adding an excess of a hydrophilic solvent such as water to the hydrophobic solvent can form an oil-in-water emulsion. Since the surface of the silica shell is hydrophilic and disperses more easily in water than in a hydrophobic solvent, the dispersion medium may be changed from a hydrophobic solvent to water. In this case, the hydrophobic solvent and active substance supported within the hollow portion do not mix with water, so they can be stably maintained within the hollow portion without leakage to the outside.

[0067] In some embodiments, the hydrophobic solvent may include an unsaturated hydrocarbon solvent. The unsaturated hydrocarbon solvent may include at least partially unsaturated hydrocarbons having 10 to 50 carbon atoms. Preferably, it may have 10 to 40, 20 to 50, or 20 to 40 carbon atoms. The unsaturated hydrocarbon may contain 1 to 20, 1 to 10, 1 to 5, 5 to 20, or 5 to 10 unsaturated bonds (double or triple bonds). For example, the unsaturated hydrocarbon solvent may include squalene.

[0068] In some embodiments, the hollow mesoporous silica rod may include a capping layer that caps the mesoporous pores of the silica shell. The capping layer can prevent material from entering through the mesoporous pores. In some embodiments, the capping layer may fill the internal space of the mesoporous pores of the silica shell, or it may partially or completely cover the outer surface of the silica shell.

[0069] For example, the active substance may include a hydrophilic substance. The hydrophilic substance may be dissolved in a hydrophilic solvent. Because the surface of the silica shell is hydrophilic, the active substance moves easily from the inside to the outside in a hydrophilic solvent, and the active substance introduced into the hollow portion during this process is also easily released to the outside. In this case, the mesoporous pores may be capped with a capping layer to prevent the release of the active substance from the hollow portion.

[0070] In some embodiments, the cap layer may be formed of inorganic silica. In this case, the polymerization reaction of the inorganic silica precursor can easily cap the outer surface of the silica shell, effectively preventing the release of the active pharmaceutical ingredient inside.

[0071] One embodiment of the present invention provides a method for manufacturing a hollow mesoporous silica rod. The method for manufacturing a hollow mesoporous silica rod may include the steps of: preparing a rod-shaped inorganic silica core; forming a mesoporous organic silica shell on the surface of the inorganic silica core to manufacture a core-shell type silica rod; and removing the inorganic silica core from within the core-shell type silica rod.

[0072] Referring to Figure 5, a hollow mesoporous silica rod can be manufactured by preparing a rod-shaped inorganic silica core; forming a mesoporous organic silica shell on the surface of the inorganic silica core to produce a core-shell silica rod; and then removing the inorganic silica core from within the core-shell silica rod.

[0073] Referring to Figure 1, in the process of preparing a rod-shaped inorganic silica core, an oil-in-water emulsion containing an alcohol solvent and a polymeric surfactant can be prepared. The oil-in-water emulsion can be produced by mixing the alcohol solvent and surfactant with a hydrophilic solvent such as water.

[0074] In some embodiments, the alcohol solvent may include monohydric or polyhydric alcohols with 2 to 20 carbon atoms. For example, the alcohol solvent may include methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, and the like.

[0075] The polymeric surfactant may include polyvinylpyrrolidone or polyoxyalkylene block copolymer. In some embodiments, the polymeric surfactant may be at least one selected from the group consisting of polyvinylpyrrolidone (PVP) with an average molecular weight of 10,000 Da to 100,000 Da, Brij52, Brij58, Brij30, Brij76, Brij78, Brij97, Brij35, TritoxX-100, TritonC-114, Tween20, Tween40, Tween60, Tween80, Span40, PluronicL121, PluronicL64, PluronicP103, PluronicP123, PluronicF68, PluronicF127, PluronicF88, Tetronic908, Tetronic901, and Tetronic90R4.

[0076] In some embodiments, an ionic stabilizer can be added to the oil-in-water emulsion. The ionic stabilizer may include trisodium citrate, for example. In this case, the emulsified state of the oil-in-water emulsion can be stably maintained.

[0077] Inorganic silica precursors can be added to an oil-in-water emulsion to grow inorganic silica into rod-shaped structures.

[0078] The inorganic silica precursor may contain a 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 the same or different. The inorganic silica precursor may be, for example, tetramethyl orthosilicate, tetraethyl orthosilicate, or tetrapropyl orthosilicate.

[0079] The inorganic silica precursor is hydrophobic and can preferentially dissolve in an alcohol solvent before diffusing into water for hydration. The hydrated precursor can first form spherical inorganic silica through a condensation reaction. Residual water in the oil-in-water emulsion adheres to one side of the silica, allowing the hydrated precursor to grow the spherical inorganic silica in only one direction, forming an inorganic silica rod. In this case, the aspect ratio of the silica rod can be controlled by adjusting the amount of inorganic silica precursor used.

[0080] In some embodiments, inorganic silica may be formed by the Stöber process. For example, a silica-forming catalyst such as ammonia may be added to an oil-in-water emulsion, and in the presence of the catalyst, the inorganic silica precursor may form SiO2. An alcohol corresponding to the alkoxy group of the tetraalkoxysilane may be further added to the oil-in-water emulsion.

