Micro-implement and method for producing same

Abstract

Provided are a micro-implement having an excellent effect in administering a functional component from a microneedle and a method for producing a micro-implement that can form a desired shape with good shape quality even when a microneedle is formed from maltose on a substrate and that can freely form the microneedles in the desired arrangement at excellent productivity. Specifically, a substrate (1) comprising a polymer material to which maltose can adhere, and microneedles (2) disposed on the surface (1a) of the substrate (1) and formed using pure maltose or a maltose composite material with which one or more functional components have been mixed are provided. The plurality of fine needles (2) are disposed at least partially irregularly in plan view on the surface (1a) of the substrate (1) and are provided freely arranged by each being individually formed.

Description

Microimplement and manufacturing method thereof

[0001] In particular, the present invention relates to a micro-implement, which is a medical dosage form for administering functional ingredients such as drugs, biological substances, cosmetics, or nutrients to the surface layer of the skin and / or the stratum corneum of the skin, and a method for producing the same.

[0002] In recent years, the importance of transdermal administration devices utilizing microdevice technology has been increasingly recognized in the medical industry, given the need for easy treatment, friendliness (friendliness), and high-precision administration. A typical example of the transdermal administration device is a microneedle. However, most conventional microneedles have been made of metal or plastic due to the need for materials that are easy to process with high precision. However, these materials are foreign bodies in the human body, and in some cases, there is a risk of problems occurring if they remain in the body.

[0003] In order to avoid the above-mentioned problem of foreign substances remaining in the body, there has been a demand for biodegradable materials that are easily compatible with the human body and have excellent degradability as materials for transdermal administration devices, and polylactic acid is a representative example of such materials. However, polylactic acid takes a long time, on the order of weeks, to dissolve in the body, and therefore has not by any means solved the above-mentioned problem.

[0004] Meanwhile, recent technological developments based on material exploration have led to the development of microneedles that can be used as even safer substances in the body, and among the materials used to make them, maltose is establishing itself as a central material. For these reasons, maltose is being used as a material for microneedles. However, unlike conventional microneedles, microneedles made from maltose dissolve and disappear in the body's water during use (water-soluble), and therefore are equivalent to medical dosage forms rather than medical devices. In other words, microneedles made from maltose are significantly different in characteristics and technical attributes from conventional microneedles, and are therefore referred to as microimplements in this specification.

[0005] A new function of the micro-implements described above, which is not available in conventional microneedles, is that functional or medicinal ingredients can be mixed into maltose, and when administered to the body, the ingredients can be penetrated simultaneously with the dissolution of the micro-needles. As mentioned above, such micro-implements are classified as medical dosage forms rather than medical devices, and the realization of their functions is important. In fact, micro-implements having micro-needles containing various functional ingredients on the surface of a substrate can deliver various functional ingredients to the surface layer and / or stratum corneum of the skin without causing pain to the user, and are therefore highly anticipated from the perspectives of medicine, cosmetics, and the like. Examples of functional ingredients delivered through the skin by micro-implements include drugs, biological substances, cosmetics, and nutrients. Their applications are not limited to skin treatment, cosmetics, and cosmetic modifications, but can also be applied to advanced treatments of immune system diseases deep under the skin and throughout the body, and are therefore particularly expected as painless and minimally invasive medical dosage forms.

[0006] As the microneedles described above, in addition to the above-mentioned maltose, it is also possible to use those whose main component is a material that is easily dissolved in the human body and highly safe, such as hyaluronic acid, collagen, elastin, gelatin, starch, etc., and various functional components can be mixed, encapsulated, coated, etc. In recent years, maltose has been increasingly used as a material for microneedles from the viewpoint of its excellent solubility and safety, as described above. Maltose has a lower melting point than other materials, and therefore has the advantage of being easily dissolved in the human body and less likely to remain undissolved as a foreign substance, as described above.

[0007] Conventionally, in consideration of effectively realizing various functions of functional components, a micro-implement has often been used in which, for example, a plurality (a large number) of micro-needles are regularly arranged in a roughly lattice pattern on a substrate (see Figure 20 of Patent Document 1). Furthermore, Example 3 of Patent Document 1 describes the use of a multi-cavity mold in which recessed cavities for 20 micro-needles are arranged in a line.

[0008] JP 2015-205094 A

[0009] In the microimplement disclosed in Patent Document 1, as described above, a plurality of microneedles are provided in a regular arrangement on a substrate. However, when the microneedles are provided in such an arrangement, there is a problem that the microneedles do not fit well with the skin surface, making it difficult to administer the functional ingredient uniformly and effectively to the surface layer of the skin and / or the stratum corneum.

[0010] Furthermore, when a multi-cavity mold as described above is used to form a large number of microneedles made of maltose on a substrate using conventional methods, the overall size of the mold increases, resulting in a large heat capacity and a slow cooling rate of the mold during microneedle formation. Therefore, when forming multiple microneedles from maltose, which has a low melting point, it becomes difficult to lower the temperature of the mold, making it difficult to fix and form the maltose attached to the substrate into the desired shape at high speed.

[0011] Furthermore, when using a conventional multi-cavity mold, for example, to manufacture a wide variety of micro-implements each having a different layout pattern, it is necessary to create and replace the mold according to the specifications of each. Therefore, the more varieties of micro-implements are manufactured, the more frequently the mold needs to be replaced, which may result in a decrease in productivity.

[0012] In recent years, the arrangement specifications of microneedles in microimplements have become more diverse to suit various applications, the number of varieties has increased significantly, and higher quality is required for medical or cosmetic applications, etc. Therefore, there is a demand for microimplements that further improve the effect of administering functional ingredients from the microneedles to the surface layer of the skin and / or the stratum corneum of the skin, and there has also been a strong demand for a method that can easily accommodate changes in the arrangement specifications of the microneedles and that can form microneedles with excellent shape precision.

[0013] The present invention has been made in consideration of the above problems, and aims to provide a microimplement that is excellent in the effect of administering a functional ingredient from a microneedle. Another aim of the present invention is to provide a method for manufacturing a microimplement that is excellent in productivity, and that can form microneedles in a desired shape with high shape accuracy, even when forming microneedles on a substrate from maltose, which has a low melting point, and can freely form the microneedles in a desired arrangement.

[0014] In order to solve the above problems, the present inventors conducted extensive research. As a result, they discovered that by using maltose for multiple microneedles provided on a substrate in a microimplementation process, and by forming at least some of the microneedles on the surface of the substrate in an irregular arrangement in a planar view and individually forming them so that they can be freely arranged, the administration effect of functional ingredients from the microneedles is enhanced compared to when all of the microneedles are arranged in a regular arrangement. They also discovered that when forming multiple microneedles in an irregular arrangement so that they can be freely arranged, by repeatedly heating and cooling the micromold head for forming the microneedles while continuously forming the multiple microneedles individually, it is possible to form the microneedles in a desired shape with high shape accuracy, even when forming the microneedles using maltose, which has a low melting point. Furthermore, they discovered that by continuously forming multiple microneedles using the above method, it is possible to freely form the microneedles in a desired arrangement and easily accommodate changes in the arrangement specification, etc., and thus completed the present invention.

[0015] That is, the present invention provides a microimplement comprising a substrate made of a polymeric material to which maltose can be attached, and microneedles arranged in multiple numbers on the surface of the substrate, the microneedles being made of either pure maltose or a maltose composite material mixed with one or more functional components, wherein at least a portion of the multiple microneedles are arranged irregularly in a planar view on the surface of the substrate, and each microneedle is individually formed so as to be freely arranged.

[0016] In the above-mentioned aspect of the microimplement of the present invention, a configuration can be adopted in which each of the plurality of microneedles contains a mixture of any one of two or more different types of functional components.

[0017] In the above-mentioned aspect, the microimplement of the present invention can employ a structure in which the plurality of microneedles are provided on the surface of the substrate in a state in which the functional component is mixed in advance.

[0018] In the above-mentioned aspect, the microimplement of the present invention can adopt a structure in which the plurality of microneedles are arranged so as to overlap the positions of the functional components that have been dispersed and arranged in advance on the surface of the substrate, and the functional components are taken in and mixed and / or encapsulated.

[0019] In the above-described aspect, the microimplement of the present invention may further employ a structure in which a microprotrusion is provided between the substrate and each of the plurality of microneedles.

[0020] In the above-mentioned aspect, the microimplement of the present invention may further comprise a microprotrusion between the substrate and each of the plurality of microneedles, with a plurality of the microprotrusions being arranged for each of the plurality of microneedles, each containing one of two or more different functional components, and each of the plurality of microneedles may have a structure in which the microneedles made of pure maltose incorporate and mix and / or encapsulate two or more different functional components.

