Microneedle containing a microfiber network structure

Abstract

The present invention relates to a microneedle containing a microfiber network structure, and more particularly, to a microneedle containing an insoluble microfiber network structure in a dissolvable microneedle base, so that even if a drug is not contained in the needle, a large amount of an aqueous drug solution can be delivered to the skin through a drug injection hole on the back of the patch regardless of the drug type.

Description

TECHNICAL FIELD

[0001] This application claims priority based on Korean Application No. 10-2020-0080091 filed on June 30, 2020 and Korean Application No. 10-2021-0055845 filed on April 29, 2021, the disclosure of which is incorporated by reference herein in its entirety.

[0002] The present application relates to a microneedle patch containing a microfiber network structure. BACKGROUND

[0003] In a transdermal drug delivery system, the stratum corneum, which is the outermost layer of the skin, plays the most important barrier role of 10 to 15 microns in thickness. A microneedle, which is several hundred microns in length, can physically penetrate the skin with minimal invasion, and can effectively deliver drugs to the skin simply and painlessly, and thus has been widely studied in various fields such as cosmetics and biomedicine. Since the development of a silicon microneedle manufactured using semiconductor process technology by the Prausnitz group at the Georgia Institute of Technology in the United States in 1998, various solid microneedles made of metal, ceramic, or glass have been developed to generate a temporary microchannel on the skin, thereby delivering drugs coated on the needle or drugs topically applied to the skin. However, there is a problem in that if the needle is broken in the skin or something such as a small particle is left in the body, it can induce an inflammatory reaction. On the other hand, dissolving microneedles made of a water-soluble polymer are manufactured by containing a drug, and after permeating the skin, the drug is released as the needle dissolves. Although it has various advantages such as being easy to manufacture, not leaving a residue on the skin, etc. compared to solid microneedles, the active compounds that can be carried are limited to hydrophilic substances. In addition, the amount of drug that can be carried inside the microneedle is limited due to the several hundred micrometer size, and thus only a small amount of drug can be delivered, and thus this can not be sufficient to produce efficacy. Furthermore, in the process of manufacturing the microneedle, there is a problem in that unstable active substances are denatured.

[0004] Accordingly, several studies for improving the drug loading amount of dissolving microneedles have been reported. It has been reported that the same drug is loaded in a dissolving microneedle and a topical preparation, respectively, the topical preparation is applied, and then the needle is applied, thereby improving the drug delivery efficiency compared to when the needle is used alone (see Non-Patent Documents 1 and 2). In addition, a system for simultaneously delivering two phases of a drug and a castor oil by applying castor oil to the edge of a dissolving microneedle patch containing a hydrophilic drug has also been reported. However, the above methods have not been able to significantly improve the amount of drug delivery, and there are great inconveniences in use, such as the needle should be applied after the preparation applied to the skin is properly dried, or the needle should be applied to the skin after the oil phase is applied to the needle, etc.

[0005] In the entire present specification, a number of documents are referenced and citations are given. The disclosures of the documents cited are incorporated herein in their entirety by reference to more clearly illustrate the level of the art and the invention.

[0006] [Related Art Documents]

[0007] Patent Document 1: Korean Patent Laid-Open No. 10-2017-0103698

[0008] Non-Patent Document 1: Molecular pharmaceutics 14 (2017) 2024-2031

[0009] Non-Patent Document 2: Journal of cosmetic dermatology 18 (2019) 1083-1091

[0010] Non-Patent Document 3: Journal of cosmetic dermatology 18 (2019) 936-943 SUMMARY

[0011] Technical Problem

[0012] Therefore, in order to solve the above problems, the present invention recognizes that when a microneedle patch is manufactured by adding an insoluble microfiber network structure to a dissolvable microneedle, various drugs supplied additionally after skin perforation by the microneedle patch not only rapidly spread along the network structure formed by the above microfiber structure, but also are delivered in large amounts to the skin deep in the entire area of the patch, and the present invention is completed.

[0013] Therefore, the object of the present invention relates to a microneedle containing a microfiber network structure, and more specifically, to provide a microneedle containing an insoluble microfiber network structure in a dissolvable microneedle base, so that an aqueous drug solution can be delivered in large amounts and regardless of the type of drug to the skin through the back of the patch.

[0014] More specifically, the object of the present invention is to provide the following specific examples.