[0081] In some embodiments, the inorganic silica rod formation reaction may be carried out at a temperature of 20°C to 37°C, and in some embodiments, the inorganic silica rod formation reaction may be carried out for 12 to 18 hours.

[0082] In some embodiments, the steps for preparing a rod-shaped inorganic silica core may include: preparing inorganic silica nanoseeds by adding a silica precursor to a solution containing an alcohol solvent and a silica-forming catalyst; preparing an oil-in-water emulsion containing inorganic silica nanoseeds, an alcohol solvent, and a surfactant; and growing inorganic silica in a rod shape by adding the inorganic silica precursor to the oil-in-water emulsion.

[0083] In some embodiments, the silica-forming catalyst may include ammonia, amine compounds, alkali metal or alkaline earth metal hydroxides, transition metal catalysts, inorganic acids such as hydrochloric acid, and the like.

[0084] For example, the step of preparing a rod-shaped inorganic silica core may further include the step of preparing inorganic silica nanoseeds with a size (diameter) of 200 nm to 1 μm. In this case, the inorganic silica nanoseeds may be formed by the Stöber method. The inorganic silica nanoseeds may also be spherical.

[0085] In some embodiments, inorganic silica nanoseeds may be formed by adding an inorganic silica precursor to a solution containing an alcohol solvent and a silica-forming catalyst, and stirring the solution. For example, inorganic silica seeds may be synthesized by adding an inorganic silica precursor to a solution containing ethanol, water, and ammonia, and stirring the solution.

[0086] Inorganic silica seeds can be formed at temperatures between 20°C and 37°C. Inorganic silica seeds can also be formed by a reaction lasting 12 to 18 hours.

[0087] Referring to Figure 3, inorganic silica seeds may be added to an oil-in-water emulsion. In this case, rod-shaped inorganic silica cores can be synthesized by growing them one-dimensionally from inorganic silica seeds, and inorganic silica seeds can be used to produce more uniform rod-shaped inorganic silica cores.

[0088] Oil-in-water emulsions may contain an alcohol solvent and a surfactant.

[0089] The alcohol solvent may include monohydric or polyhydric alcohols with 2 to 20 carbon atoms. For example, the alcohol solvent may include methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, and the like. In some embodiments, the alcohol solvent may be a mixture of two or more alcohols. For example, the alcohol solvent may include ethanol and pentanol.

[0090] The surfactant may include a polymeric surfactant. For example, the polymeric surfactant may include polyvinylpyrrolidone or a polyoxyalkylene block copolymer. In some embodiments, the polymeric surfactant may be at least one selected from the group consisting of polyvinylpyrrolidone (PVP) with an average molecular weight of 10,000 Da to 100,000 Da, Brij52, Brij58, Brij30, Brij76, Brij78, Brij97, Brij35, TritoxX-100, TritonC-114, Tween20, Tween40, Tween60, Tween80, Span40, PluronicL121, PluronicL64, PluronicP103, PluronicP123, PluronicF68, PluronicF127, PluronicF88, Tetronic908, Tetronic901, and Tetronic90R4.

[0091] In some embodiments, the oil-in-water emulsion may further contain an ionic surfactant and / or a silica-forming catalyst.

[0092] The ionic surfactant may also include cationic surfactants such as cetrimonium bromide (CTAB), cetrimonium chloride (CTAC), cetylpyridinium chloride (CPC), benzalkonium chloride (BAC), benzethonium chloride (BZT), dimethyldioctadecylammonium chloride, or dioctadecyldimethylammonium bromide (DODAB).

[0093] The silica-forming catalyst may contain ammonia, amine compounds, alkali metal or alkaline earth metal hydroxides, transition metal catalysts, inorganic acids such as hydrochloric acid, etc.

[0094] Inorganic silica precursors can be added to an oil-in-water emulsion to grow inorganic silica into rod-shaped structures.

[0095] The inorganic silica precursor may contain a 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 the same or different. The inorganic silica precursor may be, for example, tetramethyl orthosilicate, tetraethyl orthosilicate, or tetrapropyl orthosilicate.

[0096] In some embodiments, inorganic silica rods can be formed at temperatures of 20°C to 70°C, 20°C to 60°C, 20°C to 50°C, 20°C to 40°C, or 20°C to 37°C.

[0097] In some embodiments, inorganic silica rods can be formed by a reaction lasting 12 to 18 hours.

[0098] In some embodiments, the aspect ratio of the inorganic silica rod may match the aspect ratio of the hollow mesoporous silica rod. For example, the aspect ratios are 1:2-1:100, 1:2-1:90, 1:2-1:80, 1:2-1:70, 1:2-1:60, 1:2-1:50, 1:2-1:40, 1:2-1:30, 1:2-1:20, 1:3-1:100, 1:3-1:90, 1:3-1:80, 1:3-1:70, 1:3-1:60, 1:3-1:50, 1:3-1:40, 1:3-1:30, 1:3-1:2 It could be 0, 1:4~1:100, 1:4~1:90, 1:4~1:80, 1:4~1:70, 1:4~1:60, 1:4~1:50, 1:4~1:40, 1:4~1:30, 1:4~1:20, 1:5~1:100, 1:5~1:90, 1:5~1:80, 1:5~1:70, 1:5~1:60, 1:5~1:50, 1:5~1:40, 1:5~1:30, or 1:5~1:20.