[0021] In the above-described aspect of the microimplement of the present invention, the plurality of microneedles may have a structure in which the functional component is coated on the surface of the microneedles made of pure maltose.

[0022] In the above-mentioned aspect, the microimplement of the present invention can adopt a configuration in which the functional component is any one or a combination of two or more selected from the group consisting of vitamins, hormones, glycoproteins, collagen, proteins, peptides, enzymes, coenzymes, vaccine components, biological signaling substances, intracellular signaling substances, extracellular signaling substances, neurotransmitters, information polymers, biological energy substances, drugs, nutrients, nutritional supplements, cosmetics, antibody testing agents, anticancer drugs, detoxification agents, artificial cells, color materials for internal use, metals for internal use, metal oxides for internal use, and components or component granules for internal use of magnetic substances.

[0023] In the above-described aspect of the microimplement of the present invention, the polymer material used for the substrate may be any one of polyvinyl alcohol, pullulan, hyaluronic acid, gelatin, and collagen.

[0024] In the above-described aspect, the microimplement of the present invention can employ a structure in which the plurality of microneedles have at least the tip side thereof a cone shape selected from the group consisting of triangular pyramids, square pyramids, cones, bullet shapes, and polygonal pyramids having pentagonal or higher sides.

[0025] In the above-described aspect of the microimplement of the present invention, a structure can be adopted in which the plurality of microneedles each have a different shape.

[0026] The present invention provides a method for manufacturing a microimplement, which uses pure maltose or a maltose composite material mixed with one or more functional components to form a plurality of microneedles on the surface of a substrate, and is characterized in that the substrate is made of a polymeric material to which the maltose can adhere, and the method includes a microneedle molding step in which the plurality of microneedles are individually and continuously formed by repeatedly heating and cooling a micromold for microneedle molding, which has a cavity for freely forming the microneedles from the pure maltose or the maltose composite material, so that at least some of the plurality of microneedles formed on the surface of the substrate are irregularly arranged in a planar view.

[0027] In the above-mentioned aspect of the microimplement manufacturing method of the present invention, the microneedle molding step can employ a method in which the microneedle molding step comprises: an attachment process in which, when the microneedle molding micromold head approaches the substrate, the microneedle molding micromold head is heated by a heater to attach the maltose or the maltose composite material in a softened state to the surface of the substrate; and a solidification process in which, when the microneedle molding micromold head is released from the substrate, the heating of the microneedle molding micromold head by the heater is stopped and the microneedle molding micromold head is allowed to cool, thereby solidifying the pure maltose or the maltose composite material attached to the surface of the substrate while allowing it to grow, by repeating these steps to continuously form a plurality of microneedles on the surface of the substrate.

[0028] In the above-described aspect, the method for manufacturing a microimplement of the present invention can further employ a component mixing step of mixing a functional component with the maltose to prepare the maltose composite material before the microneedle molding step.

[0029] In the above-mentioned aspect of the micro-implement manufacturing method of the present invention, the component mixing step can employ a method in which the maltose composite material is prepared in multiple batches using two or more different functional components, each containing a different functional component, and the micro-needle molding step can employ a method in which the multiple micro-needles are continuously formed so that each micro-needle contains one of the two or more different functional components.

[0030] In the above-mentioned aspect, the manufacturing method of the microimplement of the present invention further includes a spraying step prior to the microneedle forming step, in which the functional component is attached to the surface of the substrate in an irregular arrangement so as to be freely arranged, and the microneedle forming step can employ a method in which the multiple microneedles are formed so as to overlap at the positions of the functional component attached to the surface of the substrate.

[0031] In the above-described aspect of the method for producing a microimplement of the present invention, the spraying step can employ a method in which two or more different functional components are attached to the surface of the substrate so as to be freely arranged in an irregular arrangement.

[0032] In the above-mentioned aspect, the method for manufacturing a micro-implement of the present invention may further include a component coating step of coating the surfaces of the plurality of micro-needles made of pure maltose with the functional component after the micro-needle molding step.

[0033] In the above-mentioned aspect, the manufacturing method of the microimplement of the present invention may further include a microprotrusion forming step, prior to the microneedle forming step, in which a plurality of microprotrusions are formed on the surface of the substrate in an irregular arrangement so as to be freely arranged, and the microneedle forming step may employ a method in which the microneedle is formed on each of the plurality of microprotrusions.

[0034] In the above-mentioned aspect of the micro-implement manufacturing method of the present invention, the micro-protrusion molding process may form a plurality of micro-protrusions on the surface of the substrate, each of which is a mixture of any of two or more different functional components, and the micro-needle molding process may form a micro-needle made of pure maltose on each of the plurality of micro-protrusions.

[0035] According to the microimplement of the present invention, as described above, maltose or a maltose composite material is used for the multiple microneedles provided on the substrate, and at least some of the microneedles are arranged irregularly in a planar view on the surface of the substrate, and each is individually formed so that they can be freely arranged. This makes it easier for the microneedles to be administered to the surface layer of the skin and / or the stratum corneum than when all the microneedles are arranged in a regular array, resulting in excellent compatibility with the living body. Furthermore, the administration effect of functional ingredients from the microneedles is enhanced, thereby achieving more pronounced effects, for example, from medical treatments and cosmetic procedures.

[0036] According to the microimplant manufacturing method of the present invention, when forming multiple microneedles in an irregular arrangement on the surface of a substrate, as described above, a method is adopted in which multiple microneedles are individually and continuously formed by repeatedly heating and cooling a micromold for forming microneedles. This allows microneedles to be formed with high accuracy in the desired shape, even when formed from maltose or a maltose composite material with a low melting point, and allows the microneedles to be formed in the desired arrangement, making it easy to accommodate changes in the arrangement specification. Furthermore, since the tips of the microneedles can be formed more sharply, painless and effective administration to the surface layer and / or stratum corneum of the skin is possible, making it possible to successfully produce microimplants that provide a more pronounced feel when used and the effects of therapeutic and cosmetic treatments.

[0037] Other objects, features and advantages of the present invention will become apparent from the following description of the preferred embodiments of the present invention, which proceeds with reference to the accompanying drawings.

[0038] FIG. 1A is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a perspective view of one of a plurality of microneedles provided on the surface of a substrate. FIG. 1B is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a perspective view of an example of a microimplement in which a plurality of microneedles are provided on the surface of a substrate in an irregular arrangement. FIG. 2A is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a plan view of an example of arrangement positions and non-arrangement positions of microneedles in a lattice pattern when a plurality of microneedles are provided on the surface of a substrate in an irregular arrangement. FIG. 2B is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a perspective view of another example of a microimplement in which a plurality of microneedles are provided on the surface of a substrate in an irregular arrangement. Fig. 3 is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a perspective view of an example of a microimplement having a plurality of microneedles arranged in an irregular arrangement on the surface of a substrate, each of which has a different size. Fig. 4A is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a plan view of an example of a microimplement having a plurality of microneedles arranged on the surface of a substrate, each of which contains a different functional component. Fig. 4B is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a perspective view of an example of a microimplement having a plurality of microneedles arranged in an irregular arrangement on the surface of a substrate, each of which contains a different functional component. Fig. 5A is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing a perspective view of an example of a microimplement having functional components dispersed and attached to the surface of a substrate, with microneedles superimposed on each of the functional components.Fig. 5B is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing an example of a microimplement in which a plurality of different functional components are dispersed and attached in an irregular arrangement on the surface of a substrate, and microneedles of different shapes and sizes are provided thereon. Fig. 6A is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing an example of a microimplement in which a plurality of microprotrusions are provided on the surface of a substrate, and microneedles are provided thereon. Fig. 6B is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing an example of a microimplement in which a plurality of microprotrusions of different shapes and sizes are provided in an irregular arrangement on the surface of a substrate, and microneedles are provided thereon. Fig. 7A is a diagram for schematically explaining an embodiment of a microimplement and a method for manufacturing the same according to the present invention, showing an example of a microimplement in which a plurality of microprotrusions of different shapes and sizes are provided in an irregular arrangement on the surface of a substrate, and microneedles are provided thereon. Fig. 7B is a diagram for schematically explaining an embodiment of a microimplement and a manufacturing method thereof according to the present invention, and is a perspective view showing an example of a microimplement in which a plurality of microprotrusions, each of which has a different shape, is provided in an irregular arrangement on the surface of a substrate, and a microneedle is provided on each of the microprotrusions. Fig. 7C is a diagram for schematically explaining an embodiment of a microimplement and a manufacturing method thereof according to the present invention, and is a perspective view showing an example of a microimplement in which a plurality of microprotrusions, each of which has a different shape, is provided in an irregular arrangement on the surface of a substrate, and a microneedle and a functional component are provided on each of the microprotrusions. Fig. 8 is a diagram for schematically explaining an embodiment of a microimplement manufacturing method according to the present invention, and is a schematic view showing an example of a microneedle molding process in which a plurality of microneedles are individually and continuously formed by repeatedly heating and cooling a microneedle-forming micromold.