[0015] Specific Example 1. A microneedle comprising: a microfiber network structure; and a microneedle forming material.

[0016] Specific Example 2. The microneedle according to Specific Example 1, characterized in that the microfiber forming the above network structure is selected from one or more of the group consisting of cellulose fiber, acrylic fiber, chitosan fiber, polyethylene fiber, polypropylene fiber, polyethylene terephthalate fiber, polyimide fiber, and polyamide fiber.

[0017] Example 3. The microneedle according to any one of the preceding examples, wherein the microneedle includes a needle portion formed with a plurality of needles and a substrate portion to which the plurality of needles are attached, and the microfiber network structure is contained in the substrate portion.

[0018] Example 4. The microneedle according to any one of the preceding examples, wherein the microfiber network structure is not contained in the needle portion.

[0019] Example 5. The microneedle according to any one of the preceding examples, wherein the microneedle-forming substance swells or dissolves in the skin.

[0020] Example 6. The microneedle according to any one of the preceding examples, wherein the microneedle-forming substance includes a water-soluble polymer.

[0021] Example 7. The microneedle according to any one of the preceding examples, wherein the microneedle-forming substance includes one or more selected from the group consisting of hyaluronic acid or a salt thereof, carboxymethyl cellulose or a salt thereof, vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinylpyrrolidone, and a saccharide.

[0022] Example 8. The microneedle according to any one of the preceding examples, wherein the content of the microfiber network structure contained in the microneedle is 0.01% by weight or more and less than 13.6% by weight, relative to the total weight of the microneedle.

[0023] Example 9. The microneedle according to any one of the preceding examples, wherein a drug injection hole is formed in the substrate portion of the microneedle.

[0024] Example 10. The microneedle according to any one of the preceding examples, wherein, when a drug is injected through the drug injection hole, the drug diffuses to the entire area of the microneedle patch through the microfiber network structure contained in the substrate portion.

[0025] Example 11. The microneedle according to any one of the preceding examples, wherein the microfiber network structure is an aqueous dispersion of oxidized biocellulose microfiber networks.

[0026] Example 12. The microneedle according to any one of the preceding examples, wherein, for the oxidized biocellulose, 0.8 mmol / g cellulose or more of all alcohol groups contained in the biocellulose before oxidation are substituted with carboxyl groups.

[0027] Example 13. A microneedle kit including the microneedle according to any one of the preceding examples and a drug separately provided.

[0028] Specific Example 14. A method of effectively injecting an effective component into skin for cosmetic purposes, comprising: a step of preparing the microneedle described in any one of the preceding specific examples; and a step of injecting the effective component through the drug injection hole formed on the substrate portion of the microneedle.

[0029] Another object and advantage of the present application will become more apparent from the following detailed description of the application, claims, and drawings.

[0030] Technical Solution

[0031] One aspect of the present application is to provide a microneedle comprising: a microfiber network structure; and a microneedle forming material.

[0032] As a means to solve the above problem, a dissolvable microneedle forming material is mixed with a water-insoluble microfiber network structure, and a microneedle patch is manufactured by a micromolding method, which is a conventional manufacturing method of dissolvable microneedles.

[0033] The microfiber network structure described above cannot enter the mold cavity that forms the needle portion because it has a three-dimensional interwoven network structure, and because it is uniformly dispersed only in the rear portion of the substrate portion, a double-layer microneedle patch is manufactured that includes (i) a needle portion in which a plurality of needles that swell or dissolve due to moisture in the skin are formed and (ii) a substrate portion in which the water-insoluble microfiber network structure is impregnated in the microneedle forming material.

[0034] That is, the needle portion is composed only of water-soluble components, and the substrate portion functions as a reservoir that can immediately absorb an aqueous drug solution injected through the solution injection hole in the back of the substrate portion while being insoluble in water and continuously deliver the drug to the microneedle. In addition, it was confirmed that the needle portion of the lower end of the substrate dissolves in the skin and the aqueous drug solution at the same time, forming a flow path along which a large amount of drug can quickly penetrate into the skin. As a result, a system was developed that can deliver a large amount of drug without the effort of maintaining drug stability and pre-treatment processes (e.g., drug surface modification and coating) and the like in order to load the drug in the microneedle.