[0099] The length of the inorganic silica rod (length of the long axis) may be 10 μm or more. For example, the length of the inorganic silica rod may be 12 μm or more, 15 μm or more, or 18 μm or more. Alternatively, the length of the inorganic silica rod may be 100 μm or less.

[0100] The thickness of the inorganic silica rod (length or diameter of the first or second minor axis) may be 5 μm or less. For example, the thickness of the inorganic silica rod may be 4 μm or less, 3 μm or less, or 2 μm or less. Alternatively, the thickness of the inorganic silica rod may be 0.1 μm or more.

[0101] Core-shell type silica rods can be manufactured by forming a mesoporous organic silica shell on the surface of an inorganic silica core. For example, the mesoporous organic silica shell may cover part or all of the surface of the inorganic silica core.

[0102] In some embodiments, mesoporous organic silica shells can be formed by reacting an inorganic silica core with a surfactant and an organic silica precursor in a mixed solvent of water and an alcohol solvent. For example, an inorganic silica core may be dispersed in a mixed solvent, and a surfactant and an organic silica precursor may be added and reacted to form a mesoporous organic silica shell. The surfactant can induce mesopores in the organic silica shell.

[0103] In some embodiments, the alcohol solvent may include monohydric or polyhydric alcohols with 2 to 20 carbon atoms. For example, the alcohol solvent may include methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, and the like.

[0104] For example, the ratio of water to alcohol-based solvent in the mixed solvent may be 40:60-90:10, 40:60-80:20, 40:60-70:30, 40:60-65:35, 50:50-90:10, 50:50-80:20, 50:50-70:30, 50:50-65:35, 60:40-90:10, 60:40-80:20, 60:40-70:20, or 60:40-65:35. In this case, mesoporous organic silica shells can be effectively formed on rod-shaped inorganic silica rods with a uniform thickness.

[0105] The surfactant may include an ionic surfactant. The surfactant can be used after being dissolved in an alcohol solvent.

[0106] In some embodiments, 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, or dioctadecyldimethylammonium bromide (DODAB).

[0107] In some embodiments, the silica-forming catalyst may be used in the organic silica shell formation reaction. The silica-forming catalyst may include ammonia, amine compounds, alkali metal or alkaline earth metal hydroxides, transition metal catalysts, inorganic acids such as hydrochloric acid, and the like.

[0108] The organic silica precursor contains an organic alkoxysilane. The organic alkoxysilane is a compound in which the silicon central atom is substituted with a hydrocarbon group in addition to the alkoxy group, and may also contain an alkoxysilylalkylene in which two or more alkoxysilyl groups are linked by alkylene groups.

[0109] In some embodiments, the organosilica 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).

[0110] In some embodiments, the organic silica shell may be formed by two or more shell-forming steps. For example, the organic silica shell may be formed by a first shell-forming step and a second shell-forming step, the first shell-forming step being the same 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 be carried out in the supernatant.

[0111] For example, the second shell formation step may use a smaller amount of ionic surfactant compared to the first shell formation step. For instance, the second shell formation step may use a smaller amount of ionic surfactant compared to the first shell formation step, for example, about 70% or less, about 60% or less, or about 50% or less.

[0112] In some embodiments, the silica-forming catalyst may not be used in the second shell-forming step. For example, the silica-forming catalyst may be used in the first shell-forming step but not in the second shell-forming step.

[0113] The inorganic silica core within the core-shell type silica rod may be removed. The internal space of the core-shell type silica rod from which the inorganic silica core is removed may be provided as a hollow section.

[0114] In some embodiments, the step of removing the inorganic silica core may include etching the core-shell type silica rod with an alkaline solution. For example, the core-shell type silica rod may be dispersed in water, and the inorganic silica core may be removed by adding an alkaline solution to the dispersion. The alkaline solution has higher etching selectivity for the inorganic silica core than for the organic silica shell, and the inorganic silica core can be removed while preserving the organic silica shell.

[0115] In some embodiments, the alkaline solution may contain an alkali metal hydroxide. The alkali metal hydroxide may include LiOH, NaOH, KOH, and the like. For example, the alkaline solution may be an aqueous solution of an alkali metal hydroxide.

[0116] In some embodiments, the reaction temperature between the dispersion and the alkaline solution may be 50°C to 90°C. Preferably, the temperature of the alkaline solution may be 50°C to 80°C, 60°C to 90°C, or 60°C to 80°C. In this case, the alkaline solution may have higher etching selectivity for the inorganic silica core compared to the organic silica shell.

[0117] One embodiment of the present invention provides a method for supporting an active substance within a hollow mesoporous silica rod. This method may include the steps of: mixing the hollow mesoporous silica rod with the active substance; and injecting the active substance into the hollow portion of the hollow mesoporous silica rod.