[0039] Hereinafter, embodiments of the microimplement and its manufacturing method according to the present invention will be described in detail with reference to the drawings as appropriate. Note that in the drawings used in the following description, characteristic portions may be shown slightly enlarged for the sake of convenience in order to make the features of the microimplement of the present invention and the microimplement manufacturing apparatus used in its manufacturing method easier to see, and the dimensional ratios of each component may differ from the actual ones. Furthermore, the materials, dimensions, etc. exemplified in the following description are merely examples, and the present invention is not limited to them. Appropriate modifications may be made within the scope of the present invention.

[0040] The microimplement according to the present invention comprises microneedles made of maltose, a disaccharide carbohydrate, disposed on a substrate. As mentioned above, the microneedles dissolve and disappear in the body's water during use, making it a medical dosage form. In other words, the technical concept of the microimplement according to the present invention is completely different from that of conventional microneedles classified as medical devices, which use metals and plastics that are extremely difficult to dissolve in the body, or polylactic acid, which takes a very long time to dissolve. Therefore, the inventors refer to the above-mentioned microneedles made of maltose disposed on a substrate as a microimplement.

[0041] <Structure of Microimplement> The structure of the microimplement of this embodiment will be described in detail mainly with reference to Figures 1A and 1B to 7A, 7B and 7C, taking the first to seventh example microimplements shown in each of these figures.

[0042] 1B, 2A, and 2B, the microimplement of this embodiment includes a substrate 1 made of a polymeric material to which maltose can be attached, and a plurality of microneedles 2 arranged on the surface 1a of the substrate 1, the microneedles 2 being made of maltose as a solid material or a maltose composite material mixed with one or more functional components. In the microimplement of this embodiment, at least a portion of the plurality of microneedles 2 are arranged irregularly in a plan view on the surface 1a of the substrate 1, and each microneedle 2 is individually formed so as to be freely disposed.

[0043] 1A and 1B, a microimplement 10 according to a first example of the present embodiment will be described in detail below. Fig. 1A is a perspective view showing one of a plurality of microneedles 2 provided on the surface 1a of a substrate 1 in the microimplement 10 of this example. Fig. 1B is a perspective view showing the microimplement 10 of this example, in which a plurality of microneedles 2 are provided on the surface 1a of the substrate 1 so as to be freely arranged in an irregular arrangement.

[0044] As shown in the partial view of Fig. 1A, the microimplement 10 has the base end 21 of the microneedles 2 welded (adhered) to the surface 1a of the substrate 1, so that the microneedles 2 are attached in an upright position to the substrate 1. As shown in Fig. 1B, the microimplement 10 has a plurality of microneedles 2 arranged freely in an irregular arrangement on the surface 1a of the substrate 1. In the illustrated example, a total of 10 microneedles 2 are provided, with some empty space provided on the surface 1a of the substrate 1. For ease of understanding, Fig. 1B shows intended attachment locations 11 in the case where the microneedles 2 are filled in a regular arrangement in the empty space on the surface 1a of the substrate 1, and a total of six locations are shown in the figure.

[0045] The substrate 1 functions as a base for the microimplement 10, and as described above, a plurality of microneedles 2 are provided on the surface 1a, while the back surface 1b functions as a pressing portion when the user of the microimplement 10 presses the surface 1a against their skin. The material of the substrate 1 is not particularly limited as long as it is made of a polymer material to which the maltose composite material, which is the material of the microneedles 2, can be adhered, and for example, any of polyvinyl alcohol, pullulan, hyaluronic acid, gelatin, and collagen can be selected and used. Among these materials, it is preferable to use a cosmetic material made of polyvinyl alcohol for the substrate 1 from the viewpoint of safety to human skin as well as the adhesiveness of the maltose composite material.

[0046] The size of the substrate 1 is not particularly limited, and for example, a plate made of a polyvinyl alcohol thin film having a thickness of 50 to 2000 μm and having a planar size and shape appropriate for the application of the microimplementation can be used. The planar shape of the substrate 1 can be, for example, square, rectangular, circular, elliptical, or the like, and can be appropriately set taking into consideration the area where the microimplementation will be used. The same applies to the planar size of the substrate 1; if the substrate 1 is configured as a square in plan view, it can be, for example, approximately 0.3 to 50 x 0.3 to 50 mm, and if it is configured as a circle in plan view, it can be, for example, approximately 0.3 to 50 mm in diameter.

[0047] As described above, the microneedles 2 have a sharp tip and are made of maltose alone or a maltose composite material. The illustrated microneedles 2 have a base end 21 that is the welding site to the surface 1a of the substrate 1, a body 22 that grows from the base end 21 toward the tip 24, a tapered (needle-like) needle portion 23 that gradually reduces in diameter from the body 22 toward the tip 24, and the tip 24.

[0048] When using the microimplement 10, the microneedles 2 are inserted into the skin from the surface of the skin, for example, by pressing them into the skin from the back surface 1b of the substrate 1 in a stamping manner, and reach the superficial layer and / or stratum corneum of the skin, and have the property of dissolving in each layer in a short time of minutes. Therefore, for example, when the microneedles 2 are made of pure maltose, they can be used to form holes in the surface of the skin. Furthermore, when the microneedles 2 are made of a maltose composite material mixed with a functional component, the functional component for achieving a desired effect can be effectively administered to the superficial layer and / or stratum corneum of the skin.

[0049] The number and density of the microneedles 2 arranged on the surface 1a of the substrate 1 are not particularly limited and can be set appropriately taking into consideration the application of the microimplement 10. For example, if the purpose is to form pores or penetrate functional ingredients into a wide area of ​​the user's skin, it is sufficient to arrange many microneedles 2 on the surface 1a of the substrate 1. However, if the distance between the microneedles 2 is too close, i.e., if the formation density of the microneedles 2 on the surface 1a of the substrate 1 is too high, mutual interference will occur in the surface layer of the skin and / or the stratum corneum, which will lengthen the time it takes for the microneedles 2 to dissolve and the time required for the functional ingredients to penetrate, so this point must be taken into consideration.

[0050] The maltose composite material that makes up the microneedles 2 is primarily composed of maltose, a sugar material that has a low melting point and is easily soluble in the skin. Maltose takes approximately 2-3 minutes to dissolve at human body temperature (internal body temperature), a much shorter time than other materials, such as sodium hyaluronate (approximately 8 hours), providing the advantage of achieving the desired functionality in a short period of time. Furthermore, maltose is water-soluble and has superior solubility in the skin compared to other materials such as sodium hyaluronate and starch, eliminating concerns about residual material. Furthermore, since maltose is a naturally occurring substance in the body, it is an extremely safe material.

[0051] The shape of the microneedles 2 is not particularly limited, and various shapes can be used as long as the tip shape allows easy insertion into the surface layer of the skin and / or the stratum corneum and reduces pain to the user. Examples of such shapes of the microneedles 2 include those in which at least the tip portion (tip) 24 side is conical, as shown in Figure 1A, etc. Furthermore, the shape of the tip portion 24 side of the microneedles 2 is not limited to a conical shape, and can be any cone shape selected from the group consisting of triangular pyramids, square pyramids, cones, bullet shapes, and polygonal pyramids with pentagonal or higher sides.

[0052] Furthermore, by adjusting the molding conditions using a micromold head for forming microneedles, which will be described in detail later, it is also possible to use a thorn-shaped microneedle that curves while shrinking toward the tip.Furthermore, it is also possible to use a microneedle that is roughly barrel-shaped, having an enlarged portion at or near the middle in the axial direction where the cross-sectional area is larger than at other positions, or a microneedle that has a narrowed portion at or near the middle in the axial direction where the cross-sectional area is smaller than at other positions, and has various shapes such as a roughly hourglass shape, bowling pin shape, or jewel shape.

[0053] The size of the microneedles 2, i.e., the axial length, the maximum diameter and tip diameter when the microneedles 2 are formed into a conical shape, etc., are not particularly limited and may be appropriately set depending on the application of the microimplement 10. For example, the maximum diameter and tip diameter of the microneedles 2 may be determined taking into consideration the ease of insertion from the skin surface as well as the strength of the microneedles 2. The length of the microneedles 2 may also be determined depending on the application, such as whether the insertion position is to be only the surface layer and / or stratum corneum of the skin, or whether it is to be inserted deeper. When the microneedles 2 are inserted up to the surface layer and / or stratum corneum of the skin, the length may be, for example, about 0.3 to 0.7 mm, and when the microneedles 2 are inserted deeper than the surface layer and / or stratum corneum of the skin, the length may be, for example, about 1.0 to 2.0 mm.