[0035] Therefore, the present application provides a microneedle patch as a microneedle comprising a needle portion in which a plurality of needles are formed and a substrate portion to which the plurality of needles are attached, a microfiber network structure is included in the substrate portion and is not included in the needle portion.

[0036] In a preferred embodiment, a drug injection hole can be formed in the substrate portion of the microneedle described above, and when a drug is injected through the drug injection hole, an effect of diffusing the drug through the microfiber network structure contained in the substrate portion to the entire area of the microneedle patch can be obtained.

[0037] In the microneedle patch of the present application, those having a diameter of 1 nm to 100 nm or less, preferably 20 nm to 80 nm or less, of the microfibers forming the network structure described above can be used. In addition, polymer fibers, carbon fibers, conductive polymer fibers, etc. having an aspect ratio of 4 to 5000 are included, but are not necessarily limited thereto.

[0038] As for the content of the microfibers, if less than 0.01% by weight of the dry weight of the microneedle patch is used, the function of rapidly absorbing an aqueous drug solution is reduced, and when 13.6% or more is added, it is difficult to manufacture a needle with a tip, and thus it is preferable that the content of the microfiber network structure contained be 0.01% by weight or more and less than 13.6% by weight.

[0039] The microfibers forming the network structure described above preferably mean fibers that can be dispersed in water or are modified so as to be dispersible in water, and for example, one or more selected from the group consisting of cellulose fibers, acrylic fibers, chitosan fibers, polyethylene fibers, polypropylene fibers, polyethylene terephthalate fibers, polyimide fibers, and polyamide fibers can be used, but are not necessarily limited thereto.

[0040] Preferably, the microfiber network structure described above can be a water dispersion of oxidized biocellulose microfibers having high water absorption capacity and water retention capacity and being insoluble. Biocellulose is a cellulose microfiber synthesized by bacteria, and has excellent properties such as thin fiber diameter, high physical strength, and high crystallinity compared to cellulose derived from plants, but mainly has a gel or sheet-like morphology, and thus it is difficult to apply to cosmetic formulations and the like. The inventors of the present application have developed a water dispersion of biocellulose microfibers capable of being dispersed in water by substituting alcohol groups of biocellulose with carboxyl groups in Patent Document 1.

[0041] Therefore, when biocellulose is used as the microfiber forming the microfiber network structure described above, oxidized biocellulose in which part or all of the alcohol groups are substituted with carboxyl groups should be used, and preferably, those in which 0.8 mmol / g cellulose or more of the total alcohol groups contained in the biocellulose described above are substituted with carboxyl groups can be used.

[0042] When using unoxidized ordinary biological cellulose, due to strong hydrogen bonds between fibers, agglomerates are formed in water-soluble substances (microneedle forming substances), and network structures cannot be formed. That is, when using unoxidized ordinary biological cellulose, the following problems can occur: network structures cannot be formed, needles cannot be formed, or needles enter the needle portion and leave residues on the skin.

[0043] In the microneedle of the present application, the above-mentioned microneedle forming substance can swell or dissolve in the skin, and for example, can include water-soluble polymers such as hyaluronic acid or a salt thereof, carboxymethyl cellulose or a salt thereof, vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, and polyvinyl pyrrolidone; saccharides such as xylose, sucrose, maltose, lactose, and trehalose; or a mixture thereof, but is not limited thereto.

[0044] More specifically, the above-mentioned microneedle forming substance, as a water-soluble substance that can well swell or dissolve in the skin, can include hyaluronic acid or a salt thereof, sodium carboxymethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylate, a saccharide, or a mixture thereof.

[0045] In addition, the above-mentioned microneedle forming substance, taking into account the skin penetration strength of the microneedle, the dissolution speed in the skin, and the like, can further include a plasticizer, a surfactant, a preservative, and the like.

[0046] As the above-mentioned plasticizer, for example, polyhydric alcohols such as ethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, and glycerine can be used alone or in a mixture.

[0047] In addition, the microneedle of the present application, which contains a microfiber network structure and a microneedle forming substance, can further contain a drug inside. That is, the present application does not exclude the case where a drug is contained inside the dissolvable microneedle as in the past.

[0048] The structure or form of the microneedle of the present application, as viewed from the base portion to the tip portion, can be any form, such as a tetrapod pyramid shape, a tripyramid shape, a stepped pyramid shape, a microknife shape, a bullet shape, or the like, in which the width of the base portion is wider than the width of the tip portion, and is preferably those having a size in the range of 20 μm to 2 mm in length, but is not limited thereto.