[0118] Referring to Figure 6, a hollow mesoporous silica rod can be dispersed in a solution containing an active substance, an oil-in-water emulsion can be formed from that solution, and the solution can move into the hollow mesoporous silica rod, thereby allowing the active substance to be supported within the hollow mesoporous silica rod.

[0119] The active substance may contain hydrophobic or hydrophilic substances. The active substance may be dissolved in a suitable solvent. For example, the solution may contain both the solvent and the active substance. The solvent, solution, and active substance may each be hydrophilic or hydrophobic.

[0120] In some embodiments, the active substance includes a hydrophobic substance, and the step of injecting the active substance may include forming an oil-in-water emulsion from a mixed solution of the hollow mesoporous silica rod and the active substance. When forming the oil-in-water emulsion, the hydrophobic substance on the outside of the hollow mesoporous silica rod may be injected into the hollow portion.

[0121] When a hollow mesoporous silica rod is dispersed in a hydrophobic solvent containing an active substance, the active substance can be supported within the hollow mesoporous silica rod via mesopores along with the hydrophobic solvent. Adding an excess of a hydrophilic solvent such as water to the hydrophobic solvent can form an oil-in-water emulsion. Since the surface of the organic silica shell is hydrophilic and disperses more easily in water than in a hydrophobic solvent, the dispersion medium may be changed from a hydrophobic solvent to water. In this case, the hydrophobic solvent and active substance supported within the hollow portion do not mix with water, so they can be stably maintained within the hollow portion without leakage to the outside.

[0122] In some embodiments, the hydrophobic solvent may include an unsaturated hydrocarbon solvent. The unsaturated hydrocarbon solvent may include at least partially unsaturated hydrocarbons having 10 to 50 carbon atoms. Preferably, it may have 10 to 40, 20 to 50, or 20 to 40 carbon atoms. The unsaturated hydrocarbon may contain 1 to 20, 1 to 10, 1 to 5, 5 to 20, or 5 to 10 unsaturated bonds (double or triple bonds). For example, the unsaturated hydrocarbon solvent may include squalene.

[0123] In some embodiments, the method for supporting the active substance may further include a step of removing any remaining active substance not injected into the hollow portion by centrifugation.

[0124] In some embodiments, the method for supporting the active material may further include the step of capping the mesoporous pores present in the shell of the silica rod into which the active material has been injected.

[0125] For example, after moving the solution, the mesoporous pores of the organic silica shell may be capped. For example, the mesoporous pores can be filled or capped by forming a capping layer that covers the silica shell.

[0126] In some embodiments, the solution may contain a hydrophilic solvent and a hydrophilic active substance. The hydrophilic active substance may be dissolved in the hydrophilic solvent. Because the surface of the organosilica shell is hydrophilic, the active substance moves easily from the inside to the outside within the hydrophilic solvent, and any active substance introduced into the hollow portion during this process is also easily released to the outside. In this case, the mesoporous pores may be capped with a capping layer to prevent the release of the active substance from within the hollow portion.

[0127] In some embodiments, the cap layer may be formed from inorganic silica. In this case, the polymerization reaction of the inorganic silica precursor can easily cap the outer surface of the organic silica shell, thereby effectively preventing the release of the active pharmaceutical ingredient from inside. The cap layer may be formed using substantially the same method as that used for the inorganic silica core.

[0128] In one embodiment of the present invention, a cosmetic composition is provided that contains a hollow mesoporous silica rod as an active ingredient.

[0129] In some embodiments, the cosmetic composition may be used for skin whitening, wrinkle improvement, hair removal, soothing acne-prone skin, alleviating hair loss symptoms, improving elasticity, or moisturizing the skin.

[0130] Hollow mesoporous silica rods may be included in cosmetic compositions in amounts of 0.1 wt% to 10 wt%. Specifically, hollow mesoporous silica rods may be included in amounts of 0.1 wt% to 9 wt%, 0.1 wt% to 8 wt%, 0.1 wt% to 6 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt%, 0.1 wt% to 2 wt%, 0.1 wt% to 1 wt%, 0.2 wt% to 10 wt%, 0.2 wt% to 9 wt%, 0.2 wt% to 8 wt%, 0.2 wt% to 6 wt%, 0.2 wt% to 5 wt%, 0.2 wt% to 3 wt%, 0.2 wt% to 2 wt%, 0.2 wt% to 1 wt%, 0 It may be present in amounts of 0.3wt%~10wt%, 0.3wt%~9wt%, 0.3wt%~8wt%, 0.3wt%~6wt%, 0.3wt%~5wt%, 0.3wt%~3wt%, 0.3wt%~2wt%, 0.3wt%~1wt%, 0.5wt%~10wt%, 0.5wt%~9wt%, 0.5wt%~8wt%, 0.5wt%~6wt%, 0.5wt%~5wt%, 0.5wt%~3wt%, 0.5wt%~2wt%, or 0.5wt%~1wt%.

[0131] For example, the content of hollow mesoporous silica rods is not particularly limited, but it is preferably 0.1 to 5 parts by weight based on 100 parts by weight of the cosmetic composition.