[0054] Furthermore, when the microneedles 2 are conical, the maximum diameter is preferably about 50 to 200 μm from the above viewpoint, and the diameter of the tip 24 is preferably about 1 to 10 μm. The shape of the tip 24 is not particularly limited, and it may be, for example, a flat surface, but from the viewpoint of preventing the user from feeling pain when the microneedles 2 are inserted into the skin, it is more preferable that the tip 24 be spherical.

[0055] As described above, pure maltose can be used for the microneedles 2, but it is also possible to use maltose composite materials mixed with functional components to impart various functions to the microimplements. Examples of such functional components include, but are not limited to, vitamins, hormones, glycoproteins, collagen, proteins, peptides, enzymes, coenzymes, vaccine components, biosignal substances, intracellular signal substances, extracellular signal substances, neurotransmitters, information polymers, bioenergy substances, medicines, nutrients, nutritional supplements, cosmetics, antibody testing agents, anticancer drugs, antidotes, artificial cells, color materials for internal use, metals for internal use, metal oxides for internal use, and magnetic substances. These components or granular components may be any one or a combination of two or more selected from the group consisting of: vitamins, hormones, glycoproteins, collagen, proteins, peptides, enzymes, coenzymes, vaccine components, biosignal substances, intracellular signal substances, extracellular signal substances, neurotransmitters, information polymers, bioenergy substances, medicines, nutrients, nutritional supplements, cosmetics, antibody testing agents, anticancer drugs, antidotes, artificial cells, internal color materials, internal metals, internal metal oxides, and internal magnetic substances.

[0056] The form in which the functional component is mixed into the maltose composite material constituting the microneedles 2 is not particularly limited, and examples thereof include a form in which the functional component is mixed into the maltose composite material, a form in which the functional component is contained in the internal space, and a form in which the functional component is coated on the surface of the molded microneedles 2. When the multiple microneedles 2 are made of pure maltose, as described above, a structure in which the surfaces of the multiple molded microneedles 2 are coated with the functional component can be adopted. Furthermore, when the multiple microneedles 2 are made of a maltose composite material mixed with a functional component, a maltose composite material in which the functional component has been mixed in advance can be used.

[0057] When the microneedles 2 are made of a maltose composite material containing a functional component, the content ratio of maltose to the functional component is not particularly limited and may be set appropriately while taking into consideration the expression of the function of the functional component. On the other hand, in order to ensure that the microneedles 2 have a predetermined strength for insertion into the surface layer of the skin and / or the stratum corneum of the skin, it is preferable to maintain the content ratio of maltose relative to the total amount of the maltose composite material at 80 mass% or more.

[0058] The surface configuration of the microneedles 2 is not particularly limited, but a structure that is water-repellent and can prevent moisture from penetrating into the interior of the microneedles 2 is preferable. This can prevent the microneedles 2 from being softened by atmospheric moisture, for example.

[0059] In the microimplement of this embodiment, as described above, the multiple microneedles 2 provided on the surface 1a of the substrate 1 are arranged in an irregular manner by being freely disposed, thereby achieving a high administration effect that is more compatible with the living body or human skin than when the microneedles 2 are arranged in a regular manner as in the past. In other words, the multiple microneedles 2 are arranged in an irregular and free manner, which makes it easier for the multiple microneedles 2 to dissolve and be administered in the surface layer of the skin and / or the stratum corneum of the skin, and also provides the effect of increasing the permeability of the functional ingredient.

[0060] When using the microimplant 10, the user first takes out the microimplant 10, which is stored in a container (not shown) or temporarily attached to a sterilized mount or the like, and presses the front surface 1a of the substrate 1, on which the multiple microneedles 2 are provided, against the desired position on the skin surface. Then, by pressing the back surface 1b of the substrate 1 with a finger or the like, the microneedles 2 are inserted into the surface layer of the skin and / or the stratum corneum, and this state is maintained for a predetermined time until the microneedles 2 are completely dissolved.

[0061] Here, the microimplement according to the present invention uses pure maltose or maltose composite material as the material for the microneedles 2, so the microneedles 2 dissolve completely under the skin surface in approximately 2 to 3 minutes. Therefore, the microneedles 2 do not remain as solid foreign bodies, making it safe and enabling the desired function to be obtained in a short time.

[0062] In this example, in order to further improve the ease of handling for the user, for example, a structure may be adopted in which a pressure assist mechanism (not shown) is provided on the rear surface 1b side of the substrate 1. This makes it possible to more effectively apply pressure from the user's finger or the like when pressing the microimplement 10 against the skin.

[0063] [Second Example] A microimplementation according to a second example of this embodiment will now be described with reference to Figures 2A and 2B. Figure 2A is a plan view showing an example of the positions where microneedles 2 are arranged and where no microneedles are arranged (see the intended attachment locations indicated by reference numeral 11) in a grid pattern when a plurality of microneedles 2 are individually and freely arranged in an irregular arrangement on the surface 1a of the substrate 1. Figure 2B is a plan view showing an example where a plurality of microneedles 2 are provided on the surface 1a of the substrate 1 in an irregular arrangement so as to be freely arranged.

[0064] The grid pattern shown in Fig. 2A is used to determine the placement positions of the microneedles 2 in, for example, the microimplement 10 of the first example shown in Fig. 1B and the microimplement 10A of the second example shown in Fig. 2B. In Fig. 2A, a raster pattern consisting of grid-like virtual lines 12 is placed on the surface 1a of the substrate 1, and then multiple planned attachment locations 11 for the microneedles 2 are virtually assigned to the intersections of each virtual line 12. Then, positions at which the microneedles 2 are to be provided are determined, either regularly or irregularly, from among the multiple virtually assigned planned attachment locations 11.

[0065] The microimplement 10A shown in Figure 2B is obtained by vector drawing, in which the microneedles 2 are arranged at any position without any constraints, based on the grid pattern shown in Figure 2A. In the illustrated example, the microneedles 2 are irregularly arranged at a total of eight locations on the surface 1a of the substrate 1.

[0066] According to the microimplement 10A of this example, by adopting the above-described arrangement of the microneedles 2 and arranging the microneedles 2 in a specific pattern, it is possible to draw specific designs or characters in the planar direction of the microimplement 10A. As a result, for example, when the microimplement 10A is used in a hospital or the like, it is possible to draw numbers, names, etc. that can prevent problems such as mix-ups between patients. In determining the arrangement positions of such microneedles 2, it is also possible to apply a traveling salesman model, which is commonly known as AI (Artificial Intelligence), to enable efficient drawing.

[0067] [Third Example] A microimplement 10B according to a third example of this embodiment will now be described with reference to Fig. 3. Fig. 3 is a perspective view showing a microimplement 10B in which a plurality of microneedles 2a to 2j are provided on the surface 1a of the substrate 1 in an irregular arrangement so as to be freely disposable, and the plurality of microneedles 2a to 2j are each of different sizes.

[0068] The microimplement 10B shown in Figure 3 has a plurality of microneedles 2a-2j each having a conical tip, each with a different outer diameter and height, resulting in different shapes. Because the microneedles 2a and 2i have a larger outer diameter than the other microneedles, they can contain a larger amount of functional component, allowing for an appropriate and sufficient amount of functional component to be mixed into the microimplement 10B. Furthermore, as shown in the example, the microneedles 2a-2j are each provided with different dimensions and shapes and can be arranged in an irregular pattern, which allows them to better fit into the skin of a living organism and human beings, thereby making each microneedle 2a-2j more easily dissolve in the surface layer of the skin and / or the stratum corneum. This also improves the administration of functional components by each microneedle 2a-2j.

[0069] Furthermore, according to the illustrated example of microimplement 10B, by mixing different amounts of functional components into each of the microneedles 2a to 2j, it is possible to create a gradation (gradualness) in the amount of components in the planar direction of microimplement 10B depending on the application.

[0070] [Fourth Example] A microimplement 10C according to a fourth example of this embodiment will now be described with reference to Figures 4A and 4B. Figure 4A is a plan view showing an example of the microimplement 10C configured such that different functional components are mixed into each of multiple microneedles 2A-2O provided on the surface 1a of the substrate 1. Figure 4B is a perspective view showing an example of the microimplement 10C configured such that two different types of functional components are mixed into each of multiple microneedles 2, 2A.

[0071] In the microimplement of this embodiment, each of the multiple microneedles can be configured to contain a mixture of two or more different functional components. For example, as shown in Figure 4A, if multiple microneedles 2A-2O are arranged over the entire surface 1a of the substrate 1, all of the 16 microneedles 2A-2O can be configured to contain different functional components (16 types). It is also possible to configure some of the multiple microneedles 2A-2O to contain the same functional component.