[0049] Another aspect of the present application is to provide a microneedle kit comprising the above-described microneedle and a separately provided liquid drug.

[0050] Another aspect of the present application is to provide a method for effectively injecting a cosmetic drug into the skin for cosmetic purposes, comprising the steps of preparing a microneedle comprising a microfiber network structure and a microneedle forming material and having a drug injection hole formed in the base portion of the microneedle, and injecting a cosmetic drug through the drug injection hole formed in the base portion of the microneedle.

[0051] The microneedle patch comprising a microfiber network structure provided in the present application, when a drug (preferably an aqueous drug solution) is injected through the drug injection hole on the back of the patch, can function to rapidly absorb the injected drug solution by the microfiber and continuously deliver it to the reservoir of the microneedle portion, so that a large amount of drug is delivered to the skin through the microchannels formed by the dissolution of the microneedle due to the body fluid and the drug solution. In addition, since the needle does not carry the drug, there is no denaturation of the drug or limitation on the amount of drug carried during the manufacturing process of the needle, and thus can be usefully applied to the cosmetics or pharmaceutical industries.

[0052] All of the ingredients described in the present application are preferably not more than the maximum use value prescribed in the relevant regulations, standards, etc. (for example, the relevant regulations (Korea), the cosmetic safety technical standards (China), etc.) of Korea, China, the United States, Europe, Japan, etc. That is, preferably, the microneedle of the present application and the drug used according to the present application and the microneedle kit comprising the above-described drug include the ingredients of the present application within the content limit allowed in the relevant regulations and standards of each country.

[0053] Effects of the Invention

[0054] When the microneedle is manufactured by adding the microfiber network structure to the water-soluble microneedle forming material, the microfiber structure cannot enter the mold cavity for forming the needle because it has a three-dimensional interwoven network structure, and thus, by being uniformly dispersed only in the rear portion of the substrate portion, a microneedle patch having a double structure of a water-soluble needle portion and an insoluble substrate portion can be provided by one casting using the existing microneedle manufacturing method, i.e., the molding technique.

[0055] On the other hand, when the drug injection hole is formed on the back surface of the substrate of the microneedle of the present application and the drug is injected therefrom, the microfiber can function as a reservoir that rapidly absorbs the drug and continuously delivers it to the microneedle portion, so that a large amount of the drug is delivered to the skin through the microchannels formed by the microneedles swollen or dissolved due to the moisture in the skin.

[0056] In addition, when the drug injection hole is formed on the back surface of the substrate and the drug is injected therefrom, it is not necessary to necessarily contain the drug in the needle, so it has the effect of solving the problem of denaturation of the drug during the manufacturing process of the microneedle or the limitation of the drug loading amount due to the size of the microneedle. BRIEF DESCRIPTION OF DRAWINGS

[0057] Figure 1 is a schematic diagram showing the manufacturing process of a microneedle patch containing a microfiber network structure.

[0058] Figure 2 is a schematic diagram showing the drug delivery principle of a microneedle patch containing a microfiber network structure.

[0059] Figure 3 is a photograph showing the microstructure of the microfiber network structure of one embodiment of the present application and the microneedle patch manufactured in Example 1.

[0060] Figure 4 is the shape of the microneedle patch manufactured in Comparative Example 1.

[0061] Figure 5 is a photograph showing the difference in solubility in water and structural properties of Example 1 and Comparative Example 2.

[0062] Figure 6 is the result of applying Example 1 and Comparative Example 2 to pig skin and confirming the skin perforation rate of the microneedle.

[0063] Figure 7 is the result of attaching Example 1 and Comparative Example 2 to pig skin and applying a model drug aqueous solution, and confirming the horizontal / vertical delivery of the drug.

[0064] Figure 8 is the result of attaching Example 1 and Comparative Example 2 to pig skin and applying a model drug aqueous solution, and analyzing the skin permeation amount of the drug. DETAILED DESCRIPTION

[0065] Hereinafter, the present application will be described in greater detail by examples. These examples are only for a more concrete illustration of the present application, and it will be obvious to those skilled in the art to which the present application pertains that the scope of the present application is not limited to these examples.