[0132] Cosmetic compositions may be formulations commonly used in cosmetics. In one embodiment, a composition may be manufactured as a formulation comprising a lotion (skin lotion), emollient, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nourishing lotion, massage cream, nourishing cream, moisturizing 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, sheet, or aerosol composition. Furthermore, a composition may be applied in various forms suitable for supplying moisture to the skin, such as a gel or cream, paste, or solid form, specifically in the form of a gel cream having a particulate texture such as a sherbet or slush. Such formulations may be manufactured using methods conventional in the art.

[0133] In one embodiment, the composition may further contain at least one selected from the group consisting of oil, purified water, emulsifier, dispersant, pigment, fragrance, sunscreen, sweetener, vitamin, and metal ion chelating agent. Furthermore, in one embodiment, the composition may further contain a preservative in an amount of 0.1 wt% to 3.0 wt%. The amount of additional components such as oil can be easily selected by those skilled in the art, within a range that does not impair the purpose and effects of the present invention.

[0134] In one embodiment of the present invention, a pharmaceutical composition is provided that contains a hollow mesoporous silica rod as an active ingredient. For example, the hollow mesoporous silica rod may carry an active substance therein, and the active substance can exert a pharmaceutically effective effect.

[0135] Hollow mesoporous silica rods may be included in the pharmaceutical composition in amounts of 0.1 wt% to 10 wt%. Specifically, the amounts of hollow mesoporous silica rods may be 0.1 wt% to 9 wt%, 0.1 wt% to 8 wt%, 0.1 wt% to 6 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt%, 0.1 wt% to 2 wt%, 0.1 wt% to 1 wt%, 0.2 wt% to 10 wt%, 0.2 wt% to 9 wt%, 0.2 wt% to 8 wt%, 0.2 wt% to 6 wt%, 0.2 wt% to 5 wt%, 0.2 wt% to 3 wt%, 0.2 wt% to 2 wt%, 0.2 wt% to 1 wt%, 0 It may be present in amounts of 0.3wt%~10wt%, 0.3wt%~9wt%, 0.3wt%~8wt%, 0.3wt%~6wt%, 0.3wt%~5wt%, 0.3wt%~3wt%, 0.3wt%~2wt%, 0.3wt%~1wt%, 0.5wt%~10wt%, 0.5wt%~9wt%, 0.5wt%~8wt%, 0.5wt%~6wt%, 0.5wt%~5wt%, 0.5wt%~3wt%, 0.5wt%~2wt%, or 0.5wt%~1wt%.

[0136] In one embodiment, the pharmaceutical composition may contain conventionally pharmaceutically acceptable carriers, excipients, or additives. The pharmaceutical composition may be formulated using conventional methods and may be manufactured in various oral administration forms such as tablets, pills, powders, capsules, syrups, emulsions, and microemulsions, or in parenteral administration forms such as intramuscular, intravenous, or subcutaneous administration.

[0137] When the pharmaceutical composition is manufactured in an oral administration form, 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, and diluents. When the pharmaceutical composition of the present invention is manufactured in the form of an injection, the additives or carriers may include water, physiological saline, aqueous glucose solution, aqueous pseudosugar solution, alcohol, glycol, ether (e.g., polyethylene glycol 400), oil, fatty acid, fatty acid ester, glyceride, surfactant, suspending agent, and emulsifier.

[0138] The present invention will be described in more detail below with reference to the following examples. However, the following examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples. [Examples]

[0139] Example 1.1: Manufacture of an inorganic silica rod

[0140] A PVP / PeOH solution was prepared by dissolving polyvinylpyrrolidone (PVP, Aldrich) with an average molecular weight of 40,000 in 1-pentanol (PeOH) at a concentration of 1 g / 10 mL.

[0141] To 30 mL of PVP / PeOH solution, 0.96 mL of 6.75 mM trisodium citrate (TSC) aqueous solution, 3 mL of ethanol, and 0.7 mL of ammonia were added, and the mixture was vigorously stirred for 1 minute to prepare an emulsion.

[0142] To this emulsion, 0.1 mL to 5 mL of tetraethyl orthosilicate (TEOS), a silica precursor, was added according to the target length, and the mixture was reacted in a constant temperature water bath at 20°C to 37°C for 18 hours to produce silica rods.

[0143] The prepared silica rods were washed with ethanol, acetic acid / ethanol (10 v / v%), and water by centrifugation (5,000 rpm, 4 min), and then further centrifuged with ethanol (1,800 rpm, 7 min) to remove by-products. After drying, purified inorganic silica rods were obtained.

[0144] Figure 2 shows scanning electron microscope (SEM) images of inorganic silica rods manufactured using this embodiment. As can be seen from Figure 2, inorganic silica rods with various aspect ratios can be manufactured using a simple method.

[0145] Example 1.2: Production of inorganic silica rods using silica seeds

[0146] A mixed solution of 30 mL of ethanol, 1.5 mL of water, and 4.0 mL of ammonia was stirred at 400 rpm at 20°C to 37°C, 4 mL of TEOS, a silica precursor, was added, and the mixture was then reacted for 18 hours to obtain inorganic silica nanoseeds (300-450 nm).