[0072] 4B, it is also possible to employ a structure in which two types of microneedles 2, 2A each containing a different functional component are arranged in a randomly arranged manner. In the illustrated example, there are a total of six microneedles 2 and four microneedles 2A, each of which is arranged in a randomly arranged manner.

[0073] According to the microimplement 10C of this example, by configuring the plurality of microneedles 2 from a mixture of different functional components, it becomes possible to impart a plurality of functions to the microimplement 10C.

[0074] [Fifth Example] Hereinafter, microimplements 10D and 10E of a fifth example of this embodiment will be described with reference to Figures 5A and 5B. Figure 5A is a perspective view showing a microimplement 10D of an example in which functional components 5 are dispersed and attached to the surface 1a of a substrate 1, and microneedles 2P are provided so as to be superimposed on each of the functional components. Figure 5B is a perspective view showing a microimplement 10E of an example in which a plurality of different functional components 5A, 5B, and 5C are dispersed and attached in an irregular arrangement to the surface 1a of the substrate 1, and microneedles 2Q, 2R, and 2S of different shapes or sizes are provided on each of the functional components.

[0075] In this embodiment, as in the microimplement 10D of this example shown in Fig. 5A, a plurality of microneedles 2P are provided so as to overlap the positions of functional components 5 that have been dispersed and arranged in advance on the surface 1a of the substrate 1, and the functional components 5 can be taken in and mixed. In the illustrated example, the functional components 5 in the form of component particles or aggregates are irregularly and freely arranged at a total of 12 positions on the surface 1a of the substrate 1, and the microneedles 2P are provided at a total of 9 of these positions by being targeted and arranged using a learning mechanism.

[0076] The illustrated microimplement 10D has multiple microneedles 2P formed by selectively attaching pure maltose or a maltose composite material that has been heat-softened using a manufacturing method described in detail below to the surface 1a of the substrate 1 so as to capture and cover the functional component 5. This structure is effective when a functional component is used that is difficult to form microneedles by mixing it with maltose in advance, and when it is difficult to arrange the component particles or aggregates in an orderly manner on the surface 1a of the substrate 1. In other words, by selectively arranging multiple microneedles so as to target and capture functional components that are randomly scattered on the surface 1a of the substrate 1, a microimplement 10D that can handle any functional component can be realized.

[0077] 5B, each of the microneedles 2Q, 2R, and 2S provided in a plurality of pieces can be selectively provided at the positions of the functional components 5A, 5B, and 5C that have been dispersed and arranged in advance on the surface 1a of the substrate 1, respectively, and can incorporate and contain any of the functional components. In the illustrated example, the microneedle 2Q incorporates the functional component 5A, the microneedle 2R incorporates the functional component 5B, and the microneedle 2S incorporates and contains the functional component 5C. Although reference numerals are omitted in FIG. 5B, the other microneedles provided on the surface 1a of the substrate 1 also incorporate different functional components.

[0078] In the illustrated example of the microimplement 10E, the multiple microneedles each have different dimensions and shapes, and the chip-like component particles or aggregates (see also reference numerals 5A and 5B) made of the functional components have unspecified shapes. In this way, when multiple different functional components each have unspecified different shapes and it is difficult to manufacture and arrange them uniformly, a structure can be adopted in which functional components of different shapes are arranged and microneedles are arranged on each of them, as in the microimplement 10E of this example shown in Figure 5B.

[0079] [Sixth Example] A microimplement 10F of a sixth example of this embodiment will be described below with reference to Figures 6A and 6B. Figure 6A is a perspective view showing one of a plurality of microprotrusions 3 provided on the surface 1a of a substrate 1, each with a microneedle 2 provided thereon. Figure 6B is a perspective view showing a state in which a plurality of microprotrusions 3 are provided in an irregular arrangement on the surface 1a of the substrate 1 so as to be freely disposable, each with a microneedle 2 provided thereon.

[0080] In this embodiment, as in the illustrated microimplement 10F, a structure can be employed in which a microprotrusion 3 is provided between the substrate 1 and each of the plurality of microneedles 2. The microprotrusions 3 may be made of, for example, pure maltose, as in the case of the microneedles 2, a maltose composite material in which functional components are contained in maltose, or a water-soluble material different from maltose that contains functional components described below.

[0081] Furthermore, although detailed illustration is omitted in Figure 6B, it is also possible to arrange multiple microprotrusions 3 on the surface 1a of the substrate 1 for multiple microneedles 2, each containing one of two or more different functional components, and to have a structure in which multiple microneedles 2 using maltose alone each incorporate and mix and / or encapsulate different functional components.

[0082] When the microimplement 10F of this example is configured with a plurality of microneedles 2 made of pure maltose and microprojections 3 made of a maltose composite material in which a functional component is mixed with maltose, the user can use it by the following procedure. First, the surface 1a of the substrate 1 on which the plurality of microprojections 3 and microneedles 2 are provided is pressed against the surface of the user's skin, thereby causing the plurality of microneedles 2 to preliminarily open micropores in the surface of the user's skin. Then, the functional component contained in the microprojections 3 gradually penetrates into the surface layer of the skin and / or the stratum corneum through the micropores that have been pre-opened in the skin surface.

[0083] [Seventh Example] Hereinafter, microimplements 10G, 10H, and 10I of a seventh example of this embodiment will be described with reference to Figures 7A and 7B. Figure 7A is a perspective view showing the microimplement 10G, Figure 7B is a perspective view showing the microimplement 10H, and Figure 7C is a perspective view showing the microimplement 10I, respectively.

[0084] The example microimplement 10G shown in Figure 7A has microprotrusions 3, 3T, 3U, etc., each having a different arbitrary shape and size, arranged irregularly and freely on the surface 1a of the substrate 1, and microneedles 2, 2T, 2U, etc., having arbitrary dimensions and shapes, which can be freely arranged at any position.

[0085] In addition, the example micro-implement 10H shown in Figure 7B has multiple micro-protrusions 3V, etc., having various shapes such as a star shape when viewed from above, arranged at irregular and freely selected positions on the surface 1a of the substrate 1, and micro-needles 2V are provided on each of them.

[0086] The microimplement 10I shown in FIG. 7C is similar to the above, with multiple microprotrusions 3V, etc., of various shapes, such as a star shape in plan view, arranged at irregular and arbitrary positions on the surface 1a of the substrate 1, and functional component chips 5D are arranged on each of them in addition to microneedles 2V. The microimplement 10I can be formed, for example, by a process similar to that of the microimplement 10H shown in FIG. 7B, up to the point where multiple microprotrusions of various shapes are provided on the surface 1a of the substrate 1. The microimplement 10I shown in FIG. 7C is formed by placing functional component chips 5D of component particles in the empty spaces on the microprotrusions 3V where the microneedles 2V are not provided. That is, after the microneedles 2V are molded on the microprotrusions 3V using the method described below, functional component chips 5D of heat-resistant component particles are placed at room temperature.

[0087] 7C , a user can use the microimplement 10I in the following manner. First, the surface 1a of the substrate 1, on which the plurality of microprojections 3V and microneedles 2V are provided, is pressed against the user's skin surface with a finger, causing the plurality of microneedles 2V to form micropores in advance on the user's skin surface. Then, the functional ingredient chip 5D placed on the microprojections 3V gradually penetrates into the surface layer and / or stratum corneum of the skin through the micropores previously formed on the skin surface.

[0088] <Method for Manufacturing Microimplement> The method for manufacturing a microimplement according to this embodiment will be described below using an example in which a microimplement manufacturing apparatus (hereinafter sometimes simply referred to as the manufacturing apparatus) 100 shown in FIG. 8 is used.

[0089] Figure 8 is a diagram explaining the manufacturing method of the microimplement of this embodiment (hereinafter sometimes simply referred to as the manufacturing method), and is a schematic diagram showing the microneedle molding process in which multiple microneedles 2 are individually and continuously formed by repeatedly heating and cooling the micromold 120 for microneedle molding.

[0090] The manufacturing method of this embodiment is a method for producing a microimplement by forming a plurality of microneedles 2 on the surface 1a of the substrate 1 using maltose alone or a maltose composite material mixed with one or more functional components. Furthermore, the manufacturing method of this embodiment uses a substrate 1 made of a polymeric material to which maltose can be attached. The manufacturing method of this embodiment also includes a microneedle molding step in which a microneedle-forming micromold head (hereinafter sometimes simply referred to as a micromold) 120 having cavities 122 for forming microneedles 2 from maltose or a maltose composite material is repeatedly heated and cooled, thereby successively forming a plurality of microneedles 2 individually, so that at least some of the microneedles 2 formed on the surface 1a of the substrate 1 are irregularly arranged in a planar view. By employing a method including the microneedle molding step as described above, each of the microimplements shown in the first to seventh examples (see FIGS. 1A, 1B to 7A, 7B, and 7C) can be produced.