[0066] EXAMPLE

[0067] Experimental Example 1. Fabrication of Microneedle Patches Containing Microfiber Aqueous Dispersion Networks

[0068] The mixture used in the synthesis of microneedle patches consists of Aqua Cellulose Solution, provided by The Garden of Natural Solution, as a water-insoluble substance. TM (Aqueous dispersion of bio-cellulose microfibers, in which the alcohol groups of bio-cellulose are replaced by carboxyl groups to enable water dispersion, 1.5%, distilled water 95.5%, hexanediol 3%) and water-soluble substances including hyaluronic acid, carboxymethyl cellulose, trehalose, glycerin, and distilled water (refer to Table 1). This mixture was coated onto a silicone mold, vacuumed for 30 minutes, and then dried at 50°C for 3 hours. The dried patch was separated from the mold, and a 6 mm diameter drug injection hole was punched in the center of the patch (refer to Table 1). Figure 1 ).

[0069] [Table 1]

[0070] Substance Example 1 Comparative Example 1 Comparative Example 2 Hyaluronic acid 2.2 2.2 2.2 Carboxymethyl cellulose 1.8 1.2 2.55 Trehalose 3.0 3.0 3.0 Glycerin 2.3 2.3 2.3 Aqua Cellulose Solution TM ]]> 50.0 91.4 0 Distilled water To 100 To 100 To 100 Manufacture or not ○ X ○ Final patch weight of microfibers (%) 7.5 13.6 0

[0071] In Table 1 above, Example 1 is a microneedle patch containing a microfiber aqueous dispersion network (7.5% by dry weight).

[0072] Comparative Example 1 is a microneedle patch containing a microfiber aqueous dispersion network (13.6% by dry weight).

[0073] Comparative Example 2 is a soluble microneedle patch that does not contain a microfiber aqueous dispersion network.

[0074] Figure 3 Scanning electron microscope (SEM) images of the microneedle patches manufactured in Example 1 are shown, including SEM images showing the structure of the bio-cellulose microfibers used in Example 1 and Comparative Example 1. Figure 3 It was confirmed that, when measuring the microstructure of the microneedle patch manufactured in Example 1, almost no microfibers were observed on the needle surface and the front side of the patch, but a dual structure was observed on the back side of the patch, with microfibers uniformly distributed throughout the entire area (see reference). Figure 3 ).

[0075] Furthermore, the weight of the bio-cellulose microfiber aqueous dispersion capable of manufacturing microneedle patches (which can form microneedle tips well) should be less than 13.6%. When this amount is added, it was confirmed that the patch cannot be used because the needle tips are not formed (refer to Comparative Example 1 and 2 in Table 1). Figure 4 ).

[0076] Experimental Example 2. Confirmation of structural properties of a microneedle patch containing microfibers

[0077] To compare the structure and dissolution properties of the micro-needle patch containing micro-fibers (Example 1) and the micro-needle patch not containing micro-fibers (Comparative Example 2) manufactured in the above Experimental Example 1, a small amount (0.1 mL) of water was dropped on each patch before the drug injection hole, and the shape change was observed. As a result, it was confirmed that in Comparative Example 2, the entire patch including the needle was dissolved in water, and thus the form disappeared (refer to FIG. 4C and D), while in Example 1, only the needle portion was dissolved and the form of the patch substrate portion was maintained (refer to FIG. 4A and B). Figure 5 Figure 5

[0078] Experimental Example 3. Comparison of skin perforation rates of microneedle patches with and without microfibers The micro-needle patch containing micro-fibers (Example 1) and the micro-needle patch not containing micro-fibers (Comparative Example 2) manufactured in the above Experimental Example 1 were respectively attached to pig skin, and after 10 seconds of application of a force of 20 N, the patch was removed, and the micro-channels generated on the skin were dyed with an aqueous trypan blue solution, thereby comparing the skin perforation rate. As a result, it was shown that the skin perforation rate was 90% or more regardless of the presence or absence of micro-fibers (refer to FIG. 5A and B).