[0147] The synthesized inorganic silica nanoseeds were washed several times with ethanol and water by centrifugation (5,000 rpm, 4 minutes), and then dispersed in 60 mL of water.

[0148] Polyvinylpyrrolidone (PVP, Aldrich) with an average molecular weight of 55,000 was dissolved in 1-pentanol (PeOH) at a concentration of 1 g / 10 mL, and then 80 mL of ethanol (EtOH) was added to prepare a PVP / PeOH / EtOH solution.

[0149] To 40 mL of PVP / PeOH / EtOH solution, 0.8 mL of synthesized inorganic silica nanoseed dispersion, 1.12 mL of 7.5 mM trisodium citrate (TSC) aqueous solution, and 1.12 mL of ammonia were added, and the mixture was vigorously stirred for 1 minute to prepare an emulsion.

[0150] 0.1 mL to 5 mL of the precursor tetraethyl orthosilicate (TEOS) was added to the emulsion, and the mixture was reacted in a constant temperature water bath at 20°C to 37°C for 12 to 18 hours to produce silica rods.

[0151] The prepared silica rods were washed with ethanol, acetic acid / ethanol (10 v / v%), and water by centrifugation (5,000 rpm, 4 min), and then further centrifuged with ethanol (1,800 rpm, 7 min) to remove by-products. After drying, purified inorganic silica rods were obtained.

[0152] Figure 3 shows transmission electron microscope (TEM) images of inorganic silica rods fabricated according to several embodiments, and Figure 4 shows optical microscope and scanning electron microscope (SEM) images of inorganic silica rods fabricated according to several embodiments. Referring to Figures 3 and 4, it was confirmed that inorganic silica rods were fabricated using inorganic silica nanoparticles as seeds.

[0153] Example 2: Manufacture of a hollow mesoporous silica rod

[0154] Hollow mesoporous silica rods (HSMRs) were manufactured from silica rods according to the process shown in Figure 5.

[0155] The inorganic silica rod (28.5 mg) prepared in Example 1.1 was dispersed in 40 mL of a mixed solvent of water and methanol (40:60~90:10, v / v).

[0156] To the reaction mixture, 1 mL of cetrimonium bromide (CTAB) solution (1 g / 10 mL in methanol), 50 μL of 1,2-bis(triethoxysilyl)ethane (BTSE), and 400 μL of ammonia were added, and the mixture was reacted using a rotor (3 rpm) for 2 hours.

[0157] The supernatant was transferred to a new container, 500 μL of CTAB solution (1 g / 10 mL in methanol) and 50 μL of BTSE were added, and the mixture was reacted with a rotor (3 rpm) for 2 hours.

[0158] The supernatant was collected, washed with acetic acid / ethanol (10 v / v%), ethanol, and water by centrifugation (5000 rpm, 4 minutes), and dispersed in 40 mL of water.

[0159] The dispersion was heated to 70°C, 2 mL of NaOH (0.5 M) was added, and the mixture was reacted for 20 minutes to etch the inorganic silica rod inside. The mixture was washed with acetic acid / ethanol (10 v / v%), water, and ethanol by centrifugation (5000 rpm, 4 min), dried, and a hollow mesoporous silica rod was produced.

[0160] Figures 6 and 7 show transmission electron microscope (TEM), optical microscope, and scanning electron microscope (SEM) images of hollow mesoporous silica rods fabricated from the inorganic silica rod shown in Figure 2. Referring to Figures 6 and 7, it can be confirmed that hollow mesoporous silica rods with various aspect ratios and shapes could be fabricated using a simple method.

[0161] Example 3: Supporting of hydrophobic material

[0162] Referring to Figure 8, the active substance was supported within a hollow mesoporous silica rod.

[0163] A 9 mg hollow mesoporous silica rod was dispersed in 1 mL of squalene (Sigma-Aldrich). 4 mL of water was added to the dispersion to form an oil-in-water (O / W) emulsion. The silica rod was filtered and dried to remove the squalene and water, and a hollow mesoporous silica rod supported with squalene was prepared.

[0164] Figure 9 shows microscopic images of the mesoporous silica rod before and after squalene loading, and Figure 10 shows photographs and optical microscope images illustrating the changes observed before and after madeca loading. Referring to Figures 9 and 10, it was confirmed that squalene and madeca were stably supported within the hollow interior of the hollow mesoporous silica rod.

[0165] Example 4.1: Fluorescent labeling (tagging) of hollow mesoporous silica rods

[0166] To facilitate the evaluation of the uptake of active substances into hollow mesoporous silica rods and their ex vivo skin penetration, the hollow mesoporous silica rods and the active substances were fluorescently labeled in green or red, respectively.

[0167] 18 mg of the green fluorescent substance FITC (fluorescein isothiocyanate) was weighed and placed in a reaction vessel, and 3 mL of ethanol (purity 95%~100%) was added. The mixture was then stirred at room temperature for 10~30 minutes using a stirrer, and 20 μL of APTMS ((3-aminopropyl)triethoxysilane) was added. The mixture was stirred at room temperature for 12~18 hours to obtain a green fluorescently labeled solution. Reaction equation 1 below is a schematic diagram of the chemical reaction of the green fluorescently labeled solution.