[0091] [Microimplement Manufacturing Apparatus] The manufacturing apparatus 100 used in this embodiment will now be described. As shown in Fig. 8, the manufacturing apparatus 100 is generally configured to include a support unit 110, a micro mold 120, a heater 130, and a drive unit 140.

[0092] The support unit 110 supports the substrate 1 so that the front surface 1a of the substrate 1 faces a cavity 122 that opens in an end surface 121 of the micro mold 120. The support unit 110 in the illustrated example is configured so that the rear surface 1b of the substrate 1 is attached to the attachment surface 111. The support unit 110 is not particularly limited, but a heat-resistant plate-like member can be used.

[0093] As described above, the micro mold 120 has a cavity 122 for forming the microneedles 2 from maltose or a maltose composite material, and the opening side of this cavity 122 is an end face 121 that faces the substrate 1. The cavity 122 in the illustrated example forms a roughly triangular pyramid-shaped space with the end face 121 side serving as the bottom.

[0094] The micro mold 120 can be made of the same metal material as molds conventionally used in this field, has one cavity 122 corresponding to one microneedle 2, and is ultra-small, taking into consideration the ability to cool (cool) in a short period of time.

[0095] The heater 130 is a means for heating the micro mold 120, and is configured, for example, to include an electric heater (not shown) inside a metal housing. The heater 130 can be provided, for example, integrally with the micro mold 120, or can be disposed so as to be in close contact with the micro mold 120. In the illustrated example, the heater 130 is configured to be attached so as to be in close contact with the underside of the micro mold 120.

[0096] The drive unit 140 reciprocates the micro mold 120 in the X-axis direction shown in FIG. 8 so as to move the micro mold 120 toward and away from the substrate 1. The drive unit 140 in the illustrated example is configured such that the tip of a drive shaft 141 protruding from the main body is connected to the micro mold 120, and the reciprocating movement of the drive shaft 141 can reciprocate the micro mold 120 at high speed. The drive unit 140 is not particularly limited, but for example, a drive unit configured to reciprocate the drive shaft 141 using an electromagnetic valve, a motor, or the like can be used. The manufacturing apparatus 100 described in this example is configured such that the micro mold 120 can repeatedly heat and cool at high speed while the drive unit 140 reciprocates the micro mold 120.

[0097] 8, the manufacturing apparatus 100 is further provided with an X-Z stage unit that can freely move the support unit 110 vertically and horizontally in the Y-axis direction and Z-axis direction in Fig. 8 along the planar direction of the substrate 1. By including the X-Z stage unit (not shown), the manufacturing apparatus 100 is able to continuously form a plurality of microneedles 2 one by one on the surface 1a of the substrate 1 at high speed using the micro mold 120 while freely moving the substrate 1 vertically and horizontally along the planar direction.

[0098] [Example of Manufacturing Method (1)] As an example of the manufacturing method of this embodiment, Example (1) for manufacturing the microimplement 10 shown in Figures 1A and 1B will be described in detail. The manufacturing method of this example further includes a component mixing step of mixing functional components with maltose to prepare a maltose composite material before the above-mentioned microneedle molding step.

[0099] (Component Mixing Step) First, using a component mixer (not shown), components selected from the above-mentioned functional components are mixed with maltose in a dissolved state in amounts such that the mass ratio to maltose falls within a predetermined range, and the mixture is stirred or kneaded so that the functional components are uniformly contained. This allows the preparation of a maltose composite material.

[0100] The prepared maltose composite material is then supplied to the next step, the microneedle molding step. That is, the dissolved maltose composite material prepared in a component preparer (not shown) is discharged and supplied into the cavity 122 of the micro mold 120 using a nozzle (not shown). At this time, the maltose composite material is continuously supplied little by little in an amount corresponding to approximately one microneedle 2, in accordance with the reciprocating movement of the micro mold 120 in the X-axis direction in the next step.

[0101] When the microneedles 2 are formed from pure maltose, the component mixing step does not need to be performed. That is, when the microneedles 2 are formed from pure maltose material, the maltose is heated to a melted state and sent as is to the next step, the microneedle forming step.

[0102] (Microneedle Forming Step) Next, in the microneedle forming step, a plurality of microneedles 2 made of a maltose composite material are formed on the surface 1 a of the substrate 1 using the manufacturing apparatus 100 described above.

[0103] Specifically, in the microneedle forming process of this embodiment, the adhesion process and solidification process shown in (A) and (B) below are repeated at high speed to continuously and quickly form a plurality of microneedles 2 on the surface 1a of the substrate 1, each of which can be individually arranged. (A) Adhesion process: When the micromold 120 approaches the substrate 1, the micromold 120 heated by the heater 130 adheres a softened maltose composite material to the surface 1a of the substrate 1. When the microneedles 2 are formed from maltose alone, the adhesion process involves adhering the softened maltose to the surface 1a of the substrate 1. (B) Solidification process: When the micromold 120 is released from the substrate 1, the heating of the micromold 120 by the heater 130 is stopped and the micromold 120 is allowed to cool, causing the maltose composite material adhered to the surface 1a of the substrate 1 to grow and solidify, thereby forming the microneedles 2. When the microneedles 2 are grown from pure maltose, the maltose attached to the surface 1a of the substrate 1 is solidified as it grows in the solidification process.

[0104] In the microneedle molding process, in the above-mentioned (A) adhesion process, an appropriate amount of the dissolved or softened maltose composite material, i.e., an amount that can be accommodated in the cavity 122 of the micro mold 120, is adhered to the surface 1a of the substrate 1 in a shape that corresponds to the internal shape of this cavity 122.

[0105] Next, in the solidification process (B) above, the micromold 120 is released from the substrate 1 while the softened maltose composite material remains attached to the surface 1a of the substrate 1. When the micromold 120 is released from the maltose composite material attached to the substrate 1 in this manner, a portion of the softened maltose composite material is grown by the micromold 120 moving in the direction of release from the substrate 1, resulting in a sharp tip, which is then solidified by cooling (cooling naturally). This allows the formation of a microneedle 2 in which at least the tip 24 side is roughly conical, as shown in FIG. 1A etc.

[0106] In the manufacturing method of this embodiment, the micro mold 120 is repeatedly heated and cooled so that at least some of the micro needles 2 formed on the surface 1 a of the substrate 1 are irregularly arranged in a plan view, thereby forming the micro needles 2 individually and continuously so as to be freely arranged. The micro implement 10 of the example shown in Figure 1B manufactured by this method has a total of 10 micro needles 2 formed, while leaving some empty space on the surface 1 a of the substrate 1, as described above.

[0107] The manufacturing method of this embodiment employs a micro mold 120 that is capable of forming one microneedle 2 per process, i.e., a micro mold 120 that has only one cavity 122, and uses this micro mold 120 to form the microneedles 2 one by one on the surface 1a of the substrate 1. In this way, the use of an ultra-small micro mold 120 enables the micro mold 120 to be heated and cooled repeatedly at high speed. This minimizes the heat capacity of the mold compared to conventional methods that use large molds for forming multiple microneedles in a single process, and allows the mold temperature to be controlled to change quickly and precisely, making it possible to form microneedles with excellent shape precision and a tapered shape that becomes smaller in diameter toward the tip.

[0108] The melting point of the anhydrous maltose used for the microneedles 2 is low at 108°C, which is extremely low compared to other materials conventionally used for microneedles, such as starch (256-258°C) and hyaluronic acid (209°C or higher). When maltose with such a low melting point is used as the material for the microneedles and molded using a mold, if a large, multi-cavity mold is used, it is difficult to lower the mold temperature, which creates the problem of making it difficult to form the maltose attached to the substrate into the desired shape.

[0109] In the manufacturing method of this embodiment, by employing a method of molding the microneedles 2 using the single-cavity micromold 120 as described above, it is possible to continuously heat and cool the micromold 120 at high speed. This makes it possible to continuously mold the desired shape of the microneedles 2 with excellent precision, even when maltose, which is easily soluble, is used as the microneedle material. Furthermore, by using a micromold 120 with a high cooling rate, it is also possible to form microneedles 2 using a maltose composite material containing a functional component with low heat resistance, such as an amino acid, a protein, or an unheated biological substance.