[0079] Figure 6

[0080] Experimental Example 4. Visualization of drug delivery capacity of a microneedle patch containing microfibers The micro-needle patch containing micro-fibers (Example 1) and the micro-needle patch not containing micro-fibers (Comparative Example 2) manufactured in the above Experimental Example 1 were respectively attached to pig skin, and an aqueous rhodamine B solution (300 μg / mL, 100 μL) as a model drug was injected into the hole structure of the patch, thereby comparing the horizontal distribution of the drug aqueous solution. It was confirmed that unlike Comparative Example 2 (refer to FIG. 6B), in Example 1 (refer to FIG. 6A), rhodamine B was uniformly diffused in the entire patch area. In addition, after applying an aqueous fluorescein solution (50 μg / mL, 2 mL) to the pig skin to which Example 1 was applied and the pig skin to which nothing was attached, respectively, the patch and the remaining solution were removed, and the skin was sliced, thereby confirming the vertical distribution of the drug. When the drug was applied without the micro-needle patch, only weak fluorescence of fluorescein was observed on the surface of the pig skin (refer to FIG. 7E and F), while in Example 1, strong fluorescence was observed in the deep part of the skin (refer to FIG. 7C and D). As a result, it was confirmed that the micro-needle patch containing micro-fibers can deliver the drug to the deep part of the skin in the entire area of the patch.

[0081] Figure 7 Figure 7 Figure 7 Figure 7 ​​​​​​​

[0082] Experimental Example 5. Evaluation of skin permeation of a drug using a microneedle patch containing microfibers

[0083] Example 1 and Comparative Example 2 manufactured in the above Experimental Example 1 were attached to pig skin, and a receptor was installed in a diffusion cell (Franz Cell) filled with phosphate-buffered saline (pH 7.4, Gibco). A rhodamine B aqueous solution (300 μg / mL, 100 μL) as a model drug was injected into the hole structure of each patch, and the drug permeation was allowed for 17 hours at 37 degrees and a relative humidity of 50%, after which the patch and unabsorbed solution were removed, and the amount of drug permeated to the skin and the receptor was analyzed (refer to Figure 8 A). In addition, after a fluorescein aqueous solution (50 μg / mL, 2 mL) was applied to pig skin to which the patch of Example 1 was attached and to pig skin to which no patch was attached, respectively, the amount of drug permeated was analyzed by the same procedure as described above (refer to Figure 8 B). As a result, even in the case where no drug was carried in the needle, a greater amount of drug was delivered into the skin than in the case where no patch was attached and only an aqueous solution of a model drug was applied. Furthermore, it was confirmed that a greater amount of drug could be delivered than in Comparative Example 2.

Claims

1. A method for manufacturing a microneedle, the microneedle comprising: a microfiber network structure; And the microneedle-forming material, the above manufacturing method includes: i) The step of mixing oxidized biocellulose microfibers with microneedle-forming substances; ii) The step of coating the above mixture onto a mold to form microneedles; iii) The step of separating the formed microneedles from the above-mentioned mold, and iv) A drug injection port is formed on the back side of the substrate portion of the microneedle, and The aforementioned microneedles include a needle portion having multiple needles formed thereon and a substrate portion having the multiple needles attached thereon. The aforementioned microfiber network structure is included in the aforementioned substrate portion, but not in the aforementioned needle portion. When a drug is injected through the aforementioned drug injection port, the drug diffuses through the microfiber network structure contained in the substrate portion to the entire area of ​​the microneedle patch. In the above-mentioned oxidized biological cellulose, some or all of the alcohol groups are replaced by carboxyl groups.

2. The method for manufacturing microneedles as described in claim 1, characterized in that, The aforementioned microneedle-forming substances swell or dissolve within the skin.

3. The method for manufacturing microneedles as described in claim 1, characterized in that, The aforementioned microneedle-forming substances include water-soluble polymers.

4. The method for manufacturing microneedles as described in claim 1, characterized in that, The aforementioned microneedle-forming substances include one or more selected from the group consisting of hyaluronic acid or its salts, carboxymethyl cellulose or its salts, vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinylpyrrolidone, and sugars.

5. The method for manufacturing microneedles as described in claim 1, characterized in that, The content of the microfiber network structure contained in the microneedles is more than 0.01% by weight and less than 13.6% by weight relative to the total weight of the microneedles.

6. The method for manufacturing microneedles as described in claim 1, characterized in that, For the oxidized biological cellulose mentioned above, more than 0.8 mmol / g of cellulose in all alcohol groups contained in the biological cellulose before oxidation are replaced by carboxyl groups.

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