[0168] [Reaction Equation 1] [ka]

[0169] The green fluorescent labeling solution was added to the reaction solution of Example 2 so that the weight ratio of inorganic silica rod to green fluorescent labeling solution was 10:1. The mixture was stirred at room temperature for 18 hours, and then centrifuged at 2,000 rpm for 4 minutes. The supernatant was removed from the centrifuged product, washed with 3 mL of ethanol, and dried to obtain a green fluorescent labeling hollow mesoporous silica rod.

[0170] Figure 11 is a fluorescence microscope image of a hollow mesoporous silica rod fluorescently labeled with FITC. Referring to Figure 11, we directly confirmed that the hollow mesoporous silica rod was fluorescently labeled with green fluorescence.

[0171] Figure 12 shows optical microscope images, fluorescence microscope images, and photographs of a hollow mesoporous silica rod and a fluorescently labeled hollow mesoporous silica rod. Referring to Figure 12, the difference in fluorescence labeling was confirmed by visual and microscopic observation before and after fluorescent labeling.

[0172] Example 4.2: Fluorescent labeling of active substances

[0173] The hydrophobic active substance was vitamin B1 (thiamine), and the fluorescent labeling substance was Cy5, a representative red fluorescent substance. In the chemical reaction, one end of Cy5 was in the NHS-ester form. Reaction Scheme 2 below is a schematic diagram of the chemical reaction that labels the active substance with red fluorescence.

[0174] [Reaction Scheme 2] [ka] (Red fluorescently labeled vitamin B1)

[0175] 100 mg of thiamine (Sigma-Aldrich) was weighed and placed in a reaction vessel, and 10 mL of ethanol was added. The mixture was then stirred with a stirrer for 30 minutes to 1 hour, after which 2 mg of Cy5NHS-ester was added, and the mixture was stirred at room temperature for 12 to 18 hours. After removing the reaction residue using a 500 DaCE membrane, the mixture was dried to obtain fluorescently labeled vitamin B1 (thiamine).

[0176] Example 5: Evaluation of the loading state of active material in hollow mesoporous silica rods

[0177] The fluorescently labeled hydrophobic active substance (vitamin B1) from Example 4.2 was supported in the fluorescently labeled hollow mesoporous silica rod from Example 4.1, and the support state was confirmed using a fluorescence microscope.

[0178] 5 mg of a fluorescently labeled active substance was added to 1 mL of mineral oil (Sigma-Aldrich) or oleic acid (Sigma-Aldrich) and stirred until completely dissolved. 9 mg of a fluorescently labeled hollow mesoporous silica rod was added and dispersed. 4 mL of water was added to the dispersion to form an oil-in-water (O / W) emulsion. The silica rod was filtered and dried to remove the mineral oil, oleic acid, and water, thereby producing a green fluorescently labeled hollow mesoporous silica rod on which a red fluorescently labeled active substance was supported.

[0179] 1 mg of a fluorescently labeled, active substance-supported hollow mesoporous silica rod was dispersed in 1 mL of water, and fluorescence microscope images were obtained.

[0180] Figure 13 shows a fluorescence microscope image of a hollow mesoporous silica rod loaded with a fluorescently labeled active substance. By superimposing the fluorescence images of the green and red fluorescence channels, it was confirmed that the active substance was sufficiently loaded within the hollow mesoporous silica rod.

[0181] Figure 14 shows graphs of red and green fluorescence intensities in the same cross-section of a fluorescently labeled hollow mesoporous silica rod carrying an active substance. Referring to the graph in Figure 14, it was confirmed that the shell portion is surrounded by the hollow mesoporous silica rod, and the interior is filled with the active substance.

[0182] Example 6: Confirmation of skin penetration and active substance delivery

[0183] 20 μL (10 mg / mL concentration) of an aqueous dispersion of the fluorescently labeled active substance-supported hollow mesoporous silica rod from Example 5 was applied to experimental pigskin (whole hide, 2 cm × 2 cm Franz cell membrane) for 5 minutes, then washed to produce a cryoblock, and tissue section slides were obtained. The tissue section slides were photographed under a fluorescence microscope to obtain Figure 15.

[0184] Figure 15 shows optical microscope images and fluorescence microscope images comparing the penetration of active substances in experimental pigskin (Franz cell membrane) in the example sample treatment group, the active substance treatment group alone, and the control group.

[0185] Referring to Figure 15, no red fluorescence signal was detected in the epidermis, excluding the stratum corneum, in the control group and the group treated with the active substance alone. However, in the group treated with hollow mesoporous silica rods on which the active substance was supported, it was confirmed that the active substance was delivered into the epidermis.

[0186] In particular, in the example sample treatment group, the fluorescence signal of hollow mesoporous silica appeared only in the stratum corneum, while it was confirmed that the active substance was delivered into the epidermis via the stratum corneum.

[0187] Figure 16 is a graph showing the fluorescence intensity within the epidermis, excluding the stratum corneum, of the fluorescence images of the active substance in Figure 15. The total fluorescence intensity within the epidermis of each sample was measured and divided by the measurement area to calculate the fluorescence intensity per unit area. When compared, the experimental group treated with the active substance supported on a hollow mesoporous silica rod had a 625% higher skin penetration rate compared to the experimental group treated with the active substance alone, objectively confirming superior penetration of the active substance into the epidermis.