[0110] Furthermore, in the manufacturing method of this embodiment, by adjusting the heating temperature and time and the cooling temperature and time in the control of the repeated heating and cooling of the micro mold 120 at high speed as described above, it becomes possible to form microneedles in various cone shapes, such as a cone shape, even when using a micro mold 120 having a cavity 122 consisting of a triangular pyramid-shaped space. That is, in the manufacturing method of this embodiment, by optimizing the control of the repeated heating and cooling, it becomes possible to form not only the roughly cone-shaped microneedles 2 as shown in the illustration, but also microneedles having various cone shapes, such as a triangular pyramid, a square pyramid, a bullet shape, and a polygonal pyramid with pentagonal or greater sides.

[0111] Furthermore, according to the manufacturing method of this embodiment, by employing the manufacturing apparatus 100 as described above, the shape of the microneedles can be freely set and formed using a method with 3D printer functionality, and their placement and alignment can also be freely determined. This allows the microneedles 2 to be freely formed in a desired placement pattern, and changes in the placement pattern specification can be easily accommodated without the need for mold replacement, etc., thereby further improving productivity. Furthermore, by employing the method using the micro mold 120 as described above, high-speed heating and cooling are possible, and the microneedles 2 can be formed under conditions that essentially have a high-speed temperature rise and fall function. This makes it possible to form the tips 24 of the microneedles 2 with excellent shape quality, making them sharper.

[0112] [Example of Manufacturing Method (2)] As an example (2) of the manufacturing method of this embodiment, an example of manufacturing a micro-implement 10C as shown in Figures 4A and 4B will be described, that is, a method of manufacturing the micro-implement 10C by forming micro-needles containing a mixture of different functional components on the surface 1a of the substrate 1.

[0113] In this example, two or more different functional components are used in the component mixing step, and multiple maltose composite materials are prepared so that each of the different functional components is mixed. Then, in the microneedle forming step, multiple microneedles are successively formed so that each microneedle contains one of the two or more different functional components.

[0114] Specifically, when manufacturing the microimplement 10C shown in Fig. 4A, a maltose composite material containing 16 different functional components is first prepared in the component mixing step, and then 16 microneedles 2, 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2H, 2I, 2J, 2K, 2L, 2M, 2N, and 2O, each containing a different functional component, are individually formed in the microneedle molding step.

[0115] 4B, a microimplement 10C is manufactured by first preparing two maltose composite materials containing two different functional components in the component mixing step, and then forming a plurality of microneedles 2, 2A, each made of a maltose composite material containing a different functional component, on the surface 1a of the substrate 1 in an irregular arrangement.

[0116] According to the manufacturing method of this example, by employing the above method, it becomes possible to manufacture a micro implement 10C that is endowed with a plurality of functions.

[0117] [Example of Manufacturing Method (3)] As an example (3) of the manufacturing method of this embodiment, an example of manufacturing micro-implements 10D and 10E as shown in Figures 5A and 5B will be described, that is, a method of manufacturing micro-implements 10D and 10E by arranging functional components on the surface 1a of the substrate 1 and forming micro-needles to aim at those positions.

[0118] 5A, the method may further include a spraying step of attaching a functional component 5 to the surface 1a of the substrate 1 in an irregular arrangement prior to the microneedle molding step. The microneedle molding step then forms a plurality of microneedles 2 while aligning them with the positions of the functional component 5 attached to the surface 1a of the substrate 1. In the illustrated example, the functional components 5 are arranged in a total of nine positions on the surface 1a of the substrate 1, and a plurality of microneedles 2 are formed in aligned positions at each of the nine positions.

[0119] 5B, when manufacturing a microimplement 10E, first, a spraying process attaches two or more different functional components 5A, 5B, 5C, etc. to the surface 1a of the substrate 1 in an irregular arrangement. Then, a microneedle forming process forms a plurality of microneedles 2Q, 2R, 2S, etc., while aligning them with the positions of the functional components 5A, 5B, 5C, etc. attached to the surface 1a of the substrate 1. In the illustrated example, microneedles 2Q, 2R, and 2S are formed on the functional component 5A, 5A, and 5C, respectively, with different dimensions and shapes. Microneedles are also selectively formed on the functional components at other positions on the surface 1a of the substrate 1.

[0120] According to the manufacturing method of this example, even if multiple different functional components each have different, unspecified shapes and it is difficult to manufacture and arrange them uniformly, it is possible to manufacture microimplements 10D and 10E as shown in Figures 5A and 5B.

[0121] [Example of Manufacturing Method (4)] As an example (4) of the manufacturing method of this embodiment, an example will be described in which multiple microneedles 2 are formed using maltose alone to obtain a microimplement 10 as shown in Figures 1A and 1B, and then a functional component is coated so as to cover the surfaces of the multiple microneedles 2.

[0122] In this example, although detailed illustration is omitted, a component coating step of coating the surfaces of the microneedles with a functional component can be further provided after the microneedle molding step, thereby producing a microimplement in which the functional component is coated on the surfaces of the microneedles 2 made of, for example, pure maltose.

[0123] The method for coating the surface of the microneedles 2 with the functional component is not particularly limited, but any conventionally known method can be used, such as slit coating, slide coating, blade coating, bar coating, roll coating, gravure coating, dip coating, spray coating, etc.

[0124] According to the manufacturing method of this example, by adopting a method including the component coating step as described above, the functional component is not directly exposed to a step including a heating process such as the microneedle molding step, and therefore it becomes possible to use components that are not highly heat-resistant, such as amino acids, proteins, unheated biological substances, etc., as the functional component.

[0125] [Example of manufacturing method (5)] As an example (5) of the manufacturing method of this embodiment, we will explain an example of manufacturing a micro-implement 10F in which multiple micro-protrusions 3 are provided on the surface 1a of a substrate, and micro-needles 2 are provided on each of the protrusions, as shown in Figures 6A and 6B.

[0126] 6A and 6B, a method can be adopted that includes a microprotrusion forming step, prior to the microneedle forming step, in which a plurality of microprotrusions 3 are formed on the surface 1a of the substrate 1 in an irregular arrangement. Then, in the microneedle forming step, a microneedle 2 is formed on each of the plurality of microprotrusions 3, thereby producing the microprotrusions 10F. In the microprotrusion forming step, the plurality of microprotrusions 3 can be formed from a maltose composite material in which a functional component is mixed with maltose.

[0127] According to the manufacturing method of this example, by adopting a method including the above-mentioned microprotrusion molding process, it is possible to manufacture the illustrated microimplement 10F, in which first, micropores are formed on the surface of the user's skin using a plurality of microneedles 2, and then the functional components contained in the microprotrusions 3 gradually penetrate into the surface layer of the skin and / or the stratum corneum through the micropores.

[0128] Furthermore, in the manufacturing method of this example, the microprotrusion molding step may employ a method in which a plurality of microprotrusions, each containing one of two or more different functional components, is formed on the surface 1a of the substrate 1. In such a case, in the microneedle molding step, a microneedle made of pure maltose is formed on each of the plurality of microprotrusions.

[0129] [Example of Manufacturing Method (6)] As Example (6) of the manufacturing method of this embodiment, a method for manufacturing microimplements 10G, 10H, and 10I as shown in Figures 7A, 7B, and 7C will be described. That is, in this manufacturing method, in the microprotrusion molding step, a plurality of microprotrusions 3, 3U, 3T, etc. are formed on the surface 1a of the substrate 1, and in the microneedle molding step, microneedles 2, 2U, and 2T are formed on the microprotrusions 3, 3U, 3T, etc., respectively, thereby manufacturing the microimplement 10G as shown in Figure 7A. In the illustrated example, the microimplement 10G has microneedles 2 formed on the microprotrusions 3, microneedles 2U formed on the microprotrusions 3U, and microneedles 2T formed on the microprotrusions 3T. In the illustrated example, microprotrusions are formed at a total of 16 locations on the surface 1a of the substrate 1, including microprotrusions other than the microprotrusions 3, 3U, and 3T, and microneedles are formed on a total of 10 of the microprotrusions.

[0130] In this example, in the microprojection molding step, a plurality of microprojections 3V having various shapes, such as a star shape in plan view, are formed at irregular and arbitrary positions on the surface 1a of the substrate 1, and then in the microneedle molding step, microneedles 2V are formed on each of the microprojections, thereby producing a microimplement 10H as shown in Fig. 7B. Furthermore, in this example, in the same procedure as for the microimplement 10H shown in Fig. 7B, a plurality of microprojections 3V having various shapes, such as a star shape in plan view, are formed on the surface 1a of the substrate 1, and then microneedles 2V are formed in the microneedle molding step. Furthermore, by placing a functional ingredient chip 5D on each of the plurality of microprojections, a microimplement 10I as shown in Fig. 7C can be produced.

[0131] According to the manufacturing method of this example, as described above, it is possible to manufacture micro-implements 10G, 10H, and 10I in which the micro-needles are easily dissolved, have excellent biological safety, and have an enhanced effect of administering functional ingredients from the micro-needles.

[0132] <Effects> As described above, according to the microimplement of this embodiment, maltose or a maltose composite material is used for the multiple microneedles 2 provided on the substrate 1, and a structure is adopted in which at least some of the microneedles 2 are arranged irregularly in a planar view on the surface 1a of the substrate 1, and each is individually formed and arranged freely. This makes it easier to administer the microneedles 2 to the surface layer of the skin and / or the stratum corneum of the skin than when all of the microneedles 2 are arranged in a regular array, resulting in excellent compatibility with the living body. Furthermore, the administration effect of the functional ingredient from the microneedles 2 is enhanced, so that, for example, the effects of medical treatments and cosmetic procedures can be more pronounced.

[0133] Furthermore, according to the microimplement manufacturing method of this embodiment, when forming a plurality of microneedles 2 in an irregular arrangement on the surface 1a of the substrate 1, a method is adopted in which the microneedles 2 are individually and continuously formed by repeatedly heating and cooling the microneedle-forming micromold head 120. This makes it possible to form the microneedles 2 in a desired shape with high accuracy, even when forming the microneedles 2 from solid maltose or a maltose composite material with a low melting point, and also makes it possible to freely form the microneedles 2 in a desired arrangement, easily accommodating specification changes to the arrangement, etc. Furthermore, since the tip 24 of the microneedles 2 can be formed more sharply, they can be painlessly and effectively pierced into the surface layer of the skin and / or the stratum corneum, making it possible to successfully produce a microimplement 10 that provides a more pronounced feel in use and more pronounced effects from medical and cosmetic treatments.

[0134] <Variations of the present invention> Although the embodiments of the present invention have been described in detail above, the micro-implement and its manufacturing method of the present invention are not limited to the above embodiments, and various changes and modifications can be made without departing from the principles of the present invention and the scope of the appended claims.

[0135] The microimplement of the present invention has an excellent effect in administering functional ingredients from microneedles, and the manufacturing method of the microimplement of the present invention can form the microneedles in a desired shape with high accuracy, can form sharper tips, and can freely form the microneedles in a desired arrangement. Therefore, the microimplement of the present invention is very suitable not only for skin treatment, beauty and modification, but also for advanced treatments such as treatment of immune system diseases deep under the skin or affecting the whole body, and the manufacturing method of the microimplement of the present invention is very suitable for applications in manufacturing the above-mentioned microimplements.

[0136] 10, 10A, 10B, 10C, 10D, 10E, 10F, 10G, 10H, 10I... Micro implementation 1... Board 1a... Front side 1b... Back side 11... Planned installation location 2, 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2H, 2I, 2J, 2K, 2L, 2M, 2N, 2O, 2P, 2Q, 2R, 2S, 2T, 2U, 2V, 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j... Fine needle 21... Base end part 22... Body part 23... Acicular needle part 24... Tip part 3, 3T, 3U, 3V... Fine protrusion 31... Lower surface 32... Upper surface 5, 5A, 5B, 5C... Functional component 5D... Functional component chip (functional component) REFERENCE SIGNS LIST 100... Microimplement manufacturing apparatus 110... Support unit 111... Mounting surface 120... Micromold head for forming fine needles 121... End surface 122... Cavity 130... Heater 140... Drive unit 141... Drive shaft

Claims

1. A microimplement comprising: a substrate made of a polymeric material to which maltose can be attached; and microneedles arranged in a plurality on the surface of the substrate, the microneedles being made of either pure maltose or a maltose composite material mixed with one or more functional components; wherein at least some of the microneedles are arranged irregularly in a planar view on the surface of the substrate, and each microneedle is individually formed so as to be freely arranged.

2. The microimplement according to claim 1, wherein each of said plurality of fine needles is a mixture of any of two or more different functional components.

3. A microimplement according to claim 1 or 2, characterized in that the plurality of fine needles are provided on the surface of the substrate in a state in which the functional component is mixed in advance.

4. A microimplement according to claim 1 or claim 2, characterized in that the plurality of microneedles are arranged so as to overlap the positions of the functional components that have been dispersed and arranged in advance on the surface of the substrate, and the functional components are taken in and mixed and / or encapsulated.

5. A microimplement according to claim 1 or 2, further comprising a microprotrusion provided between said substrate and each of said plurality of microneedles.

6. The microimplement according to claim 1, further characterized in that microprotrusions are provided between the substrate and each of the plurality of microneedles, and a plurality of the microprotrusions are arranged for each of the plurality of microneedles, each containing one of two or more different functional components, and each of the plurality of microneedles is made of pure maltose and incorporates, mixes and / or encapsulates, two or more different functional components.

7. The microimplement according to claim 1, wherein the plurality of microneedles are made of pure maltose and the functional component is coated on the surface of the microneedles.

8. A microimplement according to claim 1 or 2, characterized in that the functional ingredient is any one or a combination of two or more selected from the group consisting of vitamins, hormones, glycoproteins, collagen, proteins, peptides, enzymes, coenzymes, vaccine components, biosignal substances, intracellular signal substances, extracellular signal substances, neurotransmitters, information polymers, bioenergy substances, medicines, nutrients, nutritional supplements, cosmetics, antibody testing agents, anticancer drugs, antidotes, artificial cells, internally used color materials, internally used metals, internally used metal oxides, and internally used magnetic substances or component granules.

9. A microimplement according to claim 1 or 2, characterized in that the polymer material used for the substrate is any one of polyvinyl alcohol, pullulan, hyaluronic acid, gelatin, and collagen.

10. A microimplement according to claim 1 or 2, characterized in that at least the tip side of the multiple microneedles is in the shape of a cone, such as a triangular pyramid, a square pyramid, a cone, a bullet shape, or a polygonal pyramid of pentagonal or higher.

11. The microimplement according to claim 10, wherein each of said plurality of microneedles has a different shape.

12. A method for manufacturing a micro-implement, in which a plurality of micro-needles are formed on the surface of a substrate using pure maltose or a maltose composite material mixed with one or more functional components, the method comprising the steps of: using a substrate made of a polymeric material to which the maltose can adhere; and repeatedly heating and cooling a micro-mold head for micro-needle molding, which has a cavity for freely arranging the micro-needles from the pure maltose or the maltose composite material, so that at least some of the plurality of micro-needles formed on the surface of the substrate are irregularly arranged in a planar view; and forming the plurality of micro-needles individually and continuously.

13. The method for manufacturing a microimplement according to claim 12, characterized in that the microneedle molding process comprises: an attachment process in which, when the microneedle molding micromold head approaches the substrate, the maltose or the maltose composite material is attached in a softened state to the surface of the substrate by the microneedle molding micromold head heated by a heater; and a solidification process in which, when the microneedle molding micromold head is released from the substrate, the heating of the microneedle molding micromold head by the heater is stopped and the microneedle molding micromold head is allowed to cool, thereby solidifying the pure maltose or the maltose composite material attached to the surface of the substrate while growing.

14. A method for manufacturing a micro-implement according to claim 12 or 13, characterized in that it comprises a component mixing step of mixing functional components with the maltose to prepare the maltose composite material before the micro-needle molding step.

15. The method for manufacturing a microimplement described in claim 14, characterized in that the component mixing process uses two or more different functional components, and prepares multiple maltose composite materials so that each different functional component is mixed, and the microneedle molding process continuously forms multiple microneedles so that each microneedle contains one of the two or more different functional components.

16. A method for manufacturing a microimplement as described in claim 12 or claim 13, further comprising a spraying step prior to the microneedle forming step, in which the functional component is attached to the surface of the substrate in an irregular arrangement so as to be freely arranged, and in the microneedle forming step, the multiple microneedles are formed so as to overlap at the positions of the functional component attached to the surface of the substrate.

17. The method for manufacturing a microimplement according to claim 16, wherein the spraying step deposits two or more different functional components on the surface of the substrate so that each of the functional components can be freely arranged in an irregular arrangement.

18. A method for manufacturing a micro-implement according to claim 12 or 13, further comprising, after the micro-needle molding step, a component coating step of coating the functional component onto the surfaces of the plurality of micro-needles made of pure maltose.

19. A method for manufacturing a microimplement as described in claim 12 or claim 13, further comprising a microprotrusion forming step of forming a plurality of microprotrusions in an irregular arrangement on the surface of the substrate before the microneedle forming step, wherein the microneedle forming step forms a microneedle on each of the plurality of microprotrusions.

20. A method for manufacturing a microimplement as described in claim 19, characterized in that the microprotrusion molding process forms a plurality of microprotrusions on the surface of the substrate, each of which is a mixture of any of two or more different functional components, and the microneedle molding process forms a microneedle made of pure maltose on each of the plurality of microprotrusions.

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