Claims

1. Mesoporous silica shell; and The hollow portion within the silica shell, A hollow mesoporous silica rod, including, A hollow mesoporous silica rod in which the silica shell is rod-shaped and has an aspect ratio of 1:2 to 1:

100.

2. The hollow mesoporous silica rod according to claim 1, wherein the silica shell has a thickness of 5 nm to 100 nm.

3. The hollow mesoporous silica rod according to claim 1, wherein the volume of the hollow portion is 50% to 99% based on the volume defined by the outer surface of the silica shell.

4. The hollow mesoporous silica rod according to claim 1, wherein the volume of the hollow portion is 10 times or more the total volume of mesopores contained in the mesoporous silica shell.

5. The hollow mesoporous silica rod according to claim 1, wherein the silica shell is formed from organic silica.

6. The hollow mesoporous silica rod according to claim 1, wherein the hollow mesoporous silica rod further contains an active substance within the hollow portion.

7. The hollow mesoporous silica rod according to claim 6, wherein the active substance is a hydrophobic substance.

8. The hollow mesoporous silica rod according to claim 7, wherein the active substance comprises one selected from mineral oil, oleic acid, methyl oleate, vegetable oil, caprylic / capric triglyceride, ascorbyl tetraisopalmitate, oil-soluble licorice extract, α-bisabolol, retinyl palmitate, tocopherol, madeca, or terpene.

9. The hollow mesoporous silica rod according to claim 1, further comprising a capping layer that caps the mesoporous pores of the silica shell.

10. The hollow mesoporous silica rod according to claim 9, wherein the cap layer is formed from inorganic silica.

11. The hollow mesoporous silica rod according to claim 1, wherein the silica shell has an aspect ratio of 1:2 to 1:

40.

12. A method for manufacturing a hollow mesoporous silica rod: A process for preparing a rod-shaped inorganic silica core; A step of forming a mesoporous organic silica shell on the surface of the inorganic silica core to produce a core-shell type silica rod; and A step of removing the inorganic silica core from the core-shell type silica rod, A method for manufacturing a hollow mesoporous silica rod containing [a specific substance].

13. The process for preparing the aforementioned rod-shaped inorganic silica core is: A step of preparing an oil-in-water emulsion containing an alcohol solvent and a surfactant; and A step of adding the inorganic silica precursor to the oil-in-water emulsion and growing the inorganic silica into a rod shape, A method for producing a hollow mesoporous silica rod according to claim 12, including the following:

14. The process for preparing the aforementioned rod-shaped inorganic silica core is: A step of preparing inorganic silica nanoseeds by adding a silica precursor to a solution containing an alcohol solvent and a silica formation catalyst; A step of preparing an oil-in-water emulsion containing the inorganic silica nanoseed, an alcohol solvent, and a surfactant; and A step of adding an inorganic silica precursor to the oil-in-water emulsion and growing the inorganic silica into a rod shape, A method for producing a hollow mesoporous silica rod according to claim 12, including the following:

15. A method for producing a hollow mesoporous silica rod according to claim 12, wherein the mesoporous organic silica shell is formed by reacting the inorganic silica core with a surfactant and an organic silica precursor in a mixed solvent of water and an alcohol solvent.

16. A method for producing a hollow mesoporous silica rod according to claim 12, wherein the step of removing the inorganic silica core includes etching the core-shell type silica rod with an alkaline solution.

17. A method for producing a hollow mesoporous silica rod according to claim 16, wherein the alkaline solution contains an alkali metal hydroxide.

18. A method for producing a hollow mesoporous silica rod according to claim 16, wherein the reaction temperature of the alkaline solution is 50°C to 90°C.

19. A method for supporting an active substance: A step of mixing the hollow mesoporous silica rod described in claim 1 with an active substance; and A step of injecting the active substance into the hollow portion of the hollow mesoporous silica rod, A method for supporting an active substance, including [a specific substance].

20. The active substance is a hydrophobic substance, The step of injecting the active substance includes forming an oil-in-water emulsion from a mixed solution of the hollow mesoporous silica rod and the active substance. A method for supporting an active substance according to claim 19.

21. The method for supporting an active substance according to claim 19, further comprising the step of removing any remaining active substance that was not injected into the hollow portion by centrifugal separation.

22. A method for supporting an active substance according to claim 19, further comprising the step of capping the mesoporous pores present in the shell of the silica rod into which the active substance has been injected.

23. A cosmetic composition comprising a hollow mesoporous silica rod as described in claim 1, wherein the active substance is supported as an active ingredient within the hollow portion.

24. The cosmetic composition according to claim 23, which is used for whitening, improving wrinkles, removing body hair, alleviating acne-prone skin, alleviating hair loss symptoms, improving elasticity, or moisturizing the skin.

25. A pharmaceutical composition comprising a hollow mesoporous silica rod as described in claim 1, wherein the active substance is supported as an active ingredient within the hollow portion.

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